tag:theconversation.com,2011:/fr/topics/clinical-trials-2742/articlesClinical trials – The Conversation2023-07-19T04:03:59Ztag:theconversation.com,2011:article/2099702023-07-19T04:03:59Z2023-07-19T04:03:59ZAlzheimer’s drug donanemab has been hailed as a ‘turning point’ for treatment. But what does it mean for people with the disease?<figure><img src="https://images.theconversation.com/files/538167/original/file-20230719-29-ns8anb.jpg?ixlib=rb-1.1.0&rect=97%2C67%2C4895%2C2739&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/amyloid-plaques-forming-between-neurons-3d-2271276029">Shutterstock</a></span></figcaption></figure><p>Trial results of a new drug to treat Alzheimer’s disease, donanemab, shows it can <a href="https://jamanetwork.com/journals/jama/fullarticle/2807533">slow cognitive decline</a> by 35%. The drug has been hailed as a “turning point” in Alzheimer’s treatment.</p>
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<p>But as usual, there’s <a href="https://www.nature.com/articles/d41586-023-02321-1">more to the story</a>. The study only included people with early or mild disease, not more advanced symptoms. Donanemab is not a cure for Alzheimer’s. Nor is it 100% safe. </p>
<p>So what did the trial actually find? And how might this drug affect the lives of people with Alzheimer’s disease? </p>
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Read more:
<a href="https://theconversation.com/new-alzheimers-drug-what-you-need-to-know-about-donanemabs-promising-trial-results-205156">New Alzheimer’s drug: what you need to know about donanemab’s promising trial results</a>
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<h2>What is Alzheimer’s disease?</h2>
<p>There are more than 100 types of dementia, but Alzheimer’s disease is the most common, accounting for <a href="https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/alz.12068">around 70%</a> of cases. </p>
<p>The disease is caused by the accumulation of two proteins: amyloid and tau. Amyloid can accumulate for at least 20 years prior to the onset of symptoms, forming clumps in the brain. </p>
<p>Once symptoms have started and are progressing, tau, a marker of cell damage, also begins to accumulate.</p>
<p>Clinical symptoms progress, on average, over <a href="https://jamanetwork.com/journals/jamaneurology/fullarticle/783112">seven to ten years</a> after diagnosis. But in Australia, there is a lag of <a href="https://www.dementia.org.au/sites/default/files/2022-12/Dementia-Australia-annual-report-2021-2022.pdf">up to three years</a> from the point at which people first develop symptoms before a diagnosis is typically made.</p>
<h2>What have drug treatments aimed to do?</h2>
<p>The “<a href="https://www.embopress.org/doi/pdf/10.15252/emmm.201606210">amyloid hypothesis</a>”, which suggests amyloid is the key cause of the disease, has driven Alzheimer’s research for more than 25 years. </p>
<p>Multiple drugs targeting amyloid have, however, failed in clinical trials over most of that period, casting doubt on the validity of amyloid as a target – until recently.</p>
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Read more:
<a href="https://theconversation.com/what-allegations-of-alzheimers-research-fraud-mean-for-patients-187911">What allegations of Alzheimer's research fraud mean for patients</a>
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<p>Our bodies produce antibodies in response to the presence of a foreign invader such as a bacteria or virus. Mimicking the approach taken by our immune systems, scientists have developed antibodies in the lab that recognise amyloid as such an invader. </p>
<p>Specifically targeting amyloid, these drugs are known as monoclonal antibodies. Donanemab is one of three monoclonal antibodies targeting amyloid that have shown various degrees of success in clinical trials in slowing decline in people with early stage disease.</p>
<h2>OK so what did the donanemab trial find?</h2>
<p>The manufacturer’s clinical trial included 1,736 patients with very mild memory loss due to Alzheimer’s disease, and with early clinical Alzheimer’s disease. </p>
<p>Half received donanemab by intravenous infusion over an 18-month study, the remainder were treated with a placebo (a “dummy” version). </p>
<p>The results were analysed by dividing the study population into two further groups: those with low to intermediate levels of tau; and those with high tau levels (high tau correlates with the presence of more advanced brain cell damage).</p>
<p>Those with low and intermediate tau declined by 35% less than those treated with placebo. About half of the treatment group cleared amyloid from their brains below the threshold used to diagnose the disease, over 12 months of treatment. </p>
<p>The high tau group did far less well.</p>
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<a href="https://images.theconversation.com/files/538163/original/file-20230719-27-f0bjsy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="older couple holding hands with man looking confused" src="https://images.theconversation.com/files/538163/original/file-20230719-27-f0bjsy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/538163/original/file-20230719-27-f0bjsy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/538163/original/file-20230719-27-f0bjsy.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/538163/original/file-20230719-27-f0bjsy.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/538163/original/file-20230719-27-f0bjsy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/538163/original/file-20230719-27-f0bjsy.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/538163/original/file-20230719-27-f0bjsy.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">People may be delaying diagnosis because they think nothing can be done.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/retired-couple-holding-hands-looking-each-1272275779">Shutterstock</a></span>
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<p>Participants aged under 75 and those showing only mild cognitive impairment (rather than the full clinical picture of Alzheimer’s disease) had their progression slowed by around 50% over the same period.</p>
<p>Patients were assessed using both cognitive measures and measures of daily function, such as the ability to do personal and household tasks. The results translated into the treatment group showing levels of decline at 18 months that were experienced by the placebo group at 10.5 to 13.6 months, depending on the participant subgroup studied.</p>
<p>Important examples may be that they continue to be able to drive, pay bills, or attend activities outside of the home independently.</p>
<p>But both the treatment and the placebo groups declined overall. In other words, it doesn’t stop the decline, it slows it, in people with mild or early disease. </p>
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Read more:
<a href="https://theconversation.com/lots-of-breakthroughs-still-no-cure-do-the-new-dementia-drugs-bring-us-any-closer-195095">Lots of 'breakthroughs', still no cure. Do the new dementia drugs bring us any closer?</a>
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<h2>What are the downsides?</h2>
<p>At least two patients in the trial died from complications of brain swelling caused by donanemab. Around one-quarter of the treatment group showed some degree of swelling, most of which didn’t cause symptoms. </p>
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<span class="caption">Two patients in the study died from complications from brain swelling.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/alzheimers-disease-on-mri-2-664361179">Shutterstock</a></span>
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<p>The cost of donanemab will be significant, at <a href="https://www.washingtonpost.com/health/2023/07/17/alzheimers-drug-lilly-donanemab/">US$26,500</a> or around A$39,000 per year. </p>
<p>Donanemab has already been approved by the US Food and Drug Administration.
Eli Lilly, the drug’s manufacturer, has applied to the Therapeutic Goods Administration (TGA) for approval for use in Australia. </p>
<p>But TGA approval is only the first step to making the drug available here. A further assessment will determine whether the Pharmaceutical Benefits Scheme subsidises the drug to make it affordable.</p>
<p>It’s likely any PBS listing would restrict the drug’s use to people whose disease state mirrors that of those included in the clinical trial population – people with early symptoms, who have had PET scans showing the presence of amyloid (and low and intermediate tau). </p>
<p>This is not a drug for everyone with Alzheimer’s disease.</p>
<h2>Preparing for early detection and treatment</h2>
<p>People have tended to delay seeking assessment of their memory symptoms because “nothing can be done anyway”. GPs may have been reluctant to refer to other specialists for assessment for the same reason. </p>
<p>The potential for early treatment means this needs to change. We also need to develop our diagnostic and treatment infrastructure (building the necessary PET scanners and infusion centres) that will be necessary to facilitate timely diagnosis and treatment when the drug does become available locally.</p>
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Read more:
<a href="https://theconversation.com/what-is-sundowning-and-why-does-it-happen-to-many-people-with-dementia-208005">What is 'sundowning' and why does it happen to many people with dementia?</a>
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<img src="https://counter.theconversation.com/content/209970/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Steve Macfarlane has been paid to attend a number of Australian medical advisory board meetings for Eli Lilly, the manufacturer of donanemab, most recently last year. He receives funding from a number of drug companies for conducting pharmaceutical trials. He is affiliated with the RANZCP.</span></em></p>The drug has been hailed as a ‘turning point’ in Alzheimer’s treatment. But keep in mind the trial only included participants with early or mild disease. And while it slowed decline, it’s not a cure.Steve Macfarlane, Head of Clinical Services, Dementia Support Australia, & Associate Professor of Psychiatry, Monash UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2095912023-07-14T02:06:30Z2023-07-14T02:06:30ZKetamine injections for depression? A new study shows promise, but it’s one of many options<figure><img src="https://images.theconversation.com/files/537183/original/file-20230712-29-dtpug1.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C1000%2C666&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Psychedelics like ketamine affect chemical messengers in the brain.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/abstract-brain-fractal-background-digital-illustration-2212346843">Shutterstock</a></span></figcaption></figure><p>Ketamine might be better known as a recreational drug or anaesthetic. But there’s growing evidence for its use for people with hard-to-treat depression.</p>
<p>An Australasian study <a href="https://www.cambridge.org/core/journals/the-british-journal-of-psychiatry/article/efficacy-and-safety-of-a-4week-course-of-repeated-subcutaneous-ketamine-injections-for-treatmentresistant-depression-kads-study-randomised-doubleblind-activecontrolled-trial/FDBAEC51F0891B57F5B04C572D13DA17">out today</a> showed some positive results for people with treatment-resistant depression when they had ketamine injections.</p>
<p>But we don’t know if these effects are sustained in the long term, and there are other ways of delivering ketamine. There are also other treatment options for this type of depression.</p>
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Read more:
<a href="https://theconversation.com/weekly-dose-anaesthetic-and-recreational-drug-ketamine-could-be-used-to-treat-depression-81468">Weekly Dose: anaesthetic and recreational drug ketamine could be used to treat depression</a>
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<h2>What is ketamine?</h2>
<p>Ketamine has been used as a powerful <a href="https://www.nature.com/articles/s41593-022-01203-5">general anaesthetic</a> for more than 50 years.</p>
<p>It’s also an <a href="https://www.ncbi.nlm.nih.gov/books/NBK470357/">illicit drug</a> of abuse and is considered a psychedelic. Psychedelics dramatically alter some neurotransmitters (chemical messengers) in the brain <a href="https://pubmed.ncbi.nlm.nih.gov/36280799/">to create</a> a profound change in perception, mood and anxiety.</p>
<p>In early animal studies, ketamine led to increase in levels of certain brain chemicals, such as dopamine, by <a href="https://www.nature.com/articles/mp2017190">up to 400%</a>. This led researchers to trial ketamine in humans to see what would happen in our brains.</p>
<p>Now, doses of ketamine (at those lower than used as an anaesthetic) are being used to help treatment-resistant depression. That’s when someone has tried at least two antidepressants and shows no improvement.</p>
<p>It is usually prescribed under strict conditions and observation that mitigate some <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6322816/">serious risks</a>, such as increased feelings about suicide in some people. So people need to be assessed and monitored not only during treatment, but afterwards.</p>
<p>But some clinicians have resisted using ketamine due to its potential to become a <a href="https://www.ranzcp.org/getmedia/75baa529-2b71-419f-993a-2ff64ede50fe/cm-use-of-ketamine-in-psychiatric-practice.pdf">drug of abuse</a>.</p>
<p>Ketamine is also used to treat other mental health disorders such as <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8959757/">PTSD</a> (post-traumatic stress disorder).</p>
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Read more:
<a href="https://theconversation.com/hallucinations-in-the-movies-tend-to-be-about-chaos-violence-and-mental-distress-but-they-can-be-positive-too-204547">Hallucinations in the movies tend to be about chaos, violence and mental distress. But they can be positive too</a>
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<h2>How about this new study?</h2>
<p>The research involved <a href="https://www.australianclinicaltrials.gov.au/anzctr/trial/ACTRN12616001096448">multiple centres</a> across Australia and New Zealand and compared how well ketamine injected <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193034/">under the skin</a> compared with taking another drug in treating people with treatment-resistant depression.</p>
<p>The trial randomised the 184 study participants into different groups – some receiving ketamine, the rest the drug <a href="https://pubmed.ncbi.nlm.nih.gov/9258787/">midazolam</a>, twice a week over four weeks. Neither the study participants nor those assessing the results knew who had ketamine and who didn’t.</p>
<p>At the start of the study, all participants had a clinical depression score of at least 20 (moderate depression) using a particular scale known as the Montgomery-Asberg Depression Rating Scale.</p>
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<a href="https://images.theconversation.com/files/537220/original/file-20230713-25-gs9tri.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Doctor in white coat putting hand on shoulder of patient" src="https://images.theconversation.com/files/537220/original/file-20230713-25-gs9tri.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/537220/original/file-20230713-25-gs9tri.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/537220/original/file-20230713-25-gs9tri.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/537220/original/file-20230713-25-gs9tri.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/537220/original/file-20230713-25-gs9tri.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/537220/original/file-20230713-25-gs9tri.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/537220/original/file-20230713-25-gs9tri.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">The study participants had moderate depression.</span>
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<p>The researchers then looked for a score of less than 11, indicating a shift from a depression to remission.</p>
<p>After four weeks, there was a big difference between people treated with ketamine (19.6% in remission) compared with midazolam (2%). Another, less-strict way of measuring outcomes is to look for a halving of the depression score. This had an even bigger difference (29% compared with 4%). </p>
<p>However, four weeks after the treatment had ended, there was only limited sustained improvement in symptoms in the ketamine group. This suggests treatment may be needed over a longer period.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/do-psychedelics-really-work-to-treat-depression-and-ptsd-heres-what-the-evidence-says-208857">Do psychedelics really work to treat depression and PTSD? Here's what the evidence says</a>
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<h2>There are other options</h2>
<p>In the trial, ketamine was given via an injection under the skin, which is a low-cost and efficient option. But ketamine can also be delivered directly into the bloodstream via an intravenous drip. Neither of these two options are routinely available in Australia and New Zealand outside clinical trials.</p>
<p>A third option uses a <a href="https://www.nps.org.au/australian-prescriber/articles/esketamine-hydrochloride-for-treatment-resistant-depression">different form</a> of ketamine and comes in a <a href="https://www.spravato.com/">nasal spray</a> (approved for use in <a href="https://www.tga.gov.au/resources/auspmd/spravato">Australia</a> and New Zealand). </p>
<p>Each option delivers ketamine in different amounts, and research into how these work in practice, and how they compare, is <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193034/">ongoing</a>.</p>
<p>There are also other drug and non-drug options for treatment-resistant depression. These include:</p>
<ul>
<li><p><a href="https://pubmed.ncbi.nlm.nih.gov/33834408/">transcranial magnetic stimulation</a>, which stimulates parts of the brain to improve mood</p></li>
<li><p><a href="https://www.ranzcp.org/events-learning/psychedelic-assisted-therapy">psilocybin</a>, another psychedelic drug that has just been given the go-ahead for use in Australia under strict conditions as part of <a href="https://theconversation.com/psychedelic-medicine-is-on-its-way-but-its-not-doing-shrooms-with-your-shrink-heres-what-you-need-to-know-208568">psychedelic-assisted therapy</a></p></li>
<li><p><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429332/">psychotherapy</a> (talking therapy) such as cognitive behavioural therapy, <a href="https://www.psychologytoday.com/au/therapy-types/acceptance-and-commitment-therapy">acceptance and commitment therapy</a> and <a href="https://pubmed.ncbi.nlm.nih.gov/29761488/">dialectical behaviour therapy</a></p></li>
<li><p>changing some lifestyle factors, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164235/">such as diet</a> and <a href="https://pubmed.ncbi.nlm.nih.gov/28110494/">exercise</a>, or <a href="https://pubmed.ncbi.nlm.nih.gov/32985916/">practising mindfulness</a> meditation.</p></li>
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<h2>In a nutshell</h2>
<p>Serious consequences of depression include <a href="https://theconversation.com/suicide-rates-are-rising-with-or-without-13-reasons-why-lets-use-it-as-a-chance-to-talk-116434">suicide</a> or a lifetime of anguish. This latest research shows promising outcomes for people whose symptoms are harder to treat. But this option is not yet widely available outside a clinical trial. Only the ketamine nasal spray has been approved for use in Australia and New Zealand.</p>
<p>There are also other treatments. So if your existing treatment is not working for you, discuss this with your doctor who will explain what else is available.</p>
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<p><em>If this article has raised issues for you, or if you’re concerned about someone you know, call Lifeline on 13 11 14. Beyond Blue provides the free resource <a href="https://www.beyondblue.org.au/docs/default-source/resources/bl0556-what-works-for-depression-booklet_acc.pdf?sfvrsn=fe1646eb_2">A guide to what works for depression</a>.</em></p><img src="https://counter.theconversation.com/content/209591/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Michael Musker does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>This latest research provides hope for people whose symptoms are harder to treat.Michael Musker, Enterprise Fellow (Senior Research Fellow/Senior Lecturer), University of South AustraliaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2047872023-05-04T20:39:52Z2023-05-04T20:39:52ZHealth Canada should be transparent about how it’s monitoring drug safety<figure><img src="https://images.theconversation.com/files/524019/original/file-20230503-26-zdm4om.jpg?ixlib=rb-1.1.0&rect=586%2C439%2C5165%2C3388&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">When regulatory agencies like Health Canada approve a new drug, they require the drug company to continue monitoring the product's safety.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><iframe style="width: 100%; height: 100px; border: none; position: relative; z-index: 1;" allowtransparency="" allow="clipboard-read; clipboard-write" src="https://narrations.ad-auris.com/widget/the-conversation-canada/health-canada-should-be-transparent-about-how-it-s-monitoring-drug-safety" width="100%" height="400"></iframe>
<p>Regulatory bodies like Health Canada are intended to ensure that approved drugs go through a rigorous multi-stage process. However, clinical trials can’t detect every side-effect or risk. </p>
<p>Once new drugs are approved for marketing in Canada, Health Canada continues to monitor them. This is to determine if the health benefits identified in pre-market trials hold up to further scrutiny, new safety issues arise or known ones are more serious than initially anticipated, and if the drugs are being used outside of their approved uses and populations. </p>
<p>All of that information is important for doctors and pharmacists and for people who will be using the drugs and should be publicly available.</p>
<h2>Clinical trials</h2>
<p>Potential new drugs are assessed in <a href="https://www.canada.ca/en/health-canada/services/drugs-health-products/compliance-enforcement/good-clinical-practices/guidance-documents/guidance-drugs-clinical-trials-human-subjects-gui-0100.html">clinical trials</a> before they can be authorized for sale in Canada. But in order to make it easier to clearly identify if the drugs are beneficial, these trials only enrol a very selective group of patients. </p>
<p>For example, people who are accepted into these trials need to have a definite diagnosis, they should only be suffering from the disease the drug is intended to treat, they shouldn’t be taking other drugs, they may have to live near the site where the testing is ongoing — and the exclusions go on. </p>
<p>By one estimate, <a href="https://doi.org/10.1176/appi.ajp.159.3.469">out of a potential 346 patients only 29</a> or fewer than 10 per cent, qualified for a trial looking at treating major depression. In addition, <a href="https://deainfo.nci.nih.gov/advisory/ctac/archive/0309/presentations/Williams_030409.pdf">clinical trials often leave out</a> children, the elderly, women, minority groups, people with disabilities and multiple other groups.</p>
<p>Usually <a href="https://www.healthline.com/health/clinical-trial-phases#phase-ii">only 3,000 to 5,000 people</a> are exposed to an experimental drug in clinical trials. The much larger trials conducted for the COVID-19 vaccines, <a href="https://www.nih.gov/news-events/news-releases/peer-reviewed-report-moderna-covid-19-vaccine-publishes">involving 30,000</a> to <a href="https://www.pfizer.com/science/coronavirus/vaccine/about-our-landmark-trial">46,000 people</a>, were an exception to this. </p>
<figure class="align-center ">
<img alt="White pills spilling out of a bottle forming the shape of a question mark against a pink background" src="https://images.theconversation.com/files/524020/original/file-20230503-444-eml4cj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/524020/original/file-20230503-444-eml4cj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/524020/original/file-20230503-444-eml4cj.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/524020/original/file-20230503-444-eml4cj.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/524020/original/file-20230503-444-eml4cj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/524020/original/file-20230503-444-eml4cj.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/524020/original/file-20230503-444-eml4cj.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">When drugs are finally approved, there are still unanswered safety questions, including about how drugs will affect demographic groups who were left out of the trials.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
</figcaption>
</figure>
<p>Previous research has shown that in order to detect rare side-effects, a trial needs to use the <a href="https://blogs.bmj.com/bmjebmspotlight/2017/11/14/rare-adverse-events-clinical-trials-understanding-rule-three/">statistical rule of three</a>: For example, if a side-effect affects one in 1,000 patients, a trial would have to enrol at least 3,000 people (three x 1,000) to have a 95 per cent chance of seeing even a single case. This means that rare safety issues may be missed entirely. </p>
<p>The result is that when drugs are finally approved, there are still unanswered safety questions, including about how drugs will affect demographic groups who were left out of the trials.</p>
<h2>Drug safety programs</h2>
<p>That’s why when regulatory agencies like Health Canada approve a drug, they require the drug company to monitor post-market safety. These programs go by various names; in <a href="https://www.canada.ca/en/health-canada/services/drugs-health-products/reports-publications/medeffect-canada/guidance-document-submission-risk-management-plans-follow-commitments.html">Canada</a> and <a href="https://www.ema.europa.eu/en/human-regulatory/marketing-authorisation/pharmacovigilance/risk-management/risk-management-plans">Europe</a> they are Risk Management Plans (RMP) and in the United States they are <a href="https://www.fda.gov/drugs/drug-safety-and-availability/risk-evaluation-and-mitigation-strategies-rems">Risk Evaluation and Mitigation Strategies</a> (REM). </p>
<p>Canada’s current RMP system has been in place <a href="https://www.canada.ca/en/health-canada/services/drugs-health-products/reports-publications/medeffect-canada/guidance-document-submission-risk-management-plans-follow-commitments.html">since 2009</a>. According to <a href="https://www.canada.ca/en/health-canada/programs/consultation-proposed-agile-regulations-guidance-licensing-drugs-medical-devices/submitting-risk-management-plans.html">Health Canada documents</a>, RMPs are mandatory when there is a significant degree of uncertainty respecting the risks associated with a particular drug or when a drug “presents a serious risk of injury to human health that warrants measures … to reduce the probability or severity of such an injury.”</p>
<p>All new drugs that have never before been sold in Canada in any form, as well as all opioids, require RMPs to help safeguard the public. </p>
<p><a href="https://www.canada.ca/en/health-canada/services/drugs-health-products/reports-publications/medeffect-canada/profile-guidance-document-submission-risk-management-plans-follow-commitments/notice-clarification-drug-manufacturers-sponsors.html">Under these plans</a> companies may have to conduct additional safety studies, set up registries to identify patients who are taking the drug, develop educational materials for health care professionals and/or patients, restrict access to the drug and commit to undertaking a number of other measures.</p>
<p>RMPs are not perfect and won’t resolve all the safety uncertainties about new drugs. <a href="https://doi.org/10.1038/clpt.2014.184">One European study</a> estimated that after five years, only about one in five issues was settled. More definitely needs to be done to monitor post-market safety. </p>
<p>But RMPs are still a significant tool. Issues that remained unresolved in some cases were whether theoretical risks were actually seen in practice and whether there was enough information to determine if long-term data revealed new safety concerns.</p>
<h2>Access to drug monitoring information</h2>
<p>Doctors who prescribe drugs, pharmacists who fill prescriptions, researchers who study drug safety and especially patients who take the drugs all should have a right to know how safety is being monitored. </p>
<p>In the U.S., people can turn to a <a href="https://www.accessdata.fda.gov/scripts/cder/rems/index.cfm">Food and Drug Administration website</a> that lists all the drugs with REMS. There they can read about the goals of the REMS, a summary of the measures included in it, look at the materials that have been developed and how the effectiveness of the REMS plan is going to be assessed. </p>
<p>In European countries like <a href="https://laegemiddelstyrelsen.dk/en/licensing/licensing-of-medicines/medicines-authorised-with-a-summary-of-the-risk-management-plan/">Denmark there is a similar list of drugs</a> with a RMP. Click on a hyperlink and it takes you to a summary of the RMP for the drug in question.</p>
<p>Health Canada currently has no such website, and acknowledges that <a href="https://nlpb.ca/media/Health-Canada_QA-for-HCP_RMP_EN_Updated_2022-07-07.pdf">this is an information gap</a>. Two of <a href="https://www.canada.ca/en/health-canada/programs/consultation-proposed-agile-regulations-guidance-licensing-drugs-medical-devices/submitting-risk-management-plans.html">Health Canada’s stated goals</a> in implementing a system of RMPs are to “support Canadians’ timely access to safe, efficacious and high quality drugs and support ongoing evaluation of information that could have an impact on the benefit-risk profile of health products.” </p>
<p>But without access to current information on specific drugs, Canadians cannot assess those risks for themselves, nor can they evaluate the monitoring program. </p>
<p>On top of this lack of transparency, <a href="https://shpm.info.yorku.ca/files/2020/09/Health-Canada-funding-distribution-2004-2020.pdf">Health Canada spends only one-third as much money and has only one-third as many employees</a> monitoring drug safety compared to the amount of money and the number of people who are involved in approving new drugs.</p>
<p>Since February 2019, Health Canada has been a world leader in <a href="https://www.bmj.com/content/365/bmj.l1825">releasing the information that it used in deciding to approve new drugs</a>. It has a <a href="https://www.canada.ca/en/health-canada/services/drug-health-product-review-approval/submissions-under-review.html?_ga=2.233746589.2014837886.1506726303-1326787507.1398655537#_Submissions_currently_under">website</a> that lists drugs that weren’t approved and what drugs it’s considering for approval. There is a <a href="https://www.ec.gc.ca/ese-ees/default.asp?lang=En&n=B68C1BAF-1">website with RMPs for substances that are harmful</a> to the environment and human health, albeit with data from 2016. </p>
<p>It’s time for Health Canada to do the same for drug RMPs. <a href="https://canadagazette.gc.ca/rp-pr/p1/2022/2022-12-17/html/reg1-eng.html">When Canada’s Food and Drugs Act regulations are amended</a>, transparency for drug RMPs needs to be made mandatory. But Health Canada does not need to wait until then to make this information available to Canadians.</p><img src="https://counter.theconversation.com/content/204787/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>In 2019-2022, Joel Lexchin received payments for writing briefs on the role of promotion in generating prescriptions for two legal firms. He is a member of the Foundation Board of Health Action International and the Board of Canadian Doctors for Medicare. He receives royalties from University of Toronto Press and James Lorimer & Co. Ltd. for books he has written. </span></em></p>Health Canada continues to monitor newly approved drugs to determine if the benefits identified in the pre-market trials hold up to further scrutiny. Canadians need better access to that information.Joel Lexchin, Professor Emeritus of Health Policy and Management, York University, CanadaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2029352023-04-05T12:25:12Z2023-04-05T12:25:12ZOne way to speed up clinical trials: Skip right to the data with electronic medical records<figure><img src="https://images.theconversation.com/files/519333/original/file-20230404-15-mnljji.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2463%2C1216&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">It takes around 17 years for medical research to translate into clinical practice.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/touching-base-with-the-medical-community-royalty-free-image/1167942823">shapecharge/E+ via Getty Images</a></span></figcaption></figure><p>Scientific knowledge, as measured by numbers of papers published, has been estimated to <a href="https://doi.org/10.1057/s41599-021-00903-w">double every 17.3 years</a>. However, it takes an <a href="https://doi.org/10.1258%2Fjrsm.2011.110180">average of about 17 years</a> for health and medical research – going from basic lab studies on cell cultures and animals to clinical trials in people – to result in actual changes patients see in the clinic.</p>
<p>The typical process of medical research is generally <a href="https://theconversation.com/90-of-drugs-fail-clinical-trials-heres-one-way-researchers-can-select-better-drug-candidates-174152">not well equipped</a> to respond effectively to quickly evolving pandemics. This has been especially evident for the COVID-19 pandemic, in part because the virus the causes COVID-19 mutates frequently. Scientists and public health officials are often left <a href="https://theconversation.com/18-months-of-the-covid-19-pandemic-a-retrospective-in-7-charts-166881">continually scrambling</a> to develop and test new treatments to match emerging variants. </p>
<p>Fortunately, scientists may be able to bypass the typical research timeline and study treatments and interventions as they are used in the clinic nearly in real time by leveraging a common source of existing data – electronic medical records, or EMRs.</p>
<p>We are a team composed of an <a href="https://scholar.google.com/citations?user=0BCX1qIAAAAJ&hl=en">epidemiologist</a>, <a href="https://scholar.google.com/citations?user=LNTsvI8AAAAJ&hl=en">pharmacist</a> and <a href="https://profiles.dom.pitt.edu/card/faculty_info.aspx/Marroquin5220">cardiologist</a> at the University of Pittsburgh Medical Center. During the COVID-19 pandemic, we realized the need to quickly study and disseminate accurate information on the most effective treatment approaches, especially for patients at high risk of hospitalization and death. In our <a href="https://doi.org/10.7326/M22-1286">recently published research</a>, we used EMR data to show that early treatment with one or more of five different monoclonal antibodies substantially reduced the risk of hospitalization or death compared with delayed or no treatment. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/519338/original/file-20230404-18-reloqo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Two surgeons reviewing medical records in front of computer screens" src="https://images.theconversation.com/files/519338/original/file-20230404-18-reloqo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/519338/original/file-20230404-18-reloqo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/519338/original/file-20230404-18-reloqo.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/519338/original/file-20230404-18-reloqo.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/519338/original/file-20230404-18-reloqo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/519338/original/file-20230404-18-reloqo.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/519338/original/file-20230404-18-reloqo.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">EMRs contain a wealth of clinical data that could be used for research.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/nurses-plan-surgical-paperwork-royalty-free-image/140175520">Reza Estakhrian/The Image Bank via Getty Images</a></span>
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<h2>Using EMR data for research</h2>
<p>In the U.S., health care systems typically use EMR systems for documenting patient care and for administrative purposes like billing. While data collection is not uniform, these systems typically contain <a href="https://www.cms.gov/medicare/e-health/ehealthrecords">detailed records</a> that can include sociodemographic information, medical history, test results, surgical and other procedures, prescriptions and billing charges.</p>
<p>Unlike <a href="https://worldpopulationreview.com/country-rankings/countries-with-single-payer">single-payer health care systems</a> that integrate data into a single EMR system, such as in the U.K. and in Scandinavian countries, many large health care systems in the U.S. collect patient data using <a href="https://www.definitivehc.com/blog/most-common-inpatient-ehr-systems">multiple EMR systems</a>. </p>
<p>Having multiple EMR systems adds a layer of complexity to using such data to conduct scientific research. To address this, the University of Pittsburgh Medical Center developed and maintains a clinical data warehouse that compiles and harmonizes data across the seven different EMR systems its 40 hospitals and outpatient clinics use.</p>
<h2>Emulating clinical trials</h2>
<p><a href="https://doi.org/10.1007%2Fs00392-016-1025-6">Using EMR data for research</a> is not new. More recently, researchers have been looking into ways to use these large health data systems to <a href="https://doi.org/10.1093/aje/kwv254">emulate randomized controlled trials</a>, which are considered the gold standard study design yet are often costly and take years to complete.</p>
<p>Using this emulation framework, our team used the EMR data infrastructure at our institution to <a href="https://doi.org/10.7326/M22-1286">evaluate five different monoclonal antibodies</a> for which the Food and Drug Administration granted emergency use authorization to treat COVID-19. Monoclonal antibodies are human-made proteins designed to prevent a pathogen – in this case the virus that causes COVID-19 – from entering human cells, replicating and causing serious illness. Initially the authorizations were based on clinical trial data. But as the virus mutated, subsequent evaluations based on cell culture studies suggested a loss of effectiveness. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/519339/original/file-20230404-473-eyylv1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Close-up of health care provider accessing medical record on tablet" src="https://images.theconversation.com/files/519339/original/file-20230404-473-eyylv1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/519339/original/file-20230404-473-eyylv1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/519339/original/file-20230404-473-eyylv1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/519339/original/file-20230404-473-eyylv1.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/519339/original/file-20230404-473-eyylv1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/519339/original/file-20230404-473-eyylv1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/519339/original/file-20230404-473-eyylv1.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">EMR data could be used to confirm that the results of cell culture studies would apply in the clinic.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/nurse-using-portable-computer-royalty-free-image/104509052">Solskin/DigitalVision via Getty Images</a></span>
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<p>We wanted to confirm that the findings of cell-based studies applied to actual patients. So we evaluated anonymous clinical data from 2,571 patients treated with these monoclonal antibodies within two days of COVID-19 infection, matching them with data from 5,135 patients with COVID-19 who were eligible for but either did not receive these treatments or received them three or more days after infection. </p>
<p>We found that overall, people who received monoclonal antibodies within two days of a positive COVID-19 test reduced their risk of hospitalization or death by 39% compared with those who did not receive the treatment or received delayed treatment. In addition, patients with compromised immune systems reduced their risk of hospitalization or death by 55%, regardless of their age.</p>
<p>Our near-real-time analysis of COVID-19 patients treated with monoclonal antibodies during the pandemic confirmed the findings of the cell culture studies. Our findings suggest that by using data in this way, researchers may be able to evaluate treatments in times of urgency without having to perform clinical trials.</p>
<h2>Appropriate EMR data use</h2>
<p>Many health care institutions have EMR systems that researchers can harness to rapidly answer important research questions as they arise. However, because this clinical data is not specifically collected for research purposes, researchers need to <a href="https://doi.org/10.1146/annurev-publhealth-032315-021353">carefully design their studies</a> and use rigorous data validation and analysis. They also need to take great care to harmonize data from different EMR systems, select appropriate patient samples and minimize all sources of potential bias. </p>
<p>New pandemics and significant public health challenges are likely to emerge abruptly and in unpredictable ways. Given the treasure trove of data routinely collected across U.S. health care systems, we believe that careful use of these data can help answer urgent health questions in ways that are representative of who’s actually receiving care.</p><img src="https://counter.theconversation.com/content/202935/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Erin McCreary has served on scientific advisory boards for Shionogi, Inc and Merck.</span></em></p><p class="fine-print"><em><span>Kevin Kip and Oscar Marroquin do not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>In health care crises, researchers can avoid waiting for clinical trial results by using data from health care systems to analyze the effectiveness of treatments for COVID-19 and other illnesses.Kevin Kip, Vice President of Clinical Analytics, University of PittsburghErin McCreary, Clinical Assistant Professor of Medicine, University of PittsburghOscar Marroquin, Associate Professor of Medicine, Epidemiology and Clinical and Translational Science, University of PittsburghLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1982332023-02-26T19:06:02Z2023-02-26T19:06:02ZIs there a vaccine for RSV or respiratory syncytial virus? After almost 60 years, several come at once<figure><img src="https://images.theconversation.com/files/510804/original/file-20230217-22-p39gna.jpg?ixlib=rb-1.1.0&rect=1%2C4%2C997%2C556&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/close-asian-little-baby-boy-treated-1589743531">Shutterstock</a></span></figcaption></figure><p>You might not have heard of respiratory syncytial virus, or RSV. But it caused more than <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)00478-0/fulltext">100,000 global deaths</a> in 2019, making it a leading cause of death in children under one year old.</p>
<p>In Australia, child deaths are thankfully <a href="https://pubmed.ncbi.nlm.nih.gov/34845151/">rare</a>. But infection sends thousands to hospital each year, particularly <a href="https://www.mja.com.au/journal/2019/210/10/respiratory-syncytial-virus-associated-hospitalisations-australia-2006-2015">babies and young children</a>.</p>
<p>So for kids, this virus is a very big deal. And despite almost 60 years of research, there are no licensed vaccines to prevent it.</p>
<p>That may change soon. We’ve recently had results of late-stage clinical trials of RSV vaccines from <a href="https://www.statnews.com/2023/01/17/moderna-says-rsv-vaccine-worked-setting-stage-for-competition-with-gsk-and-pfizer/">Pfizer, Moderna and GSK</a>. These vaccines are being assessed (or will be shortly) for regulatory approval in the United States.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1627678804960497664"}"></div></p>
<p>However, these trials were conducted in adults and pregnant women, not children. So we still have a way to go before RSV vaccines are tested in children, shown to be safe and effective, are approved for use, then become widely available.</p>
<p>Here’s why it’s taken so long to develop a RSV vaccine and what we can expect next.</p>
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<em>
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Read more:
<a href="https://theconversation.com/rsv-experts-explain-why-rates-of-this-virus-are-surging-this-year-194403">RSV: experts explain why rates of this virus are surging this year</a>
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<h2>What is RSV?</h2>
<p>RSV is a contagious virus causing respiratory infections in both adults and children.</p>
<p>The virus is transmitted from person to person by droplets when someone coughs or sneezes, or by touching their nose or eyes after touching contaminated surfaces.</p>
<p>Infections usually surge in winter, causing symptoms such as a runny nose, sneezing, sore throat, fever, headache and cough. Adults and children can be hospitalised with RSV and its complications, which include pneumonia and <a href="https://www.rch.org.au/kidsinfo/fact_sheets/Bronchiolitis/">bronchiolitis</a>.</p>
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<em>
<strong>
Read more:
<a href="https://theconversation.com/rsv-faq-what-is-rsv-who-is-at-risk-when-should-i-seek-emergency-care-for-my-child-195292">RSV FAQ: What is RSV? Who is at risk? When should I seek emergency care for my child?</a>
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<h2>We’ve had a few setbacks</h2>
<p>The <a href="https://journals.asm.org/doi/10.1128/CVI.00609-15">first RSV vaccine</a> was given to infants and children in the mid-1960s. </p>
<p>Although this inactivated vaccine (composed of dead RSV particles) seemed to be well tolerated, it later caused a rare side effect called vaccine-enhanced disease. This is where the vaccine caused more serious RSV symptoms when infants and toddlers caught the virus, instead of protecting them.</p>
<p>This was almost 60 years ago, and the science of vaccine development has come a long way. Even though scientists later found new vaccine strategies, this disaster has unfortunately slowed down RSV vaccine research and development.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/randomised-control-trials-what-makes-them-the-gold-standard-in-medical-research-78913">Randomised control trials: what makes them the gold standard in medical research?</a>
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<hr>
<h2>Newer technologies, fresh hope</h2>
<p>Advances in what we know about the virus, and newer vaccine technologies, mean researchers are now more optimistic about the prospect of a RSV vaccine.</p>
<p>Ten years ago, <a href="https://www.science.org/doi/10.1126/science.1234914">scientists identified</a> the structure of the RSV viral protein it uses to attach and enter human host cells. This allowed scientists to change strategies and develop protein-based RSV vaccines.</p>
<p>Protein-based vaccines consist of injecting a purified protein from the target virus that stimulates the immune cells. This technology is used in many existing vaccines, such as those for hepatitis B and pertussis (whooping cough).</p>
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<p>But it’s not been plain sailing for protein-based vaccines either.</p>
<p>In 2019, Novavax <a href="https://ir.novavax.com/2019-02-28-Novavax-Announces-Topline-Results-from-Phase-3-PrepareTM-Trial-of-ResVax-TM-for-Prevention-of-RSV-Disease-in-Infants-via-Maternal-Immunization">announced</a> its prototype protein-based RSV vaccine (ResVax) failed to prevent “medically significant” RSV in babies born to mothers who had been given the vaccine as part of a late-stage clinical trial.</p>
<p>Although the vaccine was shown to be safe, and protected babies from severe RSV, including hospitalisations, the vaccine has not yet made it to market, and further clinical trials <a href="https://www.precisionvaccinations.com/vaccines/resvax-rsv-vaccine">are ongoing</a>.</p>
<p>In recent years, we’ve seen another major technology development – mRNA vaccines. These have proved effective and robust during the COVID pandemic. </p>
<p>These mRNA vaccines involve injecting the information required for the human host cells to produce the viral protein, to later stimulate immune cells.</p>
<p>The front-runner RSV candidate vaccines – from GSK, Pfizer and Moderna – are either protein-based or use mRNA technology.</p>
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<strong>
Read more:
<a href="https://theconversation.com/the-fascinating-history-of-clinical-trials-139666">The fascinating history of clinical trials</a>
</strong>
</em>
</p>
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<h2>The GSK vaccines</h2>
<p>GSK is going with protein-based technology for two of its candidate RSV vaccines.</p>
<p>One (known as RSVPreF3 OA), has had good results in late-stage clinical trials in adults 60 years or older, with data published <a href="https://www.nejm.org/doi/10.1056/NEJMoa2209604">in recent weeks</a>. The US Food and Drug Administration (FDA) <a href="https://www.gsk.com/en-gb/media/press-releases/gsk-s-rsv-oa-vaccine-candidate-granted-priority-review-by-us-fda/">is reviewing</a> the vaccine, with results expected in May.</p>
<p>Another of GSK’s candidate RSV vaccines (GSK3888550A, RSVPreF3) is taking a different approach. The idea is to vaccinate pregnant women to confer immunity to the unborn baby.</p>
<p>Results of late-stage trials in healthy pregnant women aged 18-49 years are <a href="https://www.gsk.com/en-gb/media/press-releases/gsk-starts-phase-3-study-of-rsv-maternal-candidate-vaccine/">set to report in 2024</a>. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9200160/">Earlier studies</a> in non-pregnant women showed the vaccine was well tolerated and activated a good immune response.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/511905/original/file-20230223-24-5r593v.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Pregnant Muslim woman clutching belly looking at phone in hand in front of window" src="https://images.theconversation.com/files/511905/original/file-20230223-24-5r593v.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/511905/original/file-20230223-24-5r593v.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/511905/original/file-20230223-24-5r593v.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/511905/original/file-20230223-24-5r593v.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/511905/original/file-20230223-24-5r593v.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/511905/original/file-20230223-24-5r593v.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/511905/original/file-20230223-24-5r593v.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Some candidate RSV vaccines are given to pregnant women to protect their babies.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/young-pregnant-arab-woman-hijab-using-1407599552">Shutterstock</a></span>
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<h2>The Pfizer vaccine</h2>
<p>Pfizer has also gone with a protein-based RSV vaccine (RSVpreF). But this time it’s a bivalent vaccine. It contains proteins to stimulate immune protection against two types of RSV – RSV A and B. Again, the idea again is to vaccinate pregnant women to immunise their babies in the womb.</p>
<p>In November 2022, Pfizer <a href="https://www.pfizer.com/news/press-release/press-release-detail/pfizer-announces-positive-top-line-data-phase-3-global">announced</a> interim results of its <a href="https://clinicaltrials.gov/ct2/show/NCT04424316?term=RSVpreF+pfizer&phase=2&draw=2&rank=2">late-stage clinical trial</a> showing 81.8% efficacy in protecting against severe disease in babies (one to 90 days old) of vaccinated pregnant women. Over time, that immunity decreased.</p>
<p>Final clinical trial results are expected <a href="https://www.pfizer.com/news/press-release/press-release-detail/us-fda-accepts-biologics-license-application-pfizers">any day now</a>, and the vaccine is being submitted to the FDA for priority review, with a result expected in August.</p>
<h2>The Moderna vaccine</h2>
<p>Moderna is using mRNA technology for its candidate RSV vaccine (called mRNA-1345). It uses similar technology to its COVID mRNA vaccines.</p>
<p>It has been tested in <a href="https://clinicaltrials.gov/ct2/results?term=mRNA-1345&age_v=&gndr=&type=&rslt=&Search=Apply">late-stage clinical trials</a> in people over the age of 60. The <a href="https://investors.modernatx.com/news/news-details/2023/Moderna-Announces-mRNA-1345-an-Investigational-Respiratory-Syncytial-Virus-RSV-Vaccine-Has-Met-Primary-Efficacy-Endpoints-in-Phase-3-Trial-in-Older-Adults/default.aspx">company announced</a> earlier this year that the vaccine was mostly well tolerated and had an efficacy of 83.7%.</p>
<p>The company is set to make a <a href="https://investors.modernatx.com/news/news-details/2023/Moderna-Granted-FDA-Breakthrough-Therapy-Designation-for-mRNA-1345-An-Investigational-Respiratory-Syncytial-Virus-RSV-Vaccine-Candidate/default.aspx">full submission</a> to the FDA in the first half of 2023.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/3-mrna-vaccines-researchers-are-working-on-that-arent-covid-157858">3 mRNA vaccines researchers are working on (that aren't COVID)</a>
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</em>
</p>
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<h2>Several hurdles ahead</h2>
<p>Another candidate vaccine, <a href="https://www.janssen.com/janssen-announces-respiratory-syncytial-virus-rsv-adult-vaccine-candidate-maintains-high-efficacy">from Janssen</a>, uses a different type of technology (adenovirus vector technology), and is not so far advanced through clinical trials as the others. But it has shown <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9417128/">promising preliminary results</a> <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2207566?query=recirc_curatedRelated_article">to date</a> in adults.</p>
<p>And that’s the sticking point with all the RSV vaccines mentioned. They’ve only been tested in adults. To have the greatest impact, the vaccines must also be evaluated in young children and infants. </p>
<p>The biggest question is what age should a baby be vaccinated against RSV once it loses the immunity from its mother?</p>
<p>While we wait for RSV vaccines, the best way of slowing the spread of this viral illness are measures we’ve become used to during COVID. If you or your children have RSV, make sure you wear a mask, wash your hands and maintain your distance from others.</p>
<hr>
<p><em>We would like to thank Masters (Doctor of Medicine) student Chloe Scott from Griffith University for her critical review and assistance with this article.</em></p><img src="https://counter.theconversation.com/content/198233/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Lara Herrero receives funding from NHMRC
</span></em></p><p class="fine-print"><em><span>Wesley Freppel does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Here’s why it’s taken so long to develop a vaccine for respiratory syncytial virus and what we can expect next.Lara Herrero, Research Leader in Virology and Infectious Disease, Griffith UniversityWesley Freppel, Research Fellow, Institute for Glycomics, Griffith UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1994872023-02-09T16:31:46Z2023-02-09T16:31:46ZLack of diversity in clinical trials is leaving women and patients of color behind and harming the future of medicine – Podcast<figure><img src="https://images.theconversation.com/files/509021/original/file-20230208-15-u9tmxa.jpg?ixlib=rb-1.1.0&rect=73%2C196%2C2652%2C1495&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Most clinical trials overrepresent young white males. </span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/illustration-of-a-group-of-people-wearing-royalty-free-illustration/1267173084?phrase=medicine%20diverse&adppopup=true">Andresr/Digital Vision via Getty Images</a></span></figcaption></figure><p>Its a great day when you find a piece of clothing that fits perfectly. A good shirt, the right pair of shoes or a well-cut dress is comfortable, looks nice and feels like it was made just for you. Now imagine a world where every shirt was the same size, every shoe was the same design and there weren’t even differences between the cut of men’s and women’s clothing. Getting dressed in the morning would be clunky, and clothes would be uncomfortable. In other words, one size does not fit all.</p>
<p>Yet, this lack of bespoke options is more or less the reality of medicine today. Despite the many biological differences between people of different genders, races, ages and life histories, chances are that if two people walk into a doctor’s office with the same symptoms, they are going to get roughly the same treatment. As you can imagine, a whole range of treatments – from drugs to testing – could be much more effective if they were designed to work with many different kinds of bodies, not just some abstract, generic human. </p>
<p>In this episode of <a href="https://theconversation.com/uk/topics/the-conversation-weekly-98901">The Conversation Weekly</a> podcast, we speak to three researchers who are looking at ways to make medicine better suited to you. It starts with simply making sure that clinical trial participants look like the actual population of patients a drug is meant to treat. And as we explore in this episode, in the future, precision medicine could help each person get <a href="https://theconversation.com/how-to-use-precision-medicine-to-personalize-covid-19-treatment-according-to-the-patients-genes-142142">medical care that is tailored to their own biology</a>, just like a custom shirt.</p>
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<p><iframe id="tc-infographic-561" class="tc-infographic" height="100" src="https://cdn.theconversation.com/infographics/561/4fbbd099d631750693d02bac632430b71b37cd5f/site/index.html" width="100%" style="border: none" frameborder="0"></iframe></p>
<p>In 1977, the U.S. Food and Drug Administration released a set of policy guidelines that explicitly banned “women of childbearing age” from <a href="https://www.womenshealth.gov/30-achievements/04">participating in clinical trials</a> of new drugs. Though done out of a fear of causing birth defects, the result was that for more than a decade, new drugs were going to market with little information about how they might affect women. Due to systemic biases, research has found that people of color are routinely underrepresented in clinical trials today, too. For the most part, medical research has been done on <a href="https://www.verywellmind.com/racial-disparities-clinical-trials-5114529">healthy, young and middle-aged men of European descent</a>.</p>
<p>This is a problem in the U.S, according to <a href="https://scholar.google.com/citations?user=wd-fP1EAAAAJ&hl=en&oi=sra">Jennifer Miller, a bioethicist at Yale University</a>. “If you’re not included in the trial, this raises questions about whether the drug’s safety and efficacy information applies to patients like you,” she says.</p>
<p>In recent years, a number of researchers across the U.S. – like <a href="https://www.msm.edu/about_us/FacultyDirectory/Medicine/JuliaLiu/index.php">Julia Liu</a>, a professor of medicine at Morehouse School of Medicine – have been trying to figure out ways to improve the diversity of clinical trial participants. Part of the problem, Liu explains, stems from a myth within medicine that Black people don’t like to participate in medical research due to the history of abuses the U.S. medical system has inflicted on African Americans, like the infamous Tuskegee Experiment. But when Liu began running her own trials on a new prostate cancer test at a hospital that serves a majority-African American population, she <a href="https://theconversation.com/yes-black-patients-do-want-to-help-with-medical-research-here-are-ways-to-overcome-the-barriers-that-keep-clinical-trials-from-recruiting-diverse-populations-185337">found quite the opposite</a>. </p>
<p>“It turned out that just about everyone I asked said, ‘I would love to do that,’” explains Liu. “Half of the eligible patients agreed.” Black patients were just as eager to participate in research as white patients, and according to Liu, a big reason for lack of diversity in clinical trials is that they are mostly run out research hospitals in wealthier, whiter cities, not out of hospitals with diverse patients.</p>
<p>According to Miller’s research, only <a href="https://doi.org/10.1001/jamanetworkopen.2021.7063">4% of trials in recent years used a representative population</a>, but she is optimistic. Women are now much better represented in trials, and with regard to equal racial representation, “that 4% does tell us is that it’s possible to get this right.” </p>
<p>Efforts like those of Liu and Miller are similar to how companies make shirts in different sizes to better fit different bodies. Once researchers do this work, health care providers can choose which drugs are likely to work better and have fewer risks for different patients based on their individual demographics. </p>
<p>Better representation is a start, but anyone who has been lucky enough to get custom-made clothing knows just how well a shirt can really fit. This is the idea behind precision medicine. According to <a href="https://profiles.ucsf.edu/Keith.Yamamoto">Keith Yamamoto</a>, who directs the precision medicine center at the University of California, San Francisco, in the U.S., in the near future it may be possible to “achieve an understanding of health and disease to the extent that we could give advice to Dan Merino, not just people like Dan.” </p>
<p>This approach to medicine would incorporate basic biology, a person’s individual genetics and life history and the wealth of all existing medical research – precision medicine is an information and computation problem. To work, it needs good data – the representative data missing from clinical trials. As Yamamoto said, “Precision medicine will fail if we don’t address those issues in a head-on way.”</p>
<p>Listen to the full episode of <a href="https://theconversation.com/uk/topics/the-conversation-weekly-98901">The Conversation Weekly</a> to find out more. </p>
<hr>
<p>This episode of The Conversation Weekly was produced by Katie Flood. It was written by Katie Flood and Daniel Merino. Sound design is by Eloise Stevens, and the theme music is by Neeta Sarl.</p>
<p>You can find us on Twitter <a href="https://twitter.com/TC_Audio">@TC_Audio</a>, on Instagram at <a href="https://www.instagram.com/theconversationdotcom/">@theconversationdotcom</a> or <a href="mailto:podcast@theconversation.com">via email</a>. You can also sign up for The Conversation’s <a href="https://theconversation.com/newsletter">free emails here</a>. A transcript of this episode will be available soon. </p>
<p>Listen to The Conversation Weekly via any of the apps listed above, download it directly via our <a href="https://feeds.acast.com/public/shows/60087127b9687759d637bade">RSS feed</a> or find out <a href="https://theconversation.com/how-to-listen-to-the-conversations-podcasts-154131">how else to listen here</a>.</p><img src="https://counter.theconversation.com/content/199487/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jennifer Miller has served on the advisory board for Alexion Pharmaceuticals and directs the Good Pharma Scorecard. She receives funding from from the FDA, NIH and Arnold Ventures and sits on the board of the nonprofit Bioethics International.
Keith Yamamoto sits on the scientific advisory board of Mate Bioservices. He is the President of the American Association for the Advancement of Science (AAAS), chair of the Coalition for the Life Sciences, co-chair of the NASEM Roundtable on Aligning Incentives for Open Science and of the Science and Technology Action Committee, vice chair of the California Initiative to Advance Precision Medicine Advisory Council. He is a member of the Boards of Directors of the Public Library of Science, Research! America and Rapid Science, the Governing Board of the California Institute for Regenerative Medicine, the Board of Counselors for the Radiation Effects Research Foundation, the Advisory Board for Lawrence Berkeley National Laboratory and the Council of EBRC. </span></em></p><p class="fine-print"><em><span>Julia Liu does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Medicine works better when the treatments are tailored to fit each individual person’s biology and history. A first step is increasing diversity in clinical trials, but the end goal is precision medicine.Daniel Merino, Associate Science Editor & Co-Host of The Conversation Weekly Podcast, The ConversationNehal El-Hadi, Science + Technology Editor & Co-Host of The Conversation Weekly Podcast, The ConversationLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1925902022-10-26T12:29:17Z2022-10-26T12:29:17ZDrugs – 4 essential reads on how they’re made, how they work and how context can make poison a medicine<figure><img src="https://images.theconversation.com/files/489907/original/file-20221016-16-3m74ut.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2121%2C1412&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Constraining drugs to a single function in the body may be limiting their full potential.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/red-and-white-pharma-pill-pattern-on-pastel-blue-royalty-free-image/1288588418">Israel Sebastian/Moment via Getty Images</a></span></figcaption></figure><p>Pandemics and disease outbreaks put a spotlight on the hurdles researchers face to get a drug on the shelves. From finding prospective drug candidates to balancing time and financial pressures with ensuring safety and efficacy, there are many aspects of drug development that determine whether a treatment ever makes it out of the lab. </p>
<p>Broadening the definition of “medicine” and where it can be found, however, could help expand the therapeutic options available for both researchers and patients.</p>
<p>Here are four facets of how drugs are developed and how they work in the body, drawn from stories in The Conversation’s archive.</p>
<h2>1. Matching drug to target</h2>
<p>The most effective drugs are, in a sense, the product of good matchmaking – they bind to a specific disease-causing receptor in the body, elicit a desired effect and ideally ignore healthy parts of the body.</p>
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<figcaption><span class="caption">Factors such as your age, genetics and diet can affect how well your body processes a drug.</span></figcaption>
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<p>Drugs <a href="https://theconversation.com/how-do-drugs-know-where-to-go-in-the-body-a-pharmaceutical-scientist-explains-why-some-medications-are-swallowed-while-others-are-injected-182488">travel through the bloodstream</a> to reach their targets. Because of this, most drugs circulate throughout the body and can bind to unintended sites, potentially causing undesired side effects.</p>
<p>Researchers can increase the precision and effectiveness of a drug by designing different ways to take it. An inhaler, for example, delivers a drug directly to the lungs without its having to travel through the rest of the body to get there.</p>
<p>Whether patients take drugs as prescribed is also essential to ensuring the right dose gets to where it needs to be often enough to have a desired effect. “Even with all the science that goes into understanding a disease well enough to develop an effective drug, it is often up to the patient to make it all work as designed,” writes pharmaceutical scientist <a href="https://www.researchgate.net/profile/Thomas-Anchordoquy">Tom Anchordoquy</a> of the University of Colorado Anschutz.</p>
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Read more:
<a href="https://theconversation.com/how-do-drugs-know-where-to-go-in-the-body-a-pharmaceutical-scientist-explains-why-some-medications-are-swallowed-while-others-are-injected-182488">How do drugs know where to go in the body? A pharmaceutical scientist explains why some medications are swallowed while others are injected</a>
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<h2>2. Searching for drug candidates</h2>
<p>Researchers have discovered a number of drugs by chance, including <a href="https://www.pbs.org/newshour/health/the-real-story-behind-the-worlds-first-antibiotic">penicillin</a> for bacterial infections, <a href="https://www.bbc.com/future/article/20200928-how-the-first-vaccine-was-born">vaccines for smallpox</a> and <a href="https://doi.org/10.1038/nrcardio.2017.172">warfarin</a> for blood clots. While serendipity still plays a role in modern drug discovery, most drug developers take a systematic approach.</p>
<p>Scientists typically start by identifying a particular molecular target, usually receptors that trigger a specific response in the body. Then, they look for chemical compounds that react with that target. Technology called <a href="https://theconversation.com/discovering-new-drugs-is-a-long-and-expensive-process-chemical-compounds-that-dupe-screening-tools-make-it-even-harder-175972">high-throughput screening</a> allows researchers to quickly test thousands of potential drug candidates at once. Compounds that match screening criteria advance to further development and refinement. Once optimized for their intended use, compounds go on to safety and efficacy testing in animals and people.</p>
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<figcaption><span class="caption">Scientists have been isolating medicinal compounds from natural products for centuries.</span></figcaption>
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<p>One way to ease the search for optimal drug candidates is to work with compounds that are already optimized to work in living beings. <a href="https://theconversation.com/nature-is-the-worlds-original-pharmacy-returning-to-medicines-roots-could-help-fill-drug-discovery-gaps-176963">Natural products</a>, derived from organisms like microbes, fungi, plants and animals, share similar structures and functions across species. Though not without their own development challenges, they could aid the search for related compounds that work in people.</p>
<p>“There are thousands of microorganisms in the ocean left to explore as potential sources of drug candidates, not to mention all the ones on land,” writes medical chemist <a href="https://scholar.google.com/citations?user=8_T1ueYAAAAJ&hl=en">Ashu Tripathi</a> of the University of Michigan. “In the search for new drugs to combat antibiotic resistance, natural products may still be the way to go.”</p>
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<em>
<strong>
Read more:
<a href="https://theconversation.com/nature-is-the-worlds-original-pharmacy-returning-to-medicines-roots-could-help-fill-drug-discovery-gaps-176963">Nature is the world's original pharmacy – returning to medicine's roots could help fill drug discovery gaps</a>
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<h2>3. A drug by any other name may be just as effective</h2>
<p>Existing drugs can find a second (or third, fourth and fifth) life through repurposing. </p>
<p>Most drugs <a href="https://theconversation.com/many-medications-affect-more-than-one-target-in-the-body-some-drug-designers-are-embracing-the-side-effects-that-had-been-seen-as-a-drawback-184922">have many functions</a> beyond what researchers originally designed them to do. While this multifunctionality is often the cause of unwanted side effects, sometimes these results are exactly what’s needed to treat a completely unrelated condition.</p>
<p>Sildenafil, for example, failed to treat severe chest pain from coronary artery disease, but proved to be potent at inducing erections as Viagra. Similarly, thalidomide, a compound that caused birth defects in thousands of infants around the world as a morning sickness drug, found redemption as a cancer treatment. </p>
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<figcaption><span class="caption">While thalidomide was disastrous for morning sickness, it has proved effective for other diseases.</span></figcaption>
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<p>Because drugs inherently have more than one function in the body, <a href="https://theconversation.com/repurposing-generic-drugs-can-reduce-time-and-cost-to-develop-new-treatments-but-low-profitability-remains-a-barrier-174874">repurposing existing drugs</a> can help fill a gap where pharmaceutical companies and other developers cannot or will not. <a href="https://scholar.google.com/citations?user=iDKZaA4AAAAJ&hl=en">Gregory Way</a>, a researcher at the University of Colorado Anschutz, uses artificial intelligence to predict the various effects a drug can have and believes that this lack of specificity is something to explore rather than eliminate. Instead of trying to home in on one specific target, he suggests that scientists “embrace the complexity of biology and try to leverage the multifaceted effects drugs can offer.”</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/many-medications-affect-more-than-one-target-in-the-body-some-drug-designers-are-embracing-the-side-effects-that-had-been-seen-as-a-drawback-184922">Many medications affect more than one target in the body – some drug designers are embracing the 'side effects' that had been seen as a drawback</a>
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<h2>4. Poison as medicine</h2>
<p>If so many drugs can have toxic effects in the body, be it through side effects or taking the wrong dose or for the wrong condition, what determines whether a drug is a “medicine” or a “poison”?</p>
<p>Biomedical scientists evaluate drugs based on their active ingredient, or a specific compound that has a specific effect in the body. But reducing medicines to just a single molecule ignores another important factor that determines whether a drug is therapeutic – the context in which it is used. Opioids treat intractable pain but can lead to debilitating and lethal addiction when improperly administered. Chemotherapy kills tumors but causes collateral damage to healthy tissues in the process.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/410863/original/file-20210712-27-cocyqt.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Historical illustration of a plant with leaves and large tubers" src="https://images.theconversation.com/files/410863/original/file-20210712-27-cocyqt.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/410863/original/file-20210712-27-cocyqt.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=796&fit=crop&dpr=1 600w, https://images.theconversation.com/files/410863/original/file-20210712-27-cocyqt.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=796&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/410863/original/file-20210712-27-cocyqt.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=796&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/410863/original/file-20210712-27-cocyqt.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1000&fit=crop&dpr=1 754w, https://images.theconversation.com/files/410863/original/file-20210712-27-cocyqt.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1000&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/410863/original/file-20210712-27-cocyqt.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1000&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Aconite is a poisonous herb that was used to treat cold symptoms in ancient Chinese medical practice.</span>
<span class="attribution"><a class="source" href="https://www.loc.gov/resource/lcnclscd.2012402216.1A010/?sp=3">Library of Congress, Asian Division, Chinese Rare Books</a></span>
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</figure>
<p>Another pharmaceutical paradigm, <a href="https://theconversation.com/poison-or-cure-traditional-chinese-medicine-shows-that-context-can-make-all-the-difference-163337">traditional Chinese medicine</a>, has historically acknowledged the malleability of drugs through the use of poisons as therapeutics. </p>
<p><a href="https://scholar.google.com/citations?user=4q0hYSwAAAAJ&hl=en">Yan Liu</a>, a medical historian at University of Buffalo who studies this practice, notes that ancient texts did not distinguish between poisons and nonpoisons – rather, Chinese doctors examined drugs based on a continuum of potency, or ability to harm and heal. They used different processing and administration techniques to adjust the potency of poisons. They also took a personalized approach to treatment, aware that each drug works differently based on a number of different individual factors.</p>
<p>“The paradox of healing with poisons in traditional Chinese medicine reveals a key message: There is no essential, absolute or unchanging core that characterizes a medicine,” Liu writes. “Instead, the effect of any given drug is always relational – it is contingent on how the drug is used, how it interacts with a particular body and its intended effects.”</p>
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Read more:
<a href="https://theconversation.com/poison-or-cure-traditional-chinese-medicine-shows-that-context-can-make-all-the-difference-163337">Poison or cure? Traditional Chinese medicine shows that context can make all the difference</a>
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<p><em>Editor’s note: This story is a roundup of articles from The Conversation’s archives.</em></p><img src="https://counter.theconversation.com/content/192590/count.gif" alt="The Conversation" width="1" height="1" />
Despite technological advancements, many challenges remain in getting a drug from lab to pharmacy shelf. Reframing what is a “medicine” could expand treatment options for researchers and patients.Vivian Lam, Associate Health and Biomedicine EditorLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1853372022-09-08T12:32:16Z2022-09-08T12:32:16ZYes, Black patients do want to help with medical research – here are ways to overcome the barriers that keep clinical trials from recruiting diverse populations<figure><img src="https://images.theconversation.com/files/483100/original/file-20220906-4642-3md5uc.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2121%2C1412&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Creating a safe space for patients to ask questions and provide fully informed consent could help increase clinical trial recruitment.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/ethnic-woman-in-medical-consultation-with-female-royalty-free-image/1168998661">FatCamera/E+ via Getty Images</a></span></figcaption></figure><p>Clinical trial participants are <a href="https://doi.org/10.1001/jamanetworkopen.2021.11516">predominantly white</a>. Despite Black and Hispanic people respectively making up 12% and 16% of the U.S. population in 2011, together they made up <a href="https://www.fda.gov/science-research/womens-health-research/dialogues-diversifying-clinical-trials">only 6% of clinical trial participants</a> overall that year. </p>
<p><a href="https://www.nimhd.nih.gov/resources/understanding-health-disparities/diversity-and-inclusion-in-clinical-trials.html">Clinical trials that are representative</a> of all patients are essential to ensure that treatments are effective for everyone. Drugs work differently for each person <a href="https://theconversation.com/why-prescription-drugs-can-work-differently-for-different-people-168645">based on different factors</a>. Including diverse patient populations in clinical trials makes sure these factors are accounted for. But the <a href="https://doi.org/10.1016/j.cpcardiol.2018.11.002">perception that recruiting white patients</a> is easier, less time-consuming and more cost-efficient than recruiting underrepresented or underserved patients contributes to health disparities seen today.</p>
<p>We are <a href="https://www.researchgate.net/profile/Julia-Liu-9">gastroenterology researchers</a> at Morehouse School of Medicine who run clinical trials and study ways to improve participant diversity. Identifying and addressing the barriers to enrolling in research that patients face can not only increase participation, but can also lead to better patient care.</p>
<h2>The problem of access</h2>
<p>Barriers to clinical trial participation start with a <a href="https://doi.org/10.1177%2F107327481602300404">lack of access to trials</a>. </p>
<p>Clinical trials have specific eligibility criteria, and may require a number of study-related visits to the hospital where they’re conducted. But underserved and underrepresented populations often aren’t seen in practices that recruit patients for clinical trials. </p>
<p>Typically, clinical trials are designed by research-focused physicians working in <a href="https://www.cancertodaymag.org/summer2017/a-new-look-for-clinical-trials-diversity/">urban medical centers</a>. The majority of Black and Hispanic patients have <a href="https://doi.org/10.1377/hlthaff.2021.01409">limited access to the health care system</a> as a whole, and the centers that serve them often do not have the research infrastructure or resources to run clinical trials.</p>
<p>While researchers have made attempts to <a href="https://doi.org/10.1093/ibd/izac124">increase the diversity of clinical trial participants</a>, <a href="https://doi.org/10.1016/j.cpcardiol.2018.11.002">misconceptions and biases</a> within the medical community about underrepresented populations limit these outreach efforts. For example, <a href="https://doi.org/10.1353%2Fhpu.2006.0126">beliefs persist</a> that Black patients aren’t willing to participate in research studies and are noncompliant and mistrustful due to historical abuse from medical researchers, such as in the <a href="https://doi.org/10.1093%2Fqje%2Fqjx029">Tuskegee syphilis study</a>.</p>
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<iframe width="440" height="260" src="https://www.youtube.com/embed/7qAld9bGwlA?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Limited access to clinical trials is both a product of and driving factor behind health disparities.</span></figcaption>
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<h2>A colon cancer case study</h2>
<p>One example of how lack of diversity in clinical trial participation can lead to poor health for patients is outcomes for <a href="https://www.cdc.gov/ibd/what-is-IBD.htm">inflammatory bowel disease</a>. IBD is a chronic condition that comes in two forms, ulcerative colitis and Crohn’s disease. Patients with IBD have an <a href="https://doi.org/10.3748%2Fwjg.v20.i29.9872">increased risk of developing colorectal cancer</a>.</p>
<p>Black patients account for 75% of IBD cases at Morehouse School of Medicine. Many of our current patients were either previously misdiagnosed or only treated for their symptoms in the emergency room without further investigation. This has led to many of our patients getting diagnosed with IBD when the disease is already at an advanced stage, making it more difficult to treat.</p>
<p>Julia Liu started Morehouse’s <a href="https://clinicaltrials.gov/ct2/show/NCT04369053">first colorectal cancer clinical trial</a> in 2021. The Prevention of Colorectal Cancer Through Multiomics Blood Testing study evaluated whether a particular blood test could aid in early colorectal cancer screening. Due to misconceptions about Black patients’ interest in research, we anticipated few patients would participate in the trial because our patient base is 90% African American. The sponsor for the study expected an enrollment rate as low as one to three patients per week at our site. </p>
<p>However, when enrollment began, we saw high interest among our Black patients. After three months, we had enrolled <a href="https://eposters.ddw.org/ddw/2022/ddw-2022/353760/krystal.mills.fact.or.myth.black.patients.do.not.want.to.participate.in.html?f=listing%3D1%2Abrowseby%3D8%2Asortby%3D2%2Amedia%3D2%2Ace_id%3D2236%2Alabel%3D24500%2Aot_id%3D26916">100 patients, 85% of whom were Black</a>.</p>
<p>So how did we do it?</p>
<h2>Identifying barriers</h2>
<p>First, we identified the participation barriers our Black and Hispanic patients faced.</p>
<p>We conducted a pilot study to identify more broadly the main barriers to research participation in underserved and underrepresented populations in our area. We reviewed enrollment rates, failures to meet eligibility and data issues, among others, from our past studies to see where we could improve.</p>
<p>We evaluated the role of mistrust by <a href="https://doi.org/10.1093/ibd/izac124">surveying patients at an IBD education conference</a>. Although patients often cited mistrust of health care providers and systems as a major barrier to trial participation, 70% of patients with a college education trusted their gastroenterologists, and 100% of patients with less than a college education trusted their doctors. Moreover, while 83% of respondents knew about the Tuskegee syphilis study, only 23% indicated that their decision to not participate in research was influenced by that study.</p>
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<a href="https://images.theconversation.com/files/483278/original/file-20220907-12-uce7s.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Clinician showing clipboard to patient in exam room" src="https://images.theconversation.com/files/483278/original/file-20220907-12-uce7s.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/483278/original/file-20220907-12-uce7s.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/483278/original/file-20220907-12-uce7s.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/483278/original/file-20220907-12-uce7s.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/483278/original/file-20220907-12-uce7s.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/483278/original/file-20220907-12-uce7s.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/483278/original/file-20220907-12-uce7s.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">There often isn’t enough time to talk about the details of participating in a clinical trial during an office visit.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/doctor-with-a-tablet-computer-royalty-free-image/898328226">FatCamera/E+ via Getty Images</a></span>
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<p>We also identified other barriers based on our experience working with Black patients in other clinical trials. A significant one was low levels of <a href="https://medlineplus.gov/healthliteracy.html">health literacy</a>, or the ability to understand and make informed health care decisions. Another was limited access to specialty care, particularly when patients have been waiting for months for an appointment. Lack of transportation was another.</p>
<p>Time was another barrier. Because many of our patients have limited exposure to clinical studies, they have many questions and concerns that most clinicians <a href="https://doi.org/10.1016/j.cpcardiol.2018.11.002">do not have the time</a> to answer in the space of a standard appointment. Patients also could not afford the time commitment required for complex clinical trials. An informed consent process can take over an hour, and many trials require frequent and prolonged hospital visits, for which patients may not be able to take paid time off.</p>
<h2>Implementing solutions</h2>
<p>After identifying these barriers, we worked to create solutions to help our patients participate in research.</p>
<p>We pre-screened potential study participants by looking through their electronic medical records and provider referrals. This helped us identify qualifying patients and proactively reach out to them.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/483274/original/file-20220907-12-jyw7dk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Two researchers looking at test tube" src="https://images.theconversation.com/files/483274/original/file-20220907-12-jyw7dk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/483274/original/file-20220907-12-jyw7dk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/483274/original/file-20220907-12-jyw7dk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/483274/original/file-20220907-12-jyw7dk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/483274/original/file-20220907-12-jyw7dk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/483274/original/file-20220907-12-jyw7dk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/483274/original/file-20220907-12-jyw7dk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Training research and clinical staff on cultural competency could increase trial recruitment and improve care.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/detection-of-the-pathogen-coronavirus-infection-in-royalty-free-image/1207087144">valentinrussanov/E+ via Getty Images</a></span>
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<p>We also trained research staff as well as hospital administration, faculty, staff and students on the study, offering tips on how to interact with underserved and underrepresented patients.</p>
<p>Most importantly, we encouraged our clinicians and researchers to create a safe space for participants to be able to ask questions. This also provides an opportunity to work out ways to accommodate a patient’s schedule. </p>
<h2>Making an effort</h2>
<p>Working with diverse participants can be challenging, but so is every other aspect of clinical research. Our results showed that intentional recruitment, flexibility and creative solutions can help increase enrollment of underrepresented populations in clinical trials.</p>
<p>Partnering with an institution dedicated to serving underserved populations can also help. But above all, research participants are looking for a genuine interest in their well-being.</p><img src="https://counter.theconversation.com/content/185337/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The authors do not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Overcoming the access barriers and biases that underrepresented and underserved communities face could not only improve research participation but also improve care.Julia Liu, Professor of Medicine, Morehouse School of MedicineRaKetra Snipes, Physician Assistant in Gastroenterology, Morehouse School of MedicineLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1872012022-08-17T16:20:01Z2022-08-17T16:20:01ZClinical trials without humans – why computer simulations could make drugs a lot cheaper<p>Before a drug or medical device is approved for use in humans, it must undergo a clinical trial. Clinical trials ultimately aim to answer two simple questions: is the drug or device safe? And does it do what it’s supposed to do?</p>
<p>The downside to clinical trials is that they are complex, take years to complete and are extremely expensive. However, a recent development called “in silico clinical trials” (trials conducted using <a href="https://www.ijclinicaltrials.com/index.php/ijct/article/view/105">computer simulation</a>) are beginning to show their potential for substantially speeding up trials and drastically reducing their costs. And drugs regulators are starting to pay attention.</p>
<p>Indeed, evidence from an in silico clinical trial has already been used to get approval for a new type of pacemaker. </p>
<p>About <a href="https://pubmed.ncbi.nlm.nih.gov/15826268/">75% of patients</a> fitted with a pacemaker will need an MRI scan at some stage, but these devices run the risk of overheating in an MRI machine and burning heart tissue. A novel pacemaker was developed and approved in 2011 that was safe to use in MRI machines. </p>
<p>Testing this new pacemaker using a standard clinical trial would have required thousands of participants to catch those few occasions where the pacemaker overheated. Instead, the evidence from the in silico clinical trial was accepted by the US Food and Drug Administration (FDA) and the device was <a href="https://www.nejm.org/doi/full/10.1056/nejmra1512592#">approved</a>.</p>
<p>In silico trials have also been used to reduce the amount of animal testing. In 2008, the FDA approved one such trial to replace the use of dogs when testing insulin control loops in type 1 diabetes (a device that lets an insulin pump communicate with a continuous glucose monitor). Since then, more than 140 control loops have been tested in this way, avoiding <a href="https://pubmed.ncbi.nlm.nih.gov/28427321/">experimentation on hundreds of dogs</a>.</p>
<figure class="align-center ">
<img alt="A beagle looking out of its cage." src="https://images.theconversation.com/files/479417/original/file-20220816-1453-edol3i.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/479417/original/file-20220816-1453-edol3i.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/479417/original/file-20220816-1453-edol3i.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/479417/original/file-20220816-1453-edol3i.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/479417/original/file-20220816-1453-edol3i.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/479417/original/file-20220816-1453-edol3i.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/479417/original/file-20220816-1453-edol3i.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">In silico trials have saved on the use of dogs in clinical trials.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/dog-behind-cage-304277162">TONG4130/Shutterstock</a></span>
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<p>There has since been a flurry of attempts to develop in silico clinical trials in conditions ranging from <a href="https://www.frontiersin.org/articles/10.3389/fneur.2020.558125/full">stroke</a>, to <a href="https://pubmed.ncbi.nlm.nih.gov/29237680/">atrial fibrillation</a> (a potentially life-threatening irregular heartbeat), to assessing the <a href="https://www.frontiersin.org/articles/10.3389/fphys.2017.00668/full">toxicity of drugs</a>. Although none of these recent computer trials have attempted to get regulatory approval, they are paving the way for future in silico clinical trials to be used in regulatory approval of the drug or device.</p>
<p>These simulations have the potential to reduce the estimated <a href="https://theconversation.com/90-of-drugs-fail-clinical-trials-heres-one-way-researchers-can-select-better-drug-candidates-174152">failure rate of 90%</a> of new drugs in getting to market. Changes to the design or dosing of the medicine may improve clinical trial outcomes and reduce failure rates, but these are often not explored because of the huge costs of rerunning the clinical trials. But they can be explored cheaply using in silico trials.</p>
<h2>Widely used in other industries</h2>
<p>Manufacturing industries have long used computer simulations. Cars, planes and nuclear reactors are all designed and tested on a computer before building begins. What is new is the use of these simulations to predict disease, and the effect of a drug or medical device on that disease, for a general population.</p>
<p>Medical regulators such as the FDA are increasingly interested in assessing in silico clinical trials as they can reduce the cost, time and failure rate when developing a new treatment. Estimates of drug or medical device development costs range from <a href="https://bmjopen.bmj.com/content/10/6/e038863">US$50 million</a> (£41 million) to over <a href="https://jamanetwork.com/journals/jama/fullarticle/2762311">US$1 billion</a> (£828 million). Any reduction in these costs should result in cheaper medicines.</p>
<p>Research has reached a point where computational power and understanding of biology allow highly specific predictions to be made on how a medicine will affect the human body. However, this in no way means that these in silico clinical trials will fully replace human trials. There are too many “unknown unknowns” in understanding medical interventions, which means 100% accuracy at simulating reality is never guaranteed.</p>
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Read more:
<a href="https://theconversation.com/the-human-body-has-37-trillion-cells-if-we-can-work-out-what-they-all-do-the-results-could-revolutionise-healthcare-185654">The human body has 37 trillion cells. If we can work out what they all do, the results could revolutionise healthcare</a>
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<p>Regulatory acceptance is another hurdle that must be overcome. While there are promising signs from the FDA that in silico trials can be accepted as evidence, there is still a need for clear regulatory guidance for this to become the norm. As more successful in silico trials are developed, regulators around the world will probably accept them as valid evidence.</p>
<p>While in silico clinical trials will never completely replace real-world clinical trials, the two questions – is the medicine safe, and does it do what it’s supposed to do? – will increasingly be answered by a combination of humans and computer simulations of humans.</p><img src="https://counter.theconversation.com/content/187201/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Wahbi El-Bouri receives funding from The Royal Society and EPSRC. He is affiliated with the Avicenna Alliance and InSilico UK communities that seek to drive adoption of in silico clinical trials for patient safety and benefit. </span></em></p>In silico clinicial trials have the potential to speed up trials and cut costs.Wahbi K. El-Bouri, Research Fellow, University of LiverpoolLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1842872022-08-08T17:23:34Z2022-08-08T17:23:34ZAltruism – but also vulnerability – drive healthy volunteers to take part in clinical research<p>When UK authorities granted permission in October 2020 for the <a href="https://www.biospace.com/article/releases/open-orphan-hvivo-signs-contract-with-uk-government-for-the-development-of-a-Covid-19-human-challenge-study-model/">first controlled infection study</a> to be carried out to test the anti-Covid-19 vaccine Oxford University had just developed, reactions ranged from disbelief to disapproval.</p>
<p>Yet this type of experiment, which exposes healthy volunteers to an infection to assess the efficacy of a vaccine or treatment (it is sometimes called a <a href="https://presse.inserm.fr/infecter-deliberement-les-volontaires-pour-accelerer-la-recherche-vaccinale-Covid-19-vraiment/41183/">‘human infection challenge’</a>), is not just a widespread practice but also an irreplaceable one in clinical research.</p>
<p>But involving healthy people in biomedical research is not risk-free, as recent tragedies have shown. In what context are these healthy volunteers enlisted? What motivates them? And how are they protected?</p>
<h2>The uncertainty of clinical research</h2>
<p>In March 2006, the firm TeGenero sought to assess the tolerance of an antibody designed to fight diseases like rheumatoid arthritis, multiple sclerosis and some leukaemias. Initial results from animal testing had proved relatively safe, so the firm decided to test the new molecule on humans. For this, TeGenero enlisted six healthy volunteers. When the drug was first administered to them, all six quickly suffered multiple organ failure. These unexpected complications were later explained: the antibody that was tested stimulated T-Cells that had previously been activated by other infections. <a href="https://www.apmnews.com/freestory/10/163717/les-graves-complications-de-l-essai-clinique-de-tegenero-seraient-dues-a-un-effet-imprevu-de-l-anticorps-tgn1412-sur-les-lymphocytes-t">These T cells are thought to have migrated to healthy organs and damaged them</a>.</p>
<p>Ten years later, in January 2016, a study commissioned by Portuguese firm Bial to test a molecule designed to relieve pain and anxiety had an even more dramatic outcome: <a href="https://www.lemonde.fr/sante/article/2016/10/11/essai-clinique-de-rennes-un-drame-en-cinq-questions_5011900_1651302.html">one of the six healthy volunteers enlisted was admitted to hospital on the fifth day of receiving daily doses of the experimental drug</a>. His condition worsened, prompting medical authorities to declare him brain dead the next day. He died a few days later.</p>
<p>These two examples are proof that biomedical research, by its very nature, leaves little clue about the benefits participants might gain from it. Yet we cannot deny the considerable scientific and social value of <a href="https://theconversation.com/essais-cliniques-pratiques-et-reglementation-en-france-53331">clinical research</a>: it has helped to develop and greenlight many treatments and operations that have increased the quality and duration of countless patients’ lives.</p>
<p>But therein lies the issue: a patient supposedly knows what the purpose of the research into their own disease is, whereas ‘healthy’ people used in clinical research have different motivations and a different understanding of the research involved.</p>
<h2>In what contexts does clinical research call on healthy volunteers?</h2>
<p>In France, any research conducted on humans is referred to, in the country’s public health code, as <a href="https://www.legifrance.gouv.fr/codes/article_lc/LEGIARTI000032722870/">‘research involving human beings’</a> without prior distinction between an ill volunteer and a healthy one.</p>
<p>Beyond preventive trials and phase-1 clinical research of medical products specific to them, healthy volunteers take part in biomedical studies that can differ wildly from one to the other. Worldwide, most studies involving healthy volunteers assess ‘bioequivalence’. Such studies are carried out to show similarity between blood levels produced by pioneering medicines and their generic versions. They are mostly conducted by specialist firms (‘Contract Research Organisations’) for pharmaceutical companies.</p>
<p>A 2017 survey identified more than <a href="https://www.cambridge.org/core/journals/cambridge-quarterly-of-healthcare-ethics/article/healthy-volunteers-for-clinical-trials-in-resourcepoor-settings-national-registries-can-address-ethical-and-safety-concerns/5D8FA3301ED03122C90DEE3F4B158096">1,000 studies involving molecules being administered to tens of thousands of healthy volunteers</a>, especially in India, China, and North America.</p>
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À lire aussi :
<a href="https://theconversation.com/essais-cliniques-pratiques-et-reglementation-en-france-53331">Essais cliniques : pratiques et réglementation en France</a>
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<p>Healthy volunteers can also be part of a <a href="https://player.vimeo.com/video/59735666">cohort</a> – a group of individuals who accept to be monitored, sometimes over several decades, to provide helpful data in epidemiology and disease evolution. Some cohorts have helped form stores of biological samples (‘biobanks’), which are subsequently used as benchmarks in clinical research.</p>
<p>The Pasteur Institute, for instance, has hosted the <a href="http://www.biobanques.eu/en/nous-connaitre/membres/item/plateforme-icareb-institut-pasteur-paris">ICAReB platform</a> since 2008. ICAReB stores biological samples from around 300 healthy donors. Other biobanks help to assess behavioural mechanisms. For example, the Paris Brain Institute hosts the <a href="https://prismeicm.wixsite.com/prisme-icm">PRISME platform</a>, which lists around 2,000 volunteers available to help develop technological solutions that assess real-life behaviour in a range of settings (waiting room, confined environments, public spaces, etc.), among others.</p>
<p>In a different context, healthy volunteers also serve as ‘comparators’ in research monitoring the victims of the <a href="https://theconversation.com/paris-terror-attacks-france-now-faces-fight-against-fear-and-exclusion-50703">13 November 2015 Paris terrorist attacks</a>.</p>
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À lire aussi :
<a href="https://theconversation.com/13-novembre-et-traumatisme-la-memoire-collective-influence-profondement-la-memoire-individuelle-150005">13 Novembre et traumatisme : « La mémoire collective influence profondément la mémoire individuelle »</a>
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<h2>What are the different “checks” that control clinical research on healthy volunteers in France?</h2>
<p>In line with the country’s public health code, any research conducted on humans in France is subject <a href="https://www.legifrance.gouv.fr/codes/article_lc/LEGIARTI000032722870/">to rulings that ensure participants’ safety and the study’s relevance</a>.</p>
<p>Just as in the case of ill volunteers, healthy individuals have to receive transparent, comprehensible information about how the study will unfold, and the risks involved. This helps formalise their consent. A medical check-up determines whether their participation complies with the criteria of inclusion and exclusion defined in the study’s formal procedure approved by France’s relevant regulatory bodies (research ethics board; ANSM, France’s public agency for assessing health risks from drugs). At any moment, a volunteer can choose to leave the study without having to justify their decision.</p>
<p>In France, healthy volunteers who take part in clinical research are registered in a national database used to track their participation, the amount they have received in compensatory payments, and their waiting period between two studies. A national database entitled <a href="https://vrb.sante.gouv.fr/">VRB</a> (a French acronym meaning ‘volunteers in biomedical research’) lists those who consent to take part in biomedical research. It is worth noting that France and <a href="https://www.hra.nhs.uk/about-us/committees-and-services/the-over-volunteering-prevention-system/">the United Kingdom</a> are the only countries in the world that have set up such a database. The measure is designed to avoid a trend in ‘career’ healthy volunteers, <a href="https://www.newscientist.com/article/mg20327181-500-perils-of-the-professional-lab-rat/">as has arisen in the US</a>.</p>
<h2>What motivates healthy volunteers?</h2>
<p>Being a volunteer in a vaccine trial, a pharmacokinetic study (which examines the fate of a drug in the body) or a cohort gives the participant a sense of belonging to a high-minded community that helps further knowledge.</p>
<p>This kind of approach can be more natural to a volunteer whose everyday activity relates to a particular field of research, like a student in healthcare. Healthy volunteers can also be people with a loved one suffering from a disease – their discovery of clinical research, their awareness of related challenges and their desire to help advance these studies boost participation rates in clinical trials. Whatever a volunteer claims drives them, the importance of their commitment for society is far from trivial.</p>
<p>Some people claim they volunteer for clinical research out of altruism, but others <a href="https://www.anrs.fr/sites/default/files/2018-04/volontaires_etudes_cliniques_prevention.pdf">do so to receive compensatory payments for taking part</a>. Could financial vulnerability be the key factor driving some into volunteering? In France, there is a cap on the yearly amount of compensatory payments a volunteer may receive for the constraints they have to undergo. But for many people, this amount still represents a sizeable sum, especially for those who are in a precarious situation.</p>
<p>Lastly, it is worth noting that not all segments of the population are equally aware of clinical research, which calls into question the ability to make research results relevant to all.</p>
<h2>Ethics and utilitarianism</h2>
<p>It is even trickier to evaluate how financial vulnerability factors in a healthy volunteer’s motivation in countries with weak ethical controls, or even in developed countries with very liberal political systems. Such case-scenarios challenge the very notion of voluntary service, especially as some research conducted <a href="https://www.lexpress.fr/culture/tele/2061-deces-attribues-aux-essais-cliniques-en-inde_1322142.html">outside of adequate regulatory frameworks</a> or on vulnerable <a href="https://www.nature.com/news/human-experiments-first-do-harm-1.9980">populations in developed countries</a> has created a climate of distrust in which healthy volunteers feel exploited.</p>
<p>A volunteer can be led to commit to a clinical study by believing the benefit they gain from taking part – whether it be income or access to primary healthcare in some economic contexts – outweighs any risk they are taking. Yet a volunteer’s vulnerable situation cannot be a criterion of exclusion from any research, as such exclusion would aggravate the volunteer’s vulnerability in two ways: materially, by stripping them of the benefit they expect, and symbolically, by stripping them of their freedom of choice.</p>
<p>Torn between utilitarian guilt and a desire to serve society, researchers are helpless in the face of this dilemma.</p>
<h2>Reducing vulnerable situations</h2>
<p>Though our societies have set standards of arbitration and validation through bodies that regulate research, healthy volunteers should be able to be truly free to decide whether to join the handful of people who take on a risk for the common good.</p>
<p>It is therefore crucial to reduce vulnerable situations so that ethical research can be conducted with respect for healthy volunteers. This can be achieved by helping them <a href="https://www.hal.inserm.fr/inserm-02111121/document">better understand the challenges of the research they will accept to contribute to</a>, and better assess the risks they will be taking. Moreover, information provided to garner <a href="https://www.hal.inserm.fr/inserm-02111121/document#page=5">informed consent</a>, a critical dimension of clinical research, should be tailored to potential cases of vulnerability – especially economic and educational – specific to healthy volunteers. Lastly, widespread global use of national databases, like those used in France and the UK, would help better regulate research that involves healthy volunteers and therefore protect them.</p>
<p>Exposing healthy volunteers to risks that are not always under control routinely calls into question the dilemma between research that can be very useful to many and a risk taken by a few. In the current pandemic, this dilemma has prompted France to give up on infecting healthy volunteers to test anti-Covid-19 vaccines.</p>
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<p><em><a href="https://dndi.org/our-people/bompart/">François Bompart</a>, chair of the access committee at the Drugs for Neglected Diseases Initiative (DNDi), a Swiss non-profit research organisation that develops treatments for neglected diseases, contributed to this article. The authors would also like to thank Mylène Botbol-Baum, Didier Dreyfuss, Christine Lemaitre, Pierre Lombrail, Flavie Mathieu, and Corinne Sebastiani, the other members of the working group <a href="https://www.inserm.fr/en/ethics/ethics-committees-theme-based-think-tanks/">‘Health Research in Resource-Limited Countries’</a>, part of the ethics committee of INSERM, a French public institute for health and medical research.</em></p>
<p><em>This text was published following activities developed as part of the European project <a href="http://www.trust-project.eu">‘Creating and Enhancing TRUSTworthy, Responsible and Equitable Partnerships in International Research’</a>. It was translated from the French by Thomas Young for <a href="http://www.fastforword.fr/en">Fast ForWord</a></em></p><img src="https://counter.theconversation.com/content/184287/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Les auteurs ne travaillent pas, ne conseillent pas, ne possèdent pas de parts, ne reçoivent pas de fonds d'une organisation qui pourrait tirer profit de cet article, et n'ont déclaré aucune autre affiliation que leur organisme de recherche.</span></em></p>What prompts healthy volunteers to take part in clinical research? And how are they protected?Isabelle Remy-Jouet, Ethicienne, Membre du comité Éthique de l'Inserm, Mission DD&RS, Université d'AngersFrançois Eisinger, Professeur associé en santé publique, praticien hospitalier au centre de lutte contre le cancer Institut Paoli-Calmettes, InsermFrançois Hirsch, Membre du comité d'éthique de l'Inserm, InsermLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1874962022-07-21T22:44:14Z2022-07-21T22:44:14ZBiden tests positive for COVID-19: An infectious disease doctor explains the risks and treatments available for the 79-year-old president<figure><img src="https://images.theconversation.com/files/475533/original/file-20220721-9733-d32d24.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C5946%2C3862&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">President Joe Biden tested positive for COVID-19 on July 21, 2022, but was reportedly feeling well enough to work and take calls, as seen in this photo released by the White House.</span> <span class="attribution"><a class="source" href="https://newsroom.ap.org/detail/VirusOutbreakBidenCOVID/81ebae96118f4047846a19e4b36e2315/photo?Query=biden%20covid&mediaType=photo&sortBy=&dateRange=now-24h&totalCount=39&currentItemNo=35">Adam Schultz/The White House via AP</a></span></figcaption></figure><p><em>On July 21, 2022, U.S. President Joe Biden said he had <a href="https://www.cnn.com/2022/07/21/politics/joe-biden-covid-19/index.html">tested positive for COVID-19 and was experiencing mild symptoms</a>. In a letter to the public, Biden’s doctor explained that the president had a slight runny nose, some fatigue and the occasional dry cough, and that Biden had already begun taking the antiviral drug Paxlovid. <a href="https://scholar.google.com/citations?user=NAnp8WsAAAAJ&hl=en&oi=ao">Patrick Jackson</a>, an assistant professor of infectious diseases at the University of Virginia, explains the risks that someone like Biden faces from a bout of COVID-19 and the treatments available.</em></p>
<h2>1. What are the important risk factors for Biden?</h2>
<p>The most important risk factor for developing severe COVID-19 is age. If you are 79 years old when you become infected with COVID-19, like President Biden, you are <a href="https://www.cdc.gov/coronavirus/2019-ncov/covid-data/investigations-discovery/hospitalization-death-by-age.html">eight times more likely to become hospitalized and 140 times more likely to die</a> compared with someone who gets COVID-19 at age 20. Preexisting health conditions – like obesity, cancer and chronic kidney or lung disease – also increase the risk of severe illness. But Biden is <a href="https://www.whitehouse.gov/wp-content/uploads/2021/11/President-Biden-Current-Health-Summary-November-2021.pdf">reported to be fairly healthy</a>.</p>
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<p>Fortunately, preexisting immunity from vaccination or from a previous episode of COVID-19 is <a href="https://doi.org/10.1056/NEJMoa2203965">highly protective against severe disease</a>. Researchers only have limited data on the BA.5 variant that is responsible for <a href="https://covid.cdc.gov/covid-data-tracker/#variant-proportions">most recent COVID-19 cases in the U.S.</a> – and likely Biden’s, too – but the level of protection from vaccines is likely similar to that of the previous strains BA.1 and BA.2. While the BA.1 and BA.2 omicron variants of SARS-CoV-2 were very adept at infecting people who are vaccinated and boosted, the data shows that prior immunity from vaccines provides strong <a href="https://doi.org/10.1056/NEJMoa2203965">protection against severe or fatal disease</a>. During the first omicron wave in California, COVID-19 patients who did not have immunity from vaccination or previous infection were <a href="https://doi.org/10.1016/j.lana.2022.100297">much more likely to be hospitalized, be admitted into an intensive care unit or die</a> compared with people who were vaccinated and boosted.</p>
<h2>2. What is the first line of treatment for someone like Biden, and why?</h2>
<p>Current best medical practice is to give antiviral treatments to patients who have recently developed mild to moderate COVID-19 symptoms and are at higher risk of severe illness. The goal of antivirals is to stop the virus from replicating in the body in order to prevent hospitalization or death. </p>
<p>Currently there are four antiviral drugs available in the U.S. for the treatment of COVID-19 in outpatients: nirmatrelvir-ritonavir, better known by the brand name <a href="https://www.fda.gov/media/155051/download">Paxlovid</a>, <a href="https://www.gilead.com/-/media/files/pdfs/medicines/covid-19/veklury/veklury_patient_pi.pdf">remdesivir</a>, <a href="https://www.fda.gov/media/156153/download">bebtelovimab</a> and <a href="https://www.fda.gov/media/155055/download">molnupiravir</a>. The best drug for a particular patient depends on preexisting health conditions, accessibility and drug interactions with other medications. Paxlovid is widely used because it was shown to be <a href="https://doi.org/10.1056/NEJMoa2118542">highly effective in a clinical trial</a> and is available in pill form.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/475534/original/file-20220721-14443-g4gj9m.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A pill packet labeled with Paxlovid leaning on a box." src="https://images.theconversation.com/files/475534/original/file-20220721-14443-g4gj9m.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/475534/original/file-20220721-14443-g4gj9m.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/475534/original/file-20220721-14443-g4gj9m.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/475534/original/file-20220721-14443-g4gj9m.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/475534/original/file-20220721-14443-g4gj9m.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/475534/original/file-20220721-14443-g4gj9m.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/475534/original/file-20220721-14443-g4gj9m.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">President Joe Biden is taking Paxlovid, an antiviral drug shown to reduce the risk of hospitalization and death in people infected with COVID-19.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/march-2022-berlin-the-drug-paxlovid-against-covid-19-from-news-photo/1238868437?adppopup=true">Picture Alliance/Contributor via Getty Images</a></span>
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<h2>3. How does Paxlovid work, and what are its shortcomings?</h2>
<p><a href="https://theconversation.com/what-is-paxlovid-and-how-will-it-help-the-fight-against-coronavirus-an-infectious-diseases-physician-answers-questions-on-the-covid-19-pill-181998">Paxlovid</a> is an <a href="https://doi.org/10.1126/science.abl4784">oral antiviral drug</a> that is used to treat some patients with mild to moderate COVID-19 who do not require hospitalization. Paxlovid is a combination of two medications. One is nirmatrelvir, a drug that works by <a href="https://doi.org/10.1126/science.abl4784">disrupting the coronavirus’ ability to make functioning proteins</a>. The other is ritonavir, an HIV drug that <a href="https://doi.org/10.3390/scipharm86040043">boosts the level of nirmatrelvir in the blood</a> by blocking an enzyme in the liver that breaks down nirmatrelvir.</p>
<p>A clinical trial of Paxlovid showed that the drug <a href="https://doi.org/10.1056/NEJMoa2118542">significantly reduces the risk of hospitalization or death</a> when given to infected patients within five days of their first COVID-19 symptoms. This trial looked at Paxlovid given to people who had no prior immunity to COVID-19 from vaccines or previous infection. The effectiveness of Paxlovid in the treatment of patients who have preexisting immunity from vaccination or prior infection is less clear, though <a href="https://assets.researchsquare.com/files/rs-1705061/v1/ed7100f4-9dba-4cd5-8581-3548721bfa0d.pdf?c=1654110344">some studies</a> suggest that older vaccinated patients may still benefit from the drug. Paxlovid <a href="https://www.pfizer.com/news/press-release/press-release-detail/pfizer-reports-additional-data-paxlovidtm-supporting">has not been found to reduce symptoms</a> or make patients feel better more quickly.</p>
<p>Paxlovid is not a panacea. It cannot be used for <a href="https://www.fda.gov/media/155050/download">some patients who have significant kidney or liver problems</a>, and it interacts negatively with a <a href="https://www.fda.gov/media/158165/download">large number of other medications</a>. Some patients cannot take Paxlovid because of the other drugs they use, but physicians can sometimes manage these interactions.</p>
<p>For example, Biden <a href="https://www.whitehouse.gov/wp-content/uploads/2021/11/President-Biden-Current-Health-Summary-November-2021.pdf">is reportedly</a> taking a blood thinner called apixaban. This drug <a href="https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/management-of-drug-interactions-with-nirmatrelvirritonavir-paxlovid/">interacts negatively with Paxlovid</a>. It is likely Biden’s doctor has instructed him to reduce his dose of apixaban or stop it briefly while on Paxlovid.</p>
<h2>4. What will Biden’s health care team be on the lookout for?</h2>
<p>Biden’s doctors will be monitoring his symptoms and checking his blood oxygen level. If Biden’s symptoms – like cough, shortness of breath or fever – worsen or he needs supplemental oxygen, it is possible he would be hospitalized where he may get treated with additional drugs, including steroids. </p>
<p>Some patients experience an initial improvement <a href="https://doi.org/10.1001/jama.2022.9925">followed by a “rebound” of their COVID-19 symptoms</a>. It is not clear how often rebounds happen or if they are associated with COVID-19 treatment. <a href="https://doi.org/10.1093/cid/ciac481">Rebounds appear to be generally mild</a> and not associated with hospitalization or death, though they can prolong the required period of isolation.</p>
<p>It is still too early to tell how mild or severe Biden’s bout of COVID-19 will be. With most mild cases only lasting around a week, the U.S. should only need to wait a few days to get a sense of what kind of fight the president is facing.</p><img src="https://counter.theconversation.com/content/187496/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Patrick Jackson receives research funding from the National Institutes of Health and the Ivy Foundation. He is a consultant for Moleculin Biotech. He is affiliated with Indivisible Charlottesville.</span></em></p>According to a letter from Biden’s doctor, the president has a runny nose, mild fatigue and a slight cough. The letter also noted that Biden began taking an antiviral drug the morning he tested positive.Patrick Jackson, Assistant Professor of Infectious Diseases, University of VirginiaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1834272022-05-26T12:27:33Z2022-05-26T12:27:33ZHow important is the COVID-19 booster shot for 5-to-11-year-olds? 5 questions answered<figure><img src="https://images.theconversation.com/files/464830/original/file-20220523-16-fzudrg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">About 8 million U.S. children have received two shots of COVID-19 vaccine and are now eligible for a third.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/young-girl-watching-her-being-injected-with-covid-royalty-free-image/1339290664?adppopup=true">KoldoyChris/Moment via Getty Images</a></span></figcaption></figure><p><em>COVID-19 case numbers are rising again in the U.S. – including <a href="https://www.aap.org/en/pages/2019-novel-coronavirus-covid-19-infections/children-and-covid-19-state-level-data-report/">among children</a>. In mid-May 2022, the Food and Drug Administration authorized a booster shot of the COVID-19 vaccine for <a href="https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-expands-eligibility-pfizer-biontech-covid-19-vaccine-booster-dose">U.S. children ages 5 to 11</a>, and the Centers for Disease Control and Prevention followed by <a href="https://www.cdc.gov/media/releases/2022/s0519-covid-booster-acip.html#">recommending a booster shot</a> for this age group.</em> </p>
<p><em>Naturally, many parents are wondering about the importance and safety of a booster shot for their school-age children. <a href="https://uvahealth.com/findadoctor/profile/debbie-ann-shirley">Debbie-Ann Shirley</a>, a <a href="https://scholar.google.com/citations?user=M6zP_sMAAAAJ&hl=en">pediatric infectious disease specialist</a> at the University of Virginia, answers some common questions about COVID-19 and booster shots in kids that she hears in her practice and explains the research behind why booster shots are recommended for children ages 5 to 11.</em> </p>
<h2>1. How important is a booster shot for children?</h2>
<p>COVID-19 is generally milder in children than adults, but severe disease can occur.
As of late May 2022, more than 15,000 children ages 5 to 11 <a href="https://www.cdc.gov/media/releases/2022/s0519-covid-booster-acip.html#">have been hospitalized</a> with COVID-19 and <a href="https://data.cdc.gov/d/3apk-4u4f/visualization">180 children</a> have died. During the height of the recent winter surge of <a href="https://theconversation.com/will-omicron-the-new-coronavirus-variant-of-concern-be-more-contagious-than-delta-a-virus-evolution-expert-explains-what-researchers-know-and-what-they-dont-169020">the highly transmissible omicron variant</a>, 87% of the children in the 5-to-11 age group <a href="https://www.cdc.gov/mmwr/volumes/71/wr/mm7116e1.htm?s_cid=mm7116e1_w">who became hospitalized with COVID-19 were unvaccinated</a>. </p>
<p>In addition, the rare but serious condition that can follow in the weeks after COVID-19 infection, known as <a href="https://www.cdc.gov/mis/mis-c.html">Multisystem Inflammatory Syndrome in Children</a>, or MIS-C, most commonly occurs among children ages 5 to 11. Over <a href="https://covid.cdc.gov/covid-data-tracker/#mis-national-surveillance">3,800 cases of MIS-C have been reported</a> in that 5-to-11 age group, and <a href="https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2022-05-19/06-COVID-Oliver-508.pdf">93% of the children</a> who developed this complication were unvaccinated. </p>
<p>For some vaccines – including those for COVID-19 – effectiveness wanes over time. <a href="https://theconversation.com/why-its-normal-for-covid-19-vaccine-immunity-to-wane-and-how-booster-shots-can-help-171786">Booster shots</a> help to bolster the immune response. Several <a href="https://www.cdc.gov/vaccines/schedules/hcp/imz/child-adolescent.html#note-dtap">childhood vaccines</a>, such as the tetanus and diphtheria vaccines, require booster shots. </p>
<p>COVID-19 boosters have been shown to improve waning protection <a href="https://www.cdc.gov/mmwr/volumes/71/wr/mm7109e3.htm?s_cid=mm7109e3_w">in adolescents</a> and <a href="https://doi.org/10.1001/jama.2022.0470">adults</a>. Side effects are similar to those reported with the initial series. The risk of myocarditis, or heart inflammation – a rare side effect that can occur following COVID-19 vaccination – seems to be less after a third dose than <a href="https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2022-05-19/06-COVID-Oliver-508.pdf">after the second</a>. </p>
<h2>2. How well is immunity holding up from the initial COVID-19 shots?</h2>
<p>When administered to children 5 to 11 years old, the Pfizer-BioNTech vaccine generated levels of antibody response similar to that in 16-to-25-year-olds in <a href="https://doi.org/10.1056/NEJMoa2116298">a clinical trial</a>, which was the basis for the <a href="https://www.fda.gov/news-events/press-announcements/fda-authorizes-pfizer-biontech-covid-19-vaccine-emergency-use-children-5-through-11-years-age">FDA’s initial authorization of the shots</a> in October 2021. But <a href="https://doi.org/10.1001/jama.2022.7493">studies after the shots were authorized</a> found that <a href="https://doi.org/10.1001/jama.2022.7319">vaccine effectiveness rapidly waned</a> in the 5-to-11 age group during the omicron surge. Despite that, the shots continued to be <a href="https://www.cdc.gov/mmwr/volumes/71/wr/mm7109e3.htm?s_cid=mm7109e3_w">protective against severe disease and hospitalization</a>. </p>
<p>Vaccination has also <a href="https://www.cdc.gov/mmwr/volumes/71/wr/mm7102e1.htm#">been shown to be be highly protective</a> against Multisystem Inflammatory Syndrome in Children.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/x4llSK2DWYY?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">How to talk to kids about getting vaccinated.</span></figcaption>
</figure>
<h2>3. Does a third dose make a difference in children?</h2>
<p>In a clinical trial, researchers tested the Pfizer vaccine in children 5 to 11 using a 10-microgram booster dose, which is the same dose children received for the primary series and is one-third the dose used for adolescents and adults. When tested among 401 children, <a href="https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2022-05-19/05-COVID-Sabharwal-508.pdf">no new safety concerns arose</a>, and in the smaller subset of children in which the immune response was tested, the third shot <a href="https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-announce-data-demonstrating-high-immune">significantly increased antibody responses</a>, including against the omicron variant. Hence, a third dose seems beneficial for boosting immunity in this age group, similar to older age groups. </p>
<p>The booster dose can be given <a href="https://www.cdc.gov/media/releases/2022/s0519-covid-booster-acip.html#">five months or more</a> after the second shot. But as of late May 2022, fewer than <a href="https://www.aap.org/en/pages/2019-novel-coronavirus-covid-19-infections/children-and-covid-19-vaccination-trends/#">one-third</a> of children ages 5 to 11 had received two shots, meaning that only <a href="https://www.aap.org/en/pages/2019-novel-coronavirus-covid-19-infections/children-and-covid-19-vaccination-trends/">about 8 million</a> school-age children were eligible to start receiving the booster. This could prove an important layer of protection for them and <a href="https://cai.burbio.com/school-opening-tracker/">help limit disruptions</a> on schooling and summer activities, particularly as <a href="https://www.nytimes.com/explain/2022/03/01/us/mask-mandates-us">mask mandates have gone by the wayside</a>.</p>
<p>Children with <a href="https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-conditions.html#immunocompromised">weakened immune systems</a> who were at first authorized to receive three initial doses of COVID-19 vaccine may now also receive a booster shot – or a fourth dose – <a href="https://www.cdc.gov/vaccines/covid-19/clinical-considerations/interim-considerations-us.html#immunocompromised">as soon as three months</a> after their third dose.</p>
<h2>4. Is the COVID-19 vaccine safe for kids?</h2>
<p>As of late May 2022, more than <a href="https://covid.cdc.gov/covid-data-tracker/#vaccinations_vacc-total-admin-rate-total">18.5 million</a> doses of the COVID-19 vaccine had been administered to children in the 5-to-11 age group. Most <a href="https://www.cdc.gov/mmwr/volumes/70/wr/mm705152a1.htm?s_cid=mm705152a1_w">COVID-19 vaccine side effects</a> – such as pain at the injection site – have been mild and short-lived in children. Fatigue, headache and muscle aches are other common side effects. </p>
<p>Reports suggest that most cases of myocarditis that follow vaccination typically <a href="https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/myocarditis.html">improve quickly with medicine and rest</a>. Rates of myocarditis <a href="https://www.cdc.gov/mmwr/volumes/71/wr/mm7114e1.htm?s_cid=mm7114e1_w">have been lower</a> in children ages 5 to 11 than in teens. In any age group, myocarditis is more likely to occur <a href="https://www.cdc.gov/mmwr/volumes/71/wr/mm7114e1.htm?s_cid=mm7114e1_w">after infection</a> than vaccination. </p>
<h2>5. What about the kids under 5?</h2>
<p>For parents of kids ages 6 months to 5 years, COVID-19 vaccines are also finally within sight. On May 23, 2022, Pfizer <a href="https://investors.pfizer.com/Investors/News/news-details/2022/Pfizer-BioNTech-COVID-19-Vaccine-Demonstrates-Strong-Immune-Response-High-Efficacy-and-Favorable-Safety-in-Children-6-Months-to-Under-5-Years-of-Age-Following-Third-Dose/default.aspx">released new data for this age group</a>, stating that three shots generated strong antibody responses, were well tolerated with no new safety concerns and, based on preliminary data, the series was 80% effective at preventing COVID-19 infection. In late April 2022, <a href="https://investors.modernatx.com/news/news-details/2022/Moderna-Files-for-Authorization-of-Its-COVID-19-Vaccine-in-Young-Children-Six-Months-to-Under-Six-Years-of-Age/default.aspx">Moderna</a> released similar data showing that two doses of its vaccine stimulated good antibody responses and were tolerated well by kids under age 6.</p>
<p>The FDA is <a href="https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-announces-tentative-advisory-committee-meeting-schedule-regarding">set to meet in June 2022</a> to discuss new low-dose formulations of the <a href="https://investors.modernatx.com/news/news-details/2022/Moderna-Files-for-Authorization-of-Its-COVID-19-Vaccine-in-Young-Children-Six-Months-to-Under-Six-Years-of-Age/default.aspx">Moderna</a> and <a href="https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-provide-update-rolling-submission">Pfizer</a> vaccines for this group. </p>
<p>If it is authorized by the FDA, the CDC will then provide recommendations on its use for the more than 20 million children ages 6 months to 5 years in the U.S.</p><img src="https://counter.theconversation.com/content/183427/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Debbie-Ann Shirley does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>The COVID-19 vaccines continue to be effective against severe illness leading to hospitalization and death in all age groups, including children ages 5 to 11.Debbie-Ann Shirley, Associate Professor of Pediatrics, University of VirginiaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1819262022-05-04T12:33:24Z2022-05-04T12:33:24ZWill new vaccines be better at fighting coronavirus variants? 5 questions answered<figure><img src="https://images.theconversation.com/files/461072/original/file-20220503-24-26xibt.jpg?ixlib=rb-1.1.0&rect=63%2C34%2C3190%2C2008&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Dozens of coronavirus vaccines are in clinical trials in the U.S.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/coronavirus-vaccine-vials-on-a-laboratory-shelf-royalty-free-image/1301805656?adppopup=true">Joao Paulo Burini/Moment via Getty Images</a></span></figcaption></figure><p><em>The first three coronavirus vaccines earned Emergency Use Authorization more than a year ago. To date, no other vaccines have been put into use in the U.S – but that will soon change. <a href="https://covid19.trackvaccines.org/country/united-states-of-america/">More than 40 vaccines are undergoing clinical trials</a> in the U.S., employing a number of different approaches to protecting people from the coronavirus. <a href="https://scholar.google.com/citations?user=TyYJ1hkAAAAJ&hl=en&oi=ao">Vaibhav Upadhyay</a> and <a href="https://pharmacy.cuanschutz.edu/about-us/profile/krishna-mallela">Krishna Mallela</a> have been studying the coronavirus spike protein since the outbreak of the pandemic and are developing COVID-19 therapeutics. Together, they explain what vaccines are in development and why some of the vaccines should be better than what’s available now.</em></p>
<h2>1. Why are companies working on new vaccines?</h2>
<p>A major reason why new vaccines are important – and why the world is still dealing with COVID-19 – is the continued emergence of <a href="https://theconversation.com/what-are-covid-19-variants-and-how-can-you-stay-safe-as-they-spread-a-doctor-answers-5-questions-163697">new variants</a>. Most of the differences between variants are <a href="https://theconversation.com/will-omicron-the-new-coronavirus-variant-of-concern-be-more-contagious-than-delta-a-virus-evolution-expert-explains-what-researchers-know-and-what-they-dont-169020">changes in the spike protein</a>, which is on the surface of the virus and helps it enter and infect cells. </p>
<p>Some of these small changes in the spike protein have allowed the coronavirus to <a href="https://theconversation.com/will-omicron-the-new-coronavirus-variant-of-concern-be-more-contagious-than-delta-a-virus-evolution-expert-explains-what-researchers-know-and-what-they-dont-169020">infect human cells more efficiently</a>. These changes have also made it so that previous vaccinations or infections with COVID-19 <a href="https://doi.org/10.1038/s41586-021-04385-3">provide less protection against the new variants</a>. Updated or new vaccines could be better at detecting these different spike proteins and better at protecting against new variants.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/461073/original/file-20220503-12-amifz1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A number of vaccine vials on a production line." src="https://images.theconversation.com/files/461073/original/file-20220503-12-amifz1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/461073/original/file-20220503-12-amifz1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=420&fit=crop&dpr=1 600w, https://images.theconversation.com/files/461073/original/file-20220503-12-amifz1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=420&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/461073/original/file-20220503-12-amifz1.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=420&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/461073/original/file-20220503-12-amifz1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=528&fit=crop&dpr=1 754w, https://images.theconversation.com/files/461073/original/file-20220503-12-amifz1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=528&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/461073/original/file-20220503-12-amifz1.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=528&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Vaccines fall generally into four categories: whole virus vaccines, viral vector vaccines, protein-based vaccines and nucleic acid-based vaccines.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/covid-19-vaccine-production-line-royalty-free-image/1290225107?adppopup=true">Andriy Onufriyenko/Moment via Getty Images</a></span>
</figcaption>
</figure>
<h2>2. What kinds of vaccines are in the works?</h2>
<p>So far, <a href="https://covid19.trackvaccines.org/">38 vaccines have been approved around the world</a>, and the U.S. has approved three of those. There are <a href="https://covid19.trackvaccines.org/">currently 195 vaccine candidates</a> at different stages of development worldwide, out of which <a href="https://covid19.trackvaccines.org/country/united-states-of-america/">41 are in clinical trials in U.S.</a> Vaccines against SARS-CoV-2 can be broadly divided into four classes: whole virus, viral vector, protein-based and nucleic acid-based vaccines. </p>
<p>Whole virus vaccines generate immunity using a complete, though weakened – called inactivated or attenuated – SARS-CoV-2 virus. Currently there are two of these vaccines in clinical trials in the U.S. Viral vector vaccines are a variation on this approach. Instead of using the whole coronavirus, they use a modified version of a <a href="https://theconversation.com/how-does-the-johnson-and-johnson-vaccine-compare-to-other-coronavirus-vaccines-4-questions-answered-155944">harmless adenovirus that carries parts of the coronavirus spike protein</a>. The Johnson & Johnson vaccine is a viral vector vaccine, and there are <a href="https://covid19.trackvaccines.org/country/united-states-of-america/">15 more candidates in this category in clinical trials in the U.S.</a>.</p>
<p>Protein-based vaccines use just the spike protein or part of the spike protein to generate immunity. Since the spike protein is one of the most functionally important parts of the coronavirus, an immune response that just targets this one part is sufficient to prevent or overcome an infection. The U.S. currently has <a href="https://covid19.trackvaccines.org/country/united-states-of-america/">five protein-based vaccines undergoing clinical trials</a>.</p>
<p>Nucleic acid-based vaccines are currently the most widely used in the U.S. These are made of genetic material, like DNA or RNA, that <a href="https://theconversation.com/how-mrna-vaccines-from-pfizer-and-moderna-work-why-theyre-a-breakthrough-and-why-they-need-to-be-kept-so-cold-150238">codes for the coronavirus’ spike protein</a>. Once a person gets one of these shots, their body reads the genetic material and produces the spike protein. This in turn generates an immune response. There are <a href="https://covid19.trackvaccines.org/country/united-states-of-america/">17 RNA and two DNA vaccines in clinical trials in the U.S.</a> Some of these are using the genetic material from newer variants, including updated versions of the Moderna and Pfizer vaccines.</p>
<h2>3. Will new vaccines be better than existing ones?</h2>
<p>The Moderna, Pfizer and J&J vaccines are based on the original strain of the coronavirus and are <a href="https://doi.org/10.1016/j.cell.2021.03.013">less potent when facing new variants</a>. Vaccines based on new variants would provide better protection against those newer strains than existing vaccines, and some are under development. Nucleic acid-based vaccines <a href="https://theconversation.com/how-can-scientists-update-coronavirus-vaccines-for-omicron-a-microbiologist-answers-5-questions-about-how-moderna-and-pfizer-could-rapidly-adjust-mrna-vaccines-172943">are the easiest to update</a> and make up the majority of variant-targeted vaccines. Moderna has already produced a vaccine that <a href="https://www.cnbc.com/2022/04/19/moderna-redesigned-covid-vaccine-produced-stronger-immunity-against-omicron-than-current-shots.html">contains mRNA from both the beta and omicron variants</a>, and some recently published clinical data shows that it is more effective against newer variants than Moderna’s original shot.</p>
<p>While updating nucleic acid vaccines is important, some research suggests that viral vector or whole virus vaccines could be <a href="https://doi.org/10.1016/j.vaccine.2021.08.018">more effective against new variants – without the need for updating</a>.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/461071/original/file-20220503-12-4pbyjy.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A model of the coronavirus." src="https://images.theconversation.com/files/461071/original/file-20220503-12-4pbyjy.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/461071/original/file-20220503-12-4pbyjy.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/461071/original/file-20220503-12-4pbyjy.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/461071/original/file-20220503-12-4pbyjy.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/461071/original/file-20220503-12-4pbyjy.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/461071/original/file-20220503-12-4pbyjy.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/461071/original/file-20220503-12-4pbyjy.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Whole virus vaccines use an inactivated, harmless version of the coronavirus – seen here – to produce a strong immune response.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Coronavirus._SARS-CoV-2.png#/media/File:Coronavirus._SARS-CoV-2.png">Alexey Solodovnikov, Valeria Arkhipova via WikimediaCommons</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<h2>4. What are the advantages of whole virus vaccines?</h2>
<p>Nucleic acid-based and protein-based vaccines use only the spike protein to produce an immune response. With a whole virus vaccine, the immune system not only recognizes the spike protein, but all other parts of the coronavirus, too. The other parts of the virus help to quickly generate a strong immune response that involves many different <a href="https://doi.org/10.1038/s41541-021-00292-w">branches of the immune system and lasts a long time</a>.</p>
<p>Another benefit of whole virus and viral vector vaccines is the ease of storage and shipping. Viral vector vaccines can be <a href="https://doi.org/10.1016/j.biologicals.2014.05.007">stored in common household refrigerators</a> for months, sometimes years. By comparison, the Moderna and Pfizer mRNA vaccines must be <a href="https://theconversation.com/keeping-coronavirus-vaccines-at-subzero-temperatures-during-distribution-will-be-hard-but-likely-key-to-ending-pandemic-146071">stored and shipped at ultra-low temperatures</a>. These infrastructure requirements make whole-virus vaccines much more feasible for use in remote locations of the U.S., as well as across the world.</p>
<h2>5. What are some disadvantages of whole virus vaccines?</h2>
<p>There are some downsides to whole virus vaccines.</p>
<p>To produce inactivated virus vaccines, you must first produce a huge amount of live coronavirus and then inactivate it. There is a <a href="https://doi.org/10.1016/j.vaccine.2021.02.023">small, but legitimate biohazard risk</a> associated with producing a lot of live coronavirus. A second disadvantage is that inactivated virus and viral vector vaccines <a href="https://doi.org/10.1111/j.1469-0691.2012.03971.x">might not produce strong protection in immunocompromised patients</a>. </p>
<p>Finally, producing whole virus vaccines is much more labor intensive compared to making mRNA vaccines. You must grow, then purify and then inactivate the virus while carefully checking the quality at each step. This long production process makes it hard to produce large amounts of the vaccine. For the same reasons, redesigning or updating whole-virus vaccines for future variants is more difficult compared to <a href="https://theconversation.com/how-can-scientists-update-coronavirus-vaccines-for-omicron-a-microbiologist-answers-5-questions-about-how-moderna-and-pfizer-could-rapidly-adjust-mrna-vaccines-172943">simply changing the code of nucleic acid-based</a> or protein-based vaccine.</p>
<p>Looking at the pros and cons of each vaccine type, we believe virus-based vaccines could play an important role in generating a long-lasting, broad immunity against a rapidly mutating virus. But easily updated mRNA or protein-based approaches that can be fine-tuned to the latest variants can also be key in containing the spread of the pandemic. With vaccines of all types in the works, public health officials and governments around the world will have more tools at their disposal to deal with whatever the coronavirus brings next.</p>
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<p class="fine-print"><em><span>The authors do not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Existing coronavirus vaccines are not as effective against newer variants of the virus. Two vaccine experts explain how new vaccines currently in development will likely offer better protection.Vaibhav Upadhyay, Postdoctoral Fellow of Pharmaceutical Science, University of Colorado Anschutz Medical CampusKrishna Mallela, Professor of Pharmaceutical Science, University of Colorado Anschutz Medical CampusLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1805862022-04-19T01:24:06Z2022-04-19T01:24:06ZLonger-acting eye treatment could reduce vision loss for Indigenous Australians<figure><img src="https://images.theconversation.com/files/457284/original/file-20220411-23-z8jc37.jpg?ixlib=rb-1.1.0&rect=36%2C18%2C5907%2C3926&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://image.shutterstock.com/image-photo/woman-looking-refractometer-eye-test-600w-764143345.jpg">Shutterstock</a></span></figcaption></figure><p>Indigenous people in Australia experience <a href="https://healthinfonet.ecu.edu.au/key-resources/publications/?id=35922&title=Review+of+eye+health+among+Aboriginal+and+Torres+Strait+Islander+people">three times more vision loss than non-Indigenous people</a>, creating a concerning <a href="https://mspgh.unimelb.edu.au/__data/assets/pdf_file/0006/1984173/roadmap-summary-september-2015.pdf">gap for vision</a>.</p>
<p>Much of this is due to diabetic macular oedema (DMO). Here, blood vessels in the back of the eye (the retina) are damaged by high blood sugar levels. Over time, this <a href="https://www.mdfoundation.com.au/about-macular-disease/diabetic-eye-disease/about-diabetic-retinopathy/">causes swelling (oedema) of the central part of the retina (the macula)</a>. </p>
<p>Macular oedema blurs the central vision, diminishing the ability to recognise people’s faces, to drive and work, and perform other essential tasks. DMO affects around <a href="https://www.sciencedirect.com/science/article/pii/S0161642016322564">23,000 Indigenous people in Australia</a>, with most of them of working age. Similar trends are reported in other developed states with Indigenous populations, including <a href="https://pubmed.ncbi.nlm.nih.gov/24157988/">New Zealand</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/16043760/">Canada</a> and the <a href="https://pubmed.ncbi.nlm.nih.gov/29924846/">United States</a>.</p>
<p>The good news is DMO is treatable, with medications known as <a href="https://www.mdfoundation.com.au/about-macular-disease/diabetic-eye-disease/treatment-for-diabetic-retinopathy/">anti-VEGF agents</a>. We undertook a world-first <a href="https://onlinelibrary.wiley.com/doi/abs/10.1111/ceo.14079">clinical trial</a> to test longer-acting DMO treatment for Indigenous Australians. In doing so, we also learned about undertaking culturally sensitive research on Country. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/how-can-the-new-closing-the-gap-dashboard-highlight-what-indicators-and-targets-are-on-track-163809">How can the new Closing the Gap dashboard highlight what indicators and targets are on track?</a>
</strong>
</em>
</p>
<hr>
<h2>A longer-lasting treatment</h2>
<p>When injected into the eye by an ophthalmologist (an eye surgeon), anti-VEGF drugs are safe and effective for treating DMO. The injections don’t hurt, since the eye is anaesthetised. The catch is that anti-VEGF agents are relatively short-acting, requiring them to be re-administered as often as every month. </p>
<p>Many Indigenous patients find it impractical, for complex and varied reasons, to attend <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042588/">ten to 12 eye appointments a year</a>. There is, therefore, a need for an alternative. </p>
<p>Longer-acting medications do exist. One example is a dexamethasone implant (commercially known as <a href="https://www.ozurdex.com/Content/pdf/DME_Patient_Brochure.pdf">Ozurdex(R)</a>), a steroid injected into the eye. The dexamethasone implant only needs to be dosed every three months. </p>
<p>The dexamethasone implant is PBS approved for DMO in Australia but has never been evaluated in an Indigenous population. This is important because a possible side effect of steroid medications is increased pressure in the eye. If left untreated, this can lead to a condition called steroid-induced <a href="https://www.aao.org/eye-health/diseases/what-is-glaucoma">glaucoma</a>. </p>
<p>Glaucoma is thought to occur <a href="https://bjo.bmj.com/content/103/2/191.abstract?casa_token=XV8H0UCusPIAAAAA:CdA9CdW8b4XT2j5xn2NmpQRW2abVqgyftnqBfLl7ssce6jmgyxPQYwt-4_2kEDfOOBgcASlWOEd_">less commonly overall among Indigenous people</a>, suggesting differences in the physiology of eye pressure between Caucasian and Indigenous eyes. Additionally, the incidence of steroid-induced subtype glaucoma has never been studied among Indigenous people. This is particularly important for people in remote locations, since glaucoma is a “silent disease”, requiring regular check ups for detection and treatment. </p>
<p>The <a href="https://www.mja.com.au/journal/2015/203/1/facilitators-and-barriers-implementation-pragmatic-clinical-trial-aboriginal">historical barriers preventing this sort of research</a> include cultural and geographical factors, as well as a lack of endorsement from Indigenous health services and “staff champions”.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/458470/original/file-20220419-22-c414kc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="woman checks eyes of a second woman" src="https://images.theconversation.com/files/458470/original/file-20220419-22-c414kc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/458470/original/file-20220419-22-c414kc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=497&fit=crop&dpr=1 600w, https://images.theconversation.com/files/458470/original/file-20220419-22-c414kc.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=497&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/458470/original/file-20220419-22-c414kc.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=497&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/458470/original/file-20220419-22-c414kc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=625&fit=crop&dpr=1 754w, https://images.theconversation.com/files/458470/original/file-20220419-22-c414kc.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=625&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/458470/original/file-20220419-22-c414kc.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=625&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Kerry Woods, from the clan Plangermairreenner of the Ben Lomond people, is an Aboriginal eye health coordinator involved in the study. She said it gave her ‘insight to the treatments available for diabetic eye disease and the monthly injections required to manage this condition […] Working closely with patients I have the opportunity to yarn about the treatments and if they are happier with the new timeframe.’</span>
<span class="attribution"><span class="license">Author provided</span></span>
</figcaption>
</figure>
<h2>Not just what to research, but how</h2>
<p>At the <a href="https://www.lei.org.au/">Lions Eye Institute</a>, we sought to overcome these barriers with the <a href="https://clinicaltrials.gov/ct2/show/NCT04619303">OASIS Study</a> – a world-first clinical trial in ophthalmology to exclusively recruit Indigenous patients. </p>
<p>We framed our study around ten key factors for success including support from all participating Aboriginal Medical Services, free and safe treatment, free transport, appointment reminders, and cultural safety training for all trial staff. Wherever possible, study visits were performed within patients’ usual Aboriginal Medical Service. Study participants could have friends, family and staff members present. This helped communication and a sense of safety and trust.</p>
<p>Over two years, we recruited 38 Indigenous patients and 52 eyes (some patients had DMO in both eyes). Patients were recruited from both Perth and country Western Australia. On enrolment, they were randomly assigned to receive dexamethasone implant or an anti-VEGF agent called <a href="https://www.aao.org/eye-health/drugs/avastin">Avastin</a>. Follow up was performed for check ups and re-treatments. After 12 months, we analysed all our data, to compare the safety and effectiveness of the two drugs.</p>
<p><a href="https://onlinelibrary.wiley.com/doi/abs/10.1111/ceo.14079">The results</a> showed patients who received dexamethasone implant gained four extra letters on a standard eye chart, equivalent to a 6.2% improvement in their vision. Those who received the anti-VEGF agent, meanwhile, lost 5.5 letters on average, representing an 8.9% decline. </p>
<p>Taken together, these results represented a 15% (9.5 letter) visual advantage for patients who received dexamethasone implant. In real world terms, this meant patients met the <a href="https://austroads.com.au/publications/assessing-fitness-to-drive/ap-g56/vision-and-eye-disorders/medical-standards-for-licensing-11">visual requirements for a private driver’s license</a>. Those who received the anti-VEGF agent did not. </p>
<p>This disparity was most pronounced in country towns, where dexamethasone implant had a 37% (24 letter) advantage over the anti-VEGF agent. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/457286/original/file-20220411-13-h1gbu6.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="map of WA with dot identifiers" src="https://images.theconversation.com/files/457286/original/file-20220411-13-h1gbu6.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/457286/original/file-20220411-13-h1gbu6.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=750&fit=crop&dpr=1 600w, https://images.theconversation.com/files/457286/original/file-20220411-13-h1gbu6.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=750&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/457286/original/file-20220411-13-h1gbu6.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=750&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/457286/original/file-20220411-13-h1gbu6.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=943&fit=crop&dpr=1 754w, https://images.theconversation.com/files/457286/original/file-20220411-13-h1gbu6.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=943&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/457286/original/file-20220411-13-h1gbu6.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=943&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Trial participants came from all over Western Australia.</span>
<span class="attribution"><span class="license">Author provided</span></span>
</figcaption>
</figure>
<h2>Why it works</h2>
<p>As we suspected, the reason for the dexamethasone implant’s better performance related to its less frequent, hence more pragmatic, dosing regime. </p>
<p>Over 12 months, patients who were meant to receive four dexamethasone implant injections, received an average of 3.3 injections. This meant that, on average, they received 82.5% of their intended treatments.</p>
<p>Anti-VEGF patients, meanwhile, received 7.2 of their scheduled 12 injections. This equated to only 60% of their intended treatments, and reflects the difficulty of attending monthly appointments in the real world. Anti-VEGF patients had more than twice as many injections as dexamethasone implant patients, yet ended up with poorer vision.</p>
<p>Not all the results were positive. One third of patients who received dexamethasone implant developed high pressure in the eye – a recognised side effect of steroid injections. While not painful, this requires treatment with pressure-lowering drops and close follow up, to prevent <a href="https://www.aao.org/eye-health/diseases/what-is-glaucoma">glaucoma</a>. </p>
<p>Secondly, steroid injections speed up <a href="https://www.aao.org/eye-health/diseases/what-are-cataracts">cataract</a> formation (a clouding of the lens in the eye). This requires access to cataract surgery, which is not always simple to arrange in remote locations. Based on these caveats, we developed guidelines for the judicious use of dexamethasone implant among Indigenous patients, <a href="https://onlinelibrary.wiley.com/doi/abs/10.1111/ceo.14079">published in March</a>.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/a-new-way-to-keep-first-nations-people-with-dementia-connected-to-country-community-family-and-culture-171293">A new way to keep First Nations people with dementia connected to Country, community, family and culture</a>
</strong>
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<h2>Reducing the burden, closing the vision gap</h2>
<p>While dexamethasone implants are not perfect, we believe the OASIS Study provides hope for reducing vision loss and the “burden of treatment” for Indigenous Australians with diabetes. </p>
<p>The ability to perform culturally safe clinical trials means new treatments may be similarly evaluated in the future, with consideration given to input from patients through <a href="https://findanexpert.unimelb.edu.au/scholarlywork/1415807-building-trust-and-sharing-power-for-co-creation-in-aboriginal-health-research--a-stakeholder-interview-study">community-controlled research</a>.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/racism-is-a-public-health-crisis-but-black-death-tolls-arent-the-answer-176453">Racism is a public health crisis – but Black death tolls aren't the answer</a>
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<img src="https://counter.theconversation.com/content/180586/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>This study was funded by Allergan Australia Pty Ltd which produces the treatment Ozurdex mentioned in this article. None of the authors received personal payment. The funder had no role in study design, data collection, data analysis, data interpretation, or writing of the report. </span></em></p>Our study found a better way to treat eye problems in Indigenous communities – and some key considerations for undertaking culturally safe clinical trials.Hessom Razavi, Associate professor, The University of Western AustraliaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1777482022-03-17T01:42:27Z2022-03-17T01:42:27ZA poo dose a day may keep bipolar away. When it comes to mental health, what else could poo do?<figure><img src="https://images.theconversation.com/files/451146/original/file-20220309-793-6zoqhi.jpg?ixlib=rb-1.1.0&rect=1%2C28%2C997%2C669&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/woman-toilet-160277366">Shutterstock</a></span></figcaption></figure><p>In a world first, two Australians with bipolar have had poo transplants, their symptoms improved, and their cases written up in <a href="https://journals.sagepub.com/doi/abs/10.1177/0004867420912834">peer-reviewed</a> <a href="https://pubmed.ncbi.nlm.nih.gov/35165993/">journals</a>.</p>
<p>One of us (Parker) treated the second of these patients with so-called faecal microbiota transplantation, and published his case study in recent weeks. The other (Green) is part of a team recruiting people with depression to a poo transplant clinical trial.</p>
<p>We’d be the first to admit it’s early days for this type of treatment for bipolar or other mental health issues. There are many hurdles before we could see poo transplants for these become commonplace.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1500188402901159937"}"></div></p>
<p>So we do not advocate people abandon their existing medication, try this at home or demand their psychiatrist offer them a “crapsule” (a poo capsule and yes, that’s a word).</p>
<p>Yet the limited results for bipolar so far are promising. Here’s what the evidence tells us about the prospect of poo transplants for mental health.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/poo-transplants-beyond-the-yuck-factor-what-works-what-doesnt-and-what-we-still-dont-know-82265">Poo transplants beyond the yuck factor: what works, what doesn't and what we still don't know</a>
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<h2>Let’s start with bipolar</h2>
<p>There are different types of <a href="https://theconversation.com/what-is-bipolar-disorder-the-condition-kanye-west-lives-with-143198">bipolar disorder</a>. This is when people have distinct periods of <a href="https://www.mind.org.uk/information-support/types-of-mental-health-problems/hypomania-and-mania/about-hypomania-and-mania/">mania (or a form known as hypomania)</a> – with, for example, elevated mood, increased activity and decreased sleep – and periods of depression.</p>
<p>People with bipolar usually take medication to manage their symptoms, generally for life. These medications are mainly mood stabilisers (such as lithium), but many also take antipsychotics. These medications come with risks and side effects, which depend on the medication. Side effects can include weight gain, sedation and <a href="https://library.neura.edu.au/bipolar-disorder/physical-features-bipolar-disorder/functional-changes-physical-features-bipolar-disorder/bodily-functions/motor-dysfunction-3/">movement disorders</a>.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1288402621837893632"}"></div></p>
<h2>What happened to the two patients?</h2>
<p>In 2020, Russell Hinton, a private psychiatrist, <a href="https://journals.sagepub.com/doi/abs/10.1177/0004867420912834">described how he treated</a> the first patient. This was a woman who had tried more than a dozen different medications for her bipolar. She had been hospitalised ten times, had gained considerable weight and judged she had no quality of life.</p>
<p>After a poo transplant from her husband, she became symptom-free over the next five years, lost 33 kilograms, required no medication and her career bloomed.</p>
<p>Gordon Parker and colleagues at the University of New South Wales <a href="https://pubmed.ncbi.nlm.nih.gov/35165993/">reported their results</a> with the second patient last month. This was a young man who developed bipolar as a teenager, had tried numerous medications and became progressively intolerant of their side effects.</p>
<p>After a poo transplant, he was able to progressively cease all medications over the next year, and had virtually no mood swings. He also noted an improvement in his anxiety and ADHD (attention deficit hyperactivity disorder).</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/adhd-looks-different-in-adults-here-are-4-signs-to-watch-for-178639">ADHD looks different in adults. Here are 4 signs to watch for</a>
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</em>
</p>
<hr>
<h2>How could this possibly work?</h2>
<p>Trillions of bacteria live in our guts. This so-called gut microbiome has a huge impact on our health in general, not just the health of our brain.</p>
<p>Differences in gut bacteria have been linked to <a href="https://www.nature.com/articles/s41367-019-0011-7">obesity</a>, <a href="https://www.thelancet.com/journals/ebiom/article/PIIS235239641930800-X/fulltext">diabetes</a> and <a href="https://www.gastrojournal.org/article/S0016-5085(19)34649-9/fulltext">irritable bowel syndrome</a>.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/YB-8JEo_0bI?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">What is the human microbiome?</span></figcaption>
</figure>
<p>The idea behind poo transplants is to change the gut microbiome. You take poo, with all its micro-organisms, from a healthy person and give it to the one being treated.</p>
<p>You can do this “top down”, for example, by swallowing poo capsules (crapsules), or by delivering poo through a tube inserted into the nose, to the stomach or intestine. </p>
<p>Alternatively, you can insert the poo “bottom up”. You can do this with an enema, a simple, painless procedure in which a syringe transfers the poo into the rectum. Or you can use a colonoscopy, a procedure performed under a general anaesthetic involving inserting a tube higher up into the colon.</p>
<p>Poo transplants are already <a href="https://theconversation.com/poo-transplants-and-probiotics-does-anything-work-to-improve-the-health-of-our-gut-65480">used to treat</a> the often life-threatening gut infection caused by the bacterium <em>Clostridium difficile</em>.</p>
<p>They have also been trialled, with various degrees of success, in people with <a href="https://pubmed.ncbi.nlm.nih.gov/33345703/#:%7E:text=Preliminary%20data%20suggest%20that%20FMT,UC%20being%20the%20most%20compelling">irritable bowel syndrome, ulcerative colitis</a>, <a href="https://www.nature.com/articles/s41467-021-21472-1">HIV</a> and <a href="https://pubmed.ncbi.nlm.nih.gov/32279172/">hepatitis</a>, among other medical conditions.</p>
<p>Side effects from poo transplants <a href="https://pubmed.ncbi.nlm.nih.gov/33345703/#:%7E:text=Preliminary%20data%20suggest%20that%20FMT,UC%20being%20the%20most%20compelling">are rare</a>, and usually relate to the way in which they are given, for example side effects of the anaesthetic from poo transplants delivered by colonoscopy.</p>
<h2>So how about mental health?</h2>
<p>Abnormal gut microbiomes <a href="https://www.nature.com/articles/s41380-022-01456-3">have been linked</a> to bipolar, depression and schizophrenia.</p>
<p>When poo from depressed humans is given to rats, they appear to develop a <a href="https://pubmed.ncbi.nlm.nih.gov/27491067/">rat version of depression</a>. Likewise, when mice are given poo from someone with schizophrenia, they <a href="https://www.science.org/doi/10.1126/sciadv.aau8317">develop a mouse version of schizophrenia</a>.</p>
<p>These are indirect findings. Yet they suggest poo transplants may have the potential to treat some mental health conditions.</p>
<p>So how exactly do bacteria in the gut impact mental health? There are many <a href="https://pubmed.ncbi.nlm.nih.gov/31460832/">different ways</a>, each complicated and interacting with each other. </p>
<p>For example, these bacteria act directly on the gut wall, sending signals to the brain via the vagus nerve. The bacteria also produce large quantities of chemicals (for example, <a href="https://pubmed.ncbi.nlm.nih.gov/31460832/">short-chain fatty acids</a>), which impact virtually all body systems including the immune system. We know brain function relies heavily on immune cells.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/stomach-and-mood-disorders-how-your-gut-may-be-playing-with-your-mind-50847">Stomach and mood disorders: how your gut may be playing with your mind</a>
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</em>
</p>
<hr>
<h2>Don’t try this at home</h2>
<p>At this stage, any evidence suggesting poo transplants may help people with depression or bipolar is, essentially, anecdotal.</p>
<p>Some people have tried their own version at home, involving poo donors who have not been screened for diseases.</p>
<p>One high-profile example is Dave Hosking from the Australian band Boy & Bear. He used a “<a href="https://www.rollingstone.com/music/music-features/boy-bear-dave-hosking-fecal-transplant-919384/">poo roadie</a>” to provide him with transplants on tour to help manage his depression and anxiety.</p>
<p>We wouldn’t recommend this. Poo transplants should only be carried out under the supervision of medical professionals, using an approved and thoroughly screened poo product.</p>
<p>Poo transplants are <a href="https://www.legislation.gov.au/Details/F2021C01065">tightly regulated in Australia</a>. Donations must be screened for harmful bacteria, fungi, parasites or viruses. Donors must also not have any health condition thought to be associated with gut bacteria, such as an autoimmune condition, cancer or obesity.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/boosting-your-gut-health-sounds-great-but-this-wellness-trend-is-vague-and-often-misunderstood-155472">Boosting your ‘gut health’ sounds great. But this wellness trend is vague and often misunderstood</a>
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</em>
</p>
<hr>
<h2>What happens next?</h2>
<p>We need larger, well-designed studies to show poo transplants have a real effect, and any improved symptoms cannot be explained by other factors. </p>
<p>We also need to look for markers in the microbiome that could predict a successful result. If we knew those markers, we could optimise treatment and better measure the results. </p>
<p>The first author’s centre is recruiting <a href="https://foodandmoodcentre.com.au/projects/movingmoods/">people with depression</a> to trial poo transplants. The study will randomise participants to have an enema or placebo enema. If successful, a larger study is planned. </p>
<p>In Canada, there are three such studies under way evaluating poo transplants. These are for <a href="https://pubmed.ncbi.nlm.nih.gov/34261526/">bipolar</a>, <a href="https://clinicaltrials.gov/ct2/show/NCT04805879">depression</a>, with or without <a href="https://clinicaltrials.gov/ct2/show/NCT05174273?cond=fmt&draw=8">irritable bowel syndrome</a>. </p>
<p>Though promising, we cannot conclude at this time whether poo transplants work for bipolar or depression.</p>
<p>Until the results of these studies are in, it’s too early to say if the early results with bipolar can be replicated on a larger scale.</p>
<hr>
<p><em>If this article has raised issues for you, or if you’re concerned about someone you know, call Lifeline on 13 11 14.</em></p><img src="https://counter.theconversation.com/content/177748/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jessica Green is affiliated with:
1. Food & Mood Centre, IMPACT, Deakin University
2. Department of Psychiatry, Peninsula Health
3. Monash Alfred Psychiatry Research Centre, Monash University</span></em></p><p class="fine-print"><em><span>Gordon Parker is affiliated with the Discipline of Psychiatry and Mental Health
School of Clinical Medicine, University of New South Wales
</span></em></p>Two Australians with bipolar have been successfully treated with poo transplants, allowing them to come off, or reduce, their medications. Here’s where the science is up to.Jessica Green, PhD Candidate and Consultant Psychiatrist, Deakin UniversityGordon Parker, Scientia Professor, UNSW SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1741522022-02-23T19:30:41Z2022-02-23T19:30:41Z90% of drugs fail clinical trials – here’s one way researchers can select better drug candidates<figure><img src="https://images.theconversation.com/files/446585/original/file-20220215-13-1cb5lri.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2000%2C1500&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The majority of drug failures are attributed to lack of clinical efficacy and high toxicity.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/medicine-capsules-in-test-tube-royalty-free-image/146592215">Andrew Brookes/Image Source via Getty Images</a></span></figcaption></figure><p>It takes <a href="https://doi.org/10.1038/d41573-021-00190-9">10 to 15 years</a> and <a href="https://doi.org/10.1001/jama.2020.1166">around US$1 billion</a> to develop one successful drug. Despite these significant investments in time and money, <a href="https://doi.org/10.1038/nrd.2016.136">90% of drug candidates</a> in clinical trials fail. Whether because they don’t adequately treat the condition they’re meant to target or the side effects are too strong, many drug candidates never advance to the approval stage.</p>
<p>As a <a href="https://scholar.google.com/citations?user=Ufab1aYAAAAJ&hl=en">pharmaceutical scientist</a> working in drug development, I have been frustrated by this high failure rate. Over the past 20 years, <a href="https://pharmacy.umich.edu/sun-lab">my lab</a> has been investigating ways to improve this process. We believe that <a href="https://doi.org/10.1016/j.apsb.2022.02.002">starting from the very early stages</a> of development and changing how researchers <a href="https://doi.org/10.1016/j.apsb.2022.02.015">select potential drug candidates</a> could lead to better success rates and ultimately better drugs.</p>
<h2>How does drug development work?</h2>
<p>Over the past few decades, drug development has followed what’s called a <a href="https://doi.org/10.1038/nrd4578">classical process</a>. Researchers start by finding a molecular target that causes disease – for instance, an overproduced protein that, if blocked, could help stop cancer cells from growing. They then screen a library of chemical compounds to find potential drug candidates that act on that target. Once they pinpoint a promising compound, researchers optimize it in the lab.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/w3ykU52K-Hw?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Drugs go through a number of stages of development and testing before they’re given to people in clinical trials.</span></figcaption>
</figure>
<p><a href="https://doi.org/10.1016/j.apsb.2022.02.002">Drug optimization</a> primarily focuses on two aspects of a drug candidate. First, it has to be able to strongly block its molecular target without affecting irrelevant ones. To optimize for potency and specificity, researchers focus on its <a href="https://dx.doi.org/10.1007%2F978-1-62703-342-8_6">structure-activity relationship</a>, or how the compound’s chemical structure determines its activity in the body. Second, it has to be “<a href="https://doi.org/10.2174/138161209788682479">druglike</a>,” meaning able to be absorbed and transported through the blood to act on its intended target in affected organs.</p>
<p>Once a drug candidate meets the researcher’s optimization benchmarks, it goes on to <a href="https://www.fda.gov/patients/learn-about-drug-and-device-approvals/drug-development-process">efficacy and safety testing</a>, first in animals, then in clinical trials with people.</p>
<h2>Why does 90% of clinical drug development fail?</h2>
<p>Only <a href="https://doi.org/10.1038/nrd.2016.136">1 out of 10 drug candidates</a> successfully passes clinical trial testing and regulatory approval. A 2016 analysis identified <a href="https://doi.org/10.1038/nrd.2016.184">four possible reasons</a> for this low success rate. The researchers found between 40% and 50% of failures were due to a lack of clinical efficacy, meaning the drug wasn’t able to produce its intended effect in people. Around 30% were due to unmanageable toxicity or side effects, and 10%-15% were due to poor pharmacokinetic properties, or how well a drug is absorbed by and excreted from the body. Lastly, 10% of failures were attributed to lack of commercial interest and poor strategic planning. </p>
<p>This high failure rate raises the question of whether there are other aspects of drug development that are being <a href="https://doi.org/10.1016/j.apsb.2022.02.002">overlooked</a>. On the one hand, it is challenging to truly confirm whether a chosen molecular target is the best marker to screen drugs against. On the other hand, it’s possible that the current drug optimization process hasn’t been leading to the best candidates to select for further testing.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/446645/original/file-20220215-15-1ftjn5e.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Diagram depicting failure rate at each step of the drug development process, with more than 10,000 candidates at the compound screening stage, fewer than 250 at the next stage and steadily decreasing through the phases." src="https://images.theconversation.com/files/446645/original/file-20220215-15-1ftjn5e.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/446645/original/file-20220215-15-1ftjn5e.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=352&fit=crop&dpr=1 600w, https://images.theconversation.com/files/446645/original/file-20220215-15-1ftjn5e.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=352&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/446645/original/file-20220215-15-1ftjn5e.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=352&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/446645/original/file-20220215-15-1ftjn5e.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=443&fit=crop&dpr=1 754w, https://images.theconversation.com/files/446645/original/file-20220215-15-1ftjn5e.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=443&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/446645/original/file-20220215-15-1ftjn5e.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=443&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">With each successive step of the drug development process, the probability of success gets increasingly smaller.</span>
<span class="attribution"><span class="source">Duxin Sun and Hongxiang Hu</span></span>
</figcaption>
</figure>
<p>Drug candidates that reach clinical trials need to achieve a delicate balance of giving just enough drug so it has the intended effect on the body without causing harm. Optimizing a drug’s ability to pinpoint and act strongly on its intended target is clearly important in how well it’s able to strike that balance. But my research team and I believe that this aspect of drug performance has been overemphasized. Optimizing a drug’s ability to reach diseased body parts in adequate levels while avoiding healthy body parts – its <a href="https://doi.org/10.1016/j.apsb.2022.02.015">tissue exposure and selectivity</a> – is just as important.</p>
<p>For instance, scientists may spend many years trying to optimize the potency and specificity of drug candidates so that they affect their targets at very low concentrations. But this might be at the expense of ensuring that enough drug is reaching the right body parts and not causing harm to healthy tissue. My research team and I believe that this <a href="https://doi.org/10.1016/j.apsb.2022.02.002">unbalanced drug optimization process</a> may skew drug candidate selection and affect how it ultimately performs in clinical trials.</p>
<h2>Improving the drug development process</h2>
<p>Over the past few decades, scientists have developed and implemented many successful tools and <a href="https://doi.org/10.1038/s41573-020-0087-3">improvement strategies</a> for each step of the drug development process. These include <a href="https://doi.org/10.1038/nrd3368">high-throughput screening</a> that uses robots to automate millions of tests in the lab, speeding up the process of identifying potential candidates; <a href="https://doi.org/10.1038/d43747-021-00045-7">artificial intelligence-based</a> drug design; new approaches to predict and test for <a href="https://doi.org/10.1016/j.yrtph.2020.104662">toxicity</a>; and more precise <a href="https://doi.org/10.1038/nature15819">patient selection</a> in clinical trials. Despite these strategies, however, the success rate <a href="https://doi.org/10.1111/cts.12980">still hasn’t changed</a> by much.</p>
<p>My team and I believe that exploring new strategies focusing on the earliest stages of drug development when researchers are selecting potential compounds may help increase success. This could be done with new technology, like the gene editing tool <a href="https://doi.org/10.1126/scitranslmed.aaw8412">CRISPR</a>, that can more rigorously confirm the correct molecular target that causes disease and whether a drug is actually targeting it. </p>
<p>And it could also be done through a new <a href="https://doi.org/10.1016/j.apsb.2022.02.015">STAR system</a> my research team and I devised to help researchers better strategize how to balance the many factors that make an optimal drug. Our STAR system gives the overlooked <a href="https://doi.org/10.1016/j.apsb.2022.02.015">tissue exposure and selectivity</a> aspect of a drug equal importance to its potency and specificity. This means that a drug’s ability to reach diseased body parts at adequate levels will be optimized just as much as how precisely it’s able to affect its target. To do this, the system groups drugs into four classes based on these two aspects, along with recommended dosing. Different classes would require different optimization strategies before a drug goes on to further testing.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/446647/original/file-20220215-23-vjtr5a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Diagram depicting the STAR drug classication system, with specificity/potency on the vertical axis and tissue exposure/selectivity on the horizontal axis" src="https://images.theconversation.com/files/446647/original/file-20220215-23-vjtr5a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/446647/original/file-20220215-23-vjtr5a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=444&fit=crop&dpr=1 600w, https://images.theconversation.com/files/446647/original/file-20220215-23-vjtr5a.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=444&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/446647/original/file-20220215-23-vjtr5a.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=444&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/446647/original/file-20220215-23-vjtr5a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=558&fit=crop&dpr=1 754w, https://images.theconversation.com/files/446647/original/file-20220215-23-vjtr5a.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=558&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/446647/original/file-20220215-23-vjtr5a.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=558&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The STAR system provides a systematic way to approach drug candidate selection, taking into account different factors that play a role in how clinically successful a drug may be.</span>
<span class="attribution"><span class="source">Duxin Sun and Hongxiang Hu</span></span>
</figcaption>
</figure>
<p>A Class I drug candidate, for instance, would have high potency/specificity as well as high tissue exposure/selectivity. This means it would need only a low dose to maximize its efficacy and safety and would be the most desirable candidate to move forward. A Class IV drug candidate, on the other hand, would have low potency/specificity as well as low tissue exposure/selectivity. This means it likely has inadequate efficacy and high toxicity, so further testing should be terminated.</p>
<p>Class II drug candidates have high specificity/potency and low tissue exposure/selectivity, which would require a high dose to achieve adequate efficacy but may have unmanageable toxicity. These candidates would require more cautious evaluation before moving forward.</p>
<p>Finally, Class III drug candidates have relatively low specificity/potency but high tissue exposure/selectivity, which may require a low to medium dose to achieve adequate efficacy with manageable toxicity. These candidates may have a high clinical success rate but are often overlooked.</p>
<h2>Realistic expectations for drug development</h2>
<p>Having a drug candidate reach the clinical trial stage is a big deal for any pharmaceutical company or academic institution developing new drugs. It’s disappointing when the years of effort and resources spent to push a drug candidate to patients so often lead to failure.</p>
<p>Improving the drug optimization and selection process may significantly improve success of a given candidate. Although the nature of drug development may not make reaching a 90% success rate easily achievable, we believe that even moderate improvements can significantly reduce the cost and time it takes to find a cure for many human diseases.</p>
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<p class="fine-print"><em><span>Duxin Sun receives funding from NIH, FDA, and Pharmaceutical Industries for research in his lab at The University of Michigan </span></em></p>Drug development is a long and costly process that often ends in failure. Improving the way potential drug candidates are optimized could help boost success rates.Duxin Sun, Professor of Pharmaceutical Sciences, University of MichiganLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1715872021-12-22T13:13:00Z2021-12-22T13:13:00ZMedical technologies have been central to US pandemic response – but social behaviors matter just as much<figure><img src="https://images.theconversation.com/files/438295/original/file-20211218-19-1tip125.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C1024%2C683&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">COVID-19 vaccines and treatments aren't societal silver bullets when health disparities persist.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/pedestrian-walks-in-front-of-a-covid-19-vaccination-site-in-news-photo/1236679829">Michael Nagle/Xinhua via Getty Images</a></span></figcaption></figure><p>Before COVID-19, there was tuberculosis. Twentieth century British physician Thomas McKeown <a href="https://dx.doi.org/10.2105%2Fajph.92.5.725">controversially proposed</a> that the sharp declines in infectious disease death rates in the late 1900s were due to improved economic and social conditions – not medical and public health measures like antibiotics and improved sanitation.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/438283/original/file-20211217-13-mtazkf.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Graph showing mortality rate of tuberculosis in Massachusetts from 1861-1970 and in the US overall from 1900-2014" src="https://images.theconversation.com/files/438283/original/file-20211217-13-mtazkf.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/438283/original/file-20211217-13-mtazkf.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=434&fit=crop&dpr=1 600w, https://images.theconversation.com/files/438283/original/file-20211217-13-mtazkf.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=434&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/438283/original/file-20211217-13-mtazkf.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=434&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/438283/original/file-20211217-13-mtazkf.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=546&fit=crop&dpr=1 754w, https://images.theconversation.com/files/438283/original/file-20211217-13-mtazkf.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=546&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/438283/original/file-20211217-13-mtazkf.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=546&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">This graph shows the tuberculosis death rate in Massachusetts from 1861-1970 and in the U.S. overall from 1900-2014, using merged data from the U.S. Census Bureau and the Centers for Disease Control and Prevention. While not the same graph that McKeown used, it shows a similar trend that highlights the steep decrease in death rates that occurred before antibiotics and vaccination became available.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Tuberculosis_in_the_USA_1861-2014.png">Ljstalpers/Wikimedia Commons</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>His theory was <a href="https://doi.org/10.1093/shm/1.1.1">later partly discredited</a>. But the central question behind it – whether medical interventions or social factors make the biggest impact on infectious diseases – remains relevant in the current pandemic.</p>
<p>When COVID-19 first arrived in the U.S., the only tool public health officials had to stop its spread was behavior change through <a href="http://dx.doi.org/10.15585/mmwr.mm6935a2">lockdowns</a>, <a href="https://graphics.reuters.com/HEALTH-CORONAVIRUS/USA/qmypmkmwpra/">social distancing</a> and <a href="https://ballotpedia.org/State-level_mask_requirements_in_response_to_the_coronavirus_(COVID-19)_pandemic,_2020-2021">face masks</a>. With <a href="https://www.fda.gov/news-events/press-announcements/fda-takes-key-action-fight-against-covid-19-issuing-emergency-use-authorization-first-covid-19">vaccines</a>, the tide seemed to turn. But with <a href="https://www.npr.org/2021/11/27/1059534796/covid-19-vaccine-makers-combat-omicron-variant">new variants</a>, <a href="https://doi.org/10.1038/d41586-021-03674-1">waning immunity</a> and ongoing <a href="https://www.pewtrusts.org/en/research-and-analysis/blogs/stateline/2021/03/02/covid-19-vaccine-hesitancy-slows-race-to-defang-the-virus">vaccine hesitancy</a>, the pandemic is still <a href="https://www.npr.org/sections/coronavirus-live-updates/2021/12/14/1063802370/america-us-covid-death-toll">far from over</a>.</p>
<p>So which are more successful at driving down rates of disease and death – social behaviors or medical technologies?</p>
<p>As an <a href="https://scholar.google.com/citations?user=7dOF204AAAAJ&hl=en&oi=ao">infectious disease and social epidemiologist</a>, I have been particularly interested in how new medical technologies affect existing health disparities. I believe that understanding the interplay between behavior and technology will be key to surviving the pandemic and emerging as a stronger society.</p>
<h2>Do technologies help or make things worse?</h2>
<p>Biomedicine has clearly played a critical role in mitigating COVID-19. Less than a year after discovering the virus that causes COVID-19, researchers were able to develop multiple vaccines that are <a href="https://www.yalemedicine.org/news/covid-19-vaccine-comparison">highly effective</a> in preventing severe infection and transmission from most variants. They’re also likely to <a href="https://doi.org/10.1016/S1473-3099(21)00460-6">reduce the risk of long COVID-19</a>, the ongoing symptoms that can persist for months after initial recovery. COVID-19 vaccines are estimated to have <a href="https://doi.org/10.1377/hlthaff.2021.00619">saved almost 140,000 lives in the U.S.</a> in the first five months of 2021.</p>
<p>There has also been remarkable medical progress in other arenas. Even though antivirals are <a href="https://cen.acs.org/pharmaceuticals/drug-discovery/antiviral-drug-development-covid-19/99/i19">notoriously difficult to manufacture</a>, there are finally <a href="https://combatcovid.hhs.gov/possible-treatment-options-covid-19/monoclonal-antibodies-high-risk-covid-19-positive-patients">options for treating COVID-19</a>. Merck’s <a href="https://www.merck.com/news/merck-and-ridgebacks-investigational-oral-antiviral-molnupiravir-reduced-the-risk-of-hospitalization-or-death-by-approximately-50-percent-compared-to-placebo-for-patients-with-mild-or-moderat/">molnupiravir</a> cuts hospitalization risks for adults in half, and Pfizer’s <a href="https://www.statnews.com/2021/12/14/pfizers-covid-pill-remains-89-effective-in-final-analysis-company-says/">paxlovid</a> has 89% efficacy at preventing hospitalization and death. Additional treatments are <a href="https://www.npr.org/sections/health-shots/2021/11/30/1059926089/new-antiviral-drugs-are-coming-for-covid-heres-what-you-need-to-know">expected in the coming months</a>.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/438512/original/file-20211220-49229-14dieqg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A health care worker holds up a Moderna COVID-19 vaccine vial." src="https://images.theconversation.com/files/438512/original/file-20211220-49229-14dieqg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/438512/original/file-20211220-49229-14dieqg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/438512/original/file-20211220-49229-14dieqg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/438512/original/file-20211220-49229-14dieqg.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/438512/original/file-20211220-49229-14dieqg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/438512/original/file-20211220-49229-14dieqg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/438512/original/file-20211220-49229-14dieqg.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Although currently available COVID-19 vaccines still provide protection against infection, ongoing vaccine hesitancy has made herd immunity increasingly unlikely as new variants emerge.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/health-worker-shows-a-bottle-of-moderna-covid-19-vaccine-to-news-photo/1235973935">Moch Farabi Wardana/Pacific Press/LightRocket via Getty Images</a></span>
</figcaption>
</figure>
<p>Researchers have also developed and scaled up a variety of innovative diagnostic technologies. These range from using <a href="https://doi.org/10.1126/science.abh0635">PCR tests</a> to predict the trajectory of the pandemic to implementing <a href="https://www.cdc.gov/coronavirus/2019-ncov/lab/multiplex.html">blood tests</a> that can simultaneously measure antibody levels against COVID-19 and other pathogens for quicker diagnosis.</p>
<p><a href="https://www.csis.org/analysis/beyond-covax-importance-public-private-partnerships-covid-19-vaccine-delivery-developing">Collaboration</a> across both public and private sectors has also been fairly unprecedented. Large-scale government funding has aided these efforts. The U.S. National Institutes of Health’s <a href="https://www.nih.gov/research-training/medical-research-initiatives/radx">Rapid Acceleration of Diagnostics, or RADx</a>, initiative, for example, has worked to <a href="https://www.nih.gov/news-events/news-releases/nih-funded-covid-19-testing-initiative-aims-safely-return-children-person-school">contain outbreaks in schools</a> by providing COVID-19 test kits across the country.</p>
<h2>Social factors as drivers of health</h2>
<p>Despite these technological advancements, the COVID-19 pandemic has illuminated long-standing <a href="https://doi.org/10.1073/pnas.2101386118">health disparities</a>. In 2020, Latino and Black people died from COVID-19 at a rate almost three times higher than white people.</p>
<p>Systemic structural and social inequities are some of the reasons behind these disparities in the U.S. For example, communities of color are disproportionately represented in <a href="https://dx.doi.org/10.1002%2Fwmh3.358">essential</a> occupations that are at the front lines of potential COVID-19 exposure. In addition, Black and Hispanic Americans have <a href="https://www.brookings.edu/blog/up-front/2020/08/07/black-and-hispanic-americans-at-higher-risk-of-hypertension-diabetes-obesity-time-to-fix-our-broken-food-system/">higher rates of obesity, hypertension and type 2 diabetes</a>, known risk factors for severe COVID-19 complications. Children in communities of color also experienced the death of a primary caregiver at a rate <a href="https://doi.org/10.1542/peds.2021-053760">up to 4.5 times higher</a> than non-Hispanic white children.</p>
<figure class="align-center ">
<img alt="People wearing face masks inside an outdoor market." src="https://images.theconversation.com/files/438293/original/file-20211218-21-44hqf5.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C1024%2C676&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/438293/original/file-20211218-21-44hqf5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=396&fit=crop&dpr=1 600w, https://images.theconversation.com/files/438293/original/file-20211218-21-44hqf5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=396&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/438293/original/file-20211218-21-44hqf5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=396&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/438293/original/file-20211218-21-44hqf5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=498&fit=crop&dpr=1 754w, https://images.theconversation.com/files/438293/original/file-20211218-21-44hqf5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=498&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/438293/original/file-20211218-21-44hqf5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=498&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Communities of color and low-income populations are disproportionately burdened by COVID-19 hospitalizations and deaths.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/people-wear-face-coverings-inside-grand-central-market-on-news-photo/1359215939">Mario Tama/Getty Images</a></span>
</figcaption>
</figure>
<p>Technologies intended to improve health care can themselves exacerbate health disparities. This results in a <a href="https://doi.org/10.1038/s41746-021-00413-8">digital divide</a> where certain populations continue to have poor health despite technological improvements. For example, the safety and convenience of remote videoconferencing is a privilege unavailable for those who need to go to public workspaces to access these technologies.</p>
<p>This divide extends to medical devices used in routine care. <a href="https://theconversation.com/more-health-inequality-black-people-are-3-times-more-likely-to-experience-pulse-oximeter-errors-152359">Oximeters</a> that measure oxygen levels in the blood tend to produce inflated results for people with darker skin because they were calibrated in clinical trials with mostly white participants. This racial bias may result in denial of care if someone with darker skin gets a normal reading despite actually having dangerously low oxygen levels.</p>
<h2>Health disparities persist despite technology</h2>
<p>These inequities are often derived from ongoing historical biases and discrimination.</p>
<p>Socioeconomic status, occupation and economic mobility are <a href="https://doi.org/10.1056/NEJMp2019445">primary drivers of unequal health outcomes</a>. In 2020, 5.4 million laid-off workers became uninsured <a href="https://www.familiesusa.org/resources/the-covid-19-pandemic-and-resulting-economic-crash-have-caused-the-greatest-health-insurance-losses-in-american-history/">in just four months</a>. In 2019, <a href="https://shift.hks.harvard.edu/essential-and-vulnerable-service-sector-workers-and-paid-sick-leave/">55% of retail and food workers</a> at large firms didn’t have access to paid sick leave. Many immigrants, whether undocumented or legal U.S. residents, are likely to <a href="https://www.kff.org/racial-equity-and-health-policy/fact-sheet/public-charge-policies-for-immigrants-implications-for-health-coverage/">avoid the health care system</a> due to fear of deportation and limited insurance coverage and public assistance.</p>
<p>Difficulty parsing through health information is another factor. In addition to <a href="https://www.kff.org/coronavirus-covid-19/press-release/covid-19-misinformation-is-ubiquitous-78-of-the-public-believes-or-is-unsure-about-at-least-one-false-statement-and-nearly-at-third-believe-at-least-four-of-eight-false-statements-tested/">abundant misinformation</a> about COVID-19, nearly <a href="https://nnlm.gov/guides/intro-health-literacy">9 in 10 adults</a> struggle with health literacy. A <a href="https://doi.org/10.1001/jamanetworkopen.2020.12403">July 2020 study</a> found that Black men were less likely to know about COVID-19 symptoms and how the virus spreads than white men. For some groups, <a href="https://www.healthypeople.gov/2020/topics-objectives/topic/social-determinants-health/interventions-resources/health-literacy">limited English proficiency and cultural beliefs</a> are barriers to health communication.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/438513/original/file-20211220-19-wzxt9h.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Anti-vaccine protesters holding up signs reading 'NO VAX MANDATE FOR KIDS'" src="https://images.theconversation.com/files/438513/original/file-20211220-19-wzxt9h.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/438513/original/file-20211220-19-wzxt9h.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/438513/original/file-20211220-19-wzxt9h.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/438513/original/file-20211220-19-wzxt9h.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/438513/original/file-20211220-19-wzxt9h.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/438513/original/file-20211220-19-wzxt9h.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/438513/original/file-20211220-19-wzxt9h.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">People with limited health literacy are especially vulnerable to misinformation about COVID-19.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/myra-cuevas-of-chatsworth-opposed-to-lausds-student-vaccine-news-photo/1237098534">David Crane/MediaNews Group/Los Angeles Daily News via Getty Images</a></span>
</figcaption>
</figure>
<p>Even more critical is distrust in the medical system. Historical <a href="https://www.cdc.gov/tuskegee/index.html">unethical experimentation</a> and <a href="https://www.covidcollaborative.us/content/vaccine-treatments/coronavirus-vaccine-hesitancy-in-black-and-latinx-communities">everyday racism</a> have led to a lack of confidence in scientists and clinicians among vulnerable populations. <a href="https://www.covidcollaborative.us/content/vaccine-treatments/coronavirus-vaccine-hesitancy-in-black-and-latinx-communities">Two-thirds</a> of Black adults believe the government can rarely or never be trusted to look out for the interests of their community. </p>
<p>Conversely, that COVID-19 hospitalizations and deaths disproportionately affect lower-income populations and communities of color reinforces the need for greater diversity in clinical research participants. Over 80% of participants in the Pfizer-BioNTech COVID-19 vaccine trial <a href="https://www.kff.org/racial-equity-and-health-policy/issue-brief/racial-diversity-within-covid-19-vaccine-clinical-trials-key-questions-and-answers/">identified as white</a>. Having clinical trials that reflect the patients who will be treated ensures that the drug will work for all and encourages confidence among those communities.</p>
<h2>The importance of social factors in health</h2>
<p>While technology has greatly improved U.S. pandemic response, broader societal ills continue to impede the nation’s ability to control COVID-19.</p>
<p>The McKeown debate exposes a common misconception that improving health is a binary: a choice between improving social conditions or developing new technologies and medicines. But a growing body of research shows that <a href="https://doi.org/10.1177/0022146510383498">social factors</a>, or the <a href="https://health.gov/healthypeople/objectives-and-data/social-determinants-health">conditions where people live</a>, work and play, are key to health outcomes.</p>
<p>There are <a href="https://doi.org/10.1056/NEJMp2021209">numerous strategies</a> that can increase health equity in this time of crisis. These include tackling food insecurity, flexibility in work conditions, <a href="https://publichealth.jhu.edu/2021/carrying-equity-in-covid-19-vaccination-forward-guidance-informed-by-communities-of-color">targeted vaccine initiatives</a> and <a href="http://dx.doi.org/10.5888/pcd17.200245">culturally competent health care</a>. <a href="https://covid19community.nih.gov/">Engaging with communities</a> as partners in health also advances the nation’s ability to cope during a crisis.</p>
<p>Nobel prize-winning economist <a href="https://www.penguinrandomhouse.com/books/163962/development-as-freedom-by-amartya-sen/">Amartya Sen</a> hypothesized that increases in life expectancy in the 20th century occurred in periods marked by a strong emphasis on social sharing and public provision of health care. To me, it’s clear that the time has come to invest not just in new technologies and medical treatments, but also in communities.</p>
<p>[<em>Get the best of The Conversation’s politics, science or religion articles each week.</em><a href="https://memberservices.theconversation.com/newsletters/?source=inline-best">Sign up today</a>.]</p><img src="https://counter.theconversation.com/content/171587/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Eyal Oren receives funding from the National Institutes of Health.</span></em></p>Vaccines and medical treatments can only go so far in an unequal society. Facing the ongoing history of racial discrimination and bias in the US would help end the pandemic.Eyal Oren, Professor of Epidemiology, San Diego State UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1735542021-12-15T19:49:31Z2021-12-15T19:49:31ZHow effective are vaccines against omicron? An epidemiologist answers 6 questions<figure><img src="https://images.theconversation.com/files/437635/original/file-20211214-15-12p1fq7.jpg?ixlib=rb-1.1.0&rect=134%2C0%2C5856%2C3880&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Understanding how much protection a vaccine offers is not as simple as it sounds.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/covid-19-vaccine-royalty-free-image/1287544065?adppopup=true">Andriy Onufriyenko/Moment via Getty Images</a></span></figcaption></figure><p><em>The pandemic has brought many tricky terms and ideas from epidemiology into everyone’s lives. Two particularly complicated concepts are vaccine <a href="https://theconversation.com/pfizer-vaccine-what-an-efficacy-rate-above-90-really-means-149849">efficacy and effectiveness</a>. These are not the same thing. And as time goes on and new variants like omicron emerge, they are changing, too. Melissa Hawkins is an <a href="https://www.american.edu/cas/faculty/mhawkins.cfm">epidemiologist and public health researcher</a> at American University. She explains the way researchers calculate how well a vaccine prevents disease, what influences these numbers and how omicron is changing things.</em></p>
<h2>1. What do vaccines do?</h2>
<p>A <a href="https://www.cdc.gov/vaccinesafety/ensuringsafety/history/index.html">vaccine</a> activates the <a href="https://theconversation.com/how-mrna-vaccines-from-pfizer-and-moderna-work-why-theyre-a-breakthrough-and-why-they-need-to-be-kept-so-cold-150238">immune system to produce antibodies</a> that remain in your body to fight against exposure to a virus in the future. All three vaccines currently approved for use in the U.S. – the Pfizer-BioNTech, Moderna and Johnson & Johnson vaccines – showed <a href="https://www.cdc.gov/vaccines/covid-19/clinical-considerations/covid-19-vaccines-us.html">impressive success in clinical trials</a>. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/437637/original/file-20211214-19-kx4h5b.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A medical professional getting a shot." src="https://images.theconversation.com/files/437637/original/file-20211214-19-kx4h5b.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/437637/original/file-20211214-19-kx4h5b.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/437637/original/file-20211214-19-kx4h5b.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/437637/original/file-20211214-19-kx4h5b.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/437637/original/file-20211214-19-kx4h5b.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/437637/original/file-20211214-19-kx4h5b.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/437637/original/file-20211214-19-kx4h5b.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Clinical trials are used to calculate the efficacy of a vaccine but don’t necessarily represent real-world conditions.</span>
<span class="attribution"><a class="source" href="https://newsroom.ap.org/detail/VirusOutbreakGeorgiaVaccineTrial/47e7e14cbd864228b79581d3e5bd8c23/photo?Query=vaccine%20trial&mediaType=photo&sortBy=&dateRange=Anytime&totalCount=605&currentItemNo=5">AP Photo/Ben Gray</a></span>
</figcaption>
</figure>
<h2>2. What is the difference between vaccine efficacy and effectiveness?</h2>
<p>All new vaccines must undergo clinical trials in which researchers test the vaccines on thousands of people to examine how well they work and whether they are safe. </p>
<p><a href="https://www.cdc.gov/csels/dsepd/ss1978/lesson3/section6.html">Efficacy</a> is the measure of <a href="https://theconversation.com/pfizer-vaccine-what-an-efficacy-rate-above-90-really-means-149849">how well a vaccine works</a> in clinical trials. Researchers design the trials to include two groups of people: those who receive the vaccine and those who receive a placebo. They calculate the vaccine’s efficacy by comparing how many cases of the illness occur in each group, vaccinated versus placebo.</p>
<p><a href="https://www.cdc.gov/csels/dsepd/ss1978/lesson3/section6.html">Effectiveness</a>, on the other hand, describes how well a vaccine performs in the real world. It is calculated the same way, by comparing illness among vaccinated and unvaccinated people.</p>
<p>Efficacy and effectiveness are usually close to each other but won’t necessarily be the same. How the vaccines work will vary a bit from the trial results once millions of people are getting vaccinated.</p>
<p>Many factors influence how a vaccine performs in the real world. New variants like delta and omicron may change things. The number and age of people enrolled in the trials matter. And the health of those receiving the vaccine is also important.</p>
<p><a href="https://doi.org/10.1001/jamapsychiatry.2021.2497">Vaccine uptake</a> – the proportion of a population that gets vaccinated – can also influence vaccine effectiveness. When a large enough proportion of the population is vaccinated, herd immunity begins to come into play. Vaccines with <a href="https://www.cdc.gov/flu/vaccines-work/effectivenessqa.htm">moderate or even low efficacy can work very well</a> at a population level. Likewise, vaccines with high efficacy in clinical trials, like coronavirus vaccines, may have <a href="https://www.nature.com/articles/d41586-021-00728-2">lower effectiveness</a> and a small impact if there isn’t high vaccine uptake in the population.</p>
<p>The distinction between efficacy and effectiveness is important, because one describes the risk reduction achieved by the vaccines under trial conditions and the other describes how this may vary in populations with different exposures and transmission levels. Researchers can calculate both, but they can’t design a study that will measure both simultaneously. </p>
<h2>3. How do you calculate efficacy and effectiveness?</h2>
<p>Both <a href="https://pubmed.ncbi.nlm.nih.gov/33301246/">Pfizer</a> and <a href="https://www.cdc.gov/mmwr/volumes/69/wr/mm695152e1.htm?s_cid=mm695152e1_w">Moderna</a> reported that their vaccines demonstrated more than 90% efficacy in preventing symptomatic COVID-19 infection. Stated another way, among those individuals who received the vaccine in the clinical trials, the risk of getting COVID-19 was reduced by 90% compared with those who did not receive the vaccine. </p>
<p>Imagine conducting a vaccine trial. You randomize 1,000 people to receive the vaccine in one group. You randomize another 1,000 to be given a placebo in the other group. Say 2.5% of people in the vaccinated group get COVID-19 compared with 50% in the unvaccinated group. That means the vaccine has 95% efficacy. We determine that because (50% – 2.5%)/50% = .95. So 95% indicates the reduction in the proportion of disease among the vaccinated group. However, a vaccine with 95% efficacy does not mean 5% of vaccinated people will get COVID-19. It’s even better news: Your risk of illness is reduced by 95%.</p>
<p>Vaccine effectiveness is calculated the exact same way but is determined through <a href="https://dx.doi.org/10.17269%2Fs41997-021-00554-z">observational studies</a>. Early on, vaccines were well over <a href="https://www.statnews.com/2021/03/29/real-world-study-by-cdc-shows-pfizer-and-moderna-vaccines-were-90-effective/">90% effective</a> at preventing severe illness in the real world. But, by their very nature, <a href="https://doi.org/10.1038/d41586-021-03619-8">viruses change</a>, and this can change effectiveness. For example, a study found that by August 2021, when delta was surging, the Pfizer vaccine was <a href="http://dx.doi.org/10.15585/mmwr.mm7034e3">53% effective at preventing severe illness in nursing home residents</a> who had been vaccinated in early 2021. Age, health issues, waning immunity and the new strain all lowered effectiveness in this case.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/437638/original/file-20211214-23-1e9wqqp.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A model of the coronavirus." src="https://images.theconversation.com/files/437638/original/file-20211214-23-1e9wqqp.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/437638/original/file-20211214-23-1e9wqqp.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/437638/original/file-20211214-23-1e9wqqp.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/437638/original/file-20211214-23-1e9wqqp.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/437638/original/file-20211214-23-1e9wqqp.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/437638/original/file-20211214-23-1e9wqqp.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/437638/original/file-20211214-23-1e9wqqp.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">New variants of the coronavirus are all slightly different from the original strain that vaccines were based on, so immunity to variants may be different.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Coronavirus._SARS-CoV-2.png#/media/File:Coronavirus._SARS-CoV-2.png">Alexey Solodovnikov, Valeria Arkhipova/WikimediaCommons</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<h2>4. What about the omicron variant?</h2>
<p>The preliminary data about omicron and vaccines is <a href="https://www.reuters.com/business/healthcare-pharmaceuticals/pfizer-covid-19-vaccine-partially-protective-against-omicron-bloomberg-news-2021-12-07/">coming in quickly</a> and is revealing lower vaccine effectiveness. Best estimates suggest vaccines are around <a href="https://www.medpagetoday.com/special-reports/exclusives/96172">30%-40% effective at preventing infections</a> and <a href="https://www.reuters.com/business/healthcare-pharmaceuticals/pfizer-vaccine-protecting-against-hospitalisation-during-omicron-wave-study-2021-12-14/">70% effective at preventing severe disease</a>.</p>
<p>A <a href="https://www.medrxiv.org/content/10.1101/2021.12.07.212%2067432v1">preprint study</a> – one not formally reviewed by other scientists yet – that was conducted in Germany found that antibodies in blood collected from people fully vaccinated with Moderna and Pfizer showed <a href="https://doi.org/10.1038/d41586-021-03672-3">reduced efficacy in neutralizing the omicron variant</a>. Other small preprint <a href="https://doi.org/10.1101/2021.12.08.21267417">studies in South Africa</a> and <a href="https://www.medrxiv.org/content/10.1101/2021.12.10.21267534v1.full">England</a> showed a significant decrease in how well antibodies target the omicron variant. More <a href="https://www.npr.org/sections/goatsandsoda/2021/12/14/1063947940/vaccine-protection-vs-omicron-infection-may-drop-to-30-but-does-cut-severe-disea">breakthough infections are expected</a>, with decreased immune system ability to recognize omicron compared with other variants. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/437636/original/file-20211214-15-862uwa.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A sign outside of a pharmacy saying vaccines are available for walk-in appointments." src="https://images.theconversation.com/files/437636/original/file-20211214-15-862uwa.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/437636/original/file-20211214-15-862uwa.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/437636/original/file-20211214-15-862uwa.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/437636/original/file-20211214-15-862uwa.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/437636/original/file-20211214-15-862uwa.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/437636/original/file-20211214-15-862uwa.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/437636/original/file-20211214-15-862uwa.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Most people in the U.S. are now eligible to get a booster coronavirus vaccine which could help protect against the omicron variant.</span>
<span class="attribution"><a class="source" href="https://newsroom.ap.org/detail/VirusOutbreakIllinois/07e30f89e82f47a8a6a575d3c2e8080b/photo?Query=booster%20vaccine%20sign&mediaType=photo&sortBy=&dateRange=Anytime&totalCount=50&currentItemNo=4">AP Photo/Nam Y. Huh</a></span>
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<h2>5. Do boosters boost immunity against omicron?</h2>
<p>Initial data reinforces that <a href="https://theconversation.com/should-i-get-my-covid-vaccine-booster-yes-it-increases-protection-against-covid-including-omicron-172965">a third dose would help boost</a> immune response and protection against omicron, with estimates of <a href="https://www.cnbc.com/2021/12/10/boosters-give-70percent-75percent-protection-against-mild-disease-from-omicron-uk-health-security-agency-says.html">70%-75% effectiveness</a>. </p>
<p><a href="https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-provide-update-omicron-variant">Pfizer has reported</a> that people who have received two doses of its vaccine are susceptible to infection from omicron, but that a <a href="https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-provide-update-omicron-variant">third shot improves antibody activity against the virus</a>. This was based on lab experiments using the blood of people who have received the vaccine. </p>
<p>Booster doses can increase the amount of antibodies and the ability of a person’s immune system to protect against omicron. However, unlike the U.S., much of the <a href="https://ourworldindata.org/covid-vaccinations">world does not have access</a> to booster doses.</p>
<h2>6. What does this all mean?</h2>
<p>Despite the lowered effectiveness of vaccines against omicron, it is clear that vaccines do work and are among the <a href="https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6019a5.htm">greatest public health achievements</a>. Vaccines have varying levels of effectiveness and are still useful. The flu vaccine is usually <a href="https://www.cdc.gov/flu/vaccines-work/vaccineeffect.htm">40%-60% effective</a> and prevents illness in millions of people and hospitalizations in more than 100,000 people in the U.S. <a href="https://www.cdc.gov/flu/about/burden-averted/2019-2020.htm">annually</a>.</p>
<p>Finally, vaccines protect not only those who are vaccinated, but those who can’t get vaccinated as well. Vaccinated people are <a href="https://theconversation.com/no-vaccinated-people-are-not-just-as-infectious-as-unvaccinated-people-if-they-get-covid-171302">less likely to spread</a> COVID-19, which reduces new infections and offers protection to society overall.</p>
<p>[<em><a href="https://memberservices.theconversation.com/newsletters?nl=science&source=inline-science-corona-important">Get The Conversation’s most important coronavirus headlines, weekly in a science newsletter</a></em>]</p><img src="https://counter.theconversation.com/content/173554/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Melissa Hawkins receives funding from USDA/NIFA. </span></em></p>For a number of reasons, as time goes on vaccines become less effective. So how do researchers calculate how well vaccines are working?Melissa Hawkins, Professor of Public Health, American UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1712172021-11-17T05:15:01Z2021-11-17T05:15:01ZCOVID vaccines don’t violate the Nuremberg Code. Here’s how to convince the doubters<p>People opposing vaccine mandates, or COVID vaccines more broadly, <a href="https://www.facebook.com/groups/138599678102481/permalink/184874376808344">have claimed</a> the vaccines violate the Nuremberg Code.</p>
<p>They say COVID vaccines are <a href="https://twitter.com/VigilantFox/status/1458925515205660678">experimental and people have been coerced</a> into vaccination. They say this breaches the ethical code drawn up after the second world war to guide medical research and human clinical trials.</p>
<p>But this argument is flawed. Here’s why the Nuremberg Code doesn’t apply, and how to correct this misunderstanding. </p>
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<strong>
Read more:
<a href="https://theconversation.com/no-thats-not-the-law-the-danger-of-using-pseudolegal-arguments-against-covid-19-rules-170630">No, that's not the law: the danger of using pseudolegal arguments against COVID-19 rules</a>
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<h2>What is the Nuremberg Code?</h2>
<p>The Nuremberg Code was a direct response to atrocities Nazi doctors performed in concentration camps during WWII. They perpetrated this so-called medical experimentation on people with no capacity to consent, and this frequently led to lifelong disability, or death. </p>
<p>The doctors who performed these experiments <a href="https://www.nejm.org/doi/full/10.1056/nejm199711133372006">were tried</a> in Nuremberg in 1947.</p>
<p>The doctors’ defence argued their experiments were not significantly different to other research practices. So two American doctors working for the prosecution produced a document that aimed to draw together what made for ethical research.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1435603579646132226"}"></div></p>
<p>This document identified <a href="https://www.nejm.org/doi/full/10.1056/nejm199711133372006">three ethical, legal, and scientific requirements</a> for conducting human experiments, which were later expanded to ten. This ten-point document became known <a href="https://jamanetwork.com/journals/jama/fullarticle/2649074">as the Nuremburg Code</a>.</p>
<p>It details the process of seeking legally valid voluntary consent, covers the need to establish the humanitarian nature and purpose of the experiment, as well as ensuring the scientific integrity and obligations of the investigator to the subjects’ welfare. </p>
<p>However, the Nuremberg Code is no longer used to guide research ethics. The World Medical Association’s <a href="https://www.wma.net/what-we-do/medical-ethics/declaration-of-helsinki/">Declaration of Helsinki</a> replaced it in 1964. And there’s been more ethical guidance since.</p>
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Read more:
<a href="https://theconversation.com/two-steps-forward-one-step-back-how-world-war-ii-changed-how-we-do-human-research-39929">Two steps forward, one step back: how World War II changed how we do human research</a>
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<h2>No, COVID vaccines are not experimental</h2>
<p>Online commentary <a href="https://twitter.com/AbolishtheFeds/status/1428751073448181770">says</a> COVID vaccines are “experimental”.</p>
<p>But COVID vaccines have been thoroughly tested, and they have been <a href="https://theconversation.com/how-well-do-covid-vaccines-work-in-the-real-world-162926">shown to work</a>. Their side-effects have been extensively examined. They have been approved for use around the world and have been credited for <a href="https://theconversation.com/how-many-lives-have-coronavirus-vaccines-saved-we-used-state-data-on-deaths-and-vaccination-rates-to-find-out-169513">saving many lives</a>.</p>
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<em>
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Read more:
<a href="https://theconversation.com/how-well-do-covid-vaccines-work-in-the-real-world-162926">How well do COVID vaccines work in the real world?</a>
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<p>So COVID vaccines are not “experimental”. Now COVID vaccines are part of standard public health response, it is not appropriate to refer to codes or documents developed to guide clinical trials and other research studies. </p>
<h2>How do you convince someone?</h2>
<p>If you come across someone claiming COVID vaccines are experimental, you can try the “<a href="https://www.independent.co.uk/news/health/coronavirus-vaccines-misinformation-scientists-truth-sandwich-b1783401.html">truth sandwich</a>” to try to <a href="https://medium.com/wehearthealthliteracy/the-truth-sandwich-a-better-way-to-mythbust-8021d2cf8730">myth bust</a>.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1330728487938904064"}"></div></p>
<p>If you imagine two pieces of bread, then the filling in the middle, you are on your way to using the truth sandwich.</p>
<p>First, we take a piece of bread, where we state the truth:</p>
<blockquote>
<p>COVID vaccines have been tested in pre-clinical and clinical trials, and their efficacy and effectiveness has been proven, and their side effects profiles have been extensively examined. </p>
</blockquote>
<p>Then we come to the filling in the middle, where we talk about a false claim and how it relates to the truth:</p>
<blockquote>
<p>You may have heard someone suggest the COVID-19 vaccine program infringes people’s rights under the Nuremberg Code. But the claim that COVID-19 vaccines are experimental is simply not true. Regulatory authorities have approved these vaccines nationally and internationally. Safety monitoring is ongoing, but these processes are routine and commonly used for other vaccines or drugs. Check out <a href="https://ausvaxsafety.org.au/safety-data/covid-19-vaccines">AusVaxSafety</a>.</p>
</blockquote>
<p>Our final piece of bread comes next, repeating the truth:</p>
<blockquote>
<p>The Nuremberg Code focuses on clinical research on humans. Therefore, it is no longer relevant once a vaccine moves beyond the clinical trial phase and has been authorised or approved for use globally. </p>
</blockquote>
<h2>The issue of informed consent</h2>
<p>Online commentary usually cites the <a href="https://www.ushmm.org/information/exhibitions/online-exhibitions/special-focus/doctors-trial/nuremberg-code">first clause</a> of the Nuremberg Code about the need for informed consent in human experiments:</p>
<blockquote>
<p>The voluntary consent of the human subject is absolutely essential.</p>
</blockquote>
<p>This argument is used as evidence there’s something unethical about using COVID vaccines or introducing mandates.</p>
<p>Indeed, voluntary informed consent is an ethical bedrock for clinical research. Any form of compulsion is unacceptable because clinical research has inherent risks and can’t be quantified precisely. Research also may not have any direct benefit for participants, which again requires consent. </p>
<p>To be ethical, therefore, researchers must ensure participants in clinical trials understand potential risks and benefits, and give voluntarily consent to participate.</p>
<h2>How do you convince someone?</h2>
<p>Again, we can use the “truth sandwich” to myth bust. </p>
<p>Take your first piece of bread, stating the truth (the facts): </p>
<blockquote>
<p>The Nuremberg Code relates to research, where the emphasis of informed consent is on “<a href="https://www.usatoday.com/story/news/factcheck/2021/08/10/fact-check-covid-19-vaccine-mandates-nuremberg-code-not-related/5530548001/">preventing research participants from being used as a means to an end</a>”. The need for informed consent is still required for receiving a COVID-19 vaccine (or any vaccine) but the need does not stem from the Nuremberg Code. </p>
</blockquote>
<p>Here’s the filling (the false claim and how it relates to the truth):</p>
<blockquote>
<p>The introduction of a vaccine mandate is not medical research but rather a public health intervention. In every setting where COVID vaccines are mandated, no-one is being forced to be vaccinated against their will or consent. Informed consent is still sought before vaccination, and people retain the right to choose whether to be vaccinated. </p>
<p>However, in these settings, the public health goal of COVID-19 vaccination is seen as outweighing the rights of the individual to remain un-vaccinated. Other people in these settings have a right to health and security. Therefore there are outcomes for those who don’t comply. Exemptions are provided for those who cannot receive the vaccine for medical reasons. </p>
</blockquote>
<p>If you want to expand further:</p>
<blockquote>
<p>Mandates of this nature have previously been used in occupational settings to reduce the risk from vaccine preventable diseases for the employee and for the people they come into contact with, whether they be hospital patients or aged care residents. Beyond these settings, we have accepted vaccines as requirements of travel (such as yellow fever) both to protect ourselves and to reduce any risk of bringing this infection back to Australia. </p>
</blockquote>
<p>Final piece of bread (repeating the truth):</p>
<blockquote>
<p>There has been misinformation about linking COVID-19 vaccination, and/or the requirements within some occupations to the Nuremberg Code. The code relates to research and claims that mandates violate it are not accurate. </p>
</blockquote>
<h2>Why is this important?</h2>
<p>This type of misinformation often thrives in situations <a href="https://fullfact.org/health/how-to-fact-check-coronavirus/">where feelings are manipulated</a>. And emotional posts on social media referring to Nazi doctors and Nuremberg are more likely to be shared.</p>
<p>We can keep fact checking. But it’s also time for every one of us to get out there with our truth sandwiches.</p><img src="https://counter.theconversation.com/content/171217/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Holly Seale is an investigator on research studies funded by NHMRC and has previously received funding for investigator driven research from NSW Ministry of Health, as well as from Sanofi Pasteur and Seqirus. She is the Deputy Chair of the Collaboration on Social Science and Immunisation.</span></em></p><p class="fine-print"><em><span>Ben Harris-Roxas is an investigator on projects funded by the Cancer Institute NSW, the National Health and Medical Research Council (NHMRC), the Sydney Partnership for Health Education Research & Enterprise (SPHERE), and NSW Health. In the past he has received funding from the Australian Research Council, the World Health Organization, the Australian Government Department of Health, the Public Health Agency of Canada, the Heart Foundation, NPS MedicineWise, the Sax Institute, and the City of Gold Coast.</span></em></p><p class="fine-print"><em><span>Bridget Haire has received funding from National Health and Medical Research Council (NHMRC)</span></em></p>Emotive claims, like COVID vaccination being unethical or coercive, are more likely to be shared on social media. But we can fight back.Holly Seale, Associate professor, UNSW SydneyBen Harris-Roxas, Senior Lecturer, UNSW SydneyBridget Haire, Postdoctoral Research Fellow, Kirby Institute, UNSW SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1705152021-11-12T13:36:22Z2021-11-12T13:36:22ZThe FDA’s lax oversight of research in developing countries can do harm to vulnerable participants<figure><img src="https://images.theconversation.com/files/430539/original/file-20211105-9885-4tg5rc.jpg?ixlib=rb-1.1.0&rect=0%2C30%2C6800%2C5059&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Nearly 80% of participants in FDA-reviewed research trials live in foreign countries.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/approved-concept-rubber-stamp-with-fda-and-medicine-royalty-free-image/1215516118?adppopup=true">Bet_Noire/iStock via Getty Images</a></span></figcaption></figure><p><em>The <a href="https://theconversation.com/us/topics/research-brief-83231">Research Brief</a> is a short take about interesting academic work.</em></p>
<h2>The Big Idea</h2>
<p>The Food and Drug Administration provides <a href="https://doi.org/10.1177/1060028020906484">less stringent oversight</a> of overseas research trials used in deciding whether to approve a drug than those conducted domestically. That was the finding of <a href="https://doi.org/10.1002/jcph.1976">my recent study</a>, published in the Journal of Clinical Pharmacology.</p>
<p>My study highlighted loopholes in the agency’s oversight processes that exploited vulnerable people and led to faulty data for drug approval decisions. Until the early 2000s, participants in FDA-reviewed research trials came almost entirely from the U.S. But a 2010 report from the Department of Health and Human Services found that <a href="https://oig.hhs.gov/oei/reports/oei-01-08-00510.pdf">78% of research participants</a> were enrolled overseas. Faster research subject recruitment and lower expenses – paired with these regulatory loopholes – seem to be driving this shift. </p>
<p>It isn’t clear how often these gaps allow problematic trials to slip through the system, because trials that go wrong can simply not be disclosed, and there are virtually no on-site inspections. </p>
<p>In one example, a 2001 trial based in India allowed the <a href="https://doi.org/10.1136/bmj.332.7541.566-a">use of placebo control</a> in patients with severe mental illness when there were effective alternative therapies available. In another Indian trial, patients were untruthfully told that their <a href="https://www.somo.nl/wp-content/uploads/2008/02/Examples-of-unethical-trials.pdf">medication to treat mania was no longer available</a> and that they could receive only an experimental drug or placebo. Some patients did not even know they were in a trial.</p>
<p>In a study I published in 2020, I cited a trial performed in India in which <a href="https://doi.org/10.1177/1060028020906484">electrocardiograms filed for multiple people</a> were later discovered to be fraudulent copies from a single person. I also came across an example of large-scale data manipulation from Chinese study sites to make an experimental drug seem more effective than it really was.</p>
<p>The number of drugs that are approved but later had to be withdrawn or have new serious warnings for adverse events has increased from <a href="https://doi.org/10.1377/hlthaff.2014.0122">21 per 100 drugs before 2012 to 27 per 100 drugs</a> thereafter. This coincides with the dramatic shift to overseas clinical trials intended for FDA drug approval.</p>
<h2>Why it matters</h2>
<p>Before researchers can begin human testing of experimental drugs in research subjects on U.S. soil, companies must submit “<a href="https://www.fda.gov/drugs/types-applications/investigational-new-drug-ind-application">Investigational New Drug</a>” applications to the FDA. These applications describe the lab-based testing they conducted and all the trials they plan to carry out on U.S. citizens. The FDA can prevent unethical trials from beginning in the U.S. given its authority under the <a href="https://www.senate.gov/artandhistory/history/minute/Interstate_Commerce_Act_Is_Passed.htm#:%7E:text=On%20February%204%2C%201887%2C%20both,%E2%80%9D%E2%80%94to%20regulating%20railroad%20rates.&text=The%20bill%20passed%20the%20House%2C%20but%20not%20the%20Senate">Interstate Commerce Act of 1887</a> but only because the experimental drug crosses state lines.</p>
<p>But a <a href="https://doi.org/10.1002/jcph.1976">loophole exists for overseas research</a>, since the experimental drug does not need to cross U.S. state lines. This means companies can begin overseas research trials <a href="https://doi.org/10.1002/jcph.1976">before the FDA assesses the drug application</a>, and they do not have to disclose all the research they intend to perform.</p>
<p>To get an experimental drug approved by the FDA, the companies must submit a <a href="https://www.fda.gov/drugs/types-applications/new-drug-application-nda">New Drug Application</a> to the agency. For research trials that were previously proposed to the FDA, the companies are required to include all trial data. However, when trials are conducted overseas unbeknownst to the FDA, companies can <a href="https://doi.org/10.1177/1060028020906484">cherry-pick supportive trials</a> and leave out those with negative findings. Thus, the FDA may not have a complete picture of the drugs’ potential benefits and adverse events when deciding if it should be approved.</p>
<h2>What’s next</h2>
<p>Since the 1990s, the FDA has been increasingly funded by <a href="https://theconversation.com/why-is-the-fda-funded-in-part-by-the-companies-it-regulates-160444">user fees from the companies it regulates</a>. These fees cover the costs of many FDA functions, including product approvals and manufacturing facility inspections. They are paid by pharmaceutical, biotechnology and device companies as well as generic drug manufacturers. User fees were initially introduced to speed up the drug approval process for HIV medications early in the HIV/AIDS epidemic.</p>
<p>These <a href="https://www.fda.gov/industry/fda-user-fee-programs">user fees are negotiated</a> between the FDA and the companies and then approved by Congress. In 2022, the newly negotiated fees are set to go into effect for five years. During the last negotiation in 2017, the <a href="https://doi.org/10.1177/1060028020906484">FDA proposed a fee to fund trial site inspections</a> in developing countries, but the companies refused. As a result, foreign clinical trial sites are <a href="https://oig.hhs.gov/oei/reports/oei-01-08-00510.pdf">27 times less likely to be inspected by the FDA</a> than those in the U.S.</p><img src="https://counter.theconversation.com/content/170515/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>C. Michael White does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Regulatory loopholes for research conducted off US soil allow for questionable trials and misleading data to slip under the FDA’s radar.C. Michael White, Distinguished Professor and Head of the Department of Pharmacy Practice, University of ConnecticutLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1694592021-11-11T01:24:16Z2021-11-11T01:24:16ZMarket immunity? How public safety warnings have little impact on drug sales volumes or company share prices<figure><img src="https://images.theconversation.com/files/431212/original/file-20211110-25-1vhthsp.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C5967%2C3721&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>The race by pharmaceutical companies to find effective vaccines for COVID-19 has shone a global spotlight on the trade-offs regulators face in approving new drugs.</p>
<p>Under the system used by drug regulators in the US, Europe and elsewhere, drug companies need only show from clinical trials that new drugs have short-term safety and efficacy in order to gain approval.</p>
<p>So, what happens if something goes wrong longer term? </p>
<p>Specifically, does the market itself punish drug companies when regulators issue warnings about a product’s safety, or withdraw it entirely? <a href="https://onlinelibrary.wiley.com/doi/epdf/10.1002/hec.4440">Our latest research</a> set out to answer that question.</p>
<h2>Warnings after the fact</h2>
<p>Companies don’t need to demonstrate a drug’s long-term safety and efficacy. The limited length of clinical trials is allowed in order to keep the cost of developing drugs from being so high that new drugs don’t get developed.</p>
<p>There are also ethical problems with long trials – would you like to spend three years randomly assigned to take a drug you quickly realise is ineffective, or worse?</p>
<p>But our system brings the risk that new drugs can turn out to cause long-term problems undetected at the time of approval – opioid pain killers being a prime example.</p>
<p>Instead, after a drug gets approved, doctors or patients can report “adverse drug events” which regulators can investigate. The regulators may issue a new warning to go on a drug’s label or, in extreme cases, the drug may be withdrawn from the market, as happened with the <a href="https://www.npr.org/2007/11/10/5470430/timeline-the-rise-and-fall-of-vioxx">painkiller Vioxx</a> in 2004.</p>
<figure class="align-center ">
<img alt="Covid vaccine vials" src="https://images.theconversation.com/files/431219/original/file-20211110-13-svzf9w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/431219/original/file-20211110-13-svzf9w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/431219/original/file-20211110-13-svzf9w.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/431219/original/file-20211110-13-svzf9w.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/431219/original/file-20211110-13-svzf9w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/431219/original/file-20211110-13-svzf9w.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/431219/original/file-20211110-13-svzf9w.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=424&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">COVID vaccine development has highlighted the trade-offs regulators face in approving new drugs.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
</figcaption>
</figure>
<h2>Regulation versus market signals</h2>
<p>New safety warnings can vary in seriousness, with examples in our sample ranging from risk of permanent skin discolouration from certain <a href="https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-reporting-permanent-skin-color-changes-associated-use-daytrana">dermal patches</a>, up to increased risk of potentially fatal <a href="https://www.empr.com/uncategorized/avandia-label-updated-to-include-cardiovascular-risk-warnings/">heart</a> or <a href="https://www.drugwatch.com/news/2014/01/28/fda-limits-acetaminophen-liver-damage/">liver damage</a>, or <a href="https://www.webmd.com/depression/news/20070502/new-antidepressant-suicide-warning">suicidal ideation</a>. </p>
<p>In the US, the Food and Drug Administration (FDA) therefore further distinguishes between new regular warnings and more serious “boxed” warnings that are urgent enough to be framed and placed at the top of a drug’s information label.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/the-price-of-a-drug-should-be-based-on-its-therapeutic-benefits-not-just-what-the-market-will-bear-149586">The price of a drug should be based on its therapeutic benefits – not just what the market will bear</a>
</strong>
</em>
</p>
<hr>
<p>Do regulators get the balance right between encouraging new drug creation and safeguarding public health from unforeseen problems with newly approved drugs? </p>
<p>The burden would not fall on regulators alone if markets tended to “punish” companies whose drugs turn out to cause longer-term problems. This would create additional market incentives for companies to avoid such outcomes. </p>
<p>So do markets help keep us safe when we take approved drugs?</p>
<h2>Testing the market</h2>
<p>We first tested how total sales volumes of individual drugs across four broad categories in the US and the UK hospital and retail sectors are affected when each country’s respective regulator issues new safety warnings. </p>
<p>Some of these drugs were sold by only one or two companies, while others were sold by many, but we focused on whether warnings significantly affected total sales of individual drugs. </p>
<p>We included individual drugs across the four drug categories of diabetes, analgesic pain relievers (including opioids), nervous system analeptics for calming (including antipsychotics), and nervous system psychoanaleptic stimulants (including antidepressants).</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/how-pharma-can-build-trust-in-covid-19-vaccines-transparency-on-trials-and-side-effects-150270">How pharma can build trust in COVID-19 vaccines: Transparency on trials and side-effects</a>
</strong>
</em>
</p>
<hr>
<p>Beyond asking whether warnings affected total sales volumes of individual drugs, we next tested whether they affected the share price of the individual publicly listed companies selling the drug, in the days surrounding the announcement of the safety warning.</p>
<p>Share prices matter because they should capture whether shareholders in the affected company believe the warning will lower its future profits. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/431215/original/file-20211110-13-10el7qr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/431215/original/file-20211110-13-10el7qr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/431215/original/file-20211110-13-10el7qr.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/431215/original/file-20211110-13-10el7qr.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/431215/original/file-20211110-13-10el7qr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/431215/original/file-20211110-13-10el7qr.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/431215/original/file-20211110-13-10el7qr.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Prescription opioids were hailed as a breakthrough in pain management but created an addiction epidemic.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
</figcaption>
</figure>
<h2>Little impact on sales</h2>
<p>We followed new warnings, sales and share prices for the US and UK over 12 years, from 2006 to 2017. Across a variety of statistical methods, we found surprisingly little evidence that new safety warnings affect the sales volume of the relevant drugs within our four categories.</p>
<p>The exceptions were in the US (with the UK regulator’s warnings never having a measurable effect on sales in that country). Specifically, if we excluded diabetic drugs, FDA warnings significantly lowered subsequent US sales of the other three drug categories if pooled together, but didn’t significantly lower sales if each broad category of drug was considered separately. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/covid-vaccine-trials-were-a-triumph-now-we-need-a-similar-system-for-antibiotics-162130">COVID vaccine trials were a triumph – now we need a similar system for antibiotics</a>
</strong>
</em>
</p>
<hr>
<p>Similarly, having “at least one new boxed warning” during our sample period significantly lowered US hospital sales volume for all four categories of drug combined, but not significantly for each category separately, and not for US retail sales. </p>
<p>At the extreme, we found having at least ten new FDA warnings, or at least three new FDA boxed warnings, significantly lowered total sales volumes in all categories in both US retail and hospitals. </p>
<h2>Share prices unaffected</h2>
<p>We found even less evidence that warnings affected drug company share prices. The effects of warnings were small, sensitive to our choice of time span around the warning, and statistically insignificant. The single significant exception used a 25-day time span following warnings issued by the UK regulator.</p>
<p>We conclude that if society judges the problems identified by post-approval warnings to be rare or mild, then perhaps there is no reason to think sales volume or company share price should take a hammering.</p>
<p>The current system might then be doing a good job of balancing the cost of new drug development with safeguarding public health against the risk of unforeseen negative side effects.</p>
<p>But if society does judge the problems being identified in new warnings to be too common or serious, then the balance of our evidence is that markets do not punish companies that sell such drugs. </p>
<p>If the market does not fulfil this function, then, it must fall to regulators alone to insist that pre-approval drug trials be run for longer periods for more patients.</p><img src="https://counter.theconversation.com/content/169459/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The authors do not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>A new study suggests the market alone will not deter or punish pharmaceutical companies whose products turn out to have adverse effects after they have been approved.Jeremy Edmund Clark, Associate Professor, Department of Economics and Finance, Business School, University of CanterburyJedrzej Bialkowski, Professor and Head of Department, Economics and Finance, University of CanterburyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1681922021-09-22T19:56:20Z2021-09-22T19:56:20ZIvermectin shows us how hard it is to use old drugs for COVID. Here’s how to do better next time<figure><img src="https://images.theconversation.com/files/422516/original/file-20210922-27-16rb7hb.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C998%2C658&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/pills-world-map-shape-267836303">Shutterstock</a></span></figcaption></figure><p>Many hopes have been pinned on repurposing existing drugs, such as ivermectin and hydroxychloroquine, to treat COVID-19. However, we shouldn’t be too surprised these drugs haven’t yet lived up to the hype. </p>
<p>Our study, published today in <a href="https://www.science.org/doi/10.1126/scitranslmed.abd5524">Science Translational Medicine</a>, shows it’s notoriously difficult to repurpose existing drugs for new diseases or for new uses. </p>
<p>Here’s what we need to consider for this pandemic — and the next.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/a-major-ivermectin-study-has-been-withdrawn-so-what-now-for-the-controversial-drug-164627">A major ivermectin study has been withdrawn, so what now for the controversial drug?</a>
</strong>
</em>
</p>
<hr>
<h2>Repurposing old drugs may sound great</h2>
<p>Repurposing existing drugs <a href="https://www.mja.com.au/journal/2020/212/10/drug-repurposing-era-covid-19-call-leadership-and-government-investment">may sound attractive</a>, during a pandemic or not. Doctors are used to prescribing them, we know a lot about how safe they are for existing conditions and patients generally tolerate them well.</p>
<p>There are also well-publicised success stories of repurposed drugs that skew our perception of how hard this is to actually pull off. For instance, <a href="https://theconversation.com/thalidomide-the-drug-with-a-dark-side-but-an-enigmatic-future-50330">thalidomide</a> was released in the 1950s as a sedative and repurposed to be used against cancer 50 years later.</p>
<p>But we show this example is the rare exception rather than the rule.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/thalidomide-the-drug-with-a-dark-side-but-an-enigmatic-future-50330">Thalidomide: the drug with a dark side but an enigmatic future</a>
</strong>
</em>
</p>
<hr>
<h2>Oh, but it’s great in the test tube</h2>
<p>Let’s say an antidepressant drug kills a virus in a test tube. But this antiviral activity, picked up in a laboratory assay (or test), will likely be misleading. </p>
<p>Many drugs may well kill the virus in such an assay but this is only at concentrations much higher than those used to treat the condition for which the drug was initially developed. Humans often cannot tolerate these higher concentrations.</p>
<p>At these high concentrations, drugs also display all sorts of biological activities that may appear useful but <a href="https://www.nature.com/articles/513481a">are just noise</a> and destined for repurposing failure.</p>
<p>Yet these sneaky drugs, including those that <a href="https://www.science.org/doi/10.1126/science.abi4708">sound promising for COVID-19</a>, can end up in peer-reviewed publications.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1440135107780628480"}"></div></p>
<p>Or let’s say you find an anticancer drug that kills a virus in a test-tube assay. Do not assume it is immediately useful and safe to treat viral infections in humans. </p>
<p>Drugs are only approved for specific uses after analysing the relationship between how the body treats the drug (pharmacokinetics) and how the drug treats the body (pharmacodynamics). Experts call this PK-PD.</p>
<p>The same drug can give very different PK-PD profiles depending on the dose, how often it is given, and whether the drug is administered by mouth, intravenously, or under the skin. </p>
<p>Drug concentrations safe and effective for one disease may not immediately translate to another. Higher, more frequent doses may be required, with increased risk of unintended toxicity or even death. </p>
<p>So drugs intended for repurposing still need to be thoroughly studied in animals and clinical trials to make sure a new dosing regime is safe and effective. Repurposing may not be the short cut you think it is.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/the-fascinating-history-of-clinical-trials-139666">The fascinating history of clinical trials</a>
</strong>
</em>
</p>
<hr>
<h2>Oh, I forgot about the intellectual property</h2>
<p>It’s not just the virus that kills: intellectual property barriers could also stop repurposing dead in its tracks. </p>
<p>The ultimate test that a drug is safe and effective is a phase 3 clinical trial. <a href="https://www.nature.com/articles/nrd.2018.198">This costs</a> a median of around US$19 million.</p>
<p>Assuming the new antiviral activity you discovered for the anticancer drug is both potent and “real”, there may be no way to proceed with essential and costly clinical trials without a patent.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/three-simple-things-australia-should-do-to-secure-access-to-treatments-vaccines-tests-and-devices-during-the-coronavirus-crisis-136052">Three simple things Australia should do to secure access to treatments, vaccines, tests and devices during the coronavirus crisis</a>
</strong>
</em>
</p>
<hr>
<p>That’s because pharmaceutical companies and investors are businesses. They need to legally possess the rights to the drug so they can make a return on their investment into high-risk clinical trials essential for marketing approval.</p>
<p>If you don’t have patent rights to the drug but want to commercialise your antiviral discovery, you will need to negotiate some complex agreements with the patent owner with no guarantee of success. </p>
<p>If the anticancer drug you hope to repurpose has been on the market for more than 20 years, the patent may have expired so you don’t need to negotiate — there is no patent owner. </p>
<p>That’s great, but finding investment to fund well-designed clinical trials will be difficult because investors, keen on a financial return, won’t go ahead without patent protection in place.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/when-trump-pushed-hydroxychloroquine-to-treat-covid-19-hundreds-of-thousands-of-prescriptions-followed-despite-little-evidence-that-it-worked-140156">When Trump pushed hydroxychloroquine to treat COVID-19, hundreds of thousands of prescriptions followed despite little evidence that it worked</a>
</strong>
</em>
</p>
<hr>
<h2>A little tweak here and another tweak there</h2>
<p>This is where “molecular engineering” or medicinal chemistry comes into its own. This is when existing drugs are tweaked — a new atom here, a new bond there.</p>
<p>This allows researchers to find improved, novel and patentable versions of the initial drug.</p>
<p>This is no longer repurposing, but more useful. </p>
<p>That said, a pandemic is a special case where even an old, out-of-patent drug could attract governmental and philanthropic funding for clinical trials, if it truly has promise.</p>
<h2>Don’t always believe what you see</h2>
<p>If you test large numbers of drugs and find antiviral activity, you should assume this activity is misleading until proven otherwise. These signals are likely “<a href="https://www.nature.com/articles/513481a">false positives</a>”, especially at higher testing concentrations.</p>
<p>Any chemical compound, including herbal supplements, can also generate <a href="https://pubs.acs.org/doi/10.1021/acs.jnatprod.5b00947">false positive results</a>.</p>
<p>In the US alone, supplements such as <a href="https://pubs.acs.org/doi/10.1021/acs.jmedchem.6b00975">curcumin</a> (found in turmeric) have attracted more than US$150 million of federal funding and studied in more than 120 clinical trials. Not surprisingly there’s no tangible evidence curcumin can be used to treat any human affliction.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/have-australian-researchers-developed-an-effective-covid-19-treatment-potentially-but-we-need-to-wait-for-human-trials-161085">Have Australian researchers developed an effective COVID-19 treatment? Potentially, but we need to wait for human trials</a>
</strong>
</em>
</p>
<hr>
<h2>Don’t always believe what you read</h2>
<p>The explosion of research in the race to be the first to discover new drugs for COVID-19 has led to some <a href="https://www.mja.com.au/journal/2020/213/11/changes-medical-scientific-publication-associated-covid-19-pandemic">poor-quality studies</a> published in peer reviewed journals.</p>
<p>Now with social media amplifying those results, <a href="https://theconversation.com/why-is-it-so-hard-to-stop-covid-19-misinformation-spreading-on-social-media-134396">misinformation</a> has become extreme.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1253781771453374465"}"></div></p>
<p>So it’s easy for non-experts to latch onto preliminary or unsubstantiated research about repurposed drugs and give this more prominence than it deserves.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/why-is-it-so-hard-to-stop-covid-19-misinformation-spreading-on-social-media-134396">Why is it so hard to stop COVID-19 misinformation spreading on social media?</a>
</strong>
</em>
</p>
<hr>
<h2>There are other ways</h2>
<p>We know of successful and well-practised ways of developing new drugs. This includes screening many compounds at once (known as high-throughput screening), then intensive optimisation (tweaking) using medicinal chemistry.</p>
<p>Yet many labs around the world daily are testing known drugs with the hope of repurposing, perhaps under perceived pressure by funding providers.
Seldom anything eventuates except flawed publications. </p>
<p>With the right approach, drug repurposing can work and provide new medicines for unmet needs and there are actually some good examples of this, beyond thalidomide. For example the veterinary antiparasitic drug moxidectin was repurposed to treat river blindness.</p>
<p>But for repurposing to work, there needs a considered and specialised scientific and commercial approach, specific to each drug and problem being solved. </p>
<p>It is too easy to focus on the relatively few repurposing successes to jump to the conclusion drug repurposing is a panacea for all ills.</p><img src="https://counter.theconversation.com/content/168192/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jonathan Baell receives funding from National Health and Medical Research Council, MS Research Australia, Therapeutic Innovation Australia, Tour de Cure, Cyclotek Pty Ltd. Funding has previously also been received from US Department of Defense, Australia-India Strategic Research Fund, Australian Research Council, National Institutes of Health (USA), Drugs for Neglected Diseases Initiative, Cure for MND,</span></em></p><p class="fine-print"><em><span>Michael Jennings receives funding from the National Health and Medical Research Council, the Australian Research Council, the National Institutes of Health, USA, the US Department of Defense, theBiomedical Translation Bridge (BTB) Program, The Bourne Foundation, Tour de Cure, BioProperties Australia, Bard 1. Michael Jennings has previously received funding from GSK, Queensland State Government Smart State Schemes, Mizutani Foundation, World Health Organisation.</span></em></p><p class="fine-print"><em><span>Michael Parker receives funding from the National Health and Medical Research Council, the Australian Research Council, the National Foundation for Medical Research and Innovation, MS Research Australia, SPARK Melbourne, and the Victorian Government. Michael Parker has previously received funding from CSL, Janssen Pharmaceuticals, the Australian Cancer Research Foundation, Cancer Council Victoria, the Yulgilbar Foundation, and the Alzheimer's Drug Discovery Foundation.</span></em></p>The path to using old drugs for COVID is full of potholes. So why are we using the same old flawed methods when we actually know what works?Jonathan Baell, Research Professor in Medicinal Chemistry and Drug Discovery, Monash Institute of Pharmaceutical Sciences, Monash UniversityMichael Jennings, Professor and Deputy Director/NHMRC Fellow, Institute for Glycomics, Griffith UniversityMichael Parker, Professor Biochemistry and Pharmacology and Director, Bio21 Institute, The University of MelbourneLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1670462021-09-01T22:54:49Z2021-09-01T22:54:49ZI work at a COVID-19 vaccine clinic. Here’s what people ask me when they’re getting their shot — and what I tell them<figure><img src="https://images.theconversation.com/files/418799/original/file-20210901-17-5618xv.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C3647%2C2528&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">People getting vaccinated may still have questions about COVID-19 vaccines, like why it takes two doses — and then two weeks — to take full effect.
</span> <span class="attribution"><span class="source">THE CANADIAN PRESS/Ryan Remiorz </span></span></figcaption></figure><iframe style="width: 100%; height: 175px; border: none; position: relative; z-index: 1;" allowtransparency="" src="https://narrations.ad-auris.com/widget/the-conversation-canada/i-work-at-a-covid-19-vaccine-clinic--here-s-what-people-ask-me-when-they-re-getting-their-shot---and-what-i-tell-them" width="100%" height="400"></iframe>
<p>As a medical student working with Alberta Health Services to vaccinate people against COVID-19, I have been asked my fair share of questions about the COVID-19 vaccines — from the need for booster doses to rare side effects.</p>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/410911/original/file-20210712-19-geybnm.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/410911/original/file-20210712-19-geybnm.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/410911/original/file-20210712-19-geybnm.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/410911/original/file-20210712-19-geybnm.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/410911/original/file-20210712-19-geybnm.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/410911/original/file-20210712-19-geybnm.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/410911/original/file-20210712-19-geybnm.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption"></span>
<span class="attribution"><a class="source" href="https://theconversation.com/ca/topics/vaccine-confidence-in-canada-107061">Click here for more articles in our series about vaccine confidence.</a></span>
</figcaption>
</figure>
<p>A few days ago, I told an individual who was about to receive her second dose of the Moderna vaccine, “We are expecting about 95 per cent immunity two weeks from today.” She paused and asked, “What does that even mean?” </p>
<p>That scenario has repeated itself a few more times since then. I usually respond with, “It means you have 95 per cent less chance of developing COVID-19 two weeks after you have been vaccinated with the second dose of an mRNA vaccine.” </p>
<p>But what’s the long story behind that?</p>
<h2>mRNA vaccines</h2>
<p>There are multiple vaccines against COVID-19. I’ll focus on the Moderna and Pfizer-BioNTech mRNA vaccines used in Canada. They both received emergency use authorization from the <a href="https://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-19/covid-19-vaccines">U.S. Food and Drug Administration (FDA)</a> and <a href="https://covid-vaccine.canada.ca/">Health Canada</a> in December 2020. The Pfizer-BioNTech vaccine also <a href="https://www.fda.gov/news-events/press-announcements/fda-approves-first-covid-19-vaccine">received full FDA approval in August 2021</a>. Now that it is fully approved, the Pfizer-BioNTech vaccine is also known by a brand name — Comirnaty — but it’s the exact same vaccine that’s been in use since December 2020. </p>
<p>Both the Moderna and Pfizer-BioNTech vaccines require two doses given at least three to four weeks apart. The mRNA (or messenger RNA) in the vaccines contains the instructions for how to make the now-well-known <a href="https://theconversation.com/know-your-target-fundamental-science-will-lead-us-to-coronavirus-vaccines-136952">spike protein</a> on the surface of SARS-CoV-2, the virus that causes COVID-19. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/418805/original/file-20210901-19-1tpc2kl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="An arm getting an injection" src="https://images.theconversation.com/files/418805/original/file-20210901-19-1tpc2kl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/418805/original/file-20210901-19-1tpc2kl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/418805/original/file-20210901-19-1tpc2kl.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/418805/original/file-20210901-19-1tpc2kl.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/418805/original/file-20210901-19-1tpc2kl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/418805/original/file-20210901-19-1tpc2kl.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/418805/original/file-20210901-19-1tpc2kl.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Once the mRNA vaccine is injected, it carries instructions to cells for how to make the SARS-CoV-2 virus’s spike protein, so the immune system can learn to recognize it and build an immune response to it.</span>
<span class="attribution"><span class="source">(AP Photo/Rogelio V. Solis)</span></span>
</figcaption>
</figure>
<p>Once it is injected into a muscle in the upper arm, this mRNA gives the muscle’s cells the instructions to make the spike protein. The immune system practises combating this protein and learns how to react when it recognizes something that has that spike protein on it. </p>
<p>Down the line, if we are exposed to the actual SARS-CoV-2 virus, our body knows how to defend against the virus because it has built immunity by making antibodies against the spike protein on the surface of the virus. These antibodies are our bodies’ protective proteins against SARS-CoV-2.</p>
<h2>Efficacy vs. effectiveness</h2>
<p>The Pfizer-BioNTech and the Moderna vaccines are extremely efficacious and effective against COVID-19. But what do efficacious and effective mean in the context of a vaccine? </p>
<p>Vaccine efficacy is defined as the reduction in the rate of developing disease in vaccinated people compared to unvaccinated people. First, we would calculate the difference in cases between the two groups and then divide it by the rate of unvaccinated cases. For example, if eight out of 21,830 vaccinated people and 162 out of 21,830 unvaccinated people develop the disease, the efficacy of that vaccine would be calculated as:</p>
<blockquote>
<p>(162 / 21830 - 8 / 21830) / (162 / 21830) = 95 per cent </p>
</blockquote>
<p>These numbers are the actual numbers out of <a href="https://www.nytimes.com/2020/12/13/learning/what-does-95-effective-mean-teaching-the-math-of-vaccine-efficacy.html">the Pfizer-BioNTech trial</a>, which reported <a href="https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-conclude-phase-3-study-covid-19-vaccine">95 per cent efficacy</a> in its clinical trials. Moderna reported a <a href="https://investors.modernatx.com/news-releases/news-release-details/modernas-covid-19-vaccine-candidate-meets-its-primary-efficacy">similar number (94.5 per cent efficacy)</a> in its trials. </p>
<p>Vaccine efficacy is usually measured under specific controlled environments and in the setting of double-blind <a href="https://theconversation.com/how-effective-are-covid-19-vaccines-heres-what-the-stats-mean-and-what-they-dont-164755">randomized controlled trials</a> (RCTs). A double-blind RCT is a study in which the participants are randomly assigned to either a placebo (no vaccine) or intervention (vaccine) group and neither the researchers nor the participants are aware which group they are assigned to. This setting reduces bias and increases the accuracy of the studies. </p>
<p>Now that we know how efficacy is measured, let’s see what 95 per cent efficacy really means. In simple terms, 95 per cent efficacy means that vaccinated people have a 95 per cent lower chance of developing COVID-19. So, if out of 10,000 unvaccinated people, 100 people get the disease, out of 10,000 vaccinated people, only five people might get the disease.</p>
<h2>Real-world effectiveness</h2>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/418809/original/file-20210901-21-11tx0j.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="People getting vaccinated at an arena set up as a mass vaccination clinic" src="https://images.theconversation.com/files/418809/original/file-20210901-21-11tx0j.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/418809/original/file-20210901-21-11tx0j.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/418809/original/file-20210901-21-11tx0j.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/418809/original/file-20210901-21-11tx0j.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/418809/original/file-20210901-21-11tx0j.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/418809/original/file-20210901-21-11tx0j.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/418809/original/file-20210901-21-11tx0j.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">People receive a dose of the COVID-19 vaccine at a mass vaccination clinic at Scotiabank Arena in Toronto on June 27, 2021. For those getting a second dose, the vaccine would take full effect two weeks later.</span>
<span class="attribution"><span class="source">THE CANADIAN PRESS/Cole Burston</span></span>
</figcaption>
</figure>
<p>Vaccine effectiveness, however, is different from efficacy. Effectiveness is how well a vaccine works in reducing the rate of disease in vaccinated people compared to unvaccinated people under real-world conditions.</p>
<p>It’s worth noting that most studies have defined developing disease as testing positive for COVID-19 and having at least one symptom. The efficacy numbers can change based on the circumstances under which the vaccines are tested. For example, the location of testing, the method of testing, the presence of specific strains or variants of a disease-causing virus and the diversity of the participants can affect the efficacy numbers. That’s why demographic information is collected in clinical trials, <a href="https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/Moderna.html">including Moderna</a>’s and <a href="https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/Pfizer-BioNTech.html">Pfizer-BioNTech</a>’s vaccine trials. </p>
<p>This means we can’t directly compare the efficacy of one vaccine to another if they have not been tested under the exact same conditions.</p>
<h2>How well are the mRNA vaccines working?</h2>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/418810/original/file-20210901-19-1fkk48n.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Empty vials of Moderna's COVID-19 vaccine" src="https://images.theconversation.com/files/418810/original/file-20210901-19-1fkk48n.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/418810/original/file-20210901-19-1fkk48n.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/418810/original/file-20210901-19-1fkk48n.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/418810/original/file-20210901-19-1fkk48n.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/418810/original/file-20210901-19-1fkk48n.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/418810/original/file-20210901-19-1fkk48n.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/418810/original/file-20210901-19-1fkk48n.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Preliminary studies suggest mRNA vaccines are about 90 per cent effective under real-world circumstances.</span>
<span class="attribution"><span class="source">THE CANADIAN PRESS/Lars Hagberg</span></span>
</figcaption>
</figure>
<p>With <a href="https://ourworldindata.org/covid-vaccinations">more than five billion doses</a> administered around the world, we are at a point where we can also look at the effectiveness of the COVID-19 vaccines. <a href="https://www.cdc.gov/coronavirus/2019-ncov/vaccines/effectiveness.html">Preliminary studies</a> have shown that both mRNA vaccines are about 90 per cent effective in the real world against COVID-19. <a href="https://edmonton.ctvnews.ca/here-s-how-effective-covid-19-vaccines-have-been-in-alberta-1.5456656">The Alberta government has reported</a> 93 per cent effectiveness from the Moderna and 90 per cent effectiveness from the Pfizer-BioNTech vaccine.</p>
<p>And why does it take two weeks to develop that level of immunity? The process of a vaccine making our bodies immune against a disease has <a href="https://theconversation.com/covid-19-vaccines-how-pfizers-and-modernas-95-effective-mrna-shots-work-149957">multiple steps</a>. Remember the protective proteins called antibodies? One of the last steps in the immunity process is making those antibodies. </p>
<p><a href="https://www.theatlantic.com/health/archive/2021/03/how-long-wait-fully-vaccinated/618303/">Based on the studies done by the vaccine makers</a>, at around 14 days after the second dose, our bodies have made enough antibodies to recognize and fight SARS-CoV-2, hence the two-week rule before you are considered fully vaccinated.</p>
<p>One important statistic that needs to be mentioned is that both mRNA vaccines have been shown to prevent hospitalizations and deaths. This means that even in the rare case of a vaccinated individual developing COVID-19, the likelihood of them being hospitalized or dying is very much lower than if they hadn’t been vaccinated.</p>
<h2>How do COVID-19 vaccines compare to others?</h2>
<p>Another question I’ve been asked is how the effectiveness from the COVID-19 vaccines compares to the vaccines made for other diseases. Well, the MMR vaccine is <a href="https://www.cdc.gov/vaccines/vpd/mmr/public/index.html">97 per cent effective against measles and rubella and 88 per cent against mumps</a>. The effectiveness of the DTaP vaccine (diphtheria, tetanus, acellular pertussis) is between <a href="https://www.immunize.org/askexperts/experts_per.asp">80-85 per cent</a>. The effectiveness of the flu vaccine hovers <a href="https://www.cdc.gov/flu/vaccines-work/past-seasons-estimates.html">between 10-60 per cent</a> depending on the year, the strains the vaccine protects against each year and the actual strains causing influenza and influenza-like diseases.</p>
<p>These numbers all reflect the reduction in the rate of disease between vaccinated and unvaccinated people. So next time you hear a vaccine is 95 per cent effective, that doesn’t mean five per cent of the people who got the vaccine will develop the disease; it means that vaccinated people have 95 per cent less chance of developing the disease compared to unvaccinated people.</p>
<p><em>Do you have a question about COVID-19 vaccines? Email us at <a href="mailto:ca-vaccination@theconversation.com">ca‑vaccination@theconversation.com</a> and vaccine experts will answer questions in upcoming articles.</em></p><img src="https://counter.theconversation.com/content/167046/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Ehsan Misaghi does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>A medical student answers questions he gets asked at a COVID-19 vaccine clinic: Efficacy versus real-world effectiveness, immune response and how the mRNA vaccines compare to vaccines already in wide use.Ehsan Misaghi, Clinician-Scientist Trainee, Faculty of Medicine & Dentistry and Faculty of Science, University of AlbertaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1667092021-08-26T21:39:32Z2021-08-26T21:39:32ZPfizer’s COVID-19 vaccine now has full FDA approval. Here’s what that means for unvaccinated people, organizations and pharma<figure><img src="https://images.theconversation.com/files/418126/original/file-20210826-547-ksvhwl.jpg?ixlib=rb-1.1.0&rect=299%2C80%2C4664%2C3338&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">FDA approval of Pfizer's COVID-19 vaccine may boost vaccination rates among those who have been hesitant to get the shot.</span> <span class="attribution"><span class="source"> (AP Photo/Jessica Hill) </span></span></figcaption></figure><iframe style="width: 100%; height: 175px; border: none; position: relative; z-index: 1;" allowtransparency="" src="https://narrations.ad-auris.com/widget/the-conversation-canada/pfizer-s-covid-19-vaccine-now-has-full-fda-approval--here-s-what-that-means-for-unvaccinated-people--organizations-and-pharma" width="100%" height="400"></iframe>
<p>The <a href="https://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-19/comirnaty-and-pfizer-biontech-covid-19-vaccine">U.S. Food and Drug Administration approved</a> the Pfizer-BioNTech coronavirus vaccine for use in people 16 and older on Aug. 23. Describing FDA approval as “the gold standard,” <a href="https://www.whitehouse.gov/briefing-room/speeches-remarks/2021/08/23/remarks-by-president-biden-on-the-covid-19-response-and-the-vaccination-program-7/">U.S. President Joe Biden</a>, heralded the moment as “a key milestone in our nation’s fight against COVID.”</p>
<p>This milestone was achieved as a result of the unprecedented pace of <a href="https://theconversation.com/explainer-how-clinical-trials-test-covid-19-vaccines-146061">vaccine development</a>. The <a href="https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html?action=click&module=Top%20Stories&pgtype=Homepage#pfizer">Pfizer-BioNTech vaccine</a> moved from concept to pivotal clinical trial to the FDA granting an emergency use authorization in record time. Since Dec. 11, 2020, <a href="https://www.statista.com/statistics/1198516/covid-19-vaccinations-administered-us-by-company/#statisticContainer">205 million doses</a> of the vaccine have been administered in the U.S., and <a href="https://health-infobase.canada.ca/covid-19/vaccination-coverage/#a6">more than 26 million</a> in Canada.</p>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/410911/original/file-20210712-19-geybnm.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/410911/original/file-20210712-19-geybnm.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/410911/original/file-20210712-19-geybnm.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/410911/original/file-20210712-19-geybnm.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/410911/original/file-20210712-19-geybnm.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/410911/original/file-20210712-19-geybnm.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/410911/original/file-20210712-19-geybnm.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption"></span>
<span class="attribution"><a class="source" href="https://theconversation.com/ca/topics/vaccine-confidence-in-canada-107061">Click here for more articles in our series about vaccine confidence.</a></span>
</figcaption>
</figure>
<p>But what’s the difference between an FDA emergency use authorization and full approval? And what impact is FDA approval likely to have on unvaccinated people, doctors, organizations and the pharmaceutical industry?</p>
<p>With surging numbers of cases and hospitalizations driven by the <a href="https://theconversation.com/covid-19-delta-variant-in-canada-faq-on-origins-hotspots-and-vaccine-protection-162653">Delta variant</a>, the hope is that FDA approval will provide a timely boost to vaccination rates.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/UD0K7D3ieYc?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">President Biden urges unvaccinated Americans to get the Pfizer COVID-19 now that it has full FDA approval.</span></figcaption>
</figure>
<p><a href="https://www.whitehouse.gov/briefing-room/speeches-remarks/2021/08/23/remarks-by-president-biden-on-the-covid-19-response-and-the-vaccination-program-7/">President Biden</a> appealed directly to those yet to receive the vaccine: “If you are one of the millions of Americans who said that they will not get the shot until it has full and final approval of the FDA, it has now happened. The moment you have been waiting for is here. It is time for you to go and get your vaccination.”</p>
<h2>What is emergency use authorization?</h2>
<p>In the event of a public health emergency, an <a href="https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization">emergency use authorization</a> allows the FDA to make an unapproved medical product available for use. The <a href="https://www.fda.gov/regulatory-information/search-fda-guidance-documents/emergency-use-authorization-medical-products-and-related-authorities">FDA may grant such authorization</a> provided the available evidence makes it “reasonable to believe that the product may be effective” and there is “no adequate, approved and available alternative.” Importantly, the authorization is limited to the duration of the health emergency.</p>
<p>Recognizing that COVID-19 vaccines would be administered to millions of healthy people, the FDA set a <a href="https://blog.petrieflom.law.harvard.edu/2021/06/15/whats-the-difference-between-vaccine-approval-bla-and-authorization-eua/">high evidentiary bar for authorization</a>. Evidence supporting the vaccine’s safety and efficacy from a well-conducted clinical trial with at least two months of followup is required.</p>
<p>The FDA’s emergency use authorization of the Pfizer-BioNTech vaccine was based on review of a clinical trial with 44,000 people, half of whom had received the vaccine and half the placebo. The trial demonstrated the vaccine prevents 95 per cent of symptomatic COVID-19.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/iGkwaESsGBQ?wmode=transparent&start=100" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Under emergency use authorization, the FDA can provide more timely access to urgently needed drugs and medical products.</span></figcaption>
</figure>
<h2>What does FDA approval add?</h2>
<p><a href="https://blog.petrieflom.law.harvard.edu/2021/06/15/whats-the-difference-between-vaccine-approval-bla-and-authorization-eua/">FDA approval</a> is based on review of a biologics license application, the standard mechanism for the review of novel drugs and vaccines. The product must be demonstrated to be “safe, pure and potent.” For coronavirus vaccines, this means completion of well-conducted clinical trials with six months of followup as well as review of the manufacturing process.</p>
<p>For the Pfizer-BioNTech vaccine, <a href="https://www.wsj.com/articles/the-fda-covid-vaccine-sprint-pfizer-full-approval-11629752800">the FDA reviewed 340,000 pages of data</a> supporting the vaccine’s safety and efficacy — about three times the amount of data contained in the application for emergency use. Additionally, the FDA inspected manufacturing facilities and negotiated the labelling information.</p>
<p>The FDA’s approval of the vaccine will likely affect unvaccinated people, organizations, doctors and the pharmaceutical industry.</p>
<h2>Unvaccinated people</h2>
<figure class="align-right ">
<img alt="A hand preparing a dose of Pfizer's COVID-19 vaccine" src="https://images.theconversation.com/files/418138/original/file-20210826-4978-dxlwt1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/418138/original/file-20210826-4978-dxlwt1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=738&fit=crop&dpr=1 600w, https://images.theconversation.com/files/418138/original/file-20210826-4978-dxlwt1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=738&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/418138/original/file-20210826-4978-dxlwt1.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=738&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/418138/original/file-20210826-4978-dxlwt1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=927&fit=crop&dpr=1 754w, https://images.theconversation.com/files/418138/original/file-20210826-4978-dxlwt1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=927&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/418138/original/file-20210826-4978-dxlwt1.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=927&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">FDA approval sends a clear message that the COVID-19 vaccine is safe and effective.</span>
<span class="attribution"><span class="source">THE CANADIAN PRESS/Jonathan Hayward</span></span>
</figcaption>
</figure>
<p>FDA approval has sent a clear message that the Pfizer-BioNTech vaccine is both safe and effective. Evidence from clinical trials and surveillance of roughly 92 million vaccinated Americans provide a robust foundation for this claim. </p>
<p>The hope is that FDA approval will entice some of the <a href="https://www.nytimes.com/2021/08/23/health/pfizer-vaccine-approval-fda.html">85 million eligible but unvaccinated Americans to get the shot</a>. Maryland School of Public Health <a href="https://www.washingtonpost.com/health/2021/08/23/pfizer-vaccine-full-approval/">professor Sandra C. Quinn</a> explains that “full approval takes away that ‘Oh, it’s experimental’ kind of language. For some people, it might make a difference. They will feel more confident and comfortable.”</p>
<p>How much of a difference might FDA approval make? A June 2021 poll conducted by the <a href="https://www.kff.org/coronavirus-covid-19/poll-finding/kff-covid-19-vaccine-monitor-june-2021/">Kaiser Family Foundation COVID-19 Vaccine Monitor</a> found “three in 10 unvaccinated adults, rising to about half of those in the ‘wait and see’ group, say they would be more likely to get vaccinated if one of the vaccines … were to receive full approval from the FDA.”</p>
<h2>Physicians</h2>
<p>What impact does FDA approval have on doctors? The main difference is that once a drug or vaccine is approved for use, physicians are free to prescribe it for off-label indications, which are uses other than those specifically approved. </p>
<p>Dr. Eric Topol, professor of molecular medicine at non-profit Scripps Research, <a href="https://www.mercurynews.com/2021/08/23/how-fda-approval-will-change-covid-19-vaccinations/">worries that FDA approval</a> of the Pfizer-BioNTech vaccine “will usher in millions of prescriptions by doctors.” Booster shots for fully vaccinated healthy adults would run ahead of FDA’s review of boosters expected in September.</p>
<p><a href="https://www.nytimes.com/2021/08/23/health/pfizer-vaccine-approval-fda.html">Acting FDA Commissioner Janet Woodcock describes</a> the prospect of physicians prescribing vaccine to children as “of great concern.” The proper dose of vaccine and its safety in children under 12 has yet to be established, and widespread prescribing may undermine ongoing clinical trials.</p>
<h2>Organizations</h2>
<figure class="align-right ">
<img alt="A sign outside a restaurant stating " src="https://images.theconversation.com/files/418137/original/file-20210826-13-1qr8joa.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/418137/original/file-20210826-13-1qr8joa.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/418137/original/file-20210826-13-1qr8joa.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/418137/original/file-20210826-13-1qr8joa.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/418137/original/file-20210826-13-1qr8joa.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/418137/original/file-20210826-13-1qr8joa.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/418137/original/file-20210826-13-1qr8joa.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">FDA approval of Pfizer’s COVID-19 vaccine may result in more organizations requiring vaccination.</span>
<span class="attribution"><span class="source">(AP Photo/Haven Daley)</span></span>
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<p>FDA approval of the Pfizer-BioNTech vaccine has green-lighted vaccine mandates across government and the private sector. Although FDA approval <a href="https://blog.petrieflom.law.harvard.edu/2021/06/15/whats-the-difference-between-vaccine-approval-bla-and-authorization-eua/">may not be legally required for vaccine mandates</a>, cautious employers put potential mandates on hold awaiting approval. </p>
<p>Monday’s announcement thus triggered a wave of vaccine mandates. The <a href="https://www.nytimes.com/2021/08/23/us/pfizer-vaccine-mandates.html">Pentagon announced</a> that it is “moving ahead with plans to require all active-duty troops to be vaccinated.” New York City’s <a href="https://www.nytimes.com/2021/08/23/nyregion/nyc-schools-employee-vaccine-mandate.html">Department of Education will now require</a> all employees to be vaccinated. Oil producer <a href="https://www.nytimes.com/2021/08/23/business/chevron-coronavirus-vaccine-mandate.html">Chevron will mandate</a> vaccination for all field workers.</p>
<h2>Pharma industry</h2>
<p>FDA approval allows a drug company to market a drug or vaccine for approved indications. Further, unlike an emergency use authorization that is time limited, approval is open-ended. </p>
<p>The short-term impact of approval for the Pfizer-BioNTech vaccine is likely to be minor simply because it is already in use globally. Pfizer-BioNTech currently has contracts with the United States for <a href="https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-provide-us-government-additional-200">one billion doses</a> and the European Union for <a href="https://ec.europa.eu/commission/presscorner/detail/en/ip_21_2548">1.8 billion doses</a>. Canada’s agreement with Pfizer guarantees <a href="https://www.canada.ca/en/public-services-procurement/services/procuring-vaccines-covid19.html">65 million doses over the next two years</a>. </p>
<p>FDA approval of the Pfizer-BioNTech vaccine does, however, make it <a href="https://blog.petrieflom.law.harvard.edu/2021/06/15/whats-the-difference-between-vaccine-approval-bla-and-authorization-eua/">more difficult for a new vaccine to be granted an emergency use authorization</a>. Recall that such an authorization requires that there be no approved alternative. Any new vaccine will be unable to meet this requirement, and this will give existing approved or authorized vaccine makers a strategic advantage.</p>
<p>Finally, FDA approval is an endorsement of the novel messenger RNA vaccine platform. <a href="https://theconversation.com/3-mrna-vaccines-researchers-are-working-on-that-arent-covid-157858">Novel mRNA vaccines against influenza, malaria and even cancer</a> are currently in development. In the long term, this may be the greatest boon for pharma companies using this technology. </p>
<p><em>Do you have a question about COVID-19 vaccines? Email us at <a href="mailto:ca-vaccination@theconversation.com">ca-vaccination@theconversation.com</a> and vaccine experts will answer questions in upcoming articles.</em></p><img src="https://counter.theconversation.com/content/166709/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Charles Weijer receives consulting income from Cardialen, Eli Lilly & Company, and Research Triangle Institute International.</span></em></p>The U.S. FDA has approved the first COVID-19 vaccine. How is approval different from emergency use authorization, and what difference will it make to a vaccine that’s already in global use?Charles Weijer, Professor of medicine, epidemiology & biostatistics, and philosophy, Western UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1648952021-08-22T08:14:59Z2021-08-22T08:14:59ZWHO guidelines on human genome editing: why countries need to follow them<figure><img src="https://images.theconversation.com/files/416551/original/file-20210817-24-17i09fv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Getty Images</span></span></figcaption></figure><p>The World Health Organisation (WHO) recently called on countries to stop any research that might lead to the birth of genetically edited human beings. The call was made with the release of the <a href="https://www.who.int/publications-detail-redirect/9789240030381">recommendations on human genome editing</a>. </p>
<p><a href="https://medlineplus.gov/genetics/understanding/genomicresearch/genomeediting/">Human genome editing</a> has great potential. It can improve human health and medicine by making changes to DNA in cells to correct, introduce or delete almost any DNA sequence which may cause disease. Other potential benefits include new ways to diagnose, treat and prevent genetic disorders, novel ways to treat infertility, increasing knowledge of human biology and contributing towards vaccine development. </p>
<p>The potential of this technology came into the spotlight in 2018 when Chinese scientist <a href="https://www.nature.com/articles/d41586-019-00673-1">He Jiankui</a> announced that he had edited the genomes of <a href="https://www.technologyreview.com/2019/12/03/131752/chinas-crispr-babies-read-exclusive-excerpts-he-jiankui-paper/">twin girls</a>. His announcement was met with consternation among many scientists because it highlighted a significant gap in regulation.</p>
<p>In response, the WHO established a committee made up of a global multi-disciplinary panel of 18 experts. The committee was asked to develop standards for human genome editing. </p>
<p>After nearly three years the panel recently <a href="https://www.who.int/publications/i/item/9789240030381">published</a> its recommendations. These give advice on appropriate institutional, national, regional and global governance mechanisms for human genome editing. </p>
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<a href="https://theconversation.com/human-gene-editing-who-decides-the-rules-128434">Human gene editing: who decides the rules?</a>
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<p>The report provides a governance framework for genome editing which countries can use to develop their own regulations. It acknowledges that regulation may look different in each country. Nevertheless it asks that each one builds in core values and principles into these frameworks.</p>
<p>The committee produced a series of nine key recommendations. These consider some broader issues associated with the governance of human genome editing. It’s important for countries to try to implement the guidelines so that there can be consensus and a uniform global approach to genome editing. </p>
<h2>A guide to best practice</h2>
<p>The report breaks down genome editing into five areas. These correspond to the various potential uses of genome editing. The first is making changes to somatic cells (adult body cells) after a person is born. The second involves making changes to somatic cells in utero (in the womb). The third involves making changes to germline cells (embryos, sperm, eggs). The fourth involves making changes to the DNA code, and the fifth making changes to enhance a person. </p>
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Read more:
<a href="https://theconversation.com/limits-for-human-embryo-research-have-been-changed-this-calls-for-public-debate-162305">Limits for human embryo research have been changed: this calls for public debate</a>
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<p>Its recommendations included: </p>
<p><strong>Leadership by the WHO and its director-general:</strong> The committee recommended that the director-general of the WHO show scientific and moral leadership by being open about the challenges and the opportunities inherent in human genome editing. He should also point out the consequences of developing and using technologies without first thinking about these issues, and of making decisions in a collaborative way. </p>
<p><strong>International collaboration:</strong> The report recommended that the WHO work with others to develop an international process to create a system to govern human genome editing. To do this, it would need to set up meetings with regulators from different countries to look at the possibility of <a href="https://en.wikipedia.org/wiki/International_law">international agreements</a> to govern the technology. It would also be necessary for countries to discuss their vision for human genome editing, as well as similarities and differences. </p>
<p><strong>Human genome editing registries:</strong> The committee recommended that the WHO ensure that any <a href="https://clinicaltrials.gov/">clinical trial</a> involving this technology be approved by the appropriate research ethics committee and then included in the registry of human genome editing clinical trials. In this way there would be a repository of all clinical trials taking place worldwide. </p>
<p><strong>International research and medical travel:</strong> The director-general should make a policy statement that research on the technology should only be done in countries with oversight mechanisms to regulate its use. This will prevent people from <a href="https://wwwnc.cdc.gov/travel/page/medical-tourism">travelling to countries</a> where this technology is not regulated. </p>
<p><strong>Illegal, unregistered, unethical or unsafe research and other activities:</strong> The WHO should create a mechanism to allow illegal, unregistered, and unethical uses of human genome editing to be reported. </p>
<p><strong>Intellectual property:</strong> The registration of <a href="https://www.wto.org/english/tratop_e/trips_e/intel1_e.htm">intellectual property rights</a> has the potential to prevent technology from becoming inaccessible. The recommendation is that the WHO should encourage the holders of intellectual property rights to make sure that the technology is accessible. </p>
<p><strong>Education, engagement and empowerment:</strong> The WHO should drive a process to facilitate global dialogue on human genome editing. This should include the creation of educational materials, and models of public engagement. </p>
<p><strong>Ethical values and principles for use by WHO:</strong> The committee recommended that the WHO create a set of ethical values and principles, which could be used by its expert committees. </p>
<p><strong>Review of the recommendations:</strong> The report specified that the recommendations should be reviewed by the WHO in three years. This would look at what progress was made to implement them, as well as how science, technology and society had changed in that time. </p>
<h2>The future of gene editing</h2>
<p>The recommendations pave the way for a uniform approach to human genome editing. They aim to assist countries to create regulatory frameworks for the technology, including provisions to prevent unethical uses of the technology. </p>
<p>Significantly, the recommendations build on previous reports on human genome editing, and include ethical values and principles which were not included in previous reports. The panel was also committed to ensuring that <a href="https://theconversation.com/equity-and-access-need-to-be-at-the-forefront-of-innovation-in-human-genome-editing-161794">access to human genome editing</a> is fair, equitable and not only available to a select few.</p>
<p>This technology is developing at a rapid pace. These recommendations form an important first step in regulation of human genome editing. With appropriate implementation, they will contribute to the safe, effective and ethical uses of human genome editing so that all everyone can benefit from the great potential of these technologies.</p><img src="https://counter.theconversation.com/content/164895/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Sheetal Soni is a lecturer at the University of KwaZulu-Natal </span></em></p>Potential benefits of human genome editing include new ways to diagnose, treat and prevent genetic disorders. But there’s a significant gap in regulation.Sheetal Soni, Researcher, Lecturer, Attorney, University of KwaZulu-NatalLicensed as Creative Commons – attribution, no derivatives.