tag:theconversation.com,2011:/ca/topics/placebo-1573/articlesPlacebo – The Conversation2024-01-19T18:09:40Ztag:theconversation.com,2011:article/2208292024-01-19T18:09:40Z2024-01-19T18:09:40ZSix surprising things about placebos everyone should know<figure><img src="https://images.theconversation.com/files/569889/original/file-20240117-27-yzesqg.jpg?ixlib=rb-1.1.0&rect=97%2C14%2C4880%2C2552&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/medicine-placebo-box-drugs-3d-illustration-1064571812">esoxx/Shutterstock</a></span></figcaption></figure><p>Placebos have been studied more than any treatment in the history of medicine, yet they remain mysterious. </p>
<p>I’ve been studying placebos for 20 years and I’ve done some of the <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6288933/">key studies</a> that have <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3655171/">advanced the scientific knowledge</a> in this area. Here are six facts about this strange effect that still fascinate me.</p>
<h2>1. Placebos have a dark cousin: nocebos</h2>
<p>A 29-year-old builder went to the hospital after having jumped onto a <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5471339/">15cm nail</a> that pierced his boot. Moving the nail was so painful he had to be sedated with powerful drugs (fentanyl and midazolam) to remove it. But when he took off his boot, the medics discovered that the nail had gone between his toes. The builder’s pain was caused by the wrong belief that the nail had penetrated his foot. </p>
<p>The detrimental effects of negative expectations are called nocebo effects. For evolutionary reasons (survival depends on avoiding danger), nocebo effects are larger than placebo effects. </p>
<p>Unfortunately, patients are often told more about the bad things that might happen than the good things, which can result in a self-fulfilling prophecy. For example, learning that a drug has a possible side-effect of nausea or pain can actually <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7368797/">cause nausea or pain</a>.</p>
<figure class="align-center ">
<img alt="A builder about to step on a nail" src="https://images.theconversation.com/files/570058/original/file-20240118-15-d5qvgd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/570058/original/file-20240118-15-d5qvgd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/570058/original/file-20240118-15-d5qvgd.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/570058/original/file-20240118-15-d5qvgd.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/570058/original/file-20240118-15-d5qvgd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/570058/original/file-20240118-15-d5qvgd.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/570058/original/file-20240118-15-d5qvgd.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">
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<span class="caption">The nocebo effect is much stronger than the placebo effect.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/construction-worker-has-accident-while-walks-1398989114">Gustavo MS_Photography/Shutterstock</a></span>
</figcaption>
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<h2>2. Placebos work even if people know they are placebos</h2>
<p>Linda Buonanno suffered so badly from irritable bowel syndrome that she often couldn’t <a href="https://www.theguardian.com/lifeandstyle/2017/may/22/knew-they-were-sugar-pills-felt-fantastic-rise-open-label-placebos">leave the house</a> for weeks. She signed up for a trial of “honest” (open-label) placebos, which is a placebo that patients know is a placebo. </p>
<p>The Harvard doctors in the trial <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3008733/">told her</a> the pills were “placebo pills made of an inert substance, like sugar pills, that have been shown in clinical studies to produce significant improvement in [irritable bowel] symptoms through mind-body self-healing processes”.</p>
<p>The honest placebos worked so well that she was able to resume a normal life. </p>
<p>Honest placebos have <a href="https://pubmed.ncbi.nlm.nih.gov/28452193/">worked in other trials</a> for treating depression, back pain and attention deficit hyperactivity disorder (ADHD). </p>
<p>Honest placebos work because of our subconscious expectations. Our past experiences of doctors and hospitals can generate subconscious expectations that activate our body’s inner pharmacy, which produces morphine (endorphins) and other beneficial drugs. </p>
<h2>3. Honest placebos are ethically acceptable</h2>
<p>It is often considered unethical for doctors to give placebos to patients because this supposedly <a href="https://link.springer.com/article/10.1007/s11724-014-0400-1">involves lying</a> (telling patients that a sugar pill is a powerful medication). But honest placebos do not involve lying, so there is no ethical barrier. </p>
<p>In one <a href="https://pubmed.ncbi.nlm.nih.gov/34805194/#:%7E:text=Introduction%3A%20Open%2Dlabel%20placebos%20have,label%20placebos%20in%20acute%20pain.">ongoing trial</a>, doctors asked patients whether they would be willing to try a mix of real painkillers and honest placebos. Patients in this trial have the same level of pain relief following surgery, but are less likely to become dependent on painkillers.</p>
<h2>4. Placebo effects are part of most treatment effects</h2>
<p>When a doctor prescribes ibuprofen for back pain, the effects are due to the ibuprofen and the patient’s beliefs and expectations, which can be influenced by the doctor’s communication. Doctors who offer positive messages in a warm, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6047264/">empathic manner</a> will increase the effect of the drugs. </p>
<p>The <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2359128/">size and colour</a> of the pill can also influence the effect. A large, orange pill can reduce pain more than a small, red one. </p>
<p>By contrast, blue pills generally have a sedative effect – except for Italian men, for whom blue pills have an <a href="https://www.amherst.edu/system/files/media/1601/moerman_explanatory%20mechanisms%20for%20placebo%20effects.pdf">excitative effect</a>), probably because their revered football team wears blue. </p>
<p>Doctors’ ethical duty to benefit patients suggests it is an ethical duty to maximise the placebo effects of all treatments they provide.</p>
<h2>5. You don’t need placebos to have placebo effects</h2>
<p>In one trial, patients were given morphine <a href="https://pubmed.ncbi.nlm.nih.gov/15488461/">via an intravenous line</a> following surgery. However, only half of the patients were told they were receiving morphine. The patients who were told this had 50% more pain relief than those who were not told they were receiving morphine. This is an example of a placebo effect without a placebo.</p>
<h2>6. You can generate placebo (and nocebo) effects in yourself</h2>
<p>All communication can have a beneficial or harmful effect. One study found that teaching communication skills to families <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4915212/">reduced anxiety and depression</a>. On the other hand, couples who dwell on problems and negative aspects of their relationships were shown in a study to have <a href="https://www.sciencedirect.com/science/article/abs/pii/S0306453022003304?via%3Dihub">weaker immune systems</a>. </p>
<p>Acts of altruism, focusing on a brighter future, or gratitude are proven ways to reduce the effect of negative communication. An easy way to generate positive placebo effects for yourself is by performing a <a href="https://www.mentalhealth.org.uk/explore-mental-health/kindness-and-mental-health/random-acts-kindness">random act of kindness</a>, such as making a colleague a cup of tea, or simply smiling and saying hello.</p>
<p>You can learn more about the amazing effects of placebos and nocebos in my <a href="https://www.press.jhu.edu/books/title/12830/power-placebos">latest book</a>, The Power of Placebos: How the Science of Placebos and Nocebos can Improve Health Care.</p><img src="https://counter.theconversation.com/content/220829/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jeremy Howick has received funding from the Medical Research Council (MRC), National Institute for Health and Care Research (NIHR), the General Medical Council (GMC). He is currently funded by the Stoneygate Trust.</span></em></p>Placebos are the closest thing to magic that medicine has discovered.Jeremy Howick, Professor and Director of the Stoneygate Centre for Excellence in Empathic Healthcare, University of LeicesterLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1979192023-01-25T22:08:38Z2023-01-25T22:08:38ZPlacebos reduce feelings of guilt – even when people know they’re taking one<figure><img src="https://images.theconversation.com/files/506085/original/file-20230124-4836-ieb3gv.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2370%2C1695&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-vector/translucent-ghostly-hands-beating-man-concept-1028358583">GoodStudio/Shutterstock</a></span></figcaption></figure><p>Guilt is a double-edged sword. It can be a <a href="https://link.springer.com/article/10.1007/s11031-017-9612-z">reminder to improve</a> and a motivation to apologise. It can also lead to <a href="https://espace.library.uq.edu.au/view/UQ:674717">pathological perfectionism and stress</a> and is also closely associated with <a href="https://onlinelibrary.wiley.com/doi/10.1002/jts.21963">depression and post-traumatic stress disorder</a>.</p>
<p>Unfortunately, good and bad <a href="https://www.tandfonline.com/doi/full/10.1080/13548506.2020.1859558">guilt are common</a>, and there are few proven treatments to reduce unhealthy guilt.</p>
<p>To help solve the problem of too much guilt, a recent study published in Nature found that <a href="https://www.nature.com/articles/s41598-022-25446-1">placebos can reduce feelings of guilt</a>, even when the person taking them knows they’re receiving placebos.</p>
<p>In the study, 112 healthy volunteers between the ages of 18 and 40 took part. Their guilt was measured at the beginning using questionnaires including the <a href="https://gospel-app.com/wp-content/uploads/2018/10/SSGS.pdf">state shame and guilt scale (SSGS)</a>. This questionnaire asks people whether they feel remorse or bad about something they’ve done. Next, the participants did an exercise intended to make them feel more guilty. The exercise involved writing a story about a time they had treated someone they loved unfairly.</p>
<p>The participants were then divided into three groups. One group received a “deceptive placebo”: a blue pill they were told was a real drug. Specifically, they were told that the pill contained phytopharmacon, a substance designed to reduce the feeling of guilt by making whoever took it feel calmer.</p>
<p>Another group received an “open-label placebo” – the same blue pill, but this group was told it was a placebo. They were told that placebos benefit many people through mind-body self-healing mechanisms.</p>
<p>The third group did not receive any treatment at all. This was the “control” group.</p>
<p>After getting the treatment, the guilty feelings were measured using the same questionnaires to see whether the deceptive placebo or open-label placebo was more effective than no treatment.</p>
<p>The main outcome reported in the study was that the deceptive placebo and the open-label placebo <em>combined</em> were more effective at reducing guilt than no treatment.</p>
<figure class="align-center ">
<img alt="A doctor holding a blue pill." src="https://images.theconversation.com/files/506135/original/file-20230124-12-u60slt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/506135/original/file-20230124-12-u60slt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=401&fit=crop&dpr=1 600w, https://images.theconversation.com/files/506135/original/file-20230124-12-u60slt.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=401&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/506135/original/file-20230124-12-u60slt.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=401&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/506135/original/file-20230124-12-u60slt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=504&fit=crop&dpr=1 754w, https://images.theconversation.com/files/506135/original/file-20230124-12-u60slt.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=504&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/506135/original/file-20230124-12-u60slt.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=504&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">This blue pill will help to reduce your negative feelings of guilt.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/doctor-holding-blue-pill-163687727">Milos Vucicevic/Shutterstock</a></span>
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<h2>Overcoming the placebo paradox</h2>
<p>Open-label placebos are important because they overcome the “placebo paradox”. The paradox is that on the one hand <a href="https://pubmed.ncbi.nlm.nih.gov/23690944/">placebos have effects</a>, especially for pain, and <a href="https://pubmed.ncbi.nlm.nih.gov/29681327/">we know how they work</a>. Doctors are ethically bound to help their patients and this ethical force pushes them towards prescribing placebos. </p>
<p>On the other hand, traditional placebos are deceptive (patients think they are, or could be, a real treatment). Doctors are also ethically bound to avoid deceiving patients (<a href="https://pubmed.ncbi.nlm.nih.gov/20013484/">usually</a>) and this ethical force pushes them away from prescribing placebos (although it seems that most doctors have prescribed placebos <a href="https://pubmed.ncbi.nlm.nih.gov/23526969/">at least once</a>). Because open-label placebos do not involve deception, they overcome the paradox and pave the way for ethical (open-label) placebos to help patients, where appropriate.</p>
<p>While the novelty of this study must be applauded, it is not without it’s weaknesses.</p>
<p>First, the participants were healthy volunteers. They were not suffering from guilt before the experiment. It is unclear whether research in <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1447950/pdf/0931261.pdf">healthy volunteers translates</a> to people in actual clinical practice. Also, the measures of guilt were only taken up to 15 minutes after the placebos were given. The long-term effects (and real-life usefulness) of the placebos are therefore not known.</p>
<p>A bigger problem was that it lumped the effects of deceptive and open-label placebos together. The novelty of the study is that it uses open-label placebos, so lumping their effects with those of deceptive placebos dilutes the novelty. This was rather odd because when I dug into the supplementary material, it was clear that open-label placebos <em>alone</em> were more effective than no treatment for reducing guilt. It’s a shame that this was not the headline result.</p>
<h2>Encouraging</h2>
<p>The fact that open-label placebos can reduce pathological guilt, even by a tiny amount, is encouraging because <a href="https://pubmed.ncbi.nlm.nih.gov/26840547/">they can be used ethically</a> in cases where better treatments do not exist. Future studies need to look at the effects of open-label placebos in actual patients and follow them up for longer.</p>
<p>It is also a small leap from the promising results of this study to believe that if open-label placebos work, we might be able to “placebo ourselves” by giving ourselves <a href="https://www.tandfonline.com/doi/abs/10.1080/17439760.2020.1818807?journalCode=rpos20">positive suggestions</a> that make us feel better.</p><img src="https://counter.theconversation.com/content/197919/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jeremy Howick receives funding from the Medical Research Council (MRC) in the UK to investigate nocebo effects.</span></em></p>A novel study from Switzerland used dummy pills to help people overcome bad guilt.Jeremy Howick, Professor and Director of the Stoneygate Centre for Excellence in Empathic Healthcare, University of LeicesterLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1953942022-11-28T17:18:14Z2022-11-28T17:18:14ZCannabis is no better than a placebo for treating pain – new research<figure><img src="https://images.theconversation.com/files/497650/original/file-20221128-17-vrmqf1.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C4920%2C3292&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Many people use cannabis to manage pain.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/indoors-marijuana-growing-planting-cannabis-holding-501493168">photolona/ Shutterstock</a></span></figcaption></figure><p>Cannabis is one of the most <a href="https://pubmed.ncbi.nlm.nih.gov/31657733/">widely used drugs</a> in the world. While there are only a few countries where cannabis is legal for recreational use, many more countries have legalised the use of cannabis for <a href="https://pubmed.ncbi.nlm.nih.gov/28549263/">medical reasons</a>. </p>
<p><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231516/">Reducing pain</a> is one of the most common reasons people report using medical cannabis. According to a US national survey, <a href="https://pubmed.ncbi.nlm.nih.gov/28549263/">17% of respondents</a> who had reported using cannabis in the past year had been prescribed medical cannabis. When it comes to self-medication, the numbers are even higher – with estimates that <a href="https://pubmed.ncbi.nlm.nih.gov/28549263/">between 17-30%</a> of adults in North America, Europe and Australia reporting they use it to manage pain. </p>
<p>Although cannabis (and cannabis-derived products, such as CBD) may be widely used for reducing pain, how effective it really is in doing this is still unclear. This is what our recent systematic review and meta-analysis sought to uncover. Our study, published in the Journal of the American Medical Association, suggests cannabis is <a href="https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2799017?utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_term=112822">no better at relieving pain</a> than a placebo.</p>
<p>To conduct our study, we looked at the results of randomised controlled trials in which cannabis was compared with a placebo for the treatment of clinical pain. We specifically included studies that compared the change in pain intensity before and after treatment. In total, we looked at 20 studies involving almost 1,500 people altogether. </p>
<p>The studies we included looked at a variety of different pain conditions (such as neuropathic pain, which is caused by damage to the nerves, and multiple sclerosis) and types of cannabis products – including THC, CBD and synthetic cannabis (such as nabilone). These treatments were administered in a variety of ways, including via pill, spray, oil and smoked. </p>
<p>The majority of the study’s participants were female (62%) and aged between 33 and 62. Most of the studies were conducted in the US, UK or Canada – though we also included studies from Brazil, Belgium, Germany, France, the Netherlands, Israel, the Czech Republic and Spain.</p>
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<img alt="An assortment of cannabis products, including pills and oils." src="https://images.theconversation.com/files/497651/original/file-20221128-533-1uod5w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/497651/original/file-20221128-533-1uod5w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/497651/original/file-20221128-533-1uod5w.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/497651/original/file-20221128-533-1uod5w.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/497651/original/file-20221128-533-1uod5w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/497651/original/file-20221128-533-1uod5w.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/497651/original/file-20221128-533-1uod5w.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">Our review included studies which looked at a variety of different cannabis products.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/green-leaves-medicinal-cannabis-extract-oil-1928703866">Bukhta Yurii/ Shutterstock</a></span>
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<p>Our meta-analysis showed that pain was rated as being significantly less intense after treatment with a placebo, with a moderate to large effect depending on each person. Our team also observed no significant difference between cannabis and a placebo for reducing pain.</p>
<p>This corroborates the <a href="https://pubmed.ncbi.nlm.nih.gov/32804836/">results of a 2021 meta-analysis</a>. In fact, this 2021 meta-analysis also found that higher-quality studies with better blinding procedures (where both participants and researchers are unaware of who is receiving the active substance) actually had higher placebo responses. This suggests that some placebo-controlled cannabis trials fail to ensure correct blinding, which may have led to an overestimation of the effectiveness of medical cannabis. </p>
<p>Our study also revealed many participants can distinguish between a placebo and active cannabis, despite having the same odour, taste and appearance. If they are aware that they are receiving or not receiving cannabinoids, they are more likely to provide a biased assessment of the effectiveness of the intervention. So to ensure researchers are observing the actual effect of cannabis, participants can’t know what they receive.</p>
<h2>Media coverage</h2>
<p>Our study also examined the way the studies were covered by the media and academic journals to see whether it related to the therapeutic effect participants reported. We did this because research has shown media coverage and information on the internet can <a href="https://www.nejm.org/doi/10.1056/NEJMra1907805">affect the expectations</a> that a person has of a treatment.</p>
<p>Media presence was measured through Altmetric, which is a method of evaluating mentions of a study in the media, blogs and on social media. Academic impact was measured in terms of citations by other researchers. We found a total of 136 news items in the media and blogs. </p>
<p>We categorised coverage as positive, negative or neutral depending on how the results were presenting concerning the effectiveness of cannabis for treating pain. The overwhelming majority of news items reported that cannabis had a positive effect for treating pain. This means that media coverage towards cannabis tends to be positive, regardless of what a study’s outcomes actually were.</p>
<p>There are numerous examples of the relationship between <a href="https://www.bmj.com/content/370/bmj.m1668">treatment expectations and placebo responses</a>. If a person thinks they will experience relief from their pain by using a certain product or treatment, this can change the way they <a href="https://pubmed.ncbi.nlm.nih.gov/30122170/">end up perceiving</a> incoming pain signals – making them think their pain is less severe. Recent evidence suggests that the placebo effect may work even if we’re presented with evidence that <a href="https://www.nature.com/articles/s41562-018-0455-8">contradicts our initial expectations</a>. </p>
<p>We cannot say with 100% certainty that media coverage is responsible for the high placebo response observed in our review. But given placebos were shown to be just as good as cannabis for managing pain, our results show just how important it is to think about the placebo effect and how it can be influenced by external factors – such as media coverage. For treatments, such as cannabinoids, that receive a lot of media attention, we need to be extra rigorous in our clinical trials.</p><img src="https://counter.theconversation.com/content/195394/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Filip Gedin 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>Our study also examined the way media coverage may affect a patient’s expectations of cannabis in treating pain.Filip Gedin, Postdoctoral Researcher, Pain research, Karolinska InstitutetLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1813932022-05-12T12:14:01Z2022-05-12T12:14:01ZFor some people, religious leaders might be most effective at communicating the importance of COVID-19 vaccination<figure><img src="https://images.theconversation.com/files/462095/original/file-20220509-16-m42mc4.jpg?ixlib=rb-1.1.0&rect=429%2C36%2C7750%2C5420&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The Washington National Cathedral hosted a public vaccination event in March 2021 to help demonstrate trust by faith leaders of all denominations in the COVID-19 vaccines.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/mariann-budde-bishop-of-episcopal-diocese-of-washington-news-photo/1307482259?adppopup=true">Alex Wong/Getty Images</a></span></figcaption></figure><p>Vaccinating a substantial portion of society has been found to be the best way to bring the COVID-19 pandemic <a href="https://www.who.int/emergencies/diseases/novel-coronavirus-2019/covid-19-vaccines">under control</a>, but the pace of vaccination has slowed down since the vaccines were first made available to the public in <a href="https://www.usatoday.com/story/news/health/2020/12/29/covid-vaccine-floridas-roll-out-seniors-gets-off-rocky-start/4067324001/">December 2020</a>. As of May 2022, only <a href="https://covid.cdc.gov/covid-data-tracker/#vaccinations_vacc-people-onedose-pop-5yr">66% of the eligible population</a> in the United States was fully vaccinated, even as <a href="https://www.nbcnews.com/news/us-news/covid-19-vaccinations-decline-new-lows-n1291240">vaccines were going unused</a> around the country. </p>
<p>Some groups, such as political conservatives, <a href="https://www.theatlantic.com/politics/archive/2021/04/rural-americans-are-much-less-likely-get-vaccine/618573/">rural residents</a> and <a href="https://www.nytimes.com/2021/04/05/us/covid-vaccine-evangelicals.html">evangelical Christians</a>, are less likely to get vaccinated. Low vaccination rates could lead to more deaths and prolong the pandemic.</p>
<p>Experts <a href="https://doi.org/10.1080/10410236.2020.1838096">believe</a> that effective public health messages are needed to encourage people to receive a COVID-19 vaccination. People are more likely to follow advice if it comes from someone they can trust. </p>
<p>As <a href="https://www.sdstate.edu/directory/filip-viskupic">political</a> <a href="https://www.sdstate.edu/directory/david-wiltse">scientists</a>, we found in our recent study that religious leaders are more effective messengers than medical and political leaders.</p>
<h2>Religious leaders and COVID-19 messaging</h2>
<p>In April 2021, <a href="https://doi.org/10.1017/S104909652200004X">we surveyed</a> 709 unvaccinated registered voters in South Dakota, a state with a large proportion of Republican voters, rural residents and evangelical Christians.</p>
<p>We wanted to find out whether public health messaging from three different types of leaders – political leaders, medical leaders or religious leaders – might increase the willingness of the unvaccinated population to receive a COVID-19 vaccine. We also wanted to find out which messenger would be most successful in delivering this message.</p>
<p>As a part of the survey, we conducted what social scientists call a “<a href="https://doi.org/10.1017/9781108777919">survey experiment</a>,” which is similar to experiments that scientists conduct in laboratories. Participants were randomly assigned into one of four groups: three treatment groups and one control group. </p>
<p>Participants in each of the treatment groups received an identical message encouraging COVID-19 vaccination. This message came either from a political leader, medical leader or a religious leader from South Dakota. </p>
<p>For scientific validity, participants in the fourth group read a short message unrelated to the COVID-19 pandemic (similar to a placebo in a clinical trial). Afterward, all participants answered the same question about their vaccination intentions.</p>
<p>We found that of the three messengers, only the religious messenger succeeded in pushing the interest of the unvaccinated toward getting the shot. Compared to the participants in the control group, those who received a message from the religious leader showed a 12% greater likelihood of getting vaccinated. We also saw that messaging from a religious leader increased evangelical Christians’ interest in getting vaccinated by 14% compared with those in the control group. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/462099/original/file-20220509-18-h338kd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A woman in a white shirt, holding a sign saying 'I fear God, not COVID.'" src="https://images.theconversation.com/files/462099/original/file-20220509-18-h338kd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/462099/original/file-20220509-18-h338kd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/462099/original/file-20220509-18-h338kd.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/462099/original/file-20220509-18-h338kd.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/462099/original/file-20220509-18-h338kd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/462099/original/file-20220509-18-h338kd.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/462099/original/file-20220509-18-h338kd.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">A protestor opposing COVID-19 vaccine mandates holds a sign in front of City Hall in downtown Los Angeles.</span>
<span class="attribution"><a class="source" href="https://newsroom.ap.org/detail/APTOPIXVirusOutbreakCaliforniaVaccine/c45970b57e9a4ba5a029aeeefdaac916/photo?Query=vaccine%20protests&mediaType=photo&sortBy=&dateRange=Anytime&totalCount=1308&currentItemNo=9">AP Photo/Damian Dovarganes</a></span>
</figcaption>
</figure>
<p>Conversely, we found that the same message delivered by both the medical and political leaders failed to persuade the unvaccinated population to receive a COVID-19 vaccine. When we asked every respondent about their interest in learning more about the vaccines, we found a backlash against the medical messenger. Compared with the control group, respondents who received an encouragement from the medical messenger were 9% less likely to seek out information about vaccines. </p>
<h2>A reason for cautious optimism?</h2>
<p>The good news of our study is that attitudes toward vaccination are not set and the vaccine-hesitant are responsive to certain kinds of encouragements. </p>
<p>Our findings are in line with existing studies that showed the high levels of trust clergy enjoy in the society. For example, a Pew survey conducted last year <a href="https://www.pewresearch.org/religion/2021/10/15/most-americans-who-go-to-religious-services-say-they-would-trust-their-clergys-advice-on-covid-19-vaccines/">reported</a> that over 60% of congregants have at least “a fair amount” of confidence in their religious leaders to provide guidance about getting a COVID-19 vaccine. The Pew survey also found that the congregants’ confidence in state and local elected officials as well as news media was lower – at 50% and 41%, respectively. A scientific study <a href="https://doi.org/10.1073/pnas.2101723118">found</a> that a religious message from an evangelical leader led more evangelicals to see wearing face masks as important.</p>
<p>Discouragingly, we found that messaging from medical leaders had little to no effect. Our data shows that this is largely attributed to the politicization of the COVID-19 pandemic. Unfortunately, public health authorities in particular have become part of the political skirmish surrounding vaccination. </p>
<p>For example, Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases and chief medical adviser to the president, and other scientists have been <a href="https://www.nytimes.com/2020/07/17/us/politics/fauci-trump-coronavirus.html">repeatedly criticized</a> by several Republican politicians, including former President Donald Trump. It is likely that many among those who are unvaccinated may not heed scientists’ advice about COVID-19 vaccines.</p>
<p>Overall, the findings of our study should be interpreted as cautious optimism. COVID-19 vaccine hesitancy is challenging to overcome, but we argue that there are ways to break through some of the hesitancy and skepticism.</p><img src="https://counter.theconversation.com/content/181393/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>Two political scientists in their study in South Dakota found people trusted medical professionals the least when it came to public health messages.Filip Viskupič, Assistant Professor of Political Science, South Dakota State UniversityDavid Wiltse, Associate Professor of Political Science, South Dakota State UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1738452022-02-11T13:34:32Z2022-02-11T13:34:32ZIn research studies and in real life, placebos have a powerful healing effect on the body and mind<figure><img src="https://images.theconversation.com/files/445014/original/file-20220208-19-1dce055.jpg?ixlib=rb-1.1.0&rect=38%2C76%2C5078%2C3322&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The concept of placebos – which are sometimes called "sugar pills" – has been around since the 1800s.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/pharmaceutical-research-conceptual-image-royalty-free-image/185760489?adppopup=true">Wladimir Bulgar/Science Photo Library via Getty Images</a></span></figcaption></figure><p>Did you ever feel your own shoulders relax when you saw a friend receive a shoulder massage? For those of you who said “yes,” congratulations, your brain is using its power to create a “placebo effect.” For those who said “no,” you’re not alone, but thankfully, the brain is trainable. </p>
<p>Since the 1800s, <a href="https://doi.org/10.1001/jama.1955.02960340022006">the word placebo</a> has been used to refer to a fake treatment, meaning one that does not contain any active, physical substance. You may have heard of placebos referred to as “sugar pills.” </p>
<p>Today, placebos play a crucial role in medical studies in which some participants are given the treatment containing the active ingredients of the medicine, and others are given a placebo. These types of studies help tell researchers which medicines are effective, and how effective they are. Surprisingly, however, in some areas of medicine, placebos themselves provide patients with <a href="https://doi.org/10.1016/S0140-6736(09)61706-2">clinical improvement</a>. </p>
<p>As two psychologists interested in how <a href="https://scholar.google.com/citations?hl=en&user=LFOKsvwAAAAJ&view_op=list_works&gmla=AJsN-F7HTmfem-T2-tGORhXc3ZwClbf_3X8_ap-HWeyTOTMcJPTzWkutZ6ZL85CJwi2v87spWvAQmnmkjzKIh4ULAdFAV8KVFSBRBC6VQ8ky36RvnyreDoY">psychological factors affect physical conditions</a> and <a href="https://ihpi.umich.edu/our-experts/schrodeh">beliefs about mental health</a>, we help our patients heal from various <a href="https://ihpi.umich.edu/our-experts/ehpatter">threats to well-being</a>. Could the placebo effect tell us something new about the power of our minds and how our bodies heal?</p>
<h2>Real-life placebo effects</h2>
<p>Today, scientists define these <a href="http://programinplacebostudies.org/">so-called placebo effects</a> as the positive outcomes that cannot be scientifically explained by the physical effects of the treatment. Research suggests that the placebo effect is caused by <a href="https://doi.org/10.1038/nrn3976">positive expectations</a>, the provider-patient relationship and the <a href="https://doi.org/10.1016/S0140-6736(09)61706-2">rituals around receiving medical care</a>.</p>
<p>Depression, pain, fatigue, allergies, <a href="https://doi.org/10.1186/s13063-017-1964-x">irritable bowel syndrome</a>, Parkinson’s disease and even <a href="https://doi.org/10.1056/nejmoa013259">osteoarthritis of the knee</a> are just <a href="https://doi.org/10.1159/000490354">a few of the conditions</a> that <a href="https://www.npr.org/2020/05/11/853753307/all-the-worlds-a-stage-including-the-doctor-s-office">respond positively to placebos</a>. </p>
<p>Despite their effectiveness, there is stigma and debate about <a href="https://doi.org/10.1159/000514435">using placebos in U.S. medicine</a>. And in routine medical practice, they are rarely used on purpose. But based on new understanding of how non-pharmacological aspects of care work, safety and patient preferences, some experts have begun recommending <a href="https://doi.org/10.1159/000490354">increasing the use of placebos in medicine</a>.</p>
<p>The U.S. Food and Drug Administration, the organization that regulates which medicines are allowed to go to the consumer market, requires that all new medicines be tested in randomized controlled trials that show they are <a href="https://www.regdesk.co/fdas-guidance-on-placebos/#">better than placebo treatments</a>. This is an important part of ensuring the public has access to high-quality medications. </p>
<p>But studies have shown that the placebo effect is so strong that many drugs don’t provide more relief <a href="https://doi.org/10.1017/S2045796018000240">than placebo treatments</a>. In those instances, drug developers and researchers sometimes see placebo effects as a nuisance that masks the treatment benefits of the manufactured drug. That sets up an incentive for drug manufacturers to try to do away with placebos so that drugs pass the FDA tests.</p>
<p>Placebos are such a problem for the enterprise of drug development that a company has developed a <a href="https://verasci.com/the-placebo-control-reminder-script-now-available-on-pathway/">coaching script to discourage patients</a> who received placebos from <a href="https://doi.org/10.1038/s41386-020-00911-5">reporting benefits</a>.</p>
<h2>Treating depression</h2>
<p>Prior to the COVID-19 pandemic, about 1 in 12 U.S. adults had a <a href="https://www.cdc.gov/nchs/products/databriefs/db303.htm">diagnosis of depression</a>. During the pandemic, those numbers rose to <a href="https://www.bu.edu/articles/2021/depression-rates-tripled-when-pandemic-first-hit/">1 in 3 adults</a>. That sharp rise helps explain why <a href="https://www.businesswire.com/news/home/20210426005303/en/Global-Antidepressants-Market-Report-2021-COVID-19-Causes-a-Surge-in-Demand-for-Antidepressant-Drugs-as-Mental-Health-Problems-Rise---ResearchAndMarkets.com">US$26.25 billion worth of antidepressant medications</a> were used across the globe in 2020.</p>
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<figcaption><span class="caption">Brain-imaging studies show that the brain has an identifiable response to the expectations and context that come with placebos.</span></figcaption>
</figure>
<p>But according to psychologist and placebo expert Irving Kirsch, who has studied placebo effects for decades, a large part of <a href="https://doi.org/10.3389/fpsyt.2019.00407">what makes antidepressants helpful</a> in alleviating depression is the placebo effect – in other words, the belief that the medication will be beneficial. </p>
<p>Depression is not the only condition for which medical treatments are actually functioning at the level of placebo. Many well-meaning clinicians offer treatments that appear to work based on the fact that patients get better. But a recent study reported that <a href="https://www.sciencealert.com/around-90-percent-of-your-medical-treatments-isn-t-backed-by-high-quality-evidence">only 1 in 10</a> <a href="https://doi.org/10.1016/j.jclinepi.2020.08.005">medical treatments sampled</a> met the standards of what is considered by some to be the gold standard of high quality evidence, according to <a href="https://www.cochrane.org/evidence">a grading system</a> by an international nonprofit organization. This means that many patients improve even though the treatments they receive have not actually been proved to be better than the placebo. </p>
<h2>How does a placebo work?</h2>
<p>The power of the placebo comes down to the power of the mind and a person’s skill at harnessing it. If a patient gets a <a href="https://www.hopkinsmedicine.org/health/conditions-and-diseases/headache/tension-headaches">tension headache</a> and their trusted doctor gives them a medicine that they feel confident will treat it, the relief they expect is likely to decrease their stress. And since <a href="https://www.mayoclinic.org/diseases-conditions/tension-headache/in-depth/headaches/art-20046707">stress is a trigger for tension headaches</a>, the magic of the placebo response is not so mysterious anymore.</p>
<p>Now let’s say that the doctor gives the patient an expensive brand-name pill to take multiple times per day. Studies have shown that it is even more likely to make them feel better because all of those elements subtly convey the message that they <a href="https://doi.org/10.1016/bs.irn.2018.07.014">must be good treatments</a>.</p>
<p>Part of the beauty of placebos is that <a href="https://www.nytimes.com/2016/01/25/books/review-in-cure-accepting-the-minds-role-in-a-bodys-health.html">they activate existing systems</a> of <a href="https://www.aapb.org/i4a/pages/index.cfm?pageID=3386">healing within the mind and body</a>. Elements of the body once thought to be outside of an individual’s control are now known to be modifiable. A legendary example of this is Tibetan monks who <a href="https://doi.org/10.1371/journal.pone.0058244">meditate to generate enough body heat</a> to dry wet sheets in 40-degree Fahrenheit temperatures.</p>
<p>A field called <a href="https://bensonhenryinstitute.org/mission-history/">Mind Body Medicine</a> developed from the work of cardiologist Herbert Benson, who observed those monks and other experts mastering control over automatic processes of the body. It’s well understood in the medical field that <a href="https://us.macmillan.com/books/9780805073690#">many diseases are made worse</a> by the automatic changes that <a href="https://www.hsph.harvard.edu/nutritionsource/stress-and-health/">occur in the body under stress</a>. If a placebo interaction reduces stress, it can <a href="https://www.apa.org/topics/stress/body#">reduce certain symptoms</a> in a scientifically explainable way. </p>
<p>Placebos also work by creating expectations and conditioned responses. Most people are familiar with <a href="https://pubmed.ncbi.nlm.nih.gov/29262194/">Pavlovian conditioning</a>. A bell is rung before giving dogs meat that makes them salivate. Eventually, the sound of the bell causes them to salivate even when they do not receive any meat. A recent study from Harvard Medical School successfully used the same conditioning principle to help patients <a href="https://doi.org/10.1097/j.pain.0000000000002185">use less opioid medication for pain following spine surgery</a>. </p>
<p>Furthermore, multiple brain imaging studies demonstrate changes in the brain in response to successful placebo treatments for pain. This is excellent news, given the <a href="https://theconversation.com/oxycontin-created-the-opioid-crisis-but-stigma-and-prohibition-have-fueled-it-167100">ongoing opioid epidemic</a> and the need for effective pain management tools. There is even evidence that individuals who respond positively to placebos <a href="https://doi.org/10.1126/science.1093065">show increased activity in areas of the brain</a> that release naturally occurring opioids. </p>
<p>And emerging research suggests that even when people know they are receiving a placebo, the inactive treatment still has <a href="https://doi.org/10.1038/s41467-020-17654-y">effects on the brain and reported levels of improvement</a>. </p>
<h2>Placebos are nontoxic and universally applicable</h2>
<p>In addition to the ever-increasing body of evidence surrounding their effectiveness, placebos offer multiple benefits. They have no side effects. They are cheap. They are not addictive. They provide hope when there might not be a specific chemically active treatment available. They mobilize a person’s own ability to heal through multiple pathways, including those studied in the <a href="https://www.pnirs.org/">field of psychoneuroimmunology</a>. This is the study of relationships between the immune system, hormones and the nervous system. </p>
<p>By defining a placebo as the act of setting positive expectations and providing hope through psychosocial interactions, it becomes clear that placebos can enhance traditional medical treatments.</p>
<h2>Using placebos to help people in an ethical way</h2>
<p>The placebo effect is recognized as being powerful enough that the American Medical Association considers it <a href="https://www.ama-assn.org/delivering-care/ethics/use-placebo-clinical-practice#">ethical to use placebos</a> to enhance healing on their own or with standard medical treatments if the patient agrees to it.</p>
<p>Clinically, doctors use the principles of placebo in a more subtle way than it is used in research studies. A 2013 study from the U.K. found that <a href="https://doi.org/10.1371/journal.pone.0058247">97% of physicians</a> acknowledged in a survey having used some form of placebo during their career. This might be as simple as expressing a strong belief in the likelihood that a patient will feel better from whatever treatment the doctor prescribes, even if the treatment itself is not chemically powerful. </p>
<p>There is now even an international <a href="https://placebosociety.org/home">Society for Interdisciplinary Placebo Studies</a>. They have written <a href="https://doi.org/10.1159/000490354">a consensus statement</a> about the use of placebos in medicine and recommendations for <a href="https://doi.org/10.1159/000510738">how to talk with patients about it</a>. In the past, patients who improved from a placebo effect might have felt embarrassed, as if their ailment were not real. </p>
<p>But with the medical field’s growing acceptance and promotion of placebo effects, we can envision a time when patients and clinicians take pride in their skill at harnessing the placebo response.</p>
<p>[<em>Get fascinating science, health and technology news.</em> <a href="https://memberservices.theconversation.com/newsletters/?nl=science&source=inline-science-fascinating">Sign up for The Conversation’s weekly science newsletter</a>.]</p><img src="https://counter.theconversation.com/content/173845/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>Drug manufacturers often shun the use of placebos in clinical trials. But research suggests that placebos could play an important role in the treatment of depression, pain and other maladies.Elissa H. Patterson, Clinical Assistant Professor of Psychiatry and Neurology, University of MichiganHans Schroder, Clinical Assistant Professor of Psychiatry, University of MichiganLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1659992021-09-08T09:57:41Z2021-09-08T09:57:41ZIt’s still not fully understood how placebos work – but an alternative theory of consciousness could hold some clues<figure><img src="https://images.theconversation.com/files/416991/original/file-20210819-25-1jtm3hw.jpg?ixlib=rb-1.1.0&rect=21%2C31%2C3516%2C1988&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/3d-rendering-brain-1031892406">Shutterstock</a></span></figcaption></figure><p>If you’ve had both of your COVID vaccinations, you may have suffered some <a href="https://theconversation.com/why-some-people-dont-experience-vaccine-side-effects-and-why-its-not-a-problem-159282">side-effects</a> – perhaps headaches, fatigue, fever or a sore arm. These effects are mainly caused by your immune system’s reaction to the vaccine. But most scientists agree that there is another cause: the human mind. </p>
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<p>The ability of the mind to generate the symptoms of illness is known as the “nocebo” effect. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4804316/">The nocebo effect</a> is the unpopular twin brother of the placebo effect. Whereas the placebo effect alleviates pain and the symptoms of illness, the nocebo effect does the opposite: it generates pain and symptoms.</p>
<p>A <a href="https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-018-3042-4">2018 study</a> found that almost half of participants in placebo trials experience side-effects, even though they are taking inert substances. There was a <a href="https://www.nejm.org/doi/10.1056/NEJMoa2034577">similar finding</a> in the first major trial of the Pfizer COVID vaccine in 2020. In the placebo group – who were not given the vaccine – between a quarter and a third of people reported fatigue, a similar number reported headaches, and around 10% reported muscle pain. </p>
<p>Indeed, Martin Michaelis and Mark Wass, bioscientists at the University of Kent, <a href="https://www.kent.ac.uk/news/science/28135/explainer-why-do-covid-19-vaccines-cause-side-effects">recently suggested that</a> “for some vaccinated people the knowledge that they have been vaccinated may be sufficient to drive side-effects”.</p>
<h2>Your brain on placebos</h2>
<p>Unlike its unpopular brother, <a href="https://theconversation.com/placebos-what-theyre-made-of-matters-124189">the placebo effect</a> is so well known that it needs little introduction. But in many ways, the placebo effect has become so familiar that it’s easy to forget how strange it really is. It’s bizarre that <a href="https://www.frontiersin.org/articles/10.3389/fncom.2016.00045/full">pain relief and healing</a> can take place without actual treatment. And that powerful positive physiological effects can occur without any real physiological intervention. </p>
<p>Research has shown that a vast array of different conditions benefit from placebos. This includes <a href="https://pubmed.ncbi.nlm.nih.gov/22677304/">acne</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/19900628/">Crohn’s disease</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4828269/">epilepsy</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2014313/">ulcers</a>, <a href="https://n.neurology.org/content/53/4/679">multiple sclerosis</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/31043548/">rheumatism</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/25304530/#:%7E:text=Neuroimaging%20studies%20have%20demonstrated%20that,neurons%20using%20single%2Dcell%20recording">Parkinsons’s disease</a> and <a href="https://pubmed.ncbi.nlm.nih.gov/9178676/#:%7E:text=Conclusions%3A%20In%20trials%20of%20active,visits%20(more%20than%20three).">colitis</a>. A <a href="https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2762993">recent study</a> also found that placebos had a highly significant effect on erectile dysfunction. </p>
<figure class="align-center ">
<img alt="MRI brain scan image." src="https://images.theconversation.com/files/416958/original/file-20210819-15-gguy16.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/416958/original/file-20210819-15-gguy16.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/416958/original/file-20210819-15-gguy16.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/416958/original/file-20210819-15-gguy16.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/416958/original/file-20210819-15-gguy16.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/416958/original/file-20210819-15-gguy16.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/416958/original/file-20210819-15-gguy16.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">
<figcaption>
<span class="caption">How placebos work is still not quite understood.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/mri-magnetic-resonance-image-head-brain-588977774">Shutterstock</a></span>
</figcaption>
</figure>
<p>Comparisons of placebos to antidepressants suggest that the placebo effect can play an important role in the treatment of depression. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2253608/">A 2008 study</a> found no significant difference between leading antidepressants and placebos. In <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5889788/#__ffn_sectitle">a 2018 study</a>, antidepressants fared slightly better, but their effect was still only found to be “mostly modest” compared with placebos. </p>
<p>All of this isn’t simply a matter of suggestion or delusion: real and measurable physiological changes occur. Studies have found that, when taken as painkillers, placebos <a href="https://www.frontiersin.org/articles/10.3389/fncom.2016.00045/full">decrease neurological activity</a> related to pain and make use of many of the same neurotransmitters and <a href="https://jamanetwork.com/journals/jamapsychiatry/fullarticle/482600">neural pathways as opioids</a>. Similarly, <a href="https://pubmed.ncbi.nlm.nih.gov/25304530/#:%7E:text=Neuroimaging%20studies%20have%20demonstrated%20that,neurons%20using%20single%2Dcell%20recording.">researchers have found</a> that, when taken by people with Parkinson’s disease, placebos can stimulate the release of dopamine, which reduces the symptoms of the condition. </p>
<h2>Mind control and consciousness</h2>
<p>Researchers looking into placebos have found that some factors, such as expectancy of treatment, different personality types and the <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3962549/">patient-physician relationship</a>, can have some bearing on the effects. </p>
<p>We also know that placebos can activate reward pathways in the brain – and increase levels of <a href="https://www.nature.com/articles/npp201081#:%7E:text=Large%20placebo%20responses%20were%20associated,deactivation%20of%20dopamine%20and%20opioids.">opioid and dopamine activity</a>. That said, the underlying causes of the placebo effect are <a href="https://www.ncbi.nlm.nih.gov/books/NBK513296/">still mysterious</a>. </p>
<figure class="align-center ">
<img alt="Brain, consciousness concept inside woman's head on purple background." src="https://images.theconversation.com/files/416787/original/file-20210818-21-15zgdlk.jpg?ixlib=rb-1.1.0&rect=50%2C31%2C4198%2C2790&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/416787/original/file-20210818-21-15zgdlk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=399&fit=crop&dpr=1 600w, https://images.theconversation.com/files/416787/original/file-20210818-21-15zgdlk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=399&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/416787/original/file-20210818-21-15zgdlk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=399&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/416787/original/file-20210818-21-15zgdlk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=502&fit=crop&dpr=1 754w, https://images.theconversation.com/files/416787/original/file-20210818-21-15zgdlk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=502&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/416787/original/file-20210818-21-15zgdlk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=502&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Placebos also affect activity in higher brain regions like the prefrontal cortex, amygdala, and striatum.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/double-multiply-exposure-abstract-portrait-dreamer-1502881307">Shutterstock</a></span>
</figcaption>
</figure>
<p>Perhaps though, nocebo and placebo effects only seem mysterious because we are looking at them from the wrong perspective. And by this, I mean maybe if we consider an alternative view of consciousness, the placebo and nocebo effect could begin to make more sense.</p>
<h2>The brain and the mind</h2>
<p>In modern western culture, the mind is usually seen as a <a href="https://plato.stanford.edu/entries/mind-identity/">byproduct of the brain</a> – a kind of shadow cast by neurological processes. Mental phenomena such as thoughts, memories and feelings are thought to be produced by brain activity. </p>
<p>If we have psychological problems, they are thought to be due to neurological imbalances that can be corrected by medication. But if this assumption is correct, how is it possible for mental processes to influence the body as well as the brain in such a powerful way?</p>
<p>Indeed, the difficulties of explaining consciousness purely in terms of brain processes have grown so acute that <a href="https://onlinelibrary.wiley.com/doi/full/10.1111/zygo.12649">some philosophers and scientists</a> have adopted an alternative view: that consciousness is not a direct product of the brain, but a <a href="https://theconversation.com/spiritual-science-how-a-new-perspective-on-consciousness-could-help-us-understand-ourselves-116451">fundamental universal quality</a> – like mass or gravity. </p>
<p>This is something I look at in my recent book, <a href="https://www.stevenmtaylor.com/books/spiritual-science">Spiritual Science</a> and it’s a view
that has been adopted by some contemporary philosophers – including David Chalmers and Thomas Nagel. <a href="http://consc.net/papers/puzzle.html">Chalmers suggests</a> that consciousness “does not seem to be derivable from physical laws” and believes it could be “considered a fundamental feature, irreducible to anything more basic.” Nagel also suggests that the “mind is not just an afterthought or an accident or add on, but a basic aspect of nature.” </p>
<p>Other scientists and philosophers - such as <a href="https://twitter.com/Philip_Goff/status/1257319582311706627?s=20">Christof Koch and Phillip Goff</a> - have adopted similar theories, which suggest that the mind or consciousness is a basic quality of material particles. </p>
<p>These approaches are <a href="https://www.scottaaronson.com/blog/?p=1799">not yet widely accepted</a>, and <a href="https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1004286">would need to gather more evidence</a> to support them. And there are some difficult issues that need to be addressed: for example, if consciousness is a fundamental quality, how does it end up in individual conscious beings such as ourselves? Or, if consciousness exists in particles of matter, how does the consciousness of those particles combine to produce larger conscious entities such as human beings? </p>
<p>More mainstream scientists still hope that a neurological explanation of consciousness will be found, that will help to throw some light on “rogue” phenomena like the nocebo and placebo effects. But taking the philosophical idea of consciousness as fundamental might suggest that the mind is in some way more powerful than the brain and the body, and so could influence the latter in a profound way – and it might help explain one day why placebo pills can bring about real physiological and neurological changes in many people.</p><img src="https://counter.theconversation.com/content/165999/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Steve Taylor 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>The mind is a powerful thing – it can generate both symptoms of illness and symptoms of healing. Here’s what this could tell us about consciousness.Steve Taylor, Senior Lecturer in Psychology, Leeds Beckett UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1499452021-01-06T13:13:29Z2021-01-06T13:13:29ZThe fascinating story of placebos – and why doctors should use them more often<figure><img src="https://images.theconversation.com/files/375475/original/file-20201216-13-19t3fri.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C374%2C282&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">By - https://www.nlm.nih.gov/hmd/emotions/self.html , , Public Domain, https://commons.wikimedia.org/w/index.php?curid=1684469</span> <span class="attribution"><a class="source" href="http://en.wikipedia.org/wiki/Image:Cebocap.jpg">Elaine and Arthur Shapiro/Wikimedia Commons</a></span></figcaption></figure><p>Plato’s <a href="http://www.perseus.tufts.edu/hopper/text?doc=Perseus%3Atext%3A1999.01.0176%3Atext%3DCharm.%3Asection%3D155e">cure for headaches</a> involved:</p>
<blockquote>
<p>a certain leaf, but there was a charm to go with the remedy; and if one uttered the charm at the moment of its application, the remedy made one perfectly well; but without the charm there was no efficacy in the leaf.</p>
</blockquote>
<p>We would now call Plato’s “charm” a placebo. Placebos have been around for thousands of years and are the most widely studied treatments in the history of medicine. Every time your doctor tells you that the drug you take has been proved to work, they mean that it has been <a href="https://onlinelibrary.wiley.com/doi/book/10.1002/9781444342673">proved to work better than a placebo</a>. Every tax or insurance dollar that goes towards a treatment that is “proved” to work is proved to work because it is (supposed to be) better than a placebo. </p>
<p>Despite their importance, doctors are not allowed to use placebos to help patients (at least, officially), and there are debates about whether we still need them in clinical trials. Yet the science of placebos has evolved to the point where our views should – but have not – changed our prejudice against placebos in practice and the privileged position of placebo controls in clinical trials. </p>
<p>In this whistle-stop tour of the history of placebos, I will show what progress has been made and suggest where knowledge of placebos might go in the near future.</p>
<h2>From pleasing prayers to pleasing treatments</h2>
<p>The word “placebo”, as it is used in medicine, was introduced in Saint Jerome’s fourth-century translation of the Bible into Latin. Verse 9 of Psalm 114 became: <a href="https://www.biblestudytools.com/vul/psalms/114-9.html"><em>placebo Domino in regione vivorum</em></a>. “Placebo” means “I will please”, and the verse was then: “I will please the Lord in the land of the living.” </p>
<p>Historians are keen to point out that his translation isn’t quite correct. The Hebrew transliteration is <em>iset’halekh liphnay Adonai b’artzot hakhayim</em>, which means, “I will walk before the Lord in the land of the living.” I think historians are making much ado about not much: why would the Lord want to walk with anyone who wasn’t pleasing? Still, arguments about what placebos <a href="https://philpapers.org/rec/HOWTRO-24">“really” are continue</a>.</p>
<figure class="align-center ">
<img alt="Painting of Saint Jerome by Caravaggio." src="https://images.theconversation.com/files/375451/original/file-20201216-17-1wmk2um.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/375451/original/file-20201216-17-1wmk2um.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=414&fit=crop&dpr=1 600w, https://images.theconversation.com/files/375451/original/file-20201216-17-1wmk2um.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=414&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/375451/original/file-20201216-17-1wmk2um.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=414&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/375451/original/file-20201216-17-1wmk2um.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=520&fit=crop&dpr=1 754w, https://images.theconversation.com/files/375451/original/file-20201216-17-1wmk2um.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=520&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/375451/original/file-20201216-17-1wmk2um.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=520&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Saint Jerome by Caravaggio.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/w/index.php?curid=48395984">Caravaggio/Wikimedia Commons</a></span>
</figcaption>
</figure>
<p>At that time, and even today, the mourning family provided a feast for those who attended the funeral. Because of the free feast, distant relatives, and – this is the important point – people who pretended to be relatives attended the funeral singing “placebo”, just to get the food. This deceptive practice led <a href="http://sites.fas.harvard.edu/%7Echaucer/teachslf/parst-tran.htm">Chaucer to write</a>, “Flatterers are the Devil’s chaplains, always singing Placebo.”</p>
<p>Chaucer also named one of the characters in The Merchant’s Tale, Placebo. The protagonist of the tale is Januarie. Januarie was a wealthy old knight who desired recreational sex with a younger woman called May. To legitimise his desire, he considers marrying her. Before making his decision, he consults his two friends Placebo and Justinius. </p>
<p>Placebo is keen to gain favour with the knight and approves of Januarie’s plans to marry May. Justinius is more cautious, citing Seneca and Cato, who preached virtue and caution in selecting a wife. </p>
<p>After listening to them both, Januarie tells Justinius that he didn’t give a damn about Seneca: he marries May. The theme of deception arises here, too, because Januarie is blind and does not catch May cheating on him.</p>
<p>In the 18th century, the term “placebo” moved into the medical realm when it was used to describe a doctor. In his 1763 book, Dr Pierce describes a visit to his friend, a Lady who was ill in bed. He finds <a href="https://www.jameslindlibrary.org/quoted-in-sutherland-a-attempts-to-revive-ancient-medical-doctrines/">“Dr. Placebo” sitting at her bedside</a>. </p>
<p>Dr Placebo had impressive long curly hair, he was fashionable and he carefully prepared his medicine at the patient’s bedside. When Dr Pierce asks his friend how she was doing, she replies: “Pure and well, my old friend the Doctor has been just treating me with some of his good drops.” Pierce seems to imply that any positive effect Dr Placebo had was due to his great bedside manner, rather than the actual contents of the drops.</p>
<p>Eventually, the word “placebo” started being used to describe treatments. The Scottish obstetrician William Smellie (in 1752) is the first person I’m aware of who <a href="https://www.jameslindlibrary.org/smellie-w-1752/">uses the term “placebo” to describe a medical treatment</a>. He wrote: “it will be convenient to prescribe some innocent Placemus, that she may take between whiles, to beguile the time and please her imagination”. (“Placemus” is another form of the word “placebo”.)</p>
<h2>Placebos in clinical trials</h2>
<p>Placebos were first used in clinical trials in the 18th century to debunk so-called quack cures. Which is paradoxical because the so-called “non-quack” cures at the time included bloodletting and feeding patients the undigested material from the intestines of an oriental goat. These were considered to be so effective that no trials were needed.</p>
<p>The earliest example I’m aware of where a placebo control was used is in a trial of “Perkins tractors”. In the late 18th century, an American doctor called Elisha Perkins developed two metal rods he claimed conducted what he called pathogenic “electric” fluid away from the body. </p>
<figure class="align-center ">
<img alt="Cartoon of a quack treating a patient with Perkins Patent Tractors." src="https://images.theconversation.com/files/375465/original/file-20201216-15-1rwftf5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/375465/original/file-20201216-15-1rwftf5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=475&fit=crop&dpr=1 600w, https://images.theconversation.com/files/375465/original/file-20201216-15-1rwftf5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=475&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/375465/original/file-20201216-15-1rwftf5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=475&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/375465/original/file-20201216-15-1rwftf5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=597&fit=crop&dpr=1 754w, https://images.theconversation.com/files/375465/original/file-20201216-15-1rwftf5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=597&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/375465/original/file-20201216-15-1rwftf5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=597&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">A quack treating a patient with Perkins Patent Tractors.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/w/index.php?curid=36346200">James Gillray/Wikimedia Commons</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>He received the first medical patent issued under the Constitution of the United States for his device in 1796. The tractors were very popular, and even <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2601307/pdf/yjbm00545-0050.pdf">George Washington is said to have bought a set</a>. </p>
<p>They reached Britain in 1799 and became popular in Bath, which was already a hub for healing because of its <a href="https://pubs.rsc.org/en/content/articlelanding/1981/AP/AP9811800002#!divAbstract">natural mineral waters and associated spa, which have been used since Roman times</a>. Dr John Haygarth, however, thought tractors were bunk and proposed to <a href="https://www.jameslindlibrary.org/haygarth-j-1800/">test their effects in a trial</a>. To do this, Haygarth made wooden tractors that were painted to appear identical to Perkins’ metal tractors. But because they were made of wood, they could not conduct electricity. </p>
<p>In a series of ten patients (five treated with real, and five with fake tractors), the “placebo” tractors worked as well as the real ones. Haygarth concluded that tractors didn’t work. Interestingly, the trial did not show that the tractors did not benefit people, but merely that they did not produce their benefit via electricity. Haygarth himself admitted that the fake tractors worked very well. He attributed this to faith.</p>
<p>Other early examples of placebo controls tested the effects of homeopathy tablets compared with bread pills. One of these early trials revealed that doing nothing was better than both <a href="https://journals.sagepub.com/doi/10.1177/014107680609900726">homeopathy and allopathic (standard) medicine</a>. </p>
<p>By the middle of the 20th century, placebo-controlled trials were prevalent enough for Henry Knowles Beecher to produce one of the earliest examples of a “systematic review” that estimated how powerful placebo were. Beecher served in the United States Army during the second world war. Working on the front line in southern Italy, supplies of morphine were running out, and Beecher reportedly saw something that surprised him. A nurse injected a wounded soldier with saltwater instead of morphine before an operation. The soldier thought it was real morphine and didn’t appear to feel any pain.</p>
<p>After the war, Beecher reviewed 15 placebo-controlled trials of treatments for pain and a number of other ailments. The studies had 1,082 participants and found that, overall, 35% of the patients’ symptoms were relieved by placebo alone. In 1955, he published his study in his famous article <a href="https://jamanetwork.com/journals/jama/article-abstract/303530">The Powerful Placebo</a>.</p>
<p>In the 1990s, <a href="https://www.sciencedirect.com/science/article/abs/pii/S0895435697002035">researchers questioned Beecher’s estimates</a>, based on the fact that the people who got better after taking the placebos might have recovered even if they had not taken the placebo. In philosophy-speak the possibly mistaken inference that the placebo caused the cure is called the <em>post hoc ergo propter hoc</em> (after, therefore because of) fallacy. </p>
<p>To test whether placebos really make people better, we have to compare people who take placebos with people who take no treatment at all. Danish medical researchers Asbjørn Hróbjartsson and Peter Gøtzsche did just that. They looked at three-armed trials that included active treatment, placebo control, and untreated groups. Then they checked to see whether the placebo was better than doing nothing. They found a tiny placebo effect that they said could have been an artefact of bias. They concluded that “there is little evidence that placebos, in general, have powerful clinical effects”, and published their results in an article called <a href="https://www.nejm.org/doi/full/10.1056/nejm200105243442106">Is the placebo powerless?</a>, which contrasted directly with the title of Beecher’s paper.</p>
<p>However, Hróbjartsson and Gøtzsche corrected Beecher’s mistake only to introduce one of their own. They included anything labelled as a placebo in a trial for any condition. Such a comparison of apples and oranges is not legitimate. If we looked at the effect of any treatment for any condition and found a tiny average effect, we could not conclude that treatments were not effective. I <a href="https://pubmed.ncbi.nlm.nih.gov/23690944/">exposed this error in a systematic review</a>, and now it is widely accepted that just as some treatments are effective for some things but not everything, some placebos are effective for some things – especially pain.</p>
<h2>Placebo surgery</h2>
<p>Recently, placebo-controlled surgery trials have been used. In perhaps the most famous of these, American surgeon Bruce Moseley found 180 patients who had such severe knee pain that even the best drugs had failed to work. He gave <a href="https://www.nejm.org/doi/full/10.1056/nejmoa013259">half of them real arthroscopy and the other half placebo arthroscopy</a>. </p>
<p>Patients in the placebo arthroscopy group were given anaesthetics and a small incision was made in their knees, but there was no arthroscope, no repairing of damaged cartilage, and no cleaning out of loose fragments of bone. </p>
<p>To keep the patients ignorant about which group they were in, the doctors and nurses talked through a real procedure even if they were performing the placebo procedure. </p>
<p>The fake surgery worked as well as the “real” surgery. A review of over 50 placebo-controlled surgery trials found that placebo surgery was as good as the real surgery in more than half the trials.</p>
<figure class="align-center ">
<img alt="Surgeon operating on a patient's knee." src="https://images.theconversation.com/files/375489/original/file-20201216-21-15cumi0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/375489/original/file-20201216-21-15cumi0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/375489/original/file-20201216-21-15cumi0.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/375489/original/file-20201216-21-15cumi0.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/375489/original/file-20201216-21-15cumi0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/375489/original/file-20201216-21-15cumi0.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/375489/original/file-20201216-21-15cumi0.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">
<figcaption>
<span class="caption">Placebo knee surgery works as well as the real thing.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/arthroscope-surgery-463356068">Samrith Na Lumpoon/Shutterstock</a></span>
</figcaption>
</figure>
<h2>Honest placebos</h2>
<p>A placebo can work even if a patient does not believe it is a “real” treatment. </p>
<p>In the first of the studies of open-label placebos (placebos that patients know are placebos) I know of, two Baltimore doctors by the names of Lee Park and Uno Covi <a href="https://pubmed.ncbi.nlm.nih.gov/14258363/">gave open-label placebos to 15 neurotic patients</a>. They presented the placebo pills to the patients and said: “Many people with your kind of condition have been helped by what are sometimes called sugar pills and we feel that a so-called sugar pill may help you, too.” </p>
<p>The patients took the placebos, and many of them got better after having the placebo – even though they knew it was a placebo. However, the patients were neurotic and a bit paranoid so they didn’t believe the doctors. After the placebo made them better, they thought the doctors had lied and actually given them the real drug. </p>
<p>More recently, <a href="https://pubmed.ncbi.nlm.nih.gov/28452193/">several higher-quality studies confirm that open-label placebos can work</a>. These “honest” placebos may work because patients have a conditioned response to an encounter with their doctor. Just like an arachnophobe’s body can react negatively to a spider even if they know it’s not poisonous, someone can react positively to treatment from a doctor even if they know the doctor is giving them a sugar pill.</p>
<h2>The history of learning how placebos work</h2>
<p>An early study investigating the inner pharmacology of placebo mechanisms is Jon Levine and Newton Gordon’s 1978 <a href="https://pubmed.ncbi.nlm.nih.gov/80579/">study of 51 patients</a> who had impacted molars extracted. All 51 patients had received a painkiller called mepivacaine for the surgical procedure. Then, at three and four hours after the surgery, the patients were given either morphine, a placebo or naloxone. The patients didn’t know which one they had received.</p>
<p>Naloxone is an opioid antagonist, which means that it stops drugs such as morphine and endorphins from producing their effects. It literally blocks the cell receptors, so it stops morphine (or endorphins) from docking onto those receptors. It’s used to treat morphine overdose. </p>
<p>The researchers found that naloxone blocked the painkilling effect of placebos. This shows that placebos cause the release of painkilling endorphins. Since then, many experiments have confirmed these results. Hundreds of others have shown that <a href="https://global.oup.com/academic/product/placebo-effects-9780198705086?cc=us&lang=en&">placebo treatments affect the brain and body</a> in several ways.</p>
<p>The main mechanisms by which placebos are believed to work are expectancy and conditioning.</p>
<p>In a comprehensive study published in 1999 of conditioning and expectancy mechanisms, Martina Amanzio and Fabrizio Benedetti <a href="https://pubmed.ncbi.nlm.nih.gov/9870976/">divided 229 participants into 12 groups</a>. The groups were given a variety of drugs, were conditioned in a number of ways and were given different messages (to induce high or low expectancy). The study found that placebo effects were caused by both expectancy and conditioning.</p>
<p>Despite the progress, some researchers argue – and I agree – that there is something mysterious about how placebos work. In a personal communication, Dan Moerman, a medical anthropologist and ethnobotanist, explained it better than I can:</p>
<blockquote>
<p>We know from all the MRI people that it’s easy enough to see what happens inside to the amygdala, or whatever other bit might be involved, but what moved the amygdala, well, that takes some work.</p>
</blockquote>
<h2>History of placebo ethics</h2>
<p>The accepted view in clinical practice is that placebos are not ethical because they require deception. This view has not yet fully accounted for the evidence that we don’t need deception for placebos to work.</p>
<p>The history of the ethics of placebo controls is more complex. Now that we have many effective treatments, we can compare new treatments with proven therapies. Why would a patient agree to enrol in a trial comparing a new treatment with a placebo when they could enrol in a trial of a new treatment compared with a proven one?</p>
<p>Doctors who take part in such trials may be violating their ethical duty to help and avoid harm. The World Medical Association <a href="https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/">initially banned</a> placebo-controlled trials where a proven therapy was available. Yet in 2010, they reversed this position and said we sometimes needed placebo-controlled trials, even if there is a proven therapy. They claimed there were “scientific” reasons for doing this.</p>
<p>These so-called scientific reasons have been presented using <a href="https://www.tandfonline.com/doi/abs/10.1080/15265160903090041">obscure (to most people) concepts such as “assay sensitivity” and “absolute effect size”</a>. In plain English, they boil down to two (mistaken) claims:</p>
<ol>
<li><p>They say we can only trust placebo controls. This was true in the past. Historically, treatments like bloodletting and cocaine were used to treat a number of ailments yet were often harmful. Say we’d done a trial comparing bloodletting with cocaine for anxiety, and it turned out bloodletting was better than cocaine. We couldn’t infer that bloodletting was effective: it could have been worse than a placebo or doing nothing. In these historical cases, it would have been better to compare those treatments against a placebo. But now, we have effective treatments that can be used as benchmarks. So if a new drug came along for treating anxiety, we could compare it with the proven effective treatment. If the new treatment proved to be at least as good as the old one, we could say it is effective.</p></li>
<li><p>They say only placebo controls provide a constant baseline. This is based on the mistaken view that placebo treatments are “inert” and therefore have constant, invariable effects. This, too, is mistaken. In a systematic review of placebo pills in ulcer trials, the <a href="https://anthrosource.onlinelibrary.wiley.com/doi/epdf/10.1525/maq.2000.14.1.51">placebo response ranged from 0% (not having any effect) to 100%</a> (complete cure).</p></li>
</ol>
<p>As the arguments supporting placebo-controlled trials are being questioned, there is now a movement urging the World Medical Association needs to do <a href="https://www.tandfonline.com/doi/abs/10.1080/15265160903090041">another U-turn</a>, back to its original position.</p>
<h2>Whither placebo?</h2>
<p>For centuries, the word “placebo” was closely linked to deception and pleasing people. Recent studies of open-label placebos show that they need not be deceptive to work. Contrariwise, studies of placebos show that they are not inert or invariable and the basis for the current World Medical Association position has been undermined. The recent history of placebos seems to pave the way for more placebo treatments in clinical practice and fewer in clinical trials.</p>
<p><em>I acknowledge the James Lind Library, the writing of Ted Kaptchuk, Jeffrey Aronson, and the mentorship of Dan Moerman.</em></p><img src="https://counter.theconversation.com/content/149945/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jeremy Howick 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 whistle-stop tour of the history of placebos.Jeremy Howick, Director of the Oxford Empathy Programme, University of OxfordLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1463652020-09-21T18:14:55Z2020-09-21T18:14:55ZCoronavirus vaccine: why it’s important to know what’s in the placebo<figure><img src="https://images.theconversation.com/files/359044/original/file-20200921-22-uou1bq.jpg?ixlib=rb-1.1.0&rect=0%2C33%2C7348%2C4869&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/female-doctor-stethoscope-on-shoulder-holding-1692105757">siam.pukkato/Shutterstock</a></span></figcaption></figure><p>Some researchers conducting clinical trials on a COVID-19 vaccine have not revealed to the public what the placebo contains, but they should. This is because the placebo ingredients influence how effective or harmful the active treatment, with which the placebo is compared, appears. Our new guideline published in <a href="https://journals.plos.org/plosbiology/article?id=10.1371/journal.pmed.1003294">PLOS Medicine</a> remedies this problem by providing a template for reporting what’s in placebo controls.</p>
<p>In some COVID-19 vaccine trials, participants in the control group (the group receiving a placebo) are injected with a saline solution. In other trials, they receive an actual treatment. For example, in the COVID-19 vaccine developed by the University of Oxford, the control group receives a <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31604-4/fulltext">meningitis and septicaemia vaccine</a> as a placebo. </p>
<p>The benefit of using an actual vaccine as the placebo control is that it will cause a similar reaction at the site of the injection as the COVID-19 vaccine, such as muscle pain and soreness. This prevents patients from knowing whether they are getting the placebo or the real treatment. The scientific term for hiding knowledge of who got what treatment is “blinding”. </p>
<p>If patients know they are getting the real thing, they may expect to get better, and their expectations can make them <a href="https://journals.sagepub.com/doi/full/10.1177/0141076818769477">get better a bit faster</a>. And if they know they are getting the placebo, they could <a href="https://onlinelibrary.wiley.com/doi/book/10.1002/9781444342673">drop out of the trial</a> because they know they aren’t getting the actual treatment. Adding an actual vaccine to the placebo control helps the trial remain blinded and so prevents bias arising from differing expectations.</p>
<h2>Active placebos</h2>
<p>The main problem with including something active in the placebo, such as another vaccine, is that it can confuse researchers when they measure side-effects. </p>
<p>We determine whether an active treatment has a particular side-effect, such as redness and swelling at the site where the needle went in, by comparing it with a placebo. In the same way that we conclude that an active treatment works if it is better than a placebo, we conclude that it is harmful if it has more side-effects than the placebo. </p>
<p>What researchers are looking for is a difference. So if the active vaccine causes more numbness at the site of injection than the placebo, you can reliably say that numbness is a side-effect of the active vaccine. But if the placebo is designed to cause the side-effect (like redness and swelling), then the normal way of detecting side-effects doesn’t work. Since the placebo <em>causes</em> the side-effect, we will no longer be able to detect a difference. In other words, the two side-effects, being the same, negate each other. </p>
<p>The problem is that we rarely know how to interpret side-effect information in trials because researchers rarely report what’s in placebo. Reporting <a href="https://onlinelibrary.wiley.com/doi/abs/10.1111/eci.13169">placebo ingredients</a>, <a href="https://ebm.bmj.com/content/early/2020/03/17/bmjebm-2019-111331">specifically in vaccine trials</a>, is not common. This makes it difficult to tell what the true harms of the vaccine are. The same applies to most treatments tested in trials with unknown placebos.</p>
<figure class="align-center ">
<img alt="Researcher in a white lab coat writing on a clipboard." src="https://images.theconversation.com/files/359048/original/file-20200921-24-1sfuuni.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/359048/original/file-20200921-24-1sfuuni.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/359048/original/file-20200921-24-1sfuuni.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/359048/original/file-20200921-24-1sfuuni.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/359048/original/file-20200921-24-1sfuuni.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/359048/original/file-20200921-24-1sfuuni.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/359048/original/file-20200921-24-1sfuuni.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">
<figcaption>
<span class="caption">Researchers rarely report what’s in a placebo.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/portrait-southeast-asian-male-medical-doctor-292069121">poloje/Shutterstock</a></span>
</figcaption>
</figure>
<p>Placebo controls are rightly the gold standard against which new treatments are measured. If a new treatment proves to be better than a placebo, it is taken to be effective. Otherwise, it isn’t. The problem is that until today, there has been no standard for placebos, which made estimates of side-effects confusing. Our <a href="https://journals.plos.org/plosbiology/article?id=10.1371/journal.pmed.1003294">new guideline fixes this problem</a> by encouraging rigorous reporting of placebo ingredients. </p>
<p>We’ve known about the failure – and need – to report what’s in <a href="https://pubmed.ncbi.nlm.nih.gov/20956710/">placebos for 15 years</a>. By following the new guideline, we can get more accurate information about how beneficial and harmful treatments tested in placebo-controlled trials are.</p><img src="https://counter.theconversation.com/content/146365/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jeremy Howick 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>Researchers rarely report what’s in a placebo.Jeremy Howick, Director of the Oxford Empathy Programme, University of OxfordLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1381972020-06-02T12:13:49Z2020-06-02T12:13:49ZFrom the research lab to your doctor’s office – here’s what happens in phase 1, 2, 3 drug trials<figure><img src="https://images.theconversation.com/files/334221/original/file-20200512-66644-10tznjn.jpg?ixlib=rb-1.1.0&rect=43%2C0%2C4800%2C3140&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Finding a cure for the coronavirus requires more than anecdotal evidence.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/doctor-wearing-ppe-or-isolation-grown-suite-for-royalty-free-image/1208754898?adppopup=true">Skaman306/Moment via Getty Images</a></span></figcaption></figure><p>For COVID-19, like all illnesses, the drugs and vaccines to treat or prevent the disease must be backed by rigorous evidence. <a href="https://www.nia.nih.gov/health/what-are-clinical-trials-and-studies">Clinical trials</a> are the source of this evidence. </p>
<p>With vaccines and drugs for the coronavirus already entering human testing, it is important to know what the different phases of clinical trials are testing for. <a href="https://keck.usc.edu/faculty-search/mindy-aisen/">I am a neurologist</a> with the <a href="https://keck.usc.edu/atri/">Alzheimer’s Therapeutic Research Institute</a> at the University of Southern California. Our team has been developing and overseeing all phases of clinical trials for decades. I am here to help you understand this complicated and important process. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/l0ZBZ2Zy7Lw?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
</figure>
<h2>Preclinical trials</h2>
<p>The earliest indications about whether an intervention is effective and safe come from preclinical trials. This research is done in the laboratory using cells or animals.</p>
<p>Researchers can get some information about safety and efficacy of a treatment from preclinical trials, but the results do not say whether what they are testing is safe or works in people. </p>
<p>Once a treatment shows promise in preclinical trials, researchers begin the process of working through the phases that have been established by the <a href="https://www.fda.gov/patients/drug-development-process/step-3-clinical-research">U.S. Food and Drug Administration</a>. These phases are designed <a href="https://www.fda.gov/science-research/science-and-research-special-topics/clinical-trials-and-human-subject-protection">to do two things</a>: protect patients during the process and make sure that the drug or treatment works. </p>
<h2>Phase 1 trials</h2>
<p>Phase 1 trials are <a href="https://www.nia.nih.gov/health/what-are-clinical-trials-and-studies">focused on safety</a>. Researchers monitor kidney, liver, hormone and cardiac functions to look for adverse affects in human volunteers. They also look for biological signs of efficacy related to what they are hoping to treat. For example, if a trial was testing a vaccine, researchers might monitor immune activity to see if it increases.</p>
<p>Phase 1 clinical trials <a href="https://www.nia.nih.gov/health/what-are-clinical-trials-and-studiesand">typically take around two months</a> and involve small numbers of participants, usually 20 to 100 healthy volunteers or people with the condition that the intervention may treat. Researchers give the participants a range of medication dosages to help determine the lowest possible effective but safe dose. Some, but not all, phase 1 studies are randomized and placebo controlled, meaning that some portion of the subjects are given the real treatment and some <a href="https://www.nia.nih.gov/health/placebos-clinical-trials">get a placebo</a> that does nothing. Neither the subject nor clinician knows who is receiving which treatment. </p>
<p>Drugs that pass phase 1 trials can be considered likely safe, but whether they work or not still remains to be seen.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/334227/original/file-20200512-66681-pk6env.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/334227/original/file-20200512-66681-pk6env.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/334227/original/file-20200512-66681-pk6env.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=384&fit=crop&dpr=1 600w, https://images.theconversation.com/files/334227/original/file-20200512-66681-pk6env.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=384&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/334227/original/file-20200512-66681-pk6env.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=384&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/334227/original/file-20200512-66681-pk6env.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=483&fit=crop&dpr=1 754w, https://images.theconversation.com/files/334227/original/file-20200512-66681-pk6env.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=483&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/334227/original/file-20200512-66681-pk6env.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=483&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 people are used in the testing process, the U.S. Food and Drug Administration gets involved.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/the-outside-of-the-food-and-drug-administration-news-photo/496532228?adppopup=true">Al Drago/CQ Roll Call via Getty Images</a></span>
</figcaption>
</figure>
<h2>Phase 2 trials</h2>
<p>In phase 2 trials, researchers focus on seeing if the treatment works, finding the safest effective dose and determining what symptoms, tests or outcomes are the best measures of efficacy of the treatment. Determining the best measures of success is important for designing the final stage of testing.</p>
<p>All phase 2 trials are randomized and placebo controlled.</p>
<p>This stage of research can take months to years, and only about <a href="https://www.fda.gov/patients/drug-development-process/step-3-clinical-research">one-third of drugs in phase 2 trials make it to the next phase</a>.</p>
<p>In phase 2 trials, researchers give the drug to hundreds of subjects and watch for safety through regular testing. To measure effectiveness, researchers look at clinical responses such as the length of illness, severity of the illness or survival rates. Direct measures of a disease – such as the amount of virus in a person’s cells – are also monitored, as well as <a href="https://dx.doi.org/10.1177%2F1535370217750088">biomarkers</a> – signals in the body that researchers <a href="https://www.clinicaltrials.gov/ct2/show/NCT04322513">know are changed by the targeted disease</a>.</p>
<p>At this point, the researchers will use all the information they have gained to design the phase 3 trial. They decide what measures to use, the doses to test and the type, or <a href="https://www.cancer.gov/publications/dictionaries/cancer-terms/def/cohort">cohort</a>, of people to test. </p>
<p>If there is evidence in either phase 1 or phase 2 that the drug or vaccine is unsafe or ineffective, the teams will stop the trial. </p>
<h2>Phase 3 trials</h2>
<p>Phase 3 trials are where researchers look to see if people that get the treatment are statistically better off than those don’t. The trials are randomized and placebo controlled, and use the measures of success chosen from the phase 2 trial. Phase 3 trials are also designed to find any rare side effects of a treatment. </p>
<p>In order to get statistically meaningful data, phase 3 trials are big, normally including a few hundred to 3,000 people. </p>
<p>This is the final step before a drug is approved for public use. After a phase 3 trial is finished, the FDA puts together a panel of independent scientists to review the data. The panel decides, based on evidence of success and prevalence of side effects, if the benefits of the drug outweigh the risks enough to approve it for widespread use.</p>
<p>According to the FDA, only <a href="https://www.fda.gov/patients/drug-development-process/step-3-clinical-research">25%-30% of drugs in phase 3 trials get approved</a>.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/338641/original/file-20200529-78867-1mjk2mt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/338641/original/file-20200529-78867-1mjk2mt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/338641/original/file-20200529-78867-1mjk2mt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/338641/original/file-20200529-78867-1mjk2mt.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/338641/original/file-20200529-78867-1mjk2mt.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/338641/original/file-20200529-78867-1mjk2mt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/338641/original/file-20200529-78867-1mjk2mt.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/338641/original/file-20200529-78867-1mjk2mt.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">Neither the researchers, physicians nor patients know whether they are handing real drugs or placebos for randomized placebo-controlled clinical trials.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/drug-research-doctor-working-in-hospital-writing-a-royalty-free-image/959237242?adppopup=true">krisanapong detraphiphat/Moment via Getty Images</a></span>
</figcaption>
</figure>
<h2>Phase 4 trials</h2>
<p>Phase 4 trials are used to test approved treatments for the same medical condition but in a different dose or time frame or group of people. For example, a phase 4 trial could be used to test if a drug that’s already approved for adults is safe and effective for children.</p>
<p>When a drug that’s been approved for one purpose is studied for a different medical condition – for example, testing the malaria drug hydroxychloroquine as a potential treatment for COVID-19 – this is not a phase 4 trial. This is a phase 2 or 3 trial because it is designed to answer those early questions about how well the treatment works for the new condition.</p>
<h2>A critical eye for medical news</h2>
<p>News headlines are full of <a href="https://www.msn.com/en-us/money/markets/coronavirus-live-updates-oxford-readying-a-phase-2-vaccine-trial-cases-surge-in-india/ar-BB14smVc">trial results concerning COVID-19 interventions</a>. It’s easy to get excited when reading about a new drug or vaccine. But early successes do not guarantee a treatment will work.</p>
<p>COVID-19, like <a href="https://www.actcinfo.org/projects/">Alzheimer’s</a>, is a complex disease, and clinical trials to test treatments are particularly challenging, with highly variable outcomes. The process for drug and treatment approval is long, but is designed to guarantee that what a physician gives you will do help, not hurt, you.</p>
<p>[<em>You need to understand the coronavirus pandemic, and we can help.</em> <a href="https://theconversation.com/us/newsletters?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=upper-coronavirus-help">Read The Conversation’s newsletter</a>.]</p><img src="https://counter.theconversation.com/content/138197/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Mindy Aisen 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>Drugs and vaccines to fight the coronavirus are already in clinical trials. It is important to understand the difference between each step in this process as efforts to fight COVID-19 continue.Mindy Aisen, Clinical Professor of Neurology, University of Southern CaliforniaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1372212020-05-13T12:38:52Z2020-05-13T12:38:52ZWhat is a clinical trial? A health policy expert explains<figure><img src="https://images.theconversation.com/files/332860/original/file-20200505-83740-e7ubth.jpg?ixlib=rb-1.1.0&rect=14%2C7%2C4852%2C3246&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Over 2,000 drugs are approved by the FDA for human use. </span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/top-view-of-various-pills-and-tablets-on-the-blue-royalty-free-image/1177505480">Yulia Reznikov/Movement via Getty Images</a></span></figcaption></figure><p>A commonly used malaria drug was recently proposed as a treatment for COVID-19 during a <a href="https://www.whitehouse.gov/briefings-statements/remarks-president-trump-vice-president-pence-members-coronavirus-task-force-press-briefing-6/">White House press briefing</a>, even though it hadn’t yet been properly evaluated in clinical trials or approved for this use. Does the urgency of the current pandemic give doctors a good reason to skip evaluation and rush an untested drug to patients?</p>
<p>The field of medicine considers <a href="http://dx.doi.org/10.1136/adc.2004.058222">randomized-controlled trials</a>, also known as “clinical trials,” as the gold standard for assessing the effectiveness of new treatments. These studies set up a fair test for treatments and enable researchers to rule out alternate explanations. Without randomized-controlled trial evidence to guide them, doctors risk wasting resources on ineffective treatments or causing harm to patients.</p>
<h2>What is a randomized-controlled trial?</h2>
<p>A controlled trial means that study participants are split into two groups: One group is given the treatment and the other (the control group) is not. The control group may be given a <a href="https://www.nia.nih.gov/health/placebos-clinical-trials">placebo that mimics the actual treatment</a>, but does not contain the treatment being tested.</p>
<p>For example, a sugar pill or an injection of saline solution may be used instead of a dose of the drug. This ensures the only meaningful difference between the two groups is whether they received the treatment or not. </p>
<p>The control group helps researchers learn what would have happened to the treatment group if they hadn’t received the treatment. For example, some patients may recover on their own. Researchers need to know how often this happens, so they don’t attribute all recoveries to the effect of the treatment.</p>
<figure class="align-left zoomable">
<a href="https://images.theconversation.com/files/332859/original/file-20200505-83721-8fxo5i.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/332859/original/file-20200505-83721-8fxo5i.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/332859/original/file-20200505-83721-8fxo5i.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/332859/original/file-20200505-83721-8fxo5i.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/332859/original/file-20200505-83721-8fxo5i.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/332859/original/file-20200505-83721-8fxo5i.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/332859/original/file-20200505-83721-8fxo5i.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/332859/original/file-20200505-83721-8fxo5i.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"></a>
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<span class="caption">Randomization ensures apples are compared to apples.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/man-flipping-one-pound-coin-pounds-sterling-royalty-free-image/159615167">Monty Rakusen/Cultura via Getty Images</a></span>
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<p>Study participants are <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3942596/">randomly assigned</a> to one group or the other, a process similar to a coin toss. Just as a coin toss is equally likely to end up heads or tails, study participants are equally likely to end up in the treatment or the control group. With enough study participants, this results in two groups that closely resemble each other. The only difference is that one group got “heads” while the other got “tails.”</p>
<p>The randomization of randomized-controlled trials with large enough samples ensures that all possible differences are accounted for, even those that may not be observed, such as genetic traits. </p>
<p>If the treatment and control groups are similar at the start of the study but end up with different outcomes, the treatment is the most likely cause. The randomized-controlled trial allows researchers to rule out alternative explanations.</p>
<h2>What if patients aren’t randomly assigned?</h2>
<p>If doctors were allowed to choose which patients received the treatment, it’s likely the treatment and control groups would not resemble each other, making it much harder to rule out different factors at play. </p>
<p>For example, malaria drugs aren’t approved for use against COVID-19, but may be prescribed to patients under <a href="https://www.fda.gov/news-events/public-health-focus/expanded-access">the Food and Drug Administration’s “expanded access” program</a>. It allows certain drugs to be used as a last resort to treat seriously ill patients when no other treatments are available. </p>
<p>These “last resort” patients are frailer than those who had a milder form of the disease or who responded well to other treatments. When you’re comparing very sick patients to healthier patients, the effect of the treatment is hard to see because it may be obscured by important differences such as <a href="https://www.healthypeople.gov/2020/about/foundation-health-measures/Determinants-of-Health">age, diet, cigarette use, heart disease or obesity</a>.</p>
<p>If frail patients on treatment fared significantly better than strong patients without it, researchers could conclude the treatment was effective. But this situation is extremely rare, which is why doctors <a href="http://dx.doi.org/10.1097/MLR.0b013e3181dbebe3">generally can’t draw valid conclusions</a> about a drug’s effectiveness in a “last resort” situation. Too many other factors are likely at play.</p>
<p>Some researchers may be able to use sophisticated statistics techniques to account for the differences between frail and strong patients. But there is a long list of potential differences between frail and strong patients, so it is hard to address them all. Gauging the <a href="https://doi.org/10.1086/420936">quality of such statistical analysis</a> is also difficult, so these studies should be viewed with skepticism.</p>
<h2>Approving drugs prematurely</h2>
<p>Without results from randomized-controlled trials, doctors can’t be sure whether a potential new treatment will help patients, harm them or prove ineffective. </p>
<p>The case of the malaria drug hydroxychloroquine as a potential treatment for COVID-19 underscores this concern. In an early wave of optimism, doctors prescribed and some even stockpiled so much hydroxychloroquine that <a href="https://jamanetwork.com/channels/health-forum/fullarticle/2764607">pharmacies reported shortages</a> of the drug. </p>
<p>While <a href="https://www.covid19treatmentguidelines.nih.gov/antiviral-therapy/">there is insufficient evidence</a> from U.S.-based randomized-controlled trials to determine the effectiveness this treatment for COVID-19, it has caused some patients to develop <a href="https://www.fda.gov/drugs/drug-safety-and-availability/fda-cautions-against-use-hydroxychloroquine-or-chloroquine-covid-19-outside-hospital-setting-or">serious heart rhythm problems</a>. Prematurely prescribing this treatment to all but the “last resort” cases may instill false hope, waste medical resources and, most importantly, put patients at risk.</p>
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<p><em>This article was updated to clarify that as of May 15, 2020, randomized controlled trials have not yet provided enough evidence to know whether or not hydroxychloroquine is an effective treatment for COVID-19.</em></p><img src="https://counter.theconversation.com/content/137221/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Zoë McLaren 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 only way to know if a medical treatment actually works is with a randomized-controlled trial.Zoë McLaren, Associate Professor of Public Policy, University of Maryland, Baltimore CountyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1241892019-10-01T07:40:54Z2019-10-01T07:40:54ZPlacebos: what they’re made of matters<figure><img src="https://images.theconversation.com/files/294640/original/file-20190928-185399-fqignw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/download/confirm/549397639?src=hUJIwA63gpjyIayuaFJZrg-1-0&size=medium_jpg">Video_Creative/Shutterstock</a></span></figcaption></figure><p>Placebo controls are a gold standard against which new treatments are often measured. If a new treatment consistently proves to be better than a placebo and safe, it can be marketed, sold and prescribed. Otherwise, it can’t – or at least shouldn’t. The problem is that, as our <a href="https://onlinelibrary.wiley.com/doi/abs/10.1111/eci.13169">latest study reveals</a>, researchers don’t report what placebos contain. Different placebos have different effects, and the choice of what’s in a placebo can lead to mistaken inferences about a new treatment’s benefits or harms.</p>
<p>Here are a few examples. <a href="https://www.nature.com/articles/375530a0">Olive oil</a> was previously used as a placebo control for cholesterol-lowering drugs before it was discovered that olive oil has cholesterol-lowering properties of its own. It may explain the effect of these drugs in some trials, which was lower than expected. </p>
<p>In trials of oseltamivir (Tamiflu) the <a href="https://www.bmj.com/content/348/bmj.g2545">placebo contained dehydrocholic acid</a>, presumably to mimic the bitter taste of the drug. But dehydrocholic acid can cause gastrointestinal upset, as can oseltamivir. The trial found an increased risk of nausea and vomiting in the oseltamivir group compared with the placebo group. But this was probably an underestimate of the true incidence of harm because the placebo contained an ingredient that can cause the same side effects as the actual drug.</p>
<p>Why don’t researchers report what’s in placebos? One problem is that people believe the placebo or sham intervention is “inert”. If they were inert, there would be no point in reporting what’s in them. In fact, <a href="https://philpapers.org/rec/HOWTRO-24">placebos are not inert</a> – no substance is.</p>
<p><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2359128/">Pink tablets</a> have a greater stimulating effect (get the adrenaline pumping) than <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(72)90996-8/fulltext">blue ones</a> (except for <a href="https://link.springer.com/article/10.1007/BF00560290">Italian men</a>, in whom blue tablets produce a stimulating effect, possibly because their national football team wears blue). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1505530/">Branded</a>, <a href="https://www.ncbi.nlm.nih.gov/pubmed/18319411">expensive</a> tablets have greater painkilling effects than cheap generic ones, possibly because they influence patients’ expectations. And two placebos are <a href="https://www.ncbi.nlm.nih.gov/pubmed/10594490">better than one</a>.</p>
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<img alt="" src="https://images.theconversation.com/files/294641/original/file-20190928-185379-1qnah43.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/294641/original/file-20190928-185379-1qnah43.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/294641/original/file-20190928-185379-1qnah43.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/294641/original/file-20190928-185379-1qnah43.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/294641/original/file-20190928-185379-1qnah43.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/294641/original/file-20190928-185379-1qnah43.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/294641/original/file-20190928-185379-1qnah43.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">
<figcaption>
<span class="caption">Same ingredient. Different effect.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/download/confirm/1183552576?src=ISxUINAuGrexStD9ynpniA-1-62&size=medium_jpg">Alina Ches/Shutterstock</a></span>
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<p>Of course, not all placebos are pills. They also include minimally invasive surgery, acupuncture needles that don’t pierce acupuncture points, manipulations, and others. Some evidence suggests that <a href="https://www.ncbi.nlm.nih.gov/pubmed/10787112">injections are more effective</a> than pills and sham <a href="https://www.ncbi.nlm.nih.gov/pubmed/18541604">surgery is the most powerful placebo</a> of all. The mechanisms by which these different placebo/sham interventions work go <a href="https://www.jneurosci.org/content/25/45/10390">beyond the expectation of clinical improvement</a>.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/we-should-use-placebos-more-often-especially-in-surgery-55180">We should use placebos more often, especially in surgery</a>
</strong>
</em>
</p>
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<p>Sometimes placebos are recognisably different from the active treatment they are meant to control for. A 2016 review found that 64% of placebo control interventions <a href="http://www.readcube.com/articles/10.1186/s12874-016-0111-9">did not match the physical properties of the drug being tested</a>. If patients can identify the placebo, then the trial is not “blinded”. </p>
<p>Unblinded patients who know they are receiving a mere placebo may have lower expectations about recovery. These lower expectations can then affect the trial outcome, especially when symptoms are subjective and susceptible to suggestion. This kind of thing <a href="https://www.ncbi.nlm.nih.gov/pubmed/14974002">is common</a> in depression trials. </p>
<p>Patients who believe they’re taking the real drug, whether they are or not, may develop higher expectations about feeling better, activate the brain’s reward mechanism so that it produces more dopamine, then actually feel better. Meanwhile, the opposite happens to patients who are given a placebo. Patients who know they are taking a placebo may even have a “nocebo” effect, which is the effect of a negative expectation. Expectations have led to <a href="https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD003012.pub2/full">exaggerated drug effects</a> in antidepressant trials.</p>
<p>The examples of placebo components leading to mistaken inferences about apparent benefits or harms of active treatments might be the exception, but we can’t be sure until we know what’s in placebos. </p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/placebos-work-even-when-patients-know-what-they-are-77074">Placebos work even when patients know what they are</a>
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<h2>Guidelines ignored</h2>
<p>A <a href="https://www.ncbi.nlm.nih.gov/pubmed/20956710">2010 systematic review</a> found that between 8% and 27% of trials described the placebo or sham intervention. Since then, guidelines for reporting on placebos in clinical trials have been published and are recommended by top journals, such as the BMJ. </p>
<p>The “template for intervention description and replication” (TIDieR) checklist includes 12 items that researchers should report about the components of the new treatment, including what’s in them, who delivered them and how long the treatment lasted.</p>
<p>Unfortunately, these guidelines have barely improved how well placebo components are reported. Our latest study identified 94 placebo or sham-controlled trials published in top journals in 2018. None were completely reported according to TIDieR guidance, with most trials reporting only half of what we need to know about placebos. Within lesser journals, the reporting quality of placebo controls was worse, but not by much.</p>
<p>There are many reasons placebo or sham controls are not well reported. As mentioned above, it is mistakenly assumed that they are inert, and reporting what’s in something inert seems redundant. Using the same word “placebo” (or “sham”) to describe these interventions also makes it appear as though they are all the same, and again not worth describing. And journals have strict word limits which might squeeze out full descriptions of placebo or sham controls. However, online appendices are making the word count problem redundant.</p>
<p>Placebo-controlled trials are among the most trusted methods for determining whether new treatments are effective and safe. To be worthy of this trust, we need to know what the placebo or sham contains.</p><img src="https://counter.theconversation.com/content/124189/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jeremy Howick receives funding from the NIHR.</span></em></p>Placebos come in different shapes, colours that can all have different effects.Jeremy Howick, Director of the Oxford Empathy Programme, University of OxfordLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1226712019-09-26T16:34:56Z2019-09-26T16:34:56ZWhy drug trials are only part of the answer to making sure medicines work<figure><img src="https://images.theconversation.com/files/293658/original/file-20190923-54775-g5cdx6.jpg?ixlib=rb-1.1.0&rect=5%2C0%2C992%2C666&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Clinical trials are important, but can't get us to medicine prescribing that is 100% effective.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/clinical-trial-174168614">Image Point Fr/Shutterstock.com</a></span></figcaption></figure><p>There was a moment when, as a pharmacist, I realised that a lot of people to whom I gave medicine were going to receive little benefit, or even none at all. Healthcare staff make clinical decisions of when to use one medicine or another based upon evidence drawn from clinical trials. Clinical trials give us the data that show the probability that a medicine will have the desired effect – but there is also the chance that it will not.</p>
<p>Clinical trials are a good way of identifying drugs that, on the whole, are effective at achieving a specific outcome. But “on the whole” doesn’t take into account the wide variation among humans that means patients may react very differently to the drugs they’re given. The promise of <a href="https://theconversation.com/personalised-medicine-how-science-is-using-the-genetics-of-disease-to-make-drugs-better-30747">personalised medicine</a> is that through a more accurate understanding of a patient’s genetic makeup, alongside factors such as their lifestyle, diet and environment, they can be prescribed different drugs depending on what we know about how those drugs will affect them personally, rather than “on the whole”.</p>
<h2>Clinical trial mathematics</h2>
<p>Clinical trial data are <a href="https://bestpractice.bmj.com/info/toolkit/learn-ebm/how-to-calculate-risk/">based on probabilities</a>. Most controlled trials test a drug against a placebo or an existing drug, and the outcomes – such as not having a heart attack, or experiencing a side effect – are counted up to compare. </p>
<p>The likelihood that a patient will experience an event is known as <em>absolute risk</em>. This <a href="https://academic.oup.com/ndt/article/32/suppl_2/ii13/3056571">is calculated</a> by dividing the number of events by the number of people. For example, if eight of a group of 100 people have a heart attack in a single year, the absolute risk is 8/100 = 0.08 (or 8%). Say that during a drug trial the absolute risk for those given the drug is 0.03, and for the placebo group it is 0.08, the drug on trial would be said to have achieved an <em>absolute risk reduction</em> of 0.05 (or 5%). </p>
<p>However, there is a risk that people experience an event whether or not they are taking the drug. This <em>relative risk</em> is calculated by dividing the absolute risk of the group taking the drug by the absolute risk of the control group given the placebo. The drug’s efficiency taking into account background risk – the <em>relative risk reduction</em> – is calculated by dividing the absolute risk reduction by the absolute risk of the placebo group. Using the same example above, it would be 0.05/0.08, or 0.625 (or 62.5%). </p>
<p>Crucially, if you are in the business of manufacturing and selling medicines, expressing a drug’s effectiveness by its relative risk reduction offers a better impression than by its absolute risk: let’s face it, a reduction of 62.5% sounds much more impressive than a reduction of 5%.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/294361/original/file-20190926-51438-1582u4s.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/294361/original/file-20190926-51438-1582u4s.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/294361/original/file-20190926-51438-1582u4s.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/294361/original/file-20190926-51438-1582u4s.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/294361/original/file-20190926-51438-1582u4s.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/294361/original/file-20190926-51438-1582u4s.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/294361/original/file-20190926-51438-1582u4s.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">Side effects are common, but those that don’t benefit from the drug shouldn’t have to put up with them.</span>
<span class="attribution"><span class="source">Sherry Yates Young/Shutterstock</span></span>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/personalised-medicine-how-science-is-using-the-genetics-of-disease-to-make-drugs-better-30747">Personalised medicine: how science is using the genetics of disease to make drugs better</a>
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<h2>Patients as individuals</h2>
<p>Using these methods on clinical trial data help us gauge the effectiveness of medicines, but they don’t take into account the differences among the patients taking them. Through genetic variation, <a href="https://theconversation.com/how-your-genes-influence-what-medicines-are-right-for-you-46904">human bodies vary considerably in the way they interact with drugs</a>, potentially making them more effective, less effective, or something else entirely. For example, people with high cholesterol, something that runs in families, are in the UK currently <a href="https://www.nice.org.uk/guidance/cg71/chapter/Recommendations#case-finding-and-diagnosis">offered DNA testing</a> to confirm their diagnosis, and start treatment much earlier. </p>
<p>To see how much these factors affect how medicines work: an estimate of the number of people that must take a drug for one person to get the desired outcome is known as the <a href="https://www.bmj.com/content/310/6977/452"><em>number needed to treat</em></a>. Using the same example of a drug trial with an absolute risk reduction of 0.05 (5%), this means that, statistically, 20 people (20x5%=100%) would need to be given the drug for one to feel the benefits. As we don’t know which of the 20 will benefit from taking the drug, we must give it to all of them.</p>
<p>This is a problem because medicines are not without harms: almost all have side effects, which the other 19 may suffer even without experiencing the drug’s benefits. This is known as <a href="https://www.bmj.com/content/347/bmj.f4869"><em>number needed to harm</em></a>, where harm could be anything from headaches and rashes to internal bleeding or even death. Clearly, if taking a medicine you would want to know that the benefit outweighs the harm.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/why-i-donated-my-entire-genome-sequence-to-the-public-83741">Why I donated my entire genome sequence to the public</a>
</strong>
</em>
</p>
<hr>
<h2>Minimising medicines</h2>
<p>As an example, statins are drugs commonly used to lower cholesterol and reduce the risk of having heart attacks and strokes. The drug will reduce the relative risk of heart attack or stroke by about 25%, but may also generate side effects. The patient and prescriber need to balance the benefit versus the harm. This decision can be guided using <a href="https://www.nice.org.uk/guidance/cg181/resources/patient-decision-aid-pdf-243780159">patient decision aids</a>, developed to help patients understand the balance of benefits and harms in the context of how they may have to change their lifestyle while taking the medicine.</p>
<p>There has been interest in a recent trial of the <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)31791-X/fulltext">polypill</a>, a tablet containing blood pressure-lowering medicine and a statin, which was given to around 3,400 people over the age of 50 in Golestan province, Iran. At a population level it led to a reduction in cardiovascular events, but the same approach will also mean more people will experience side effects compared to an approach that targets only those at high risk. In low and middle-income countries that lack the resources to diagnose and target many individuals, this may be a price worth paying.</p>
<p>Which brings us back to the promise of personalised medicine: ideally we would be able to identify the hypothetical one in 20 patients given a drug that benefit from it, and prescribe the medicine to them alone. Beyond the benefit to the patient, there are cost benefits to the health service and to society, but chiefly there are benefits for the other 19 who need not take a drug that won’t benefit them and may cause them side effects or adverse drug interactions. Better understanding of our genome and how it affects our risk of disease will provide the tools to <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)61730-X/fulltext">identify those most at risk</a>, and target them alone.</p>
<hr>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/315932/original/file-20200218-11040-p9wweg.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/315932/original/file-20200218-11040-p9wweg.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=112&fit=crop&dpr=1 600w, https://images.theconversation.com/files/315932/original/file-20200218-11040-p9wweg.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=112&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/315932/original/file-20200218-11040-p9wweg.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=112&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/315932/original/file-20200218-11040-p9wweg.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=140&fit=crop&dpr=1 754w, https://images.theconversation.com/files/315932/original/file-20200218-11040-p9wweg.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=140&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/315932/original/file-20200218-11040-p9wweg.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=140&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
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<p><em>This article is part of a series tied to Medicine made for you, a series by The Anthill podcast on the future of healthcare and how it could soon get a lot more personal. <a href="https://theconversation.com/uk/topics/medicine-made-for-you-82269">Read more here</a>.</em></p><img src="https://counter.theconversation.com/content/122671/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Alison Astles 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>Clinical trials are used to establish that medicines work. But these don’t take into account the genetic differences between us that can mean very different outcomes for different patients.Alison Astles, Subject Leader in Pharmacy, University of HuddersfieldLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/932822018-03-15T05:12:31Z2018-03-15T05:12:31ZSpeaking with: Andrew Leigh on why we need more randomised trials in policy and law<figure><img src="https://images.theconversation.com/files/210870/original/file-20180317-104635-kisec6.jpeg?ixlib=rb-1.1.0&rect=0%2C0%2C1175%2C1177&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">AndrewLeigh.com</span>, <span class="license">Author provided</span></span></figcaption></figure><p><a href="https://theconversation.com/randomised-control-trials-what-makes-them-the-gold-standard-in-medical-research-78913">Randomised controlled trials</a> are the gold standard in medical research. Researchers divide participants into two groups using the equivalent of flipping a coin, with one group getting a new treatment and a control group getting either the standard treatment or a placebo. It’s the best way to prove that a new treatment works.</p>
<p>But the benefits of randomised trials aren’t limited to medical applications. Big businesses – like Amazon, Google, <a href="https://theconversation.com/facebook-will-continue-experimenting-on-users-under-closed-guidelines-32510">Facebook</a> and even media organisations – are increasingly <a href="https://theblog.okcupid.com/we-experiment-on-human-beings-5dd9fe280cd5">using randomised trials</a> to test designs and processes that increase their engagement with users and customers. Every time you Google something you’re probably participating in a randomised trial.</p>
<p>And that world of randomisation is the subject of Andrew Leigh’s new book, <a href="https://www.blackincbooks.com.au/books/randomistas">Randomistas: How radical researchers changed our world</a>. Leigh is the current federal member for Fenner, and Labor’s shadow assistant treasurer. But prior to his political life he was a professor of economics at Australian National University.</p>
<p>He spoke with the University of Melbourne’s Fiona Fidler about how we should be using randomised trials more to drive decisions and policy in public life and why we might be missing out on better results in social policy because we’re afraid to test our assertions.</p>
<hr>
<p><em>Andrew Leigh’s <a href="https://www.blackincbooks.com.au/books/randomistas">Randomistas: How radical researchers changed our world</a> is out now from Black Inc books. His podcast on living a health, happy and ethical life, The Good Life, is available on <a href="https://itunes.apple.com/au/podcast/the-good-life-andrew-leigh-in-conversation/id1147502226?mt=2">Apple Podcasts</a> or wherever you stream your podcasts.</em></p>
<p><em><a href="https://itunes.apple.com/au/podcast/speaking-with.../id934267338">Subscribe</a> to The Conversation’s Speaking With podcasts on Apple Podcasts, or <a href="http://tunein.com/radio/Speaking-with---The-Conversation-Podcast-p671452/">follow</a> on Tunein Radio.</em></p>
<p><strong>Music</strong></p>
<ul>
<li><a href="http://freemusicarchive.org/music/Blue_Dot_Sessions/The_Contessa/Wisteria">Free Music Archive: Blue Dot Sessions - Wisteria</a></li>
</ul><img src="https://counter.theconversation.com/content/93282/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Fiona Fidler receives funding from the Australian Research Council and IARPA.</span></em></p>Economist, author and MP Andrew Leigh spoke to Fiona Fidler about how we should be using randomised trials more to drive decisions and policy in public life.Fiona Fidler, Associate Professor, School of Historical and Philosophical Studies, The University of MelbourneLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/770742017-05-05T12:50:53Z2017-05-05T12:50:53ZPlacebos work even when patients know what they are<figure><img src="https://images.theconversation.com/files/167995/original/file-20170504-21635-1q0sx3j.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/download/confirm/450599851?src=UzHgg1TrUXQ9X3wQKdo-BA-1-0&size=medium_jpg"> rzstudio/shutterstock</a></span></figcaption></figure><p>Lying to patients is almost always unethical. But, in order for placebos to work, we have to believe they are “real” treatments, which means the doctor would have to lie to us and say that <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1198039/">the placebo was actually a real treatment</a>. Or, in the case of a clinical trial, that it might be a real treatment. After all, if a doctor handed you a pill and said, “this is just a sugar pill”, you’d probably assume it wouldn’t work. But sometimes our assumptions are mistaken.</p>
<p>I led a team that recently conducted a systematic review – considered to offer the highest quality evidence – containing data from <a href="https://www.ncbi.nlm.nih.gov/pubmed/28452193">five trials of open-label placebos</a> (placebos that patients know are placebos). We found that open-label placebos seem to benefit patients with back pain, depression, allergic rhinitis, irritable bowel syndrome (IBS) and attention deficit hyperactivity disorder (ADHD).</p>
<p>The history of open-label placebos can be traced back to at least 1965 when Baltimore doctors, Lee Park and Uno Covi, gave open placebos to <a href="http://jamanetwork.com/journals/jamapsychiatry/article-abstract/488749">15 neurotic patients</a>. They told the patients: “Many people with your kind of condition have been helped by what are sometimes called sugar pills and we feel that a so-called sugar pill may help you too.” Many of the patients got better. Paradoxically, since these were neurotic patients, they thought that the doctors had lied to them and given them real drugs.</p>
<p>Since Park and Covi’s pioneering study, many more rigorous ones have been undertaken. In a typical recent study that was included in our review, Ted Kaptchuk of Harvard Medical School randomly allocated <a href="http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0015591">80 patients with severe IBS</a> to receive either placebo pills presented as “placebo pills made of an inert substance, like sugar pills, that have been shown in clinical studies to produce significant improvement in IBS symptoms through mind-body self-healing processes” or no treatment (the control group). After three weeks, the researchers found that the open-label placebo group improved by 15% more than those in the control group. </p>
<p>One of the participants in the trial, Linda Buannono, had been suffering from IBS for years and nothing had helped. On some days she was in so much pain she could barely leave the house. The open-label placebo had a big effect on her, so much so that she said: “I never felt better in my life.” But, at the end of the trial, she stopped receiving the placebos and her IBS became worse again. She went to her pharmacist to ask for some open-label placebos, but he told her it would be unethical for him to do so.</p>
<p>The trials in our systematic review were all quite small and weren’t “blinded”. (Blinding is where the participants and/or the researchers don’t know who’s getting what.) In these types of trials, participants and researchers need to know who is getting the open-label placebo and who isn’t, so it’s not possible to blind them. Trials that are not blinded are considered to be somewhat biased. However, the trials were consistently positive and we also know a bit about how open-label placebos work, suggesting that bias cannot explain away these results.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/168110/original/file-20170505-21027-1wgh5ji.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/168110/original/file-20170505-21027-1wgh5ji.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/168110/original/file-20170505-21027-1wgh5ji.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/168110/original/file-20170505-21027-1wgh5ji.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/168110/original/file-20170505-21027-1wgh5ji.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/168110/original/file-20170505-21027-1wgh5ji.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/168110/original/file-20170505-21027-1wgh5ji.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">
<figcaption>
<span class="caption">Take these sugar pills. You’ll feel much better.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/download/confirm/572899216?src=ToCgNqNDc4-AVvRhbVrpCw-1-6&size=medium_jpg">Andrei_R/Shutterstock</a></span>
</figcaption>
</figure>
<h2>Lifting the lid on open-label placebos</h2>
<p>Open-label placebos probably work in <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4590042/">two ways</a>. The first is expectation. Open-label are usually given with a positive suggestion (the doctor will tell the patient the pill is just a placebo but adds that it “produces significant improvement for patients like you”. This positive suggestion creates a positive expectation, which can activate the reward mechanisms in the brain and help the body produce its own substances, such as painkilling endorphins.</p>
<p>The second is conditioning. Just as Pavlov’s dogs learned to associate the sound of a bell with food and began salivating whenever they heard the bell, most of us have been conditioned to expect a positive outcome when a trusted doctor gives a treatment. So even though we know a pill is a placebo, our bodies may react in a way that helps us heal. There have been several studies, including one in humans, showing that the immune system can be activated much in the same way that Pavlov’s dogs salivated at the mere sound of a bell.</p>
<p>Since open-label placebos work, does this mean doctors should start handing them out like Smarties? That may be unwise because it would support a pill-popping, overmedicalised culture. Fortunately, our review of open-label placebos demonstrates something more general: placebo effects are real for many common conditions. And we can benefit from placebo effects without actually using placebo pills. Doctors who give <a href="http://www.sciencedirect.com/science/article/pii/S1876382017300604">positive messages</a> and take time to communicate with <a href="http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD011934/abstract">enhanced empathy</a> to patients can have positive benefits whether or not they give pills. Far from being unethical, since placebo effects can benefit many patients it is probably unethical not to exploit them.</p><img src="https://counter.theconversation.com/content/77074/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jeremy Howick has received funding from the National Institute for Health Research (NIHR) and the Medical Research Council (MRC), both in the United Kingdom. </span></em></p>In many trials, patients have been told they’re getting the sugar pill. They still got better.Jeremy Howick, Senior Researcher: placebo effects, epidemiology, evidence-based medicine, University of OxfordLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/714332017-02-06T10:34:01Z2017-02-06T10:34:01ZAre over-the-counter painkillers a waste of money?<figure><img src="https://images.theconversation.com/files/154035/original/image-20170124-465-125m2sp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Horses for courses?</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/paracetamol-on-white-background-382039522?src=IPwPgPK4D9nnVUMq0XwMew-1-1">Shutterstock</a></span></figcaption></figure><p>Simple painkillers (such as aspirin, paracetamol and ibuprofen) are widely bought over the counter and prescribed by doctors. But the stark truth is that most of these medicines don’t work very well. </p>
<p>Professionals can’t be satisfied advising consumers and patients to take ineffective medicines. And consumers and patients can’t be happy that they’re spending cash or NHS resources on something that doesn’t do the job. But those with minor ailments who opt for such drugs aren’t necessarily wasting their money – and may well be saving yours by reducing the burden on health services.</p>
<p>An evidence-based approach to pain relief must consider realistic alternatives. Trials demonstrate that simple over-the-counter (OTC) painkillers, such as <a href="http://www.cochrane.org/CD012230/BACK_paracetamol-low-back-pain">paracetamol for low back pain</a> and <a href="http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD011888.pub2/abstract">aspirin for episodic tension-type headaches in adults</a>, work no better than placebo. But in practice, we need to consider how harmful this really is – and what people would do if they weren’t popping their favourite pills. </p>
<p>Cochrane reviews are internationally-recognised <a href="http://uk.cochrane.org/about-us">systematic reviews</a>. The most recent <a href="http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD011888.pub2/abstract">review of asprin</a> for the treatment of occasional, acute, tension-type headache tells us that patients taking active medication are unlikely to be pain free. However, over half the patients taking aspirin were satisfied with their treatment, as were one third taking placebo. </p>
<p>Similarly, in a <a href="http://www.cochrane.org/CD012230/BACK_paracetamol-low-back-pain">Cochrane review</a> of paracetamol for the treatment of acute low back pain, 4g of paracetamol daily was found to be no more effective than placebo. </p>
<p>In both studies, active and placebo treatments had similarly low rates of side-effects. </p>
<h2>More placebo, please</h2>
<p>This isn’t a good situation, but the placebo effect itself is often overlooked or treated with disdain. Which is a pity – it could be better employed in the fight against pain. <a href="https://www.ncbi.nlm.nih.gov/pubmed/12406519">A 2002 review</a> of placebo effects in clinical pain killer trials concluded: </p>
<blockquote>
<p>If the factors that contribute to placebo analgesia are identified, they could be optimised in clinical practice whereby the general effectiveness of pain treatments could be enhanced.</p>
</blockquote>
<p>And placebo effects were greater when studies specifically tried to investigate how placebos work. In another context, a <a href="https://www.ncbi.nlm.nih.gov/pubmed/19246102">2009 meta-analysis of anti-depressant trials</a> concluded: </p>
<blockquote>
<p>The placebo effect accounted for 68% of the effect in the drug groups. Whereas clinical trials need to control the placebo effect, clinical practice should attempt to use its full power.</p>
</blockquote>
<p>Patient demand for pain relief in the UK is clear, around <a href="http://www.pagb.co.uk/consumer-healthcare-industry/">£575m a year is spent on OTC analgesics</a> and another £567m on analgesics prescribed in <a href="http://content.digital.nhs.uk/catalogue/PUB20200/pres-cost-anal-eng-2015-rep.pdf">primary care</a>. The primary care spend includes £90m on products that could be bought OTC and £115m on compound painkillers that are the next step up the pain ladder. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/154036/original/image-20170124-455-1bs097w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/154036/original/image-20170124-455-1bs097w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=318&fit=crop&dpr=1 600w, https://images.theconversation.com/files/154036/original/image-20170124-455-1bs097w.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=318&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/154036/original/image-20170124-455-1bs097w.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=318&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/154036/original/image-20170124-455-1bs097w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=400&fit=crop&dpr=1 754w, https://images.theconversation.com/files/154036/original/image-20170124-455-1bs097w.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=400&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/154036/original/image-20170124-455-1bs097w.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=400&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">It could all be in the mind.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/hand-man-holding-paracetamol-pill-tablet-525244381?src=IPwPgPK4D9nnVUMq0XwMew-1-7">Shutterstock</a></span>
</figcaption>
</figure>
<p>Indeed, people may be willing to pay significant sums for pain relief, which is a measure of economic benefit – a few pounds to relieve everyday pain, tens of pounds to relieve post-operative pain, and hundreds of pounds to relieve chronic pain. </p>
<p>But the current supermarket price for paracetamol is little more than 1p per tablet – and stronger painkillers use codeine and related drugs, which significantly increase the risk of harmful side-effects. </p>
<p>For acute pain, simple safe painkillers are cheap (it’s certainly worth <a href="https://theconversation.com/why-do-people-choose-expensive-branded-drugs-over-cheap-generics-52461">buying generic</a> rather than more expensive branded varieties) and promote active self-management of minor ailments. They may also help to engage the placebo effect. The evidence for effectiveness beyond the placebo effect is mixed (as the Cochrane reviews demonstrate), but doing something <a href="http://www.nhs.uk/Conditions/Back-pain/Pages/Treatment.aspx">does have an effect</a> and painkillers may actively help in some cases. </p>
<p>When people buy these painkillers, they also save the NHS – and taxpayers – the expense of visiting a doctor and having them prescribed. Generic paracetamol costs 19-30p for 16 in the supermarket and 35p on prescription. However, consultation and dispensing costs are considerable.</p>
<p>The spend on OTC painkillers might therefore be like buying a lottery ticket – they will work really well for some people, and rather less well for others. Either way, the losses are insignificant. If there’s a chance that they’ll work for you, then it’s a small price to pay.</p>
<h2>The bigger picture</h2>
<p>Nevertheless, non-pharmacological actions (for example, rest, fluids, change in activities) are equally or more helpful than painkillers <a href="http://www.nhs.uk/conditions/Headache/Pages/Introduction.aspx">in many cases</a>. So people should buy, obtain or use their painkillers in a supportive environment. For example, non-branded medicines are nearly as cheap in pharmacies as supermarkets, and your pharmacist should be able to talk you through the options and offer other advice, too. Doctors, meanwhile, need more time to explore problems with patients and shouldn’t need to write prescriptions to signal the end of a consultation. Their time could be better spent.</p>
<p>Imagine there was enough evidence to ban the OTC sale and prescription supply of simple painkillers. The supply of tea and sympathy would certainly have to increase. It is likely that the demand for compound pain killers or untested treatments would also increase, which risks more serious harm. There would also likely be an increase in visits to the doctor.</p>
<p>A goal to reduce the use of ineffective medicines is desirable. But we must also consider the alternatives and consequences. The treatment of pain isn’t the only area of clinical practice where hope is maximised over effectiveness. Improving the safety and effectiveness of chronic pain relief is a higher priority than reducing acute painkiller consumption. For now, people will keep using cheap (perhaps even quite expensive) OTC painkillers – and it’s hard to say they’re acting irrationally.</p><img src="https://counter.theconversation.com/content/71433/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jonathan Silcock receives funding from the National Institute for Health Research. He provides advice to Health Education England about pharmacy training reforms. He is a member of the Royal Pharmaceutical Society. </span></em></p>They’re often no more effective than placebo, but that shouldn’t necessarily stop us using them.Jonathan Silcock, Senior Lecturer in Pharmacy Practice, University of BradfordLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/642282016-10-30T19:06:52Z2016-10-30T19:06:52ZSurgery isn’t always the best option, and the decision shouldn’t just lie with the doctor<figure><img src="https://images.theconversation.com/files/142121/original/image-20161018-12454-11m0fyv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Weighing up the evidence for surgery is just one thing to consider before going under the knife.</span> <span class="attribution"><a class="source" href="http://www.shutterstock.com/dl2_lim.mhtml?src=G5r9D6sZtKvWkj3xzKlPTw-1-19&id=210890980&size=medium_jpg">from www.shutterstock.com</a></span></figcaption></figure><p>Surgeons often decide to perform procedures because that’s what’s usually done, it’s what they’re taught, it sounds logical or it fits with observations from their own practice.</p>
<p>If the surgeon’s decision is in line with evidence from scientific studies, there’s little problem. But if the two conflict, either the surgeon’s opinion or the evidence is wrong.</p>
<p>The best way to test whether surgery works (particularly when the outcome is subjective, such as with pain) is to compare it with a sham or placebo procedure. The idea is to keep the patients and those who measure the effectiveness “blinded” to which treatment is given.</p>
<p>A <a href="http://www.bmj.com/content/348/bmj.g3253">review of studies</a> comparing surgery to sham or placebo surgery showed surgery was no better than placebo in just over half of the studies. And in studies where surgery was better than placebo, the difference was generally small.</p>
<p>As an example, two studies compared placebo surgery to keyhole surgery (arthroscopy) of the knee in patients with degenerative conditions (arthritis, meniscus tears and catching and clicking). Both studies showed no important difference in surgery outcomes between the two groups.</p>
<h2>What about other options?</h2>
<p>We don’t always need to compare surgery with a sham. Sometimes comparing surgery with non-surgical treatment (like physiotherapy or medications) is more appropriate.</p>
<p>One <a href="http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0096745">study</a> looked at all orthopaedic surgical procedures performed on more than 9,000 patients in three hospitals over three years. Only half the procedures were compared with non-operative treatment. And of that half, about half were no better than not operating.</p>
<p>So there are two problems in surgery: an evidence gap (in which there’s a lack of high quality evidence) and an evidence-practice gap (where there’s high quality evidence that a procedure doesn’t work, yet is still performed).</p>
<p>Part of the problem is that operations are often introduced before there’s good quality evidence of their effectiveness in the real world. The studies comparing them to non-operative treatment or placebo often come much later – if at all.</p>
<h2>When should surgery be funded?</h2>
<p>Doctors should not perform surgical procedures and taxpayers should not have to cover their cost until there’s high quality evidence they work. It should be unethical for surgeons to introduce a new technique without studying whether or not <a href="http://www.ncbi.nlm.nih.gov/pubmed/24484092">it works</a>.</p>
<p>Unfortunately, the opposite is true: ethical approval is not required before surgeons can start performing new procedures, but it is required to study the effectiveness of that procedure.</p>
<p>Often, procedures surgeons consider effective are later shown not to be.</p>
<p>In the US in the 1980s, a new procedure for the lung disease emphysema touted removing some lung tissue. Animal studies and (non-comparative) human studies were encouraging. So the procedure became common. </p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/142124/original/image-20161018-12459-vq1dx6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/142124/original/image-20161018-12459-vq1dx6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/142124/original/image-20161018-12459-vq1dx6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=399&fit=crop&dpr=1 600w, https://images.theconversation.com/files/142124/original/image-20161018-12459-vq1dx6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=399&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/142124/original/image-20161018-12459-vq1dx6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=399&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/142124/original/image-20161018-12459-vq1dx6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=501&fit=crop&dpr=1 754w, https://images.theconversation.com/files/142124/original/image-20161018-12459-vq1dx6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=501&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/142124/original/image-20161018-12459-vq1dx6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=501&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Weighing up the evidence for surgery could shed light on whether it should be funded.</span>
<span class="attribution"><a class="source" href="http://www.shutterstock.com/dl2_lim.mhtml?src=lfFyW8Ym2fcj54AIiy-Tfw-1-0&id=89667058&size=medium_jpg">from www.shutterstock.com</a></span>
</figcaption>
</figure>
<p>Some surgeons called for a trial comparing the procedure to non-operative treatment. But proponents of the procedure said this would deprive many people of the procedure’s benefits, the effectiveness of which was obvious.</p>
<p>Medicare in the US decided only to fund the surgery if patients took part in a trial comparing it to non-surgical treatment. The <a href="http://www.nejm.org/doi/full/10.1056/NEJMoa030287#t=article">trial</a> was done and the surgery was found wanting, with no overall benefit over non-operative treatment. The trial cost the government some money, but much less than paying for the procedure for decades until someone else studied it.</p>
<p>This type of solution should be considered in Australia: new procedures should only be funded by the public if they are performed as part of a trial to adequately test their effectiveness.</p>
<p>Once evidence is available, the key is using it to make good decisions about the effectiveness of a particular procedure for an individual patient. So how should surgeons do that? The answer lies in measuring the right outcomes to begin with and then making shared decisions.</p>
<h2>How do we know if surgery works?</h2>
<p><a href="http://www.theaustralian.com.au/national-affairs/health/budget-2016-healthcare-waste-costs-20bn-a-year/news-story/37475d4c7c3a7adfcd65b8216b8ed015">Billions</a> are spent worldwide on surgical procedures that may not be <a href="https://www.mja.com.au/journal/2012/197/10/over-150-potentially-low-value-health-care-practices-australian-study">effective</a>. But how should we define effectiveness?</p>
<p>There is a growing acceptance that doctors should partner with patients to identify outcomes important to them. These might include avoiding complications and an unexpectedly long stay in hospital. But they should also consider longer-term quality of life, disability and <a href="https://www.ncbi.nlm.nih.gov/pubmed/25689756">survival</a>.</p>
<p>This is important when a good operation might be a bad choice. Some medical conditions herald a terminal decline in health, for which living longer is not as good as living well. A good operation may also be a bad choice in cases where attempts at prolonging life are futile.</p>
<h2>Sharing decisions</h2>
<p>Shared decision-making takes into account beliefs, preferences and views of the patient as an expert in what is right for them, supported by clinicians who are the experts in effective therapeutic options.</p>
<p>Patients should have the opportunity to ask further questions when deciding whether to go ahead with surgery to see if surgery is consistent with their values and lifestyle goals. For the critically ill, frail or confused, this discussion should often include the person’s spouse, family or next of kin.</p>
<p>The right decisions in surgery are patient-centred, based on good evidence, clearly communicated and made in a supportive environment. Everyone – doctors, other health professionals, the patient, sometimes their family, and the public – have a right and a responsibility to be included.</p><img src="https://counter.theconversation.com/content/64228/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Ian Harris receives no direct payment or funding for research projects. He is an investigator on research projects funded by NHMRC, HCF Research Foundation, AO Trauma Asia Pacific, Lincoln Centre, UNSW, Arthritis Australia, AOA Research Foundation, MAA and SIRA</span></em></p><p class="fine-print"><em><span>Professor Paul Myles receives research funding from the NHMRC and the Australian and New Zealand College of Anaesthetists. </span></em></p>There’s often limited evidence for many common types of surgery. Understanding what makes good evidence is the key to deciding what’s best for you.Ian Harris, Professor of Orthopaedic Surgery, UNSW SydneyProfessor Paul Myles, Chair of the Department of Anaesthesia and Perioperative Medicine, Monash UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/551802016-03-10T14:29:32Z2016-03-10T14:29:32ZWe should use placebos more often, especially in surgery<figure><img src="https://images.theconversation.com/files/112959/original/image-20160225-15174-163tpxz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Placebo surgery is not used often enough.</span> <span class="attribution"><a class="source" href="http://www.shutterstock.com/cat.mhtml?lang=en&language=en&ref_site=photo&search_source=search_form&version=llv1&anyorall=all&safesearch=1&use_local_boost=1&autocomplete_id=&search_tracking_id=uIeI2XrVArRZl_jRPk4SRw&searchterm=surgeon&show_color_wheel=1&orient=&commercial_ok=&media_type=images&search_cat=&searchtermx=&photographer_name=&people_gender=&people_age=&people_ethnicity=&people_number=&color=&page=1&inline=226271230">www.shutterstock.com</a></span></figcaption></figure><p>You’re ill, probably scared, not sure of the future. Your doctor talks to you about your condition and says that, unfortunately, there are no effective treatments. However, she knows of a clinical trial for a new drug, and they’re currently recruiting participants. The problem is that you’ll be “randomised” to one of two groups. One will receive the new treatment and the other a placebo. The odds of getting the new treatment are 50:50.</p>
<p>So, what are you going to do?</p>
<h2>What is a placebo?</h2>
<p>Placebo treatment is a dummy or inactive treatment. Clinical trials are designed so that you (and often your doctor) don’t know whether you’re getting the experimental treatment or the placebo. This “blinded” trial design helps to avoid “bias”. If a patient knows they’re getting the real pill, they may be more likely to report feeling better. </p>
<p>Blinded trials let researchers compare outcomes from those that get the new treatment with those that don’t without any bias corrupting the results. In the case of drug treatment, a placebo will look like a real drug (a pill or infusion) but it won’t contain an active ingredient. In surgical research, the placebo may involve creating an incision in the skin and nothing more.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/114636/original/image-20160310-26271-1dbwo8l.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/114636/original/image-20160310-26271-1dbwo8l.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=399&fit=crop&dpr=1 600w, https://images.theconversation.com/files/114636/original/image-20160310-26271-1dbwo8l.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=399&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/114636/original/image-20160310-26271-1dbwo8l.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=399&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/114636/original/image-20160310-26271-1dbwo8l.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=501&fit=crop&dpr=1 754w, https://images.theconversation.com/files/114636/original/image-20160310-26271-1dbwo8l.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=501&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/114636/original/image-20160310-26271-1dbwo8l.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=501&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">A placebo pill is indistinguishable from the real thing.</span>
<span class="attribution"><a class="source" href="http://www.shutterstock.com/cat.mhtml?lang=en&language=en&ref_site=photo&search_source=search_form&version=llv1&anyorall=all&safesearch=1&use_local_boost=1&autocomplete_id=&search_tracking_id=CwLmbnZLDgijE_XxDU0XPg&searchterm=pills&show_color_wheel=1&orient=&commercial_ok=&media_type=images&search_cat=&searchtermx=&photographer_name=&people_gender=&people_age=&people_ethnicity=&people_number=&color=&page=1&inline=89193115">www.shutterstock.com</a></span>
</figcaption>
</figure>
<h2>Why we need placebos?</h2>
<p>If you’re given an experimental treatment then there might be two ways in which you’ll benefit. The treatment could improve the underlying condition, as it’s designed to do. </p>
<p>Alternatively, even if it doesn’t work, the fact that you’re getting something that you believe (or hope) will make you better might in fact make you feel better. This is the placebo effect, and it can convince people that the treatment works even when it’s ineffective. So it’s important that the researchers take this into account (“control for it” in medical parlance) when testing to see if a treatment is effective. </p>
<p>Placebo controls are particularly important when the outcome of the clinical trial is “soft” or subjective. For example, the amount of pain someone feels is dependent, in part, on the person’s state of mind. People often report a reduction in pain when they are given a drug, even a placebo. “Harder”, more objective, outcomes (such as the shrinkage of a tumour) are less prone to being influenced by the beliefs of the patient and doctor.</p>
<h2>Weighing up your options</h2>
<p>But even given the scientific need for placebos, why should you agree to take part? At the start of a study no one knows if the experimental treatment will benefit patients; if they did, there would be no need for the study. The scientists who are designing the study might believe that it will help (after all they have worked hard to develop their treatment), but that’s very different from knowing. Indeed, the majority of new treatments never make it to clinical practice. They also carry a risk – no drug or intervention is totally risk free. </p>
<p>So if you take part in the trial you risk either getting an experimental treatment that may not work and may cause harm, or having a placebo that is less harmful but is not going to treat your medical problem. Of course, you may get a new treatment that works. You will also be helping the development of new treatments for that condition.</p>
<h2>Placebo surgery</h2>
<p>Placebo controlled trials should be used more often in surgery to see if treatments work or not, as highlighted by recent Royal College of Surgeons <a href="https://www.rcseng.ac.uk/policy/documents/placebo-surgery-position-statement-february-2016.pdf">guidelines</a>. There are too few surgical studies that use placebo; only 53 had been published up to November 2013. What’s astounding is that half of these studies showed no benefit of the surgical intervention over placebo. In many cases the operations are still routinely performed. This means that many patients underwent the risk and inconvenience of a surgery for no benefit. The ethical failing is not that the studies used placebo controls, but that the studies weren’t done earlier.</p>
<p>The use of placebo is a vital, though often misunderstood, part of medical research. But the careful and proper use of placebo is not only good science, it is good ethics.</p><img src="https://counter.theconversation.com/content/55180/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Andrew George is Chair of the National Research Ethics Advisors' Panel of the UK's Health Research Authority.</span></em></p>A placebo is an important tool for finding out if a treatment works or not. A dummy pill is one thing, but is it right to perform placebo surgery on someone?Andrew George, Deputy Vice-Chancellor, Brunel University LondonLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/552192016-02-23T04:04:24Z2016-02-23T04:04:24ZExplainer: what is the placebo effect and are doctors allowed to prescribe them?<figure><img src="https://images.theconversation.com/files/112457/original/image-20160223-16459-1q7uhhg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The placebo effect is real and powerful, despite it having a bad rap.</span> <span class="attribution"><span class="source">from www.shutterstock.com.au</span></span></figcaption></figure><p>Suppose you discovered that some past prescription a GP gave you was actually a placebo. The treatment made you feel better, but now you know that the perceived benefit was really a placebo effect. Would you be upset at the deception, or pleased the doctor had found a way to help you?</p>
<p>There is little research on how often Australian doctors prescribe placebos. But, if they are at all like doctors in other countries, it is a <a href="http://bmcmedicine.biomedcentral.com/articles/10.1186/1741-7015-8-15">common practice</a>. Doctors break no law in using a placebo, but may cross an ethical boundary in choosing to deceive a patient, or to facilitate a patient’s self-deception.</p>
<h2>What are placebos?</h2>
<p>It’s important to distinguish between pure and impure placebos. A pure placebo is a straightforwardly fake treatment – a saline injection or a sugar pill, for instance, that is represented as a drug. </p>
<p>An impure placebo is a substance or treatment that does have clinical value, but not for the condition for which it is being prescribed.</p>
<p>Impure placebos can be vitamins, nutritional supplements, antibiotics for viral infections, sub-clinical doses of drugs, unproven complementary and alternative medicines, or unnecessary blood tests to calm an anxious patient.</p>
<p>A <a href="http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0058247">2012 survey in the United Kingdom</a> found 1% of GPs use pure placebos and 77% use impure placebos at least once a week. </p>
<p>Pure placebos involve an outright lie. Whether impure placebos should be characterised as deceptive is less obvious. With an impure placebo, the patient knows what he or she is actually taking, but may not realise the doctor does not expect the treatment to work.</p>
<p>The placebo effect is unquestionably real but not yet fully understood. It is now believed there are <a href="http://www.nature.com/npp/journal/v36/n1/full/npp201081a.html">different types of placebo effect</a> involving <a href="http://www.ncbi.nlm.nih.gov/pubmed/24754688">different mechanisms</a>. These include response conditioning based on prior experience, expectation and reward effects mediated through the dopamine system and natural analgesia through the production of endorphins, the body’s own painkillers.</p>
<p>What triggers the placebo effect, though, is belief: the belief that you are receiving a treatment and that it will be effective. The placebo itself is simply a prop to sustain the illusion. <a href="http://www.theatlantic.com/health/archive/2014/10/the-power-of-drug-color/381156/coloured">Studies suggest</a> coloured pills
are more effective than white pills, <a href="https://www.psychologytoday.com/blog/brain-sense/201201/the-placebo-effect-how-it-works">two pills</a> are more effective than one, <a href="https://books.google.com.au/books?id=hNY7P1z6qBoC&pg=PA163&lpg=PA163&dq=placebo+coloured+pills+are+more+effective+than+white+pills,+two+pills+are+more+effective+than+one,+injections+are+more+effective+than+pills+for+some+population&source=bl&ots=q5l_d9jqOw&sig=MFLGEuqbO5shH5KG5ZNfxYZDdgU&hl=en&sa=X&ved=0ahUKEwinmYvb74zLAhWCnZQKHTfwDhwQ6AEILTAE#v=onepage&q=placebo%20coloured%20pills%20are%20more%20effective%20than%20white%20pills%2C%20two%20pills%20are%20more%20effective%20than%20one%2C%20injections%20are%20more%20effective%20than%20pills%20for%20some%20population&f=false">injections</a> are more effective than pills, placebos <a href="https://books.google.com.au/books?id=wk-OxcTKyi4C&pg=PA110&lpg=PA110&dq=placebo+injections+more+effective+than+drugs&source=bl&ots=AWvQF3vlzh&sig=7gUcBhjSZ-WfQowr9M8iVxXpA94&hl=en&sa=X&ved=0ahUKEwjv7oCg8YzLAhVIqJQKHby7DRMQ6AEINTAF#v=onepage&q=placebo%20injections%20more%20effective%20than%20drugs&f=false">administered in hospital</a> are more effective, treatments perceived to be expensive are more effective than cheaper ones and brand-name drugs are <a href="http://www.ncbi.nlm.nih.gov/pubmed/24754688">more effective than generics</a>.</p>
<p>The placebo effect has an evil twin, the nocebo effect, where a patient experiences adverse side effects from a harmless placebo, or where the expectation of negative symptoms precipitates those symptoms. The placebo effect is ubiquitous, which is why placebo-controlled trials are important in drug evaluation.</p>
<p>A drug’s effectiveness is measured in terms of the extent to which it is better than a placebo. Not all of the benefits of drugs derive from the pharmaceutical compound itself. For many drugs, some part of the benefit depends on the patient’s beliefs.</p>
<h2>Are placebos ethical?</h2>
<p>The placebo phenomenon raises some difficult questions about truth and consent in medicine. The two primary ethical duties of doctors are to act in the patient’s best interests and to respect the patient’s autonomy.</p>
<p>The doctrine of informed consent dictates that patients have an absolute right to make treatment decisions based on full information about the risks and benefits of proposed treatments.</p>
<p>Yet the placebo effect suggests that complete information and unvarnished honesty are not always in the patient’s best interests. Sometimes it may be beneficial for patients to have expectations their doctors do not share.</p>
<p>Similarly, there is an emerging concern in the literature that telling patients about all the possible side effects of a treatment can trigger a nocebo effect, causing some patients to <a href="http://www.tandfonline.com/doi/abs/10.1080/15265161.2015.1074302?journalCode=uajb20#.VsumMYx96X0">experience adverse side effects</a>.</p>
<p>It is obviously important to know about the side effects of treatments, both for deciding whether to take a drug and to be alert to possible problems. But this kind of information is not therapeutically neutral. It can condition expectations or focus anxieties in harmful ways.</p>
<p>A cognitive intervention that can produce significant pain relief and measurable improvement for a variety of other symptoms is, unquestionably, medically important. It’s questionable, however, whether we should incorporate such an intervention into standard practice, given it requires deception.</p>
<p>Essentially, the issue is the placebo effect has a serious image problem. Discovering that an apparently helpful medicine was merely a placebo can be embarrassing, even shameful. It is often seen as implying gullibility or delusion, or perhaps that the illness was exaggerated.</p>
<p>The emphasis on deception frames the placebo effect as a kind of illusion that is “all in the mind”. But the placebo effect is not a weird anomaly. It shows us something about how the body’s <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2391024/">responses to injury and disease</a> function.</p>
<p>If beliefs, expectations and dispositions are involved in the neuro-physical mechanisms governing pain response, then it may matter a great deal how we understand, imagine and anticipate our own pain.</p>
<hr>
<p><em>David Neil is a guest on tonight’s episode of Insight on placebos, at 8.30pm on SBS.</em></p><img src="https://counter.theconversation.com/content/55219/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>David Neil 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>Doctors break no law in using a placebo, but may cross an ethical boundary in choosing not deceive a patient, or to facilitate a patient’s self-deception.David Neil, Lecturer, University of WollongongLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/524612015-12-18T16:56:56Z2015-12-18T16:56:56ZWhy do people choose expensive branded drugs over cheap generics?<p>The Australian federal court <a href="http://www.theguardian.com/business/2015/dec/14/nurofens-maker-admits-misleading-consumers-over-contents-in-painkillers">has accused</a> Reckitt Benckiser of misleading consumers. The UK-based company has been marketing products in their Nurofen range for specific types of pain. The truth is, they all contain the same active ingredient: an analgesic drug called ibuprofen. Ibuprofen can’t be targeted at any specific pains. </p>
<p>No real harm done, you might think, except that these products were sold for twice the price of “standard” Nurofen. </p>
<h2>Profiteering or just brilliant marketing?</h2>
<p>While there may be some value in allowing people to shop by symptom, rather than active ingredient, the price seems inappropriately high. But perhaps not high enough to warrant the media outrage expressed. Is the real issue that we’re squeamish about companies making a profit from our suffering?</p>
<p>A time-starved generation of “baby boomers” convinced that “we’re worth it”, together with the entitled narcissism of the “millennials”, believe that when we’re in pain, we want the absolute best thing there is to treat it, quickly, with no compromise. As well as the simplified choices of shopping by symptom, products seemingly designed to treat our exact discomforts (period pain, headaches, hangovers) are likely to be seen as more effective than a general purpose painkiller. </p>
<p>Also, we believe in science – and particularly medical science – as a credible, rational source of authority; hence all those ads featuring men (usually men) in white coats. Surely these patricians wouldn’t mislead us, just for profit? </p>
<h2>Does the court’s decision really benefit us?</h2>
<p>The Australian federal court’s protective policing may benefit the consumer in the short term, but there is a flip side. We are likely to be reassured by this that future claims will be “legal, decent, honest and truthful”, making us more likely to give them credence, rather than taking a look at the small print and thinking for ourselves a little – the last thing that most brands would want.</p>
<p>So far, so heinous. Such claims - identical products, different promises, and different prices - seem worthy of an Apprentice facing the boardroom wrath of Lord Sugar for shady dealing on a market stall.</p>
<p>However, imagine for a moment that you’re a GP in private practice. Concerned parents of a six-year-old in pain bring her to see you. With no underlying trauma or organic condition to treat, you decide that the pain will certainly stop after a few days. A mild analgesic will help a little in the meantime, but the effects will be significantly boosted if the little patient can be convinced that her medicine is made specially to treat her tummy-ache. Even more so, if her loving parents also believe this. And, for her parents to really believe, you will need to charge them many times what they would pay for the same drug at a chemist. What price truth then?</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/106351/original/image-20151216-30098-17qll1x.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/106351/original/image-20151216-30098-17qll1x.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/106351/original/image-20151216-30098-17qll1x.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/106351/original/image-20151216-30098-17qll1x.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/106351/original/image-20151216-30098-17qll1x.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/106351/original/image-20151216-30098-17qll1x.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/106351/original/image-20151216-30098-17qll1x.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">
<figcaption>
<span class="caption">This is expensive, so it’s going to work.</span>
<span class="attribution"><a class="source" href="http://www.shutterstock.com/cat.mhtml?autocomplete_id=&language=en&lang=en&search_source=&safesearch=1&version=llv1&searchterm=placebo&media_type=photos&media_type2=photos&searchtermx=&photographer_name=&people_gender=&people_age=&people_ethnicity=&people_number=&color=&page=1&inline=325195844">www.shutterstock.com</a></span>
</figcaption>
</figure>
<h2>The power of belief</h2>
<p>Numerous studies have demonstrated the potency of the placebo effect. So, although at face value it seems unfair to market an identical ibuprofen product for specific aliments or to different consumer segments (leading perhaps to multiple purchases where one would have sufficed), there may be an argument that doing so can genuinely increase its effectiveness in the areas specified through the <a href="http://www.ncbi.nlm.nih.gov/pubmed/17550344">sheer power of the belief</a>. </p>
<p>While “rational” commentators can decry this as foolish, the science would suggest it works. Further, because of our tendency to alter our views to reduce cognitive dissonance (the mental discomfort we feel when we hold two or more conflicting ideas or values), by charging a premium for such “targeted” products, we – the consumer – may well <a href="http://www.neurology.org/content/early/2015/01/28/WNL.0000000000001282">amplify any placebo effect</a> present in order to justify our purchase (as when people claim fantastic efficacy for expensive branded wrinkle creams, while thinking the “Lidl equivalent” to be ineffective).</p>
<p>Although there is nothing in the public domain to suggest any noble purpose on the part of Reckitt Benckiser, an unintended effect of removing this “targeted” range may be to leave some consumers less able to treat their pain. Placebos add a tint of grey to ethical considerations in medical treatment. Greater leeway might be of genuine value, beyond just profit, in how some products are described or positioned. Rather than simply exploiting our fears and playing to our baser instincts, perhaps effective marketing, in this arena at least, could contribute something to the sum of human happiness.</p><img src="https://counter.theconversation.com/content/52461/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Leslie Hallam 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>Packaging and pricing have their own healing properties says an expert on the psychology of advertising.Leslie Hallam, Course Director, Psychology of Advertising Masters Programme, Lancaster UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/380252015-09-06T20:08:31Z2015-09-06T20:08:31ZBack to black: why melancholia must be understood as distinct from depression<figure><img src="https://images.theconversation.com/files/93483/original/image-20150901-25748-1pqq056.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Melancholia may be a distinct type of depression, with its own clinical signs and symptoms</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/helga/4723657763/">Helga Weber/flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span></figcaption></figure><p>First described by Hippocrates, “melancholia” or melancholic depression was considered a specific condition that commonly struck people out of the blue – and put them into the black. In modern times, it came to be described as “<a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1979411/">endogenous depression</a>” (coming from within) in contrast to depression stemming in response to external stressors. </p>
<p>In 1980, the third edition of the Diagnostic and Statistical Manual (<a href="http://www.terapiacognitiva.eu/dwl/dsm5/DSM-III.pdf">DSM-III</a>), the official classificatory system of the <a href="http://www.psychiatry.org/">American Psychiatric Association</a>, re-modelled depressive disorders. The new classification operated largely on degrees of severity, comprising “major” depression and several minor depressions. </p>
<p>This is how depression came to be modelled as a single entity, varying only by severity (this is known as the dimensional model). And over the last decade, this model has been extended to include “sub-clinical depressions”, which is basically when someone is sad or down but not diagnosable by formal mental illness criteria. </p>
<h2>Problematic model</h2>
<p><a href="http://www.oup.com.au/titles/academic/psychology/9780199921577">The changes generated concern</a> about the extension of “clinical depression” to include and “pathologise” sadness. While everyone feels down or sad sometimes, normally these moods pass, with little if any long-term consequences. </p>
<p>The boundary between this everyday kind of feeling down and clinical depression is imprecise. But the latter is associated with a greater severity of symptoms, such as losing sleep or thinking life isn’t worth living, lasts for longer and is much more likely to require treatment.</p>
<p>The dimensional model is intrinsically limited; “major depression” is no more informative a diagnosis than “major breathlessness”. It ignores the differing – biological, psychological and social – causes that may bring about a particular depressive condition and which inform the most appropriate therapeutic approach (be it an antidepressant drug, psychotherapy or social intervention). </p>
<p>Ignoring the cause of depression leads to both under-treatment, such as failure to prescribe an effective medication, and over-treatment, such as prescription of medication that’s unnecessary and may have side effects.</p>
<p>The model also essentially marginalised melancholia as a categorically different type of depression, with progressive DSM manuals according it insignificant status as a major depression “specifier” (an addendum to a diagnosis intended to provide more detail). </p>
<p>As a specifier, and not a disorder in its own right, melancholia is not considered categorically separate to other types of depression. And this matters – much less research and training is devoted to it as a result, and doctors are often unaware of its clinical implications. </p>
<h2>A distinct pattern</h2>
<p><a href="http://www.blackdoginstitute.org.au/public/research/meetourresearchers/gordonparker.cfm">My research team</a> is trying to establish melancholia’s categorical status and detection, and so improve its management. Here’s what we know – or think we know - about the distinctness of melancholia.</p>
<p>First, it shows a relatively clear pattern of <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3733615/">symptoms and signs</a>. The individual experiences profound bleakness and has no desire to socialise, for instance, finding it hard to obtain any pleasure in life or to be cheered up. </p>
<p>Sufferers also experience a lack of energy and have difficulty concentrating, although they generally show “diurnal variation”, reporting improvement in mood and energy as the day goes on. Reflecting changes to their sleep/wake cycle, people with melancholia tend to wake early in the morning. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/93498/original/image-20150901-25759-1obstd7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/93498/original/image-20150901-25759-1obstd7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=440&fit=crop&dpr=1 600w, https://images.theconversation.com/files/93498/original/image-20150901-25759-1obstd7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=440&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/93498/original/image-20150901-25759-1obstd7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=440&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/93498/original/image-20150901-25759-1obstd7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=554&fit=crop&dpr=1 754w, https://images.theconversation.com/files/93498/original/image-20150901-25759-1obstd7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=554&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/93498/original/image-20150901-25759-1obstd7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=554&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">People with melancholic depression may feel no pleasure in socialising or regular activities.</span>
<span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-161548835/stock-photo-lone-man-is-sitting-at-the-table-in-conference-hall-rear-view.html?src=TSYwkSoBp1HczwYLv80nxA-3-3">Maxin Blinkov/shutterstock</a></span>
</figcaption>
</figure>
<p>Episodes commonly emerge “out of the blue”. Even if it follows a stressor, it’s disproportionately more severe than might be expected and lasts longer than the stressor. </p>
<p>We’ve <a href="http://www.ncbi.nlm.nih.gov/pubmed/22868058">progressively developed</a> a clinician-rated measure (the SMPI or Sydney Melancholia Prototype Index) that has about 80% accuracy in differentiating melancholic and non-melancholic depression. When we add course of illness, causal and other clinical factors, we’ve been able to statistically <a href="http://www.ncbi.nlm.nih.gov/pubmed/25565428">differentiate melancholic and non-melancholic depression</a> at a high level.</p>
<h2>Physical underpinnings</h2>
<p>Melancholia has a strong genetic contribution, with sufferers likely to report a family history of “depression”, bipolar disorder or suicide. It’s largely biologically underpinned rather than caused by social factors (stressors) or psychological factors, such as personality style.</p>
<p>The illness is also unlikely to respond to placebo, whereas major depression has a <a href="http://www.ncbi.nlm.nih.gov/pubmed/1388334">placebo response rate</a> in excess of 40%. But melancholia shows greater response to physical treatments, such as antidepressant drugs (especially those that work on a broader number of neurotransmitters), and to ECT (electroconvulsive therapy). ECT is rarely required, however, if appropriate medications are prescribed. </p>
<p>Melancholia shows a lower response to psychotherapy, counselling and psychosocial interventions - these treatments are more salient and effective for non-melancholic depression. </p>
<p>It’s useful to draw an analogy here with diabetes: while Type 1 is more a biological disease state and generally requires drug treatment (insulin), Type II is more likely to reflect other factors, such as obesity. The latter generally benefits most from non-drug strategies, such as exercise and dietary changes. </p>
<p>Melancholia shows similar “treatment specificity”, with medication being the treatment of choice.</p>
<h2>Tracing biological origins</h2>
<p>Melancholia has long been thought to have <a href="http://www.ncbi.nlm.nih.gov/pubmed/7458567">primary biological origins</a>, including perturbations in the hypothalamic-pituitary-adrenal (HPA) axis, in sleep architecture and in neural circuits.</p>
<p>Early this year, our research team <a href="http://www.ncbi.nlm.nih.gov/pubmed/1388334">published a neuroimaging study</a> that suggested a differential key “signature” marker found only in people with melancholic depression (when compared to people with non-melancholic depression and non-depressed controls). </p>
<p>We showed incoming connections to the brain system that control attention (the insula) were halved, while connections from the insula to the brain’s executive control centre were also decreased. </p>
<p>The implications of these findings will require further investigation, but they could mean that a disruption to brain connectivity may explain some of melancholia’s symptoms. </p>
<p>Clearly, melancholia needs to be recognised as a distinct psychiatric condition – not simply as a more severe expression of depression. This recognition could lead to improved clinical and community awareness, which is important because managing melancholia requires a specific treatment approach.</p><img src="https://counter.theconversation.com/content/38025/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Gordon Parker receives funding from the National Health and Medical Research Council and has been a paid speaker for several drug companies. He is affiliated with the University of New South Wales and was the founding director of the Black Dog Institute <a href="http://www.blackdoginstitute.org.au/">http://www.blackdoginstitute.org.au/</a>.</span></em></p>Melancholia has a strong genetic contribution, so it’s largely biologically underpinned rather than caused by social factors (stressors) or psychological factors, such as personality style.Gordon Parker, Scientia Professor , UNSW SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/335972014-11-21T03:29:54Z2014-11-21T03:29:54ZIce bath after exercise? The benefits might be in your head<figure><img src="https://images.theconversation.com/files/63521/original/wxv4xvhs-1414991479.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">How much of an ice bath is a placebo?</span> <span class="attribution"><a class="source" href="http://www.flickr.com/photos/andreasnilsson1976/2903953102">Andreas Nilsson/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span></figcaption></figure><p>Whether an athlete has endured the repeated joint stresses of a marathon run, or the relentless battery of hits during a football match, many will opt for a post-activity polar plunge into an ice-cold bath. </p>
<p>There is method to this madness, though – many studies show that ice baths allow athletes to recover faster, train harder and ultimately perform better, and are thought to accelerate the body’s recovery, preparing it for the next gruelling training session. </p>
<p>Given the subjective nature of muscle soreness, might the supposed benefits of ice baths be psychological? It is perfectly plausible that an athlete may simply expect the cold stimulus to help recovery and in fact, a <a href="http://www.ncbi.nlm.nih.gov/pubmed/24674975">study published</a> in the journal Medicine and Science in Sports and Exercise by me and colleagues at Victoria University shows this may be the case.</p>
<h2>Ice is nice</h2>
<p>Ice baths are believed to improve the recovery of strength, power and flexibility, as well as recovery from muscle damage and swelling – but we aren’t entirely sure <em>why</em> they have this effect. Recent <a href="http://www.ncbi.nlm.nih.gov/pubmed/21947816">research</a> endorses the use of ice baths solely for alleviating muscle soreness following strenuous exercise, with its role on muscle function less clear. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/tcNwFC91P5k?wmode=transparent&start=77" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Could you do 10 minutes in an ice bath?</span></figcaption>
</figure>
<p>Previous research on ice baths has overlooked the possibility of a placebo effect, a fascinating phenomenon by which a normally ineffective treatment may result in improvements. The intriguing influence of the placebo effect has <a href="http://www.ncbi.nlm.nih.gov/pubmed/19317519">long been acknowledged</a> in medicine and medical research, often used as a therapeutic intervention and routinely controlled for in clinical trials for over 50 years. </p>
<p>The placebo effect is so strong that it has even been controlled for in the testing of new surgical techniques. For example, patients having a knee arthroscope to treat arthritis <a href="http://www.ncbi.nlm.nih.gov/pubmed/12110735">reported similar improvements</a> in knee pain and function as those who received a placebo or “sham” surgical procedure. </p>
<p>The placebo effect has also been shown to influence sport performance, where simply <a href="http://www.ncbi.nlm.nih.gov/pubmed/17876973">expecting an intervention</a> to have a positive effect can improve performance. A <a href="http://www.ncbi.nlm.nih.gov/pubmed/18702709">2008 study</a> showed an 8% decrease in perceived fatigue and a 12% increase in leg extension strength when supplying a caffeine placebo. </p>
<h2>Mind power</h2>
<p>So, are ice baths actually helping our muscles to recover, or is it all in our heads? </p>
<p>Our research investigated this issue, comparing the effects of an ice bath with a placebo condition that participants were tricked into thinking was as effective as an ice bath. </p>
<p>We recruited 30 young, healthy men who we considered “recreationally active” and got them to perform a maximal cycling bout (4 x 30s “all-out” sprints on a bike) followed by one of three recovery conditions: </p>
<ol>
<li>an ice bath (around 10C)</li>
<li>a warm bath control (around 35C)</li>
<li>a placebo (around 35C). </li>
</ol>
<p>The placebo participants were shown a fake brochure detailing the benefits of a newly-developed “recovery oil”, and were led to believe it was as effective as an ice bath for the recovery of athletic performance. </p>
<p>To deceive them, we simply put a common skin cleanser into the bath, in plain sight of the participants, immediately before their bath. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/64774/original/z8nvm4qn-1416271256.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/64774/original/z8nvm4qn-1416271256.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/64774/original/z8nvm4qn-1416271256.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/64774/original/z8nvm4qn-1416271256.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/64774/original/z8nvm4qn-1416271256.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/64774/original/z8nvm4qn-1416271256.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/64774/original/z8nvm4qn-1416271256.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/64774/original/z8nvm4qn-1416271256.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"></a>
<figcaption>
<span class="caption"></span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/57336354@N00/5180673144">susan/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span>
</figcaption>
</figure>
<p>Interestingly, participants in both the ice bath and placebo conditions rated their belief in the benefits of their assigned recovery condition similarly, which in turn translated into a similar recovery of leg extension strength over a 48-hour post-exercise period.</p>
<p>On top of this, the recovery of leg strength was faster for the placebo condition when compared with the warm bath control, even though the two conditions were identical. </p>
<p>By deceiving participants into thinking they were receiving a beneficial treatment, subjective ratings of psychological well-being were improved, and a superior performance was witnessed. These results support the notion that belief has a <a href="http://www.ncbi.nlm.nih.gov/pubmed/24194442">powerful effect</a> on exercise performance. </p>
<p>Where to next? Smart coaches can harness this belief effect to maximise the benefits of everything that they do with athletes. This is particularly important for the so called placebo effect “responders”, as it is <a href="http://www.ejmh.eu/mellekletek/2011_2_196_Berdi_etal.pdf">well documented</a> that some individuals show remarkable responses to placebo interventions, while others may not at all. </p>
<p>A strong belief in ice baths, combined with any potential physiological benefits, will maximise its potential to enhance an athlete’s recovery from exercise. For the rest of us, a warm bath will do just fine.</p><img src="https://counter.theconversation.com/content/33597/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>James Broatch receives funding from Exercise & Sports Science Australia.</span></em></p>Whether an athlete has endured the repeated joint stresses of a marathon run, or the relentless battery of hits during a football match, many will opt for a post-activity polar plunge into an ice-cold…James Broatch, PhD Candidate in Exercise Physiology, Victoria UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/315212014-11-06T19:26:47Z2014-11-06T19:26:47ZWhy placebos for chemotherapy side effects are hard to swallow<figure><img src="https://images.theconversation.com/files/63820/original/q48s7qst-1415237805.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Vomiting, nausea and diarrhoea are common chemotherapy side effects that can be so severe that patients may refuse further treatment.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/evilerin/3158385504">Emergency Brake/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>It’s unthinkable to give a placebo to someone to treat their cancer, but could we use one to treat chemotherapy’s well-known side effects? Unfortunately, we may never be able to answer this question because the biggest obstacle to finding out whether it would work is emotional rather than scientific.</p>
<p>Let’s first consider the reason for the proposition. <a href="http://dx.doi.org/10.1016/j.annemergmed.2014.03.017">Recent research</a> shows placebos are just as effective as prescribed medicines for treating emergency room patients with nausea. As nausea and vomiting are also common side effects in chemotherapy, there’s a clear scientific rationale to using them for cancer patients as well. </p>
<p>And there are medically valid reasons for trials to test whether this could work, especially as a way to reduce the large number of medicines cancer patients usually need. But cancer is much more emotive than other diseases and despite good reasons and intentions, we may never find the idea palatable enough to test whether it works.</p>
<h2>The ethics of placebos</h2>
<p>A placebo is a medicine that doesn’t contain an active drug ingredient but still has a therapeutic effect. Many studies have demonstrated a strong <a href="http://www.webmd.com/pain-management/what-is-the-placebo-effect">placebo effect</a>. They can work <a href="http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0015591">even when people are told</a> they are being given a placebo (although they work better when people are not told). But the ethics of placebo use is rather complicated.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/yfRVCaA5o18?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">The strange powers of the placebo effect.</span></figcaption>
</figure>
<p>Consider the ethics of these two scenarios using placebos - treating a psychosomatic disorder and testing a new drug. </p>
<p>For a placebo to work for a psychosomatic disorder, the patient has to be unaware they’re taking an inactive substance. In this situation, the doctor has prioritised their patient’s interest in getting better over their right to make an informed decision about whether or not to take a “medicine”.</p>
<p>Placebos are also used in clinical trials to help researchers identify whether a new drug works better compared to an inactive alternative. The best clinical trials use a “double-blinded” approach, where the participants know they may be given a placebo but neither they, nor the person giving them the drug, knows if they have. </p>
<p>There are no ethical problems with using placebos in clinical trials, assuming participants have been properly informed and given consent. But it’s not as clear-cut for psychosomatic disorders. </p>
<p>Even if someone’s condition is pyschosomatic, their symptoms can feel just as real and debilitating as any other ailment. In this scenario, no harm is done when the placebo works. But there could be an ethical problem if the placebo doesn’t work as anticipated.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/63822/original/58fxjxnt-1415238426.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/63822/original/58fxjxnt-1415238426.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=428&fit=crop&dpr=1 600w, https://images.theconversation.com/files/63822/original/58fxjxnt-1415238426.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=428&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/63822/original/58fxjxnt-1415238426.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=428&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/63822/original/58fxjxnt-1415238426.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=538&fit=crop&dpr=1 754w, https://images.theconversation.com/files/63822/original/58fxjxnt-1415238426.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=538&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/63822/original/58fxjxnt-1415238426.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=538&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The seriousness of cancer means it’s unethical to give cancer patients placebos because they would very likely die without effective treatment.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/philandpam/223015379">Phil and Pam Gradwell/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
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<p>Recall that doctors don’t usually tell these patients they were given a placebo because it works better that way. So, when the placebo doesn’t alleviate the symptoms it was prescribed for, it becomes a case of missed therapy, which may result in harm or a delay in other appropriate treatment. </p>
<h2>Chemotherapy and placebos</h2>
<p>Generally, the seriousness of cancer means it’s unethical to treat cancer patients with placebos because they would very likely die without effective treatment. But reducing the number of drugs they have to take is desirable because it can be a burden on patients to remember to take the right medications at the right times and missed doses can have serious complications.</p>
<p>Most cancer patients taking chemotherapy drugs will also be given a cocktail of other drugs to treat the side effects of those medicines. These can include drugs to prevent them getting infections, such as antibiotics, chemotherapy adjuvants, drugs to boost blood production and pain killers.</p>
<p>Other common side effects of chemotherapy are vomiting, nausea and diarrhoea. These can be so severe that patients may refuse further chemotherapy. What’s more, after the first round of chemotherapy, some patients can experience nausea and vomiting not from the treatment itself but from previously innocuous things, such as the strong antiseptic smell of a hospital or even the sight of the building (a psychosomatic response). </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/63823/original/bjmdwfhn-1415238543.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/63823/original/bjmdwfhn-1415238543.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=398&fit=crop&dpr=1 600w, https://images.theconversation.com/files/63823/original/bjmdwfhn-1415238543.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=398&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/63823/original/bjmdwfhn-1415238543.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=398&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/63823/original/bjmdwfhn-1415238543.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=500&fit=crop&dpr=1 754w, https://images.theconversation.com/files/63823/original/bjmdwfhn-1415238543.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=500&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/63823/original/bjmdwfhn-1415238543.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=500&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">It’s desirable to try to reduce the overall number of medicines a chemotherapy patient needs to take.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/penmachine/466679962">Derek K. Miller/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span>
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</figure>
<p><a href="http://familydoctor.org/familydoctor/en/drugs-procedures-devices/over-the-counter/antiemetic-medicines-otc-relief-for-nausea-and-vomiting.html">Anti-emetic drugs</a> are usually used to treat chemotherapy-induced nausea and vomiting, and patients generally respond well. But why not try to reduce the overall number of medicines a chemotherapy patient needs to take?</p>
<p>If the patient is fully informed and aware they could be given a placebo during treatment, especially if their nausea is psychosomatic, there would be no ethical dilemma. But placebos are most effective when the patient doesn’t know they are taking one. </p>
<p>Cancer is a much more emotive disease and chemotherapy is far removed from the rapid decision-making environment of the hospital emergency room, which is where the nausea-placebo study was conducted. In those situations, medical teams make decisions without consulting the patient or their family and may unilaterally decide to use a placebo for nausea. </p>
<p>In contrast, family and friends tend to be much more involved with cancer patients in their treatment decision making. Many may find the idea of their loved one being given a placebo unpalatable.</p>
<p>So what do you think? Should medical staff consider the use of placebos to treat the chemotherapy side effects of cancer patients? Would you be happy if your mother, father, sister or brother was given a placebo while undergoing chemotherapy?</p><img src="https://counter.theconversation.com/content/31521/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Nial Wheate in the past has received funding from the ACT Cancer Council, Tenovus Scotland, Medical Research Scotland, Scottish Crucible and the Scottish Universities Life Sciences Alliance for research into anticancer drugs.</span></em></p><p class="fine-print"><em><span>Betty Chaar has received funding in the past from: NSW Health, Pharmacy Board and the Pharmacy Guild for research conducted on drug and alcohol issues in pharmacy, professional ethics in pharmacy and the role of pharmacy in enhancing health literacy.</span></em></p>It’s unthinkable to give a placebo to someone to treat their cancer, but could we use one to treat chemotherapy’s well-known side effects? Unfortunately, we may never be able to answer this question because…Nial Wheate, Senior Lecturer in Pharmaceutical Chemistry, University of SydneyBetty Chaar, Senior Lecturer, University of SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/324302014-10-28T03:55:44Z2014-10-28T03:55:44ZAntidepressants may be no better than a placebo, so why take them?<figure><img src="https://images.theconversation.com/files/62954/original/99h7fp4p-1414462199.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A growing body of research suggests placebos may be as good as real drugs for treating depression.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/v1ctor/8325573561">Victor/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>Seventeenth-century Oxford scholar Robert Burton’s lifework, <a href="http://www.gutenberg.org/ebooks/10800">The Anatomy of Melancholy</a>, weighs in at a door-stopping 1,400 pages. But his cure for the “Black Choler” of depression came down to just six words: “Be not solitary, be not idle.” Writing today, he might add: “And maybe take a placebo.”</p>
<p>Placebos are sham treatments that work even though they lack an active ingredient. Pills made of sugar or corn starch <a href="http://www.sciencedirect.com/science/article/pii/S0140673609617062">have improved</a> Parkinson’s disease, anxiety and pain. Now <a href="http://www.ncbi.nlm.nih.gov/pubmed/25213159">research suggests</a> placebos may be as good as real drugs for treating depression.</p>
<h2>Placebo power</h2>
<p>In this <a href="http://www.ncbi.nlm.nih.gov/pubmed/25213159">most recent study</a>, people with at least moderate depression received support and encouragement alone, or coupled with an antidepressant or a placebo. Those who received an antidepressant or placebo did better than those who got only support. But placebos improved depression nearly as much as the active drug and the difference wasn’t significant.</p>
<p>An <a href="http://www.ncbi.nlm.nih.gov/pubmed/20051569">earlier review</a> found antidepressants offered minimal benefit over placebos except in very severe depression, where the benefit was substantial. <a href="http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.0050045">And a 2008 study</a> found antidepressants were no more effective even in severe depression; very depressed people were just less responsive to placebos.</p>
<p>One theory suggests placebos work because people <a href="http://psycnet.apa.org/psycinfo/2004-11156-007">expect them to</a>. A grave doctor and austere consulting room help convince patients a drug works. Indeed, believing a dummy pill stops pain <a href="http://www.nature.com/nrn/journal/v6/n7/full/nrn1705.html">triggers endorphins</a> in the same brain area targeted by real painkillers.</p>
<p>Another theory cites Pavlov’s dogs, who, after a while, just had to see the white coats of the assistants who brought their food to start drooling. This <a href="http://www.ncbi.nlm.nih.gov/pubmed/9081556">conditioning theory</a> suggests people only need to see the pill, cream or syringe to get the intended effect, even without the active drug. </p>
<p>But we know active drugs cause placebo effects too. Painkillers work a <a href="http://www.ncbi.nlm.nih.gov/pubmed/17550344">lot better</a> when a medical person says they will work. A 1998 study claimed placebo effects <a href="http://psycnet.apa.org/psycinfo/1999-11094-001">accounted for an estimated 75%</a> of the effects of antidepressants.</p>
<p>Nonetheless, the drugs still figure prominently in <a href="http://www.beyondblue.org.au/resources?type=publications&cats=c983c749-451e-4102-85d2-bd33b313fce9">Australian guidelines</a> and in 2012-13 Australian doctors wrote <a href="https://mhsa.aihw.gov.au/resources/prescriptions/">20.5 million prescriptions</a> for antidepressants.</p>
<h2>The right fit</h2>
<p>But if antidepressants are little better than a placebo, why do so many people take them? Well, the <a href="http://blogs.plos.org/mindthebrain/2012/12/26/the-antidepressant-wars-a-sequel-how-the-media-distort-findings-and-do-harm-to-patients/">placebo data have been criticised</a>, among others, for selective analysis of studies. They may be wrong. </p>
<p>And there are reasons why doctors and patients might favour medication that could help even a little. A busy waiting room makes speedy prescription writing attractive; advertising could make doctors think of drugs as the first option; patients often want a “quick fix”; and our culture reinforces drugs as a natural response to illness. </p>
<p>A trickier question is whether doctors should even prescribe antidepressants if they are really just placebos. But placebos can be powerful and <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2692248/">some argue</a> we shouldn’t jeopardise their strength by telling patients. <a href="http://www.ncbi.nlm.nih.gov/pubmed/18948346">A 2008 US study</a> of 1,200 doctors found more than half prescribe placebos, often vitamin pills.</p>
<p>But there may be differences between countries too. Direct-to-consumer advertising of prescription drugs, legal only in the United States and New Zealand, may <a href="http://link.springer.com/article/10.1007%2Fs10551-013-1805-0">influence placebo responses</a>. Advertisements for drugs show dramatic improvements that heighten expectations. Pictures of smiling people and beautiful scenery also promote <a href="http://www.tandfonline.com/doi/abs/10.1080/15265161.2013.776127#.VEm8BfmUd8E">positive attitudes and beliefs</a>.</p>
<p><a href="http://psycnet.apa.org/psycinfo/2004-11156-007">Some think</a> advertising is the reason placebos in antidepressant drug trials have become <a href="http://jama.jamanetwork.com/article.aspx?articleid=194819">14% more effective</a> in the last 20 years. </p>
<p>And people with depression may show stronger placebo responses. Psychologist <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2582668/">Irving Kirsch thinks</a> this is because hopelessness is so dominant in depression. Placebos give hope so they may work better for this particular illness. </p>
<h2>Limiting placebo use</h2>
<p>Nonetheless, the American Medical Association has <a href="http://academicdepartments.musc.edu/humanvalues/pdf/Placebo.useinclinicalpractice.pdf">vetoed</a> the use of deceptive placebos, saying they undermine trust, frustrate patient autonomy and delay proper treatment. But <a href="http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0015591">a 2010 study</a> showed placebos work even if you tell the patient. </p>
<p>Others argue real drugs are actually superior placebos. In blinded drug trials, people who get side effects often <a href="http://www.newsweek.com/why-antidepressants-are-no-better-placebos-71111">work out</a> they’re on the real drug and not the placebo. This makes them expect to improve, so the placebo effect kicks in.</p>
<p>But this too gets complicated because placebos can also cause side effects. This “nocebo” phenomenon happens when people expect bad things from a sugar pill. Maybe placebos will work better if the doctor “suggests” some side effects too?</p>
<p>An alternative to grappling with this often conflicting information is to raise the profile of non-drug treatments for depression. Psychotherapies such as cognitive behavioural therapy are <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2748674/">as good as drugs</a>, except for people with severe depression. </p>
<p>But adding another twist is a <a href="http://www.ncbi.nlm.nih.gov/pubmed/23552610">recent study</a> that showed psychotherapy isn’t significantly better than a pill placebo for depression. Still, psychotherapy does provide important knowledge that <a href="http://mitpress.mit.edu/books/ethical-treatment-depression">promotes autonomy</a>, a factor not measured in study comparisons.</p>
<p>Many active treatments are effective partly because of the placebo effect. The effect is strong in antidepressants, a fact that may need to be disclosed to patients to ensure fully informed consent. Whether sugar placebos should ever enter medical practice is another question entirely, and one that invites wide community debate.</p><img src="https://counter.theconversation.com/content/32430/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Paul Biegler has received funding from the Australian Research Council. He is a former emergency physician and the author of The Ethical Treatment of Depression: Autonomy through Psychotherapy (MIT Press 2011) which won the Australian Museum Eureka Prize for Research in Ethics.</span></em></p>Seventeenth-century Oxford scholar Robert Burton’s lifework, The Anatomy of Melancholy, weighs in at a door-stopping 1,400 pages. But his cure for the “Black Choler” of depression came down to just six…Paul Biegler, Adjunct Research Fellow in Bioethics, Monash UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/226952014-05-06T20:37:56Z2014-05-06T20:37:56ZThink positively about sleep by all means, but you can’t fool your body<figure><img src="https://images.theconversation.com/files/47272/original/7fm4b9nq-1398755965.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Just telling yourself you're well rested doesn't mean you can override how your body is experiencing lack of sleep.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/williambrawley/4045524560">William Brawley/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>Sleep – elusive, precious, restful sleep – is a topic close of many of our hearts. Such is the importance of this activity that sometimes people cling on to half-baked ideas about it with an unnatural fervour.</p>
<p>Consider a paper on <a href="http://www.ncbi.nlm.nih.gov/pubmed/24417326">sleep research published</a> early this year, for instance, which garnered widespread media coverage. Thinking positively about how you slept may help you perform better at school and work, it claimed. </p>
<p>That’s a novel idea and it’s based on some truth - but really? Can positive thinking about sleep quality fool both the body and mind into doing better than if they “knew” they were exhausted?</p>
<p>Like all attractive but false ideas, this notion of placebo sleep has a grain of truth in it. Research shows insomniacs <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3277880/">misperceive their sleep</a>, often overestimating the amount of <a href="http://www.ncbi.nlm.nih.gov/pubmed/12150323">time they spend awake</a>. And if they feel they haven’t slept well, this may make them feel worse when awake.</p>
<p>Still, sleep – and the lack of it – has physiological impacts. And just telling yourself you’re well rested doesn’t mean you can override how your body is experiencing its lack.</p>
<h2>How sleep works</h2>
<p>Sleep is comprised of two core stages, non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. The former is divided into four sub-stages that typically become deeper. </p>
<p>In adults, a normal nocturnal sleep period involves four to five cycles of both types of sleep, each lasting about 90 to 100 minutes. </p>
<p>While <a href="http://www.ncbi.nlm.nih.gov/pubmed/16251951">NREM and REM sleep</a> may serve slightly different functions – NREM sleep is thought to be important for tissue growth and repair, immunity to help fight disease and illness, and energy conservation, whereas REM sleep may be involved in brain development, memory and learning – most researchers generally agree both are equally important to maintain optimal waking functions.</p>
<p>Sleep loss, whether from staying up all night or simply not getting enough (for instance due to work, or a new baby, or staying up late), is widely associated with cognitive impairment, including increased reaction time and poor vigilance, concentration and decision-making.</p>
<p>It also has consequences for physiological functioning, such as changes to stress hormones (cortisol), metabolic factors (glucose metabolism, growth hormone secretion, appetite hormones) and immunity. These are critical for health and well-being, and for maintaining optimum performance at school and work.</p>
<h2>‘Placebo sleep’?</h2>
<p>The placebo sleep study suggests you can improve your cognitive performance by changing how you think about your sleep quality. But there are many holes in how the study authors reached that conclusion.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/47273/original/kdr9s4vc-1398756382.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/47273/original/kdr9s4vc-1398756382.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=253&fit=crop&dpr=1 600w, https://images.theconversation.com/files/47273/original/kdr9s4vc-1398756382.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=253&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/47273/original/kdr9s4vc-1398756382.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=253&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/47273/original/kdr9s4vc-1398756382.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=318&fit=crop&dpr=1 754w, https://images.theconversation.com/files/47273/original/kdr9s4vc-1398756382.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=318&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/47273/original/kdr9s4vc-1398756382.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=318&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">There’s no substitute for sleep when it comes to good health and optimal performance.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/davidwithacamera/8575714726">David Simmonds</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
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</figure>
<p>Researchers randomly assigned 164 students to either an above or below average sleep quality condition or a control condition. Participants were not aware the experiment was focusing on sleep quality.</p>
<p>All students were given a brief lesson on sleep and told that, on average, adults spend between a fifth and a quarter of their total sleep in REM sleep, and that people with less than 20% REM sleep perform worse on tests of learning and memory while those who get 25% or more perform better. </p>
<p>All were then briefly attached to equipment measuring their waking brainwave activity and told it would determine the amount of REM sleep they had the night before.</p>
<p>Although students were asked to report how they’d slept the night before, the actual amount wasn’t recorded. So, there’s no way of knowing if the results of the performance measures were because of the experiment and not simply due to the amount of sleep the students got the night before.</p>
<p>The group assigned to above average sleep quality were told they spent 28.7% of their total sleep time in REM sleep, while the below average group was told they spent 16.2%. When cognitive performance was assessed, students in the first group tended to perform better than those who thought they had less REM sleep.</p>
<p>Although the results indicated performance was correlated to how participants perceived their sleep quality, the differences between the two groups were only small. It’s unlikely such small differences would have a significant effect on performance in the real world. </p>
<h2>The prosaic truth</h2>
<p>Still, the authors interpreted this to indicate that mindset about sleep quality influences cognitive performance.</p>
<p>If you agree with that conclusion, it seems the way you think about how you slept can change the way we feel when awake. In other words, if you think you had a restless sleep the night before, you might feel worse during the day, and vice versa.</p>
<p>But while changing what you think about the sleep you’ve had may make you feel better, and maybe even perform better in tests and the like in the short term, biology and the drive for sleep will ultimately determine how well or poorly people perform during the day.</p>
<p>There’s no substitute for sleep when it comes to good health and optimal performance. There’s no fancy fix; the best thing you can do for this is have a regular routine that gives you seven hours of sleep every night.</p>
<p>Going to bed and getting up at the same time each day, natural light in the morning and exercise can all help improve sleep quality over the long term, and maximise cognitive performance at school and work. Perhaps the best lesson from this study is that you shouldn’t think too much about sleep, it’ll just make matters worse.</p><img src="https://counter.theconversation.com/content/22695/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Gemma Paech has no conflicts of interest to disclose. </span></em></p><p class="fine-print"><em><span>Siobhan Banks 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>Sleep – elusive, precious, restful sleep – is a topic close of many of our hearts. Such is the importance of this activity that sometimes people cling on to half-baked ideas about it with an unnatural…Gemma Paech, Research Associate, Centre for Sleep Research, University of South AustraliaSiobhan Banks, Senior Research Fellow, Centre for Sleep Research, University of South AustraliaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/110042013-12-16T19:13:26Z2013-12-16T19:13:26ZTo understand placebo, first take it out of medicine’s black box<figure><img src="https://images.theconversation.com/files/36877/original/g34vzbk7-1386127946.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Placebos have played an important part in medicine for two centuries.</span> <span class="attribution"><span class="source">jared/ flickr</span></span></figcaption></figure><p>Placebos have a longer history than medicine as we know it, and have a huge effect on all kinds of diseases and health conditions. But it may now be time to rethink their role. </p>
<p>The placebo made its <a href="http://www.ncbi.nlm.nih.gov/pubmed/10692902">debut in the medical literature</a> some 200 years ago, although the administration of inert agents in medical practice has a considerably longer history. In fact, such practice is probably <a href="http://jama.jamanetwork.com/article.aspx?articleid=336847">as old as medicine</a> itself. </p>
<p>Placebos took on a more studied role with the increasing application of the scientific method to health care that really took off around the middle of the last century. In this context, placebo interventions have been used as a control to test the efficacy of certain treatments.</p>
<h2>What is it anyway?</h2>
<p>Recently, the increasing incorporation of best-available scientific evidence into medical care (evidence-based practice) has sparked debate around placebos. </p>
<p>Most often, these debates centre on whether a particular treatment <a href="https://theconversation.com/mind-over-matter-the-ethics-of-using-the-placebo-effect-3752">works only via placebo</a>, and what implications this might have for policy-makers, clinicians, and patients.</p>
<p>Unsurprisingly, there’s also <a href="http://www.biomedcentral.com/1741-7015/8/15">significant ethical controversy</a> concerning the practice of clinicians knowingly providing inert treatments (placebos) to their patients.</p>
<p>But two important considerations are sometimes lost in the midst of these debates. The first is the question of just how powerful the placebo effect really is; that is, how much benefit do patients actually gain due to the administration of placebo intervention? </p>
<p>This issue is far from resolved, with the answer lying somewhere between “<a href="http://www.ncbi.nlm.nih.gov/pubmed/11372012">bugger-all</a>” and “<a href="http://www.ncbi.nlm.nih.gov/pubmed/12406519">quite a lot</a>”. </p>
<p>The <a href="http://www.ncbi.nlm.nih.gov/pubmed/22893511">second issue</a> is possibly of even greater significance. It concerns the theoretical underpinning of placebos and placebo effects themselves.</p>
<h2>Why we need to understand</h2>
<p>Attempts to try and define placebos and placebo effects have <a href="http://www.ncbi.nlm.nih.gov/pubmed/14979775">a chequered history</a>. The short version of the story is that no one has been able to propose a definition palatable to the bulk of the players in the field. </p>
<p>The problem with coming to an agreed definition stems from a logical paradox – how can an inert agent (a placebo intervention) have a real effect (a placebo effect)?</p>
<p>Some researchers have tried to overcome this problem by introducing terms such as “non-specific” or “contextual” to the placebo definition, but all of these require that the placebo itself is no longer inert. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/36881/original/4bjh63wf-1386128536.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/36881/original/4bjh63wf-1386128536.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=397&fit=crop&dpr=1 600w, https://images.theconversation.com/files/36881/original/4bjh63wf-1386128536.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=397&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/36881/original/4bjh63wf-1386128536.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=397&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/36881/original/4bjh63wf-1386128536.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=498&fit=crop&dpr=1 754w, https://images.theconversation.com/files/36881/original/4bjh63wf-1386128536.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=498&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/36881/original/4bjh63wf-1386128536.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">
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<span class="caption">Coming to terms with how a placebo can have a real affect has proven challenging.</span>
<span class="attribution"><span class="source">Marquette La/ Flickr</span></span>
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<p>This leads to questions about what is and isn’t a placebo, and blurs the lines between placebo interventions and “real” interventions.</p>
<p>Currently, the placebo exists as a kind of mysterious black box that sits between administration of a treatment that doesn’t work the way we think it should, and a beneficial effect for a patient. So what purpose does this black box serve? </p>
<p>If there <em>is</em> an effect (the patient gets better), then seeking the reason or cause of this effect would seem useful. </p>
<p>This <a href="http://www.ncbi.nlm.nih.gov/pubmed/14979775">work has already begun</a>; the two most promising lines of research investigate how patients’ expectations affect their outcome, and explore the role of <a href="http://en.wikipedia.org/wiki/Classical_conditioning">classical conditioning</a> in the placebo effect.</p>
<h2>Rethinking placebo</h2>
<p>There’s also research seeking to better understand the effect of manipulating the context of treatment and features of the patient-practitioner interaction – factors that often fall under the cloak of the placebo. These might include empathy shown by the practitioner, the connection or bond patients feel and the beliefs of the practitioner regarding the patient or condition.</p>
<p>Considering these factors as effective treatment components in their own right offers a way to understand how interventions work and, potentially, an insight into the nature of the condition being treated.</p>
<p>Improving understanding of how treatments work, and what features of the clinical context influence outcome has self-evident advantages for clinicians and their patients. And reconceptualising the outdated notion of an inert placebo can help resolve some of the ethical issues surrounding its use. </p>
<p>From a research perspective, hanging onto the placebo idea also appears to serve little purpose. Simply designating a control intervention as a “placebo” tells us nothing about what the control intervention <em>actually</em> controls for. </p>
<p>A number of different interventions may all be called placebos, and all of them may control for different aspects of the intervention being tested. </p>
<p>Dispensing with the idea of a placebo arm in clinical trials could have the benefit of forcing trial designers to more carefully consider and define what they seek to control for, and assist interpretation of clinical trials.</p>
<p>The placebo effect emerged and gained prominence in an era when health care was moving from a semi-mystical past toward the scientific present. </p>
<p>Over this time, numerous treatments have been abandoned as understanding of biology, anatomy and pathology improved. It’s possible the current concept of placebo, which served as a useful tool in the past, has reached its use-by date.</p><img src="https://counter.theconversation.com/content/11004/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Steve Kamper receives funding from The National Health and Medical Research Council of Australia.</span></em></p>Placebos have a longer history than medicine as we know it, and have a huge effect on all kinds of diseases and health conditions. But it may now be time to rethink their role. The placebo made its debut…Steve Kamper, Postdoctoral Research Fellow, The EMGO+ Institute, VU University Medical Centre, Amsterdam and, University of SydneyLicensed as Creative Commons – attribution, no derivatives.