tag:theconversation.com,2011:/global/topics/experimental-medicine-6506/articlesExperimental medicine – The Conversation2014-11-11T10:39:48Ztag:theconversation.com,2011:article/338842014-11-11T10:39:48Z2014-11-11T10:39:48ZShould dying patients have the right to access experimental treatments?<figure><img src="https://images.theconversation.com/files/64151/original/xqdhycf7-1415638993.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Who pays for experimental treatments? Stock image from </span> <span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-110115209/stock-photo-medical-ampoules-and-syringe.html?src=migwAGrIPnNFpA0LI1jSfQ-1-12">www.shutterstock.com</a></span></figcaption></figure><p><a href="http://www.washingtonpost.com/blogs/wonkblog/wp/2014/11/05/voters-in-arizona-just-overwhelmingly-backed-a-dallas-buyers-club-law-will-it-help-patients/">In the last six months</a> Colorado, Louisiana, Missouri, Michigan and, most recently, <a href="http://www.washingtonpost.com/blogs/wonkblog/wp/2014/11/05/voters-in-arizona-just-overwhelmingly-backed-a-dallas-buyers-club-law-will-it-help-patients/">Arizona</a> have passed “right to try” laws that allow terminally ill patients to access treatments that have only passed FDA Phase I clinical trials. All patients need is permission from a drug company and a prescription from a doctor. </p>
<p>Right to try laws are designed to ensure that terminally ill patients taking part in clinical trials are true volunteers and have no incentive to cheat the clinical trials system as has happened in the past.</p>
<p>Recently, these laws have been critiqued as <a href="https://theconversation.com/right-to-try-laws-are-compassionate-but-misguided-33440">misguided</a>, and the ethics of allowing patients to use experimental drugs are still <a href="http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)61315-5/fulltext">up for debate</a>. These laws do not guarantee access to experimental treatments and patients may have to pay for them out of pocket. </p>
<p>Critics of these laws <a href="http://www.ncbi.nlm.nih.gov/pubmed/2649701">worry</a> that alternative trial designs, or access to such experimental drugs outside the clinical trials system will significantly delay the development of effective therapies. </p>
<p>Right to try laws are ethically defensible because they give desperately ill patients a choice. They can decide to participate in placebo controlled clinical trials <em>or</em> to access experimental agents as a possible last-chance treatment. The clinical trial system demands that participants are true volunteers. But, without right to try laws, terminally ill patients have no choice but to access these experimental treatments through placebo controlled trials. </p>
<h2>AIDS and the origins of ‘right to try’</h2>
<p>Throughout the 1980s, AIDS activists and patients fought to change the clinical trials system. Dying from what was then a terminal illness, many people with AIDS insisted on the right to access experimental drugs that had successfully passed Phase I clinical trials.</p>
<p>Phase I trials are designed to establish the toxicity profile of a particular drug. A <a href="http://www.theguardian.com/society/2006/mar/19/health.medicineandhealth">small group of volunteers</a> (often not more than a handful) test the drug to find out whether it has serious side-effects. They don’t have to be patients, because the objective is to determine what negative effects, if any, the short-term use of the experimental agents could have. </p>
<p>The only option for AIDS patients in the 1980s was to join a post-Phase I placebo controlled trial or go without access to experimental agents that might give them a shot at survival. These drugs trials are <a href="http://www.med.nyu.edu/content?ChunkIID=21849">typically double-blind</a>. Double-blind means that neither the doctors nor the patients know who receives the experimental agent and who receives the placebo. This aims to eliminate any bias that might arise from patients or doctors knowing who receives what.</p>
<p>Taking part in clinical drug trials meant that AIDS patients faced the chance of being assigned to the placebo control group, and not the group receiving the experimental treatment. These patients understood perfectly well the steep odds against these drugs working. But at least there was a chance. The same cannot be said of placebos.</p>
<p>There is a sound methodological reason to test a new experimental agent against a placebo control when we have no gold standard of care. We need to know whether the new agent does better or worse than the existing standard of care. Even in cases where there is no effective or well-developed standard of care we are usually, but not always, justified in undertaking placebo controlled trials. </p>
<p>But, we expect patients participating in clinical trials to be true volunteers. Patients need to choose to participate and give first person voluntary informed consent. </p>
<p>AIDS patients charged that the clinical trials system was essentially coercive. To access experimental treatments, these patients were more or less forced to take part in these clinical trials. If they did not volunteer to participate in a placebo controlled trial, they couldn’t access experimental treatments. </p>
<p>Many patients grew frustrated with this system and, often in collusion with their doctors and pharmacists, <a href="http://www.tandfonline.com/doi/full/10.1080/15265161.2014.957626#.VFuPor6JnzI">lied and cheated</a> to access particular clinical trials. They analyzed who got placebos and who got the experimental drugs, and shared the drugs. Patients dropped out of clinical trials they believed offered trial designs not conducive to their own survival. Controlled trials become nearly impossible under such circumstances. </p>
<p>Undoubtedly this made it harder to get a sense of what drugs worked and what didn’t and may have delayed the development of life-preserving anti-HIV medication. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/64152/original/2mvcvwms-1415639478.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/64152/original/2mvcvwms-1415639478.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=165&fit=crop&dpr=1 600w, https://images.theconversation.com/files/64152/original/2mvcvwms-1415639478.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=165&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/64152/original/2mvcvwms-1415639478.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=165&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/64152/original/2mvcvwms-1415639478.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=207&fit=crop&dpr=1 754w, https://images.theconversation.com/files/64152/original/2mvcvwms-1415639478.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=207&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/64152/original/2mvcvwms-1415639478.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=207&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Drug companies control access to experimental treatments.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/t_trace/3028211311">Taiyo FUJII/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<h2>Right to try, but not right to access</h2>
<p>Since the 1980s special access protocols have been implemented in the United States, Canada and other countries. These protocols meant to ensure that catastrophically ill patients can access experimental agents outside the clinical trials’ system. </p>
<p>At least in theory. In practice, things are different. Right to try laws do not guarantee the right to access experimental treatments. Even with laws in place, access is still controlled by drug manufacturers. </p>
<p>In Canada the government permits people with terminal illnesses to access drugs that are in the clinical trials system, and they can do so without having to participate in the trials. In return they promise to have their doctors monitor the impact of the drug carefully and report it back to the manufacturer or whoever runs the clinical trial. </p>
<p>Access to these treatments depends on the goodwill of pharmaceutical companies keen on recruiting patients into their clinical trials. Drug manufacturers effectively coerce terminally ill patients into their trials by refusing access to the experimental agents. Experimental drugs are sometimes released outside of clinical trials on <a href="http://link.springer.com/article/10.1007/s11673-014-9580-x">so-called</a> compassionate grounds, but that doesn’t always happen. </p>
<p>And who pays for these experimental treatments? For good reasons insurance plans in the US (or, in Canada, government programs assisting uninsured patients) will not pay for drugs that are untested and are not known to work. As a result of this patients in both Canada and the US must pay out of pocket for these experimental agents. </p>
<p>Pharmaceutical companies are free to charge whatever they wish for these agents, and so, arguably, are in a situation to exploit financially desperate dying patients. This also gives them an opportunity to deny patients access in order to coerce them into trial participation. Regulators need to look at this problem as a matter of urgency. </p>
<p><strong><em>For another view of the ethics of right to try laws see: <a href="https://theconversation.com/right-to-try-laws-are-compassionate-but-misguided-33440">‘Right to try’ laws are compassionate, but misguided</a></em></strong></p><img src="https://counter.theconversation.com/content/33884/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Udo Schüklenk 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>In the last six months Colorado, Louisiana, Missouri, Michigan and, most recently, Arizona have passed “right to try” laws that allow terminally ill patients to access treatments that have only passed…Udo Schüklenk, Ontario Research Chair in Bioethics and Public Policy, Queen's University, OntarioLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/334402014-10-30T09:46:31Z2014-10-30T09:46:31Z‘Right to try’ laws are compassionate, but misguided<figure><img src="https://images.theconversation.com/files/63058/original/dnfjxjkq-1414519462.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">What if an experimental treatment seems to hold a terminal patient's only hope?</span> <span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-58807303/stock-photo-time-for-a-refill.html?src=csl_recent_image-2">Pill bottle image via www.shutterstock.com</a></span></figcaption></figure><p>On November 4, the state of Arizona will decide whether to join Colorado, Missouri, Louisiana and Michigan in passing so-called right to try laws. If passed, the “Arizona Terminal Patients’ Right To Try” ballot referendum will grant terminally-ill patients access to experimental treatments that the US Food and Drug Administration (FDA) has not yet approved.</p>
<p>If approved, patients could access drugs, biological products or devices that have successfully passed only <a href="http://www.nlm.nih.gov/services/ctphases.html">Phase I clinical trials</a>, which are conducted in a small group of volunteers to determine things like side effects and toxicity. Normally, drugs must then advance through further, more rigorous testing before securing FDA approval.</p>
<p>This ballot measure has worthy intentions and highlights certain misgivings inherent in the current system for approving drugs in the United States. That said, neglecting the FDA’s role in guaranteeing drugs that are safe and effective is inappropriate. </p>
<h2>What right to try would skip</h2>
<p>The intent of Phase I testing is <strong>not</strong> to directly benefit patients, but to evaluate a drug’s maximum tolerated dose, its safety and its side effects as determined by testing in a small number of volunteers. Subsequent testing to assure that drugs are actually effective – especially in larger numbers of patients – can take years to complete. For patients who are dying this can present a significant and, at times, insurmountable hurdle. </p>
<p>The <a href="http://web.archive.org/web/20140927195938/http://www.azsos.gov/election/2014/Info/PubPamphlet/english/prop303.htm">Arizona referendum</a> requires each patient to provide informed consent for the use of the still-under-investigation treatment. It states the probable risk associated with the agent must not exceed the probable risk from the patient’s disease. In the absence of adequate testing, it’s unclear how such a determination can be reached or how patients can provide fully informed consent.</p>
<h2>Experimental drug ≠ miracle drug</h2>
<p>Importantly, experimental drugs may result in harm. For example, in the early 1990s, <a href="http://www.cancer.gov/cancertopics/factsheet/Therapy/bone-marrow-transplant">autologous bone marrow transplantation</a> was adopted for certain patients with metastatic breast cancer based on yet-to-be substantiated early-phase clinical trial <a href="http://www.ncbi.nlm.nih.gov/pubmed/7595697">evidence</a>. Ultimately, this treatment proved unsuccessful. Subsequent trials <a href="http://www.ncbi.nlm.nih.gov/pubmed/10768448">showed</a> it to have no benefit and were unable to recreate the findings suggested by the original trial that was found to have been poorly designed. Some patients actually did much worse, including some who died.</p>
<p>What was meant as a compassionate step aimed to help those who were in the greatest need – vulnerable patients who understandably may be willing to try anything – backfired and had serious repercussions.</p>
<h2>Current access to experimental drugs</h2>
<p>Presently, terminal patients interested in using a non-clinically proven agent must petition the FDA through a program called <a href="http://www.fda.gov/ForPatients/Other/ExpandedAccess/ucm20041768.htm">compassionate use</a>. The FDA decides each petition on a case-by-case basis; even when it finds in favor of patients, the process can take time, time that some patients may not have.</p>
<p>At heart, like the right to try bills that preceded it, the Arizona referendum remains a compassionate use program. The difference is that it removes the FDA from the calculus.</p>
<h2>Complications</h2>
<p>Even with a right to try law, patients and doctors would still need to petition the drug company, which is under no obligation to release the experimental drug. In fact, companies may balk at doing so. Releasing treatments early could compromise ongoing trials of the agent and prove quite costly. Often companies only produce a very limited supply of drugs under development and may have little if any additional supply to offer for compassionate use.</p>
<p>Another concern is that by bypassing the existing approval process, some drugs that may not be safe and ready for widespread use will suddenly have an avenue to be tried without fear of consequences. Some manufacturers might see this as a way to test their drugs in a way that they otherwise would not be able to. Companies might petition doctors to refer terminal and potentially desperate patients who may not be ideal candidates for a particular drug. One might also imagine doctors being offered certain incentives to do so.</p>
<h2>Redesigning the approval process</h2>
<p>The plight of terminal patients is a tragic one – especially when a treatment in development that holds the promise for potential benefit is beyond their reach. In such cases, one might imagine revamping certain aspects of clinical trials for terminally ill patients who have few, if any, meaningful options to extend their lives.</p>
<p>When a particular experimental treatment has relatively few side effects and/or a significantly positive response, perhaps it makes sense to relax access. Here’s what I propose:</p>
<ul>
<li><p>Instead of randomizing patients as is typically practiced whereby one patient receives the experimental drug and one patient the control, we should consider allowing more patients to receive the experimental drug, say in a 2:1 or a 3:1 randomization.</p></li>
<li><p>Once a drug begins to show promise, trials could be designed to look for more modest outcomes. It should also be easier for patients randomized either to a placebo or to standard treatment to receive the experimental agent. This can be accomplished when a clinical trial is designed as a crossover trial, in which all patients eventually receive both treatment options. </p></li>
<li><p>These types of decisions should involve affected stakeholders as well as public discussion and comment. </p></li>
</ul>
<p>Especially when considering yet-to-be proven experimental interventions, although understandable, right to try laws miss the target. Greater emphasis should focus on the duty of physician-researchers to help patients and their surrogates distinguish realistic from unrealistic hope while maintaining reasonable expectations.</p>
<p><strong><em>For another view of the ethics of right to try laws see: <a href="https://theconversation.com/should-dying-patients-have-the-right-to-access-experimental-treatments-33884">Should dying patients have the right to access experimental treatments?</a></em></strong></p><img src="https://counter.theconversation.com/content/33440/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Yoram Unguru 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>On November 4, the state of Arizona will decide whether to join Colorado, Missouri, Louisiana and Michigan in passing so-called right to try laws. If passed, the “Arizona Terminal Patients’ Right To Try…Yoram Unguru, Assistant Professor of Oncology at the School of Medicine, Johns Hopkins UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/321942014-10-09T09:48:39Z2014-10-09T09:48:39ZHow thalidomide became one of the most talked about drugs in cancer therapy<figure><img src="https://images.theconversation.com/files/61148/original/mgh69qc7-1412762862.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Dark past, but looking to the future.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/darwinbell/83485181/sizes/l/in/photolist-8nTeF-cUBoE-5CsLU-51yd8-51zgZ-5YsFg-51ydb-pvJee-51fBf-51g22-51g2o-89wk4-5jWYi-32s4Vq-5jWYj-6yaxcK-cUsC6-5jWY5-7ShPi-5jWUG-4QQyU-poQBe-5jWYc-4R5DR-finwZ-5jWY8-8rULmn-AQi4b-6NeWvg-aYzhn-aDCgG-5sBGy-5sBFR-4R5G8-eWAkXy-4QQPs-4QQsD-4R5EV-PftQA-4R5CT-AVdp3-KdeGV-eWoUrK-eWAjJb-eWoRRc-eWAiaC-eWAmQb-eWoSTa-eWoTp2-fabdxH-5v8G9/">Darwin Bell</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span></figcaption></figure><p>Innovative new drugs to treat cancer frequently make the headlines, either due to great success or controversy, as pharmaceutical companies get lambasted for selling the drugs at too high a price for state systems to afford.</p>
<p>But alongside this high-budget pharmaceutical research is a different tactic being quietly waged in the background: investigating old, inexpensive drugs, originally designed for a variety of maladies, to see whether they might be able to treat cancer – essentially, repurposing old for new. </p>
<figure class="align-left ">
<img alt="" src="https://images.theconversation.com/files/61152/original/m5q98rwm-1412764022.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/61152/original/m5q98rwm-1412764022.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=452&fit=crop&dpr=1 600w, https://images.theconversation.com/files/61152/original/m5q98rwm-1412764022.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=452&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/61152/original/m5q98rwm-1412764022.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=452&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/61152/original/m5q98rwm-1412764022.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=568&fit=crop&dpr=1 754w, https://images.theconversation.com/files/61152/original/m5q98rwm-1412764022.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=568&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/61152/original/m5q98rwm-1412764022.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=568&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">What else can these do?</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/epsos/8119248181/sizes/l/in/photolist-dntgBB-f4ozF8-eprZZH-7YJenQ-5ybjn2-9z7Esb-9bH4ur-2WWySF-7V1PRy-jR9gc-8Pomnt-oeNsPd-ovZbTK-aj2pWe-nS1dkA-oH4rdU-nRPvDM-nVncj9-nvA252-nui5G2-nHZFqF-ntBYA4-sCTxH-5fWrqu-oKTyND-oK4qob-nSw4Bx-nsjjC9-9d5WGV-4M7pV-nMoT1j-oDVBBT-6q9iv9-ncFSjE-aBH2Bg-nMdbka-78ePNM-bkbW8T-5S73oK-7kihrz-dErKR5-cqiNS1-c5Q5eb-vhNSP-4xWFPc-8c3Ug-4cXa6D-4VnZrY-8deFCr-4nVDsE-9Xcshz/">epSoS.de</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>Repurposing Drugs in Oncology (ReDO), the international organisation aimed at promoting work in this area, defines repurposing as “the use of existing and well-characterised non-cancer drugs as new treatments for cancer.” ReDO believes that such drugs “may represent an untapped source of novel therapies”. Current candidates include diclofenac, an anti-inflammatory pain relief medication; clarithromycin, an antibiotic; and cimetidine, an antacid prescribed for stomach ulcers.</p>
<p>Cancers are increasingly being treated <a href="https://theconversation.com/how-science-is-using-the-genetics-of-disease-to-make-drugs-better-30747">on the basis of the mutations</a> that cause them, rather than where they are located. Seemingly distinct and unrelated cancers can arise due to the same genetic defect. Developing new drugs that target these mutations in a way that largely spares healthy cells is far from serendipitous and involves complex mathematical modelling and tens of thousands of laboratory hours to achieve even a prototype drug. All of this costs time and money.</p>
<p>Some researchers are shunning this process and instead turning to well-established drugs to improve cancer treatment. And it is an approach that is paying dividends.</p>
<h2>Rehabilitating thalidomide</h2>
<p>Infamous thalidomide, regrettably used to treat morning sickness in the late 1950s was catastrophic for developing foetuses and responsible for the birth of thousands of disabled babies. But despite this dark past, the potentially beneficial properties of thalidomide are being re-explored and it is currently one of the most talked about drugs in cancer therapy. More than 700 thalidomide clinical trials are currently registered in almost every cancer type imaginable and it is currently approved to treat a blood cancer called myeloma. </p>
<p>Although it isn’t fully understood how thalidomide works in cancer treatment, it is known to prevent the growth of new blood vessels, which can “starve” tumours and potentially cause them to shrink. There are other drugs which have similar properties, but many are expensive and come with a range of side effects. Thalidomide on the other hand is off-patent, cheap and relatively well evaluated.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/61151/original/5n8b5tzb-1412763695.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/61151/original/5n8b5tzb-1412763695.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/61151/original/5n8b5tzb-1412763695.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/61151/original/5n8b5tzb-1412763695.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/61151/original/5n8b5tzb-1412763695.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/61151/original/5n8b5tzb-1412763695.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/61151/original/5n8b5tzb-1412763695.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">100 years and counting.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/aussiegall/4348697776/sizes/o/in/photolist-7ChdkS-5ACir-7fn1Ft-4iLkgb-9LVvkB-tAaQq-fxujXU-cokKLq-78dgxd-h6z1w2-khpF-fwpPW9-cncHUQ-cncZzy-Lox5K-bEDEz-v3Xxa-ds1TVY-7Vj6Lr-ab3wqX-cAb6zJ-9Wokj2-52Qb71-v9xvx-v9xvv-djNqXn-byWuu7-5baT2d-5b6A8K-ePr6yC-5ADPN-8PZkgJ-5ADSo-5NXog6-HGkW3-7FiETN-5E5bgc-64tE2t-ai718R-7TLnqF-61arse-v9Vv7-9wmVPN-CLqJJ-eiS8ev-4TzZPs-zpZn-3BrDcE-A6VD4-4dyUn6-5YcGKD/">Aussie Gall</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>Aspirin, available commercially for more than a century, has also been investigated not only for its potential use in cancer treatment, but also in prevention. <a href="https://theconversation.com/profiles/jack-cuzick-97158">Jack Cuzick</a>, director of the centre for epidemiology at Queen Mary, University of London, <a href="http://annonc.oxfordjournals.org/content/early/2014/07/30/annonc.mdu225.abstract">led a research project</a> which earlier this year convincingly showed that daily aspirin reduces the risk of developing a variety of cancers and reduces the risk of dying from colon cancer by 40%. Cuzick practises what he preaches and has been taking aspirin daily for years, stating GPs “absolutely should recommend daily aspirin to all those over 50”.</p>
<p>These kinds of discoveries are not always made using educated guesses, and scientists often test thousands of drugs just to see if anything might work. Researchers at St Jude’s Children’s Hospital in the US <a href="http://www.stjude.org/stjude/v/index.jsp?vgnextoid=f582ccc3e3d77410VgnVCM100000290115acRCRD&vgnextchannel=363f2eecbf537410VgnVCM100000290115acRCRD&sc_cid=smd10029&sc_spid=92535816&linkId=9850037">recently tested</a> 1,300 existing medicines on medulloblastoma cells (a type of childhood brain cancer) in the lab. Two drugs typically used to treat breast cancer – gemcitabine and pemetrexed – were found to effectively kill these cells. A clinical trial has now been set up and researchers hope to improve a dismal cure rate of 40% in children with hard-to-treat medulloblastoma.</p>
<h2>Grunt work already done</h2>
<p>Alan Worsely, head of science communication for Cancer Research UK, said: “The advantage of re-using an existing drug is that much of the early work to find the correct dose of a treatment and discover any potential side effects is already done, so researchers can get on with finding out whether it can help cancer patients.”</p>
<p>Increasingly cheaper and quicker genetic testing methods mean that researchers are also now able to analyse the DNA of patients who respond atypically to normally successful treatments to figure out why. Childhood acute lymphoblastic leukaemia is one of <a href="http://leukaemialymphomaresearch.org.uk/patient-information/facts-blood-cancers">the success stories</a> of modern cancer treatment – 90% of children now survive for the long term. However, this still leaves 10% of patients who still die from the disease, mainly due to a relapse, which is very hard to treat. </p>
<p>Julie Irving, a reader in experimental haematology at Newcastle University <a href="http://www.bloodjournal.org/content/early/2014/09/23/blood-2014-04-531871.long?sso-checked=true">recently published research</a> showing that a drug called selumetinib, originally designed for tackling a faulty cell growth controlling pathway in lung and colon cancer, could be used to help children who relapse after treatment for acute lymphoblastic leukaemia but who also have the same faulty pathway.</p>
<p>The development of a new cancer therapy can cost <a href="http://www.sbns.org.uk/index.php/research/why-do-research/">upwards of a billion pounds</a> and take up to 15 years from initial development to reach patients. Mining the resource of thousands of “old” off-patent drugs is proving to be an important avenue in cancer treatment – and one which must be fully embraced by doctors and scientists.</p><img src="https://counter.theconversation.com/content/32194/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Victoria Forster 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>Innovative new drugs to treat cancer frequently make the headlines, either due to great success or controversy, as pharmaceutical companies get lambasted for selling the drugs at too high a price for state…Victoria Forster, Postdoctoral Research Associate in Cancer Research, Newcastle UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/304292014-08-12T15:31:21Z2014-08-12T15:31:21ZWHO Ebola ethics panel excluded those most affected<p>The World Health Organisation has been in a rush to deal with the Ebola outbreak in West Africa. Last week it declared it an international health emergency, and after two infected US doctors <a href="https://theconversation.com/we-need-to-fast-track-clinical-trials-of-new-drugs-to-treat-ebola-in-africa-30299">were given an experimental drug</a>, it also convened an “<a href="http://www.who.int/csr/disease/ebola/lop-ethics.pdf?ua=1">ethics panel</a>” to address the use of unregistered interventions for Ebola disease. </p>
<p>In a <a href="http://www.who.int/mediacentre/news/statements/2014/ebola-ethical-review-summary/en/">subsequent statement</a>, the WHO said drugs unproven in humans could be used on Ebola patients:</p>
<blockquote>
<p>In the particular circumstances of this outbreak, and provided certain conditions are met, the panel reached consensus that it is ethical to offer unproven interventions with as yet unknown efficacy and adverse effects, as potential treatment or prevention.</p>
<p>Ethical criteria must guide the provision of such interventions. These include transparency about all aspects of care, informed consent, freedom of choice, confidentiality, respect for the person, preservation of dignity and involvement of the community.</p>
</blockquote>
<p>Given that ethics is so central to this discussion and that deploying experimental agents in a population is <a href="https://theconversation.com/we-need-to-fast-track-clinical-trials-of-new-drugs-to-treat-ebola-in-africa-30299">fraught with difficulty</a>, it’s strange that the ethics panel it put together wasn’t really one at all. Only few of the panelists had any professional background in bioethics or medical ethics. Representatives from the countries affected by Ebola were also missing in action; the WHO added panelists from Japan, Australia, Canada and for good measure Saudi Arabia, but no one from the countries actually affected. Women were also under-represented on the panel.</p>
<p>HIV/AIDS activists fought hard in the early days of the AIDS epidemic to ensure that people affected by the disease are today represented on these kinds of panels. WHO saw it fit to do without. A remarkable turn of events. </p>
<p>Some of those on the panel may have expertise on Ebola, but with a large body of academic literature out there on the two relevant issues, namely ethics of access to experimental drugs in case of catastrophic illness and the ethics of resource allocation, the top names in bioethics and medical ethics that deal pretty much only with these issues, weren’t included on the panel. As Greg Moorlock <a href="https://theconversation.com/mistakes-in-moral-reasoning-are-as-lethal-as-medical-errors-21813">has argued previously</a> on The Conversation, this happens all too often when big decisions are being made. </p>
<p>It may well be, as some have argued, that getting African panelists at such short notice to Geneva might have been impossible due to visa constraints and similar unfortunate matters. But with some panellists participating virtually via Skype or some other video conferencing tools, it would no doubt have been possible to include some West African representatives from countries affected by Ebola. </p>
<p>The problem with haphazard activism such as that displayed by WHO is that it destroys credibility and trust. There is already a high degree of distrust of foreign aid workers in the countries affected. Talkfests, where others in Switzerland discuss what should or should not happen with access to experimental agents for people in countries of the global south but who are not at the table, is the last thing needed now.</p>
<p>One could counter that the WHO has been responding, however imperfectly, to a health emergency and that it needed to press ahead. But actually at this point in time, there isn’t an experimental agent to be distributed: the company that produced ZMapp, the drug used on the two US health workers (who have since recovered) and a Spanish missionary (who died), <a href="http://www.nbcnews.com/storyline/ebola-virus-outbreak/bioethicist-ebola-treatment-west-troubling-bad-science-n178026">has said it is out of stock</a>. </p>
<p>The Nigerian government <a href="http://www.theguardian.com/society/2014/aug/07/ebola-patients-west-africa-denied-experimental-drugs-us-nigeria">also recently said</a> that Nigerians wouldn’t be able to access the drug for at least a few months because the drug existed only in such small amounts. </p>
<p>In other words, there was no need for such a rush as far as assembling this panel was concerned. </p>
<p>Experimental agents may be used under certain ethical circumstances, which the WHO knows. And the ethics and regulatory frameworks guiding access in many countries are more sophisticated than the statement of good things the WHO panel produced. Decisions about the how and when should be the responsibility of national jurisdictions and negotiations between nation states. If there wasn’t this exotic thing called Ebola that has triggered a worldwide moral panic, demanding “action”, no doubt we would have been spared this expert statement.</p>
<p>Considering that Ebola constitutes an international public health emergency, other ethical issues such as <a href="https://theconversation.com/nigeria-was-slow-to-act-on-ebola-it-now-needs-stricter-measures-to-contain-it-30324">compulsory confinement</a> of infected people or the <a href="http://www.trust.org/item/20140812100106-n07mx">professional obligations of medical personnel</a> to patients would have been more appropriate issues for a WHO ethics panel to discuss but weren’t.</p>
<p>I suspect that the WHO wanted to be seen to be doing something. To its credit it put <a href="https://theconversation.com/mistakes-in-moral-reasoning-are-as-lethal-as-medical-errors-21813">ethics at the forefront</a> of its thinking about the crisis. Alas, it chose the wrong topic at the wrong point in time and arguably, by and large, the wrong people to do so. </p><img src="https://counter.theconversation.com/content/30429/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Udo Schüklenk 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 World Health Organisation has been in a rush to deal with the Ebola outbreak in West Africa. Last week it declared it an international health emergency, and after two infected US doctors were given…Udo Schüklenk, Ontario Research Chair in Bioethics and Public Policy, Queen's University, OntarioLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/163342013-07-25T13:28:51Z2013-07-25T13:28:51ZUsing nano gold to patch up broken hearts<figure><img src="https://images.theconversation.com/files/27926/original/593py3yh-1374587010.jpg?ixlib=rb-1.1.0&rect=0%2C1%2C1024%2C755&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Gilded patches can now aid the growth of heart tissue</span> <span class="attribution"><span class="source">Findingthenow</span></span></figcaption></figure><p>Gold is one of our most valuable commodities but its use extends far beyond jewellery and gold bars. It’s a conductive material and is helping us to develop new medical innovations such as specialised <a href="http://pubs.rsc.org/en/Content/ArticleLanding/2013/TB/c3tb20584c">patches that could be used to grow</a> new heart tissue following a heart attack.</p>
<p>Heart attacks are caused by an abrupt blockage of one or more of the blood vessels that supply blood to the heart. This immediately reduces the supply of nutrients and oxygen to the heart muscle and if the blood flow is not restored quickly, causes irreversible death of the cells and eventually affects the performance of the heart muscle. </p>
<p>Unlike cells in the liver, heart cells can’t multiply. And although the heart contains few stem cells - “mother cells” that have the potential to become any type of cell in the body - their amount is not enough to repair the tissue damaged by a heart attack.</p>
<p>Because of this, the damaged tissue following a heart attack can become tough and fibrous and the efficiency of the heart to pump blood to the rest of the body is reduced. This eventually leads to end-stage heart failure, when treatment becomes difficult, and can lead to a patient’s death.</p>
<p>Currently the only therapeutic option available to treat patients with terminal end-stage heart failure is a heart transplant. However, the scarcity of cardiac donors has led to an urgent need to develop new experimental treatments.</p>
<p>One biomaterial that we’re working on to restore heart function is a special <a href="http://pubs.rsc.org/en/Content/ArticleLanding/2013/TB/c3tb20584c">cardiac “patch” that utilises gold</a> to help stimulate tissue growth. </p>
<p>These patches are three-dimensional biomaterials that work like temporary scaffolds to support cells and promote their reorganisation into functional tissue. After they are transplanted into the body, the patch integrates with the heart’s own tissue and improves its function.</p>
<h2>Using gold to mimic ‘electrical wiring’</h2>
<p>The heart can contract when electrical stimulation from one cell spreads to neighbouring cells. This allows the cells to beat and contract together, efficiently pumping blood to the rest of the body. For the patches to work we also need to mimic the native “electrical wiring” of the heart cells. This can trigger the cells to organise into functioning heart tissue that could be transplanted.</p>
<p>Most of the biomaterials that cardiac patches are made from are non-conductive. So the scaffold basically blocks electrical signals from travelling from one beating cell to neighbouring cells, making it extremely difficult to get them all to beat in unity.</p>
<p>In our work, we are using nano fibres covered with gold nano particles - the size of one billionth of a metre - to conduct the electrical signalling.</p>
<p>As the gold increases the connectivity of the engineered scaffold, cells grown on these scaffolds are also able to mature into functioning tissue, contracting with a greater force, rate and uniformity when compared to cells grown on other kinds of scaffolds.</p>
<p>This has all been done in a lab, but the next step is to test the potential of the engineered gold-incorporated scaffolds to restore heart function after a heart attack in an animal model. If successful, it will provide the first step to creating functioning, transplantable heart tissue that can eventually be used to treat human patients.</p><img src="https://counter.theconversation.com/content/16334/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Michal Shevach has received funding from the Marian Gertner Institute for Medical Nanosystems Fellowship, The Tel Aviv University Center for Nanoscience and Nanotechnology. The work is part of her doctoral thesis at Tel-Aviv University</span></em></p>Gold is one of our most valuable commodities but its use extends far beyond jewellery and gold bars. It’s a conductive material and is helping us to develop new medical innovations such as specialised…Michal Shevach, PhD Student, Tel Aviv UniversityLicensed as Creative Commons – attribution, no derivatives.