tag:theconversation.com,2011:/us/topics/glaxosmithkline-7480/articlesGlaxoSmithKline – The Conversation2016-11-21T20:53:54Ztag:theconversation.com,2011:article/571752016-11-21T20:53:54Z2016-11-21T20:53:54ZHow changing drug patent rules will affect developing nations<p><em>After years of legal battles, a global agreement has been reached for developing countries to buy – and for drug manufacturers to produce or import – generic medicines without <a href="http://www.pharmaceutical-journal.com/news-and-analysis/news/worlds-poorest-countries-dont-need-to-protect-drug-patents-until-2033-agrees-wto/20200017.article">breaching patent rules</a>. The Conversation Africa’s Health and Medicine Editor Candice Bailey asked Natalie Schellack to explain what this means for the developing world.</em> </p>
<p><strong>Are drugs about to become cheaper for poor people in developing countries? Why?</strong></p>
<p>Through the World Trade Organisation an agreement was reached in November 2015 for the world’s poorest countries to buy –- and for drug manufacturers to produce or import –- generic medicines without breaching patent rules until <a href="http://www.pharmaceutical-journal.com/news-and-analysis/news/worlds-poorest-countries-dont-need-to-protect-drug-patents-until-2033-agrees-wto/20200017.article">January 1 2033</a>. The decision was taken by the organisation’s Council for Trade-Related Aspects of Intellectual Property Rights <a href="http://www.ip-watch.org/2016/10/31/brazil-china-india-south-africa-put-un-high-level-panel-medicines-access-trips-council-agenda/">(TRIPS)</a>.</p>
<p>Put simply, the need of a nation trumped the right to derive protected benefit from a patent. This initiative will help developing countries come up with better policies. It will provide legal certainty, which should lead to better access and more affordable drug prices. </p>
<p>The agreement is good news for all countries in the Southern African Development Community as members of the World Trade Organisation (with the exception of the Seychelles). They’ll be able to incorporate the TRIPS agreement into their national laws. The community’s protocol on Trade confirms this <a href="https://www.wto.org/english/thewto_e/countries_e/south_africa_e.htm">position</a>. </p>
<p>South Africa, as a signatory to the TRIPS agreement, is allowed to pass intellectual property legislation, inclusive of patent laws, so that intellectual property rights do not become barriers to legitimate trade while ensuring the technology is transferred and disseminated in line with <a href="http://apps.who.int/medicinedocs/documents/s18249en/s18249en.pdf">social and economic welfare</a>.</p>
<p>If South Africa actively participates in this opportunity for more generic trade, medicines should be more affordable. </p>
<p>South Africa has been fighting for access to generic drugs for some time. In the late 1990s around 40 big pharmaceutical companies such as GlaxoSmithKline and Boehringer Ingelheim filed a lawsuit to the Pretoria High Court against the South African government due to the importation of generic anti-retroviral medicine to treat the <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1119675/">HIV/AIDS pandemic</a>.</p>
<p>Millions of people were suffering from HIV/AIDS and could not afford the original brand-name medicines. The South African state was trying to find a way to guarantee their health. After three years the court overruled the patent law in this case and recognised the right to health as a basic human right of <a href="http://i-base.info/htb/4380">South African patients</a>. </p>
<p><strong>How do patents affect prices?</strong> </p>
<p>A patent in this context is when a pharmaceutical company develops a new drug for a disease. The company sells it under a “brand name”. The patent protects the pharmaceutical company’s right to manufacture and market the drug to profit from it. This helps recover the costs that have gone into developing the drug. </p>
<p>In most cases the drug patent is awarded for around 20 years. Once the patent has expired other companies can “copy” and manufacture the drug. </p>
<p>Generic drugs have to be near-identical “copies” of the branded drug. For example, they must be identical– or “bioequivalent”–to a brand name drug in dosage form, safety, strength, route of administration, quality, performance characteristics and intended use. In South Africa this is regulated by the <a href="http://www.mccza.com/documents/d259816c2.30_Biosimilars_Aug14_v3.pdf">Medicine Control Council of South Africa</a>.</p>
<p>For a developing country like South Africa, the most effective and sustainable way to bring down the price of a drug is by driving competition between different generic manufacturers. This can’t be done if a medicine is still under patent and the patent owner is not willing to allow competition. Preventing competition can drive up the price to an artificially high level. </p>
<p>Developing countries can’t afford this. Life-saving treatments for diseases such as HIV/AIDS, tuberculosis and malaria are needed. The price of medicine for people with these diseases is a matter of life or death. </p>
<p><strong>What changes and challenges has South Africa made to patent laws and how could they affect people?</strong> </p>
<p>South Africa’s draft Intellectual Property Protection Policy of 2013 is designed to reform the country’s patent law and to address various shortcomings that hamper access to medicine. The <a href="http://ip-unit.org/wp-content/uploads/2013/09/DRAFT-IP-POLICY.pdf">draft policy</a> provides public health safeguards and promotes cooperation between ministries. And more recently, South Africa’s cabinet approved a new <a href="http://www.thedti.gov.za/news2016/IPConsultativeFramework.pdf">Intellectual Property framework</a>. </p>
<p>The three-year delay in finalising the policy first set out in 2013 has affected the health of certain patients adversely. Two examples stand out. Patients with multidrug-resistant tuberculosis (MDR-TB) struggle to pay for one of the medications they need called linezolid. The hepatitis B medication, entecavir, is another example. It remains inaccessible to most people because it’s so expensive – while generic products are available outside South Africa at prices that are around <a href="http://www.fixthepatentlaws.org/?p=1080">84% lower</a>.</p>
<p>Once the policy becomes law, South Africa could be a role model for the rest of the world in prioritising people’s health over profit. </p>
<p><strong>What more needs to be done?</strong> </p>
<p>The process of finalising the Intellectual Property Protection Policy needs to be treated with urgency. The Department of Trade and Industry and all ministries involved must continue to prioritise turning it into law. </p>
<p>This will mean more affordable medicines can become available. </p>
<p>But there are other steps that can be taken too. </p>
<p>The most effective and sustainable way to bring down the price of a drug is through competition between manufacturers. </p>
<p>Investment is also needed. This can be promoted by having large pharmaceutical companies invest directly in South Africa to boost local production of medicines.
And the approval process for new medicines should be streamlined by the <a href="http://www.mccza.com/">Medicine Control Council</a>.</p>
<p>Another market in South Africa that should get more attention is clinical trial research. This would not only allow research into conditions inherent to South Africa, it would also be an investment in local specialists.</p>
<p>The distribution of medicines throughout South Africa by the National Department of Health should be streamlined to avoid medicines being unavailable. One solution could be to transfer logistical and distribution costs of medicines to the suppliers to avoid delays, additional transport costs and stock-outs.</p><img src="https://counter.theconversation.com/content/57175/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Natalie Schellack 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>After nearly two decades of legal battles and negotiations, South Africa is moving to cut the cost of medicines with policies to increase imports and local production of generic drugs.Natalie Schellack, Associate Professor and Course Leader: Post Graduate Programmes in Clinical Pharmacy in the Department of Pharmacy, Sefako Makgatho Health Sciences UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/474712015-09-17T00:06:25Z2015-09-17T00:06:25ZAntidepressant trial’s upended results show need for sharing all data<figure><img src="https://images.theconversation.com/files/95095/original/image-20150916-6275-1k24jtj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Our re-analysis
found significant increases in harms with both the antidpressants used in Study 329, compared to the placebo. </span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/destinysagent/1778953537/">Steve Smith/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span></figcaption></figure><p>In 2001, <a href="http://www.dcscience.net/keller-2001-paroxetine.pdf">a “landmark” study published</a> in the prestigious <a href="http://www.jaacap.com/article/S0890-8567%2809%2960309-9/abstract">Journal of the American Academy of Child and Adolescent Psychiatry</a> purported to show the safety and effectiveness of using a common antidepressant to treat adolescents. But soon after its publication, both researchers and journalists raised questions about the research. And in an <a href="http://www.bmj.com/cgi/doi/10.1136/bmj.h4320">article we published today</a> in the BMJ, we’ve shown that the original published findings were biased and misleading. </p>
<p>Known as Study 329, the randomised controlled trial compared paroxetine (Paxil, Seroxat, Aropax, among other brand names) with a placebo and an older antidepressant (imipramine) for treatment of adolescent depression. It was funded by SmithKline Beecham – now GlaxoSmithKline (GSK) – the manufacturer of paroxetine. </p>
<p>The research has been repeatedly criticised, and there have been numerous <a href="http://study329.org/request-to-retract-study-329/">calls for it to be retracted</a>. Our study, <a href="http://www.bmj.com/cgi/doi/10.1136/bmj.h4320">Restoring Study 329</a> was conducted under an initiative called <a href="http://www.bmj.com/content/346/bmj.f2865">restoring invisible and abandoned trials</a> (RIAT), which encourages abandoned or misreported studies to be published or formally corrected to ensure doctors and patients have complete and accurate information to make treatment decisions.</p>
<h2>Fundamental problems</h2>
<p>To re-analyse the evidence of effectiveness and safety of paroxetine, we used <a href="http://study329.org/the-data/">documents posted online by GSK</a>, including the <a href="http://www.gsk.com/media/389566/depression_329_full.pdf">clinical study report</a>, which was submitted to the US Food and Drug Administration (FDA) to gain approval for paroxetine to be prescribed to adolescents. We also had access to other <a href="http://www.healthyskepticism.org/global/news/int/hsin2010-01">publicly available documents</a> and individual participant data, as well as other documents provided by GSK. </p>
<p>The <a href="http://www.gsk.com/media/389566/depression_329_full.pdf">clinical study report</a> had significant problems; although it reported more adverse events than <a href="http://www.dcscience.net/keller-2001-paroxetine.pdf">the original article</a>, it omitted many problems our re-analysis found in the case report forms for individual patients.</p>
<p>We found that paroxetine was no more effective than a placebo, which is the opposite of the claim in <a href="http://www.dcscience.net/keller-2001-paroxetine.pdf">the original paper</a>. We also found significant increases in harms with both paroxetine and imipramine. Compared with the placebo group, the paroxetine group had more than twice as many severe adverse events, and four times as many psychiatric adverse events, including suicidal behaviours and self-harm. And the imipramine group had significantly more heart problems.</p>
<p>Our re-analysis has implications beyond Study 329; it has repercussions for all of evidence-based medicine. </p>
<p>First, we identified <a href="http://study329.org/potential-barriers-to-accurate-reporting-of-harms/">ten strategies</a> used by researchers in this clinical trial to minimise apparent harms. This included inconsistent classification of adverse events and ignoring their severity. Several of these strategies <a href="http://www.biomedcentral.com/1472-6904/1/3">can be readily identified</a> in reports of other trials. They influence the apparent safety of drugs, and can be used to present particular drugs in a favourable or unfavourable light. Many of these strategies may also be used to bias reporting of non-drug treatments.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/95094/original/image-20150916-6287-h586q9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/95094/original/image-20150916-6287-h586q9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=473&fit=crop&dpr=1 600w, https://images.theconversation.com/files/95094/original/image-20150916-6287-h586q9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=473&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/95094/original/image-20150916-6287-h586q9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=473&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/95094/original/image-20150916-6287-h586q9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=594&fit=crop&dpr=1 754w, https://images.theconversation.com/files/95094/original/image-20150916-6287-h586q9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=594&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/95094/original/image-20150916-6287-h586q9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=594&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Study 329 compared paroxetine with a placebo and an older antidepressant (imipramine) for treatment of adolescent depression.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/pyxopotamus/2457789657/">me and the sysop/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>Second and more importantly, our findings show influential peer-reviewed research published in leading medical journals can be seriously misleading. And that it’s not possible to adequately scrutinise trial outcomes, particularly in relation to harms, simply on the basis of what’s written in the body of clinical study reports, which can contain important errors. </p>
<p>We know that selective reporting is <a href="http://www.nejm.org/doi/full/10.1056/NEJMsa065779">common in psychiatric literature</a>. And there are clearly no grounds to believe that such misrepresentation is restricted to psychiatric studies. </p>
<h2>Lessons for all</h2>
<p>It’s clear to us now that access to full individual patient level data, backed up by case report forms and the pre-specified protocols, are required to judge the validity of published reports of clinical trials. Only that degree of detail allows independent researchers to check how harms are recorded and reported. And whether researchers involved in clinical trials have accurately reported outcomes. </p>
<p>Our re-analysis was demanding because we were breaking new ground. And it was extremely time consuming because the data made available to us by GSK was <a href="http://www.bmj.com/content/349/bmj.g4353">in a form</a> that made our work highly inefficient. But we have now established a methodology for this kind of work. And it’s clear that if data are provided in a user-friendly format, it’ll be possible for researchers to carry out similar re-analyses reasonably inexpensively. </p>
<p>If other trials are found to contain similar errors – whether intentional or inadvertent – it might be time to change the requirements for submissions to drug regulators (such as Australia’s <a href="https://www.tga.gov.au/">Therapeutic Goods Administration</a>, the US <a href="http://www.fda.gov/">FDA</a>, and the <a href="http://www.ema.europa.eu">European Medicines Agency</a>), who are responsible for evaluating the safety and efficacy of prescribed drugs. </p>
<p>Indeed, if other re-analysis reach the sort of conclusions we did, it should become clear to editors of medical journals that trial results should not be published unless all the data are available for independent scrutiny both before and after publication. Peer reviewers also need to become far more critical of manuscripts they review.</p>
<p>Undoubtedly, there would be resistance to such changes. But scrutiny is warranted for drugs that are likely to be prescribed to millions of patients with potentially adverse outcomes and limited benefits.</p><img src="https://counter.theconversation.com/content/47471/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jon Jureidini was a founding member of Healthy Skepticism, and has provided expert analysis and opinion for plaintiffs about Study 329 and Forest’s paediatric citalopram randomised controlled trials.</span></em></p><p class="fine-print"><em><span>Melissa Raven was a founding member of Healthy Skepticism. </span></em></p>As part of an intiative to re-examine misrepresented or abandoned studies, we re-analysed an antidepressant trial. Here’s what we found.Jon Jureidini, Research Leader, Critical and Ethical Mental Health research group, Robinson Research Institute, University of AdelaideMelissa Raven, Postdoctoral research fellow, University of AdelaideLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/190202013-10-09T12:31:31Z2013-10-09T12:31:31ZNew malaria vaccine has its flaws, but it’s better than nothing<figure><img src="https://images.theconversation.com/files/32749/original/839whnmj-1381317522.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Malaria prevention is going beyond the mosquito net.</span> <span class="attribution"><span class="source">Gates Foundation</span></span></figcaption></figure><p>The announcement that GlaxoSmithKline (GSK) aims to <a href="http://www.bbc.co.uk/news/health-24431510">register a malaria vaccine</a> came on the same day Peter Higgs and Francois Englert were awarded the <a href="https://theconversation.com/nobel-prize-in-physics-goes-to-discovery-of-the-higgs-boson-19014">Nobel prize in physics</a> for predicting the existence of the Higgs boson particle. </p>
<p>The contrast between abstruse, fundamental physical discoveries and children dying from malaria couldn’t be greater. The 30 year struggle to develop and test a malaria vaccine has gone on for almost as long as it took physicists to convince themselves that the Higgs boson exists. For malaria, however, the vaccine, known as <a href="http://www.malariavaccine.org/rd-rtss.php">RTS,S</a>, is an important first step, rather than the last word on the subject.</p>
<p>RTS,S is designed to raise antibodies that block malaria parasites from getting to or entering the liver, after mosquitoes first inject the sporozoite - the cell form that infects new hosts - into patients. It comprises part of a protein that coats sporozoites linked to a sequence from Hepatitis B, and is given with an agent designed to stimulate immune responses. </p>
<p>This strategy to engage the immune system in making antibodies seems to work well, but the next step that matters to patients – preventing disease – is harder to achieve. The vaccine succeeds about half the time in reducing the frequency of clinical attacks of malaria, although in the most vulnerable and malaria-exposed infants who were studied, only about a quarter of episodes of malaria were prevented. Generally, vaccines in current use have much higher success rates and are more than 90% effective in preventing disease. They also often work for longer than the three years that RTS,S has been shown to do.</p>
<p>So how should an imperfect vaccine such as RTS,S be used? This is one of the most pressing questions for GSK because it defines which licence will be sought for the vaccine. There was a hope RTS,S could be combined with the conventional vaccination schedules in younger infants (younger than six months) but the efficacy in this group is not as good as it is for older infants. The vaccine is also less effective in those who are exposed to malaria infections more often, a group that therefore need protection more than others. If an older group of infants is to be immunised, then this will have to be done in addition to the conventional vaccinations that children should receive.</p>
<p>The cost of the vaccine is also a consideration. If a child has a one-in-four or a one-in-two chance of benefitting from the vaccine, this means that many children who won’t benefit are going to receive immunisations. Who should pay for this? The vaccine itself has been developed by GSK but with much academic and charitable support. It would be a notably worthy decision if GSK decided to make this vaccine, with all its limitations, freely available to all for whom it is designed rather than levying any costs (be they for production or research). After all, it is the first malaria vaccine that has reached the stage where licencing is contemplated. For a disease that ravages the lives of millions every year, and takes a significant fraction of those, any intervention, however imperfect, is better than none.</p>
<p>There are <a href="http://www.who.int/vaccine_research/links/Rainbow/en/">other vaccine initiatives</a> underway, some with <a href="https://theconversation.com/new-malaria-vaccine-the-first-to-offer-complete-protection-16862">early promise</a>, that suggest better efficacy than RTS,S. But the history of malaria vaccine development is like a long walk in the hills. Just when you think you have reached a summit, the next one appears. RTS,S firmly plants its flag at basecamp, but we still have that mountain to climb.</p><img src="https://counter.theconversation.com/content/19020/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Sanjeev Krishna has been a consultant for GSK for early antimalarial drug development and is working with QuantuMDx to develop new diagnostics for malaria.</span></em></p>The announcement that GlaxoSmithKline (GSK) aims to register a malaria vaccine came on the same day Peter Higgs and Francois Englert were awarded the Nobel prize in physics for predicting the existence…Sanjeev Krishna, Professor of Molecular Parasitology and Medicine, St George's, University of LondonLicensed as Creative Commons – attribution, no derivatives.