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BMJ 2011;342:d3004 doi: 10.1136/bmj.d3004 It's time to rebuild the evidence base
With medical science so contaminated by conflicts of interest, what evidence can we trust? Ray Moynihan author, journalist, and conjoint lecturer, University of Newcastle, Australia Anyone who is in any doubt that study sponsorship is associated with more favourable outcomes needn't be. As the authors of the JAMA paper make clear, extensive research has shown that "conflicts of interest can influence the results and conclusions" of randomised controlled trials and meta-analyses. A growing body of reliable data indicates that commercial sponsors tend to get the outcomes they desire, raising serious questions about how we are supposed to trust the evidence base.
In the early 1990s researchers examined more than 50 clinical trials that compared popular anti-arthritis drugs and showed that not one of those trials found its sponsor's drug to be inferior to a comparator.2 By 2003 there were many similar pieces of For many of us, the move towards an evidence based approach research, and summaries of that research were pointing to a to medicine has largely been a welcome one. We have learnt to "systematic bias" across the medical literature, with company evaluate therapies rigorously and be highly sceptical of expert funded trials far more likely than more independently funded enthusiasm for them. Perhaps most importantly, we now try to trials to find favourable results for their products.3 In 2005 the turn routinely to summaries of the evidence rather than rely on long time editor of the BMJ, Richard Smith, wrote that "the single studies. For what we assumed were good reasons, evidence is strong that companies are getting the results they systematic reviews and meta-analyses have become gold want," and he wondered whether journals should stop publishing standards, whether we are a politician, a physician, or simply a trials that were more about marketing than medical science.4 citizen. But is it fool's gold? In our collective zeal to summarise, In 2007 a review of almost 200 trials comparing cholesterol we have too often ignored the fact that a vast and growing lowering drugs found that company funding greatly influenced proportion of those original studies are industry sponsored, a study's outcome.5 If a study found a positive result for a drug, which means that they tend to exaggerate benefits and play the study was 20 times more likely to have been funded by that down harms. Summarising that bias doesn't make it go away.
drug's maker than by the manufacturer of the comparison drug.
Medicine's prized evidence base has become debased.
In 2008 research confirmed that the world was being An international team of researchers from across Europe and fundamentally misled about the benefits of widely prescribed North America recently examined 29 meta-analyses published antidepressants, showing that many studies with unfavourable in leading medical journals.1 Those meta-analyses summarised results had simply not been published.6 In 2009 researchers results of more than 500 trials of top selling drugs for conditions demonstrated that sponsored trials of new antidiabetes drugs, such as cancer and heart disease. Almost 70% of the original and trials run by authors with financial ties to companies, tended trials that disclosed a funding source were company sponsored.
to find more favourable results for the sponsor's product: an Similarly, almost 70% of the original trials that disclosed the extremely worrying finding, given the harms associated with financial relationships of authors reported ties to drug rosiglitazone.7 And now, in 2011, the JAMA paper suggests that companies. Yet only two of the 29 meta-analyses reported who the vast majority of meta-analyses fail to report such basic facts funded the original trials, and none reported on the financial as the funding source for the original studies.
ties of authors. These alarming findings were published in JAMA "It's hard to find an area of the healthcare literature that is not earlier this year, along with the conclusion that key information contaminated," says Brett Thombs, assistant professor at McGill about potential bias is being left out of influential reviews that University in Canada and one of the authors of the JAMA paper.
guide what doctors do.
Whether it is drugs, behavioural therapies, or patient support BMJ 2011;342:d3004 doi: 10.1136/bmj.d3004 tools, "when anyone tests something they developed debased information but also offer societies the chance to take themselves," says Thombs, "there is a great risk of bias." He back the agenda in healthcare research and practice, which has and colleagues recommend several reforms to the way reviews been hijacked so effectively, and with such panache, by the drug are reported, pushing more disclosure of funding sources and of authors' financial ties.
But simply disclosing bias doesn't make it go away either. The Competing interests: RM has written many reports, articles, and books aim of any rational healthcare system is surely to generate an about evidence based medicine and medicalisation. See www.
evidence base we can trust. The argument that trials without industry funding are not feasible is disingenuous and dangerous.
Clearly, not all company sponsored studies are corrupted, and Roseman M, Milette K, Bero L, Coyne J, Lexchin J, Turner E, et al. Reporting of conflicts not all publicly funded studies are reliable, but a mountain of of interest in meta-analyses of trials of pharmacological treatments. JAMA data suggests that much current evidence is deeply contaminated Rochon P, Gurwitz JH, Simms RW, Fortin PR, Felson DT, Minaker KL, et al. A study of by commercial conflicts of interest. Of particular concern are manufacturer-supported trials of nonsteroidal anti-inflammatory drugs in the treatment of arthritis. Arch Intern Med 1994;154:157-63.
the many sponsored trials that recruit large numbers of people Lexchin J, Bero LA, Djulbegovic B, Clark O. Pharmaceutical industry sponsorship and and find very small benefits—where a hidden bias could make research outcome and quality: systematic review. BMJ 2003;326:1167-70.
Smith R. Medical journals are an extension of the marketing arm of pharmaceutical a useless and potentially harmful pill seem to be an effective companies. PLoS Med 2005;2(5):e138.
Bero L, Oostvogel F, Bacchetti P, Lee K. Factors associated with findings of published trials of drug-drug comparisons: why some statins appear more efficacious than others.
Just as the tobacco companies polluted the literature on smoking, PLoS Med 2007;4(6):e184.
and polluting industries try to distort the science of climate Turner EH, Matthews AM, Linardtos E, Tell RA, Rosenthal R. Selective publication of antidepressant trials and its influence on apparent efficacy. N Engl J Med change, the pharmaceutical giants and the doctors on their payrolls are poisoning too much of the medical science with Rattinger G, Bero L. Factors associated with results and conclusions of trials of thiazolidinediones. PLoS One 2009;4(6):e5826.
overly positive findings. The inevitable rebuilding of that evidence base may not only produce more trustworthy and less Cite this as: BMJ 2011;342:d3004



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