Iain Chalmers (Copyright: Ian Milne)
All trials registered, all results reported, a new campaign which the MRC is supporting alongside other research organisations, calls for the results of all clinical trials to be made public. Sir Iain Chalmers, Coordinator of the James Lind Initiative, says that longstanding biased under-reporting of clinical research must stop.
Successful conduct of clinical trials depends on many factors, but these studies are impossible unless patients agree to participate in them. For many patients the principal motivation for participating in clinical trials is the hope that they may receive better care, and perhaps more effective treatment. All participants in clinical trials, however, believe that their involvement will help to increase knowledge about the effects of treatments. They expect that people with health problems like theirs – and perhaps they themselves – will be able to make better informed treatment decisions in future as a result of their contributions to knowledge.
How come, then, that the research community, including research funders and regulators, have acquiesced for decades in the nonpublication of around 50 per cent of all clinical trials? Can this be characterised as anything other than a gross betrayal of the trust in researchers which motivated volunteers to participate in clinical trials in the first place? How many of them would have agreed to participate if researchers had told them “If the results of this trial don’t serve our academic or commercial interests we won’t make them public”?
After doing research on biased under-reporting of research 20 years ago, I raised these issues in an article published in the Journal of the American Medical Association entitled ‘Underreporting research is scientific misconduct’. The evidence that has accumulated over the subsequent two decades has made clear that the problem is widespread. It’s not only unethical and scientific misconduct; it is also simply a waste of precious research resources. As illustrated by numerous examples, under-reporting of research has led to harm to patients from exaggerated estimates of treatment benefits and safety, and built-in inefficiency in efforts to discover useful and safer treatments.
Until recently, the academics who have exposed biased underreporting of research have had little or no effect in persuading people with the power to do something about this scandal to put an end to it. It is true that — a decade or two after they had called for trials to be registered publicly at inception and a major drug company had beenfined for suppressing information about dangerous effects of one of its drugs — registration of trials slowly gathered momentum. Indeed, within the UK, it was the MRC that led the way in trial registration in the 1990s. However, the main consequence of trial registration has been to expose the massive extent of non-publication of clinical trials.
Yet only one medical professional organisation — the Faculty of Pharmaceutical Medicine — has so far declared non-publication to be unethical; the position of others remains unstated or ambiguous.
So what has happened to change the terms of the debate after a quarter of a century during which researchers, research funders, research regulators and politicians have failed to address the problem seriously? Two things. First, Dr Ben Goldacre, the award-winning medical journalist, published Bad Pharma — a book making clear to the public, using a mountain of evidence, why they should be concerned about the situation. In brief, his message is: ‘How can you or your doctor make an informed choice about which treatment to choose if half the relevant evidence has not been made public?’
Second, Sense about Science, an organisation campaigning to promote science to the public, has decided that non-publication of clinical trials is a stain on the public image of science, and that, after years of havering and disingenuous excuses for inaction, it must be confronted and dealt with. Following on its influential campaign to reform the English libel laws that were being used to silence scientists, Sense about Science’s new campaign — All trials registered, all trials reported — aims to achieve just what its title calls for. Sense about Science has invited those who agree with these principles to join the tens of thousands that have already signed the petition
To its great credit, the MRC was the first organisation to do so, with these words: “The MRC is pleased to sign up to this campaign and has, for many years, strongly supported the position that clinical trial results must be published in a timely manner. At the end of 2012, we made both the requirement to publish, and the need for MRC-funded researchers to share data, even more explicit: “Results of MRC-funded clinical studies (whether positive or negative) must be published within a reasonable period (generally within a year of completion) following the conclusion of the study.”
As the MRC admits, it would be surprising if, in its one hundred year history, there were no unreported or unpublished skeletons in its cupboards. While monitoring future adherence to its policy, therefore, the MRC should audit the trials it has funded. An audit of the publication record of studies funded by the Health Technology Assessment Programme has shown that 98 per cent of them have been reported. A similar finding from an audit of trials funded by the MRC would be very reassuring.
If action is not taken urgently by research funders and regulators, information on what was done and what was found in trials could be lost forever, leading to bad treatment decisions, unnecessary repetition of trials, and missed opportunities for good medical practice.
To find out more and sign the petition, visit the All Trials Registered, All Results Reported campaign web page.
This article was originally published in the Spring 2013 issue of Network.