Register all trials, report all results – it’s long overdue

Non-publication of clinical trial data is a waste of research resources, among other things. Esther Dyson

If researchers go to the effort of getting funds, recruiting patients, and following them up, you would think that they would be keen to publish the results. So it’s surprising that our best estimates show around half of all completed clinical trials have never been published in academic journals. And the half we have is biased towards trials with positive results.

Non-publication is both a waste of research resources, and a problem for decision makers attempting to use the biased set of studies they can access.

But this is not only problematic for decision makers, it also poses a dilemma for people who volunteer for medical research. Most do so because they believe they will be contributing to medical knowledge, and might be horrified to learn that the research they participated in has gone unpublished.

The latest revision of the World Medical Association’s Declaration of Helsinki - Ethical Principles for Medical Research Involving Human Subjects now rightly suggests public reporting of results is an ethical obligation.

Sometimes non-publication and selective publication occurs for commercial reasons. This is illustrated by the incomplete information in the Cochrane review of drugs for treating influenza, which has been hampered by the lack of access to the results of all studies. Roche, the manufacturer of the drug, oseltamivir or Tamiflu, has repeatedly refused to give researchers full access to the data.

One of the authors of the review, Tom Jefferson, recently said, “We identified that a large number of studies, including data from 60% of the people who have been involved in randomized, placebo-controlled phase III treatment trials of oseltamivir, have never been published. This includes the biggest treatment trial ever undertaken on oseltamivir that on its own included just over 1,400 people of all ages.”

Governments around the world have spent billions of dollars on stockpiling oseltamivir (Tamiflu) but the Cochrane review authors conclude that there’s no clear evidence of the effect of this anti-flu drug. “The evidence supports a direct oseltamivir mechanism of action on symptoms but we are unable to draw conclusions about its effect on complications or transmission,” the authors said.

But non-publication is almost as frequent among non-commercial trials. Sometimes lead authors can move jobs, become ill, retire, or (as with a 68,000 person colorectal cancer screening trial) die as the research is finishing.

Occasionally authors give up after several attempts to publish, but more often the results are never submitted for publication. A randomised trial of deworming treatment of almost a million children in India, for instance, has not been published even though it was completed in 2005 (rumour suggests in will be published early this year).

Given the extent of deworming programs in developing countries, this non-publication of crucial evidence is hampering rational decisions about such program investment - should they stop or be extended?

The problems of non-publication have been known for at least three decades. Indeed, John Simes, the director of the Clinical Trials Centre at The University of Sydney, demonstrated the problem and proposed universal registration of trials in the 1980s. Since then trial registration has improved but unfortunately, most national and international clinical trials registries are currently voluntary.

While awareness has spread and some action has been taken, a number of recent events – and the publication of Bad Pharma by Ben Goldacre – have resulted in greater awareness and willingness to act at a regulatory and political level.

It seems that we’re at a critical juncture, and pushing for more action now is vital. Hence a coalition of several organisations – Bad Science, Sense About Science, BMJ, James Lind Initiative and the Centre for Evidence-based Medicine at Oxford University – have put together the AllTrials campaign.

The alltrials website sets out the details of why action is important now, and includes a number of proposals, including a petition that everyone is urged to sign. So if you want the waste of non-published research to stop, and if you want doctors and health policymakers to base their decisions on all the research rather than a selected sample, I suggest you to sign up.