The international medical research community owes a great deal to the US National Library of Medicine and its vision to provide a publicly accessible archive of research abstracts. However, PubMed holds the results of only a portion of all biomedical research; many randomised trials, especially ones with negative results, are never published as a full paper in a peer reviewed journal. Researchers have been worried for years about the implications of publication bias for medical practice. At the beginning of June, New York State attorney general, Eliot Spitzer, accused GlaxoSmithKline of consumer fraud and of withholding negative data about the efficacy and safety of its antidepressant paroxetine. Two weeks later the American Medical Association urged the federal government to require all clinical trials to be registered in a central database, a proposal that has been backed by pharmaceutical giant Merck.
There are currently around 300 clinical trial registries, so do we really need another? Yes, but only if its goal is to contain data on every randomised controlled trial being done worldwide. The human genome project has proven the benefit of depositing data in a single repository that is freely accessible to anyone with an internet connection. An international trial database that is free to access and that has the backing of respected funders, would hugely benefit medicine. Researchers would not be the only ones to benefit: patients also need to be able to identify trials to participate in. Indeed, improving patient recruitment rates is one reason why pharmaceutical companies might be willing to submit to a central registry.
How would trial registration be enforced? Funding agencies could insist that trials are registered before delivering funds; WHO announced in April that all randomised controlled trials approved by WHO ethics review board will be assigned an International Standard Randomised Controlled Trial Number (ISRCTN). Alternatively, individual countries could introduce legislation to enforce trial registration, but it is probably unrealistic to expect this to happen throughout the world. Perhaps it would be better to tempt researchers with a carrot than to threaten them with a stick. In this regard, the International Committee of Medical Journal Editors (ICMJE)—whose members include The Lancet, The New England Journal of Medicine, and The Journal of the American Medical Association—are debating whether to make trial registration as a prerequisite for publication in their journals. If this proposal were adopted, the ICMJE would need to decide what constitutes a minimum data set. Ideally, the final protocol would be part of the database entry, but pharmaceutical companies may be reluctant to divulge their drug-development strategies. At the other extreme, supplying just the trial's title would be clearly inadequate.
Since many patients volunteer to participate in trials because they want to help further scientific knowledge, there is a clear moral obligation to publish the results of every trial even if they are negative. A central database could house these results, even if they had not been published in a journal. Some commentators believe that the results should be peer reviewed before publication in a database, but others say this is unnecessary. After all, peer review is an ongoing process that continues even after results are published, for example in correspondence columns. As long as the data are available for all to see, clinical researchers will be able to scrutinise them and advise doctors on the best treatment decisions, on the basis of all available evidence.
The logistics of a clinical trial registry are far from straightforward. However, recent rapid developments in information technology and bioinformatics mean that we now have the skills and tools to develop a fully searchable archive of clinical trials. The rewards for producing a central repository would be worth the effort. Importantly, it is unreasonable to expect the US tax payer to pick up the bill for an international resource such as this. For this reason, the US National Library of Medicine may not be the ideal host for the registry, despite its extensive experience of medical databases. It would be far better to create an international, independent database that transcends national boundaries.