Making information about clinical trials publicly availableBMJ 2009; 338 doi: http://dx.doi.org/10.1136/bmj.b2473 (Published 25 June 2009) Cite this as: BMJ 2009;338:b2473
- Rosalind L Smyth, Brough professor of paediatric medicine
- 1Institute of Child Health, University of Liverpool, Alder Hey Children’s Hospital, Liverpool L12 2AP
Recognition of the commercial and non-commercial benefits of greater transparency within clinical research has increased in the past decade. Public dissemination of the conduct and outcome of all clinical trials, including those performed as part of marketing authorisation applications, will ensure that professionals and patients have more information about how the safety and effectiveness of drugs has been evaluated. This will also prevent unnecessary duplication of research and, by encouraging greater scrutiny of clinical trials, will ensure that their ethical and scientific quality is improved. Wider dissemination of knowledge will also drive innovation and the conduct of further, more relevant, research.
This effort was considerably enhanced in 2004, when the International Committee of Medical Journal Editors (ICMJE) announced that an essential criterion for publication of a trial in one of their journals was that the details of the trial should be publicly available in a clinical trials register.1 2 These requirements have been an important factor in driving public registration of clinical trials and the development of registers that provide free access to information about the research question, methodology, intervention, funding, and sponsorship. These registers include those of the World Health Organization (www.who.int/ictrp/en/), the US National Library of Medicine (http://clinicaltrials.gov/), the International Standard Randomised Controlled Trials Registry (http://isrctn.org/), and many others.
Another major driver in Europe has come from an initiative in a previously neglected area. The European regulation on better medicines for children became law in January 2007.3 This legislation comprehensively deals with the unsatisfactory situation whereby a high proportion of drugs are used for children outside the approved conditions of their product licence, because they have not undergone clinical studies of safety and efficacy in that age group. The new legislation requires companies that wish to obtain a licence for their product in Europe to develop a paediatric investigation plan, unless the drug would never be used in children. It was also clear, however, that some companies had conducted studies in children during development programmes to market drugs and had decided not to market the drug for use in children. This may have been because the studies had not shown that the benefits outweighed the risks in this age group. Nevertheless, information from these studies was not available either in the summary of product characteristics or any publicly accessible form.
This suppression of information was widely publicised when Eliot Spitzer, New York state’s attorney general, accused GlaxoSmithKline (GSK), makers of the selective serotonin reuptake inhibitor paroxetine, of suppressing data from studies in adolescents, which either showed no benefit over placebo or a slight increase in self harm.4 Spitzer’s main complaint was that trials of paroxetine to treat major depressive disorder in childhood, as well as the safety outcomes of other trials, had been hidden from doctors by the manufacturer, and that GSK therefore deprived doctors of the information needed to evaluate the risks and benefits of prescribing paroxetine for children and adolescents with this disorder.5 The law suit was settled, and in June 2004 GSK announced a GSK clinical trial register that would provide summaries of trial protocols and results for GSK sponsored trials of marketed drugs. The company stated that this move was to restore trust in research undertaken by the drugs industry. Other companies followed suit, and it seemed that the drugs industry recognised that the benefits of more openness greatly outweighed the risks.
The European paediatric legislation made it a requirement that information about clinical trials of investigational medicinal products being conducted in Europe with children should be made publicly available on the EudraCT database, and, following a consultation, the European Commission has recently published a guideline about the data fields for which information should be provided.6 In addition, the results of clinical studies should be made available “without delay.” For studies intended for marketing authorisation this means within six months of completion of the study; sponsors of non-commercial studies can extend this to one year, if they provide a scientifically justified reason.
With the implementation of the paediatric regulation, the incongruity of the position whereby the EudraCT database provided public access to information about clinical trials with children, but not adults, became untenable. In February 2009, the European Commission published the list of data fields to be made public from the EudraCT database for all trials, and these were similar to those for children.6 The commission hopes that data about the protocols of ongoing trials will be available later this year, and the results of trials will be included about a year after this. The transatlantic position is also being harmonised. In the United States, the Food and Drug Administration Amendments Act (2007) made provision for the results of trials registered in the clinicaltrials.gov database to be made available no later than 12 months after data from the last participant were received.
Clinical research is undergoing a huge transformation. The availability of these rich and comprehensive datasets will provide important material for those who review, appraise, and synthesise information to inform drug regulation, patient care, and future research. Most importantly, it will provide reassurance to the public that information from studies, made possible by the generosity and support of patients, is being used for the benefit of all.
Cite this as: BMJ 2009;338:b2473
Competing interests: None declared.
Provenance and peer review: Commissioned; not externally peer reviewed.