Transparency and Trust
by Adam Istas
January 2007
With the issue of clinical trial registration settled, the movement to disclose all trial results is taking center stage.
Since September 2004, when the International Committee of Medical Journal Editors (ICMJE) required that trials be registered prospectively as a condition for publication, the international research community has worked to ensure greater transparency of clinical research. The ICMJE’s statement was a mandate to investigators and trial sponsors: Trials must be registered before the randomization of patients, or the results will not be published in a peer-reviewed journal. Although the journal editors’ requirements were limited to prospective trial registration, the effect of the statement has been an increased call for full reporting of all trial results.
Industry sponsors conducting trials in the United States have largely complied with the ICMJE’s stipulations by registering trials on ClinicalTrials.gov, the repository established by the U.S. National Institutes of Health to comply with the U.S. Food and Drug Administration Modernization Act, requiring the establishment of a registry for both federally funded and privately funded clinical trials.
Although trial registration is now widely accepted with limited controversy, there still is much debate over results reporting. The debate goes beyond mere transparency; when results from a clinical trial are not disclosed, systematic reviews—from which responsible, evidence-based clinical decisions are made—can be compromised. “Our perspective is quite simple,” says Nick Royle, chief executive officer of The Cochrane Collaboration, the Oxford, U.K.-based standard-bearer for systematic reviews. “We need to know the trial exists, and we need to have access to the results.” When trials with negative results are not published, bias is set in the systematic reviews, Royle says. Currently, there is no system available for universal trial registration, let alone results reporting. According to Royle, in addition to hand-searching non-electronic journals, The Cochrane Collaboration has resorted to manually searching the so-called “grey literature” that never appears in peer-reviewed journals: medical conference reports, scientific meeting abstracts and industry press releases.
The formation of a universal, one-stop registry of trial protocols and results is the primary objective of the International Clinical Trials Registry Platform (ICTRP), a project created in 2005 by the World Health Organization, in Geneva, Switzerland. Comprised of representatives from industry, government research institutions, medical journals and academia, the ICTRP’s first task was to define minimum trial registration data requirements. After two rounds of comments from stakeholders, the 20-item data set was finalized in May 2006, despite concerns from some pharmaceutical manufacturers that several items could present a competitive disadvantage. Since the creation of the ICTRP, industry is more open to embracing trial registration, Royle says. “Pharma dipped a toe in the water, and quite frankly, the water wasn’t as cold as they thought it would be,” he says.
Although the ICTRP advocates the public disclosure of results, it has not taken any tangible action to make this a reality. But the call for full results reporting is a primary concern for other organizations, such as the Ottawa Group, a collaboration of stakeholders led by Dr. Karmela Krleza-Jeric, a clinical research officer in the Randomised Controlled Trials Unit of the Canadian Institutes of Health Research, in Ottawa, Canada. While the ICTRP plays a pragmatic role in the staged implementation of trial registration, the Ottawa Group advocates a more idealistic approach. “The ICTRP is a good start, but it’s not enough,” Krleza-Jeric says.
The Ottawa Group envisions having trial results connected to the original registration, with the full trial protocol and links to all publications from the trial available from one Internet location, Krleza-Jeric says. “At the end of the study, let’s see everything,” she says. “We should be seeing a constant flow of information.”
For its part, industry has responded to the call for results by setting up free Web sites disclosing study information for approved drugs. ClinicalStudyResults.org, sponsored by the Pharmaceutical Research and Manufacturers of America (PhRMA), includes brief trial descriptions, links to published studies and summaries of results of clinical studies that have not been published. In addition to PhRMA’s collaborative efforts on behalf of its members, some individual pharmaceutical companies have established results portals for their own products. The GlaxoSmithKline Clinical Trial Register and the Eli Lilly and Company Clinical Trial Registry are two of the more thorough examples.
Achieving full transparency of clinical trial data will require the cooperation of many entities and will involve discussion and compromise with biopharmaceutical manufacturers. Regaining and retaining the public’s trust is a good incentive for industry to embrace results reporting, Krleza-Jeric says. “For now, though, agreement on the issue of registration requirements is a step in the right direction,” she says.
The best way to get trial results is through registration, Royle says. “Just getting [the trial] registered is a huge step,” he says. “If we get that done, properly policed and properly working, we’ve gone a huge way.”
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