Experts: Publish 'Invisible' and 'Abandoned' Clinical Trials

Janis C. Kelly

June 13, 2013

New freedom-of-information policies have made thousands of pages of previously confidential clinical trial documents and clinical study reports (CSRs) publicly available. In an article published online June 13 in the BMJ, a group of experts has proposed that the information be used to report previously unpublished "abandoned" or "invisible" trials and to correct previously misreported trials.

Peter Doshi, PhD, a postdoctoral fellow at Johns Hopkins University School of Medicine in Baltimore, Maryland, and colleagues further suggest that outsiders be allowed to publish reports for "restoring invisible and abandoned trials (RIAT)" if the trial researchers fail to publish within 1 year. The authors' goal is to solve 2 problems: invisibility, which occurs when a trial remains unpublished years after completion, and distortion, "which occurs when publications in medical journals present a biased or misleading description of the design, conduct, or results of a trial."

Dr. Doshi's coauthors included Kay Dickersin, PhD, director of Johns Hopkins University's Center for Clinical Trials; David Healy, MD, professor of psychiatry at Bangor University in the United Kingdom; S. Swaroop Vedula, PhD, a postdoctoral fellow at Johns Hopkins University; and Tom Jefferson, MD, a researcher from the Cochrane Collaboration, Rome, Italy. Dr. Healy has been a strong critic of the pharmaceutical industry's role in clinical research and in psychiatry continuing medical education. Dr. Jefferson is described on the Cochrane Collaboration Web site as "a high-profile campaigner against pharmaceutical and other commercial companies influencing health policy."

The authors describe abandoned trials as "either unpublished trials for which sponsors are no longer actively working to publish or published trials that are documented as misreported but for which authors do not correct the record using established means such as a correction or retraction.... Because abandonment can lead to false conclusions about effectiveness and safety, we believe that it should be tackled through independent publication and republication of trials," the authors note.

"We call on institutions that funded and investigators who conducted abandoned trials to publish (in the case of unpublished trials) or formally correct or republish (in the case of misreported trials) their studies within the next year. This should allow sufficient time for manuscript preparation, peer review, and publication."

A 'Widespread Problem'

The authors throw down the gauntlet by proposing to email a copy of their article to manufacturers of more than 100 trials and demanding that the companies "signal their intent to publish by sending an electronic response to the article within 30 days." The companies contacted would be Amgen, AstraZeneca, Bristol-Myers Squibb, GSK, Merck, Novartis, Pfizer, Roche, Rowlasha, and Takeda.

The author propose that failure to publish within 1 year after such declaration of intent would make all available data "public access data" that others are allowed to publish. The authors claim to already have in hand about 178,000 pages of previously confidential company research documents for paroxetine, quetiapine, gabapentin, oseltamivir, and clopidogrel.

This trove of information resulted from new freedom-of-information policies at the European Medicines Agency and from results of litigation over off-label marketing, which have opened thousands of pages of CSRs to public access. The data are likely to come from the CSRs manufacturers submit to the US Food and Drug Administration in new drug approval applications. CSRs are usually hundreds, if not thousands, of pages long and include a detailed summary of the planning, conduct, and results of the trial. CSRs are typically not produced for trials funded by noncommercial sponsors.

"We see RIAT as a collaborative, global effort, and over the next year we hope to discuss and debate our proposal at appropriate venues," the authors write.

They solicited volunteers "in place of those who should have but did not make trial reports visible and accessible," and they asked medical journal editors to endorse the concept of restorative authorship to "help the effort to complete and correct the scientific record."

Dr. Doshi and colleagues called for medical journal editors to endorse the concept of restorative authorship, and the editors of BMJ and of PLOS Medicine editors have answered the call.

In an accompanying editorial, Elizabeth Loder, MD, Fiona Godlee, MD, Virginia Barbour, MD, and Margaret Winker, MD, write, "Nothing better underscores the urgency and importance of the RIAT proposal than the list of abandoned trials that accompanies it. Read it and weep: on the list are clinical trials for drugs used by millions of people, including zanamivir, atorvastatin, gabapentin, and paroxetine. The number and variety of drugs on the list show clearly that incomplete reporting of clinical trial results is not an isolated occurrence, confined to a few drugs. Rather, it is an entrenched and widespread problem."

Dr. Loder is clinical epidemiology editor and Dr. Godlee is editor-in-chief of the BMJ. Dr. Barbour is editor-in-chief and Dr. Winker is senior research editor of PLOS Medicine.

Editors from the 2 journals "commit to publishing restorative clinical trial submissions."

The authors and editorialists have disclosed no relevant financial relationships.

BMJ. Published online June 13, 2013. Article full text, Editorial full text

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