Leading academic research centers are doing a poor and variable job of disseminating clinical trial results, according to a cross-sectional analysis published online February 17 in BMJ, and that is leading to serious information gaps and ethical lapses.
Despite there being moral and sometimes legal obligations to circulate results in the public domain, Ruijun Chen, MD, from the Department of Medicine, University of California, San Francisco, and colleagues found that just 29% of completed trials at 51 major research centers had been published 2 years after completion, and a mere 13% had submitted their results to ClinicalTrials.gov.
"There is no excuse for the fact that researchers are using resources and conducting experiments on humans, taking up their time and maybe exposing them to risk, and then failing to report the results. Why, is beyond me," corresponding author Harlan M. Krumholz, MD, a professor of medicine at Yale University, New Haven, Connecticut, told Medscape Medical News.
Delayed data dissemination denies healthcare providers and researchers crucial information. "If all the trial data had been made available in a timely way, then people would have realized the cardiovascular risks of Vioxx [Merck] 2 years before it was taken off the market in 2004," said Dr Krumholz, who coauthored a study of pooled trial data showing increased risk with the drug as early as 2000.
The researchers called for timely action to correct this lapse in commitment to the investigative mission and failure to follow through on the research process. "Additional tools and mechanisms are needed to rectify this lack of timely reporting and publication, as they impair the research enterprise and threaten to undermine evidence based clinical decision making," the authors write...
Across institutions, the proportion of trials that disseminated results within 24 months ranged from 16.2% (University of Nebraska) to 55.3% (University of Minnesota), and the proportion published within 24 months of completion extended from 10.8% (University of Nebraska) to 40.3% (Yale University). The overall range for results reported on ClinicalTrials.gov ran from 4.1% (Memorial Sloan-Kettering Cancer Center) to 55.4% (MD Anderson Cancer Center).
The overall rate of dissemination ran from 45.9% at the University of Nebraska to 76.7% at the universities of Minnesota and Rochester. There was also a more than twofold variation from 13.9 (University of California, Irvine) to 28.3 (Boston University) months in median time from study completion to publication or reporting.
Previous studies found similar suboptimal dissemination rates, with 25% to 50% of trials remaining unpublished several years after completion.
Dr Krumholz is at loss to understand the lapse in data sharing, which he considers immoral. "It's not hard to report your results. It only takes about an hour," he said. Nor does reporting to the national trial database jeopardize future publication in a peer-reviewed journal, he said. "Some studies are small, but you have to ask: If the results are not important enough to be reported, was the study important enough to be done? You should not have conducted the study if you can't provide timely results."
He noted that those with concerns about a drug could perhaps tap into trial results circuitously by checking relevant studies registered on ClinicalTrials.gov and asking the investigators directly to share their unreported data.
And although researchers do need adequate time to ensure accurate data, "some, inexplicably, never share their findings," Dr Krumholz said. In his view, less effort should be put into identifying reasons and more into rectifying the unjustifiable status quo: "We can spend our time understanding the causes, or we can just fix it."
Ruijun Chen, Nihar R Desai, Joseph S Ross, Weiwei Zhang, Katherine H Chau, Brian Wayda, Karthik Murugiah, Daniel Y Lu, , Amit Mittal, Harlan M Krumholz, Harold H Hines Jr. Publication and reporting of clinical trial results: cross sectional analysis across academic medical centers. BMJ published on line.
Objective To determine rates of publication and reporting of results within two years for all completed clinical trials registered in ClinicalTrials.gov across leading academic medical centers in the United States.
Design Cross sectional analysis.
Setting Academic medical centers in the United States.
Participants Academic medical centers with 40 or more completed interventional trials registered on ClinicalTrials.gov.
Methods Using the Aggregate Analysis of ClinicalTrials.gov database and manual review, we identified all interventional clinical trials registered on ClinicalTrials.gov with a primary completion date between October 2007 and September 2010 and with a lead investigator affiliated with an academic medical center.
Main outcome measures The proportion of trials that disseminated results, defined as publication or reporting of results on ClinicalTrials.gov, overall and within 24 months of study completion.
Results We identified 4347 interventional clinical trials across 51 academic medical centers. Among the trials, 1005 (23%) enrolled more than 100 patients, 1216 (28%) were double blind, and 2169 (50%) were phase II through IV. Overall, academic medical centers disseminated results for 2892 (66%) trials, with 1560 (35.9%) achieving this within 24 months of study completion. The proportion of clinical trials with results disseminated within 24 months of study completion ranged from 16.2% (6/37) to 55.3% (57/103) across academic medical centers. The proportion of clinical trials published within 24 months of study completion ranged from 10.8% (4/37) to 40.3% (31/77) across academic medical centers, whereas results reporting on ClinicalTrials.gov ranged from 1.6% (2/122) to 40.7% (72/177).
Conclusions Despite the ethical mandate and expressed values and mission of academic institutions, there is poor performance and noticeable variation in the dissemination of clinical trial results across leading academic medical centers.