Undisclosed Clinical Trial Results Across All Major Academic Medical Centers: “A Failed Moral Obligation”
Nearly one third of clinical trials conducted by researchers at academic medical centers, including some of the most high-profile clinical centers in the United States, remain unpublished or unreported upon completion, according to the results of a new analysis.
Among 51 academic centers conducting clinical trials in cancer, heart disease, metabolic disease, and behavioral and mental disorders, among other conditions, the results show that just 29% of studies are published within 2 years of completion and even fewer are publicly disseminated.
“Everybody is doing really poorly,” lead investigator Harlan Krumholz, MD, Yale University School of Medicine (New Haven, CT), told TCTMD. “We had hoped to find a place that was doing much better than everybody else, but the bottom line was that performance was really poor throughout. It is a pervasive problem. I think this is a huge issue because it means that there is an immense publication bias. There are a lot of studies that aren’t being reported.”
Failing to publish or report the results “corrupts the medical literature and undermines the ability of people to make truly informed choices,” he added. And not only is evidenced-based medicine compromised, it dishonors the participation of individuals within the study. “No one would have ever agreed to participate in a study under the assumption the results would never be shared,” said Krumholz.
Jennifer Miller, PhD, New York University Langone Medical Center (New York City), said transparency is critical for advancing patient and global public health, for innovation and conserving resources, and for respecting the integrity and well-being of the research subjects. Although not involved in the analysis, Miller, who is the executive director of Bioethics International, a not-for-profit that recently developed a scorecard ranking clinical-trial transparency among pharmaceutical companies, had similar concerns about researchers who fail to publish their work.
“We’re aiming for evidence-based medicine and it’s very hard to have evidence-based medicine when you don’t have all the evidence in the public space,” she told TCTMD. “It raises questions, ‘Are doctors capable of prescribing the right drugs to the right patients at the right time?’ In order to have confidence that can indeed take place, you really need to have all the key evidence publicly available for them.”
Wide Publication Range But All Centers Underwhelm
Published February 17, 2016 in the British Medical Journal, the analysis included 4,347 clinical trials conducted at major US academic medical centers. Such centers included the Brigham and Women’s Hospital, the Cleveland Clinic, Duke University, Johns Hopkins University, the Mayo Clinic, Stanford University, and Yale University, among others. Oncology was the most commonly studied condition, with one third of trials investigating interventions in cancer and other neoplasms. Heart and blood diseases made up 8.2% of the studies included in the analysis.
Regarding the trials, all of which were registered on ClinicalTrials.gov between 2007 and 2010, 23% enrolled more than 100 patients, 28% were double-blind, and 50% were phase 2, 3, or 4 investigations. The National Institutes of Health was listed as the primary sponsor of 424 trials while industry funded 519 studies.
In total, 2,892 of the studies (66.5%) were published or publicly reported by July 2014. The overall rate of publication/public reporting ranged across the different institutions, with the University of Nebraska reporting the results of just 45.9% of studies, Cornell University reporting 50.0% of results, and Stanford University reporting just 54.2% of trial results. On the high end, Boston University, Duke University, the Mayo Clinic, University of Rochester, University of Florida, and University of Minnesota all reported or published the results from at least 75% of their registered clinical trials.
Regarding publication alone, 56.5% of all studies were published by 2014. Again, the rates ranged across the institutions, from a low of 35% at MD Anderson Cancer Center, University of Nebraska, and Oregon Health and Science University to a high of 67% at the University of Wisconsin. Publishing the results on ClinicalTrials.gov was also poor among the academic centers, with rates as low as 4.1% to a high of 55.4%. The overall publication rate on ClinicalTrials.gov was 26.8%.
In terms of timing, approximately 36% of the studies were published or reported within 24 months of completion and 26% were published or reported beyond the 2-year mark. In total, just 29% of the studies were published in a journal within 2 years and no academic center published more than 40% of trial results within 24 months of completion. Again, there was wide variation among academic medical centers, with the University of Nebraska reporting/publishing just 16.2% of study results within 2 years compared with researchers from the University of Minnesota who reported or published 55.3% of results within 2 years. The median time from study completion until the results were published or reported ranged from 14 to 28 months.
Academic Centers Failing to Uphold Moral Obligation
Krumholz, who is the lead investigator of the Yale Open Data Access (YODA) project, noted that clinical research is now moving toward greater transparency and access, with the International Committee of Medical Journal Editors (ICMJE) requiring study authors share de-identified individual patient data as a condition of publication. Academic researchers and institutions aren’t even doing the minimum at present.
“This is the lowest possible bar,” said Krumholz. “This is just, ‘Are you sharing your results publicly?’ And there are two ways to do that primarily. One way is to put your results on ClinicalTrials.gov so people can see them. That doesn’t preclude publication and it’s recommended to be done. And the second one is that you publish. We’re looking at both of these and we’re seeing that people commonly don’t do either. Certainly within two years of completing the study, a large number of these are neither reported nor published.”
To TCTMD, Miller said science is built upon the lessons of researchers who went before them, but if these lessons aren’t publicly disclosed, it’s very difficult to build the evidence base. Importantly, health-care dollars are finite, and without full disclosure of results, even negative results, researchers might end up replicating clinical trials needlessly. Moreover, if clinical trials uncover adverse events with an intervention and these aren’t publicly disclosed, other subjects will be exposed to the same “known but undisclosed risk,” she said.
“The whole reason it is justified to experiment on humans to begin with,” she said, “is because of the potential to contribute to generalizable knowledge and advance the common good. If you don’t disclose the results publicly in some fashion, then you really aren’t contributing to generalizable knowledge. It raises questions whether you should be allowed to experiment on that group of people at all.
Krumholz said that in failing to publish/report study results, researchers are violating an ethical obligation they have with their subjects. Their analysis reveals that some of the nation’s most trusted academic medical centers are “failing to uphold their moral obligation to people who are agreeing to be in their studies,” he said.
In terms of accountability,
Krumholz told TCTMD that just as researchers must seek institutional review
board (IRB) approval from their institution and informed consent from the
subjects, academic centers have an obligation to make sure the “final step” is
taken, that being the dissemination of the study’s results.
1. Chen R, Desai NR, Ross JS, et al. Publication and reporting of clinical trial results: cross-sectional analysis across academic medical centers. BMJ 2016;352:1637.
- Dr. Krumholz and Dr. Miller report no conflicts of interest related to the publication.