The reporting of clinical trial results to a public database — mandated by a 10-year-old federal law — has improved sharply in the last two years, with universities and other nonprofit research centers leading the way, according to a STAT analysis of government data.
Overall, trial sponsors had disclosed 72 percent of required results to the federal ClinicalTrials.gov database as of September. That compares with 58 percent just two years earlier.
Unreported research data can compromise the safety of human research and slow the pace of innovation, and the increase coincided with sustained attention to the problem by advocates for transparency in science, the news media, and even then-Vice President Joe Biden.
Especially striking were the increases at major research universities, which conduct the vast majority of academic trials: Their reporting jumped from 58 percent to 77 percent of trials.
The National Institutes of Health and top recipients of its funds did even better, a sign that leaders in academic medicine are finally taking seriously the 2007 law that requires reporting the results of most human studies of medical treatments.
Drug and device companies improved more modestly.
STAT examined nearly 18,700 clinical trials whose results should have been posted to ClinicalTrials.gov from 2008 to Sept. 11, 2017. The investigation follows a similar report by STAT two years ago, which found that prestigious medical research institutions were among the most flagrant violators of the reporting law.
Many of the biggest gains were at research institutions singled out for woeful reporting in the earlier STAT investigation, including Memorial Sloan Kettering Cancer Center, the University of Pittsburgh, and Stanford University. Such formerly routine violators improved, on average, from reporting the results of just 35 percent of studies to 76 percent.
“We put everyone on notice that we consider this an extremely high priority,’’ even for busy and sometimes recalcitrant faculty, said Dr. Mark Cullen, senior associate dean for research at Stanford Medical School.
STAT was the first to examine the track records of individual institutions, and the improvement by the worst offenders suggests that naming names drove better reporting, experts said.
That investigation and assessments by other groups “shows the power of public accountability . . . for fixing what is probably the single most important flaw in the fabric of evidence-based medicine,’’ said Dr. Ben Goldacre, a fellow at the University of Oxford in the United Kingdom and a founder of projects to press for openness in clinical research.
The NIH is the largest funder of academic biomedical research in the United States and runs the clinical trials database. In a written response to questions, the agency attributed some of the improvements to clarifications made in its final rule for ClinicalTrials.gov, which took effect in January 2017, and to NIH efforts to educate researchers.
The findings weren’t all positive. Results for 4 of 10 trials were reported after the legal deadline — one year following a trial’s completion or termination — and there were notable exceptions to the overall trend.
Valeant Pharmaceuticals, Albert Einstein School of Medicine, the University of Nebraska, and the University of California Irvine, for example, continued to flagrantly violate the law. Each has failed to report even 20 percent of its trials within the legal deadlines.
In written statements, Valeant said it was working to provide results to ClinicalTrials.gov, or seeking approvals for delays from the Food and Drug Administration, and Albert Einstein said it would hire a specialist to “ensure that our researchers will come into compliance.’’ Nebraska said it had dedicated resources to compliance and vowed to “prioritize this issue going forward,’’ and UC Irvine said it had recently taken “numerous steps to improve compliance’’ and planned to “meet or exceed the best practices’’ going forward.
Millions of patients and doctors use ClinicalTrials.gov to find trials, compare the effectiveness of approved and experimental drugs and devices, and survey sometimes deadly side effects. The legal requirement to submit results began in 2008. It stemmed from many cases in which companies allegedly hid negative clinical evidence about highly profitable drugs — such as links to suicidal thoughts by teenaged users of GlaxoSmithKline’s blockbuster antidepressant Paxil.
Designed as a universal, free, and open repository of human studies, ClinicalTrials.gov was meant to compensate for deficiencies in the scholarly literature. Journals publish results selectively and in hard-to-compare formats, and often charge subscription fees. Results on ClinicalTrials.gov also honor the sacrifice of trial volunteers and help researchers plan safer, more promising follow-up studies, advocates say.
National and global public health leaders reacted to STAT’s 2015 findings with anger, as did Biden, who threatened to slash federal research funds to law-breaking recipients of government grants.
Jennifer Miller, a New York University professor who rates pharmaceutical companies’ transparency for trials on approved drugs, credited the acceleration in compliance partly to pressure by US and global health authorities, as well as to journalists, scholars, and independent watchdog groups “measuring and benchmarking the process. And what gets measured often gets done.’’
In 2015, drug and device makers, on the whole, easily outperformed universities in reporting results. The difference narrowed sharply by 2017, although both categories showed improvement overall.
Many universities and nonprofit research organizations identified as major offenders by STAT in 2015 backfilled large gaps in ClinicalTrials.gov, belying prior complaints that the system was unduly complex or burdensome. In 2015, Stanford had submitted results for only one-third of trials due — partly, an official said, because professors lacked the time and money to comply. By 2017, it had submitted results for 85 percent.
The university learned from STAT’s earlier investigation that “we had a serious problem,’’ Cullen said. Soon after, it hired six full-time employees to train and coach faculty for compliance with ClinicalTrials.gov and FDA rules.
Memorial Sloan Kettering went from providing just 20 percent of its required results in 2015 to 98 percent as of 2017. Dr. Paul Sabbatini, one of the center’s top clinical research executives, credited the addition of two dedicated reporting specialists after STAT’s coverage of his institution’s poor record.
“Everyone [now] understands that this push toward transparency is important,’’ he said. “We hopefully would have come up to speed anyway, but shining a light on it made it happen in a much easier and faster way.’’
Stellar results came from a few drug companies, including Belgium-based UCB, the top performer of any leading organization. It was among a handful of top research entities that posted all required trial results. Unlike most others, UCB did so within the time limit in the vast majority of cases. But these good performers were offset by lagging drug makers such as Valeant, whose record actually worsened from 2015 to 2017.
Two years ago, the NIH and FDA said they hadn’t penalized violators because no final rule was in place. The law gives the agencies authority to levy financial penalties — withholding grants, or in the case of drug companies, imposing fines of up to $10,000 a day. In theory, the FDA could have brought in $40 billion from corporate violators for violations as of September, STAT calculated.
That final rule has now been adopted, but in effect, it retroactively forgives any violation prior to its reporting requirements going into full force on Jan. 18. And the agencies have not expanded their enforcement staffs. The new rule clarifies definitions and requires entry of certain previously optional information, such as why some studies are stopped prior to completion, descriptions of experimental interventions, and trial start dates.
FDA spokeswoman Lauren Smith Dyer in a written statement said the agency would integrate ClinicalTrials.gov compliance and enforcement into its current monitoring program, which conducts more than 100 inspections of research organizations annually. The agency will not add staff.
The NIH said that if a grantee fails to report trial results, “NIH may take an action up to wholly or partly suspending or terminating the grant.’’ Like the FDA, it will add no staff and currently has no dedicated compliance staff.
The NIH faces an additional challenge. Beginning this year, its policies require all researchers it supports to report results on trials beyond those for drugs, medical devices, and vaccines. These include observational studies, examinations of nutritional supplements, and Phase 1 safety trials. As of 2017, nearly 800 such experiments had been completed for more than a year and would have been subject to this new reporting requirement.
Goldacre called the lack of new enforcement resources “extremely concerning.’’
Charles Piller can be reached at charles.piller@statnews.com. Follow Stat on Twitter @statnews.
