WASHINGTON — Researchers will have to publicly report the results of many more clinical trials, including some for drugs and devices that never reach the market, under new government rules announced Friday.
The federal rules, which also require more complete reporting of deaths, clarify and strengthen a 2007 law that requires researchers to report results of many human studies of experimental treatments for ailments such as diabetes, cancer, and heart disease.
A STAT investigation last year found widespread noncompliance with reporting requirements by both drug companies and academic institutions — including universities that are among the top recipients of government research funding, and by National Institutes of Health staff scientists. In the vast majority of cases, study results were reported long after statutory deadlines or not at all.
Yet not a single researcher or trial sponsor has been fined or penalized, STAT reported — though the Food and Drug Administration had the authority to fine violators more than an aggregate $25 billion since the law went into force in 2008.
Government officials said the new rules are meant to improve compliance with requirements for public registration of trials and posting of data on the ClinicalTrials.gov website. But advocates for transparency in clinical research cautioned that the success of the new rules, which take effect Jan. 18, 2017, will depend on the vigor of government enforcement.
The data help doctors and patients gauge the safety and benefits of treatments and aid researchers in making informed judgments about future research.
Citing the STAT investigation, Vice President Joe Biden called in June for defunding federal grant recipients who did not comply with the law. On Friday, while announcing parallel improvements to a National Cancer Institute clinical trials website, he said those changes and the new rules for ClinicalTrials.gov “will improve the safety, accessibility and impact of our clinical research system.” He added that the changes “will help patients today and help researchers all over the world in their quests to find new cures. And they come at a true inflection point in our fight against cancer.”
Federal officials said last year that they wouldn’t penalize offenders before clarifying the reporting rules. Now that this is happening, “I’m expecting a flood of trials to get registered,” FDA Commissioner Robert Califf told reporters during a conference call. “It would be pretty hard to hide that you are doing a clinical trial or hide the result. … I’m very optimistic about this.”
The new rules leave in place many exemptions to the results-reporting requirement for privately funded studies — including small trials examining just the safety of a new drug, small feasibility studies of medical devices, and behavioral intervention studies. NIH-funded projects of those types must report results, based on a separate NIH policy.
Most trials entered into ClinicalTrials.gov before 2008 are also exempt. The exclusions are so broad that only a fraction of all trials have been subject to the full provisions of the law; at the time STAT reviewed the data last year, just about 9,000 trials, among nearly 200,000, were subject to the reporting requirements. Under the final rules, the percentage of trials that must report results gradually should rise.
Researchers will also have to submit the race and ethnic background of trial volunteers if the information is collected, and show more details about adverse events — possible side effects of a treatment — that occur more than 5 percent of the time.
The new rules also require sponsors to update the website annually about the status of ongoing trials. Currently, some entries languish for years without new information, leaving the public and other researchers in the dark about whether a trial is still underway.
Some experts said that while the new rules should help, questions remain about the strength of enforcement to remedy lapses by companies or universities.
“It’s not enough to say that there may be certain penalties applied,” said Ben Goldacre, a fellow at the University of Oxford and cofounder of the COMPare project and Alltrials.net, which advocate for full disclosure in clinical research. Given that studies have shown that only a small fraction of trials comply with the law, he said, “That looks to me like an emergency.”
Goldacre said increased enforcement staffing at the FDA and the NIH would show the government was serious about ensuring compliance. Neither agency will add such staff, according to Califf, whose agency oversees private sector reporting, and NIH Director Francis Collins, whose agency is responsible for enforcement regarding NIH grant recipients as well as NIH staff scientists.
That’s “a big problem,” Goldacre said.
Califf said enforcement instead would be folded into the FDA’s existing bioresearch monitoring program, which collects information related to clinical trials during company inspections.
The law allows the FDA to fine companies up to $10,000 a day for noncompliance and lets the NIH withhold funds from grantees who violate the law.
“Typically, when the FDA believes there may be a violation of the law, it sends a warning letter” for voluntary correction, Califf said. He expects this method to handle most problems, and promised that the public will have “a good window of what’s going on” in compliance actions.
“I don’t think anybody wants to be on the wall of shame” — a notice in ClinicalTrials.gov that shows whether a study is in violation of the law — Collins said at the press briefing. “We’re not going to have a vast army to pursue the compliance issues, but we really don’t think that (will be) necessary.”
Both agencies will automate compliance checks to ensure trials are properly registered and results reported, and contact institutions as needed to provide all the data required to bring their trials into compliance with the law.
“We are serious about this,” Collins said, and will withhold funds if needed. “It’s hard to herd cats, but you can move their food, or take their food away,” he said.
The legislation that created ClinicalTrials.gov emerged from numerous cases of drug manufacturers withholding negative trial results, making drugs look more effective and less harmful. Efforts to market the antidepressant Paxil for teenagers more than a decade ago stimulated the push for better reporting. A recent analysis in the journal BMJ found that GlaxoSmithKline (GSK), Paxil’s manufacturer, failed to disclose 2001 data showing the drug to be no more effective than a placebo, and was linked to increased suicide attempts by teens.
“I was hoping that some of the really opaque areas of the law and policies would be clarified,” said Jennifer Miller, a New York University medical ethicist and expert on trial reporting, after reading summaries provided by NIH. “I’m just not seeing that sufficiently.”
Miller said the new rules appear to leave lingering ambiguity about whether reporting requirements for new drugs apply equally to old drugs being studied for new uses.
She also called for discussions about applying the reporting requirements to all early drug safety trials whose subjects are patients, who can be more vulnerable than the healthy volunteers often used in safety studies. This would require a change in the law or a move by the FDA to encourage voluntary reporting for such trials.
Collins said the government is serious about cleaning up the registry system. “This is about maintaining the trust that we have with participants in clinical trials,” he said. “If we fail to live up to that expectation, then that is an ethical failure.”