FDA-Funded or Not: Final Rule Makeover Means All Research Must Be Registered and Report Results

In an effort to increase transparency throughout the clinical research process, the United States Department of Health and Human Services along with the National Institutes of Health (NIH) last week announced that all clinical researchers will be required as early as next year to report all registration and results information regardless of whether their trials are covered under the Food and Drug Administration (FDA) Amendments Act of 2007.

The final rule, as the mandate is referred to, follows years of calls for increased accountability and greater compliance among US investigators and study sponsors. “There’s a long standing lack of transparency over what FDA funds and what happens with those trials, particularly for the non-FDA regulated trials,” Joseph Ross, MD, MHS (Yale School of Medicine, New Haven, CT), a clinical researcher and advocate for open data, commented to TCTMD. “This is definitely a step in the right direction.”

In a special report published online September 16, 2016, ahead of print in the New England Journal of Medicine, ClinicalTrials.gov director Deborah Zarin, MD (National Institutes of Health, Bethesda, MD), and colleagues summarize the final rule. “The days of deciding whether or not summary results are worth reporting are over: all such trials will have summary results information posted publicly on ClinicalTrials.gov,” they write. “The time to decide whether a trial is worth doing is before the trial is started, not after participants have been put at risk.”

The Biggest Changes

One of the biggest changes that comes with this announcement is specific language that now describes which studies need to be reported, Zarin and colleagues write. Previously, “the regulated community could not always be certain which trials were covered because many of the statutory terms were not fully defined,” they say.

Going forward, “all multigroup studies and all single-group interventional studies with prespecified outcome measures are considered ‘controlled,’” Zarin and colleagues report, adding that secondary and other prespecified outcome measures will also have to be clarified in the future.

In terms of transparency, the final rule requires submission of results for trials of unapproved products as well as baseline information on race or ethnic group, if associated with the primary outcome measures. All adverse-event and mortality timeframe and collection methods will need to be reported, as will full study protocols and statistical analysis plans at the same time as results submission.

Finally, the final rule will shorten the time frame in which the NIH will post submitted records, and disclaimers will be included if the data have not been certified by quality-control standards yet. This, in particular, will shorten delays and “we’re going to learn a lot more,” Ross said.

As for timing, the final rule’s effective date is January 18, 2017, with all responsible parties having until April 18, 2017, to comply.

Enforcement Questioned

While “all these little tweaks are terrific,” Ross said “now the real question is: How are they going to be able to enforce it?”

A long-standing criticism of the 2007 FDA law and ClinicalTrials.gov “is the lack of any penalties for nonregistration and nonreporting,” he continued. “That’s where we need to see improvement.”

The FDA will be held accountable for enforcing the final rule, but Ross questioned whether the organization has the ability to do just that. “My hunch would be the FDA needs more resources in order to take on additional responsibility,” he said. “They are clearly already managing plenty.”

Beyond the FDA, “the obligations of the National Library of Medicine and ClinicalTrials.gov keep growing and growing, and the question is: Is their budget at staff continuing to grow and grow?” Ross added.

And what about academic institutions that receive NIH funding? “They don’t have a staff dedicated to this the way pharmaceutical and medical device companies would. So compliance is going to be a major issue,” he said.

No Move Yet Toward Open Data

From a big picture, the final rule is “definitely a good thing,” Ross said, but it completely omitted the issue of sharing trial results after a study is completed. “In order to really maximize the time, effort, and funding going into clinical research, the next step would be sharing the data,” he observed.

“A lot more clinical studies could be done using the data that has already been collected, but it sits on somebody's work computer and it isn't available to others,” Ross explained, acknowledging that he is unsure if the final rule will serve as the first step to ultimately building out an even more transparent data-sharing system. “Getting summary data is incredibly important, but this is just one more thing that could be done,” he said.

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