Too much sunblock on clinical trial reporting

FDA and NIH urged to impose penalties on industry and academic researchers who fail to report results

Transparency supposedly solves a multitude of problems. As future Supreme Court Justice Louis Brandeis famously wrote in a 1913 Harper’s Weekly article: “Sunlight is said to be the best of disinfectants.”

The passive construction in his first iteration of that famous aphorism turns out to have been prescient. What good is sunlight if its target throws up shade?

Last week, the top Democrat on the House Committee on Energy and Commerce blasted two federal agencies for failing to enforce laws requiring drug manufacturers and taxpayer-funded researchers to publicly post the results of clinical trials in a publicly-funded database, ClinicalTrials.gov,  within a year of their completion. Citing numerous studies documenting widespread failure to report results, New Jersey Congressman Frank Pallone Jr. demanded the Food and Drug Administration and National Institutes of Health provide detailed lists of researchers sent non-compliance notices and report whether the agencies have taken any steps to impose monetary penalties on the scofflaws.

“FDA has not yet imposed any civil money penalties on any trial sponsors,” the former chairman of the committee drily noted in his letter. “The collection of these penalties would provide a stronger incentive for trial sponsors to comply.”

Congress created the clinical trial database in 1997. The original idea behind ClinicalTrials.gov was to help patients with serious illnesses identify ongoing trials that might give them access to experimental treatments not yet approved by the FDA.

A decade later, Congress expanded the types of trials that needed registering. More importantly, the bipartisan 21st Century Cures Act also required that the results of the trials be added to the database within a year of the trials’ conclusion.

Why posting results is important

The results requirement was crucial for practicing physicians and medical scientists. They needed access to that information to develop accurate clinical practice guidelines; to compare the relative effectiveness of different treatments; and to learn from other researchers’ failures.

That latter goal is especially important for current and future patients with life-threatening diseases. It allows them to ignore enrolling in similar, ongoing trials that have no chance of success and might harm the volunteers. Moreover, as the World Health Organization notes on its website: “Unreported trial results leave an incomplete and potentially misleading picture of the risks and benefits of vaccines, drugs and medical devices, and can lead to use of suboptimal or even harmful products.”

It’s also an ethical issue. Volunteers, who are often people with serious diseases, have a right to know the results of the trials in which they participate.

Medical research scientists, whether publicly or privately financed, should be the biggest backers of universal compliance with clinical trial reporting requirements. Public dissemination of failed trial results prevents the waste of scarce research dollars on duplicative experiments, and can provide clues for identifying more productive pathways for pursuing effective treatments.

Violations widespread

Yet violation of the law remains widespread in both the public and private sectors. A comprehensive review done in 2020 by United Kingdom researchers found only 40% of trials reported results within a year as required by law, with another 29% of trials reporting late. That left 31% of all trials or nearly one in three failing to report at all. An independent study by journalists at Science Magazine the same year turned up similar results.

The UK study, published in the Lancet, noted industry-funded researchers performed slightly better than NIH-funded researchers, but widespread non-compliance was common to both. An HHS Inspector General’s survey conducted last year found 35% of NIH-funded studies completed in 2018 failed to report in either 2019 or 2020.

That OIG report triggered a letter from four Republican Senators including Charles Grassley of Iowa. They requested much of the same information contained in Pallone’s letter. However, the Republicans only pursued NIH, which uses taxpayer dollars, and not the FDA, which oversees the far larger number of clinical trials conducted by drug and medical device companies.

Voluntary compliance?

As Science reported last year after seeking comment to its study: “NIH and FDA officials do not seem inclined to apply pressure.”  The magazine quoted Lyric Jorgenson, NIH deputy director for science policy, as saying her agency has been "trying to change the culture of how clinical trial results are reported and disseminated; not so much on the ‘aha, we caught you,' as much as getting people to understand the value, and making it as easy as possible to share and disseminate results."

An FDA official told the magazine that "FDA has limited resources, and we encourage voluntary compliance."

So, there you have it: A law gives federal agencies the power to impose monetary penalties for failure to comply. Yet the two main biomedical oversight and funding agencies are willing to publicly state that compliance is voluntary.

When compliance is voluntary, scofflaws go free. And the disinfecting power of sunlight is effectively blocked.

The original version of this story incorrectly listed the year of publication for Louis Brandeis’ article in Harper’s Weekly. It is 1913, not 2013.