Americans are learning a thing or two about clinical trials as they watch the tense, televised push-pull between President Trump promoting a drug combination for Covid-19 based on skimpy, preliminary clinical trial data and Dr. Anthony Fauci promoting caution about the combination. Fortunately, the federal government provides a handy resource for navigating such disputes, ClinicalTrials.gov, where drug makers and other sponsors of clinical trials must report their results.
The Food and Drug Administration bases its decisions largely on the results of such clinical trials, which reveal how effective or safe a drug or device is compared to existing options or placebos. But that decision-making machinery can be thrown off when trial sponsors don’t have to share the results of all of their trials.
We identified a loophole letting trial sponsors do just that and sued the federal government to close it. And we won. But we worry it will prove a hollow victory unless the FDA and National Institutes of Health step up enforcement of an important law, and soon.
First, some background.
The FDA is good at what it does, but it can make mistakes. Take, for example, Vioxx (rofecoxib), a blockbuster painkiller made by Merck. The FDA approved Vioxx in May 1999. After approval, Merck collected clinical trial results that linked the use of Vioxx to increased risk of heart attack, stroke, and other cardiovascular problems and shared them with the FDA — but not with independent researchers. If researchers had access to all of the data, they could have raised the alarm years before Merck took rofecoxib off the market in 2004.
Even FDA overseers need oversight, in the form of scientists and researchers who provide second opinions on data from clinical trials.
That’s why Congress passed the Food and Drug Administration Amendments Act (FDAAA) in 2007: to help prevent such tragic mistakes. It’s a transparency law, one that requires companies, universities, and government labs that sponsor important clinical trials to reveal the results to patients, physicians, and independent researchers.
On paper, the FDAAA makes it illegal for trial sponsors to cherry-pick results, meaning publishing favorable results (like data showing safety and effectiveness) while withholding unfavorable ones (like data showing toxicity or lack of effectiveness). If independent researchers have access to all of the data from all trials — favorable and unfavorable — they can double-check the work of the FDA and help keep the public informed.
In practice, the mandate isn’t working nearly as well as Congress envisaged. Results from clinical trials are supposed to be posted on ClinicalTrials.gov but often they aren’t. More than 12 years after the FDAAA went into effect, estimates from numerous independent researchers suggest that roughly one-third of applicable clinical trial results — thousands of them — are missing.
Part of the reason is that in 2016, the FDA’s parent, the Department of Health and Human Services, and the FDA’s sister agency, the NIH, created an improper legal loophole that exempted many clinical trials of FDA-approved products completed between 2007 and 2017 from any obligation to ever file their results with the ClinicalTrials.gov database.
In 2018, we brought suit in federal court to close the loophole. Last month, a federal judge ruled that HHS and NIH had frustrated the “unambiguous” text and intent of FDAAA and ordered the agencies to require reporting and posting of the missing data.
That’s the theory, anyhow. Unfortunately, our court win can’t and won’t enforce itself. When a trial sponsor fails to post results on ClinicalTrials.gov, as required by the FDAAA, the FDA and NIH are authorized to impose penalties, including a fine of up to $10,000 a day and termination of government grant money for noncompliance.
Yet despite widespread noncompliance, these agencies have never imposed a single fine, withheld a single grant, or imposed any other penalty on a noncompliant trial sponsor. One group, the University of Oxford’s Evidence Based Medicine DataLab, estimates that the FDA’s lack of enforcement is so severe (and noncompliance so widespread among trial sponsors) that the FDA has forfeited billions of dollars in uncollected fines.
Why are they ignoring this issue and the revenue it could be generating? The FDA has taken the position that enforcing the FDAAA is entirely optional. In fact, the FDA and NIH have said that even determining whether clinical trials and trial sponsors are in or out of compliance with the FDAAA is a discretionary task — a task that they have chosen not to do.
As a result of the unwillingness of the FDA and NIH to enforce the law, drug companies, device makers, universities, and other trial sponsors have come to expect that they can withhold their results from ClinicalTrials.gov with impunity. Without enforcement, the ClinicalTrials.gov database will remain incomplete and the purpose of the FDAAA will go unfulfilled. Without enforcement, Americans are at greater risk of wasting money on useless medical products and being injured by unsafe ones.
If FDA and NIH prove unequal to the task, Congress will have to step in to force the agencies’ hands.
Christopher Morten is supervising attorney at New York University’s Technology Law and Policy Project. Peter Lurie is president of the Center for Science in the Public Interest. Charles Seife is a journalist and professor at New York University.