A hundred days of hidden medical evidence, law-breaking, and FDA apathy

Over the past 100 days, several leading American research institutions have failed to make clinical trial results public as required by the law, a review by TranspariMED has found.

Student activists from Universities Allied for Essential Medicines recently wrote to Robert Califf, the new head of the FDA, asking him to finally protect patient interests and enforce the law.

While many leading institutions have improved their trial reporting in recent years, a quarter of all trials still do not make their results public as required by the 2007 FDA Amendments Act (FDAAA).

In total, over 3,300 trials are still missing results on the American trial registry.

Making clinical trial results public within 12 months as required by law is not ‘just’ a question of legal compliance. It also accelerates medical progress because trial results are shared far more rapidly than is usually the case, and the risk of research waste is minimised.

Nonetheless, the FDA keeps dragging its feet on enforcing the law, and the National Institutes of Health (NIH) continue to hand out money to institutions that fail to rapidly share trial results.

This blog highlights some FDAAA violations that occurred over the past 100 days to illustrate how lack of effective enforcement harms patients and taxpayers in America.

Massachusetts General Hospital

Most the largest trial sponsors in America have trial reporting rates of 100%, or close to 100%. Not so Massachusetts General Hospital, which has been flagged as a major violator of the law in previous TranspariMED reports. The most recent trial whose results it failed to report is NCT04022161, which involved patients undergoing cardiac surgery. Massachusetts General Hospital currently owes its patients the results of 19 clinical trials.

Effective FDA enforcement could have netted the public purse $178 million from this institution alone – enough to finance future enforcement efforts for many years to come.

University of New Mexico

While U.S. law has given the National Institutes of Health the power to cut off federal funding to institutions that fail to make trial results public, the NIH has so far failed to use its powers to crack down on costly research waste. Maybe for that reason, the University of New Mexico does not appear to be in much of a hurry to make its trial results public. With trial NCT04274686 recently becoming overdue, the university now owes its patients eight trial results.

More than half of its trials remain unreported on ClinicalTrials.gov. Meanwhile, the university continues to launch new trials, many of which are presumably funded by American taxpayers

National Cancer Institute

The National Cancer Institute has considerably improved its trial reporting in recent years, achieving a reporting rate of 95%, but its track record is still far from perfect. Over the past 100 days, it has failed to meet the reporting deadline for cancer trials NCT01693783 and NCT02572453. In total, 11 trials by the NCI are currently missing results. Patients have been waiting for the overdue results of two of those trials for more than a year now.

Global Alliance for TB Drug Development

In June 2017, the TB Alliance officially signed up to the WHO Joint Statement, committing itself to making all clinical trial results public on trial registries within 12 months of completion. (WHO best practices go beyond U.S. legal requirements because they cover all trials, not just the minority of trials covered by the FDA Amendments Act.) However, subsequent research found that many funders later failed to deliver on their promises. Sadly, the TB Alliance too appears to be falling short of its own standards: two of its tuberculosis trials are missing results, more than two months after they should have been made public.

This example illustrates that good intentions alone are not enough: they need to be backed up with strong systems to track every trial and ensure that all results are consistently reported on time.

University of Southern California

With 13 missing trial results and a reporting rate of just 55%, the University of Southern California is one of the worst-performing large trial sponsors in the United States. Most recently, it failed to report the results of trial NCT01676818, which involved patients with cervical cancer. Another USC trial is over three years overdue by now. Overall, the university has racked up $95 million in uncollected potential fines, illustrating just how badly FDA has dropped the ball on enforcing the law. To the best of TranspariMED’s knowledge, NIH has failed to cut off the university from funding for future trials – effectively throwing good public money after bad.

The Cleveland Clinic

The Cleveland Clinic is another major sponsor that seems to lack the systems and processes required to ensure that all its trials report results as required by law. Out of its 47 due trials, eight are still missing results. Most recently, it has let down colorectal surgery patients who had volunteered to participate in its trial NCT02509260. Presumably, if the FDA had collected just a fraction of the $97 million in potential fines for past violations, the clinic would be paying more attention to making its research results public.

Icahn School of Medicine at Mount Sinai

Mount Sinai is a serial offender with 11 of its clinical trials currently missing results. Out of $71 million in potential fines, the FDA has so far collected exactly zero dollars. This year alone, five of its clinical trials have been left unreported, including Covid trial NCT04390191. According to the trial’s entry on ClinicalTrials.gov, “There is surge in COVID infected patients in New York City with a shortage of hospital beds, ICU beds and ventilators. Strategies to reduce the need for all of the above are immediately needed.” While hospitals worldwide are still urgently seeking better ways to treat their Covid patients, the sense of urgency around this trial within Mount Sinai seems to have evaporated: its results are more than two months overdue.

Baylor Research Institute

Baylor Research Institute has ten due trials in its portfolio, but has made the results of only two of those trials public as required by law. Its reporting rate of 20% is far below the average for major non-commercial sponsors. Most recently, the institution has failed to upload the results of a trial evaluating the efficacy and safety of everolimus immunosuppression treatment in liver transplantation for hepatocellular carcinoma. Potential fines left uncollected by the FDA: $30 million.

VA Office of Research and Development

The U.S. Department of Veteran Affairs’ research arm boasts on its website that all its trials are intramural and that it can “quickly move scientific discovery from the research setting to advancements in health care”. Its ClinicalTrials.gov reporting record tells a different story, with five trial results missing, including one result that is 920 days overdue. Note that a key benefit of trial registries is that they accelerate results reporting and hence speed up medical innovation.

Brigham and Women's Hospital

With nine applicable trial results missing, Brigham and Women's Hospital is among America’s worst violators of the FDA Amendments Act. Four of its results are more than a year overdue, indicating a sustained lack of attention to legal compliance and patient interests. The hospital’s most recent violation involves trial NCT04510402, which tested the safety of a novel Covid nasal swab. The hospital has not updated the trial’s ClinicalTrials.gov entry since August 2020.

Is reporting all trial results within 12 months realistic?

Yes it is. Check the FDAAA Trials Tracker for yourself. Institutions and companies with a perfect or near-perfect current compliance record include:

• M.D. Anderson Cancer Center

• Mayo Clinic

• Memorial Sloan Kettering Cancer Center

• Gilead

• GlaxoSmithKline

• AstraZeneca

Institutions that wish to improve their trial reporting may consider joining the Clinical Trials Registration and Results Reporting Taskforce, a peer-to-peer support network of noncommercial trial sponsors.

(The taskforce is independent of TranspariMED and is only flagged here as a useful resource.)

Note on research methodology

Using the University of Oxford’s FDAAA Tracker, TranspariMED scanned all recent violations and pulled out some examples to illustrate how weak enforcement of a key transparency law by the FDA and the National Institutes of Health perpetuates research waste, harming both patients and taxpayers. The Tracker website was accessed on 25-26 April 2022.

A major limitation of the Tracker is that it only flags due trials stretching back to 2018, while FDAAA applies to trials stretching back to 2007. Thus, the Tracker substantially undercounts the number of trial results that are missing in violation of the law.