Clinical trials underpinning U.S. Food and Drug Administration approval of new drugs and biologics often violated a key transparency law, a new analysis has found.
A team of American researchers examined 62 products by 42 pharma companies that gained FDA approval in 2016 and 2017. Collectively, these drugs and biologics were approved based on 1,017 clinical trials involving more than 187,000 participants.
VIOLATIONS OF LEGAL TRANSPARENCY REQUIREMENTS
Around a quarter of these trials were subject to the FDA Amendments Act, a transparency law that requires drug makers to register applicable trials on a public registry within 21 days of their start date, and to make their results public on the registry within 30 days of initial FDA approval of a product.
The study team found that 55 of the 62 FDA approvals included at least one clinical trial that was subject to the transparency law. However, in the case of 13 products, these trials did not consistently meet legal registration or reporting requirements.
Large pharma companies were far more likely to comply with the law. For example, Merck Sharp & Dohme was legally responsible for registering and reporting 27 trials, and fully complied in every single case. However, several other major players – Gilead, Johnson & Johnson / Janssen, Novo Nordisk, Sanofi, and Shire – fell short of legal requirements.
Nonetheless, the study – which also covered companies’ data sharing policies – found that overall, there had been “sustained improvement” in pharma industry disclosure practices compared to previous years.
SOME TRIAL RESULTS REMAIN COMPLETELY INVISIBLE
When the research team looked at all clinical trials, i.e. not only those subject to legal disclosure requirements, they were able to find results for all trials related to only 26% of the drugs and biologics approved by the FDA, despite searching the academic literature as well as the public ClinicalTrials.gov registry.
Thus, for three quarters of FDA-approved products, at least one relevant trial result remained hidden from independent scientists, doctors and patients.
BROKEN PROMISES ON TRANSPARENCY
The FDA Amendments Act was passed in 2007 to prevent pharma companies from distorting or hiding unflattering clinical trial results, and to provide scientists and the public with an overview of the evidence base on the benefits and harms of drugs, biologics, and vaccines.
The FDA has the power to impose fines on non-compliant companies, but so far has turned a blind eye to widespread violations, leaving over $21 billion in potential fines uncollected. Around 2,800 trials are currently missing results on the registry in violation of the law.
Image source: FDAAA Trials Tracker
Joe Biden had promised to crack down on law-breaking trial sponsors when he was Vice President, but has so far failed to deliver on his promise.
“Despite several studies showing poor compliance among drug companies [with the law], the FDA has yet to systematically penalize” law-breaking pharma companies, one of the study authors told STAT News.
GAPS IN SCOPE OF LAW AND ITS ENFORCEMENT
The authors suggested widening the scope of existing transparency legislation, as well as enforcement of existing laws:
“[O]ur finding… raises questions about whether FDAAA’s scope should be expanded to address the growing number of products approved by the FDA based on ongoing trials and trials conducted entirely outside the USA by non-US-based companies.”
“The finding that 42% of FDA-approved novel drugs and biologics fail to fully meet FDAAA reporting requirements suggests the FDA may benefit from more aggressive enforcement of this law… Despite several studies showing poor FDAAA compliance among drug companies, the FDA has yet to systematically penalise non-compliant companies.”
COMPARISON WITH EUROPE
As in the U.S., overall there has been significant improvement in European companies’ and universities’ compliance with transparency rules in recent years, and various European bodies have promised to continue pushing for more transparency.
However, Science recently reported that in Europe too, some major trial sponsors continue to flout the rules. Despite the Dutch regulator repeatedly having urged trial sponsors to make results public on the European trial registry, Amsterdam University Medical Center flatly told the publication that “[w]e see no advantage in double registrations or in doubling researchers’ administrative burden.”
Even after the EU Clinical Trial Regulation becomes binding national law in all European Union member states at the end of January 2022, each country’s medicines regulator will independently decide whether and when to start imposing sanctions.