Only 30% of FDA Regulatory Actions Are Backed by Research

Experts say that for the public to have confidence in medicines, regulators must be completely open about drug safety.

According to a study that was recently published in The BMJ, less than one-third of the regulatory decisions made by the US Food and Drug Administration (FDA) are supported by published research findings or public assessments.

According to the researchers, their results, which are based on an examination of drug safety signals identified by the FDA from 2008 to 2019, show that the FDA is either taking regulatory measures on information that has not been made public or that more comprehensive safety evaluations may be required when possible safety signals are identified.

Monitoring a medicine’s safety after it is made accessible to patients (known as post-marketing pharmacovigilance) is critical for monitoring drug safety. 

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Each year, the US Food and Drug Administration (FDA) receives over two million reports of adverse events via its Adverse Event Reporting System (FAERS). The FDA evaluates all potential safety signals to decide whether or not regulatory action is necessary.

The FDA Amendments Act of 2007 mandated that the FDA publish quarterly reports on safety signals from FAERS, giving people the opportunity to examine at them and learn more about this pharmacovigilance system.

A team of US researchers, therefore, decided to analyze safety signals identified within the FAERS database. They asked how often these signals resulted in regulatory actions and whether they were corroborated by additional research.

They found that from 2008 to 2019, 603 potential safety signals identified from the FAERS were reported by the FDA, of which about 70% were resolved, and nearly 80% led to regulatory action, most often changes to drug labeling.

In a separate in-depth analysis of 82 potential safety signals reported in 2014-15, at least one relevant study was found in the literature for about 75% of the signals but most of these studies were case reports or case series.

However, less than a third (30%) of regulatory actions were corroborated by at least one relevant published research study, and none of the regulatory actions were corroborated by a public assessment, reported by the Sentinel Initiative.

These are observational findings, and the researchers acknowledge some important limitations. For example, they did not evaluate regulatory actions taken in other countries in response to these safety signals, which might have informed the FDA’s actions, nor could they consider unpublished studies or other data accessible to the agency but not publicly available.

Nevertheless, they say these findings “highlight the continued need for rigorous post-market safety studies to strengthen the quality of evidence available at the time of regulatory action, as well as the importance of ongoing efforts to leverage real-world data sources to evaluate and resolve signals identified from the FAERS and support FDA regulatory decisions.

In a linked editorial, experts argue that regulators should publish all evidence underlying their responses to drug safety signals to reduce harm and ensure public trust in medicines.

The covid-19 pandemic has exposed the tension underlying regulatory decisions and the public’s right to know about serious risks associated with medical interventions, they write. This same tension exists more broadly in medicine safety.

“Safety signals are an important step, but radical transparency about available evidence and the basis for regulatory judgments is needed to reduce the harm caused by medicines, as is adequate follow-up to ensure safer use,” they conclude.

Reference: “Characterization and corroboration of safety signals identified from the US Food and Drug Administration Adverse Event Reporting System, 2008-19: cross sectional study” by Meera M. Dhodapkar, Xiaoting Shi, Reshma Ramachandran, Evan M. Chen, Joshua D. Wallach and Joseph S. Ross, 5 October 2022, The BMJ.
DOI: 10.1136/bmj-2022-071752