A study published today in The BMJ reveals that COVID-19 vaccines and treatments were developed at “warp speed,” and now scientists are concerned about the US Food and Drug Administration’s (FDA) poor oversight of clinical trial sites.

According to regulatory records, the FDA only inspected nine of Pfizer’s 153 trial locations before it licensed its covid-19 mRNA vaccine. Similarly, Maryanne Demasi, an investigative journalist, reports that 10 of 99 Moderna trial sites and five of 73 Remdesivir trial sites were checked.

Notably, while Brook Jackson was working as a regional director, she filed a complaint with the FDA regarding wrongdoing at three clinical trial sites that were evaluating Pfizer’s covid-19 vaccine. Jackson noted a number of issues, including fabricated data, patients who weren’t blinded, and poorly trained vaccine providers who were reluctant to follow up on adverse events.

Jackson says, “I thought that the FDA was going to swoop in and take care of everything.” 

However, the aforementioned study sites were not inspected by the FDA.

The FDA’s regulation of clinical trials has been criticized as “grossly inadequate” by experts. According to them, the issue, which predates COVID-19, extends beyond a lack of inspections and also involves a failure to promptly alert the public or scientific publications when violations are discovered, effectively hiding scientific misconduct from the medical establishment.

According to David Gortler, a pharmacist and pharmacologist who served as a senior advisor to the FDA commissioner from 2019 to 2021 and an FDA medical reviewer between 2007 and 2011, the agency is “endangering public health” by keeping violations found at clinical trial sites a secret.

If the product is intended for the US market, the FDA monitors clinical trials of FDA-regulated medicines and devices both domestically and internationally. It makes routine site visits for trials, examines the records of those locations or the regional institutional review boards (IRBs), and handles complaints of noncompliance. The percentage of trial locations that the FDA inspects has no set goal.

The FDA told The BMJ that it only has 89 inspectors for its bioresearch monitoring program, which ensures the quality and integrity of data submitted to the agency in support of new product approvals and marketing applications, despite the estimated hundreds of thousands of clinical trial sites operating across the US and abroad. However, the FDA said that it is hiring more inspectors to reach its yearly average of 100.

Professor Jill Fisher from the University of North Carolina says: “I don’t think that it is a sufficient number of staff to do that kind of level of oversight.” 

She adds: “The FDA must have enough of a presence to dissuade investigative sites from committing fraud.”

The FDA suspended its site inspections between March and July 2020, when pandemic restrictions were at their strictest, and only “mission critical” inspections were conducted. However, according to Gortler, this was precisely the time when the FDA should have increased its control, not decreased it, given the rapid development of covid-19 products intended for millions of individuals.

The FDA told The BMJ that it takes the regulation of clinical trials seriously and that it has adjusted to travel restrictions by publishing draft regulatory assessment guidance for remote inspections, which describes remote records requests and virtual inspections using live streaming and video conferencing.

Demasi observes that the FDA has a lengthy history of inadequate oversight of clinical trial sites. For instance, the FDA was found to have audited less than 1% of the country’s clinical trial sites between 2000 and 2005, according to a 2007 report by the Department of Health and Human Services’ Office of the Inspector General. The report was also highly critical of the agency because it lacked a database of active clinical trial sites.

The FDA responded by forming a task force and developing “new regulations and recommendations further to improve the conduct of clinical studies and increase the protection of people participating in clinical trials,” but it denied The BMJ an interview with a member of the task force.

Furthermore, a 2020 study published in the journal Science investigating the FDA’s enforcement of clinical research standards between 2008 and 2019 found that the agency was frequently light-handed, sluggish to act, and secretive. According to the report, the FDA rarely issued penalties, and when it did formally warn researchers about breaking the law, it frequently failed to guarantee that the concerns were resolved.

Although the FDA makes its inspection reports public, it does not actively share them. Additionally, it often does not inform the general public to research wrongdoing it discovers or tell journals when a site taking part in a published clinical trial receives a serious warning.

Demasi cites claims of the FDA’s understaffed and demoralized workforce. The FDA “needs to be better funded and staffed to conduct inspections. At a minimum, the agency needs to inspect sites when complaints or concerns have been filed,” says Fisher.

Gortler disagrees, nevertheless, that the FDA lacks adequate funding. He argues that the organization needs to be leaner and more effective, with staff members who are enthusiastic about enhancing public health, given its overall budget of $6.1 billion in 2021. 

“Half of its budget, about $3bn, is discretionary, which means it could have hired contractors, retirees, or repurpose existing workers. It chose not to. The FDA was just yawning its way through the pandemic. The entire agency is broken.”

Source: 10.1136/bmj.o2628

Image Credit: Al Drago/CQ Roll Call – Getty