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The U.S. Food and Drug Administration (FDA) is conducting fewer inspections of clinical trial research sites than in past years, according to a recent report by the Government Accountability Office (GAO).
FDA officials attributed the decrease to the COVID-19 pandemic and a shortage of investigators, the federal watchdog said.
In preparing its report — which Congress commissioned — the GAO looked at FDA data and documents from fiscal years 2012 through 2023. It also interviewed an undisclosed number of FDA officials and 15 FDA investigators.
Investigative journalist Maryanne Demasi said she found the decrease in clinical research inspections “concerning.”
Demasi — who in 2022 published an investigation in The BMJ that found the FDA’s oversight in 2020 of COVID-19 vaccine clinical trials was “grossly inadequate” — told The Defender, “It appears that little has changed.”
The FDA’s lack of oversight is a big problem because the public relies on the quality and integrity of clinical trial data to ensure the safety of approved drugs, she said. “If the FDA drops the ball, as it appears to have done in the past few years, it puts people’s lives at risk.”
According to the GAO report, many FDA inspectors were frustrated, saying the agency often ignored their recommendations to take regulatory action when their inspections showed clinical research sites were out of compliance.
This is similar to what Demasi found during the COVID-19 clinical trials.
As she reported in The BMJ, a regional director overseeing Pfizer’s COVID-19 mRNA vaccine complained to an FDA inspector about a range of problems including falsified data, unblinded patients and inadequately trained vaccinators who were slow to follow up on adverse events.
“I thought that the FDA was going to swoop in and take care of everything,” the regional director told The BMJ. “What I was reporting was so important.” But the FDA did not inspect the trial sites in question.
Clinical research entities not being held accountable
According to the GAO, six of the 15 investigators said they felt clinical research entities weren’t being held accountable for the concerning observations made during inspections.
From fiscal years 2012 through 2020, the FDA classified only 3% of clinical research inspections as having serious deficiencies that would warrant regulatory actions.
This small figure is partly because the FDA downgraded more than half of the inspections completed in those years — meaning that although the inspectors initially classified the problems they found during their inspection as big enough to warrant official action, the FDA changed that to a less serious classification that didn’t require FDA action.
An example of official action is the FDA sending a warning letter to the clinical research site for not following study protocols by improperly enrolling subjects that didn’t meet eligibility requirements, or improperly administering doses of the study drug outside the required schedule, according to the GAO.
The FDA’s downgrading of the inspectors’ classifications frustrated the inspectors and affected their morale, the GAO said.
FDA inspectors take higher-paying jobs in drug industry
Relatively low pay also frustrated inspectors which, in turn, led to retention challenges. For example, two investigators who spoke with the GAO left the FDA for higher-paying industry jobs.
The FDA has increased the salary for new hires and offers up to $60,000 in student loan replacement, but FDA officials said compensation is still a challenge because the agency can’t match the salaries offered by the drug industry.
“Given that its operating budget is around $6.2 billion and half of that is discretionary, the FDA should be doing more to recruit and retain staff to meet the demands of the agency and improving morale among workers,” Demasi said.
FDA prioritizes inspections tied to new drug approvals
Each year, the FDA initially determines the total number of inspections it plans to conduct based on available staffing resources and historical trends.
But if there aren’t enough staff to complete all the planned inspections, priority is given to inspecting sites related to pending drug marketing applications to avoid delaying drug approval decisions.
That means inspections for ongoing clinical research may be delayed, the GAO said.
In other words, when the FDA doesn’t have sufficient staffing to police all clinical research sites it thinks should be inspected, it prioritizes which sites to inspect to prevent delays for the companies paying user fees.
“In negotiating the user fees with the drug industry,” the GAO report said, “FDA commits to meeting certain performance goals, such as reviewing marketing applications within a specified time frame.”
These user fees, together with annual funding from Congress, pay for the FDA’s work, according to the FDA’s website about user fees.
Additionally, the rate of inspections hasn’t kept up with the rate of drug applications.
The FDA conducted only 537 inspections in fiscal year 2022 — a 45% decline from its peak in fiscal year 2017 — even though the number of drug applications before the agency remained consistent, reported Government Executive.
“As a result of conducting fewer inspections, FDA may have less information to inform its review of marketing applications and surveillance of ongoing clinical research,” the GAO said.
FDA continues remote inspections, despite investigators’ concerns
Another issue inspectors told the GAO they were concerned about was the FDA’s continued use of remote inspections to inform its drug approval decisions.
In response to the COVID-19 pandemic, the FDA in March 2020 stopped all in-person inspections, except those deemed mission critical, and began using remote regulatory assessments to help counteract the decrease in on-site inspections.
Despite resuming normal operations for domestic inspections in July 2021 and foreign inspections in March 2022, the FDA “is exploring the continued use of remote regulatory assessments in the future, including both when on-site inspections are not feasible and for more regular use for certain entities,” the GAO said.
Most of the investigators interviewed by the GAO noted numerous challenges with remote assessments — such as issues with accessing requested electronic documents — and preferred conducting on-site inspections.
For instance, some investigators said assessing a site remotely gives pharmaceutical companies time to edit documents or create new documentation, due to the delay between when a document is requested and when it’s received for a remote assessment.
‘It’s staggering that the FDA still hasn’t got its act together’
Additionally, the GAO found that most of the FDA’s inspections occurred at domestic locations, despite a 2022 GAO recommendation that the agency improve its foreign inspection program.
More than 50% of drug manufacturers supplying the U.S. market are located overseas, the GAO noted in its 2022 report.
“Also,” Demasi said, “the [2024] GAO report indicates the FDA still doesn’t have a comprehensive list of clinical research trials sites that are eligible for inspection, which was called out by the Office of Inspector General back in 2007.”
“It’s staggering that the FDA still hasn’t got its act together,” she added.
The GAO report recommended the FDA evaluate its recruitment and retention efforts for its investigators — such as increased pay, student loan repayment and other financial incentives — to figure out whether these efforts are working.
In response, the U.S. Department of Health and Human Services (HHS) — which oversees the FDA — said the FDA is committed to following the recommendation, the GAO said.
HHS also said the FDA will use the results of that evaluation “to ensure the agency is using the most appropriate tools” to maintain its bioresearch monitoring investigator workforce.
The FDA did not immediately respond to The Defender’s request for comment.
