FDA's oversight of drug trials is dangerously lax, report says.

The FDA's oversight of volunteers in clinical drug trials is sorely lacking, according to a report from the Office of the Inspector General (OIG) for the Department of Health and Human Services, and the agency is overly reliant on voluntary compliance from drug companies even when the companies' violations of FDA policy are flagrant. The report by Inspector General Daniel Levinson, released in September, was prepared in response to congressional inquiries.

Its findings depict an agency that is disorganized, plagued with poor record-keeping, and unable to monitor subjects in clinical trials with any rigor or thoroughness. Millions of people take part in these trials and, the report suggests, their safety could be compromised.

The study set out to determine how well the FDA's Bioresearch Monitoring (BiMo) Program protects participants in trials paid for by drug and device manufacturers who are seeking FDA approval for their products. The OIG examined FDA inspections of company-financed trials that occurred from fiscal year 2000 to fiscal year 2005.

One of the key problems, the study found, is that the agency does not maintain a registry of institutional review boards (IRBs)--committees made up of medical experts with responsibility for overseeing subject safety in research trials and ensuring that researchers adhere to strict ethical guidelines. The FDA inspected very few IRBs, although "IRBs are important because their primary purpose is to ensure that clinical investigators take appropriate steps to protect the rights and welfare of human subjects," the report found.

Another problem is the apparent lack of coordination among the agency's three centers that regulate medical products--the Center for Drug Evaluation and Research, the Center for Biologics Evaluation and Research, and the Center for Devices and Radiologic Health which leads to inconsistency in inspections. "Uncertainty of timing and lack of coordination impede FDA's ability to conduct [bioresearch monitoring] inspections," Levinson wrote.

Among the study's key findings:

* The FDA inspected fewer than 1 percent of company-funded clinical trials during fiscal years 2000 to 2005.

* The agency has 200 inspectors, some of whom audit trials part time, to inspect about 350,000 sites.

* The FDA does not keep a complete database of all clinical trials it monitors, so it does not have an accurate record of how safe the trials are, or how they compare to past ones.

* Most (75 percent) of the inspections were so-called surveillance inspections, meaning they focused on the trials' clinical results, not on the well-being of the human subjects.

The OIG also expressed concern about the FDA's reliance on voluntary compliance and low rates of follow-up after discovering violations of agency policy. The FDA issues three levels of response to violations: NAI (no action indicated), VAI (voluntary action indicated), and OAI (official action indicated). The study found that in 70 percent of the OAI cases, the Center for Drug Evaluation and Research downgraded the inspectors' findings to VAI status. And of 348 OAIs, only 26 companies were disqualified from conducting further clinical trials.

The study recommended that the FDA establish a database of all ongoing trials and a complete registry of research-ethics boards, and that it maintain better records of its trial inspections. Levinson also stressed that the agency should exert more authority over those involved in designing and running the studies.

"FDA should consider seeking additional authority that covers all of the stakeholders in the management and conduct of clinical trials," he wrote. "In particular, FDA should consider seeking authority to include the colleagues and subordinates of a clinical investigator if they participate in the conduct of a clinical trial."

The full report, The Food and Drug Administration's Oversight of Clinical Trials, is available at http://oig.hhs.gov/oei/reports/oei-01-06-00160.pdf.