Many FDA-mandated postmarket studies not completed, study finds

Results of an internal FDA study show the agency has limited procedures for monitoring the progress, results of Condition of Approval studies.

Many studies mandated by the FDA as a condition for marketing approval of a medical device go uncompleted by device manufacturers, according to a report conducted by scientists within the FDA.

The FDA requires Condition of Approval (CoA) studies to address safety and effectiveness issues that may not have been fully addressed by studies supporting premarket approval applications. The requirement allows a manufacturer to market a device while collecting further information on its performance.

To characterize the use and performance of CoA studies, S. Lori Brown, PhD, MPH, a director at the FDA’s Center for Devices and Radiologic Health (CDRH), Surveillance and Biometrics Division of Postmarket Surveillance, and colleagues tried to retrieve information on the status of all premarket approvals (PMA) granted by the FDA between January 1998 and December 2000 that included a requirement for CoA studies. For such information, the researchers reviewed manufacturers’ annual reports, retrieved documents from the CDRH’s IMAGE database of scanned PMAs and surveyed the lead reviewers responsible for such studies, according to the report.

Out of 127 PMAs granted by the FDA during that time, 45 PMAs required CoA studies. However, the researchers found no information on 26 (58%) of the studies in manufacturers’ annual reports.

Additionally, six of 11 PMAs (54%) requiring CoA studies had not reported results to the Office of Device Evaluation, despite the final results being due, according to the report.

After being surveyed, reviewers reported that 10 cases (22%) had no results yet available and two (4.4%) had not yet been initiated by the sponsor. In another four cases, the reviewer was uncertain as to the status of the study.

“Overall, based on the reviewer survey, fewer than half of the PMA Condition of Approval studies (42%) were completed or in progress but not yet due. Another two Condition of Approval studies were not completed because the device was withdrawn from the U.S. market,” the authors said.

“The study also revealed that due to a lack of ... systems for tracking Condition of Approval studies, it is very difficult for anyone to obtain information on the studies or their status, unless that person has extensive knowledge of the individual products under study,” they added.

Interviews with staff at the Office of Device Evaluation also revealed that there was no formal mechanism for tracking progress of CoA studies and no formal means for determining whether the lead reviewer had received, reviewed or acted on any CoA study results, the authors noted.

“Our findings indicate that CDRH has limited procedures for monitoring manufacturers’ progress and results from Condition of Approval studies,” the authors said.

“The Approval Order Letter to the manufacturer explicitly states that failure to comply with the Conditions of Approval invalidates the approval. However, this circumstance has not been used to revoke a PMA,” they said.

To assure CoA studies get performed and monitored, the authors recommended several measures be taken. Some of these measures include:

transferring the responsibility for tracking and monitoring CoA studies to the Office of Surveillance and Biometrics, which is responsible for postmarket studies of patient safety;
requiring formal standards for tracking all CoA studies, including concrete, enforceable due dates and requiring periodic progress reports; and
establishing a procedure for taking action when commitments to conduct CoA studies are not met.

For more information:
Brown SL, Bezabeh S, Duggirala HJ. Condition of Approval Studies As a Postmarket Tool for PMA Approved Cohort 1998 - 2000. U.S. Food and Drug Administration Center for Center for Devices Evaluation and Radiological Health. Final report March 18, 2005. Available at: http://www.fda.gov/oc/whitepapers/epi_rep.pdf.