Regulatory Focus™ > News Articles > Warning Letter Analysis: Institutional Review Boards Cited for Deficiencies

Warning Letter Analysis: Institutional Review Boards Cited for Deficiencies

Posted 13 June 2012 | By

Two institutional review boards (IRBs) have been the subject of warning letters from the US Food and Drug Administration (FDA) in as many weeks after the agency discovered alleged deficiencies including failing to obtain informed consent from clinical trial participants and failing to maintain documentation on a lengthy list of categories.

Advocate Health Care (IRB)

FDA's 1 June warning letter to Advocate Healthcare's IRB Chairman, Joal Hill, references a November 2011inspection by the agency in which officials allege they found materials showing the organization "did not adhere to the applicable statutory requirements and FDA regulations governing the protection of human subjects."

Among the most prominent alleged violations include the failure of the IRB to "ensure that informed consent would be sought from each prospective subject or the subject's legally authorized representative"-a violation of 21 CFR 56.111(a)(4) and among the most basic of clinical trial principles.

The alleged deficiency affected a single trial sponsored by Advocate Hospital system in conjunction with the Emergency Medicine Foundation to test the effect of Etomidate and midazolam on patients hospitalized with sepsis and trauma.

While the study was-and is-registered on the federal government's clinical trial database,, Advocate said in a response to FDA's warning letter that it did "not make a connection" that the informed consent regulations applied to the study.

"The IRB's failure to meet this responsibility is particularly concerning because the concept of informed consent is fundamental to the conduct of ethical research," wrote FDA.

After being informed of the alleged deficiency, Advocate Health Care apparently went to some lengths to train its staff in the regulations of clinical trials, including conducting several workshops and educational sessions. In addition, it sent out a letter to all former participants in the trial in question retroactively informing them of the trial. The only problem, explained FDA, was that the IRB failed to review the letter sent to participants, further violating federal regulations.

Our Lady of Bellefonte Hospital (IRB)

In its 1 June warning letter to CEO Kevin Halter of Kentucky-based Bellefonte Hospital, FDA detailed the results of its January 2012 inspection of the hospital's IRB, saying it had found no fewer than six main deficiencies in the organization's handling of clinical trial procedures.

Among the alleged deficiencies identified by FDA:

  • The IRB failed to prepare and maintain documentation of written procedures for the functions and operations of the IRB in various circumstances, including the reporting of findings, the timeframes for reviewing projects, reviewing proposed changes and ensuring prompt reporting of any problems or changes.
  • There existed no record of the IRB's membership, their earned degrees, responsibilities, experience or conflicts of interest. Similarly, the IRB did not maintain any record of the meetings of the IRB, including press reports, meeting minutes or correspondence between the IRB and investigators.
  • The IRB reviewed proposed research at meetings in which the majority of IRB members were not present, violating regulations regarding the quorum necessary to approve research. Moreover, it was unclear whether a voting member present at the meeting was a nonscientific member, also required in federal regulations. Further, the IRB then failed to notify investigators of the board's decision in writing, leaving no paper trail for FDA investigators to look at.
  • FDA found the IRB failed to follow expedited review procedures, which exist to allow smaller portions of the group to quickly review research matters of limited importance. The IRB was found to have constituted such a committee, which then reviewed ineligible research in violation of regulations.

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