SACHRP subcommittee calls for new and clarified guidance on continuing and expedited review.

ALEXANDRIA, VA -- OHRP should clarify guidance on the required duration of IRB continuing review, because continuing review may end when all research interventions and interactions with subjects are over and data collection for research purposes is complete, as described in the IRB-approved protocol at a research site.

That was the recommendation from a subcommittee of the SACHRP presented here March 13. The charge of the subcommittee was to review and assess all provisions of Subpart A of 45 CFR 46 and relevant OHRP guidance documents, and then to provide recommendations for the full SACHRP committee.

Subcommittee chair Felix Khin-Maung-Gyi, CEO, Chesapeake Research Review, Columbia, MD, added: "The IRB must have reviewed and approved the investigator's plan for data analysis and the safeguards in place for confidentiality protections. The investigator still retains the responsibility to notify former subjects and the IRB if subsequent analysis and/or new information raise concerns about rights, safety and welfare of human subjects."

Khin-Maung-Gyi noted several examples where interminable continuing review may not be helpful, including:

* Minimal risk social science surveys;

* Individual sites in multi-center trials after activity ceases at that site, but continues elsewhere; and

* Cooperative group studies that remain open solely to collect survival data.

He pointed out that neither HHS nor FDA regulations adequately answer the question of when continuing review can stop. "HHS and FDA have different operational definitions for what constitutes human subjects research." For example, he continued, FDA frames human subjects research within the context of using a test article with patients or controls, such as, a clinical trial. HHS rules, on the other hand, includes the concept of private information in addition to intervention.

Because of this lack of clarity, IRBs do not know when their oversight responsibilities end, he said. Is it after the last subject is enrolled, after the interventions are complete, after data collection is complete or after papers are published? As such, IRBs "are forced to err on the side of keeping things open forever, and to establish local compromise solutions," said Khin-Maung-Gyi.

Another question tackled by the subcommittee was: "Are there circumstances where continuing review can appropriately be conducted less often than once per year?"

The question was asked because current HHS and FDA guidance does not contain any basis for the current content of the continuing review process itself, he said. This "limits the flexibility of IRBs to employ appropriate procedures and criteria for ongoing review. For minimal risk research, the requirement for annual review is neither related to, nor appropriate to, the degree of risk."

The SACHRP subcommittee recommended that OHRP should issue an advance notice of proposed rule making (ANPRM) to seek comments regarding changing section 46.109(e) to allow IRBs latitude in setting review dates beyond one year (but not more than two years) for minimal risk studies, but potentially for other studies, as well.

This recommendation was accepted by the full SACHRP committee and seconded.

Further, in the ANPRM, OHRP should seek comments on the regulatory application of 46.111 to continuing review, and/or adding a new section, that would define simplified criteria and the expectations for the content of continuing review being based upon current risk level.

This recommendation also was accepted by the full committee, although SACHRP chair Ernest Prentice, Ph.D., University of Nebraska Medical Center, Omaha, NE, suggested the two recommendations be combined and the ANPRM recommendation be eliminated.

In the interim, the subcommittee continued, OHRP should revise its interpretation and develop new guidance to permit IRBs to develop, within their written procedures, policies and procedures for the selective application of section 46.111 to continuing review.

Khin-Maung-Gyi also reported the subcommittee's belief that existing guidance on continuing review should be consolidated and integrated. "The absence of consolidated guidance makes regulatory compliance more difficult than necessary," he said. "IRBs must explore extensive case law in the form of FDA and OHRP determination letters and 'dear colleague letters.'"

The subcommittee's recommendation stated that OHRP "should revise its continuing review guidance and clearly delineate those continuing review actions required by the regulations and those that are derived from the regulations by interpretation."

In the area of expedited review, the subcommittee recommended that implementation of changes to approved research that "are solely clerical or administrative should not require convened or expedited IRB review. OHRP and FDA should issue guidance permitting IRBs to define in their written policies and procedures changes to approved research that can be process by qualified IRB staff."

Lastly, said Khin-Maung-Gyi, the subcommittee stated that the term "expedited review" should be changed to "delegated review." "The term 'expedited review' is widely misunderstood to imply increased speed and decreased thoroughness of review."

This last recommendation generated some disagreement among the full SACHRP committee, with some members contending there are more serious matters to be considered than terminology. But Prentice disagreed: "Investigators look at expedited review and think it is shorter than regular review. It's not. They also think that it is a simple and abbreviated review. It gives investigators the wrong impression about our efforts in human subject protection."

Prentice also stated that the Part A subcommittee will convene again this spring and will present its modified recommendations at the next meeting of the full SACHRP panel in July.

By Joseph Pickett Managing Editor