Number 95-01
Human Subjects Protections

NOTE: THIS GUIDANCE HAS BEEN REPLACED BY OHRP’S JULY 11, 2002, GUIDANCE ENTITLED, “GUIDANCE ON CONTINUING REVIEW.” CLICK HERE FOR THE JULY 11, 2002 GUIDANCE.

OPRR Reports

January 10, 1995

Subject: Continuing Review -- Institutional and Institutional Review Board Responsibilities

Dear Colleague:

This letter is being forwarded to Institutional Officials and Institutional Review Board (IRB) Chairs throughout the country as a reminder of IRB and institutional responsibilities in continuing review of research activities.

The Department of Health and Human Services (HHS) Regulations, Title 45 Code of Federal Regulations Part 46 (45 CFR 46), require at Section 46.109(e) that "an IRB shall conduct continuing review covered by this policy at intervals appropriate to the degree of risk, but not less than once per year... ."

Continuing review must be substantive and meaningful. Review by the convened IRB, with recorded vote, is required unless the research is otherwise appropriate for expedited review under Section 46.110. Ordinarily, if research did not qualify for expedited review at the time of initial review, it does not qualify for expedited review at the time of continuing review. It is also possible that research activities that were previously judged as exempt in accordance with Section 46.101(b), or were qualified for expedited review in accordance with Section 46.110, have changed or will change, such that other than expedited IRB review is now required.

OPRR interprets "not less than once per year" review to mean review on or before the 1-year anniversary date of the previous IRB review required by 45 CFR 46, even though the research activity may not begin until some time after the IRB has given approval.

The regulations at 45 CFR 46 outline the minimum requirements for continuing review. They do not provide specific instructions to institutions or IRBs on how to set up their own rules for continuing review within the framework of the regulations. To ensure adequate protection of the rights and welfare of research subjects, institutions and IRBs may impose greater or more detailed standards of protection for human subjects depending upon the nature or location of the study, the degree of risk involved to the subject population, and other factors.

Investigators must also report to the IRB planned changes in the conduct of the study, since these may affect the protection of human subjects. Minor changes proposed for previously approved research may be reviewed in an expedited manner prior to the scheduled continuing review date in accordance with Section 46.110. When a proposed change in a research study is not minor, then the IRB must review and approve changes at a convened.meeting before changes can be implemented. The only exception is the rare circumstance in which a change is necessary to eliminate apparent immediate hazards to the research subjects. In this case, the IRB should be promptly informed of the change following its implementation and should review the change to determine that it is consistent with protection of human subjects. Unanticipated risks to subjects or new information that may affect the risk/benefit assessment must be promptly reported to, and reviewed by, the IRB to ensure adequate protection of human subjects.

The regulations at Section 46.111 set forth the criteria to be satisfied if an IRB is to approve research. These include determinations by the IRB regarding risks, potential benefits, informed consent, and safeguards for human subjects. The review criteria at Section 46.111 are a requirement during continuing review just as they are in initial review.
In conducting continuing review, the IRB should review, at a minimum, the protocol and any amendments as well as a status report on the progress of the research, including (a) the number of subjects accrued; (b) a description of any: adverse events or unanticipated problems involving risks to subjects or others, withdrawal of subjects from the research, or complaints about the research; a summary of any recent literature, findings, or other relevant information, especially information about risks associated with the research; and (d) a copy of the current informed consent document. Primary reviewer systems may be employed, so long as the full IRB receives the above information. Primary reviewers should also receive a copy of the complete protocol including any modifications previously approved by the IRB.

Review of the currently approved consent document must ensure that the information is still accurate and complete. Any significant new findings that may relate to the subject's willingness to continue participation should be provided to the subject in accordance with Section 46.116(b)(5). Review of currently approved or proposed consent documents must occur during the scheduled continuing review of research by the IRB, but may be done more frequently if new information becomes available.

Institutions must make investigators aware of the IRB's policies and procedures concerning reporting and continuing review requirements. The IRB's written procedures pertaining to continuing review should be distributed throughout the institution to ensure that all those involved in research activities understand their individual responsibilities.

In summary, in approving the continuation of ongoing research, an IRB attests to its satisfaction that the research continues to be conducted in accord with all relevant provisions of 45 CFR 46. Please examine your institutional and IRB practices to ensure this.

Sincerely,

/s/

Gary B. Ellis, Ph.D.
Director
Office for Protection from Research Risks