May 31, 2000
TO: Division of Human Subject Protections
FROM: Director, Division of Human Subject Protections
SUBJECT: IRB Review of Applications for HHS Support
Department of Health and Human Services (HHS) regulations at 45 CFR 46.103(f) require that each application or proposal for HHS-supported human subject research be reviewed and approved by the Institutional Review Board (IRB).
Over the past several years, OPRR has identified numerous instances in which human subject research described in an application for HHS support differed significantly from the IRB-approved protocol that was claimed by the investigator to constitute the research in the application. In each case, the application added important elements (e.g., targeting of vulnerable subjects; additional treatment arms; different drug dosages; additional collaborators or performance sites) that were ultimately implemented without IRB review and approval.
In view of these findings, OPRR reminds IRBs that HHS regulations require that the IRB review the actual application or proposal for HHS support. The IRB=s review should ensure that all research described in the application or proposal is entirely consistent with any corresponding protocol(s) submitted to the IRB.
This review need not be undertaken by every IRB member. Rather, a designated IRB member may document that the proposed research is consistent with any relevant protocol(s) submitted to, or previously approved by, the IRB. A copy of the HHS application or proposal should be retained among IRB records and made available to any IRB member who may wish to review it.
It is important for designated IRB reviewers to have ready access to the entire application or proposal (exclusive of appendices) because information related to the protection of human subjects sometimes appears only in seemingly peripheral sections. Examples include information about (i) the number and qualifications of collaborating investigators and other members of the research team; (ii) cooperating institutions or performance sites that may require separate or additional IRB review or an Assurance of Compliance; (iii) characteristics of proposed research facilities that may affect subject safety or the confidentiality of data; (iv) the feasibility of financial commitments made to subjects; and (v) the cost of proposed subject protection measures, such as consent monitors or translators.
Application/Proposal Review Forms. IRBs are free to develop supplemental submission forms to assist designated members in the review of applications and proposals for HHS support. For example, such forms might require that investigators (i) summarize, and cross-reference to the application, the types of information described above; (ii) identify any IRB-approved protocols that cover the proposed research; and (iii) either certify that the application or proposal is entirely consistent with any corresponding IRB protocol(s) or submit protocol amendments to reconcile any discrepancies.
"Just-in-Time"IRB Review. Certain HHS Agencies permit Certification of IRB Approval to be deferred until just prior to funding. Regardless of when its review occurs, the IRB should ensure that all research described in the application or proposal is entirely consistent with any corresponding protocol(s) reviewed and approved by the IRB. Any discrepancies must be resolved prior to the involvement of human subjects.
Indefinite Plans for Human Subject Involvement. Certain types of applications and proposals lack definite plans for the involvement of human subjects either because the specific human subject activities have not yet been fully developed, or because human subject research was not anticipated at the time of the application. In such cases, the application or proposal need not be reviewed by the IRB prior to an award (see 45 CFR 46.118 and 46.119). However, the IRB must have in place mechanisms to ensure that any research supported under the award receives IRB review and approval prior to the involvement of human subjects.
Multi-Project Awards. Certain types of awards (e.g., program project and center grants) support multiple projects involving numerous investigators. Where the relevant application or proposal includes definite plans for human subject research, the designated IRB reviewer should document that the proposed research is consistent with any relevant protocol(s) submitted to, or previously approved by, the IRB. Where definite plans are lacking, the IRB must have in place mechanisms to ensure that any research supported under the award receives IRB review and approval prior to the involvement of human subjects.
Multi-Site Research. The requirement for IRB review of each application or proposal for HHS-support applies only to the awardee institution. The application or proposal need not be reviewed by the IRBs at non-awardee institutions participating in the research. However, appropriately redacted copies of funded applications or proposals should be made available to IRBs at participating institutions if requested.
Organization and Storage of IRB records. Institutions retain their discretion to organize and store IRB records in any manner that is consistent with the requirements of HHS regulations at 45 CFR 46.115. Electronic storage is acceptable as long as all records are accessible for inspection and copying by OPRR.