September 13, 1993

Subject:

Local Institutional Review Board (IRB) Review of Multicenter Clinical Trials Sponsored by the Division of Aids (DAIDS) National Institute of Allergy and Infectious Diseases (NIAID)

Dear Colleague:

This letter is being forwarded to investigators participating in multicenter clinical trials sponsored by the Division of AIDS (DAIDS), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH). Its purpose is to clarify procedures for local Institutional Review Board (IRB) review of protocols that include DAIDS - approved sample informed consent documents:

(1)

OPRR requires that each local IRB receive a copy of the DAIDS-approved sample informed consent document and the full DAIDS-approved protocol as a condition for review and approval of the local informed consent document. It is the investigator's responsibility to provide these documents to the local IRB.

(2)

Any deletion or substantive modification of information concerning risks or alternative procedures contained in the sample informed consent document must be justified in writing by the investigator and approved by the IRB. In addition, DAIDS reminds investigators that informed consent documents should fully reference all research- related procedures and their risks, even those which might be considered relatively routine in non-research contexts.

(3)

The justification for and approval of deletions or modifications of information concerning risks or alternative procedures must be reflected in the IRB minutes. Investigators must forward copies of such IRB-approved changes, with their justifications, as part of the materials required by DAIDS for site registration. DAIDS will notify OPRR when such changes raise questions regarding the adequacy of the informed consent process.

These procedures complement the requirements of Department of Health and Human Services (HHS) regulations and of Office for Protection from Research Risks (OPRR) policy. (In particular, see enclosed OPRR Reports Number 93-01, November 9, 1992). They should be implemented immediately for the initial local IRB review of any multicenter clinical trial protocol with a DAIDS-approved sample informed consent document. For trials that are currently in progress, the procedures should be implemented at the next scheduled continuing IRB review.

This policy does not reflect any change in OPRR's policy concerning the importance of local IRB review or the local IRB's profound responsibility for protecting human subjects. Only the local IRB is familiar with the particular circumstances of its research setting and is in a position to weigh critical considerations such as state and local laws, professional and community standards, institutional policies, and the needs of differing subject populations. Thus, the local IRB is in the best position to ensure that persons deciding whether or not to enroll or remain in research have the highest effective level of accurate information necessary to make that decision. Each IRB must continue to review all protocols and informed consent documents with the greatest of care, regardless of any prior reviewed at the national level.

Melody H. Lin, Ph.D. Director Division of Human Subject Protections Office for Protection from Research Risks

Joseph A. Meschino, Ph.D. Chief, Pharmaceutical and Regulatory Affairs Branch Division of AIDS, NIAID