Each revision to a research protocol shall be incorporated into the written protocol, to assure that there is only one complete protocol, with the revision dates noted on each revised page and on the first page of the protocol itself.

IRB project approvals shall advise investigators that any proposed material changes in research activity must be promptly reported to the IRB and that such changes may not be initiated without IRB review and approval except when necessary to eliminate apparent immediate hazards to subjects.

IRB project approvals shall also advise investigators that they should report promptly to the IRB any unanticipated or undisclosed problems involving risks to subjects or others, or any serious or continuing noncompliance with the protocol or with the requirements or determinations of the IRB.