The VA’s handbook for IRBs is good reference
By J. Mark Waxman, JD
General Counsel
CareGroup Healthcare System
Boston
A handbook for IRB members sets forth the policies of the IRB, and serves as a reference and working guide for members as they review protocols and carry on their work. Those looking for a guide or benchmark for such a handbook should review the Veterans Health Administrative Handbook published July 15, 2003. Although parts of the handbook relate specifically to Veterans Affairs (VA) formats and structures, the approach, definitions, and processes provide important reference points and valuable guidance.
This article provides an introduction to the Handbook and highlights several of the important comments and processes in the handbook:
• IRB composition. IRB composition is the subject of general regulatory rules (38 CFR § 16.107). The handbook identifies a process for appointment, which the regulations do not address. First, IRB members and Research & Development Committee members may forward names to the Medical Center Director. If others have recommendations, they must nevertheless forward them through the IRB or R&D Committee. Second, members are appointed by the Director for a period of three years, and may be appointed indefinitely. Finally, the Director appoints the Chair for a term of one year, who may also be reappointed indefinitely.
• IRB authority and review criteria. The handbook carefully sets forth the rules and requirements regarding IRB authority and review criteria. Several elements of the process are noteworthy. First, in determining the reasonable risk benefit ratio, the IRB is directed to consider the risks and benefits related to both biomedical research and nonbiomedical research. On the other hand, the IRB is directed not to consider "possible long-range effects of applying knowledge gained in the research (for example, the possible effects of the research or public policy) as among those research risks that fall within the purview of its responsibility."
Second, the handbook states that the IRB, as opposed to some other Institutional official, is to ensure that steps relative to either potential or real conflicts of interest have been taken.
Finally, the handbook specifically addresses the IRB duty with respect to the principal investigator, the investigator educational requirements, and necessary certification. The IRB must affirmatively determine that the investigator(s) is/are qualified through education, training, and experience to conduct the research. To meaningfully perform this task, the IRB submission would, of course, need to specifically require this information, as well as an assessment of actual experience in the area to be researched.
• IRB processes and procedures. The handbook addresses a series of important process topics including initiation of the research, communications with investigators, the written processes for ongoing IRB operations, audits, quorum requirements, ongoing project monitoring processes, and the procedures with respect to IRB records.
The handbook requires the following:
— If research is approved contingent on modifications or clarifications to the protocol, or the informed consent, the approval of the research must not and cannot occur until the subsequent IRB review.
— If approval is contingent on "specific minor conditions" (a term it might be helpful for the IRB itself to define further), the research may not begin until those conditions are met.
— The listing of necessary written IRB procedures, including procedures for reporting changes in research activity, reporting noncompliant activity, ensuring that education requirements for the IRB are met, and for suspension or termination of IRB approvals.
— Quorum requirements, and the clear statement that all IRB votes require the presence of a quorum. The handbook, however, does allow teleconferencing or video conferencing member participation.
— If continuing review does not occur within the required timeframe, the research is automatically suspended. This means new enrollments are not permitted and the research itself can only continue if there is a specific finding by the IRB or its Chair that it is in the "best interests" of the subjects to continue their participation for suspended research to resume, full IRB review and re-approval is required;
— IRB minutes must be completed within three weeks of a meeting date. The minutes must, in addition to documenting attendance on required findings, contain a summary of "controversial issues" and their resolution.
• Surrogate consent and vulnerable populations. The handbook notes that "under appropriate conditions," consent may be obtained from a legally authorized representative. The handbook authorizes patient appointed "health care agents" pursuant to a Durable Power of Attorney, with appointed guardians or next of kin in a defined order of priority, unless otherwise specified by state law: spouse, adult child (defined as 18 or older), parent, adult sibling, grandparent, or adult grandchild.
The process to determine when surrogate consent may be obtained is also set forth. The handbook also provides that if it is feasible, the attempt must be made to explain the proposed research to the subject. If the subject then refuses to participate, the research may not proceed with that subject.
Of course separate requirements exist when vulnerable populations are involved. The handbook addresses such populations in a specific Appendix, which contains its own set of definitions.
• Payment for subjects. The handbook addresses payment for subjects, initially mandating that no payments may be made to participate in research when the research is integrated into the patient’s care and make no "special demands." Payment may, however, be made if there is no direct subject benefit and the standard in affiliated non-VA institutions is to make a payment; others in multi-institutional studies are being paid; in other comparable situations, payment is appropriate; and it is appropriate to compensate for transportation costs.
In every case, the amounts must be substantiated as fair, and do not represent undue pressure or influence.
• Investigational services and drugs. The handbook details the rules applicable to investigational devices and drugs. A readable discussion of the applicable rules is presented, with concise definitions of both an investigational drug and an investigational device. The FDA regulations to the general requirements for informed consent to use an investigational drug are set forth as:
— a life-threatening situation, necessitating the use, when effective consent cannot be obtained, and there is no available alternative likely to save the life of the subject [21 CFR § 50.23 (a)];
— if immediate care is required to preserve the subject’s life and the time available is not adequate to obtain an independent determination [21 CFR § 50.23 (b)].
The IRB must be notified within five working days when an emergency exemption is used. Where devices are involved, similar requirements must be met.
Devices differ from drugs in that they must be evaluated at the outset to determine whether they represent a "significant risk." Where the study of the device is not exempt, then those devices posing significant risk must be fully compliant with the FDA’s Investigational Device (IDE) regulations (21 CFR Part 812). It is noteworthy that for IRB approval purposes, all significant risk studies are considered by the FDA to pose greater than minimal risk.
A handbook for IRB members sets forth the policies of the IRB, and serves as a reference and working guide for members as they review protocols and carry on their work.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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