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Federal regulations already exist that deal with participation of human subjects in research. In general, they act as a floor below which the performance of human research may not fall. From time to time additional standards are considered in the interests of those who may benefit.

The National Bioethics Advisory Commission (NBAC), an advisory body to the nation’s President, was established in 1995 by Executive Order. It ceased operations upon expiration of its Charter in 2001. Amongst other topics, NBAC made a report and recommendations that specifically concern persons of diminished capacity (i.e., decisionally impaired) who participate in research.

The 1998 report includes recommendations for new federal regulations. Many of the twenty-one recommendations refer to institutional review boards (IRBs). Some of them recommend standards (i.e., criteria) for IRB review. No related new federal regulations have resulted.

However, IRBs can and do take into account the report’s recommendations, the extent to which chosen by each institution and/or its IRB(s). In addition, relevant state law and/or policy of individual research institutions may exist where federal regulations either do not exist or are considered to be insufficient for adequate protection. Ask your investigator (or IRB directly) to know for sure where your research institution and/or its IRB(s) stand.

Summary points of most direct value to prospective subjects have been for your convenience. NBAC’s recommendations are not geared for direct consumption and application by prospective subjects. Rather, many, directly or indirectly, refer to IRBs and their review functions. Accordingly, liberties have been taken to restate the essence of each selected recommendation. How IRBs should review has been turned into what prospective subjects should understand and expect. The report itself is the best source for complete and accurate detail.

The summary points of value are as follows (LAR refers to legally authorized representative):

• Persons with diminished capacity should not be involved in research if others will do.
  
• More than minimal risk (MR) research, its design, and steps to minimize risk must be justified.
• Risks and benefits must be evaluated consistent with unique risks and vulnerabilities at hand.
• Subjects who are capable should make their own choices (consent).
• Subjects of diminished capacity who object (even with prior consent) must be heeded.
• More than MR research deserves specified capacity testing by a named and qualified expert.
• A diminished person must be informed of that finding before LAR permission to enroll is sought and, if given, the prospective subject must be informed and any objection heeded.
• Minimal risk research is permissible if consent properly waived by IRB or if:
  • consent is given by a capable prospective subject for him or herself,
  • a Prospective Authorization (PR) exists and LAR permission is consistent with it, or
    
  • the LAR suitably gives permission in the absence of a Prospective Authorization.
• More than MR research with the possibility of direct medical benefit is permissible if all MR-level protections, heeding of objections, and capacity testing are performed.
• More than MR research without the possibility of direct medical benefit is permissible if all protections for research with possible benefit are followed plus additional review scrutiny.
• A capable person may prepare a PR that specifies a class of research, the risks and benefits of which are understood. A LAR may later give permission consistent with it if available to monitor recruitment, participation, and withdrawal. The greater the risk the more specific should be the PR and more specific the conditions upon the LAR for giving permission.
• A LAR may give permission (consistent with other recommendations) to enroll in research a person of diminished capacity, provided:
  • the LAR decides about participation based upon a best estimation of what the subject would have chosen, if capable;
  • the LAR is available to monitor the subject’s recruitment, participation, and withdrawal from the research; and
  • the LAR is a person chosen by the subject, or is a relative or friend of the subject.
• Investigators should accept as a LAR a relative or friend who is recognized under local state law as the prospective subject’s LAR for clinical decisions.
• Investigators should establish and maintain ongoing communication with involved caregivers (whether family or professional) when research subjects with limited capacity, fluctuating capacity, or likely future incapacity are involved, while respecting choices made when capable and medical confidentiality.

(01-20-05)