Recommendation 17. Research using stored human biological materials, even when not potentially harmful to individuals from whom the samples are taken, may be potentially harmful to groups associated with the individual. To the extent such potential harms can be anticipated, investigators should, to the extent possible, plan their research so as to minimize such harm and should consult, when appropriate, representatives of the relevant groups regarding study design. In addition, when research on unlinked samples that poses a significant risk of group harms is otherwise eligible for exemption from IRB review, the exemption should not be granted if IRB review might help the investigator to design the study in such a way as to avoid those harms.
The Working Group shares NBAC’s concern that some research using human biological materials may be potentially harmful to groups. However, as NBAC points out, “federal regulations governing the protection of research subjects extend only to individuals who can be identified.33 Thus, the regulations do not include federal oversight of research that may pose risk of group harm (beyond the risks to study participants who are members of the group) except insofar as the requirements for IRB membership provide some protection for vulnerable groups.
Notwithstanding the silence of federal regulations on this point, the Working Group agrees that investigators should plan research in a manner that minimizes potential harm to groups. Consultation with representatives of relevant groups may identify potential harms and other problems as well as benefits and opportunities in the proposed research that may not have been evident to the investigator. Appropriate consultation may thus minimize harms, maximize benefits, and increase the likelihood that the research will be carried out successfully.
However, as NBAC notes, “additional work is needed to identify appropriate mechanisms for group consultation.34 Identifying the appropriate groups to consult with may, in certain instances, be a complex challenge. The researcher may identify and consult with a group regarding the proposed research only to find that another or larger group claims that the originally defined group is in fact a sub-group whose views do not reflect those of the larger group. This larger group may disagree with, and even claim the authority to override, the decision of the initial group.
A group could be an informal collection of individuals, a formal organization with identified leadership, or include competing organizations with dissimilar opinions. Therefore, even when a group is identified, individuals or sub-groups within a group may have different opinions about the relative risk and value of the proposed research, who will be affected by the results, and the best research design for the study. Furthermore, some groups explicitly authorize only certain members to determine and express group opinion. These issues all contribute to the difficulty the researcher will experience in efforts to identify appropriate formal and informal spokespersons for a group. This uncertainty about how best to conduct group consultation militates against proposing a regulatory requirement in the near future.
Nevertheless, DHHS agencies are making efforts that are in keeping with the spirit of NBAC’s call for improvement of mechanisms for group consultation. For example, NIH convened in September 2000 a community consultation to obtain input on the collection of tissue samples from members of identified populations; the results of this consultation are posted on the internet.35
In the discussion preceding Recommendation 17, NBAC points out that, for many studies involving human biological samples, the “net gain to a particular population that results from being informed about its increased risk (especially when something can be done with this knowledge at an individual level) often will outweigh the harms that come from labeling the group as high risk.36 In the United States, with one exception,37 consultation with representatives of a group does not confer the right of veto over the research to those representatives. Nonetheless, bona fide consultation requires the researcher and the IRB to carefully consider the concerns, especially the perceived potential harms, of the group and of individuals in that group. If those potential harms cannot be sufficiently minimized, it is possible that the benefit to risk assessment may require that consideration be given to not proceeding with the research.
Under 45 CFR 46.101(b)(4) and 102(f), research on unlinked or anonymized samples is not subject to the Regulations. Individual institutions and IRBs have the authority to apply a more stringent standard than that required by the Regulations. Within an institution, an IRB may require that a proposal be submitted for review even if the proposal is otherwise not subject to federal regulations. The Working Group strongly encourages efforts to minimize group harm in all research, even research that is not subject to federal regulations. In this context, the Working Group encourages IRBs and institutions to consider risk of group harm in research involving unlinked or anonymized samples and to develop strategies to minimize such risk. However, absent revision to the Regulations, IRB review of proposals to which current federal regulations do not apply is not mandated.
The Working Group proposes that the issue of group harm be addressed in the broader context of federal oversight of research involving humans that is being addressed in NBAC’s forthcoming report on Ethical and Policy Issues in Research Involving Human Participants. In the interim, the Working Group suggests that DHHS continue to encourage further studies of strategies that would identify and effectively minimize group harm, including efforts to identify appropriate mechanisms for consultation with relevant groups.
Recommendation 18. If it is anticipated that a specific research protocol poses a risk to a specific group, this risk should be disclosed during any required informed consent process.
The Working Group agrees that disclosure of foreseeable risk to groups should be included in the informed consent process. Potential subjects should have access to all information that could affect their decisions about participation. Individuals may wish to consider implications of the research design and/or results for their community in deciding whether or not to participate in a research study.
The Working Group proposes that OHRP, in consultation with FDA, consult with appropriate groups and organizations to develop guidance for implementation of this recommendation.