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This case illustrates a challenge that will become more common as the use of single institutional review boards (IRBs) for the review of multisite research increases: specifically, how best to handle local context considerations when a single IRB is required to oversee research being conducted in unfamiliar settings (Wilfond et al. [ 6]). A recent survey confirms that IRB officials consider "reviewing the local research context" to be a significant challenge associated with new single IRB review requirements (Resnik et al. [ 4]). In the case presented here, a single IRB that is more familiar with the context of civilian research settings and study populations has assumed responsibility for reviewing research that is enrolling both active-duty and former military personnel at a military medical facility for a study of genetic risk and myositis. Although the single IRB of record is aware of regulatory differences in the privacy protections that are available to military personnel and civilians who enroll in genetic research, this single IRB is faced with the difficulty of interpreting those protections and determining how best to describe them in the military site consent forms.

A potential goal of review by a single IRB is to minimize arbitrary variability in consent form language across multiple sites that are carrying out identical research procedures (Koyfman et al. [ 2]). However, this goal needs to be balanced with the single IRB's obligation to ensure that relevant contextual features of each institution under its purview, including unique aspects of the study population and local culture as well as different regulatory and policy requirements, are adequately considered. Although it would be operationally unwieldy for each relying institution in a large multisite study to submit a completely unique consent form, a single IRB best practice that has been proposed is to permit limited customization of otherwise consistent consent form language to reflect local policies. Such customization could include a relying institution's standardized descriptions of applicable privacy laws and requirements (e.g., Health Insurance Portability and Accountability Act [HIPAA]), distinct signature block requirements, and institutionally developed "boilerplate" for compensation for research-related injury and other legal requirements, for example (Splinter et al. [ 5]). This practice was not designed to allow enrollment sites to tailor consent forms based on subjective language preferences, but rather to accommodate language that is indicated by local policy requirements. In the current case, it is clear that the risks of genetic research with an active-duty military population in a military medical center setting would require some customization of consent language to describe accurately the risk of employment discrimination and relevant legal protections in that setting.

Indeed, privacy protections related to all genetic research are complex and context dependent. Because myositis is an example of a condition that could potentially affect military duties and future job placements, an IRB of record would need to understand how a study of genetic factors associated with the development of this condition could pose additional risks to participants enrolled at a military medical institution. While the Genetic Information Nondiscrimination Act (GINA) provides some protection against health insurance and employment discrimination for civilians, and discrimination based on genetic data has been relatively rare in civilian contexts (Green et al. [ 3]), GINA does not apply to military personnel, for whom a different set of protections governs how genetic information is managed (De Castro et al. [ 1]). Accordingly, one would expect the consent language describing privacy protections related to genetic research at a military enrollment site to be substantively different than the consent language for civilian enrollment sites, and it is generally appropriate for a single IRB to accommodate a military research institution's request to customize the consent forms being used in these distinct settings to reflect those substantive differences.

Yet it is also reasonable for the single IRB to question the applicability of the GINA-specific consent language that was proposed by the military site and to require that the language be presented in a clearer, more understandable manner. Although the single IRB in this case was not situated in the military setting, it appears that this IRB appreciated that the information that active-duty military personnel would need to weigh the risks and make an informed decision about voluntary enrollment in a genetic research protocol was different from the information that civilians—and perhaps retired military personnel as well—would need to make that decision. Even when a single IRB of record has a practice of allowing customization of the consent forms that are being used at different enrollment sites, that single IRB still needs to consider the consent form as a holistic document to ensure that it presents the required elements of informed consent clearly and appropriately for the populations being included in the research. Although it could be appropriate for a single IRB to accept precise "boilerplate" language that succinctly describes legal protections that apply in the military research setting, we believe it is well within the purview of the single IRB to explore whether the language could indeed be changed to ensure that enrolled participants have the relevant information that they needed.[ 1] Depending on the degree of pushback, a single IRB might need to work closely with the local (military) IRB to develop language that both adheres to what is required in the military context and to ensure that potential nonmilitary research participants have been provided the relevant information to allow them to be adequately informed of the risks and potential benefits of the research.

Finally, this case underscores a potential role for research ethics consultation as a resource for single IRBs who are facing the challenge of interpreting local context requirements. Although using the single IRB is intended to reduce the overall burden of IRB review of multisite studies, it will present additional responsibilities to the IRBs that are selected to oversee research at diverse enrollment sites. Understanding unfamiliar local context requirements is challenging and may require access to specialized expertise. Ethics consultants can help facilitate conversations between the relevant institutional representatives to augment an IRB's understanding of how local context considerations apply to the research participants in a multisite protocol and how best to reflect those considerations in associated consent form language.

The views presented are those of the authors and do not necessarily reflect the official views and policies of the National Institutes of Health (NIH) or Department of Health and Human Services (DHHS). ▪

1 Although it is difficult to tell from the information provided in the case description, the consent language in question that was proposed by the military facility enrollment site seems to be more nuanced than typical so-called "boilerplate" language. It is important to distinguish between immutable boilerplate language and "recommended" template language that an institution is comfortable with but can be flexibly adapted to specific research contexts. Ideally, both categories of language should be clear and accessible to research participants, but it may be more difficult to request revisions to legal boilerplate that has been developed in consultation with an institution's legal counsel.

2 This work was authored as part of the Contributor's official duties as an Employee of the United States Government and is therefore a work of the United States Government. In accordance with 17 USC. 105, no copyright protection is available for such works under US Law.

De Castro, M., L. G. Biesecker, C. Turner, et al. 2016. Genomic medicine in the military. Nature Partner Journals: Genomic Medicine 13 (1): 1 – 3. doi: 10.1038/npjgenmed.2015.8

Koyfman, S. A., P. Agre, R. Carlisle, et al. 2013. Consent form heterogeneity in cancer trials: The cooperative group and institutional review board gap. Journal of the National Cancer Institute 105 (13): 947 – 953. doi: 10.1093/jnci/djt143.

3 Green, R. C., D. Lautenbach, and A. L. McGuire. 2015. GINA, genetic discrimination, and genomic medicine. The New England Journal of Medicine 372 (5): 397 – 399. doi: 10.1056/NEJMp1404776.

4 Resnik, D. B., E. M. Smith, and M. Shi. 2018. How U.S. research institutions are responding to the single institutional review board mandate. Accountability in Research 25 (6): 340 – 349. doi: 10.1080/08989621.2018.1506337.

5 Splinter, K., S. C. Hull, I. A. Holm, T. L. McDonough, A. L. Wise, R. B. Ramoni, and Members of the Undiagnosed Diseases Network. 2018. Implementing the single institutional review board model: Lessons from the undiagnosed diseases network. Clinical and Translational Science 11 (1): 28 – 31. doi: 10.1111/cts.12512.

6 Wilfond, B. S., J. Zabrowski, and L. M. Johnson. 2019. The limitations of "boilerplate" language in informed consent: Single IRB review of multisite genetic research in military personnel. American Journal of Bioethics 19 (4): 81 – 82.

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By Sara Chandros Hull and Adam I. Schiffenbauer

Reported by Author; Author

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