On September 8, the Department of Health and Human Services (DHHS) issued a Notice of Proposed Rulemaking (NPRM) for revisions to the Federal Policy for the Protection of Human Subjects, or “Common Rule.” If adopted, the proposals in the NPRM will result in the most substantive revisions to the core regulation governing federally funded human subjects research in the United States since 1981.

In earlier posts, we explored a new category of activities that would be excluded from oversight under the Common Rule and proposed changes to the category of exempt research. In this week’s post, we examine NPRM proposals related to research with biospecimens. 

Overview of Biospecimens Research and Broad Consent 

The NPRM proposes to revise the definition of human subject for the purposes of the Common Rule to include biospecimens, regardless of identifiability. [__.102(e)] This change is intended to bring secondary research use of non-identified biospecimens collected in either research or non-research settings within the purview of the Common Rule.

Principal among the forces driving this change, according to the preamble of the NPRM, are people’s autonomy interests in the research use of their biospecimens, that is, the desire of individuals to know about, give permission for, and have some control over future research with biological materials collected from them. At the same time, the NPRM seeks to facilitate “cutting edge” research with biospecimens, recognizing the societal value of the information that can be generated from biospecimens for the treatment and prevention of disease. The NPRM characterizes the advancement of the research enterprise in the service of generating socially valuable knowledge as a matter of beneficence. Its proposals in this domain thus seek to strike a reasonable balance between the principles of autonomy and beneficence, so understood.

Because under the proposed rules biospecimens would be considered human subjects, the NPRM proposes requiring informed consent for the storage and secondary research use of biospecimens (i.e., use of specimens initially collected for purposes other than the currently proposed research activity), regardless of their identifiability, but allows for that consent to be broad (i.e., consent for future, unspecified research studies, rather than study-specific consent). The broad consent must be obtained via a template that is to be provided by the Secretary of the DHHS, and would include elements such as a general description of the types of research that may be conducted with the biospecimens and the information expected to be generated, and a description of the types of biospecimens that were or will be collected and for how long. [__.116(c) and__.116(d)]

When such broad consent has been obtained at the point of biospecimen collection, the storage or maintenance of those biospecimens for future, unspecified research studies, as well as secondary research use, would be exempt from further review, provided that privacy safeguards are followed and limited IRB approval of the consent process used is obtained. [__.104(f)]

The NPRM makes explicit that waiver of consent for research involving biospecimens (regardless of identifiability) will occur only in very rare circumstances. [__.116(f)]

Questions Raised by the Proposed Changes

One potential concern about these proposals is whether broad consent as described in the NPRM will constitute meaningful informed consent. Many biospecimens are collected in the context of routine care at hospitals and clinics that do not have their own research programs or infrastructures, but instead send those specimens on to other facilities that store them for future research. Thus broad consent most often would be obtained as individuals check into a clinical facility and complete other mandatory paperwork. The process would thus occur away from the expertise of research staff and individuals equipped to answer patients’ questions about the potential risks and benefits associated with the biospecimens research.

But even when biospecimens are collected in settings familiar with research and equipped with standard consent processes, the question remains whether broad consent will be meaningful qua consent. The purpose of an informed consent process is to enable individuals who are being invited to participate in research to make an informed decision about whether it is in their interest to do so, given the risks and benefits of that research. When individuals are asked to agree to have their biological specimens used for future unspecified research—where the types of research to be conducted, by whom, when, and with what outcomes, are largely unknown, and may not even be conceived at the time of consent—it is unclear, even in the hands of someone skilled at seeking research consent, how the process can amount to much more than a notification procedure.

The research oversight community is also debating whether obtaining broad consent as outlined in the NPRM can be feasibly implemented. Given that many biospecimens come from hospitals and clinics without a research infrastructure, systems and processes for obtaining and also tracking broad consent across all patients entering a facility will need to be developed and put in place.

Finally, as the community prepares its comments on the NPRM, worth considering is whether the apparent asymmetry between the way the NPRM treats biospecimens, on the one hand, and personal information and data, on the other, is justified. The NPRM requires consent for research involving biospecimens, whether identifiable or not, and whether collected for research or non-research purposes. However, under the current rules, secondary research use of non-identified private information would not require consent. Nor is consent required for secondary research use of identifiable private information if the information was collected for non-research purposes, provided that privacy safeguards are in place and prior notice of such use is given to the subjects. If identifiable private information is being collected for future research or for storage for such use, then, as with biospecimens, broad consent is required, but, unlike biospecimens, it can be obtained via oral consent. Furthermore, while the NPRM aims to make waivers of consent in the case of research use of biospecimens extremely rare, it makes no changes to the provisions around waivers related to secondary research use of identifiable private information, and in fact, supports their use as a mechanism for facilitating important research.

As we have noted, the NPRM indicates that the provisions around biospecimens are intended to acknowledge and respect people’s expressed autonomy interests in controlling their biospecimens. However, one potential question is whether people have the same autonomy interests in their private information, including, importantly, genomic data. The NPRM suggests that, with respect to private information, when privacy safeguards are in place, then the “balance” between people’s autonomy interests and the interests of advancing science come out in favor of facilitating science by not requiring informed consent. But in the case of biospecimens, even when privacy safeguards are in place, autonomy interests trump and consent is always required. It is not clear why this would be, especially if biospecimens refer only to the physical material of the specimen and not, for instance, to genomic data which could be extracted from a specimen and then be used for future research under a waiver of consent. 

Members of the research ethics and oversight community are encouraged to share their thoughts on these topics, as well as other issues raised by the NPRM, by submitting formal comments to DHHS. Comments are being accepted on the proposed rule through January 6, 2016 at 5:00 PM ET.