On January 19, 2017, the U.S. Department of Health and Human Services along with 15 other federal departments and agencies issued a revised Federal Policy for the Protection of Human Subjects referred to as the Common Rule. The intent of the revision, the first update since 1991, was to strengthen the protections of subjects participating in research while at the same time minimizing undue burden on researchers. At a recent webinar led by Pearl O’Rourke and Heather Pierce through PRIM&R, several key take-away messages were identified by GSS attendees and have been outlined below with some additional commentary on potential impact and considerations. Although it is important to be familiar with all the changes and updates in the policy, the primary focus here will be on those changes most relevant to research with biospecimens and informed consent.
In the updated policy, the definition of Human Subject was updated to clarify and align with changes made related to biospecimens, however, it is important to note that the definition of Human Subject was not modified as recommended in the Notice of Proposed Rule Making (NPRM) to expand the definition to include those biospecimens that do not have identifiers. Instead, the definition remains such that only biospecimens that are identifiable are captured in the definition. This is advantageous to researchers as it allows this type of research to move forward without unnecessary oversight given the minimal risk to subjects with the use of biospecimens that are not identifiable. In addition, there is a new requirement to reevaluate the definitions for “identifiable private information” and “identifiable biospecimen” with the appropriate experts within 1 year and at least every 4 years as well as to publish a list of technologies and techniques that could impact this definition (e.g. lead to the generation of identifiable biospecimens). It will be very important for researchers to stay engaged in these future discussions as this could have an impact on the ability to conduct genomic research depending on how the definitions and list of techniques and technologies evolve.
There were 2 new exemption categories added to the existing 6 which include 7) storage or maintenance for secondary research for which broad consent is required and 8) secondary research for which broad consent is required, both of which are in reference to use of identifiable private information and identifiable specimens. Given the complexity of these exemptions, the details around the impacts of this will be omitted here, however, it is important to understand them in the context of the overall landscape of what research now falls as exempt under these new categories. One point that is important to make related to this is that although secondary research was not defined in the definition section, there is a statement that provides insight into what this term refers to: “By “secondary research”, this exemption is referring to re-using identifiable information and identifiable biospecimens that are collected for some other “primary” or “initial” activity. The information or biospecimens that are covered by this exemption would generally be found by the investigator in some type of records (in the case of information) or some type of tissue repository (such as a hospital’s department for storing clinical pathology specimens).” It is important to note that O’Rourke and Pierce indicated that the activities do include information or biospecimens that were initially collected for both non-research and research purposes which is a very helpful clarification to guide researchers in understanding how this terminology relates to the research they are conducting. There are three important points to keep in mind about the use of broad consent. If broad consent is offered to a subject and they refuse, an IRB cannot waive informed consent for these individuals. Under the new rule, the intent of HHS is for researchers to use the mechanism of broad consent instead of waivers of informed consent for research. Finally, it is always important to be very thoughtful in the language included in the broad consent when this approach is utilized to avoid any unanticipated downstream impacts on breadth of use in the future (e.g. for instance, given the speed at which advances in technology are made, it would not be ideal to restrict use of any future technologies that may be developed unless required by regulations in that jurisdiction).
There were also some changes to informed consent including the requirement for a concise summary of information at the beginning of the document that specifies key information that a reasonable person would want to know and facilitates comprehension to help the subject make an informed decision about whether to participate in the research study. Broad consent is allowed as an optional alternative to study-specific informed consent, a waiver of informed consent or de-identification of information or biospecimens. An additional element has been added to the 8 existing basic consent elements that requires a specification as to whether identifiers might be removed and how information could be used for future research without additional consent if the research involves the collection of identifiable private information or identifiable biospecimens. Three additional data element requirements have been added to the existing 6 additional informed consent data elements which include the following statements: 7) that the subject’s biospecimens may be used for commercial profit (this applies even if identifiers are removed) and whether the subject will or will not share in any commercial profit 8) whether or not clinically relevant research results will be returned and if so, under what conditions and 9) whether the research will (if known) or might include whole genome sequencing of the biospecimens. Although many companies and institutions already include these statements in their consent documents, it will be important to ensure the language is vetted and ready to be included in any future consents as there can be some lengthy ethical discussions on return of results, for instance. There are also 12 elements for broad consent that have been outlined in the revised policy which include a statement on the length of time for storage, maintenance and use of identifiable private information or identifiable biospecimens for research purposes (time period is permitted to be specified as indefinite which is advantageous to researchers) and contact information to get answers to questions about their rights, storage and use as well as who to contact in the event of a research-related injury. It is important to note that none of the consent elements for broad consent can be omitted or altered. An interesting point regarding contact information as it relates to industry sponsored studies will be whether a contact at the biorepository will be required to be listed in the informed consent document to address storage and use questions, particularly if the length of storage is beyond the period of time that the investigator would be actively engaged in the research study.
Although the rule was issued a few weeks ago, the compliance date for most provisions is January 19, 2018 and for single IRBs is January 20, 2020. However, the fate of the final policy is a bit unclear per O’Rourke and Pierce given it was released on the last day of the outgoing Presidential administration. According to O’Rourke and Pierce, there are some factors that lie within the favor of the policy moving forward under the new administration. Given the new administration has stressed the intent to reduce regulation and the overall tone of this policy does focus on reducing the burden on researchers, it is more likely it will continue to move forward. In addition, the economic cost is much less compared to the proposals in the NPRM. Overall, the perspective from O’Rourke and Pierce was that although there are some provisions that still need guidance, the rule incorporates flexibility and importantly, took into consideration the feedback received in 2,100 comments from the research community.
As intended, this updated policy does achieve the goal of strengthening the protections of research subjects while minimizing undue burden on researchers. Specifically, the support of broad consent in the revised policy provides significant opportunities for the research community to maximize the utility of biospecimens in support of the discovery of optimal treatments for patients as well as new and improved research technologies. While at the same time, regulation changes both in the US and globally demonstrate the importance of codification of informed consent, particularly as the volume of patient consents that need to be managed increases. To support this, the Global Alliance for Genomics & Heath (GA4GH) has published codification categories for data use. Global Specimen Solutions, Inc. offers a proprietary codification schema for both specimens and data validated against 35,000 consent documents and tracked electronically in GlobalCODE®. The ability to vigilantly track consent permissions can provide reassurance to and increase trust with patients, patient advocates and regulatory agencies. In addition, the ability of organizations to access consent permissions at the click of a button provides a significant advantage by facilitating the timely conduct of research.