Despite the partial government shutdown, it’s business as usual at the Office for Human Research Protections (OHRP), and the revised Common Rule will go into effect, as planned, less than a week from today, on January 21, 2019. Last week, OHRP released a new draft guidance titled, “The Revised Common Rule Compliance Dates and Transition Provision (45 CFR 46.101(l))." Though it’s coming about six months later than would have been ideal, this is the most useful guidance related to the revised Rule to date.
The draft guidance “discusses the regulatory implications of institutional decisions to voluntarily transition research studies initiated before January 21, 2019 to the 2018 Requirements.” In other words, this guidance does not discuss studies that are initiated on or after the January 21, 2019 compliance date, but rather focuses on the voluntary decision to transition an existing study to the 2018 Requirements, whether during the “delay period” of July 19, 2018 to January 20, 2019, or at any point after the compliance date. Specifically, this draft guidance:
- Explains when and how institutions may transition ongoing studies initiated prior to January 21, 2019 to the 2018 Requirements;
- “Describes the regulatory impact transitioning a study will have on the administration of that study”; and
- Provides a Q&A section that describes various logical issues involved in transitioning a study from the pre-2018 Requirements to the 2018 Requirements.
Unfortunately, parts of the guidance are only relevant to the “delay period” that began on July 19, 2018 and will end January 20, 2019, making them obsolete at this stage. Indeed, given the helpful detail provided in this guidance about what decisions to transition entail, it is disappointing this document was not made available earlier to facilitate institutions taking advantage of what was touted as a “burden-reducing” option to transition during the six-month delay period. That said, the document is worth a close read, as it provides concrete examples of how to transition studies at various stages and the kinds of considerations to keep in mind when making the decision to do so—the sort of guidance the community has been eager for. In this post, I highlight what I take to be the most interesting and important points in the guidance.
After providing definitions and regulatory background, the document is divided into three sections: general transition principles, implementation of the transition provision, and the Q&A. It’s worth noting that OHRP encourages institutions to conduct a careful analysis of the implications of transitioning a study, including whether transition will result in “administrative benefit or administrative burden,” and whether there “might be additional protections or benefits to subjects participating in a research activity.” This is a good reminder to institutions to conduct a careful cost/benefit analysis before making the decision to transition individual studies or whole categories of research. The guidance also reminds us that transition decisions cannot be reversed.
The "General Transition Principles" section includes some helpful clarifications. The first is that, if study subjects have been enrolled in an ongoing study using a consent process that complies with the pre-2018 Requirements and the decision is made to transition that study to the 2018 Requirements, there is no need to obtain re-consent from those subjects using a consent process consistent with 2018 Requirements. However, if the study continues to enroll subjects after the transition date, consent must be obtained in accordance with the 2018 Requirements. The guidance goes on to point out, in the Q&A section, that if after an ongoing study’s transition date the IRB approves a new or amended informed consent for that study, that new or amended consent must comply with the 2018 Requirements (see the very helpful example in IV.C.1 of the guidance document for more detail). In other words, the 2018 Requirements apply only prospectively, i.e., only to study activities beginning on or after the transition date.
The guidance also clarifies that voluntarily applying some provisions of the 2018 Requirements to a study that is ongoing (and thus subject to the pre-2018 Requirements) does not itself constitute transitioning the study. Transitioning a study is something that has to be done intentionally and documented formally, and it entails a commitment to adopt all of the 2018 Requirements as a regulatory package. But there is nothing to prevent institutions from adopting specific provisions of the 2018 Requirements that they think would improve their human research protection processes or outcomes, as long as doing so is consistent with the pre-2018 Requirements with which that study must comply. An institution could decide, for example, to apply some of the new informed consent criteria to their consent documents for an ongoing study that they do not plan to transition to the 2018 Requirements, because those provisions are perfectly consistent with the pre-2018 Requirements for informed consent.
In the "Implementation of the Transition Provision" section, OHRP provides four helpful examples of studies initiated during the delay period, and the implications of different decisions regarding the studies’ transitions, and also refers the community to its Common Rule Resources website, which includes timelines that graphically depict rules for transitioning studies. In that same section, the guidance clarifies that if a decision to transition an ongoing study to the 2018 Requirements is made any time after July 19, 2018, then that study must also comply with the cooperative research provision (i.e., the single IRB requirement) when it goes into effect January 20, 2020.
The Q&A section is perhaps the most useful part of the draft guidance. It anticipates and answers questions IRBs, institutions, and investigators might have about implications of transitioning ongoing research, in the on the following three areas: 1) Transition Determinations, 2) IRB Review, and 3) Informed Consent. Below are some of the answers I found most illuminating.
In response to a question regarding which version of the Rule should be used to review protocol amendments, OHRP writes that, “as a general rule, protocol amendments must be reviewed and evaluated under the version of the Common Rule to which a study is subject, regardless of when the amendments are made.” In other words, if an ongoing study initiated prior to January 21, 2019 is not transitioned to the 2018 Requirements, then an amendment made in 2025 would be evaluated according to the pre-2018 Requirements. And, conversely, if an ongoing study initiated priority to January 21, 2019 study is transitioned in 2020 to the 2018 Requirements, then any protocol amendments on or after that transition date should be reviewed under the 2018 Requirements (though earlier amendments would have been reviewed under the pre-2018 Requirements).
The guidance also addresses the question of how an institution can decide to conduct continuing review for a study that has been transitioned to the 2018 Requirements and, under those Requirements, is not required to undergo continuing review. OHRP clarifies that there are two ways an institution can do this. First, it can as a matter of institutional policy implement any kind of additional review for the research conducted within its walls that it wants to—whether for all research, or certain types of research. Here OHRP reminds us that the Common Rule should be seen as the “regulatory floor” upon which institutions can build additional levels of protections or administrative requirements. This is not considered “regulatory” continuing review. Second, the IRB can determine that continuing review is warranted for a study, or a class of studies, even if that study would not otherwise require continuing review under the 2018 Requirements. In that case, the IRB has to document its rationale for it determination. This is considered “regulatory continuing review” and would be subject to OHRP compliance oversight.
I encourage you to read the whole guidance, as it includes more scenarios and information than I have outlined here. And for more resources on the Common Rule, be sure to check out PRIM&R’s Focus on the Revised Common Rule webpage.
With the compliance date nearly upon us, I hope OHRP will do all it can to keep useful guidance like this coming—the research community needs it. If you have suggestions for how OHRP might improve this guidance, I encourage you to submit comments. Again, comments are due by February 11, and should be submitted to the regulations.gov portal using docket number HHS–OPHS–2019–0001.