On January 21, 2019, most federally funded research will need to follow the 2018 Requirements of the Common Rule (“Revised Rule”), while research funded by the Department of Justice will need to follow the Pre-2018 Requirements of the Common Rule (“Original Rule”). Except for Department of Justice Research, research approved before January 21, 2019 can follow either the Original Rule or the Revised Rule. (I prefer using the terms “Original Rule” and “Revised Rule” because it gets confusing when, due a series of delays, the 2018 Requirements went into effect in 2019.)
An important difference between the Original and Revised Rules is the exempt categories of research and the introduction of a process called “limited IRB review.” In order to understand “limited IRB review” it is important to understand the structure of many regulations and the motivations behind the Advanced Notice of Propose Rule Making (ANPRM) and the Notice of Proposed Rule Making (NPRM).
Most regulations discuss their “applicability” that answers the question, “What do these regulations regulate?” Section 101 of both the Original Rule and the Revised Rule, titled “To what does this policy apply?” define the applicability of the regulations. They both essentially cover all research involving human subjects conducted, supported, or otherwise subject to regulation by a federal department or agency. Although the definitions of “research” and “human subject” have changed, the changes largely codify the Office of Human Research Protection’s (OHRP) historical interpretation of those terms in the Original Rule.
Many regulations also have exemptions. They are situations where something that the regulations cover based on applicability section, is not subject to regulation. Exemptions are a “carve out” from the regulation. Regulations often include exemptions to applicability. For example, the Fair Labor Standards Act (FLSA) requires employers to pay a minimum hourly wage, pay extra for overtime, etc. You may have heard the terms “exempt employee” and “non-exempt employee.” Exempt employees are employees covered by FLSA’s applicability section, but carved out of being subject to the requirements of FLSA. In the Original Rule, exempt research was research involving human subjects conducted, supported, or otherwise subject to regulation by a federal department, but not subject to (i.e., exempt from) the Original Rule.
Under the Original Rule, an investigator conducting exempt human research funded by the National Institutes of Health (NIH) needs no prior authorization or oversight. As long as the human research fell into one or more exemption categories, no federal law applied. That is fine in theory. However, the exemption criteria are complicated. Applying them correctly involves training on OHRP guidance about how to interpret the exempt criteria, as well as mentored experience. Investigators, quite understandably, would prefer that their research not require oversight, which can affect their objectivity in deciding that their research was exempt. What happens if an investigator incorrectly identifies her research as exempt? Now the investigator is conducting non-exempt research without prior IRB review and on-going IRB oversight. OHPR considers this a serious violation and holds the institution responsible. As a result, with rare exceptions, institutions that are recipients of federal funding for human research require an independent third party (usually the IRB office) to determine whether proposed research meets the criteria for exemption. If the research meets the exemption criteria, the IRB allows the research to proceed. If the research does not meet exemption criteria, the research is subject to regulation and IRB review and approval is required before proceeding with the research. IRBs commonly refer to this as “making (or granting) an exemption determination.”
Investigators dislike having a mandate that the IRB make exemption determinations, especially those whose research focus and methods exclusively fall into an exempt category. Those who read the regulations realize that the requirement for an IRB to review exempt research is an extra-regulatory burden. Now one of the goals of the ANPRM was to reduce burden and delay. As a result, the NPRM included proposals to encourage institutions to allow investigators to make their own exemption determinations (“self-exemption”). However, institutions realized that as long as OHRP would hold institutions responsible for incorrect claims of exemption by their investigators, these proposals would not eliminate IRB review of exemption. In the end, OHRP removed these proposals from the Final Revised Rule.
The ANPRM and NPRM make clear that OHRP and the public were primarily concerned with the confidentiality risks of exempt research and with consent for tissue banking for future research. OHRP could have required the IRB to make exemption determinations, and officials of OHRP’s previous incarnation, the Office for Protection from Research Risks, promoted this practice at national meetings. However, the ANPRM and NPRM make clear that OHRP and investigators also wanted to limit the IRB’s role in exempt research in order to reduce burden and delays. The outcome in the Revised Rule was “limited IRB review”. Importantly, almost everything that was exempt under the Original Rule is still exempt under the Revised Rule without the additional requirement of limited IRB review. Limited IRB review is necessary solely for new exemption options not present in the Original Rule. So one can argue that the new requirement of limited IRB review is the minimal cost of expanding the exempt categories of research.
When limited IRB review is required to confirm exempt status, an expedited reviewer (chair or experienced IRB member designated by the chair) has to determine that the research meets a subset of the exemption criteria. For two of the categories, this subset is just one criterion out of half a dozen others. However, IRBs routinely review exempt research to determine that the research meets all exemption criteria. If an institution’s IRB reviews exempt research and expedited reviewers make exemption determinations, that review already subsumes everything required for limited IRB review. No changes in policies and procedures are necessary. The reviewers just need to evaluate the research against the new exemption criteria.
If an institution does not use expedited reviewers to make exemption determination, they should consider a change. If an IRB staff member is capable of accurately making exemption determinations, that individual is capable of conducting expedited review.
Do not get confused by the term “limited IRB review” and create new processes for exemption review. In all likelihood, you are already doing a full review that subsumes “limited IRB review.”
Dr. Cooper will be presenting a workshop at MAGI East in Boston, MA on Sunday, May 5th, "Master Class: Regulatory Compliance" covering Common Rule compliance, HIPAA, COI/ICOI, regulatory enforcement environment, device regulations, controlled substances, and building a regulatory compliance department. To register, click here.