SACHRP Recommendations on OHRP Draft Guidance “Frequently Asked Questions: Limited Institutional Review Board Review and Related Exemptions”

Approved July 20, 2023

Background

On June 16, 2023, the Office for Human Research Protections (OHRP) issued a draft guidance for institutional review boards (IRBs), investigators, research administrators and other relevant institutional officials, and funding agencies that may be responsible for review or oversight of human subjects research conducted or supported by HHS, and the general public entitled “Frequently Asked Questions: Limited Institutional Review Board Review and Related Exemptions.” Limited IRB review was a new type of review introduced in the 2018 revisions to the 45 CFR 46 and is intended for the review of certain research in which the primary risks relate to privacy and confidentiality. The draft guidance discusses the concept of limited IRB review and provides information about how a limited review may be conducted.

In the revised 45 CFR 46 regulations there are four exemptions that require limited institutional review board (IRB) review:

• 45 CFR 46.104(d)(2)(iii),
• 45 CFR 46.104(d)(3)(i)(C),
• 45 CFR 46.104(d)(7), and
• 45 CFR 46.104(d)(8).

Discussion

SACHRP is pleased that OHRP is considering publishing guidance on the use of limited IRB review, as it represents a new review pathway for IRBs that may reduce administrative burdens for IRBs that review research that qualifies for the applicable exemptions while still protecting research participants.

SACHRP offers its commentary and recommendations for OHRP’s consideration.

As a general comment, SACHRP notes that two of the applicable exemptions pertain to research involving identifiable private information or identifiable biospecimens. In §46.102(e)(7) of the revised Common Rule there is a requirement that OHRP periodically reexamine the meaning of "identifiable private information" and "identifiable biospecimen." This reexamination may impact the contents of this guidance.

While the conduct of the exempt limited IRB review must be done through either a convened meeting or an expedited procedure, SACHRP believes the document would benefit from adding language regarding the relative benefits of using exempt with limited IRB review, rather than applying the expedited or convened review path and to further define or clarify when an institution would choose only exempt limited IRB review.  For example, the determinations for applying the exempt limited IRB review would be determined in instances where the research meets one of the applicable exemptions and the review need only consider privacy and confidentiality protections rather than requiring all of the considerations within 45 CFR 46.111.

SACHRP notes in the draft guidance there are numerous references to the exempt review process and the fact that 45 CFR 46 does not specify who may determine that a research activity meets an exemption category, nor does it specify how determinations required as a condition of an exemption must be made, and that institutions are free to choose their own methods for conducting, communicating, or recording exempt determinations.  SACHRP recommends that the guidance indicate that best practices include having appropriately trained members of an institution’s human research protection program or IRB office conduct exempt reviews to help ensure that all of the regulatory nuances have been appropriately considered and addressed. 

SACHRP also notes that this document does not address the issue of “engagement” as it relates to exempt activities that require limited IRB review.  SACHRP recommends that OHRP address the issue of engagement in this document and consider adding it to existing OHRP guidance and/or FAQs on exempt research.

Section I

The Draft Guidance indicates that the term “Secondary Research” is not defined within the regulations, and provides a proposed understanding that the term “generally refer[s] to the research use of identifiable private information or identifiable biospecimens that are or will be collected for a purpose other than the present research use.”  SACHRP agrees with this proposed understanding of the term “secondary research.”  However, at line 72 of the draft, the language should read “identifiable private information or identifiable biospecimens that are have been or will be collected.”

SACHRP also recommends that the guidance include definitions of the terms “intervention” and “interaction” as they are meant to be understood in the context of limited IRB review.

Section II

SACHRP notes that the guidance does not address issues that may arise when research that may qualify for limited IRB review is also subject to the single IRB requirement. It is conceivable that different IRBs and institutions may not be utilizing limited IRB review or not using it in the same manner. In addition, there may be circumstances in cooperative research where research activities at some participating sites only involve activities that meet the criteria for limited IRB review. SACHRP acknowledges that these issues may apply beyond limited IRB review, but this should be acknowledged or addressed in the guidance.

Research that qualifies for limited IRB review by its nature focuses on the collection or use of identifiable information or specimens. SACHRP recommends that ORHP emphasize in the guidance that individuals conducting limited IRB review may require expertise in both the field of research being conducted and information technology/privacy.  Additional expertise may be necessary when research involves emerging technologies and methodologies such as the use of artificial intelligence, including remote research, and decentralized trials.

Section III

The guidance notes that when conducting a limited IRB review for exemption 8 (secondary research for which broad consent is required), the reviewer need not approve a particular broad consent form or script as part of the limited IRB review; rather, the IRB would need to determine that the protection of privacy and confidentiality is adequate and that the intended use  of the data or specimens in the exempt research is covered by the content of the broad consent originally determined to meet criteria for broad consent and documented in the  consent form (future use has to be compatible with the original review).  It is the original reviewer that determined that the broad consent was adequate to satisfy the exemption requirement.   However, the guidance is silent on what would happen if the limited IRB reviewer disagrees that the research satisfies the exemption regulation or does not otherwise agree with the previous broad consent determination.  (lines 263-274)

SACHRP recommends that the guidance more clearly define the differences in the scope of the review for the two separate reviews being conducted (1) exemption determination and approval of the broad consent versus (2) the limited IRB review.  The limited IRB reviewer description should address both the role of the reviewer in limited IRB review and the scope of the limited IRB review when/if either:

• the reviewer does not agree with the previous broad consent determination or
• believes that the approved broad consent form does not meet the relevant requirements at 45 CFR 46.116.  

The guidance may benefit from the inclusion of review scenarios that touch on various aspects of a limited IRB.  For example, an individual conducting a limited IRB review may need to question:

1. Is the proposed research in the scope of broad consent?

    

2. Does the broad consent satisfy the regulations?

    

3. Will the information be obtained in accordance with the exemption?

    

4. Are the limited IRB review requirements met or should the research be sent back to original IRB (limited IRB review requirements not met)?

In the bullet that begins on line 291, more detail is needed to explain “access that they do not otherwise have to identifiable private information or identifiable biospecimens.”  For example, this could be when research staff are transferring data to others not previously engaged in the research, but this is not clear in the wording used in the draft guidance.

Section VII    

Activities that are determined to be exempt under 45 CFR 46.104 are not required to submit continuing review reports to the IRB. However, investigators are expected to consult with the appropriate institutional authority whenever questions arise about whether planned changes to an exempt study might make that study nonexempt human subjects research.

Institutional SOPs may now need to include policies and procedures for exempt research with limited IRB review on submitting certain modifications/changes to the IRB when determinations relevant to the original limited IRB may need to be reconsidered, such as changes in staffing (pertaining to allowable access to data), changes in storage or management of data (reconsider the protection of privacy/confidentiality as well as electronic protections if electronic storage is occurring).  SACHRP recommends that the guidance recommend that institutions and IRBs develop such policies and procedures.

Section VIII  

Section VIII addresses the use of expedited review procedures when conducting limited IRB review.  § 46.110 is titled “Expedited review procedures for certain kinds of research involving no more than minimal risk, and for minor changes in approved research.” (emphasis added) However, the draft guidance indicates that “studies eligible for expedited limited IRB review as described in this provision may be more than minimal risk and still qualify for expedited review.”  The guidance states that the basis for this is that as a matter of regulation the exempt categories do not require that research activities be minimal risk in order to qualify for exemption. SACHRP worries that this will allow IRBs to avoid consideration of other ethical requirements such as the Belmont principles for research activities with greater than minimal risk and believes that this will create confusion within the regulated community, where common practice is to only exempt activities that are minimal risk. Therefore, SACHRP recommends that this be addressed through additional discussion of this possibility and how reviewers conducting a limited IRB review should address any concerns they have regarding the risk level of the proposed activity. In addition, OHRP should address this in existing guidance on exempt research.

Section IX     

Section IX should make clear that the provided examples are not meant to be the only examples.

Section X       

As noted earlier, additional clarification should be provided regarding when investigators are given electronic or physical access that they do not otherwise have, including if such individuals should be required to undergo training on human subjects protection issues when working with identifiable data or specimens.  

Section XI     

Making a determination that a specific secondary study is within the scope of a broad consent can be accomplished only if the IRB who approved the broad consent materials included the terms in its review documentation about what type of research was consent given for future use. The guidance states that the IRB conducting the limited IRB review is not charged with approving the contents of the broad consent document or the consent process. Rather, it is charged with determining whether the proposed research falls within the scope of the broad consent.  However, making a determination that a proposed secondary research use of identifiable private information and identifiable biospecimens is compatible with the uses for which subjects provided broad consent can be highly subjective.

As stated previously, SACHRP recommends that OHRP use the guidance to identify the questions that should be addressed through limited IRB, and what must happen when the IRB conducting limited IRB review believes that the broad consent does not cover the proposed secondary research.  It is further recommended that the guidance include recommendations for strengthening institutional policy on the documentation of exempt determinations with limited IRB review to include details regarding what type of research consent was given for (e.g., for the PI’s sole use; for all other researchers use; for just one disease with specifics such as breast cancer only vs cancer in general; for any research).

SACHRP further recommends that OHRP address the issue of documenting the limits to future secondary research by the IRB that approved the broad consent in this guidance or through a separate guidance on broad consent.