How should IRBs approach the continuing review of research that remains active beyond long-term follow-up or data analysis, but that is eligible for expedited review under categories 8(b) or 9 of the 1998 OHRP Expedited Review List in light of the new provision at §46.109(f)(1)(i) of the 2018 Requirements, which eliminates the requirement for such continuing review unless an IRB determines otherwise?
The 2018 Requirements at Section 46.109(f)(1)(i) eliminate the continuing review requirement for research eligible for expedited review unless an IRB determines otherwise. The 2018 Requirements also include a commitment by the Secretary, HHS, to evaluate the list of research activities eligible for expedited review at least every 8 years, and to amend it, as appropriate, after consultation with other federal departments and agencies and after publication in the Federal Register for public comment (§46.110). However, the first set of revisions to the 1998 List as contemplated in this commitment has not occurred yet. Consequently, at this time, the reference in §46.109(f)(1)(i) of the 2018 Requirements to “research eligible for expedited review” refers to research that appears on the 1998 List. Therefore, research that is subject to the 2018 Requirements and that is eligible for expedited review, including research that falls into categories 8(b) or 9 of the 1998 List, would not require continuing review unless an IRB determines otherwise. However, OHRP recommends that IRBs use their discretion “to determine otherwise” under §46.109(f)(1) of the 2018 Requirements to determine that continuing review of studies that are subject to these Requirements and that meet the criteria for expedited review categories 8(b) or 9 should be conducted at the same frequency as required in the pre-2018 Requirements; that is, at intervals appropriate to their degree of risk, but not less than once per year (Pre-2018 Requirements at §46.109(e)).
OHRP believes this approach is appropriate because two important goals of the changes included in the 2018 Requirements are reducing unnecessary burden in the conduct of valuable research and better protecting human subjects in research (82 FR 7149). With these goals in mind, OHRP notes that eliminating the requirement for continuing review of research eligible for expedited review effectively reduces administrative burdens, but this must be weighed against the preeminent goal of providing meaningful protections for research subjects. In the case of research eligible for expedited review categories 8(b) or 9, continuing review is likely to provide such meaningful protections. For example, studies that qualify for expedited category 8(b) may involve interactions, interventions, or procedures that might present more than minimal risk to subjects. Therefore, continuing review provides IRBs with the opportunity to monitor these studies once recruitment begins. Similarly, continuing review of studies that qualify for expedited category 9 provides IRBs with the opportunity to evaluate the progress of ongoing research activities otherwise not included in the list of permissible expedited review categories. In both instances, OHRP believes that continuing review provides meaningful protections for human subjects, such as the opportunity to evaluate the most current risk-benefit analysis and to reapprove informed consent documents for research activities that have not been completed.
In contrast, expedited review categories 8(a) and 8(c) apply to continuing review of research activities that have been largely completed and remain active only for long-term follow-up or data analysis. In these instances, continuing review would likely provide no additional protections for research subjects since, for example, a current risk-benefit analysis or a reapproved consent form would be unnecessary where recruitment has closed and study interventions have ended. Therefore, expedited review categories 8(a) and 8(c) cover activities that, unless the IRB determines otherwise, are no longer required to undergo continuing review under §46.109(f)(1)(iii) of the 2018 Requirements. However, as stated above, in the case of studies that meet the criteria for expedited review categories 8(b) or 9, continuing review would likely provide meaningful protections for human subjects.
Therefore, OHRP recommends that IRBs use their discretion “to determine otherwise” under §46.109(f)(1) to determine that continuing review of research should be conducted at intervals appropriate to their degree of risk, but not less than once per year for research that is subject to the 2018 Requirements in the following circumstances:
- Where no subjects have been enrolled and no additional risks have been identified (expedited review category 8(b)); and
- Where (i) the research is not being conducted under an investigational new drug application or investigational device exemption, (ii) categories two (2) through eight (8) of the OHRP Expedited Review Categories (1998) do not apply, and (iii) the IRB has determined and documented at a convened meeting that the research involves no greater than minimal risk and no additional risks have been identified (expedited review category 9).
If an IRB determines that continuing review is necessary as here recommended for these two circumstances on or after January 21, 2019, the rationale for doing so must be documented in the IRB records (§46.115(a)(3)). Documenting this rationale could be a statement that the IRB has elected to follow this guidance. However, from July 19, 2018, through January 20, 2019, it is not required that IRBs document why continuing review is occurring when the regulations do not require it, including under these two circumstances (83 FR 28504).
If an IRB determines that continuing review of such research remains necessary under §46.109(f)(1) of the 2018 Requirements as here suggested, such a continuing review may be conducted in an expedited manner (see §46.110(b)(1)).
This recommendation is relevant only where the continuing review of research eligible for expedited review categories 8(b) or 9 would otherwise not be required under §46.109(f)(1)(i). This recommendation is not applicable to research that meets the conditions for expedited review categories 8(a) or 8(c), or to research that has progressed to the point that it meets the conditions of §46.109(f)(1)(iii) of the 2018 Requirements.
This recommendation is also not applicable to research that is subject to the pre-2018 Requirements or to FDA regulations. For research subject to FDA regulations, including that which is subject to both FDA regulations and the Common Rule, IRBs must continue to comply with FDA’s continuing review requirements at 21 CFR 56.109(f).
Newborn Blood Spot
Section 12 of the Newborn Screening Saves Lives Reauthorization Act of 2014 changed the ability of investigators to conduct certain federally funded research with newborn dried blood spots regardless of the identifiability of the blood spots. Are these requirements of the Act still in effect?
No. Research with nonidentified newborn dried blood spots, similar to other research with nonidentified biospecimens, is not considered research with human subjects under both the 2018 and pre-2018 Requirements, and thus, is not subject to 45 CFR part 46.
Although Section 12 of the Newborn Screening Saves Lives Reauthorization Act (NSSLRA) of 2014 stated that certain federally funded research on newborn dried blood spots would be considered human subjects research (regardless of the identifiability of the blood spots), and prohibited IRBs from waiving consent for such research, Section 12 applied only until changes to the Common Rule were promulgated. Thus, as of the effective date of the revised Common Rule (July 19, 2018), the requirements in Section 12 of the NSSLRA of 2014 are no longer in effect.