APS Response to NIH RFI on Coordinating and Harmonizing Regulations and Policies

June 11, 2018, APS provided these comments on NIH’s March 14, 2018 RFI (NOT-OD-18-152) seeking input on the following proposals:

  1. Allow investigators to submit protocols for continuing review using a risk-based methodology.

    The 2017 report “Reforming Animal Research Regulations” recommended using a risk-based methodology for protocol review: “Studies deemed low-risk, noninvasive, or minimally invasive could be exempt from full IACUC review or eligible for administrative review without concurrence by the full IACUC” (Recommendation #9 on page 16).

    • The American Physiological Society (APS) concurs with this and urges the NIH to implement risk-based reviews for all animal research protocols.

    Streamlining the review of new and continuing low-risk protocols will reduce burden both to those investigators whose protocols are being reviewed and to those who serve as IACUC members. A risk-based methodology will enhance animal welfare because by reducing the amount of time spent on reviewing low-risk protocols, IACUCs will be able to devote more time to overseeing research that may present a higher risk for pain and/or distress. This approach parallels the one used in the Common Rule governing Institutional Review Board (IRB) reviews of research with human subjects. The Common Rule already exempts some types of noninvasive research from review and makes other low-risk research protocols eligible for expedited review by a single member of the IRB. The updated Common Rule that takes effect July 19, 2018 takes additional steps to alleviate burden by eliminating the requirement for continuing review of studies that initially qualified for expedited review.

    • The APS recommends both taking a risk-based approach to initial protocol review and eliminating continuing review of low risk protocols. This approach is more administratively efficient and still maintains necessary animal protection.

    The APS further recommends that the USDA harmonize its protocol review schedule with that of the PHS Policy. Section 2.31 (d)(5) of the Animal Welfare Regulations(AWR) requires IACUCs to “conduct continuing reviews of activities covered by this subchapter at appropriate intervals as determined by the IACUC but not less than annually.” In contrast, Section IV.C.5 of the PHS Policy on Humane Care and Use of Animals requires IACUCs to conduct continuing reviews of protocols and other ongoing activities at appropriate intervals as determined by the IACUC as long as such reviews are completed once every three years.

    Memoranda of Understanding between OLAW and many federal granting agencies require institutions receiving extramural funding from these agencies to hold PHS Assurances and comply with the PHS Policy. This includes virtually all U.S. academic research institutions. Given that research involving AWA-covered species is already subject to continuing review under the PHS Policy, the USDA’s requirement for annual reviews is unnecessary.

    • The APS urges the USDA to harmonize its protocol review requirements for institutions with OLAW Assurances by allowing them to conduct such reviews at appropriate intervals as determined by the IACUC but no less than every three years.
  2. Allow annual reporting to the OLAW and USDA on the same reporting schedule and as a single report through a shared portal.

    The American Physiological Society (APS) agrees that harmonizing the schedule for annual reporting would reduce administrative burden by allowing facilities to gather information to report to both agencies at one time. However, since the reporting requirements between the agencies differ, if a single form is used for data entry, the reports it generates should convey to each agency only the information pertinent to its reporting requirements.

    • The APS also urges OLAW to make its annual report less burdensome by implementing checkboxes to indicate compliance.

    In place of entering the dates of an institution’s semi-annual facility inspections, there should be a checkbox where Assured institutions can indicate that the inspections took place. A checkbox should also be provided for institutions to verify that their IACUCs are appropriately constituted.

    Section 2.36(a) (5‐8) of the AWR lists extensive reporting requirements for animal numbers. This is an administrative requirement with no basis in the AWA. Of all these subsections, the requirement to report the number of animals being bred, conditioned, or held by the institution but not yet assigned to a study is particularly burdensome.

    • The APS recommends that USDA eliminate the requirement to report the number of animals being bred, conditioned, or held by the institution prior to assignment to a study.
    • The APS further recommends that wherever animal numbers must be reported, both USDA and OLAW should allow institutions to report ranges of animals instead of exact numbers.
  3. Harmonize the guidance from NIH and USDA to reduce duplicative considerations of alternatives to painful and distressful procedures.

    The American Physiological Society (APS) supports the idea of unified guidance on the consideration of alternatives to painful or distressful procedures as long as this guidance eliminates the emphasis on key word literature searches in USDA’s Animal Care Policy #12. Policy #12 recommends “a database search as the most effective and efficient method for demonstrating compliance with the requirement to consider alternatives to painful/distressful procedures.” However, this is not consistent with the language in AWA Section 2143(a)(3)(B), which simply states that researchers are required to consider “alternatives to any procedure likely to produce pain or distress in an experimental animal.” The language of Policy #12 also exceeds what is written in Section 2.31(d)(1)(ii) of the AWR, which tasks the IACUC with determining whether the principal investigator “has considered alternatives to procedures that may cause more than momentary or slight pain or distress to the animals, and has provided a written narrative description of the methods and sources, e. g., the Animal Welfare Information Center, used to determine that alternatives were not available.” In other words, the regulations do not place any special emphasis on database searches.

    Because conducting a key word search of the literature for every procedure in a protocol is time-consuming, and such searches rarely yield useful information, it has frequently been cited as a waste of effort. In our response to the USDA’s 2015 RFI on reducing regulatory burden, the APS pointed out the conviction of investigators that a brief written narrative concerning how reduction, refinement, and/or replacement were incorporated into the protocol “gives the review body (IACUC) much more insight into the consideration of alternatives, satisfies the regulatory objectives of the Animal Welfare Act, and reduces burden for researchers.”

    • The APS therefore urges the NIH and USDA to harmonize their guidance on consideration of alternatives by eliminating the emphasis on database searches.
  4. Provide a minimum 60-day comment period for new OLAW policy guidance.

    As an organization that takes policy development seriously, the American Physiological Society (APS) believes that agencies need to allow individual scientists and organizations sufficient time to learn about new policy proposals, engage in thoughtful discussion, and develop meaningful responses. A 60-day comment period is insufficient to do this.

    • The APS therefore recommends that OLAW implement a 90-day comment period on all new policy guidance.

    It has previously been noted by many people on many occasions that materials such as interpretive notes, procedure manuals, webinars, and journal articles have increasingly come to be considered as de facto statements of OLAW policy. Because research institutions are risk averse, the belief that institutions must comply with all the suggestions in these materials has become a significant source of regulatory burden. While this can be seen as self-imposed burden, OLAW also bears responsibility because it has encouraged the view that these materials represent agency policy.

    • For this reason, the APS strongly recommends that agency guidance materials that have been developed without the opportunity for input from the regulated community should be labeled clearly to state that they do not carry legal or regulatory force.
    • The APS also encourages both the NIH and the USDA to solicit public comments on any current guidance documents that were implemented without public comment since this will help identify additional ways to reduce regulatory burden as mandated under 21st Century Cures.

    The Cures Act also called for the establishment of a Research Policy Board to conduct assessments of regulations concerning various areas of research including the oversight of laboratory animals.

    • The APS urges that this Board be constituted as soon as possible and that any new policy guidance be submitted to this Board for review.
  5. Other approaches not previously mentioned.

    The American Physiological Society (APS) endorses the recommendations of Reforming Animal Research Regulations and wishes to highlight the following recommendations to the NIH from page 27:

    The Guide for the Care and Use of Laboratory Animals was not intended to be a regulatory document. Rather, it was intended “to assist institutions in caring for and using laboratory animals in ways judged to be professionally and humanely appropriate.” The Guide allows facilities to produce welfare outcomes for animals in diverse and innovative ways by permitting alternative strategies to “should” statements upon approval of the IACUC.

    • OLAW is strongly urged to stop using the Guide as a quasi-regulatory document.
    • In keeping with the above, OLAW should stop considering IACUC-approved strategies that differ from “should” statements in the Guide as departures or deviations.
    • Furthermore, IACUCs should not be required to include such alternative strategies in their semiannual reports to the Institutional Official. This is in line with OMB’s January 25, 2017 Agency Good Guidance Practices Bulletin (72 FR 3432) and would significantly reduce administrative burden without compromising animal welfare.
    • NIH should eliminate the requirement in Grants Policy for verification of protocol and grant congruency. Grants are not contracts. Research objectives can be expected to change due to ongoing discoveries and other developments that occur between grant submission and actual receipt of funding. Furthermore, advances made during each phase of the research may well lead to alternative strategies in subsequent phases.
    • Revise the NIH guidance in NOT-OD-05-034 regarding prompt reporting to cover only those incidents that have jeopardized the health or well-being of animals.

    With respect to semi-annual inspections and program reviews, we recommend the following:

    • The APS supports Recommendation #15 on page 21 of Reforming Animal Regulations, which calls for USDA to revise §2.31(c)(3) of the AWR as follows: “The IACUC may, at its discretion, determine the best means of conducting an evaluation of the institution’s programs and facilities that includes all members wishing to participate in the process. The IACUC may invite ad hoc consultants to assist in conducting the evaluation. However, the IACUC remains responsible for the evaluation and report.”
    • The APS recommends that USDA require program reviews annually rather than semi-annually. Section 2143(b)(3) of the AWA requires only a semiannual inspection of animal study areas and facilities, but Section 2.31(c)(1-3) of the AWR requires both semiannual inspections and program reviews. These program reviews have frequently been cited as wasted effort since IACUCs typically review programmatic issues on an ongoing basis. Requiring only annual program reviews will reduce burden to IACUCs without diminishing animal welfare.

Input is sought on the following tools and resources:

  1. Encourage the use of sections of the AAALAC International program description in applicable parts of the OLAW Animal Welfare Assurance for institutions accredited by AAALAC International.

    Using the AAALAC program description in the OLAW Assurance would not significantly reduce administrative burden because the real problem is that current Assurance requirements for these institutions are excessive. The APS instead recommends that the NIH reduce the level of detail required in Animal Welfare Assurances for AAALAC-accredited facilities. According to a 2016 survey conducted by the IACUC-Admin listserv, Assurances run an average of 24 pages. In contrast, the average Assurance to conduct research with human subjects is less than 5 pages.

    • The APS recommends that AAALAC-accredited facilities be permitted to submit an abbreviated Assurance that addresses only those aspects of the PHS Policy that are not addressed in their AAALAC, International program description.
  2. Encourage the use of the FDP Compliance Unit Standard Procedures as a repository of best practices for standard procedures used for research with animals.

    • The APS agrees that the use of the FDP Compliance Unit Standard Procedures (CUSP) could reduce burden for PIs developing animal use protocols. However, we caution against allowing these best practices to become de facto regulations.
  3. Encourage the use of the IACUC Administrators Association repository of best practices by IACUCs.

    Because the IACUC Administrators Association repository is only available to subscribers, the APS is unsure how promoting this resource would reduce regulatory burden.

  4. Encourage the use of new or existing tools to streamline protocol review through use of designated member review (DMR), DMR subsequent to full committee review, and/or Veterinary Verification and Consultation.

    OLAW should encourage the use of tools such as VVC and DMR to streamline protocol review and reduce administrative burden on IACUCs and investigators. However, some IACUCs have been hesitant to use VVC due to confusion over how it should be implemented.

    • The APS urges OLAW to provide additional guidance on this. Moreover, rather than requiring each IACUC to develop an exhaustive set of VVC procedures, the VVC policy should state that veterinarians are encouraged to use professional judgement in approving changes to ongoing protocols.
    • Explicitly authorizing veterinarians to exercise their professional judgment would improve animal welfare while also reducing unnecessary burden.
  5. Expanded IACUC training activities that focus on reducing burden on investigators.

    Since IACUC training activities are implemented on an institutional level, this recommendation does not address the emphasis of the 21st Century Cures Act, which is to reduce regulatory burden imposed on a federal level.

    • Having the NIH and the USDA explicitly state what is and is not required on guidance and policy documents and other materials would have a greater impact on reducing burden. The APS concurs with this sample language suggested by NABR: “[Agency’s] guidance documents, including this one, do not establish legally enforceable responsibilities. Guidance documents simply describe the Agency’s current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited.”