In response to the issues posed in this scenario, the U.S. Department of Agriculture Animal and Plant Health Inspection Service (USDA-APHIS) and the National Institutes of Health Office of Laboratory Animal Welfare (NIH-OLAW) provide the following clarifications.
In this scenario, the IACUC is deciding whether a pilot study is indicated to validate the reproducibility of a researcher’s established methods because of concerns raised in publications about the techniques.
USDA-APHIS response
The Animal Welfare Act regulations require an IACUC to review an animal study proposal to ensure it meets the requirements that the work avoids or minimizes pain/distress, and contains a written assurance that the activity does not unnecessarily duplicate previous experiments1,2. In addition, the regulations require a proposed activity to include a rationale for the numbers of animals to be used3. In this scenario, the IACUC is deciding whether a pilot study is indicated to validate reproducibility. The investigator however relayed that her work had been peer reviewed for Federal funding, and that pilot studies were already performed as requested by the IACUC three years ago, hence to do so again would be a waste of time and animals.
The Animal Welfare Act regulations do not give the IACUC the authority to prescribe methods or set standards of design, performance, or conduct of research4; however the IACUC has the authority to request additional information that supports the written assurance that the work is not unnecessarily duplicative, and the investigator’s rationale for the appropriateness of the numbers of animals to be used. The IACUC also has the authority to invite consultants to assist in reviewing the protocol5 before deciding whether to approve, require modifications to approve, or withhold approval for the proposed activity6.
NIH-OLAW response
As noted by other reviewers, the PHS Policy and the Guide expect the IACUC to consider whether the research design is sound7,8. Besides further pilot studies, OLAW agrees with the other reviewers that the IACUC has better options to reconcile the reproducibility concerns. The IACUC may choose to 1) ask the researcher to include the outcome of the pilot studies in the renewal protocol, 2) increase post-approval monitoring of the study to confirm consistency in the application of the techniques in question, or 3) request that the researcher provide more details of how she internally validates her techniques. Regarding NIH grant applications proposing the use of animals, it is the institution’s responsibility, not the IACUC’s, to ensure congruency between the application and the IACUC protocols9,10. Institutions have flexibility in which program carries out this responsibility.
References
Title 9 Chapter 1 Subchapter A § 2.31 (d)(1)(i)
Title 9 Chapter 1 Subchapter A § 2.31 (d)(1)(iii)
Title 9 Chapter 1 Subchapter A § 2.31 (e)(2)
Title 9 Chapter 1 Subchapter A § 2.31 (a)
Title 9 Chapter 1 Subchapter A § 2.31 (d)(3)
Title 9 Chapter 1 Subchapter A § 2.31 (c)(6)
Office of Laboratory Animal Welfare, National Institutes of Health. Public Health Service Policy on Humane Care and Use of Laboratory Animals. (US Department of Health and Human Services, Bethesda, Maryland, USA, 2015). [online]. https://olaw.nih.gov/policies-laws/phs-policy.htm.
Institute for Laboratory Animal Research. Guide for the Care and Use of Laboratory Animals, 8th edition. (National Academies Press, Washington, D.C., USA, 2011).
National Institutes of Health. Public Health Service Policy on Humane Care and Use of Laboratory Animals - Frequently Asked Questions. Protocol Review, Question D.10. (US Department of Health and Human Services, Bethesda, MD, USA, revised 2017). [online]. https://olaw.nih.gov/guidance/faqs#623.
NIH Grants Policy Statement. 4.1.1.2 Verification of IACUC Approval [online] https://grants.nih.gov/grants/policy/nihgps/html5/section_4/4.1.1_animal_welfare_requirements.htm
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Brown, P., Goldentyer, B. A Word from USDA and OLAW. Lab Anim 49, 30 (2020). https://doi.org/10.1038/s41684-019-0464-x
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DOI: https://doi.org/10.1038/s41684-019-0464-x
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