Title page

Contents

Highlights 2

Letter 6

Background 10

Requirements Governing Animal Research Conducted and Supported by NIH 10

NIH Entities' Roles and Responsibilities Related to Animal Research 11

NIH Review and Funding Processes for Proposed and Ongoing Animal Research 11

NIH Takes Various Steps to Help Ensure Animal Welfare in Research It Conducts or Supports 12

NIH's Office of Laboratory Animal Welfare Monitors Compliance with PHS Policy Requirements at the Institutional Level 12

NIH Oversight at the Project Level Includes Guidance for Reviewing Research Proposals and Progress Reports 14

OLAW Requires Institutions to Self-Report and Address Noncompliance 16

Multiple Challenges Limit the Reproducibility and Translatability of Animal Research 20

Low Success Rates 21

Modeling Human Biology 23

Study Design and Data Analysis 24

Reporting 28

NIH Has Taken Steps Intended to Enhance Reproducibility and Translatability but Has Not Assessed Its Progress 30

NIH Implemented a Rigor and Transparency Policy Aimed at Enhancing Reproducibility of Extramural Research 31

NIH Has Taken Additional Steps Intended to Enhance Reproducibility and Translatability 32

NIH Has Not Assessed Whether It Has Made Progress in Enhancing Reproducibility and Translatability of Animal Research 35

Conclusions 39

Recommendations for Executive Action 40

Agency Comments and Our Evaluation 40

Appendix I: Categories of Noncompliance with the Public Health Service Policy 42

Appendix II: Recommendations from NIH Advisory Committee to the Director to Improve Animal Research 44

Appendix III: Comments from the Department of Health and Human Services 48

Appendix IV: GAO Contacts and Staff Acknowledgments 50

Table 1. Data on Annual Reports the National Institutes of Health (NIH) Received from Institutions with Approved Animal Welfare Assurances, 2018-2023 13

Table 2. Categories of Noncompliance with the Public Health Service (PHS) Policy Most Frequently Reported to the National Institutes of Health (NIH)... 19

Table 3. National Institutes of Health's (NIH) Four Areas of Rigor for Grant Applications 31

Table 4. Categories of Noncompliance with the Public Health Service Policy Reported to the National Institutes of Health (NIH) for Cases Closed, 2021-2023 42

Table 5. Recommendations from the National Institutes of Health (NIH) Advisory Committee to the Director (ACD) Working Group on Enhancing Rigor,... 45

Figure 1. Sources of Reports of Noncompliance with Public Health Service (PHS) Policy for Research Involving Animals at Intramural and Extramural Institutions, 2023 17

Figure 2. Actions NIH Can Take in Response to Noncompliance with the Public Health Service (PHS) Policy for Research Involving Animals 20

Figure 3. Challenges That Limit the Reproducibility and Translatability of Animal Research 23

Figure 4. Different Arrangements for Placement of Animal Cages 26

Figure 5. Examples of Controllable and Less Controllable Extrinsic Factors That Can Influence Outcomes in Animal Research 29

Figure 6. Examples of Challenge Areas, Recommendations, and Steps NIH Has Taken Intended to Enhance Reproducibility and Translatability of Animal Research 34