ACD Working Group on Enhancing Rigor, Transparency, and Translatability in Animal Research

Summary

The ACD Working Group will be charged with assessing and making recommendations to enhance the rigor, transparency, and translatability in animal research by improving experimental design, optimizing translational validity, enhancing training, and increasing the transparency of research studies involving animal models.

Background

Scientific reproducibility and rigor in conducting biomedical research are key to the successful application of knowledge towards improving health outcomes. NIH has taken a number of steps in recent years, including establishment of an ACD working group in response to the 21^st Century Cures Act, to improve the reproducibility and rigor of the research it supports. In this way NIH upholds the highest standards of scientific integrity, public accountability, and social responsibility in the conduct of science it supports. As highlighted at a 2014 National Academies workshop, biomedical research involving animal models continues to be compromised in many instances by selection of animals that are not well validated models of the human disease under study, as well as additional problems with suboptimal study design and misapplication of statistical analyses.

Animal model experiments often serve as the foundation for human clinical trials. About 40% of our R01 grants use murine models, creating a substantial opportunity cost, if some models poorly represent the corresponding human disease. Large animals including non-human primates may provide biologically more relevant models, but ethical issues are more complex, the work is inherently more expensive, and the desire to reduce costs can lead to the conduct of an underpowered study. It is therefore critical that the agency focus on ways to improve the value, rigor and reproducibility of animal studies, while taking into account the impact on the overall funding landscape.

Charge

Building on the efforts already undertaken by NIH to improve rigor, reproducibility, and transparency, and taking into account work done by outside organizations, including the National Academies, the National Centre for the Replacement, Refinement, and Reduction of Animals in Research, and scientific societies e.g. American Physiological Society, Society for Neuroscience, the Working Group is charged by the NIH Director to:

• Identify gaps and opportunities to improve the rigor, reproducibility, translational validity, and transparency of studies involving animal models, including:
• selecting animal models that are most appropriate for the scientific question
• strengthening experimental design and statistical analysis, including appropriate statistical power and definition of endpoints
• achieving appropriate transparency of methodological measures
• considering how the conditions in which animals are housed and bred affects experimental outcomes
• enhancing processes to incorporate rigor and transparency into grant application, peer review process, and manuscript publication
• Evaluate how animal models of human disease are currently developed, validated, and accepted into routine use, and how this process could be improved
• Assess the current state of science for validating alternative models to animal research
• Consider the benefits and burdens of registering animal studies that aim to lead to first in human trials (e.g., preregistration of the experimental plan)
• Model the financial implications of potential changes in the average costs of grants using animal models, the number of studies funded, or the need to develop multi-lab consortia to achieve appropriate statistical power
• Consider how rigor in animal research is incorporated into training (e.g., statistical training; experimental design)

Reports

• June 11, 2021 - ACD Working Group on Enhancing Rigor, Transparency, and Translatability in Animal Research
  • Final Report (PDF – 2.74MB)
  • Presentation (PDF - 2.10MB)

Roster

CO-CHAIRS

• Barbara Wold, PhD
  Bren Professor of Molecular Biology, Caltech
• Lawrence A. Tabak, DDS, PhD
  Acting Director, NIH