Biomedical research is undergoing a paradigm shift as the National Institutes of Health (NIH) unveils a transformative initiative this week to accelerate the adoption of human-specific, non-animal models in its research programs, both internal and external. The NIH would strongly encourage the use of advanced technologies such as organoids, tissue chips, computational systems, and real-world data in the research it supports, aiming to enhance its translational accuracy and clinical relevance. This policy marks a sharp shift in NIH policy by aligning NIH funding with a similar initiative announced by the FDA, collectively designed to promote reduced animal testing in support of medical product approval.
Animal models have historically been central to biomedical research and drug development, providing valuable insights into disease mechanisms and therapeutic efficacy. However, their limitations, particularly in replicating complex, chronic, and heterogeneous human diseases such as Alzheimer’s disease, certain cancers, and autoimmune disorders, have increasingly raised concerns about their practical utility and ethical use. Data from animal experiments has a well-established low extrapolation to effects in humans owing to inter-species differences in physiology, lifespan, immune response, and organ system function. Despite that, the FDA reviewers and the scientific community at large have relied on animal tests to support the safety and effectiveness of medical products. It’s about time to revisit the traditional research models.
The NIH will establish the Office of Research Innovation, Validation, and Application (ORIVA) within the Office of the NIH Director. ORIVA will lead agency-wide coordination to support the integration of non-animal research methodologies into the biomedical research enterprise. It will serve as a central hub for advancing the development and validation of human-based models, fostering cross-agency regulatory alignment, and scaling infrastructure to facilitate widespread adoption.
The initial announcement specifically lists three alternatives to animal testing for studying human physiology and disease. These are:
- Organoids and tissue chips that model human tissue and organ-level function with high fidelity.
- Computational modeling and in silico systems capable of simulating human biological processes, drug-disease interactions, and toxicity profiles.
- Real-world data (RWD) and evidence that enable analysis of health outcomes in diverse populations and real-life clinical settings.
NIH’s policy framework will include targeted funding mechanisms that prioritize scientific rigor and human relevance over default reliance on animal systems. Grant applications will be evaluated based on methodological suitability, translational potential, and alignment with intended research outcomes. Concurrently, ORIVA will develop training programs, expand access to non-animal research platforms, and enhance institutional capacity for implementing these methods.
To foster fairness and objectivity in peer review, NIH will implement bias mitigation training for grant reviewers and incorporate experts in human-specific and alternative methodologies into review panels. These changes aim to ensure that innovative, scientifically robust approaches are fairly assessed and adequately supported.
Additionally, NIH will implement transparent, annual reporting of research expenditures, with specific tracking of funding trends related to animal-based and non-animal-based studies. This accountability mechanism will help assess progress toward a more human-centric biomedical research model. In sum, this policy aims to transition toward a more predictive, human-relevant, and ethical biomedical research ecosystem. By leveraging technological advances and improving alignment with human biology.
The use of animals in research has evolved over the last century to reduce risk to human subjects in clinical trials. Some aspects of the safety of medical products are impossible to ethically evaluate in human subjects, but are critical for widespread human use. Similarly, there are aspects of safety and effectiveness where animal data cannot be reasonably extrapolated to humans. There is a need for a pragmatic approach. The recently announced NIH and FDA policies are a step in the right direction. Now, if only they are enforced within both agencies effectively, so they can grow from a slogan to real change.
