June 12, 2023
NOT-OD-23-164: Notice to Extend the Response Date of NOT-OD-23-140: Request for Information on Catalyzing the Development and Use of Novel Alternative Methods to Advance Biomedical Research
Office of The Director, National Institutes of Health (OD)
The National Institutes of Health (NIH) seeks public input on challenges and opportunities for the further development and use of novel alternative methods (NAMs) in biomedical research. NIH investment in these methods have proven beneficial tools across basic and clinical research studies, being developed and applied to interrogate cancer, diabetes, cardiovascular disease, Alzheimer's disease, infectious disease, rare diseases, and more. Each NAM approach has unique strengths and limitations that vary depending on the specific research question being addressed.
To identify areas in which the development and use of NAMs provide the most value to biomedical research, NIH sought the assistance of the Advisory Committee to the Director (ACD), an advisory group that provides advice on matters pertinent to NIH mission responsibilities in the conduct and support of biomedical research, medical science, and biomedical communications. The purpose of this request is to inform the NIH and the development of the ACD’s recommendations on high-priority areas for future investment.
Background
Biomedical researchers rely on a combination of innovative methods, models, and technologies to answer complex questions about human health and disease. The use of any given approach is based on its ability to answer the research question under study. While animal models remain an invaluable resource for researchers' addressing the complexity of human biology, rapid advances in technology are catalyzing the development and use of complementary, nonanimal based approaches. These novel alternative methods (NAMs) include in chemico strategies (e.g., experiments on biological molecules like DNA and proteins in test tubes); in vitro methods (e.g., exploring the nature of cells and tissues by culturing them in sterile chambers); and in silico computational models that simulate how these biological systems work and predict outcomes to refine hypotheses (e.g., to define how potential drugs interact with their biological targets and to refine clinical intervention and procedures that increase patient safety and treatment efficacy). The development of these NAMs holds tremendous promise for increasing the tools available to achieve the NIH mission and potentially reduce and refine the future use of animals in some areas of research in the future.
To identify areas in which the development and use of NAMs provide the most value to biomedical research, in January 2023 , the NIH Director charged an Advisory Committee to the Director (ACD) Working Group with articulating high-priority areas for NIH investment (see ACD Working Group on Catalyzing the Development and Use of Novel Alternative Methods to Advance Biomedical Research - NIH Advisory Committee to the Director). In pursuit of its charge, the ACD Working Group has been assessing the value and limitation of NAMs and needs for the development of new and/or more effective NAMs. The ACD Working Group has also been meeting with experts across research sectors to understand both public and private sector investment and identify gaps/areas of opportunity to maximize the value of NAMs to advance biomedical research. Collectively, these activities are being summarized in the ACD Working Group’s initial landscape assessment on the challenges and opportunities in the development and use of NAMs that will be used to inform its final recommendations regarding high-priority areas for NIH investment.
Request for Information
To support the activities of the ACD Working Group, NIH is requesting information from the interested individuals and communities on challenges and opportunities for the development and use of NAMs in biomedical research. Input sought includes, but is not limited to, feedback on the following:
- The use of novel alternative methods to study human biology, circuits, systems, and disease states. The value of any modeling approach is based on the assertion that known similarities between the model and the subject matter permit conclusions that additional features observed in the model will also be observed in the domain to which the model is applied. An optimal future state is one in which our understanding of human biology is sufficient to design modeling systems that accurately reflect the complexity of that biology. NIH is particularly interested in hearing how NAMs:
- are currently being developed and/or used successfully, including features that maximize scientific utility:
- are advancing progress into understanding specific biological processes or human states, including potential limitations to addressing human variability; and
- could be truly revolutionary for understanding/treating human health, including currently underserved areas of biomedical research.
- Approaches for catalyzing the development and validation of novel alternative method technologies. Many of the issues with rigor and translatability in animal models must also be addressed for non-animal models, such as considerations of human biological relevance, study design, statistical analysis, data sharing, and reporting. However, there are additional considerations for rigor and translatability that are unique to the development of NAMs, where development of new technologies and methodologies can outpace scientific consensus on standards. NIH is particularly interested in hearing from the public on:
- challenges for building in robustness, replicability, reproducibility and reliability of the technologies and the ensuing datasets;
- strategies for bolstering technology readiness and reliability these technologies; and
- factors potentially limiting the successful integration of these technologies across research approaches and potential solutions.
- Strategies for maximizing the research value of novel alternative method technologies. Depending on the biological system or disease state, different combinations of methods may be required to provide the strongest body of evidence. NIH is particularly interested in hearing from the public on how to scale these technologies to more effectively advance scientific inquiry or improve translation, including:
- areas in which coordinated approaches across research disciplines or research sectors would dramatically advance the development and or use of these technologies.
- approaches for sharing technology deployment equitably across labs, including incentives for reliable and reproducible methods integration.
- factors for consideration when maximizing translatability and minimizing bias regarding human variability.
How to submit a response
All comments must be submitted electronically at https://osp.od.nih.gov/request-for-information-rfi-catalyzing-the-development-and-use-of-novel-alternative-methods-to-advance-biomedical-research . It is not necessary to address each question/item.
Responses must be received by 11:59:59 pm (ET) on September 5, 2023.
Responses to this RFI are voluntary and may be submitted anonymously. You may also voluntarily include your name and contact information with your response. Other than your name and contact information, please do not include in the response any personally identifiable information or any information that you do not wish to make public. Proprietary, classified, confidential, or sensitive information should not be included in your response. After OSP has finished reviewing the responses, the responses may be posted to the OSP website without redaction.
NIH Office of Science Policy
Telephone: 301-496-9838
Email: SciencePolicy@od.nih.gov
and Human Services (HHS)
