Accelerating Disease Prevention Research by New Approach Methodologies

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Topic Description

Post Date: September 3, 2026

Expiration Date: September 3, 2028

Purpose: This topic encourages the development, use, and implementation of NAMs that model precancerous and other chronic diseases’ precursor conditions (e.g., prediabetes and preclinical Alzheimer’s disease) and their disease progression process to accelerate prevention research and the discovery of novel preventative interventions.

NAMs referred within the current topic may include but are not limited to microphysiological systems (MPS) (e.g., organ-on-a-chip), 2D and 3D tissue systems, bioengineered human tissue models, in silico NAMs, and combinatorial NAMs.

Background: Disease prevention is key to improving long-term health outcomes for all people. Beyond commonly adopted modifiable risk-reduction strategies for disease prevention (e.g., adopting healthy lifestyle and smoking cessation), research on etiologic processes of initiation and progression of precursor conditions to overt pathologies presents new opportunities to improve disease prevention approach. For example, elucidation of biological basis of disease progression can lead to discovery of actionable targets and biomarkers for early detection, risk stratification, and development of novel therapeutics designed to prevent or intercept disease precursors from progressing to manifest diseases, or even promote the reversion to normal conditions. 

Animal models continue to play a vital role in studies on disease pathogenesis and drug development. Almost all modern pharmaceutical agents have moved to human clinical data based on animal data. However, only about 10% of agents entering clinical trials obtain regulatory approval. This may be due to inadequate validation of drug targets, lack of human efficacy, and/or unmanageable toxicity. Some of these challenges in translational research may be mitigated with the use of human relevant research tools that are designed to help bridge interspecies differences in pathophysiology, differential environmental factors, and disease characteristics together with in silico and AI-based tools to improve predictability of human efficacy and safety in drug development.

Understanding disease risks and etiology and pathophysiology of disease initiation and progression is a prerequisite to developing effective disease prevention strategies. In particular, human-based NAMs platforms built on systems physiobiology, multiomic molecular genomics, changes in physical tissue properties, and other basic and translational research on precursor conditions can provide human-relevant prevention research tools and help identify potentially exploitable targets for preventive interventions. However, there is a scarcity of NAMs that are designed to mimic precursor conditions and dynamic process of disease progression in humans.

Thus, development, validation, and integrated use of NAMs are high-priority unmet needs in prevention research for cancer and other chronic diseases, many of which are interconnected. 

 

 


 
This topic is being issued as part of the Make America Healthy Again initiative, which is expanding NIH and agency research into specific areas.

It aligns with:

  • New Approach Methodologies (NAMs) : The expanded use of NAMs can enable earlier, more predictive insights into chronic disease mechanisms using human-relevant models such as organoids, computational simulations, and real-world data integration. This improves prevention, diagnosis, and personalized treatment strategies while reducing reliance on animal studies that often fail to replicate complex human conditions. The Environmental Protection Agency (EPA), Food and Drug Administration (FDA), and NIH have all committed to using NAMs moving forward, when appropriate.

Participating ICOs

National Cancer Institute (NCI)

NCI seeks applications to develop or use human relevant NAMs that can accelerate research on precancer biology, cancer prevention, and discovery of interventions for cancer prevention and interception. Areas of interest include, but not limited to:

ICO Scientific Contact:
Shizuko Sei, M.D. (NAMs for discovery research in cancer prevention and interception)
[email protected]

Altaf Mohammed, Ph.D. (NAMs for development of biomarkers and pharmaceutical agents) 
[email protected]

Brian Cholewa, Ph.D. (NAMs for advanced pharmaceutical agent development) 
[email protected]

Vignesh Gunasekharan, Ph.D. (NAMs for precancer biology research)
[email protected]

Eric Johnson Chavarria, Ph.D. (Precancer NAMs technology development)
[email protected]

Linda Zane, Ph.D. (small business product development for the commercialization of NAMs)
[email protected]

Leela Rani Avula, Ph.D. (NAMs for drug discovery and evaluation for tertiary cancer prevention)
[email protected]

Piotr Grodzinski, Ph.D. (NAMs technology development for cancer dormancy and recurrence research)
[email protected]

National Center for Advancing Translational Sciences (NCATS)

NCATS is interested in advancing disease-agnostic research that leverages New Approach Methodologies (NAMs) to understand and ultimately prevent drug-induced organ injury. We encourage the development and application of human-based in vitro and/or in silico NAMs to understand the factors that are contributing to drug-induced organ injury so such reactions could be avoided or prevented. By focusing on drug-induced organ injury, these approaches can reveal actionable mechanisms for prevention of drug-induced organ injury before clinical symptoms emerge. Areas of scientific interest include, but are not limited to, innovative, scalable, and reproducible NAMs platforms that:

  • Enable earlier interventions,
  • Reduce reliance on traditional animal models, and 
  • Generate broadly applicable knowledge to
    • help treat and prevent disease onset 
    • promote long-term health across different populations
IC may dedicate funds available to support applications in this Topic area depending upon the availability of funds, the number of meritorious applications, and competing ICO priorities.
ICO Scientific Contact:
NCATS The Office of Special Initiatives (OSI)
[email protected]

National Institute on Aging (NIA)

NIA seeks applications adopting NAMs to identify biomarkers, protective pathways and preventative therapeutics for age-related conditions and diseases, including Alzheimer’s disease and related dementias (AD/ADRD), through studies of aging biology, intrinsic and extrinsic factors underlying resilience.

Areas of interest include:

  • Person-specific, cross-species and combinatorial NAMs for biomarker discovery, identification of preventative therapeutics/interventions for age-related conditions, diseases and AD/ADRD, and prediction of safety/toxicity
  • Neuronal and peripheral tissues NAMs from individuals with exceptional longevity, cognitive superagers, or individuals with resistance/resilience to AD/ADRD that can be used to identify protective pathways and test their ability to reduce or reverse disease phenotypes in iPSCs from patients with AD/ADRD
  • In silico NAMs that model behavioral, cognitive, and functional phenotypes, and extrinsic factors influencing disease risk and resilience
ICO Scientific Contact:
Suzana Petanceska
[email protected]

National Institute on Drug Abuse (NIDA)

NIDA seeks applications to develop or use human-relevant NAMs that can accelerate research on addiction biology, substance use prevention, and discovery of interventions. Areas of interest include, but not limited to:

  • Human-derived iPSCs, organoids, bioengineered tissues, or other NAMs to identify molecular changes induced by addictive drugs and mechanisms contributing to vulnerability to addiction.
  • Development and application of tools and methods, including in-silico models, to integrate and analyze data from various sources including epidemiological and electronic health records to identify potential mechanisms, biomarkers, and candidate drugs for prevention, early intervention, and treatment of substance use disorders.
  • Application of NAMs to decipher the interactions between biological (e.g. age and sex), behavioral (e.g. exercise) and environmental (e.g. nutrition, exposures to drugs and other substances) factors that influence the trajectory of addiction and its comorbidities.
IC may give special consideration to support meritorious applications in this topic area.
ICO Scientific Contact:
Subramaniam Ananthan, Ph.D.
[email protected]

Office of Research on Women's Health (ORWH)

ORWH seeks applications to develop or use human-relevant NAMs to accelerate research and discovery of interventions for diseases and conditions relevant to women’s health.

Areas of interest include:

  • Human-derived NAMs that model hormone homeostasis across the life course and sex influences on precursor conditions and disease progression
  • Identifying biomarkers in human-derived NAM for targeting early detection, prevention, translation, or risk stratification of diseases and conditions prevalent in females
  • Evaluating sex differences in human-derived organoids, MPS, iPSC-derived models, and other bioengineered tissues 
  • Human MPS or combinatorial NAMs to predict safety and toxicity in female-relevant contexts

Office of Autoimmune Disease Research in ORWH

Areas of interest include: 

  • Projects that utilize human-derived organoids, induced pluripotent stem cells, or other bioengineered human tissues and immune system models to investigate pre-clinical and established autoimmunity.
This office does not award grants. Applications must be relevant to the objectives of at least one of the participating Institutes or Centers listed in this topic.
ICO Scientific Contact:
Rajeev K. Agarwal, Ph.D.
[email protected]

Victoria Shanmugam, MBBS, FRCP, FACR, CCD
[email protected]

Tribal Health Research Office (THRO)

Tribal Health Research Office

For this topic, THRO supports the development and usage of new approach methodologies (NAMs) to prevent disease progression in American Indian and Alaska Native (AI/AN) communities. NAM studies are encouraged that model diseases that disproportionately affect AI/AN populations and health, such as diabetes and cancer. Investigators should ensure that proposed research is culturally grounded and involve AI/AN communities and practices as much as possible. 

This office does not award grants. Applications must be relevant to the objectives of at least one of the participating Institutes or Centers listed in this topic.
ICO Scientific Contact:
Sheila Caldwell, PhD
[email protected]

Christopher Barnhart, PhD
[email protected]

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