Complement-ARIE Interagency Retreat Summary

On Oct. 19-20, 2023, representatives from eight federal agencies convened in Washington, D.C., for the Complement Animal Research In Experimentation (Complement-ARIE) Inter-Agency Retreat, hosted by the National Institutes of Health (NIH) Common Fund, to discuss goals and priorities for advancing new approach methodologies (NAMs). The aim was to lay the foundation for a new Common Fund program to catalyze the development, standardization, validation, and use of human-based NAMs to transform biomedical research and improve predictions of human health and disease.

The proposed Common Fund program would:

• Develop human-based NAMs that can better model health and disease across diverse populations.
• Address the limitations of biological insights that current models provide.
• Complement traditional models to make research more efficient and effective.
• Support regulatory decisions to improve human health.

Through presentations, panel discussions, and breakout sessions, agency representatives in attendance highlighted the various NAMs underway in their respective organizations and fields. These approaches include organs-on-chips, virtual models, 3D cell cultures, organoids, stem cell models, computational methods, and more. As stated by retreat participants, scientific areas that would benefit from NAMs include cancer research, clinical trials, chronic diseases, aging, adaptive immunity, neuroscience, and precision health, among others.

Challenges and Priorities

The retreat underscored several priorities that will enable broader acceptance and impact of NAMs. Agency representatives expressed that clear standards are needed across all aspects of NAMs, from data generation methodologies to validation frameworks to reproducibility efforts. Robust standards will encourage regulatory approval and use of NAMs. According to attendees, regulatory agencies should also require that NAM data adhere to FAIR (findable, accessible, interoperable, and reusable) principles.

NAM data should be freely available, said agency partners during moderated conversations. A database as well as harmonized data-sharing networks would facilitate the development of new NAMs and highlight gaps where NAMs are unavailable, as well as areas where traditional models are not predictive of human responses.

Advancing NAMs requires bringing together diverse data, technologies, disciplines, and collaborators.

Validation of NAMs remains a significant challenge.

Training and educating early-career scientists is vital to increasing NAM adoption. There is also a need to train current and future scientists and regulators, as well as the public, on the uses and limitations of NAMs. Such efforts would increase regulatory understanding of NAMs and encourage widespread acceptance and adoption of NAMs in laboratory spaces.

Transparent communication is needed to develop public understanding of and trust in NAMs. 
The most effective, resource-efficient use of NAMs is to complement traditional models. Although creating NAMs to replace traditional models might be applicable in some situations, the goal is to create NAMs that fill knowledge gaps that current models cannot address.

Collaborative Opportunities

Partnerships between industry, agencies, and academia will be necessary to develop shared standards and processes, which in turn will aid in the adoption of NAMs Retreat attendees also discussed focusing on developing NAMs that address worldwide issues.

Industry partnerships will be essential to the continued development and eventual acceptance of NAMs.

Collaborations can also fulfill certain pressing issues. High-priority NAMs — many of which are needed to alleviate longstanding gaps in knowledge — were identified for future development and validation.

Other collaborative opportunities for NAM integration include therapeutic drug development and safety and efficacy tests for medical products.

Insights From the Breakout Sessions

Participants were separated into two groups for two breakout sessions. Both groups discussed regulatory and scientific needs for NAMs and partnership opportunities. Several high-level themes that emerged from the session follow:

• Regulatory needs and opportunities for partnership
• A database of accepted and validated NAMs could inform NAM development and regulation by helping identify areas where traditional models are not sufficient or not available.
• The amount of data available for NAM development and validation must be increased and be freely available, harmonizable, and reusable.
• Additionally, standardized, established frameworks should ensure data quality, reproducibility, and utility.
• Context of use is critical when considering regulatory acceptance.
• Communication and confidence-building about NAMs will increase acceptance across a range of collaborators. Establishing which NAMs are useful for which settings will be important in this process.
• Scientific needs for NAMs and opportunities for partnership
• Training the next generation of scientists on interdisciplinary research for developing and using NAMs is a critical need.
• Incentives are needed to encourage academics and industry to use NAMs. Current models must be improved to increase clinical relevance, predictive power, and diversity.
• Standards, benchmarks, and shared data infrastructure should guide NAM development. Interoperability should be prioritized to facilitate harmonization, which will include addressing data concept consistency and data access issues.

The Path Ahead

Retreat attendees demonstrated that demand for NAMs is strong, but the landscape is underdeveloped. Collaboration between interested parties is essential for future NAM development, validation, and dissemination. Although various federal agencies have made initial efforts to integrate NAMs, a more coordinated effort is necessary. A Common Fund program centered on NAMs could lay the foundation for global acceptance of these biomedical tools.