An ad hoc committee of the National Academies of Sciences, Engineering, and Medicine will review the Report on Carcinogens Handbook (the Handbook), with a focus on the robustness and scientific rigor of the methodology and functional utility of the Handbook. The committee will evaluate the procedures and considerations for operationalizing the principles of systematic review and evidence integration within these cancer hazard assessments, particularly the evaluation and integration of mechanistic data or new approach methodologies (NAMs). The committee will not reassess the cancer hazard evaluations of specific substances reported in Report on Carcinogen Monographs.

Aspects that will be considered during the review of the Handbook include:

1. The strengths and limitations of the methods for systematic review and evidence integration, including:

• Application of risk of bias tools
• Development of systematic evidence maps
• Evaluation of mechanistic data including key characteristics of carcinogens and NAMs
• Integration of mechanistic, human, and animal data evidence streams
• Data delivery, accessibility, and presentation.

2. The extent to which the tools and processes:

• Align with scientific best practices and advances in evidence evaluation
• Promote reproducibility and transparency
• Are flexible and responsive to technological and methodological innovations (e.g., AI-assisted review tools).

Recommendations will be prioritized as follows:

• Tier 1 – Recommended revisions to improve critical scientific concepts and issues, transparency, rigor, accessibility, consistency of the methods and, ultimately, confidence in the conclusions
• Tier 2 – Suggested revisions that are encouraged to strengthen or clarify methodological application, broaden utility, heighten confidence in the approach and conclusions, and improve readability
• Tier 3 - Considerations for future development, including research needs (but not substances to evaluate in future assessments), opportunities to pilot new methods and assure alignment with broader systematic review frameworks, and opportunities to improve throughput and data dissemination