A survey of frameworks for best practices in weight-of-evidence analyses

Abstract

The National Academy of Sciences (NAS) Review of the Environmental Protection Agency’s Draft IRIS Assessment of Formaldehyde proposed a “roadmap” for reform and improvement of the Agency’s risk assessment process. Specifically, it called for development of a transparent and defensible methodology for weight-of-evidence (WoE) assessments. To facilitate development of an improved process, we developed a white paper that reviewed approximately 50 existing WoE frameworks, seeking insights from their variations and nominating best practices for WoE analyses of causation of chemical risks. Four phases of WoE analysis were identified and evaluated in each framework: (1) defining the causal question and developing criteria for study selection, (2) developing and applying criteria for review of individual studies, (3) evaluating and integrating evidence and (4) drawing conclusions based on inferences. We circulated the draft white paper to stakeholders and then held a facilitated, multi-disciplinary invited stakeholder workshop to broaden and deepen the discussion on methods, rationales, utility and limitations among the surveyed WoE frameworks. The workshop developed recommendations for improving the conduct of WoE evaluations. Based on the analysis of the 50 frameworks and discussions at the workshop, best practices in conducting WoE analyses were identified for each of the four phases. Many of these best practices noted from the analysis and workshop could be implemented immediately, while others may require additional refinement as part of the ongoing discussions for improving the scientific basis of chemical risk assessments.

• Data integration
• human relevance
• mode of action
• risk assessment
• systematic review

Acknowledgements

We are grateful to Jennifer Taylor of ACC for her leadership in organizing the workshop. We are also grateful to Mary Hixon of Gradient for her help in preparing the framework narratives presented in the supplementary materials. We thank all of the workshop participants for their time, effort and thoughtful contributions.