Weight of Evidence Frameworks in Evaluation of Adverse Outcome Pathways

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Weight of Evidence (WoE) is an assessment mechanism used to systematically consider a collection of scientific data that addresses a specific hypothesis. WoE frameworks are used to help form a reasonable conclusion based on all available information, and are commonly utilized in risk assessment. They have recently been applied to toxicological assessments that seek to understand Adverse Outcome Pathways (AOPs), or the cascade of physiological events that link toxicant exposure to a downstream adverse health outcome. In case studies, WoE methods have proven useful in assessing AOPs and estimating pathway-based risk. However, WoE approaches vary considerably and have received criticism for their lack of transparency, reproducibility, and quantitative rigor. The subjective nature of qualitative WoE constructs has led to a push for a quantitative methodology that is consistent, objective, and robust. The purpose of this chapter is to provide a brief background on WoE methodology and its historical use in AOP discovery, as well as highlight progress in the development of a standardized quantitative WoE framework. An example of a newly proposed standardized quantitative WoE framework for AOPs is discussed, and gaps and suggested improvements are examined in order to identify next steps towards making quantitative WoE methods for AOPs more objective, transparent, and reproducible.