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5 Evidence Synthesis
Pages 64-69

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From page 64...
... IRIS process for evidence synthesis is presented in Chapters 9, 10, and 11. The purpose of these chapters is to summarize and interpret the results across all informative health effect studies within both human and animal streams and to integrate those data to draft hazard synthesis sections describing human and animal toxicity data.
From page 65...
... With the understanding that HAWC is a dynamic system, Table 9-1 is not consistent with the column headers and criteria in the HAWC interface, namely Studies, outcomes, and confidence; Summary of key findings; Factors that increase certainty (consistency, dose-response, coherence of effects, larger or concerning magnitude of effect, mechanistic evidence providing plausibility, medium or high confidence studies, other) ; and Factors that decrease certainty (unexplained inconsistency, imprecision, lack of expected coherence, evidence demonstrating implausibility, low confidence studies)
From page 66...
... Choices of Methods The evidence synthesis approach outlined in the handbook appears to be a "hybrid" of a guided expert judgment approach (e.g., Hill, 1965; IARC, 2019; Samet et al., 2020) and a more structured approach (e.g., Grading of Recommendations Assessment, Development and Evaluation [GRADE]
From page 67...
... and precision, and biological gradient/dose-response -- are closely aligned with existing systematic evidence evaluation frameworks, such as Cochrane, GRADE, NTP, and the Navigation Guide. This is appropriate because the Bradford Hill considerations encompass both evidence synthesis and evidence integration, while modern evidence evaluation frameworks make an explicit distinction between them in order to promote greater transparency and consistency.
From page 68...
... are synthesized separately, will they each receive a strength of evidence judgment, will there be a single overall strength of evidence judgment for liver toxicity, or will strength of evidence judgments occur both individually and together? Recommendation 5.2: The unit of analysis for evidence synthesis and strength of evidence conclusions should be clearly defined as specified by the refined PECO statements recommended in Chapter 3 of this report.
From page 69...
... Recommendation 5.5: EPA should remove discussion of natural experiments in the context of evidence synthesis in the handbook. That discussion could possibly be repurposed in the context of the handbook's Chapter 6 "Study Evaluation." [Tier 2]

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