Evidence Synthesis and Integration Methods used in the US Environmental Protection Agency's (EPA) Integrated Risk Information System (IRIS) Program
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US Environmental Protection Agency’s (EPA) Integrated Risk Information System (IRIS) assessments are an important source of toxicity information used by EPA, state and local health agencies, Tribes, other federal agencies, and international health organizations. IRIS assessments, which include hazard identification and dose-response analyses, are conducted using systematic review methods for identifying evidence, evaluating individual studies, summarizing the relevant evidence (i.e., evidence synthesis), and arriving at summary conclusions regarding the overall body of evidence (i.e., evidence integration). The systematic review approaches used for IRIS assessments were developed through discussions within and outside EPA and informed by multiple reviews by the National Academy of Sciences (NAS). In brief, the strength of the evidence from the available human and animal health effect studies are summarized in parallel, but separately, using a structured evaluation of an adapted set of considerations first introduced by Sir Bradford Hill in 1965. Relevant mechanistic evidence that informs the biological plausibility and coherence within the available human or animal health effect studies is also considered. The terms associated with the different strength of evidence judgments for the human and animal evidence streams are robust, moderate, slight, indeterminate, and compelling evidence of no effect. These judgments are then combined to draw an overall judgment that incorporates inferences across evidence streams, such as the human relevance of findings in animals. The final output is an evidence integration narrative with terms reflecting the summary judgment of evidence demonstrates, evidence indicates (likely), evidence suggests, evidence inadequate, or strong evidence of no effect. The expert judgements made during evidence synthesis and integration are summarized in an evidence profile tables using structured web-forms housed within the EPA’s version of Health Assessment Workspace Collaborative (HAWC). US Environmental Protection Agency’s (EPA) Integrated Risk Information System (IRIS) assessments are an important source of toxicity information used by EPA, state and local health agencies, Tribes, other federal agencies, and international health organizations. IRIS assessments, which include hazard identification and dose-response analyses, are conducted using systematic review methods for identifying evidence, evaluating individual studies, summarizing the relevant evidence (i.e., evidence synthesis), and arriving at summary conclusions regarding the overall body of evidence (i.e., evidence integration). The systematic review approaches used for IRIS assessments were developed through discussions within and outside EPA and informed by multiple reviews by the National Academy of Sciences (NAS). In brief, the strength of the evidence from the available human and animal health effect studies are summarized in parallel, but separately, using a structured evaluation of an adapted set of considerations first introduced by Sir Bradford Hill in 1965. Relevant mechanistic evidence that informs the biological plausibility and coherence within the available human or animal health effect studies is also considered. The terms associated with the different strength of evidence judgments for the human and animal evidence streams are robust, moderate, slight, indeterminate, and compelling evidence of no effect. These judgments are then combined to draw an overall judgment that incorporates inferences across evidence streams, such as the human relevance of findings in animals. The final output is an evidence integration narrative with terms reflecting the summary judgment of evidence demonstrates, evidence indicates (likely), evidence suggests, evidence inadequate, or strong evidence of no effect.