Triangulation in Environmental Epidemiology for EPA Human Health Assessments Proceedings of a Workshop (2022) / Chapter Skim
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3 Health Authority Perspectives on the Synthesis of Epidemiologic Evidence
3 Health Authority Perspectives on the Synthesis of Epidemiologic Evidence
Pages 9-17
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From page 9... ...
EPA evaluated the relationship between Libby Amphibole Asbestos and the risk of COPD, using an extended Cox proportional hazards model with two different exposure metrics, finding that the estimated slope for COPD was small and not statistically significant. The analysis provided greater confidence that the relationship between Libby Amphibole Asbestos and lung cancer was not due to uncontrolled confounding by smoking in the occupational study that had incomplete smoking data, she concluded.
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From page 10... ...
Nachman closed by saying that the examples shared "were done in the spirit of triangulation, with the goal of synthesizing results within an evidence stream. Negative control outcomes or exposures can be used to identify potential for residual or uncontrolled confounding or to rule out uncontrolled confounding.
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Agents with sufficient evidence in experimental animals together with strong mechanistic evidence based on KCs are also classified in Group 1. Group 2B is based on a single stream of evidence, such as limited evidence in humans, sufficient evidence of cancer in experimental animals, or strong mechanistic evidence based on KCs.
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From page 12... ...
The process behind establishing causal inference consists of developing evidence through research, synthesizing evidence through systematic reviews, meta-analyses, and other approaches, and integrating evidence from different streams to determine the strength of evidence for causation of an outcome by a factor. "Causal criteria" figure prominently in guiding expert judgment to reach causal inference conclusions, he said.
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NTP conducts evaluations and makes decisions using systematic review methods. Within an evidence stream, NTP uses the categories and criteria for sufficient and limited evidence established by the IARC Monographs.
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From page 14... ...
Similar to IARC, Lunn and her colleagues found differences in case-control studies and cohort studies that have different biases, but systematic evaluation by duration and other factors pointed to more consistent evidence for the carcinogenicity of persistent nightshift work. In closing, Lunn suggested considering triangulation-based concepts in the evaluation of individual studies, across studies within a stream of evidence, and across evidence streams.
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From page 15... ...
In closing, Haney highlighted some hazard identification challenges such as disparate results within an evidence stream, or disparate health endpoint results across evidence streams such as when animal study effects are not seen in epidemiological studies for any reason. The lack of tumor site concordance across species is a notable example.
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From page 16... ...
Exposure Assessment Among advances and emerging methodologies, exposure science needs to be taken into account in hazard identification and risk assessments, said Schubauer-Berigan, calling these the "most critical aspects of study quality and informativeness," in Monographs meetings. Exposure science allows judgments regarding the adequacy of exposure contrast for assessing effects and can reduce uncertainty about other aspects, such as understanding whether a target organ is likely affected.
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From page 17... ...
Publications Nachman commented on the need to include relevant supplemental material, such as relations between exposure and confounder, in publications to facilitate systematic reviews. Schubauer-Berigan agreed, noting, "Greater consideration in the scientific and epidemiologic communities as to how critical these studies are for the evaluation of health hazards and encouraging the community to make better use of supplemental materials … would be very beneficial, for bias assessment, for many purposes." Lawlor added that publication of the objectives and plans of a study in a protocol can promote progress through early engagement with a broader range of experts.
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