Evaluating biological plausibility in supporting evidence for action through systematic reviews in public health

Objectives: The objective of this research was to develop and test methods for accessing and evaluating information on the biological plausibility of observed associations between exposures or interventions and outcomes to generate scientific evidence for action consistent with practice in systematic reviews. Study design: To undertake this research, we used the example of the observed associations between antimicrobial use in food animals and increased risks of human exposures to antimicrobial-resistant pathogens of zoonotic origin. Methods: We conducted a scoping search using terms related to biological plausibility or mechanism to identify key references. As recommended by these references, we also used expert consultation with researchers and a public health informationist. We used their recommendations, which included expert consultation, to identify mechanisms relevant to biological plausibility of the association we selected to test. We used the reviews conducted by the World Health Organization (WHO) Guidelines Development Group in support of reducing antimicrobial use in food animal production to populate our model for assessing biological plausibility. Results: We were able to develop a transparent model for biological plausibility based on the adverse outcome pathway used in toxicology and ecology. We were also able to populate this model using the WHO reviews. Conclusions: This analysis of biological plausibility used transparent and validated methods to assess the evidence used in systematic reviews based on the observational studies accessed through searches of the scientific literature. Given the importance of this topic in systematic reviews and evidence-based decision-making, further research is needed to define and test the methodological approaches to access and properly evaluate information from the scientific literature.