Differential Participation, a Potential Cause of Spurious Associations in Observational Cohorts in Environmental...

Differential participation in observational cohorts may lead to biased or even reversed estimates. In this article, we describe the potential for differential participation in cohorts studying the etiologic effects of long-term environmental exposures. Such cohorts are prone to differential participation because only those who survived until the start of follow-up and were healthy enough before enrollment will participate, and many environmental exposures are prevalent in the target population and connected to participation via factors such as geography or frailty. The relatively modest effect sizes of most environmental exposures also make any bias induced by differential participation particularly important to understand and account for. We discuss key points to consider for evaluating differential participation and use causal graphs to describe two example mechanisms through which differential participation can occur in health studies of long-term environmental exposures. We use a real-life example, the Canadian Community Health Survey cohort, to illustrate the non-negligible bias due to differential participation. We also demonstrate that implementing a simple washout period may reduce the bias and recover more valid results if the effect of interest is constant over time. Furthermore, we implement simulation scenarios to confirm the plausibility of the two mechanisms causing bias and the utility of the washout method. Since the existence of differential participation can be difficult to diagnose with traditional analytical approaches that calculate a summary effect estimate, we encourage researchers to systematically investigate the presence of time-varying effect estimates and potential spurious patterns (especially in initial periods in the setting of differential participation).