Causal inference in multi-cohort studies using the target trial framework to identify and minimize sources of bias

Longitudinal cohort studies, which follow a group of individuals over time, provide the opportunity to examine causal effects of complex exposures on long-term health outcomes. Utilizing data from multiple cohorts has the potential to add further benefit by improving precision of estimates through data pooling and allowing examination of effect heterogeneity. However, the interpretation of findings can be complicated by biases that may: i) be compounded when pooling data; or, ii) contribute to discrepant findings when analyses are replicated across cohorts. The 'target trial' is a well-established and powerful tool for guiding causal inference in single-cohort studies. Here we extend this conceptual framework to address the specific challenges that can arise in the multi-cohort setting. By representing a clear definition of the target estimand, the target trial provides a central point of reference against which bias arising in each study and from data pooling can be systematically assessed. Consequently, analyses can be designed to reduce these biases and the resulting findings appropriately interpreted in light of potential remaining biases. We use a case study to demonstrate the framework and its potential to strengthen causal inference in multi-cohort studies through improved analysis design and clarity in the interpretation of findings.