In this module you will be able to gain deeper insights into population-level effect estimation. We cover one specific type of population-level effect estimation method for generating clinical evidence: comparative cohort studies. The course presents a framework for formulating comparative effect research questions and discusses what makes good and bad questions. It furthermore describes how the OHDSI tools can be used to design and execute a comparative effect study using the OHDSI software tools. This includes the use of propensity scores to adjust for confounding, varying times at risk, and different types of outcome models, such as Cox or logistic regressions. An existing published study is analyzed to demonstrate the applicability of the framework. Evaluation of a study, based on study diagnostics, as well as negative controls and empirical calibration, are discussed at length.