Matching with time-dependent treatments: A review and look forward

Observational studies of treatment effects attempt to mimic a randomized experiment by balancing the covariate distribution in treated and control groups, thus removing biases related to measured confounders. Methods such as weighting, matching, and stratification, with or without a propensity score, are common in cross-sectional data. When treatments are initiated over longitudinal follow-up, a target pragmatic trial can be emulated using appropriate matching methods. The ideal experiment of interest is simple; patients would be enrolled sequentially, randomized to one or more treatments and followed subsequently. This tutorial defines a class of longitudinal matching methods that emulate this experiment and provides a review of existing variations, with guidance regarding study design, execution, and analysis. These principles are illustrated in application to the study of statins on cardiovascular outcomes in the Framingham Offspring cohort. We identify avenues for future research and highlight the relevance of this methodology to high-quality comparative effectiveness studies in the era of big data.