Target Trial Emulation for Comparing Repeated Treatment Schedules: Pitfalls and Key Decisions

Thomas M. Menino Convention & Exhibition Center 

Target trial emulation (TTE) applies the principles of randomized trials to observational studies, often to compare sustained treatment strategies. However, its utility for comparing two different schedules of the same repeated treatment, such as annual versus biennial mammography screening, is understudied. We present key obstacles and potential sources of bias in this setting and propose solutions. We outline two analytical approaches for a treatment schedule TTE: sequential trials with clone-censor-weighting and a marginal structural model. Through simulation, we compare the performance of these approaches for estimating marginal risk differences between annual and biennial treatment schedules over time for a survival outcome. We show that TTE with pooled sequential trials results in bias when eligibility criteria do not ensure sufficient washout, and that allowing eligibility after previous treatment changes the estimand regardless of washout. These biases can be mitigated by clearly defining baseline treatment history in the target population and standardizing estimates accordingly. This work highlights the pitfalls and implicit assumptions of methods common to TTE.

Target trial emulation

Marginal structural model

Longitudinal data

Causal inference

Sequential trials

Survival analysis 

Section on Statistics in Epidemiology