Estimating the impact of treatment compliance over time on smoking cessation using data from ecological momentary assessments (EMA)

The Wisconsin Smoker's Health Study (WSHS2) was a longitudinal trial conducted to compare the effectiveness of two commonly used smoking cessation treatments, varenicline and combination nicotine replacement therapy (cNRT) with the less intense standard of care, nicotine patch. The main outcome of the WSHS2 study was that all three treatments had equivalent treatment effects. However, in-depth analysis of the compliance data collected via ecological momentary assessment (EMA) were not analyzed. Compliance to the treatment regimens may represent a confounder as varenicline and cNRT are more intense treatments and would likely have larger treatment effects if all subjects complied. In order to estimate the causal compliance effect, we view the counterfactual, the outcome that would have been observed if the subject was allocated to the treatment counter to the fact, as a missing data problem and proceed to impute the counterfactual. Our contribution to the methodological literature lies in the extension of this idea to a more general analytic approach that includes mediators and confounders of the mediator-outcome relationship. Simulation results suggest that our method works well and application to the WSHS2 data suggest that the treatment effect of nicotine patch, varenicline, and cNRT are equivalent after accounting for differences in treatment compliance.