Marginal structural models with latent class growth analysis of treatment trajectories: Statins for primary...

Latent class growth analysis is increasingly proposed as a solution to summarize the observed longitudinal treatment into a few distinct groups. When latent class growth analysis is combined with standard approaches like Cox proportional hazards models, confounding bias is not properly addressed because of time-varying covariates that have a double role of confounders and mediators. We propose to use latent class growth analysis to classify individuals into a few latent classes based on their medication adherence pattern, then choose a working marginal structural model that relates the outcome to these groups. The parameter of interest is defined as a projection of the true marginal structural model onto the chosen working model. Simulation studies are used to illustrate our approach and compare it with unadjusted, baseline covariates adjusted, time-varying covariates adjusted, and inverse probability of trajectory groups weighted adjusted models. Our proposed approach yielded estimators with little or no bias and appropriate coverage of confidence intervals in these simulations. We applied our latent class growth analysis and marginal structural model approach to a database comprising information on 52,790 individuals from the province of Quebec, Canada, aged more than 65 and who were statin initiators to estimate the effect of statin-usage trajectories on a first cardiovascular event.