Adapting the prevalent new-user study design and clone-censor-weighting approach to evaluate drug discontinuation

We described how to adapt the prevalent new user (PNU) study design to estimate the effect of drug discontinuation among patients who discontinue and clone-censor-weighting (CCW) approach to estimate the effect of drug discontinuation among an eligible population at a pre-specified time point, focusing on the differences between the target trials the two approaches emulate. While both approaches produced unbiased estimates of the effect of drug discontinuation when all confounders were adjusted for in simulations, the true estimands differed, particularly when treatment effect heterogeneity was introduced. We also applied the approaches to study the effect of statin discontinuation among United States Medicare beneficiaries who discontinued statin therapy after at least 5 years (PNU) or at approximately 5 years (CCW) of continuous use. The PNU analysis estimated a mortality rate difference (MRD) of 3.6 (95% CI, 3.3-3.9) per 100 person-years and a mortality rate ratio (MRR) of 1.41 (95% CI, 1.37-1.45), while the CCW analysis estimated a MRD of 3.4 (95% CI, 2.8-4.0) per 100 person-years and MRR of 1.55 (1.45-1.66). Researchers studying drug discontinuation should carefully consider their causal question and target population when choosing between these two newer approaches.