INTRODUCTION
Researchers have been mimicking randomized trials in nonexperimental data for decades. One persistent challenge has been allocating time experienced by individuals while different treatment regimens cannot be distinguished from one another. Randomized trials can assign patients to different durations of treatment (e.g., up to six vs up to twelve chemotherapy infusions)1 after an index date. In observational data, however, such regimens are often impossible to distinguish from one another until long after treatment assignment has occurred. Traditional analyses of these regimens in an observational context generally change the estimated quantity,2require strong assumptions to estimate that quantity,3or fail to align assessing eligibility, starting treatment, and the beginning follow-up.4, 5
One analytic solution involves cloning participants into regimens of interest, censoring clones once incompatible with their treatment regimens, and weighting uncensored clones based on their inverse probability of remaining uncensored (IPCW) (hereafter referred to as CCW for clone-censor-weighting).6, 7CCW can emulate trials of treatment regimens indistinguishable at baseline without randomization or outcome modeling using the G-formula8, 9 and compare outcomes when individuals receive the same treatment at different times (e.g., surveillance colonoscopy every 3 vs. 7 years)10 or initiate treatment within specific windows (e.g., statin initiation within 6 months vs no treatment11 or starting hormone therapy at 3 months vs at disease progression).12
Unfortunately, CCW analyses can be difficult to implement. Moreover, the causal contrast underlying a CCW analysis comparing regimens like “start treatment within 30 days” to “start treatment from 30 to 90 days” is difficult to articulate and can vary substantially across study populations, making information on the study population’s initiation timings essential context for effect estimates.13 Here, we walk through using CCW to estimate the effect of initiating aspirin or clopidogrel treatment within 30 days of first myocardial infarction (MI) vs within 90 days vs within 30-to-90 days in the Medicare Claims Synthetic Public Use Files (SynPUF) and then visualize the hypothetical interventions under study. The source cohort and commented SAS and R code are posted in a public GitHub repository at https://github.com/mawcpharmdphd/CCW_tutorial.