Correcting for noncompliance and dependent censoring in an AIDS clinical trial with inverse probability of censoring weighted (IPCW) log-rank tests

AIDS Clinical Trial Group (ACTG) randomized trial 021 compared the effect o f bactrim versus aerosolized pentamidine (AP) as prophylaxis therapy for pn eumocystis pneumonia (PCP) in AIDS patients. Although patients randomized t o the bactrim arm experienced a significant delay in time to PCP, the survi val experience in the two arms was not significantly different (p =.32). In this paper, we present evidence that bactrim therapy improves survival but that the standard intent-to-treat comparison failed to detect this surviva l advantage because a large fraction of the subjects either crossed over to the other therapy or stopped therapy altogether. We obtain our evidence of a beneficial bactrim effect on survival by artificially regarding the subj ects as dependently censored at the first time the subject either stops or switches therapy; we then analyze the data with the inverse probability of censoring weighted Kaplan-Meier and Cox partial likelihood estimators of Ro bins (1993, Proceedings of the Biopharmaceutical Section, American Statisti cal Association, pp. 24-33) that adjust for dependent censoring by utilizin g data collected on time-dependent prognostic factors.