Survivor treatment selection bias in observational studies: examples from the AIDS literature.

Unlike patients in a randomized, clinical trial, patients in an observational study choose if and when to begin treatment. Patients who live longer have more opportunities to select treatment; those who die earlier may be untreated by default. These facts are the essence of an often overlooked bias, termed "survivor treatment selection bias," which can erroneously lead to the conclusion that an ineffective treatment prolongs survival. Unfortunately, misanalysis of survivor treatment selection bias has been prevalent in the recent literature on the acquired immunodeficiency syndrome. Approaches to mitigating this bias involve complex statistical models. At a minimum, initiation of therapy should be treated as a time-dependent covariate in a proportional hazards model. Investigators and readers should be on the alert for survivor treatment selection bias and should be cautious when interpreting the results of observational treatment studies.