An analytic method for randomized trials with informative censoring: Part 1.

Consider a randomized trial in which time to the occurrence of a particular disease, say pneumocystis pneumonia in an AIDS trial or breast cancer in a mammographic screening trial, is the failure time of primary interest. Suppose that time to disease is subject to informative censoring by the minimum of time to death, loss to and end of follow-up. In such a trial, the censoring time is observed for all study subjects, including failures. In the presence of informative censoring, it is not possible to consistently estimate the effect of treatment on time to disease without imposing additional non-identifiable assumptions. The goals of this paper are to specify two non-identifiable assumptions that allow one to test for and estimate an effect of treatment on time to disease in the presence of informative censoring. In a companion paper (Robins, 1995), we provide consistent and reasonably efficient semiparametric estimators for the treatment effect under these assumptions. In this paper we largely restrict attention to testing. We propose tests that, like standard weighted-log-rank tests, are asymptotically distribution-free alpha-level tests under the null hypothesis of no causal effect of treatment on time to disease whenever the censoring and failure distributions are conditionally independent given treatment arm. However, our tests remain asymptotically distribution-free alpha-level tests in the presence of informative censoring provided either of our assumptions are true. In contrast, a weighted log-rank test will be an alpha-level test in the presence of informative censoring only if (1) one of our two non-identifiable assumptions hold, and (2) the distribution of time to censoring is the same in the two treatment arms. We also extend our methods to studies of the effect of a treatment on the evolution over time of the mean of a repeated measures outcome, such as CD-4 count.