Isotonic estimation of survival under a misattribution of cause of death.

Abstract

Several authors have indicated that incorrectly classified cause of death for prostate cancer survivors may have played a role in the observed recent peak and decline of prostate cancer mortality. Motivated by the suggestion we studied a competing risks model where other cause of death may be misattributed as a death of interest. We first consider a naïve approach using unconstrained nonparametric maximum likelihood estimation (NPMLE), and then present the constrained NPMLE where the survival function is forced to be monotonic. Surprising observations were made as we studied their small-sample and asymptotic properties in continuous and discrete situations. Contrary to the common belief that the non-monotonicity of a survival function NPMLE is a small-sample problem, the constrained NPMLE is asymptotically biased in the continuous setting. Other isotonic approaches, the supremum (SUP) method and the Pooled-Adjacent-Violators (PAV) algorithm, and the EM algorithm are also considered. We found that the EM algorithm is equivalent to the constrained NPMLE. Both SUP method and PAV algorithm deliver consistent and asymptotically unbiased estimator. All methods behave well asymptotically in the discrete time setting. Data from the Surveillance, Epidemiology and End Results (SEER) database are used to illustrate the proposed estimators.