Abstract

SummaryCompeting risk data are frequently interval-censored, that is, the exact event time is not observed but only known to lie between two examination time points such as clinic visits. In addition to interval censoring, another common complication is that the event type is missing for some study participants. In this article, we propose an augmented inverse probability weighted sieve maximum likelihood estimator for the analysis of interval-censored competing risk data in the presence of missing event types. The estimator imposes weaker than usual missing at random assumptions by allowing for the inclusion of auxiliary variables that are potentially associated with the probability of missingness. The proposed estimator is shown to be doubly robust, in the sense that it is consistent even if either the model for the probability of missingness or the model for the probability of the event type is misspecified. Extensive Monte Carlo simulation studies show good performance of the proposed method even under a large amount of missing event types. The method is illustrated using data from an HIV cohort study in sub-Saharan Africa, where a significant portion of events types is missing. The proposed method can be readily implemented using the new function ciregic_aipw in the R package intccr.

Highlights

  • Competing risks data are frequently encountered in cohort studies and clinical trials, and they refer to the situation where study participants are at risk of multiple mutually exclusive events (Kalbfleisch and Prentice, 2011; Putter and others, 2007; Bakoyannis and Touloumi, 2012)

  • Given that there is no one-to-one relationship between the cause-specific hazard (CSH) and the cumulative incidence function (CIF), such standard methods cannot be used for inference about the CIF and different methods are required (Fine and Gray, 1999; Putter and others, 2007; Bakoyannis and Touloumi, 2012)

  • We address the main limitations of the currently available methods for semiparametric analysis of the CIF with interval-censored competing risks data and missing event types under Missing at Random (MAR)

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Summary

Introduction

Competing risks data are frequently encountered in cohort studies and clinical trials, and they refer to the situation where study participants are at risk of multiple mutually exclusive events (Kalbfleisch and Prentice, 2011; Putter and others, 2007; Bakoyannis and Touloumi, 2012). In the competing risks framework, the cumulative incidence function (CIF) and the cause-specific hazard (CSH) function are the basic identifiable quantities from the observed data (Kalbfleisch and Prentice, 2011; Putter and others, 2007; Bakoyannis and Touloumi, 2012; Koller and others, 2012; Andersen and others, 2012). The sum of the CIFs for all event types is naturally bounded above by 1 for all timepoints and all (observed) covariate patterns This leads to the need for special distributions for parametric analysis (Jeong and Fine, 2007), or complex constrained optimization with nonlinear inequality constraints for a joint semiparametric analysis of the CIFs for all event types (Bakoyannis and others, 2017). We focus on making inferences about the CIF

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