Latent Subgroup Analysis of a Randomized Clinical Trial through a Semiparametric Accelerated Failure Time Mixture Model

• Published in: Biometrics Vol. 69; no. 1; pp. 52 - 61
• Main Authors: Altstein, L, Li, G
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishers 01.03.2013; Blackwell Publishing Ltd; Wiley-Blackwell
• Subjects: All-or-none noncompliance; biological treatment; BIOMETRIC METHODOLOGY; Biometrics; biometry; biopsy; Buckley-James estimator; Censored data; Censorship; Clinical trials; Competing risks; Computer Simulation; Data Interpretation, Statistical; Disease-Free Survival; EM algorithm; Estimation methods; Humans; Lymph node excision; Lymph Node Excision - standards; melanoma; Melanoma - surgery; Modeling; Models, Statistical; Nonproportional hazards model; Parametric models; Patient Compliance; patients; randomized clinical trials; Randomized Controlled Trials as Topic - methods; Simulation; Simulations; Skin cancer; Statistical estimation; Statistical models; Treatment efficacy; variance
• ISSN: 0006-341X; 1541-0420; 1541-0420
• DOI: 10.1111/j.1541-0420.2012.01818.x

This article studies a semiparametric accelerated failure time mixture model for estimation of a biological treatment effect on a latent subgroup of interest with a time‐to‐event outcome in randomized clinical trials. Latency is induced because membership is observable in one arm of the trial and unidentified in the other. This method is useful in randomized clinical trials with all‐or‐none noncompliance when patients in the control arm have no access to active treatment and in, for example, oncology trials when a biopsy used to identify the latent subgroup is performed only on subjects randomized to active treatment. We derive a computational method to estimate model parameters by iterating between an expectation step and a weighted Buckley–James optimization step. The bootstrap method is used for variance estimation, and the performance of our method is corroborated in simulation. We illustrate our method through an analysis of a multicenter selective lymphadenectomy trial for melanoma.