The Annals of Statistics

Multi-objective optimal designs in comparative clinical trials with covariates: The reinforced doubly adaptive biased coin design

Alessandro Baldi Antognini and Maroussa Zagoraiou

Full-text: Open access

Abstract

The present paper deals with the problem of allocating patients to two competing treatments in the presence of covariates or prognostic factors in order to achieve a good trade-off among ethical concerns, inferential precision and randomness in the treatment allocations. In particular we suggest a multipurpose design methodology that combines efficiency and ethical gain when the linear homoscedastic model with both treatment/covariate interactions and interactions among covariates is adopted. The ensuing compound optimal allocations of the treatments depend on the covariates and their distribution on the population of interest, as well as on the unknown parameters of the model. Therefore, we introduce the reinforced doubly adaptive biased coin design, namely a general class of covariate-adjusted response-adaptive procedures that includes both continuous and discontinuous randomization functions, aimed to target any desired allocation proportion. The properties of this proposal are described both theoretically and through simulations.

Article information

Source
Ann. Statist., Volume 40, Number 3 (2012), 1315-1345.

Dates
First available in Project Euclid: 10 August 2012

Permanent link to this document
https://projecteuclid.org/euclid.aos/1344610585

Digital Object Identifier
doi:10.1214/12-AOS1007

Mathematical Reviews number (MathSciNet)
MR3015027

Zentralblatt MATH identifier
1257.62082

Subjects
Primary: 62K05: Optimal designs 62L05: Sequential design
Secondary: 62G20: Asymptotic properties 60F05: Central limit and other weak theorems

Keywords
Balance information criteria ethics CARA designs

Citation

Baldi Antognini, Alessandro; Zagoraiou, Maroussa. Multi-objective optimal designs in comparative clinical trials with covariates: The reinforced doubly adaptive biased coin design. Ann. Statist. 40 (2012), no. 3, 1315--1345. doi:10.1214/12-AOS1007. https://projecteuclid.org/euclid.aos/1344610585


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Supplemental materials

  • Supplementary material: Supplement to “Multi-objective optimal designs in comparative clinical trials with covariates: the reinforced doubly adaptive biased coin design”. An online supplementary file contains the extension of inferential criteria C1–C5 to the case of several covariates.