A response‐adaptive randomization procedure for multi‐armed clinical trials with normally distributed outcomes

Autor: S. Faye Williamson, Sofia S. Villar
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Statistics and Probability
Gittins index
Mathematical optimization
Biometry
Patient Dropouts
Biometrics
Computer science
Endpoint Determination
Context (language use)
01 natural sciences
General Biochemistry
Genetics and Molecular Biology
010104 statistics & probability
03 medical and health sciences
Response adaptive randomization
missing data
Clinical Trials
Phase II as Topic
adaptive designs
Neoplasms
Humans
Computer Simulation
0101 mathematics
030304 developmental biology
Randomized Controlled Trials as Topic
0303 health sciences
Models
Statistical
General Immunology and Microbiology
Randomization Procedure
Adaptive Clinical Trials as Topic
Applied Mathematics
General Medicine
Variance (accounting)
Missing data
3. Good health
unknown variance
Clinical trial
Treatment Outcome
dichotomization
Biometric Methodology
continuous endpoint
General Agricultural and Biological Sciences
Algorithms
Zdroj: Biometrics
ISSN: 1541-0420
0006-341X
Popis: We propose a novel response‐adaptive randomization procedure for multi‐armed trials with continuous outcomes that are assumed to be normally distributed. Our proposed rule is non‐myopic, and oriented toward a patient benefit objective, yet maintains computational feasibility. We derive our response‐adaptive algorithm based on the Gittins index for the multi‐armed bandit problem, as a modification of the method first introduced in Villar et al. (Biometrics, 71, pp. 969‐978). The resulting procedure can be implemented under the assumption of both known or unknown variance. We illustrate the proposed procedure by simulations in the context of phase II cancer trials. Our results show that, in a multi‐armed setting, there are efficiency and patient benefit gains of using a response‐adaptive allocation procedure with a continuous endpoint instead of a binary one. These gains persist even if an anticipated low rate of missing data due to deaths, dropouts, or complete responses is imputed online through a procedure first introduced in this paper. Additionally, we discuss how there are response‐adaptive designs that outperform the traditional equal randomized design both in terms of efficiency and patient benefit measures in the multi‐armed trial context.
Databáze: OpenAIRE
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