Response‐adaptive treatment allocation for survival trials with clustered right‐censored data

• Published in: Statistics in medicine 2018-07, Vol.37 (16), p.2427-2439
• Main Authors: Su, Pei‐Fang, Cheung, Siu Hung
• Format: Article
• Language: English
• Subjects: allocation function; Clinical Studies as Topic - methods; Cluster Analysis; Computer Simulation; copula model; doubly adaptive biased coin design; Humans; Medical research; Random Allocation; Survival Analysis; test power; total expected hazard
• ISSN: 0277-6715; 1097-0258
• DOI: 10.1002/sim.7652

A comparison of 2 treatments with survival outcomes in a clinical study may require treatment randomization on clusters of multiple units with correlated responses. For example, for patients with otitis media in both ears, a specific treatment is normally given to a single patient, and hence, the 2 ears constitute a cluster. Statistical procedures are available for comparison of treatment efficacies. The conventional approach for treatment allocation is the adoption of a balanced design, in which half of the patients are assigned to each treatment arm. However, considering the increasing acceptability of responsive‐adaptive designs in recent years because of their desirable features, we have developed a response‐adaptive treatment allocation scheme for survival trials with clustered data. The proposed treatment allocation scheme is superior to the balanced design in that it allows more patients to receive the better treatment. At the same time, the test power for comparing treatment efficacies using our treatment allocation scheme remains highly competitive. The advantage of the proposed randomization procedure is supported by a simulation study and the redesign of a clinical study.