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

Abstract

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.

Comparison of treatments with ordinal responses in trials with sequential monitoring and response‐adaptive randomization

“…In particular, the target-driven response-adaptive design is considered to be an excellent design given its capability to incorporate desirable objectives, such as minimizing the number of patients who receive an inferior treatment. 12 The first target-driven response-adaptive treatment allocation procedures were constructed largely for binary and Gaussian outcomes, but these allocation procedures have recently been extended to more complex responses, such as survival outcomes, [20][21][22][23] recurrent events, 24 and ordinal outcomes. 15 The DBCD treatment-allocation scheme has a well-deserved reputation as an excellent target-driven response-adaptive treatment-allocation procedure, which is due to its being superior to other schemes in providing a viable treatment-allocation framework in which optimal criteria can be embedded.…”

“…In particular, the target‐driven response‐adaptive design is considered to be an excellent design given its capability to incorporate desirable objectives, such as minimizing the number of patients who receive an inferior treatment 12 . The first target‐driven response‐adaptive treatment allocation procedures were constructed largely for binary and Gaussian outcomes, but these allocation procedures have recently been extended to more complex responses, such as survival outcomes, 20‐23 recurrent events, 24 and ordinal outcomes 15 …”

Adaptive treatment allocation for comparative clinical studies with recurrent events data

“…However, in a clinical trial, incoming patients typically arrive sequentially. This allows a response‐adaptive treatment allocation scheme to be used (Su and Cheung, ). This type of scheme is usually implemented to achieve certain desirable objectives.…”