Response Adaptive Designs for Phase II Trials with Binary Endpoint Based on Context-Dependent Information Measures
In many rare disease Phase II clinical trials, two objectives are of interest to an
investigator: maximising the statistical power and maximising the number of patients
responding to the treatment. These two objectives are competing, therefore,
clinical trial designs offering a balance between them are needed. Recently, it
was argued that response-adaptive designs such as families of multi-arm bandit
(MAB) methods could provide the means for achieving this balance. Furthermore,
response-adaptive designs based on a concept of context-dependent (weighted) information
criteria were recently proposed with a focus on Shannon’s differential
entropy. The information-theoretic designs based on the weighted Renyi, Tsallis
and Fisher informations are also proposed. Due to built-in parameters of these
novel designs, the balance between the statistical power and the number of patients
that respond to the treatment can be tuned explicitly. The asymptotic properties
of these measures are studied in order to construct intuitive criteria for arm selection.
A comprehensive simulation study shows that using the exact criteria over
asymptotic ones or using information measures with more parameters, namely
Renyi and Tsallis entropies, brings no sufficient gain in terms of the power or proportion
of patients allocated to superior treatments. The proposed designs based
on information-theoretical criteria are compared to several alternative approaches.
For example, via tuning of the built-in parameter, one can find designs with powercomparable to the fixed equal randomisation’s but a greater number of patients
responded in the trials.