Response adaptive designs for Phase II trials with binary endpoint based on context-dependent information measures
针对罕见病II期临床试验中统计功效与治疗响应患者数之间的权衡，提出基于加权Renyi、Tsallis和Fisher信息的响应自适应设计，通过内置参数显式调节平衡，模拟表明精确准则相比渐近准则或更多参数的信息测度无显著增益。
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 power comparable to the fixed equal randomisation's but a greater number of patients responded in the trials.