Multicenter Bayesian Decision-Theoretic Clinical Trials

描述(由申请人提供)：设计、实施和解释治疗罕见但破坏性急性疾病(如中毒、中毒)的临床试验是困难的：合格受试者很少；在疗效比较证据积累的同时继续对患者进行均匀随机试验可能不道德；正确解释有限的数据可能需要专家意见或外部信息。此外，在中期分析中终止试验的决定可能最好是使用决策分析来处理。我们的广泛目标是开发贝叶斯决策理论临床试验设计，它使用部分自适应分配来最大化患者的利益。具体目标是：(1)描述这些决策理论试验设计的操作特点；(2)研究计算效率更高的试验设计的数值方法；以及(3)构建用于激发和综合专家意见以及进行实时分布式适应性试验的网络应用程序。将通过蒙特卡罗模拟和使用公开可用的软件(WinBUGS)来测试所产生的试验设计的特点。最优试验设计将与使用计算效率更高的近似方法(例如，前向搜索法)获得的设计进行比较。当这项工作完成后，模块化软件系统将公开可用于设计和实施适应性贝叶斯临床试验设计。利普斯基博士将在刘易斯博士的指导下，兼任跨部门临床试验的统计顾问，以进一步提高他在试验设计和分析方面的能力。

DESCRIPTION (provided by applicant): Designing, implementing, and interpreting clinical trials of therapies for the treatment of unusual but devastating acute illnesses (e.g., toxic exposures, envenomations) is difficult: eligible subjects are scarce; continuing to randomize patients evenly while comparative evidence on efficacy accumulates may not be ethical; and the proper interpretation of limited data may require expert opinion or external information. Further, the decision to terminate the trial at an interim analysis may be best addressed using decision analysis. Our broad objective is to develop Bayesian decision-theoretic clinical trial designs which use partially adaptive allocation to maximize patient benefit. Specific aims are: (1) to delineate the operational characteristics of these decision-theoretic trial designs; (2) to investigate numerical methods for more computationally efficient trial design; and (3) to construct web-enabled applications for the elicitation and synthesis of expert opinion and for the real-time distributed conduct of adaptive trials. The characteristics of trial designs generated will be tested by both Monte Carlo simulation and through the use of publicly-available software (WinBUGS). Optimal trial designs will be compared to designs obtained using more computationally efficient approximate methods (e.g., forward search methods). When this work is complete, the modular software system will be publicly available for the design and implementation of adaptive Bayesian clinical trial designs. Dr. Lipsky will concurrently serve as a statistical consultant for interdepartmental clinical trials, under the guidance of Dr. Lewis, to further his abilities in trial design and analysis.