Accelerating Drug and Device Evaluation through Innovative Clinical Trial Design

使用随机临床试验来评估药物和医疗器械是一个复杂的， 昂贵的过程，这是令人不安的低成功率困扰。临床试验创新 方法学，特别是适应性临床试验，可以解决传统方法的许多局限性。 试验设计，并有可能提高临床研究的效率和成功率， 所产生的科学数据的质量，以及对人类受试者的保护。最佳方法-包括 统计方法和组织过程-促进协同发展， 验证性、适应性临床试验的实施仍不清楚。该项目将解决 这个差距。在NINDS支持的神经系统紧急情况下的临床试验开发过程 治疗试验（NETT）网络1将被用作“实验室”，在其中研究 这些审判。本文的总体目标是说明和探索如何最好地使用自适应 临床试验设计，以改善药物和医疗器械的评价，并使用混合方法， 描述和理解的信念，意见，和关键股东的关注期间和之后， 发展过程第一个具体目标是设计四个创新的，适应性的临床试验， 评价用于急性神经系统疾病或损伤患者护理的药物和器械。的 适应性方法将包括频繁的中期分析，基于概率的决策规则，纵向 未知结果的建模和响应自适应随机化。第二个具体目标是 确定和定性描述与接受和执行有关的主要步骤和障碍 适应性临床试验。在接受一个或多个适应性临床试验设计后， 利益相关者，设计将被纳入赠款申请提交的资金和同行 审查. 相关性（见说明）： 随机临床试验是监管机构接受新疗法的基石， 临床医生目前，这一过程是缓慢和繁琐的，并可能导致有关实用程序的错误结论 新的治疗方法。该项目将确定设计和启动高质量、高效率和高效率的 验证性的适应性临床试验这些方法可用于加速有前途的评价 新疗法，节约资源，通过提高药物的使用率和质量来支持公共卫生， 设备开发。

The use of randomized clinical trials to evaluate drugs and medical devices is a complex and increasingly expensive process, which is plagued by disappointingly low rates of success. Innovations in clinical trial methodology, and specifically adaptive clinical trials, can address many ofthe limitations of conventional trial designs and have the potential to improve the efficiency and success rates of clinical research, the quality of resulting scientific data, and the protection of human subjects. Optimal approaches-including both statistical methods and organizational processes-iforthe collaborative development and implementation of confirmatory, adaptive clinical trials remain unclear. This project will address that gap. The process of clinical trial development within the NINDS-supported Neurological Emergencies Treatment Trials (NETT) networl< will be used as the "laboratory" in which to study the development of these trials. The overall objective ofthe proposed worl< is to illustrate and explore how best to use adaptive clinical trial designs to improve the evaluation of drugs and medical devices and to use mixed methods to characterize and understand the beliefs, opinions, and concerns of key stal<eholders during and after the development process. The first specific aim is to design four innovative, adaptive clinical trials for the evaluation of drugs and devices used in the care of patients with acute neurological illness or injury. The adaptive methods will include frequent interim analyses, probability-based decision rules, longitudinal modeling of unl<nown outcomes, and response-adaptive randomization. The second specific aim is to identify and qualitatively characterize l<ey steps and barriers related to the acceptance and implementation of adaptive clinical trials. After acceptance of one or more adaptive clinical trial designs by key stakeholders, the designs will be incorporated into grant applications submitted for funding and peer review. RELEVANCE (See Instructions): Randomized clinical trials are the cornerstone for acceptance of new therapies by regulatory agencies and clinicians. Currently, this process is slow and cumbersome and may lead to false conclusions about the utility of new treatments. This project will identify effective processes for the design and initiation of high-quality, confirmatory, adaptive clinical trials. These methods can be used to accelerate the evaluation of promising new therapies, conserve resources and support public health by improving the rate and quality of drug and device development.