Accelerating Drug and Device Evaluation through Innovative Clinical Trial Design

描述（由申请人提供）：使用随机临床试验来评估药物和医疗器械是一个复杂且日益昂贵的过程，其成功率低得令人不安。临床试验方法的创新，特别是适应性临床试验，可以解决传统试验设计的许多局限性，并有可能提高临床研究的效率和成功率，提高科学数据的质量，保护人类受试者。最佳的方法包括统计方法和组织过程，用于合作开发和实施验证性的，适应性的临床试验仍然不清楚。该项目将填补这一空白。NINDS支持的神经系统紧急情况治疗试验（NETT）网络中的临床试验开发过程将被用作研究这些试验开发的“实验室”。本文的总体目标是阐明和探索如何最好地使用适应性临床试验设计来改善药物和医疗器械的评价，以及如何使用混合方法来描述和理解开发过程中和开发过程后关键股东的信念、意见和关注点。第一个具体目标是设计四个创新的，适应性的临床试验，用于评估用于急性神经系统疾病或损伤患者护理的药物和设备。自适应方法将包括频繁的中期分析、基于概率的决策规则、未知结局的纵向建模和响应自适应随机化。第二个具体目标是识别和定性描述与接受和实施适应性临床试验相关的关键步骤和障碍。在关键利益相关者接受一个或多个适应性临床试验设计后，这些设计将被纳入提交的资助申请和同行评审中。 公共卫生相关性：随机临床试验是监管机构和临床医生接受新疗法的基石。目前，这一过程缓慢而繁琐，可能会导致关于新疗法效用的错误结论。该项目将确定设计和启动高质量、验证性、适应性临床试验的有效流程。这些方法可用于加速有前途的新疗法的评估，节省资源，并通过提高药物和器械开发的速度和质量来支持公共卫生。

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: 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.