Computer Aided Clinical Trials for Implantaule Cardiac Devices
Computer Aided Clinical Trials for Implantaule Cardiac Devices
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植入式心脏装置的计算机辅助临床试验
DOI：
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发表时间：
2018
期刊：
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通讯作者：
Rahul Mangharam
中科院分区：
文献类型：
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作者：
Kuk Jin Jang;James Weimer;Houssam Abbas;Zhihao Jiang;J. Liang;S. Dixit;Rahul Mangharam
在本文中，我们的目的是回答这个问题，“如何建模和模拟生理系统被用来评估生命关键的植入式医疗设备？”医疗器械的临床试验效率越来越低，因为它们需要数年时间才能进行，成本非常高，失败率也很高。例如，Rhythm ID Goes Head-to-head Trial（RIGHT）试图评估两种心律失常排除算法在植入式心律转复除颤器中的性能，Vitality 2与Medtronic，在首次不适当治疗的时间方面，但得出的结果与最初的假设相反-经过5年，2，000多名患者，道德和金钱成本合理。在本文中，我们描述了植入式心脏器械的计算机辅助临床试验（CACT）的设计和性能，其中既往试验信息、真实的患者数据和闭环器械模型可有效用于高置信度评价试验。我们制定的CACT的上下文中使用贝叶斯统计框架的权利。我们定义了一个分层模型的虚拟队列生成的生理模型，捕捉参数的不确定性，并允许在试验设计的系统纳入可用的信息。使用该公式，与Medtronic相比，Vitality 2的不适当治疗率估计为33.22% vs 15.62% $（mathrm{p}lt 0.001）$，与原始试验相当。最后，我们将计算机辅助临床试验的结果与RIGHT的主要终点联系起来。
In this paper we aim to answer the question, “How can modeling and simulation of physiological systems be used to evaluate life-critical implantable medical devices?” Clinical trials for medical devices are becoming increasingly inefficient as they take several years to conduct, at very high cost and suffer from high rates of failure. For example, the Rhythm ID Goes Head-to-head Trial (RIGHT) sought to evaluate the performance of two arrhythmia discriminator algorithms for implantable cardioverter defibrillators, Vitality 2 vs. Medtronic, in terms of time-to-first inappropriate therapy, but concluded with results contrary to the initial hypothesis- after 5 years, 2,000+ patients and at considerble ethical and monetary cost. In this paper, we describe the design and performance of a Computer-aided Clinical Trial (CACT) for Implantable Cardiac Devices where previous trial information, real patient data and closed-loop device models are effectively used to evaluate the trial with high confidence. We formulate the CACT in the context of RIGHT using a Bayesian statistical framework. We define a hierarchical model of the virtual cohort generated from a physiological model which captures the uncertainty in the parameters and allow for the systematic incorporation of information available at the design of the trial. With this formulation, the estimates the inappropriate therapy rate of Vitality 2 compared to Medtronic as 33.22% vs 15.62% $(mathrm{p}lt 0.001)$, which is comparable to the original trial. Finally, we relate the outcomes of the computer- aided clinical trial to the primary endpoint of RIGHT.