Division of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA.
Division of Biostatistics, Center for Devices and Radiological Health, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
J Biopharm Stat. 2020 May 3;30(3):495-507. doi: 10.1080/10543406.2019.1684309. Epub 2019 Nov 10.
In medical product development, there has been an increased interest in utilizing real-world data which have become abundant with recent advances in biomedical science, information technology, and engineering. High-quality real-world data may be analyzed to generate real-world evidence that can be utilized in the regulatory and healthcare decision-making. In this paper, we consider the case in which a single-arm clinical study, viewed as the primary data source, is supplemented with patients from a real-world data source containing both clinical outcome and covariate data at the patient-level. Propensity score methodology is used to identify real-world data patients that are similar to those in the single-arm study in terms of the baseline characteristics, and to stratify these patients into strata based on the proximity of the propensity scores. In each stratum, a composite likelihood function of a parameter of interest is constructed by down-weighting the information from the real-world data source, and an estimate of the stratum-specific parameter is obtained by maximizing the composite likelihood function. These stratum-specific estimates are then combined to obtain an overall population-level estimate of the parameter of interest. The performance of the proposed approach is evaluated via a simulation study. A hypothetical example based on our experience is provided to illustrate the implementation of the proposed approach.
在医疗产品开发中,人们越来越感兴趣地利用真实世界的数据,随着生物医学科学、信息技术和工程的最新进展,真实世界的数据已经变得非常丰富。高质量的真实世界数据可以进行分析,以生成真实世界的证据,这些证据可以用于监管和医疗保健决策。在本文中,我们考虑了一种情况,即单臂临床研究被视为主要数据源,同时补充了来自真实世界数据源的患者,这些数据源包含患者级别的临床结果和协变量数据。倾向评分方法用于根据基线特征识别与单臂研究中患者相似的真实世界数据患者,并根据倾向评分的接近程度将这些患者分层。在每个层中,通过对真实世界数据源的信息进行降权,构建感兴趣参数的复合似然函数,并通过最大化复合似然函数来获得层内特定参数的估计值。然后将这些层内特定的估计值组合起来,以获得感兴趣参数的总体人群水平估计值。通过模拟研究评估了所提出方法的性能。基于我们的经验提供了一个假设示例来说明所提出方法的实施。
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