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An Improved Matching Practice for Augmenting a Randomized Clinical Trial with External Control

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Abstract

The use of information from real world to assess the effectiveness of medical products is becoming increasingly popular and more acceptable by regulatory agencies. According to a strategic real-world evidence framework published by U.S. Food and Drug Administration, a hybrid randomized controlled trial that augments internal control arm with real-world data is a pragmatic approach worth more attention. In this paper, we aim to improve on existing matching designs for such a hybrid randomized controlled trial. In particular, we propose to match the entire concurrent randomized clinical trial (RCT) such that (1) the matched external control subjects used to augment the internal control arm are as comparable as possible to the RCT population, (2) every active treatment arm in an RCT with multiple treatments is compared with the same control group, and (3) matching can be conducted and the matched set locked before treatment unblinding to better maintain the data integrity and increase the credibility of the analysis. Besides a weighted estimator, we also introduce a bootstrap method to obtain its variance estimation. The finite sample performance of the proposed method is evaluated by simulations based on data from a real clinical trial.

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Data sharing is not applicable to this article as no new data were created or analyzed in this study.

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Author notes

  1. Yanyao Yi

    Present address: Department of Biometrics, Eli Lilly and Company, Indianapolis, IN, USA

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  1. Department of Biometrics, Eli Lilly and Company, Indianapolis, IN, USA

    Jianghao Li, Yu Du & Huayu Liu

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  1. Jianghao Li
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  2. Yu Du
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  3. Huayu Liu
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Li, J., Du, Y., Liu, H. et al. An Improved Matching Practice for Augmenting a Randomized Clinical Trial with External Control. Ther Innov Regul Sci 57, 611–618 (2023). https://doi.org/10.1007/s43441-023-00497-2

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