From theory to practice: Simple rules for improving clinical trial confidence with covariate adjustment

IF 4 2区医学 Q1 CLINICAL NEUROLOGY

Journal of Pain Pub Date : 2025-07-04 DOI:10.1016/j.jpain.2025.105489

Arthur Ooghe , Alvaro Pereira , Luana Colloca , Elizabeth Stannard , Chris Ambrose , Dmitri Lissin , Samuel Branders

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引用次数: 0

Abstract

Statistical adjustment using covariates is a well-known method for improving the sensitivity of clinical trials, particularly in drug development. However, it is yet underutilized, despite recent guidance from the FDA and relevant literature emphasizing its potential. This limited adoption may be due to the lack of clear methodologies for selecting appropriate covariates. This article aims to fill this gap by providing practical tools to define covariates that can enhance the precision of estimates. Specifically, the proposed simple rules aim to assist trialists by demystifying statistical concepts found in specialized literature. It provides a clear framework for determining which covariates to use, how many to include, and how to maximize the precision derived from them. Case studies presented here illustrates the application of these principles using data from controlled trials targeting several pain indications. Ultimately, this work underscores the importance of covariate adjustment in clinical trials and offers a structured approach to optimize its use, guiding researchers toward more reliable study outcomes.

Perspective

This work highlights the critical yet underutilized role of covariate adjustment in enhancing the sensitivity of clinical trials. By providing practical tools and a clear procedure for selecting and applying covariates, it aims to improve precision and reliability in study outcomes, addressing a gap in current trial practices.

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从理论到实践：用协变量调整提高临床试验置信度的简单规则。

使用协变量进行统计调整是一种众所周知的提高临床试验敏感性的方法，特别是在药物开发中。然而，尽管最近FDA的指导和相关文献强调了它的潜力，但它尚未得到充分利用。这种有限的采用可能是由于缺乏明确的方法来选择适当的协变量。本文旨在通过提供定义协变量的实用工具来填补这一空白，协变量可以提高估计的精度。具体地说，拟议的简单规则旨在通过消除在专业文献中发现的统计概念的神秘性来帮助试验人员。它提供了一个清晰的框架，用于确定使用哪些协变量、包含多少协变量以及如何最大化从中获得的精度。这里提出的案例研究利用针对几种疼痛指征的对照试验数据说明了这些原则的应用。最终，这项工作强调了协变量调整在临床试验中的重要性，并提供了一种结构化的方法来优化其使用，指导研究人员获得更可靠的研究结果。观点：这项工作强调了协变量调整在提高临床试验敏感性方面的关键但未充分利用的作用。通过提供实用的工具和明确的程序来选择和应用协变量，旨在提高研究结果的准确性和可靠性，解决当前试验实践中的差距。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Pain 医学-临床神经学

CiteScore

6.30

自引率

7.50%

发文量

441

审稿时长

42 days

期刊介绍： The Journal of Pain publishes original articles related to all aspects of pain, including clinical and basic research, patient care, education, and health policy. Articles selected for publication in the Journal are most commonly reports of original clinical research or reports of original basic research. In addition, invited critical reviews, including meta analyses of drugs for pain management, invited commentaries on reviews, and exceptional case studies are published in the Journal. The mission of the Journal is to improve the care of patients in pain by providing a forum for clinical researchers, basic scientists, clinicians, and other health professionals to publish original research.