Novartis Ireland Ltd, Dublin, D04A9N6, Co Dublin, Ireland.
Burrows Consulting, London, UK.
Ther Innov Regul Sci. 2023 Jul;57(4):629-645. doi: 10.1007/s43441-023-00502-8. Epub 2023 Apr 5.
This paper examines the use of digital endpoints (DEs) derived from digital health technologies (DHTs), focusing primarily on the specific considerations regarding the determination of meaningful change thresholds (MCT). Using DHTs in drug development is becoming more commonplace. There is general acceptance of the value of DHTs supporting patient-centric trial design, capturing data outside the traditional clinical trial setting, and generating DEs with the potential to be more sensitive to change than conventional assessments. However, the transition from exploratory endpoints to primary and secondary endpoints capable of supporting labeling claims requires these endpoints to be substantive with reproducible population-specific values. Meaningful change represents the amount of change in an endpoint measure perceived as important to patients and should be determined for each digital endpoint and given population under consideration. This paper examines existing approaches to determine meaningful change thresholds and explores examples of these methodologies and their use as part of DE development: emphasizing the importance of determining what aspects of health are important to patients and ensuring the DE captures these concepts of interest and aligns with the overarching endpoint strategy. Examples are drawn from published DE qualification documentation and responses to qualification submissions under review by the various regulatory authorities. It is the hope that these insights will inform and strengthen the development and validation of DEs as drug development tools, particularly for those new to the approaches to determine MCTs.
本文探讨了数字健康技术（DHT）衍生的数字终点（DE）的应用，重点关注确定有意义变化阈值（MCT）的具体考虑因素。在药物开发中使用 DHT 变得越来越普遍。人们普遍认可 DHT 支持以患者为中心的试验设计、在传统临床试验环境之外捕获数据以及生成比传统评估更能敏感反映变化的 DE 的价值。然而，从探索性终点向能够支持标签声明的主要和次要终点的转变，需要这些终点具有可重复的特定人群值的实质性内容。有意义的变化代表了患者认为重要的终点测量值的变化量，应该针对每个数字终点和考虑的人群进行确定。本文探讨了确定有意义变化阈值的现有方法，并探讨了这些方法的示例及其作为 DE 开发的一部分的用途：强调确定对患者重要的健康方面的重要性，并确保 DE 捕捉到这些感兴趣的概念并与总体终点策略保持一致。这些示例来自已发表的 DE 资格文件以及各监管机构正在审查的资格申请的回复。希望这些见解将为 DE 作为药物开发工具的开发和验证提供信息和支持，特别是对于那些新接触确定 MCT 方法的人。
