关于使用有意义评分区域来解释连续临床结局评估的治疗效果
On the use of meaningful score regions to interpret treatment effects on continuous clinical outcome assessments
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- Bayer plc（拜耳公司）
- Critical Path Institute（关键路径研究所）
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中文总结 AI 辅助
本文探讨FDA指南中用于解释连续COA评分治疗效果的有意义评分区域（MSRs）方法，通过历史证据和模拟发现以最大MSR宽度为基准可能漏检有意义疗效，并提出基于MSR成员概率的替代评估方法。
中文摘要 AI 辅助
临床结局评估（COAs），如患者报告结局（PROs），由于采用了多种评分指标而面临可解释性问题。因此，将COA评分与可解释的患者体验联系起来的证据，对于判断基于COA的临床试验终点的结果在多大程度上具有意义是必要的。美国食品药品监督管理局（FDA）于2023年发布草案形式的第四份《以患者为中心的药物开发指南》，提出使用有意义评分区域（MSRs）将COA评分划分为更易于解释的类别（例如，基于严重程度的MSRs分为“无”、“轻度”、“中度”和“重度”）。该指南建议将连续COA评分（例如，两个治疗组之间从基线平均变化的差异）的估计治疗效果大小与最大MSR宽度进行比较。在本文中，我们通过历史证据和模拟进一步探讨了这一建议，并得出结论：使用最大MSR宽度作为基准可能在实际中无法检测出有意义的治疗效果。我们提出了评估治疗效果与MSRs关系的替代方法，以每个治疗组内预期结局的MSR成员概率来描述。
英文摘要
Clinical outcome assessments (COAs), such as patient-reported outcomes (PROs), are faced with an interpretability issue due to a variety of score metrics being employed. Therefore, evidence linking COA scores to interpretable patient experiences is necessary to judge the extent to which the results of COA-based clinical trial endpoints are meaningful. The fourth Patient-Focused Drug Development guidance, published in draft form by the FDA in 2023, proposes the use of meaningful score regions (MSRs) to divide COA scores into more easily interpretable categories (e.g. severity-based MSRs of 'none', 'mild', 'moderate' and 'severe'). A recommendation is to compare the magnitude of estimated treatment effects for continuous COA scores (e.g. the difference in mean change from baseline between two treatment groups) to the maximum MSR width. In this article we explore this recommendation further, through historical evidence and simulations, and conclude that using the maximum MSR width as a benchmark may fail to detect meaningful treatment effects in practice. We suggest alternative approaches to evaluate treatment effects against MSRs, describing the expected outcome within each arm in terms of the probabilities of MSR membership.
