Ouellet D, Werth J, Parekh N, Feltner D, McCarthy B, Lalonde R L
Pfizer Global Research and Development, Ann Arbor, Michigan, New London, Connecticut, USA.
Clin Pharmacol Ther. 2009 Mar;85(3):277-82. doi: 10.1038/clpt.2008.235. Epub 2008 Dec 10.
The use of a clinical utility index (CUI) was proposed in order to compare two calcium channel alpha2delta ligands that were in development for the treatment of insomnia. The important attributes included in the CUI were two measures of residual sedation and five measures of efficacy (wake after sleep onset, sleep quality, sleep latency, and sleep stages (stage 1 and stages 3-4)). Dose-response analyses were conducted on each end point, and a sensitivity analysis was conducted to determine a clinically meaningful difference in CUI. Nonparametric bootstrap parameters were used to build confidence intervals (CIs). Peak CUI (80% CI) was 0.345 (0.25-0.43), observed at a dose of approximately 30 mg with the lead compound and 0.436 (0.35-0.52) observed at >600-mg dose for the backup. Although CUI was slightly greater for the backup, peak CUI values were observed at doses that were not considered viable, and therefore development of the ligand was discontinued. The use of the CUI allowed an efficient, quantitative, and transparent decision.
为比较两种正在研发用于治疗失眠的钙通道α2δ配体，有人提出使用临床效用指数（CUI）。CUI包含的重要属性有两项残留镇静指标和五项疗效指标（睡眠起始后觉醒、睡眠质量、睡眠潜伏期以及睡眠阶段（第1阶段和第3 - 4阶段））。对每个终点进行剂量反应分析，并进行敏感性分析以确定CUI中具有临床意义的差异。使用非参数自助法参数构建置信区间（CI）。主要化合物在约30 mg剂量时观察到的CUI峰值（80% CI）为0.345（0.25 - 0.43），备用化合物在>600 mg剂量时观察到的CUI峰值为0.436（0.35 - 0.52）。尽管备用化合物的CUI略高，但CUI峰值出现在不被认为可行的剂量下，因此该配体的研发被终止。CUI的使用实现了高效、定量且透明的决策。
