1. ¹Pfizer Global Research and Development, Ann Arbor, Michigan, New London, Connecticut, USA
2. ²Current address: GlaxoSmithKline, Clinical Pharmacology, Modeling and Simulation, PO Box 13398, Five Moore Drive, Research Triangle Park, North Carolina 27709-3398, USA

Correspondence: D Ouellet, (daniele.x.ouellet@gsk.com)

Received 1 August 2008; Accepted 12 October 2008; Published online 10 December 2008.

Abstract

The use of a clinical utility index (CUI) was proposed in order to compare two calcium channel 2 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 ~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.