title: Clinical Trial Simulation to Inform Phase 2: Comparison of Concentrated vs. Distributed First-in-Patient Study Designs in Psoriasis.
abstract: Clinical trial simulation (CTS) and model-based meta-analysis (MBMA) can increase our understanding of small, first-in-patient (FIP) trial design performance to inform Phase 2 decision making. In this work, we compared dose-ranging designs vs. designs testing only placebo and the maximum dose for early decision making in psoriasis. Based on MBMA of monoclonal antibodies in the psoriasis space, a threshold of greater than a 50 percentage point improvement over placebo effect at the highest feasible drug dose was required for the advancement in psoriasis. Studies testing only placebo and the maximum dose made the correct advancement decision marginally more often than dose-ranging designs in the majority of the cases. However, dose-ranging studies in FIP trials offer important design advantages in the form of dose-response (D-R) information to inform Phase 2 dose selection. CTS can increase the efficiency and quality of drug development decision making by studying the limitations and benefits of study designs prospectively.CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e58; doi:10.1038/psp.2013.32; published online 24 July 2013.
authors.affiliation: Department of Pharmacokinetics & Drug Metabolism, Amgen, Seattle, Washington, USA.
authors.forename: M G
authors.initials: MG
authors.lastname: Dodds
authors.forename: D H
authors.initials: DH
authors.lastname: Salinger
authors.forename: J
authors.initials: J
authors.lastname: Mandema
authors.forename: J P
authors.initials: JP
authors.lastname: Gibbs
authors.forename: M A
authors.initials: MA
authors.lastname: Gibbs