title: Decision-making in early clinical drug development.
abstract: This paper illustrates an approach to setting the decision framework for a study in early clinical drug development. It shows how the criteria for a go and a stop decision are calculated based on pre-specified target and lower reference values. The framework can lead to a three-outcome approach by including a consider zone; this could enable smaller studies to be performed in early development, with other information either external to or within the study used to reach a go or stop decision. In this way, Phase I/II trials can be geared towards providing actionable decision-making rather than the traditional focus on statistical significance. The example provided illustrates how the decision criteria were calculated for a Phase II study, including an interim analysis, and how the operating characteristics were assessed to ensure the decision criteria were robust. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Early Clinical Development Biometrics, AstraZeneca, Royston, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Frewer
authors.affiliation: Early Clinical Development Biometrics, AstraZeneca, Royston, UK.
authors.forename: Pat
authors.initials: P
authors.lastname: Mitchell
authors.affiliation: Clarostat Consulting Ltd., Alderley Edge, UK.
authors.forename: Claire
authors.initials: C
authors.lastname: Watkins
authors.affiliation: Early Clinical Development Biometrics, AstraZeneca, Royston, UK.
authors.forename: James
authors.initials: J
authors.lastname: Matcham
mesh_terms: D017321:Clinical Trials, Phase I as Topic / Q000379:methods*; D017322:Clinical Trials, Phase II as Topic / Q000379:methods*; D003627:Data Interpretation, Statistical; D003657:Decision Making; D015195:Drug Design; D006801:Humans; D012107:Research Design
keywords: decision criteria; interim analysis; operating characteristics; three-outcome designs