title: Decision-theoretic designs for small trials and pilot studies: A review.
abstract: Pilot studies and other small clinical trials are often conducted but serve a variety of purposes and there is little consensus on their design. One paradigm that has been suggested for the design of such studies is Bayesian decision theory. In this article, we review the literature with the aim of summarizing current methodological developments in this area. We find that decision-theoretic methods have been applied to the design of small clinical trials in a number of areas. We divide our discussion of published methods into those for trials conducted in a single stage, those for multi-stage trials in which decisions are made through the course of the trial at a number of interim analyses, and those that attempt to design a series of clinical trials or a drug development programme. In all three cases, a number of methods have been proposed, depending on the decision maker's perspective being considered and the details of utility functions that are used to construct the optimal design.
authors.affiliation: Division of Health Sciences, Warwick Medical School, The University of Warwick, Coventry, UK s.w.hee@warwick.ac.uk.
authors.forename: Siew Wan
authors.initials: SW
authors.lastname: Hee
authors.affiliation: Division of Health Sciences, Warwick Medical School, The University of Warwick, Coventry, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hamborg
authors.affiliation: Clinical Trials Consulting and Training Limited, Buckingham, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Day
authors.affiliation: Division of Health Sciences, Warwick Medical School, The University of Warwick, Coventry, UK.
authors.forename: Jason
authors.initials: J
authors.lastname: Madan
authors.affiliation: Department of Statistics, Stockholm University, Stockholm, Sweden.
authors.forename: Frank
authors.initials: F
authors.lastname: Miller
authors.affiliation: Section of Medical Statistics, CeMSIIS, Medical University of Vienna, Vienna, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Posch
authors.affiliation: INSERM, U1138, team 22, Centre de Recherche des Cordeliers, Université Paris 5, Université Paris 6 Paris, Paris, France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Zohar
authors.affiliation: Division of Health Sciences, Warwick Medical School, The University of Warwick, Coventry, UK.
authors.forename: Nigel
authors.initials: N
authors.lastname: Stallard
mesh_terms: D001499:Bayes Theorem; D017322:Clinical Trials, Phase II as Topic / Q000379:methods*; D003662:Decision Theory; D006801:Humans; D010865:Pilot Projects; D012107:Research Design
keywords: Bayesian decision theory; optimal clinical trial design; phase II clinical trials; utility functions