title: Potential of adaptive clinical trial designs in pharmacogenetic research.
abstract: Adaptive trial designs can be beneficial in pharmacogenetic research when prior uncertainty exists regarding the exact role and clinical relevance of genetic variability in drug response. This type of design enables us to learn about the effect of the genetic variability on drug response and to immediately use this information for the remainder of the study. For different types of adaptive trial designs, we discuss when and how the designs are suitable for pharmacogenetic research: adaptation of randomization, adaptation of patient enrollment and adaptive enrichment. To illustrate the potential benefits of an adaptive design over a fixed design, we simulated an adaptive trial based on the results of the IPASS trial. With a simple model we show that for this example an adaptive enrichment design would have led to a smaller trial, with less EGF receptor mutation-negative patients unnecessarily exposed to the drug, without compromising the α level or reducing power.
authors.affiliation: Julius Center for Health Sciences & Primary Care, University Medical Center Utrecht, The Netherlands. f.vanderbaan@umcutrecht.nl
authors.forename: Frederieke H
authors.initials: FH
authors.lastname: van der Baan
authors.forename: Mirjam J
authors.initials: MJ
authors.lastname: Knol
authors.forename: Olaf H
authors.initials: OH
authors.lastname: Klungel
authors.forename: Antoine Cg
authors.initials: AC
authors.lastname: Egberts
authors.forename: Diederick E
authors.initials: DE
authors.lastname: Grobbee
authors.forename: Kit C B
authors.initials: KC
authors.lastname: Roes
mesh_terms: D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D023381:Endpoint Determination; D006801:Humans; D010597:Pharmacogenetics / Q000379:methods*; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D018401:Sample Size