title: Operational challenges in adaptive design implementation.
abstract: Implementation of adaptive clinical trial designs raises challenges with regard to the processes by which accruing trial data is analyzed, reviewed, and acted upon. In line with current monitoring conventions, it should be viewed that inappropriate knowledge of interim results can raise concerns regarding maintaining trial integrity and interpretability of results. Here we discuss issues related to these processes in adaptive trials, and point out distinctions versus other more familiar monitoring situations. One topic involves the composition of the group of individuals who will have access to interim results in order to recommend adaptations. We discuss operational models for data review by this group; one question addressed is whether in adaptive trials a role in this process for a representative of the study sponsor could at times be warranted, and might be justified if adequate protections are in place. Another issue involves whether adaptations made based upon interim data can convey to observers an amount of information about the results, which could rise to a level of concern. We consider whether different types of adaptations might be more or less problematic with regard to this issue, and recommend steps that might be considered to mitigate this concern.
authors.affiliation: Novartis Pharmaceuticals, B&SR, One Health Plaza, East Hanover, NJ 07936, USA. paul.gallo@novartis.com
authors.forename: Paul
authors.initials: P
authors.lastname: Gallo
mesh_terms: D002986:Clinical Trials as Topic / Q000379:methods*; D003627:Data Interpretation, Statistical; D003657:Decision Making; D006801:Humans; D012107:Research Design