title: Adaptive designs undertaken in clinical research: a review of registered clinical trials.
abstract: Adaptive designs have the potential to improve efficiency in the evaluation of new medical treatments in comparison to traditional fixed sample size designs. However, they are still not widely used in practice in clinical research. Little research has been conducted to investigate what adaptive designs are being undertaken. This review highlights the current state of registered adaptive designs and their characteristics. The review looked at phase II, II/III and III trials registered on ClinicalTrials.gov from 29 February 2000 to 1 June 2014, supplemented with trials from the National Institute for Health Research register and known adaptive trials. A range of adaptive design search terms were applied to the trials extracted from each database. Characteristics of the adaptive designs were then recorded including funder, therapeutic area and type of adaptation. The results in the paper suggest that the use of adaptive designs has increased. They seem to be most often used in phase II trials and in oncology. In phase III trials, the most popular form of adaptation is the group sequential design. The review failed to capture all trials with adaptive designs, which suggests that the reporting of adaptive designs, such as in clinical trials registers, needs much improving. We recommend that clinical trial registers should contain sections dedicated to the type and scope of the adaptation and that the term 'adaptive design' should be included in the trial title or at least in the brief summary or design sections.
authors.affiliation: School of Mathematics & Statistics, Newcastle University, Herschel Building, Newcastle upon Tyne, NE1 7RU, UK.|ScHARR, University of Sheffield, 30 Regent Street, Sheffield, S1 4DA, UK.
authors.forename: Isabella
authors.initials: I
authors.lastname: Hatfield
authors.affiliation: ScHARR, University of Sheffield, 30 Regent Street, Sheffield, S1 4DA, UK.|MRC Biostatistics Unit, Cambridge Institute of Public Health, Forvie Site, Robinson Way, Cambridge Biomedical Campus, Cambridge, CB2 0SR, UK.
authors.forename: Annabel
authors.initials: A
authors.lastname: Allison
authors.affiliation: ScHARR, University of Sheffield, 30 Regent Street, Sheffield, S1 4DA, UK.
authors.forename: Laura
authors.initials: L
authors.lastname: Flight
authors.affiliation: ScHARR, University of Sheffield, 30 Regent Street, Sheffield, S1 4DA, UK.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Julious
authors.affiliation: ScHARR, University of Sheffield, 30 Regent Street, Sheffield, S1 4DA, UK. m.dimairo@sheffield.ac.uk.
authors.forename: Munyaradzi
authors.initials: M
authors.lastname: Dimairo
mesh_terms: D002986:Clinical Trials as Topic / Q000379:methods* / Q000592:standards; D003625:Data Collection; D006801:Humans; D011786:Quality Control; D012042:Registries; D012107:Research Design / Q000592:standards; D009626:Terminology as Topic
keywords: Adaptive design; Clinical trial; Flexible design