title: A stepped wedge design for testing an effect of intranasal insulin on cognitive development of children with Phelan-McDermid syndrome: A comparison of different designs.
abstract: This paper compares the power of the parallel group design, the matched-pairs design, and several options for the stepped wedge and delayed start designs for testing a possible effect of intranasal insulin with respect to placebo on developmental growth of children with a rare disorder like Phelan-McDermid syndrome. A subject-specific linear mixed effects model for the primary outcome developmental age in a longitudinal setting with five time points was assumed. Monte Carlo simulation studies with small sample sizes were applied since the rare disorder prohibits large trials. The stepped wedge designs, which were initially preferred for ethical reasons, appear to be competitive in power to other designs and were in some settings even the best. The assumed statistical model also demonstrates that all of the designs can be viewed as a stepped wedge or delayed treatment design. Our results show that the stepped wedge design is an appropriate alternative for randomized controlled trials on developmental growth with small numbers of participants under the formulated statistical conditions.
authors.affiliation: 1 Department of Mathematics and Computer Science, Eindhoven University of Technology, Eindhoven, The Netherlands.|2 Department of Epidemiology, University Medical Center Groningen, University of Groningen, Eindhoven, The Netherlands.
authors.forename: Edwin R
authors.initials: ER
authors.lastname: Van den Heuvel
authors.affiliation: 3 Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Renée J
authors.initials: RJ
authors.lastname: Zwanenburg
authors.affiliation: 3 Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Conny Ma
authors.initials: CM
authors.lastname: Van Ravenswaaij-Arts
mesh_terms: D000281:Administration, Intranasal; D056808:Biostatistics / Q000379:methods; D002648:Child; D002657:Child Development / Q000187:drug effects; D002872:Chromosome Deletion; D025063:Chromosome Disorders / Q000188:drug therapy* / Q000523:psychology*; D002892:Chromosomes, Human, Pair 22; D003071:Cognition / Q000187:drug effects; D003198:Computer Simulation; D006801:Humans; D007328:Insulin / Q000008:administration & dosage*; D016014:Linear Models; D008137:Longitudinal Studies; D009010:Monte Carlo Method; D016032:Randomized Controlled Trials as Topic / Q000379:methods* / Q000706:statistics & numerical data; D018401:Sample Size
chemical_list: D007328:Insulin
keywords: Developmental growth; Phelan-McDermid syndrome; delayed start design; random coefficient model; small trial designs; stepped wedge design