title: Sample size and screening size trade-off in the presence of subgroups with different expected treatment effects.
abstract: When designing clinical trials, sometimes we may expect a larger treatment effect in one group while others exhibit an attenuated effect. In these settings there can be a trade-off between a smaller average treatment effect with broader enrollment criteria and a larger effect with restricted criteria but longer enrollment duration. Identification of subgroups will often use a clinical decision rule, for example, biomarker cutoff, but may be imprecise, that is, with sensitivity and specificity not simultaneously 100%. We evaluate the impact of including attenuated subgroups on design operating characteristics and illustrate scenarios where overall trial duration may be shorter by not being restrictive.
authors.affiliation: a Division of Biostatistics , School of Public Health, University of Minnesota , Minneapolis , Minnesota , USA.
authors.forename: Kyle D
authors.initials: KD
authors.lastname: Rudser
authors.forename: Edward
authors.initials: E
authors.lastname: Bendert
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Koopmeiners
mesh_terms: D015415:Biomarkers; D002986:Clinical Trials as Topic / Q000379:methods / Q000592:standards*; D006801:Humans; D008403:Mass Screening / Q000379:methods / Q000592:standards*; D012107:Research Design / Q000592:standards*; D018401:Sample Size; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers