title: Statistical issues in pragmatic trials of behavioral economic interventions.
abstract: Randomized clinical trials provide gold-standard evidence for the efficacy of interventions, but have limitations, including highly selected populations that make inference on effectiveness difficult and a lack of ability to adapt and change midstream.
  
  
  
  We propose two innovations for pragmatic trial design.
  
  
  
  Evidence-based evolutionary testing, a framework that allows adaptation of interventions and rapid-cycle innovation, preserves the power of randomization while acknowledging the need for adaptation and learning. An opt-out consent framework increases the fraction of the target population who participate in trials, but may lead to dampening of effect sizes.
  
  
  
  Pragmatic trials offer numerous advantages in the evaluation of behavioral interventions in health. Statistical innovations, including evidence-based evolutionary testing and opt-out framing of consent and enrollment processes, can enhance the power of pragmatic trials and lead to more rapid progress.
authors.affiliation: Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA atroxel@mail.med.upenn.edu.
authors.forename: Andrea B
authors.initials: AB
authors.lastname: Troxel
authors.affiliation: Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA US Department of Veterans Affairs, Philadelphia, PA, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Asch
authors.affiliation: Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA US Department of Veterans Affairs, Philadelphia, PA, USA.
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Volpp
mesh_terms: D001699:Biometry / Q000379:methods*; D057186:Comparative Effectiveness Research / Q000706:statistics & numerical data*; D060909:Economics, Behavioral / Q000706:statistics & numerical data*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D013223:Statistics as Topic
keywords: Effectiveness; generalizability; innovation; opt-out consent