title: Use of an embedded, micro-randomised trial to investigate non-compliance in telehealth interventions.
abstract: Many types of telehealth interventions rely on activity from the patient in order to have a beneficial effect on their outcome. Remote monitoring systems require the patient to record regular measurements at home, for example, blood pressure, so clinicians can see whether the patient's health changes over time and intervene if necessary. A big problem in this type of intervention is non-compliance. Most telehealth trials report compliance rates, but they rarely compare compliance among various options of telehealth delivery, of which there may be many. Optimising telehealth delivery is vital for improving compliance and, therefore, clinical outcomes. We propose a trial design which investigates ways of improving compliance. For efficiency, this trial is embedded in a larger trial for evaluating clinical effectiveness. It employs a technique called micro-randomisation, where individual patients are randomised multiple times throughout the study. The aims of this article are (1) to verify whether the presence of an embedded secondary trial still allows valid analysis of the primary research and (2) to demonstrate the usefulness of the micro-randomisation technique for comparing compliance interventions.
  
  
  
  Simulation studies were used to simulate a large number of clinical trials, in which no embedded trial was used, a micro-randomised embedded trial was used, and a factorial embedded trial was used. Each simulation recorded the operating characteristics of the primary and secondary trials.
  
  
  
  We show that the type I error rate of the primary analysis was not affected by the presence of an embedded secondary trial. Furthermore, we show that micro-randomisation is superior to a factorial design as it reduces the variation caused by within-patient correlation. It therefore requires smaller sample sizes - our simulations showed a requirement of 128 patients for a micro-randomised trial versus 760 patients for a factorial design, in the presence of within-patient correlation.
  
  
  
  We believe that an embedded, micro-randomised trial is a feasible technique that can potentially be highly useful in telehealth trials.
authors.affiliation: MRC Biostatistics Unit Hub for Trials Methodology Research, Cambridge, UK lisa.law@mrc-bsu.cam.ac.uk.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Law
authors.affiliation: Philips Research Cambridge, Cambridge, UK.
authors.forename: Nuwani
authors.initials: N
authors.lastname: Edirisinghe
authors.affiliation: MRC Biostatistics Unit Hub for Trials Methodology Research, Cambridge, UK.
authors.forename: James Ms
authors.initials: JM
authors.lastname: Wason
mesh_terms: D003695:Delivery of Health Care / Q000379:methods; D006801:Humans; D010349:Patient Compliance / Q000706:statistics & numerical data*; D010865:Pilot Projects; D012107:Research Design; D018401:Sample Size; D017216:Telemedicine / Q000458:organization & administration*
keywords: Telehealth; adherence; compliance; eHealth; embedded; micro-randomisation