title: Implementing multifactorial psychotherapy research in online virtual environments (IMPROVE-2): study protocol for a phase III trial of the MOST randomized component selection method for internet cognitive-behavioural therapy for depression.
abstract: Depression is a global health challenge. Although there are effective psychological and pharmaceutical interventions, our best treatments achieve remission rates less than 1/3 and limited sustained recovery. Underpinning this efficacy gap is limited understanding of how complex psychological interventions for depression work. Recent reviews have argued that the active ingredients of therapy need to be identified so that therapy can be made briefer, more potent, and to improve scalability. This in turn requires the use of rigorous study designs that test the presence or absence of individual therapeutic elements, rather than standard comparative randomised controlled trials. One such approach is the Multiphase Optimization Strategy, which uses efficient experimentation such as factorial designs to identify active factors in complex interventions. This approach has been successfully applied to behavioural health but not yet to mental health interventions.
  
  
  
  A Phase III randomised, single-blind balanced fractional factorial trial, based in England and conducted on the internet, randomized at the level of the patient, will investigate the active ingredients of internet cognitive-behavioural therapy (CBT) for depression. Adults with depression (operationalized as PHQ-9 score ≥ 10), recruited directly from the internet and from an UK National Health Service Improving Access to Psychological Therapies service, will be randomized across seven experimental factors, each reflecting the presence versus absence of specific treatment components (activity scheduling, functional analysis, thought challenging, relaxation, concreteness training, absorption, self-compassion training) using a 32-condition balanced fractional factorial design (2IV7-2). The primary outcome is symptoms of depression (PHQ-9) at 12 weeks. Secondary outcomes include symptoms of anxiety and process measures related to hypothesized mechanisms.
  
  
  
  Better understanding of the active ingredients of efficacious therapies, such as CBT, is necessary in order to improve and further disseminate these interventions. This study is the first application of a component selection experiment to psychological interventions in depression and will enable us to determine the main effect of each treatment component and its relative efficacy, and cast light on underlying mechanisms, so that we can systematically enhance internet CBT.
  
  
  
  Current Controlled Trials ISRCTN24117387 . Registered 26 August 2014.
authors.affiliation: Sir Henry Wellcome Building for Mood Disorders Research, College of Life and Environmental Sciences, University of Exeter, Exeter, EX4 4QG, UK. e.r.watkins@exeter.ac.uk.
authors.forename: Edward
authors.identifier: 0000-0002-2432-5577
authors.initials: E
authors.lastname: Watkins
authors.affiliation: Sir Henry Wellcome Building for Mood Disorders Research, College of Life and Environmental Sciences, University of Exeter, Exeter, EX4 4QG, UK.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Newbold
authors.affiliation: Sir Henry Wellcome Building for Mood Disorders Research, College of Life and Environmental Sciences, University of Exeter, Exeter, EX4 4QG, UK.
authors.forename: Michelle
authors.initials: M
authors.lastname: Tester-Jones
authors.affiliation: Sir Henry Wellcome Building for Mood Disorders Research, College of Life and Environmental Sciences, University of Exeter, Exeter, EX4 4QG, UK.
authors.forename: Mahmood
authors.initials: M
authors.lastname: Javaid
authors.affiliation: Sir Henry Wellcome Building for Mood Disorders Research, College of Life and Environmental Sciences, University of Exeter, Exeter, EX4 4QG, UK.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Cadman
authors.affiliation: The Methodology Center and Department of Human Development and Family Studies, The Pennsylvania State University, Health and Human Development Building, University Park, PA, 16802, USA.
authors.forename: Linda M
authors.initials: LM
authors.lastname: Collins
authors.affiliation: The Methodology Center and Department of Human Development and Family Studies, The Pennsylvania State University, Health and Human Development Building, University Park, PA, 16802, USA.
authors.forename: John
authors.initials: J
authors.lastname: Graham
authors.affiliation: Sir Henry Wellcome Building for Mood Disorders Research, College of Life and Environmental Sciences, University of Exeter, Exeter, EX4 4QG, UK.
authors.forename: Mohammod
authors.initials: M
authors.lastname: Mostazir
mesh_terms: D000328:Adult; D015928:Cognitive Behavioral Therapy / Q000379:methods*; D003866:Depressive Disorder / Q000628:therapy*; D005260:Female; D006801:Humans; D020407:Internet; D008297:Male; D012107:Research Design; D016037:Single-Blind Method; D016896:Treatment Outcome; D006113:United Kingdom; D055815:Young Adult
keywords: Cognitive behavioural therapy; Depression; Factorial; MOST; Online