title: European COMPARative Effectiveness research on blended Depression treatment versus treatment-as-usual (E-COMPARED): study protocol for a randomized controlled, non-inferiority trial in eight European countries.
abstract: Effective, accessible, and affordable depression treatment is of high importance considering the large personal and economic burden of depression. Internet-based treatment is considered a promising clinical and cost-effective alternative to current routine depression treatment strategies such as face-to-face psychotherapy. However, it is not clear whether research findings translate to routine clinical practice such as primary or specialized mental health care. The E-COMPARED project aims to gain knowledge on the clinical and cost-effectiveness of blended depression treatment compared to treatment-as-usual in routine care.
  
  
  
  E-COMPARED will employ a pragmatic, multinational, randomized controlled, non-inferiority trial in eight European countries. Adults diagnosed with major depressive disorder (MDD) will be recruited in primary care (Germany, Poland, Spain, Sweden, and the United Kingdom) or specialized mental health care (France, The Netherlands, and Switzerland). Regular care for depression is compared to "blended" service delivery combining mobile and Internet technologies with face-to-face treatment in one treatment protocol. Participants will be followed up at 3, 6, and 12 months after baseline to determine clinical improvements in symptoms of depression (primary outcome: Patient Health Questionnaire-9), remission of depression, and cost-effectiveness. Main analyses will be conducted on the pooled data from the eight countries (n = 1200 in total, 150 participants in each country).
  
  
  
  The E-COMPARED project will provide mental health care stakeholders with evidence-based information and recommendations on the clinical and cost-effectiveness of blended depression treatment.
  
  
  
  France: ClinicalTrials.gov NCT02542891 . Registered on 4 September 2015; Germany: German Clinical Trials Register DRKS00006866 . Registered on 2 December 2014; The Netherlands: Netherlands Trials Register NTR4962 . Registered on 5 January 2015; Poland: ClinicalTrials.Gov NCT02389660 . Registered on 18 February 2015; Spain: ClinicalTrials.gov NCT02361684 . Registered on 8 January 2015; Sweden: ClinicalTrials.gov NCT02449447 . Registered on 30 March 2015; Switzerland: ClinicalTrials.gov NCT02410616 . Registered on 2 April 2015; United Kingdom: ISRCTN registry, ISRCTN12388725 . Registered on 20 March 2015.
authors.affiliation: Section Clinical Psychology, Vrije Universiteit Amsterdam and EMGO+ Institute for Health Care and Research, Van der Boechorststraat 1, 1081 BT, Amsterdam, The Netherlands. a.m.kleiboer@vu.nl.
authors.forename: Annet
authors.initials: A
authors.lastname: Kleiboer
authors.affiliation: Department of Psychiatry, VU University Medical Centre and EMGO+ Institute for Health Care and Research, Amsterdam, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Smit
authors.affiliation: Department of Health Sciences, Vrije Universiteit Amsterdam and EMGO+ Institute for Health and Care Research, Amsterdam, The Netherlands.
authors.forename: Judith
authors.initials: J
authors.lastname: Bosmans
authors.affiliation: Section Clinical Psychology, Vrije Universiteit Amsterdam and EMGO+ Institute for Health Care and Research, Van der Boechorststraat 1, 1081 BT, Amsterdam, The Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Ruwaard
authors.affiliation: Department of Behavioural Sciences and Learning, Swedish Institute for Disability Research, Linköping University, Linköping, Sweden.|Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Andersson
authors.affiliation: Department of Behavioural Sciences and Learning, Swedish Institute for Disability Research, Linköping University, Linköping, Sweden.
authors.forename: Naira
authors.initials: N
authors.lastname: Topooco
authors.affiliation: Department of Clinical Psychology and Psychotherapy, University of Bern, Bern, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Berger
authors.affiliation: Department of Clinical Psychology and Psychotherapy, University of Bern, Bern, Switzerland.
authors.forename: Tobias
authors.initials: T
authors.lastname: Krieger
authors.affiliation: Department of Psychology and Technology, Jaume University, Castellon, Spain.|Department of Personalidad, Evaluación y Tratamiento Psicológicos, Valencia, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Botella
authors.affiliation: Department of Personalidad, Evaluación y Tratamiento Psicológicos, Valencia, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Baños
authors.affiliation: URC-ECO, Ile-de-France (AP-HP), Paris, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Chevreul
authors.affiliation: Department of Population Health, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Araya
authors.affiliation: Department of Population Health, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Arlinda
authors.initials: A
authors.lastname: Cerga-Pashoja
authors.affiliation: Department of Psychology, Szkoła Wyzsza Psychologii Społeczne, University of Social Sciences and Humanities, Warsaw, Poland.
authors.forename: Roman
authors.initials: R
authors.lastname: Cieślak
authors.affiliation: Department of Psychology, Szkoła Wyzsza Psychologii Społeczne, University of Social Sciences and Humanities, Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Rogala
authors.affiliation: Section Clinical Psychology, Vrije Universiteit Amsterdam and EMGO+ Institute for Health Care and Research, Van der Boechorststraat 1, 1081 BT, Amsterdam, The Netherlands.
authors.forename: Christiaan
authors.initials: C
authors.lastname: Vis
authors.affiliation: Department of Psychiatry, VU University Medical Centre and EMGO+ Institute for Health Care and Research, Amsterdam, The Netherlands.
authors.forename: Stasja
authors.initials: S
authors.lastname: Draisma
authors.affiliation: Department of Psychiatry, VU University Medical Centre and EMGO+ Institute for Health Care and Research, Amsterdam, The Netherlands.
authors.forename: Anneke
authors.initials: A
authors.lastname: van Schaik
authors.affiliation: Department of Psychiatry, VU University Medical Centre and EMGO+ Institute for Health Care and Research, Amsterdam, The Netherlands.
authors.forename: Lise
authors.initials: L
authors.lastname: Kemmeren
authors.affiliation: Department of Clinical Psychology, Philipps University, Marburg, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Ebert
authors.affiliation: Department of Clinical Psychology, Philipps University, Marburg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Berking
authors.affiliation: Institut für elektronische Geschäftsprozesse, Leuphana University Lüneburg, Lüneburg, Germany.
authors.forename: Burkhardt
authors.initials: B
authors.lastname: Funk
authors.affiliation: Section Clinical Psychology, Vrije Universiteit Amsterdam and EMGO+ Institute for Health Care and Research, Van der Boechorststraat 1, 1081 BT, Amsterdam, The Netherlands.
authors.forename: Pim
authors.initials: P
authors.lastname: Cuijpers
authors.affiliation: Section Clinical Psychology, Vrije Universiteit Amsterdam and EMGO+ Institute for Health Care and Research, Van der Boechorststraat 1, 1081 BT, Amsterdam, The Netherlands.|Department of Psychiatry, VU University Medical Centre and EMGO+ Institute for Health Care and Research, Amsterdam, The Netherlands.
authors.forename: Heleen
authors.initials: H
authors.lastname: Riper
mesh_terms: D006801:Humans; D002985:Clinical Protocols; D015928:Cognitive Behavioral Therapy / Q000191:economics; D057186:Comparative Effectiveness Research; D003362:Cost-Benefit Analysis; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000191:economics / Q000523:psychology / Q000628:therapy; D005060:Europe; D017048:Health Care Costs; D020407:Internet; D011320:Primary Health Care; D012074:Remission Induction; D012107:Research Design; D011795:Surveys and Questionnaires; D013813:Therapy, Computer-Assisted / Q000191:economics; D013997:Time Factors; D016896:Treatment Outcome; D000074099:Equivalence Trials as Topic
keywords: Adults; Blended treatment; Cognitive behavioral treatment (CBT); Comparative effectiveness research (CER); Cost-effectiveness; Depression; Internet-based treatment; Randomized controlled trial (RCT); eHealth; iCBT