European Comparative Effectiveness Research on Internet-based Depression Treatment in Poland
European Comparative Effectiveness Research on Internet-based Depression Treatment in Poland
Effective, accessible, and affordable depression treatment is of high importance considering
 the large individual and economic burden of depression. There is ample support for the
 effectiveness of Internet-based Cognitive Behavioral Therapy (CBT) for depression which is
 considered a promising alternative to routine depression treatment strategies. Most evidence
 comes from randomized controlled trials, however, and not from research in routine practice.

 The European Comparative Effectiveness Research on Internet-based Depression Treatment
 (E-COMPARED) in Poland aims to compare the clinical and cost-effectiveness of blended CBT for
 adults with major depressive disorder (MDD) with treatment as usual (TAU). The trial will be
 conducted in routine mental health care in Poland, and is a part of the bigger project funded
 by European Commission (Grant Agreement No: 603098). In this randomized controlled trial, a
 total of 150 patients with MDD will be assigned to one of two conditions: 1) blended CBT, 2)
 TAU. Respondents in both conditions will be followed until 12 months after baseline (measures
 will be taken at baseline, 3 months, 6 months and 12 months).
Introduction

 Good mental health is of high value from an individual, economic and social perspective.
 Depression is a serious threat to such a good mental health and highly prevalent worldwide.
 On a yearly basis about 7% of the European population (around 30 million people) suffer from
 a major depression (MDD) (Wittchen et al., 2011). If we take subclinical forms of depression
 into account the prevalence rises up to 15%.

 Depression is not only highly prevalent; it is marked by disabling emotional and physical
 symptoms. It has a severe negative impact on mental wellbeing, quality of life and social and
 work-related functioning of those who suffer from it both on the short and longer term. This
 impact equals at least conditions such as diabetes mellitus, heart disease and arthritis
 (Sprangers et al., 2000). Depression is associated with increased morbidity, mortality,
 health care utilization and health care costs. The World Health Organisation has predicted
 that depression will be the foremost overall cause of disability by 2030 (Mathers, & Loncar,
 2006).

 Objective

 The main objective of the planned research is to compare the clinical and cost-effectiveness
 of blended Cognitive Behavioural Therapy (CBT) for adults with major depressive disorder
 (MDD) with treatment as usual (TAU).

 Study design

 The study is a two-arm randomised controlled non-inferiority and cost-effectiveness trial.
 The trial will be conducted in routine mental health care in Poland, and is a part of the
 bigger project funded by European Commission (Grant Agreement No: 603098). A total of 150
 patients with MDD will be assigned to one of two conditions: 1) blended CBT, 2) TAU.
 Respondents in both conditions will be followed until 12 months after baseline (measures will
 be taken at baseline, 3 months, 6 months and 12 months).

 Study population

 A total of 150 patients with MDD will be recruited from routine clinical practice in Poland
 and will receive either depression treatment as usual or blended CBT depression treatment.

 Treatment fidelity

 To ensure treatment fidelity it is required that: (1) a detailed treatment manual is
 available to guide therapists through the treatment, (2) regular meetings are organized
 between the therapists and the research team to prevent drift, (3) therapists will register
 the number of sessions, the frequency of the sessions, the main strategies used in each
 session and the duration of each contact.

 Randomization

 Randomization will be conducted by an independent researcher who is not involved in the
 trial. Randomisation will take place at an individual level, stratified by country, after the
 eligibility and baseline assessment. The independent researcher will create the allocation
 scheme with a computerised random number generator (Random Allocation Software). The
 allocation ratio will be 1:1. We will use block randomization with variable block sizes that
 vary between 8 and 14 allocations per block. Subjects will be randomized into two groups:
 Internet based blended depression treatment or treatment as usual. All investigators and
 clinicians will be unknown to the randomization scheme.

 Sample size calculation

 Sample size calculation is based on the non-inferiority design and calculated for the primary
 clinical outcome symptoms of depression. 150 patients in Poland will enable us to detect a
 clinically significant effect size of d=0.24 (Cuijpers et al., 2014).

 Statistical Analysis

 Multiple imputation will be used to impute missing cost and effect data. Intention-to-treat
 analyses (ITT) increase the risk of type I errors in non-inferiority (NI) trials and
 non-intention-to treat analyses are preferred over ITT analyses in NI designs. Therefore, the
 primary statistical analyses will be per protocol analyses meaning that only those patients
 that have completed the treatment will be included in the analyses. ITT analyses will be used
 in sensitivity analyses to increase confidence in the results obtained by including all
 participants in the analyses independent of whether they have completed the treatment or not.
 Blended depression treatment is considered no less effective than care-as-usual when the
 two-sided 95% confidence interval (the range of plausible differences between the two
 treatments) lies entirely above the standard mean difference of 0.20 which is the
 non-inferiority margin and the smallest clinically acceptable difference.
Inclusion Criteria:

 -  Meet DSM-IV diagnostic criteria for MDD as confirmed by the telephone administered
 MINI International Neuropsychiatric Interview version 5.0 and a score a score of 5 or
 higher on the PHQ-9 screening questionnaire.

 Exclusion Criteria:

 -  Current high risk for suicide according to the MINI Interview section C

 -  Serious psychiatric co-morbidity: substance dependence, bipolar affective disorder,
 psychotic illness, obsessive compulsive disorder, as established at the MINI interview

 -  Currently receiving psychological treatment for depression in primary or specialised
 mental health care

 -  Being unable to comprehend the spoken and written Polish

 -  Not having access to a PC and fast Internet connection (i.e. broadband or comparable).

 -  Not having a Smart phone that is compatible with the mobile component of the
 intervention that is offered or not willing to carry a Smartphone if one is provided
 with one by the research team for the study duration.