Effectiveness of an Integrated Care Pathway for Depression: Cluster Randomized Controlled Trial

Study Overview
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Brief Summary
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This a stepped wedged cluster RCT with two intervention arms--Treatment As Usual (TAU) and an Integrated Care Pathway (ICP). Eligible participants are between the ages of 13 and 18, who present to community mental health agencies with depressive symptoms as the primary concern. The primary objective is to establish the clinical effectiveness of the ICP intervention in the community setting relative to TAU, with respect to reducing evaluator-rated depressive symptoms. The secondary objectives are to explore changes in clinician-rated function and caregiver-rated symptoms for youth receiving the ICP intervention relative to TAU. The third objective is to explore the implementation effectiveness of the ICP intervention, namely investigating: feasibility, fidelity, cost and acceptability.

Detailed Description
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Background: Depression is the leading cause of disability in adolescents and a potent risk factor for adolescent suicide. Evidence-based treatments are available; however, many clinics do not provide guidelines-based treatments. Integrated Care Pathways (ICPs) are treatment algorithms based on the highest quality practice guidelines intended to facilitate the delivery of evidence-based treatment at the clinic level. Our group has already tested the feasibility of ICP for adolescent depression at an academic setting. There is still uncertainty regarding whether ICPs lead to improved outcomes in adolescent depression in community setting relative to typical care. Objective: The current study aim is to test the effectiveness of an ICP for depression in adolescents, called the CARIBOU-2 intervention, versus treatment-as-usual (TAU) in community settings. We hypothesize that participants receiving the ICP will show greater clinical improvement (in symptoms and functioning) than participants in TAU. This study will also examine important implementation outcomes. Method: The primary participants will be adolescents (N= 648), between the ages of 13 to 18 with depressive symptoms, presenting to one of six selected community mental health agencies. Through a stepped wedge design, all sites will begin in the TAU condition and transition to the ICP condition in a randomized sequence. The primary clinical outcome of interest is the difference between treatment groups in the rate of change of depressive symptoms from baseline to 24-week endpoint as measured by the Childhood Depression Rating Scale-Revised. Secondary outcomes include rate of change of functional improvement, as measured by the Children's Global Assessment Scale, and caregiver-rated internalizing symptoms as rated by the Childhood Behaviour Checklist. Generalized linear mixed-effects model is a proper choice to test our clinical hypotheses to control for covariates (e.g. demographics and baseline clinical measures), to accommodate multiple forms of the outcome (e.g. continuous, categorical and count type), and to account for clustering at individual level (for repeated measures) and at site level. Time, stage assignment and their interactions will serve as the primary predictors for the analyses. As an example, if we let Y_ijt to denote a continuous outcome of the j-th participant of the i-th site measured at time t, a linear model for Y_ijt will look like the following: Y_ijt=β_0+〖b_(0,ij)+b_(1,i)+β〗_1 t+β_2 〖Group〗_(i,t)+β_3 Group_it*t+〖β_4 X_ijt+ϵ〗_ijt of which 〖Group〗_(i,t) denotes the treatment assignment of the i-th site at time t, X_ijt, additional covariates, b_(0,ij) and b_(1,i), random effects at individual and site levels respectively, ϵ_( ijt), unexplained random error, and β's, regression coefficients. For sensitivity analyses, we will explore the use of quadratic or piecewise models when the linear model may not be adequate. We will adopt the intention-to-treat approach in general and use multiple imputation methods as the primary missing data strategy. Count data, proportions and qualitative data will be used to describe implementation outcomes. Relevance: Should our results be consistent with our hypotheses, systematic implementation of the CARIBOU-2 intervention to other community mental health agencies would be indicated.

Official Title
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Effectiveness of an Integrated Care Pathway for Adolescent Depression: a Multi-site Stepped Wedge, Cluster Randomized Controlled Trial

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Other: Treatment As Usual
* Other: CARIBOU-2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Youth is aged 13 to 18 years, inclusive. Youth and/or their caregiver is expressing that 'depression (or some synonym) is a primary concern. Clinician agrees that depressive symptoms are a primary treatment target. Mood and Feelings Questionnaire score is ≥22 at two sequential visits (screening and baseline assessment). Youth must be new to the site (in past 3 months) or have a period of no treatment for 3 months Exclusion Criteria: Known or highly suspected presentations of psychotic symptoms that are persistent, affect functioning, and have observable effects on behaviour. Severe substance use disorder, bipolar disorder, autism spectrum disorder or intellectual disability, severe eating disorder, imminent risk of suicide requiring hospitalization as per judgment of the assessing clinician. Inability to provide informed consent to the study for any reason Youth currently in Day Treatment

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: The study uses a Type 1 Hybrid Implementation Effectiveness design that focuses on the effectiveness of the clinical intervention (ICP) while exploring the implementation effectiveness of the intervention. A stepped wedge, cluster randomized controlled trial is indicated as the intervention is applied at the clinic level.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Treatment as Usual<br>Study involvement for all sites will begin in the TAU condition, which is the typical treatment at the participating community mental health agency. A range of treatments observed in our previous survey of sites will be on offer in these agencies, depending on the preferences and context of the local agency. In typical TAU in community mental health agencies, depressive symptoms and function are not systematically monitored via standardized rating scales. TAU may or may not include referral to psychotherapy and/or parent support. There are no prompts to prescribe specific medications, and/or internal and external referrals to treatment and other services, guided by local service standards. | Other: Treatment As Usual<br>* Various typical interventions for adolescents with depression.<br>|
| Experimental: CARIBOU-2<br>After the CARIBOU-1 pilot study, the Principal Investigator revised the ICP to render it more applicable to community settings as well as offer a second-line psychotherapy (Brief Psychosocial Intervention) for youth who do not engage with, or respond to, cognitive-behavioural therapy. The revised version is called the CARIBOU-2 intervention. The current iteration of the pathway involves a series of steps: (1) structured assessment, including safety assessment; (2) education on depression, sleep and exercise; (3) psychotherapy (with 1st line Cognitive Behavioural Therapy, 2nd line Brief Psychosocial Intervention); (4) a caregiver structured support group; (5) medication options (1st line fluoxetine, 2nd line sertraline); (6) team reviews every four weeks, (meeting with the youth and involved clinicians to review measures and discuss treatment changes); and, (7) discharge and follow-up planning. | Other: CARIBOU-2<br>* Integrated Care Pathway intervention for adolescents with depression.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Childhood Depression Rating Scale-Revised | A 17-item measure rated by an RA following a semi-structured interview with the adolescent relating to symptoms of depression over the past 2 weeks. The RA will be blind to treatment assignment. | Change from baseline to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Children's Global Assessment Scale | An adaptation of the Global Assessment Scale (GAS) (Endicott et al., 1976) and was designed to reflect the lowest level of functioning for children or adolescents (ages 4 to 16) during a the past month. Its values range from 1 (maximum functional impairment), to 100 (minimum functional impairment)--scores above 70 are designated as indicating normal function. | Change from baseline to 52-weeks | 
| Child Behaviour Checklist - Internalizing Broadband Scale | A 118-item caregiver-rated measure assessing the youth's behaviour and general psychopathology. It is a widely used measure with known population norms. One-week test-retest reliability was found to be 0.80-0.94. Internal consistency is reported to be high; inter-rater reliability (e.g., between two parents) was found to be moderate to high (reference needed). All subscales will be used at baseline to describe general psychopathology. The internalizing broadband scale of the CBCL (ie. anxious-depressed, depressed-withdrawn, and somatic subscales combined) will be measured longitudinally to get an impression of how the caregiver is observing any changes in mood or anxiety with treatment. | Change from baseline to 52-weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adolescents, Integrated Care Pathway, Depression, Measurement Based Care, Implementation