Early Interventions for Primary Care Patients With Stress-related Ill-health: a Non-inferiority RCT

Study Overview
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Brief Summary
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Stress-related ill-health is rated one of the largest health challenges in the western world. The most empirically supported treatment for stress-related disorders is cognitive behaviour therapy (CBT), but accessibility is low and most patients in primary care do not receive this evidence-based treatment. Collaborative care has been shown to be an effective working model for primary care patients with mental health problems. This type of care intervention has however not been compared against CBT, which is arguably the gold standard treatment for this patient group. The overarching purpose of this project is to investigate if implementation of two treatment models - collaborative care and therapist-guided self-help CBT -can be effective as early interventions for primary care patients with stress-related ill-health.

Detailed Description
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Stress-related ill-health is rated one of the largest health challenges in the western world. The most empirically supported treatment for stress-related disorders is cognitive behaviour therapy (CBT), but accessibility is low and most patients in primary care do not receive this evidence-based treatment. Collaborative care has been shown to be an effective working model for primary care patients with mental health problems. In this study collaborative care is conducted by a nurse who provides the patient with self-management support. This intervention has been implemented at Gustavsbergs primary care clinic in Stockholm as a means to increase accessibility and quality of care for the large group of patients with stress-related ill-health. This type of care intervention has however not been compared against CBT, which is arguably the gold standard treatment for this patient group. Our research group has developed and tested a therapist-guided self-help CBT (SH-CBT) that can be delivered online or as a self-help book with support by a clinician for stress-related ill health, which has been shown to be effective and also potentially very suitable for the primary care context. The overarching purpose of this project is to investigate if implementation of two treatment models - collaborative care and SH-CBT - can be effective as early interventions for primary care patients with stress-related ill-health. Main research question: Is a brief collaborative care intervention provided by a nurse at least as effective as SH-CBT delivered by a psychologist for primary care patients with mild to moderate symptoms of stress? Note: In may 2022, the research group made revisions to the study procedures in terms of administration format of CBT and inclusion criteria. These specific changes were made: (1) Participants randomized to SH-CBT are allowed to choose if they want to receive the treatment as therapist-guided online CBT or as therapist-guided bibliotherapy CBT. Participants are exposed to the same treatment content, but in the former case the material is presented on a secure website with asynchronous written therapist support and in the latter case the content is provided through a self-help book and the participant has 2-5 face-to-face appointments with the therapist; (2) It is no longer required that participants has adjustment disorder, instead participants have to have (a) a score on the Perceived Stress Scale-10 of 20 or higher, (b) stress-related ill-health as their principal problem, and (c) a duration of their problems of at least 1 month; (3) The sick-leave criterion is changed so that participants to be included are allowed to have been on full time sick-leave for maximum 2 months (instead of 50% for maximum 1 month). The revisions described above were made in order to better operationalize the patient population patients with mild to moderate stress-related ill-health and to increase the recruitment of participants to the study. When the revisions were implemented approximately 20 participants had been included in the study. The revisions were approved by the Swedish Ethical Review Authority (ID 2022-00990-02). Note 2: In the autumn of 2023, a new power calculation was conducted where full use of the 5 assessment points between baseline and post-treatment (12 weeks) was taken into account. This new power calculation, based in linear mixed models analysis for longitudinal data, showed that in order to have 80% power to demonstrate non-inferiority (non-inferiority margin d=0.3; one-sided 95% confidence interval) given a true effect difference of 0, approximately 170 participants (85 per treatment arm) will be needed.

Official Title
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Early Interventions for Primary Care Patients With Stress-related Ill-health: a Randomized Controlled Non-inferiority Trial of a Collaborative Care Intervention vs. Cognitive Behavior Therapy

Conditions
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Stress

Intervention / Treatment
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* Behavioral: Care manager intervention (nurse)
* Behavioral: CBT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 16 years of age A score of 20 or higher on the Perceived Stress Scale-10 Stress-related ill-health is the principal problem Duration of problems for at least 1 month Have symptoms in the mild to moderate range Be able to read and write in Swedish Have access to a computer with Internet connection If the participant is on sick leave then the sick leave period should have a maximum duration of 2 months (full time sick-leave for 2 months is thus allowed) Exclusion Criteria: Ongoing other psychological treatment for stress-related problems

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized controlled non-inferiority trial with two arms. A non-inferiority margin of Cohen's d 0.3 on the primary outcome Perceived Stress Scale at post-treatment (change from baseline to 12 weeks) will be used. For test of non-inferiority on the primary outcome, a one-sided 95% confidence interval (CI) will be used. If the two-sided 95% CI (exploratory analyses) does not include 0 this will be interpreted as indicating superiority of the corresponding treatment.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Care manager intervention (nurse)<br> | Behavioral: Care manager intervention (nurse)<br>* In this intervention, a primary care nurse provides the participant with self-management support to manage stress-related problems. The participant meets with the nurse face-to-face for typically 2 to 6 sessions.<br>|
| Active Comparator: Internet-based CBT<br> | Behavioral: CBT<br>* In this intervention, the participant receives therapist supported self-help CBT. The participant randomized to this arm can choose to receive the treatment via an online treatment platform or via bibliotherapy, i.e., a self-help book.The treatment is comprised of 12 modules or chapters, which entail information about stress management techniques including behavioral activation and exposure. The participant that chooses online CBT is guided by a therapist who provides feedback on homework assignments through written asynchronous text messages; the patient who chooses bibliotherapy is guided by a therapist in typically 2 to 5 face-to-face sessions at a primary care clinic.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Perceived Stress Scale (PSS-10) | Change in PSS at post-treatment and follow-up compared to baseline (scale range 0-40, higher score means more symptoms) | Baseline, weeks 3, 6, 9, 12 (post-treatment), 1-year follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Shirom-Melamed Burnout Questionnaire (SMBQ) | Change in SMBQ at post-treatment and follow-up compared to baseline (scale range 1-7, higher score means more symptoms) | Baseline, weeks 3, 6, 9, 12 (post-treatment), 1-year follow-up | 
| Insomnia Severity Index (ISI) | Change in ISI at post-treatment and follow-up compared to baseline (scale range 0-28, higher score means more symptoms) | Baseline, weeks 3, 6, 9, 12 (post-treatment), 1-year follow-up | 
| Generalized Anxiety Disorder-7 (GAD-7) | Change in GAD-7 at post-treatment and follow-up compared to baseline (scale range 0-21, higher score means more symptoms) | Baseline, week 12 (post-treatment), 1-year follow-up | 
| Patient Health Questionnaire-9 (PHQ-9) | Change in PHQ-9 at post-treatment and follow-up compared to baseline (scale range 0-27, higher score means more symptoms) | Baseline, weeks 3, 6, 9, 12 (post-treatment), 1-year follow-up | 
| Brunnsviken Brief Quality of Life Index (BBQ) | Change in BBQ at post-treatment and follow-up compared to baseline (scale range 0-96, higher score means higher quality of life) | Baseline, week 12 (post-treatment), 1-year follow-up | 
| EuroQol 5D (EQ5D) | Change in EQ5D at post-treatment and follow-up compared to baseline (the answers will be converted to utility score of health states ranging from 0 to 1 where 0 represents death and 1 full health) | Baseline, week 12 (post-treatment), 1-year follow-up | 
| Trimbos and Institute of Medical Technology Assessment of Cost Questionnaire for Psychiatry (TIC-P) | The TIC-P enables estimation of costs by collecting information about participant resource utilization and costs related to production loss. Change in costs will be analyzed at post-treatment and follow-up compared to baseline. | Baseline, week 12 (post-treatment), 1-year follow-up | 
| Sick leave | Sick leave data from the Microdata for Analysis of Social Security (MiDAS) registry. Analyzed as full day equivalents. | 1 year from baseline |