Background
Burden and significance of co-morbid depression in patients with hypertension
Health system reforms to accommodate the rise in co-existing chronic conditions
Characteristic | PRIME (PRogramme for Improving Mental health carE-SA) trial | CobALT (Co-morbid Affective Disorders and Long-term Health) trial |
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Setting | Dr. Kenneth Kaunda District, North West Province, South Africa | Dr. Kenneth Kaunda and Bojanala Districts, North West Province, South Africa |
Clinic participants | 20 primary care clinics | 40 primary care clinics |
Patient participants | Patients 18 years or older attending for hypertension treatment with a Patient Health Questionnaire score of 9 or more (n = 1000, 50 per clinic) | Patients 18 years or older attending for antiretroviral therapy (ART) with a Patient Health Questionnaire score of 9 or more (n = 2000, 50 per clinic) |
Number and unit of randomisation | 20 primary care clinics | 40 primary care clinics |
Trial participants | Patients 18 years or older attending for hypertension treatment with a Patient Health Questionnaire score of 9 or more (n = 1000, 50 per clinic) | Patients 18 years or older attending for ART with a Patient Health Questionnaire score of 9 or more (n = 2000, 50 per clinic) |
Control arm | The Integrated Services Delivery Model which includes distribution and training in the PC101 guide | Same |
Intervention arm | Three additional elements: 1. Clinical communications skills training for nurse clinicians 2. Supplementary training in the mental health components of PC101 3. Clinic-based behaviour-change counsellors equipped to provide morning talks on mental health to promote mental health literacy, manualised counselling for depression (8 sessions, individual or group) and adherence counselling (individual) | Same |
Primary mental health outcome | Response at 6 months, defined as a 50% improvement from baseline in the Patient Health Questionnaire 9 score | Same |
Primary clinical health outcome | Not applicable | Viral load suppression at 12 months |
Duration of fieldwork | April 2015 to December 2016 | April 2015 to December 2017 |
Controlled Trials Registration Number | NCT02425124 | NCT02407691 |
Funding | UK Department for International Development | National Institutes of Mental Health, United States of America |
Objectives
Methods/design
Trial design
Setting
Interventions
Provider | Role | Training | Content of training | Method and timeframe |
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Control and intervention facilities | ||||
PHC nurses | Identifies, provides brief interventions and refers | Basic onsite PC101 training | Case scenarios used for training in the identification and management of common chronic diseases, including communicable diseases, NCDs (including hypertension), women’s health and mental health. Mental health components draw on the WHO’s mhGAP guidelines [67] and adopt a syndromic approach to mental health symptoms (such as stress, insomnia, suicidal thinking) with diagnostic algorithms and treatment checklists for depression | (1) PC101 master trainers train facility trainers who train PHC nurses at the facilities |
(2) 12 weekly sessions over 12 weeks at facilities (2 of which are on mental disorders) | ||||
(3) Training uses case-scenario material of patients with chronic conditions, including co-morbid conditions | ||||
Intervention facilities | ||||
PHC nurses | Identifies, provides brief interventions and refers | Orientation and clinical communication skills training | (1) Overview of the system changes being made by the DoH in South Africa to accommodate the demands of integrated chronic care; their role as case managers within the collaborative-care model for depression | 4 2-h interactive workshops at PHC facilities/regional training centre |
(2) Orientation to patient-centred care and clinical communication skills necessary to implement patient-centred care | ||||
(3) Skills to manage patient emotions within the consultation; self-care including how to cope with their own emotions and burn-out | ||||
(4) Motivational interviewing skills to promote patient self-management | ||||
PC101 supplementary training in mental health | (1) Detection of depression and anxiety, psychoeducation and referral to counsellors and/or physician for consideration of psychotropic medication in the case of moderate to severe depression | (1) PC101 master trainers train facility trainers (2-day workshop) who train PHC nurses at the facilities | ||
(2) Detection of risky alcohol use and brief intervention for harmful/hazardous drinking and for detoxification and referral to specialist rehabilitation programmes for dependency as per the mhGAP guidelines [68] | (2) 3 weekly sessions over 3 weeks at facilities, with an additional follow-up session 1 month later | |||
(3) Assessment of suicide intent | ||||
(4) Patient review after 8 weeks to assess response to treatment and onward referral for specialist care as indicated by the mhGAP evidence-based guidelines for LMICs [68] if necessary following a treatment-to-target approach as contained in the collaborative-care model (see Fig. 3). Treatment to target involves tracking a patient’s symptom severity and adjusting or intensifying treatment should patients not show an improvement in symptoms following initial treatment [69] | (3) Training uses case scenarios case scenario material of chronic patients with co-morbid mental disorders | |||
PHC physicians | Diagnoses, initiates and monitors response to psychotropic medication | Orientation and training in mhGAP/PC101 | (1) Orientation to the importance of treating co-morbid depression | 3 1-day workshops spread over 6 months |
(2) Training in mhGAP guidelines | ||||
(3) Follow-up using case studies of patients | ||||
Behavioural health counsellors | Provides evidence-based counselling | Counselling training | (1) Manualised counselling package comprising 8 sessions (delivered individually or in groups) | 1 week of off-site training; 1 week of peer-to-peer mentoring; in-vivo supervision by a psychologist of each session; weekly follow-up group supervisory sessions, augmented where possible by weekly individual supervision sessions |
(2) Session 1: psychoeducation session on depression; the last session is a closure session; sessions 2-7 draw on problem solving and cognitive behavioural techniques, including behavioural activation to address the common triggers of depression and anxiety which, in this population, include poverty, interpersonal conflict, social isolation and avoidance, grief and loss, and stigma that emerged from qualitative interviews held with service users with depression during the formative phase of the PRIME project in South Africa in 2 provinces [70]. A prototype had been field tested in KwaZulu-Natal and positive results demonstrated in an individually randomised pilot trial [42, 71]; adherence session provides information on the chronic condition/s and chronic medication/s the patients may have as well as helping patients with adherence difficulties | ||||
(3) While developed to treat depression, the intervention has been found to promote improvements in global psychological functioning as well [42, 71], thus having the potential for trans-diagnostic effects, in line with evidence that diagnosis-specific cognitive-behavioural therapy has beneficial effects on untargeted co-morbid emotional disorders [72] | ||||
Specialists (psychologist/psychiatrist) | Training, supervision of counsellors | Orientation to task sharing | Psychologists (including interns and community service psychologists) orientated to their roles | One-off workshops |
Clinic participants
Randomisation, blinding and allocation concealment
Patient participants
Over the last 2 weeks, how often have you been bothered by any of the following problems?a | Not at all | Several days | More than half of the days | Nearly every day |
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Over the last 2 weeks, how often have you been bothered by any of the following problems?b | 0 days | 1–7 days | 8–11 days | 12–14 days |
Little interest or pleasure in doing things | 0 | 1 | 2 | 3 |
Feeling down, depressed, or hopeless | 0 | 1 | 2 | 3 |
Trouble falling or staying asleep, or sleeping too much | 0 | 1 | 2 | 3 |
Feeling tired or having little energy | 0 | 1 | 2 | 3 |
Poor appetite or overeating | 0 | 1 | 2 | 3 |
Feeling bad about yourself – or that you are a failure or have let yourself or your family down | 0 | 1 | 2 | 3 |
Trouble concentrating on things, such as reading the newspaper or watching television | 0 | 1 | 2 | 3 |
Moving or speaking so slowly that other people could have noticed? Or the opposite - being so fidgety or restless that you have been moving around a lot more than usual | 0 | 1 | 2 | 3 |
Thoughts that you would be better off dead or of hurting yourself in some way | 0 | 1 | 2 | 3 |
Please could you confirm your answer for this question: Over the last 2 weeks, how often have you been bothered by thoughts that you would be better off dead or of hurting yourself in some way | 0 | 1 | 2 | 3 |
Total score ___ = ___ + ___ + ___ | ||||
If you checked off any problems, how difficult have these problems made it for you to do your work, take care of things at home, or get along with other people?a, b | Not difficult at all | Somewhat difficult | Very difficult | Extremely difficult |
Patient screening and recruitment
Data collection and outcome measures
Outcome | ||||||
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Baseline | 6 months | 12 months | ||||
Outcome | Measurement | Source | Metric | |||
Primary measurements | ||||||
Depression symptoms | PHQ-9 | Self-reported | 50% reduction in PHQ-9 score | ●a | ●●b | ● |
Secondary mental health outcomes | ||||||
Depression symptoms | PHQ-9 | Self- reported | 50% reduction in PHQ-9 score | ● | ● | ●● |
Depression symptoms | PHQ-9 | Self- reported | Remission defined as score of < 5 on PHQ-9 | ● | ● | ●● |
Depression symptoms | PHQ-9 | Self- reported | Mean PHQ-9 scores at 6 and 12 months | ● | ●● | ●● |
Antidepressant treatment | Self- reported | Proportion with antidepressant treatment initiated or intensified | ● | ● | ●● | |
Counselling | Self- reported | Proportion receiving counselling by clinic-based counsellor | ● | ● | ●● | |
Referral to specialist mental health worker/service | Self- reported | Proportion referred | ● | ● | ●● | |
Stress | Perceived Stress Scale | Self-reported | Mean score | ● | ●● | |
Secondary hypertensive outcomes | ||||||
Blood pressure | Interviewer measured | Difference in means | ● | ●● | ●● | |
Retention in care | Self-reported; clinic records | Proportion in care | ● | ●● | ||
Integrated care outcomes | ||||||
Cardiovascular risk factors | Blood pressure, weight, Body Mass Index, waist circumference | Interviewer measured | Difference in means | ● | ● | ●● |
Diagnosis of other co-morbid illnesses | Self-reported | Proportion diagnosed | ●● | |||
Quality of chronic illness care received | Patient Assessment of Care for Chronic Conditions (PACIC) | Self-reported | Mean PACIC score | ● | ●● | |
Health economic outcomes | ||||||
Health care utilisation | Self- reported; linkage with hospitalisation databases | Incidence rate ratio | ● | ●● | ||
Productivity and economic outcomes | Self- reported | ● | ●● | |||
Disability | WHO Disability Assessment Schedule 2.0 | Self- reported | Mean score | ● | ●● | |
Safety measurements | ||||||
Hospitalisation | Self- reported; linkage with hospitalisation databases | Proportion hospitalised | ● | ● | ●● | |
All-cause mortality | Clinic, report, linkage with mortality register | Proportion who died | ● | ● | ●● | |
Suicide | Follow-up of cause of all known deaths with clinic and family interview | Proportion of suicides | ● | ● | ●● |
Limitations
Data management
Sample size and power calculations
Statistical methods
Process evaluation
Ethical considerations
Monitoring of adverse events
Type of harm | Source and method of identification | Action(s) to mitigate harm to specific participants | Reporting frequency and to whom |
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Adverse events | |||
Positive response to ninth item of the PHQ-9: ‘Thoughts that you would be better off dead or of hurting yourself in some way’ | Participant interviews (baseline, 6 month follow-up, 12 month follow-up). Flag within electronic questionnaire prompting interviewer to act | Repeat question to reduce telescoping-type reporting errors. If ≥ 8 days in last 2 weeks, immediate referral to clinic staff. If between 1 and 7 days then written educational material given | 6-monthly report to DSMB 6-monthly to IRB (with DSMB letter of recommendation) |
PHQ-9 score of ≥ 20 at 12 months suggesting persistent severe depression | Participant interviews (12-month follow-up). Data report (monthly) | Summary forwarded to clinic together with recommendations for further treatment | 6-monthly report to DSMB 6-monthly to IRB (with DSMB letter of recommendation) |
Blood pressure severely raised (≥ 180/110) placing participant at immediate risk of cardiovascular event | Participant interviews (baseline, 6-month follow-up, 12-month follow-up). Flag within electronic questionnaire prompting interviewer to act | Immediate referral to clinic staff for review | 6-monthly report to DSMB 6-monthly to IRB (with DSMB letter of recommendation) |
Raised blood pressure at follow-up representing undiagnosed or uncontrolled hypertension | Participant interviews (baseline, 6-month follow-up, 12-month follow-up). Longitudinal patient record | Summary forwarded to clinic together with recommendations for further treatment | 6-monthly report to DSMB 6-monthly to IRB (with DSMB letter of recommendation) |
Serious adverse events | |||
Hospitalisation | Participant interviews (baseline, 6-month follow-up, 12-month follow-up). Routinely collected hospitalisation data. Data report (monthly). | No immediate action other than 6-monthly review by DSMB | 6-monthly report to DSMB 6-monthly to IRB (with DSMB letter of recommendation) |
Death (excluding suicide) | Participant interviews (Loss to Follow-up Form). National Population Register. Data report (monthly) | No immediate action other than 6-monthly review by DSMB | 6-monthly report to DSMB 6-monthly to IRB (with DSMB letter of recommendation) |
Death by suicide | Participant interviews (Loss to Follow-up Form). National Population Register (providing we are able to access cause of death). Data report (weekly) | Immediate notification of PI (LF) who will follow-up with fieldwork staff to confirm suicide and establish date of suicide | Notification of IRB, DSMB and NIMH within 7 days of knowledge of confirmed suicide |