Moving on After Breast Cancer Trial for Depressed Breast Cancer Survivors in Pakistan

Official title

Clinical and Cost-effectiveness of an Integrated Psychosocial Care Plan for Comorbid Depression in Breast Cancer Survivors In Pakistan: A Sequential Multiple Assignment Randomised Trial

Overview

Breast cancer is the most common cancer among women worldwide, and many survivors experience comorbid mental health conditions such as depression and anxiety, which can significantly worsen health outcomes and increase mortality. This large-scale trial in Pakistan aims to evaluate the clinical and cost-effectiveness of a three-stage adaptive intervention to manage depression among breast cancer survivors. Using a Sequential, Multiple Assignment, Randomised Trial (SMART) design, the study will recruit 26,372 participants aged 18 and above who have completed initial breast cancer treatment (surgery and/or chemotherapy or radiotherapy). Participants will be identified through primary care units, outpatient departments, oncology clinics in public hospitals, and charitable organisations across Pakistan. Depression will be screened using the Patient Health Questionnaire PHQ-9, with diagnosis confirmed by the Structured Clinical Interview Schedule of DSM (SCID). Those randomised to the intervention arm will receive adaptive interventions: starting with low-intensity guided self-help, followed by a high-intensity cognitive behavioural therapy-based programme called "Moving On After Breast Cancer Plus" (Moving on ABC Plus), and for non-responders, an additional pharmacological component will be introduced. Participants in both adaptive intervention and enhance usual care groups will be assessed at multiple time points-baseline, 6, 18, 30, and 48 weeks post-randomisation-using validated tools to measure depression (primary outcome), and anxiety, self-esteem, intrusive thoughts, health-related quality of life, satisfaction with services, and health resource use (secondary outcomes). The study will also include qualitative interviews and focus groups discussions with patients, caregivers, healthcare providers, and policymakers to identify barriers and facilitators to implementation and ensure the intervention is both contextually appropriate and scalable.

Detailed description

Problem statement: Breast cancer is the most prevalent cancer among women globally. The comorbidity of mental health conditions, such as depression and anxiety, significantly increases mortality rates in this population. Despite the complex rehabilitation needs of breast cancer survivors, there is limited knowledge on how to provide individualised support effectively.

Aims/Objectives: The overarching aim of this trial is to evaluate the clinical and cost-effectiveness of a three-stage adaptive intervention for co-morbid depression among breast cancer survivors in Pakistan.

Methods: This study will use a Sequential, Multiple Assignment, Randomised Trial (SMART) design to recruit 26,372 breast cancer survivors who have completed initial treatment (surgery and/or radiotherapy or chemotherapy). Participants, aged 18 years and older, will be recruited from primary care units, medical outpatient units, oncology clinics in public hospitals, and charitable organisations across Pakistan. Eligible participants will be screened for Major Depressive Episode (MDE) using the Patient Health Questionnaire (PHQ-9), with a score of 10 or above indicating potential depression. Diagnosis will be confirmed through the Structured Clinical Interview Schedule (SCID). Participants randomised to the intervention arm will receive a three-stage adaptive intervention, progressing through the following levels based on response: First adaptive intervention - Low-intensity guided self-help. Second adaptive intervention - High intensity "Moving On After Breast Cancer Plus" (Moving on ABC Plus), incorporating Cognitive Behavioural Therapy (CBT). Third adaptive intervention - Moving on ABC Plus combined with pharmacological intervention. All participants, regardless of randomisation, will be assessed at baseline, 6-, 18-, 30-, and 48-weeks post-randomisation using standardised questionnaires to measure: Primary outcome: Depression. Secondary outcomes: Anxiety, self-esteem, intrusive thoughts, health-related quality of life, satisfaction with services, and resource utilisation. Additionally, in-depth interviews and focus group discussions (FGDs) will be conducted with multiple stakeholders-including healthcare providers, policymakers, patients, and caregivers-to explore barriers and facilitators of intervention implementation.

Interventions

• Other Non-specialist delivered Low intensity guided self-help (Khushi and Khatoon)
  This is a manualised intervention comprising of 8 chapters. This is being further co-adapted to contexualise this for breast cancer survivours. The original manual is focused on stories of two breast cancer survivors , Mrs Khushi, means happiness) and Khatoon, means woman in Urdu, with depression and anxiety, describing how they help themselves using CBT strategies.
• Other Moving on After Breast Cancer (ABC) plus
  This is a high intensity manualised intervention consisting of 12 sessions (60-90 minutes). This manual offers practical support and advice on life after breast cancer, managing difficulties, mindfulness, addressing fatigue, understanding the participant's model of illness, improving personal effectiveness and social relationships. The sessions also include therapist delivered psychoeducation using a CBT model of case formulation and goal setting: identification and formulation of predisposing,
• Drug Standardised pharmacological treatment (antidepressants)
  Patients will begin 12 weeks of sertraline treatment initiated at a daily dose of 50 mg for the first 4 weeks. After that, flexible titation of sertraline will be permitted, by 50mg increment every 1 to 2 weeks, as clinically indicated and tolerated to a maximum daily dose of 200 mg
• Other Enhanced Treatment As Usual (E-TAU)
  Participants in this arm will continue to follow their routine visits to healthcare facilities. They will be regularly monitored by trained research team and will be assessed at weeks 6,18,30, and 48. In addition to psychological assessment at each follow-up, this will include information leaflets based on a brief psychoeducational module to educate participants and families about the risks, symptoms, management, and referral support information for anxiety and depression

Primary outcome measures

• Hamilton Rating Scale for Depression [Time frame: Change in total score from baseline to week 48]

Secondary outcome measures (7)

• Generalized Anxiety Disorder [Time frame: Change in Total Score from baseline to week 6, 18, 30 and 48]
• EuroQol-5 Dimensions [Time frame: Change in total score from baseline to week 6, 18, 30 ans 48]
• Functional Assessment of Cancer Therapy - Breast [Time frame: Change in total score from baseline to week 6, 18, 30 and 48]
• Rosenberg Self Esteem Scale [Time frame: Change in total score from baseline to week 6, 18, 30 and 48]
• Multidimensional Scale for Perceived Social Support [Time frame: Change in total score from baseline to week 6, 18, 30 and 48]
• Client Satisfaction Questionnaire [Time frame: Change in total score from baseline to week 6, 18, 30 and 48.]
• Client Service Receipt Inventory [Time frame: Change in score from baseline to week 6, 18, 30 and 48]

Eligibility criteria

Inclusion criteria

• Women
• Aged 18 years and above
• Diagnosed with breast cancer (any stage)
• Completed initial treatment (i.e., surgery and/or radiotherapy or chemotherapy) for breast cancer (even if they are currently on hormonal therapy post-initial treatment)
• Total score of 10 or above on the Patient Health Questionnaire (PHQ-9)
• Diagnosis of current Major Depressive Episode (MDE) confirmed using the Structured Clinical Interview for DSM-5 (SCID).

Exclusion criteria

• Lacking capacity to provide informed consent, such as those identified by clinicians as having intellectual disabilities, dementia, or severe medical and/or psychiatric illnesses requiring hospitalisation
• Unable to engage in assessments or interventions, including those with stage 4 breast cancer experiencing significant symptoms (e.g., metastatic lesions in the lungs, liver, or bones requiring daily treatment for symptomatic relief, such as the daily use of two or more painkillers), which restrict their capacity to participate
• Currently receiving psychological therapy or taking antidepressant medications (e.g., SSRIs, SNRIs, or other prescribed antidepressants)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Pakistan · 1 center

• Pakistan Institute of Living and Learning — Karachi

Identifiers

NCT: NCT07015944 · Moving On ABC Plus · NIHR205561

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗