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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
26,376
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.
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, precipitating, perpetuating and protective factors of depression and/or anxiety, helping participants to identify core beliefs, where necessary, using downward arrow technique, identifying, and challenging unhealthy thinking patterns at the level of core beliefs using cognitive restructuring, and problem-solving techniques
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
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
Pakistan Institute of Living and Learning
Karachi, Sindh, Pakistan
RECRUITINGHamilton Rating Scale for Depression
Primary outcome will be depression remission at 48 weeks. This is a 17 item, clinician administered assessment measure to assess severity of depressive symptoms over past week. Total score of 0-7 is considered as "normal" (clinical remission), and a total score of 20 or higher is considered as moderate to severe.
Time frame: Change in total score from baseline to week 48
Generalized Anxiety Disorder
Severity of anxiety over last two weeks will be assessed using the Generalized Anxiety Disorder - 7 . Individuals with total score between 0 to 4 will be categories as having "minimal anxiety", 5 to 9 "mild anxiety", 10 to 14 "moderate anxiety" and 15 to 21 "severe anxiety".
Time frame: Change in Total Score from baseline to week 6, 18, 30 and 48
EuroQol-5 Dimensions
Health-related quality of life will be assessed using the EQ-5D. This questionnaire assesses quality of life by exploring 5 areas: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension is rated as one of the followings: no problems, slight problems, moderate problems, severe problems and extreme problems. Higher score indicate better quality of life. The range for EQ-5D scores is between -0.594 and 1, where 1 signifies full health. Scores below 0 indicate health states worse than death.
Time frame: Change in total score from baseline to week 6, 18, 30 ans 48
Functional Assessment of Cancer Therapy - Breast
This scale measures health-related quality of life in breast cancer patients in five domains: physical, social, emotional, functional well-being as well as a breast-cancer sub-scale Higher score indicate better quality of life. Minimum possible score on this scale is 0 and maximum possible score is 144.
Time frame: Change in total score from baseline to week 6, 18, 30 and 48
Rosenberg Self Esteem Scale
Self-esteem will be assessed using this scale. Total score on the scale ranges from 0-30. Total score between 15 to 25 is considered as within normal range and total score below 15 is indicative of low self-esteem
Time frame: Change in total score from baseline to week 6, 18, 30 and 48
Multidimensional Scale for Perceived Social Support
This scale aims to assess an individual's perception of support from 3 sources: family, friends and a significant other. Total score between 12 to 35 is categorised as "low perceived support", 36 to 60 "medium perceived support", and 61 to 84 "high perceived support".
Time frame: Change in total score from baseline to week 6, 18, 30 and 48
Client Satisfaction Questionnaire
Satisfaction with treatment/services will be assessed using this scale. Total scores range from 8 to 32, with the higher number indicating greater satisfaction.
Time frame: Change in total score from baseline to week 6, 18, 30 and 48.
Client Service Receipt Inventory
Information on participants' use of both formal and informal (such as Imams/faith healers) health services was collected at baseline and follow-up assessments using a structured form.
Time frame: Change in score from baseline to week 6, 18, 30 and 48
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