A Youth Culturally Adapted Manual Assisted Psychological Therapy (Y-CMAP) for Adolescent Pakistani Patients with a Recent History of Self-Harm.

Suicide is a serious global public health issue ranked amongst the leading causes of death in many countries. The worldwide rates of suicide have increased by 60% in the last 45 years. The 1.8% total global burden of disease attributed to suicide in 1998 is expected to increase to 2.4% by 2020. The WHO Mental Health Action Plan 2013-2020 and all the member states have committed to work towards the global target of a 10% reduction in the suicide rate by 2020. WHO's Mental Health Gap Action Programme includes suicide as one of the priority conditions and the recent WHO report "Preventing suicide: a global imperative" calls for suicide prevention to be a high priority on the global public health agenda. More than 800,000 people across the world die due to suicide each year and for each suicide there are more than 20 people attempting suicide. Self-harm is one of the strongest predictors of death by suicide in adolescence, increasing the risk approximately 10-fold. Each suicide takes the life of the individual and has a tremendous effect on friends, family and the wider community. Up to 75% of all suicides occur in in low- and middle-income countries (LMIC) where resources and services are limited for treatment and support. There is a clear gap in the robust evaluation of culturally appropriate suicide prevention strategies in LMIC. Individuals who have a history of self-harm are at much higher risk of dying by suicide than individuals who do not have such a history. The WHO recommends offering appropriate treatment as a key component of all suicide prevention strategies.
There are more than 100,000 acts of self-harm in Pakistan annually. The aim of Y-CMAP is to evaluate the clinical and cost-effectiveness of this culturally adapted psychological therapy in adolescent patients with a history of self-harm. Our study in Karachi determined the effectiveness of a 6-8 session CBT-based intervention (C MAP) in adults who had recently self-harmed. The assessments were carried out at baseline, 3 & 6 months. There was a significant reduction from baseline in suicidal ideation and hopelessness in the intervention group compared to the Treatment as Usual (TAU) group at each follow up assessment. The findings from C MAP highlight the applicability of such an intervention to health services in Pakistan for patients who present after a self-harm episode. The proposed research will be conducted in Karachi, Lahore, Rawalpindi, Multan and Hyderabad. Participants will be randomized either to the Intervention (Y-CMAP) or TAU. The existing age appropriate culturally adapted intervention (Y-CMAP) for young people includes an evaluation of the self-harm episode, crisis skills, problem solving and basic cognitive techniques to manage emotions, negative thinking and relapse prevention strategies. The intervention will be delivered in eight sessions over 12 weeks. Assessments will be conducted at baseline and at 3 months (end of intervention), 6 months and 12 months after randomization. The outcome measures will include questionnaires to measure the repetition of self-harm, severity of suicidal ideation; depression; hopelessness; and quality of life. In addition, qualitative interviews and focus groups will provide rich information regarding the experiences of participants, therapists and key stakeholders. This will inform implementation as well as the development of more effective and sensitive services for self-harm management. TAU will be standard routine care delivered by local medical, psychiatric and primary care services according to clinical judgment. A record will be kept of any treatment received by each participant. This trial will inform future research and national clinical practice guidelines. We have established contacts with the ministry of health and will enter discussions to present the results to them and attempt to influence policy change.

Technical Summary
Design: A multi-centre single blind RCT with randomisation by individual patients to compare the Y-CMAP in addition to TAU with TAU alone. There is a built in 12-month internal pilot phase with clear stop/go criteria to prove viability to proceed to a full trial across all the study sites. The pilot phase will be judged successful if sufficient GPs, schools and hospitals are recruited to enrol 200 participants in the first 12 months. Assessments will be conducted for both the groups at baseline, 3 (end of intervention),6,9 and 12 months after randomisation
Setting: Participants will be recruited from general practices, emergency departments, medical wards of participating hospitals and self-referrals.
Intervention: Y-CMAP is based on the principles of Problem Solving and CBT.
Sample size: This is based on the primary outcome, repetition of self-harm in 12-month period (yes/no). The TAU arm of the study has an expected self-harm rate of 20% and a clinically important effect would be a reduction to 7.5% in the intervention group. Under these assumptions, and assuming a 5% significance level and 90% power, a study with no clustering would require 158 patients per arm. The study has a partially nested design due to therapist clustering in the Y-CMAP arm. Based on previous analysis of therapist trials we believe that the ICC is likely to have a value between 0.01 and 0.05 for this type of outcome measure. Assuming an ICC of 0.05, and a cluster size of 16 patients per therapist, a Design Effect of 1.75 is calculated This increases the numbers required to 277 per group. Furthermore, there is expected to be a 15% loss to follow-up, and so the final numbers recruited will be 326 per group, 652 in total.
Primary outcome measure: Repetition rate of self-harm at 12 months after randomisation as measured by the adapted Suicide Attempt Self-Injury Interview (SASII). Client Service Receipt Inventory (CSRI): We will collect information on the use of health and other services.

Planned Impact
Impact on service users: The overall objective of the trial is to bring about a reduction of self-harm, overall morbidity, a reduction in rates of suicide and a better quality of life. In low income countries there is a huge treatment gap and up to 9 out of 10 people with mental health difficulties do not receive appropriate treatment. Outcomes from our earlier studies provide a strong foundation to build on and aid the translation of research into action. There can be other wide ranging positive outcomes, including increased awareness, improvements in relationships and academic performance. It is suggested that therapies which enhance self-efficacy such as Cognitive Behavioural

Therapy (CBT) may reduce relapse and recurrence rates of many mental disorders including depression and anxiety.
Community awareness: The participants understanding of mental health issues will improve. We have experience of promoting our research within the Pakistani community including presentations or seminars with community leaders, local Pakistani media (newspapers, TV & radio), and promotional material in GP surgeries. The importance of addressing mental health difficulties promoted through general public awareness will guide people to seek early clinical help for their mental health problems.

Service users as co-researchers: We organise an annual course on the fundamentals of qualitative research methods at the Pakistan Institute of Living and Learning, and service users are invited to attend. Service users on the advisory board were trained in research methods and will contribute to the qualitative analysis in the proposed trial. Our team has significant expertise in this area and we have trained over 70 users and carers in research methods. Service users provide helpful additional insights into the themes emerging from the data and contribute greatly to the interpretation of findings. We will continue to offer this training to service users and carers.
Impact on services: There is limited data available to guide treatment choices for clinicians in Pakistan. The outcome of this trial will have implications for health services, in terms of helping to improve the organization of care and interventions offered for patients who self-harm and thus improve the quality of health services with potential reduction in overall costs. One of the outputs of this study will be a portfolio of user-defined, evidence-based, manual assisted intervention; a resource pack and training programme on 'how to do it' for use across local health services. This trial will provide detailed clinical and cost-effectiveness analyses which will inform future research and national clinical practice guidelines. Together these data will be useful to inform planning of effective and culturally appropriate interventions in Pakistan.

Research and clinical capacity: There is limited research capacity in Pakistan if funded we will be able to train research assistants in robust research methods. There will be workshops on fundamentals of quantitative and qualitative research methods, which will be open for aspiring academics from outside the research team. We have developed the curriculum and trained more than 500 clinicians in Tier-1 psychosocial interventions for mental illness. We have initiated discussions with the nursing schools and departments of psychology that if the results show that Y-CMAP is effective it should be included in the curriculum.

Impact on policy: Research from the Global Mental Health Group have recommended that scaling up services for people with mental disorders is the most important priority for global mental health. We have contacts with the ministry of health (See letter of support) and once the trial is completed we will enter discussions to present the results to them to take this work towards implementation.