Title: The CONTROL (COgNitive Therapy for depRessiOn in tubercuLosis treatment) programme of research to improve outcomes for depression and TB in Pakistan and Afghanistan.
Funder: Department of Health and Social Care

Abstract: Introduction: Tuberculosis (TB) is the 10th leading cause of death globally. Common mental disorders, such as depression, are significant multimorbidities with TB in most Low and Middle Income Countries (LMIC). Pakistan is ranked fifth among TB high-burden countries. Afghanistan has an even worse TB situation due to ongoing conflict. About half of people with TB also have comorbid depression. TB and depression is a typical multimorbidity in which each disease increases the risk of poorer outcomes for the other. Importantly, depression in TB increases risk of poor treatment adherence with anti TB treatment (ATT) that can lead to Multidrug resistant TB (MDRTB) which is considered as health security risk. No effective interventions are available to treat depression in people with TB. We aim to develop and test a psychosocial intervention for treating depression in TB and improving adherence with antidepressants treatment (ATT). Research Plan: We will develop CONTROL (COgNitive Therapy for depRessiOn in tubercuLosis treatment), a complex intervention consisting of 4 key elements (i) screening for depression in TB patients using the Patient Health Questionnaire&ndash;2 (ii) a brief psychological intervention based on cognitive therapy principles consisting of six sessions (iii) intervention delivery using a cascade model of training to train TB health workers to provide therapy (iv) Integration of mental health outcomes in TB control programme. The research programme will be based in Pakistan and Afghanistan to develop and evaluate the CONTROL intervention and identify early implementation outcomes. The research programme will consist of four WPs:- Developing intervention using evidence synthesis, ethnographic and qualitative methods incorporating patients perspective Inbuilt pilot RCT to test and refine intervention with a clear progression criterion to the definitive trial. The definitive trial will test CONTROL versus Enhanced Treatment as Usual. The evaluation of intervention will consist of a combination of quantitative and qualitative methods, including a pragmatic RCT following a hybrid type-1 implementation approach. The primary effectiveness outcomes will include depressive symptoms and adherence with ATT. Implementation outcomes include cost and cost-effectiveness, adoption, feasibility and acceptability of the CONTROL to all stakeholders, intervention fidelity and barriers and facilitators of implementation assessed through process evaluation. A sample size of 560 (280 each arm) will have adequate power to test two primary outcomes (a) improvement in depression (b) adherence to ATT. Developing a strategy and plan for the scale up using theory of behaviour change approach. Capacity building, involving stakeholders, patients and public are integrated in all WPs. The research programme is geared towards implementation and scale up of the intervention in routine TB care which will help to overcome the stigma associated with TB and depression. Expected outcomes: A successful CONTROL programme will uniquely address two major problems in TB control worldwide; depression and poor treatment adherence with ATT. This will potentially have enormous public health impact by reducing TB deaths, reducing infection spread and decreasing the risk of MDRTB. With its implementation approach the programme will also enhance capacity for implementation research in LMIC.

Lay abstract: Tuberculosis (TB) is the 10th leading cause of death in the world. Pakistan ranks fifth and fourth in the world for having a high-burden of TB and Multi Drug Resistant Tuberculosis (MDR-TB) respectively. Afghanistan has an even worse TB situation due to ongoing conflict. There are over a million Afghan refugees in Pakistan. It is estimated that almost 49% of people receiving TB treatment may also have depression. Depression may be caused as a result of TB related stigma or the side effects of TB treatments. When these conditions co-exist they may raise the risk of TB reactivation, contribute to poor adherence to TB treatments and disease progression. Poor treatment adherence results in drug resistant TB (MDR-TB) which is considered to be a public health crisis and health security threat. Through 4 linked work packages we aim to develop, test and implement a brief intervention to improve the mental health in people who have TB and MDR-TB and test whether the CONTROL (COgNitive Therapy for depRessiOn in tubercuLosis treatment) intervention is effective in improving adherence to TB treatments: &middot; WP1 - We will collate current research and work with patients, carers, healthcare workers, traditional and religious healers (who play an important role in routine TB care) to develop the CONTROL intervention, which is based on principles of Cognitive Behavioural Therapy (CBT). The CBT is a therapy approach that aims to improve thinking processes that may underlie anxiety or depression and is recommended in guidelines for treatment of depression. Findings from these activities will contribute to developing the intervention and will be presented at a 3-day workshop. &middot; WP 2 - Pilot trial will be carried out to test the trial procedures at two locations in Pakistan. These locations will include the Afghan refugee population, who are residing in Pakistan. We will talk to key stakeholders about their views on the intervention sessions and the training for staff. We will assess how effective the pilot trial is, after which we will go onto the randomised control trial. &middot; WP3 - A randomised controlled trial to test if the CONTROL intervention is successful in improving the outcomes both for depression and TB and also whether the CONTROL intervention is cost effective. &middot; WP4 - A process evaluation to understand the challenges and scale-up in TB control programmes. We will interview patients, staff and policy makers to explore acceptability and experiences. We will also see how the CONTROL intervention, if successful, could be modified for other chronic infections such as Hepatitis C. Our lay-expert will co-develop key study components and provide representation on programme steering groups. Our findings will be published in journals, conferences, on a study specific website and through social media (Facebook and Twitter). We will share directly, our findings and training materials with international TB control programmes worldwide.

Research activity codes: 5.6 PSYCHOLOGICAL AND BEHAVIOURAL;6.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: MENTAL HEALTH;INFECTION