Addressing the Social Determinants and Consequences of Tuberculosis (ASCOT): a pilot randomised controlled trial and process evaluation in Nepal

BACKGROUND. Tuberculosis (TB) kills more people than any infection. Poorer people in low income countries (LICs) are disproportionately affected by TB. Once ill, people with TB face severe psychological, social, and economic (socioeconomic) challenges, including mental illness, discrimination, income loss, and catastrophic costs of accessing TB care. These challenges reduce patients' chances of cure, push households deeper into poverty, and impede global TB control efforts. To combat this, the World Health Organization (WHO) advocates socioeconomic support for TB-affected households.

RELATED WORK. In Peru, a middle-income country, members of our team previously showed that socioeconomic support for TB-affected households increases TB cure rates and reduces catastrophic costs. However, no related evidence exists in LICs with significant TB burden, like Nepal. Over the past two years funded by a Wellcome Trust Seed Award, our team worked with communities, people with TB, and the National TB Program (NTP) of Nepal to address this knowledge gap. We identified barriers to accessing TB services in Nepal including low TB knowledge, perceived stigma, isolation, and high travel costs to receive care. We then suggested feasible and locally-appropriate socioeconomic support packages to overcome these barriers, including cash transfers and peer support. We are ready to field-test these packages and select the most promising for large-scale trial evaluation.

OBJECTIVES
1. Field-test socioeconomic support packages for TB-affected households to identify which is most feasible and acceptable in Nepal;
2. Inform design and delivery of a definitive, large-scale trial to evaluate the impact of the selected support package on health, finances, and stigma of TB-affected households in Nepal; and
3. Consolidate partnerships with communities, the Nepal NTP, and WHO, to ensure the future trial is achievable, act as a model for other LICs, and informs TB policy and practice.

SETTING. Four districts of Nepal with high TB and poverty: Chitwan, Mahottari, Morang, and Pyuthan.

DESIGN. A randomised-controlled pilot trial of socioeconomic support packages for TB-affected households.

POPULATION. 100 people with TB diagnosed in NTP clinics in the study sites (25 consecutively diagnosed participants per site).

INTERVENTIONS. Computer software will randomly allocate participants to receive:

i) Control standard of care with no additional socioeconomic support;
ii) Social support through home-based peer-led mutual support groups to reduce stigma;
iii) Economic support with monthly cash transfers to mitigate costs and enable treatment adherence ; or
iv) Socioeconomic support integrating social and economic support.

Interventions will be delivered by Birat Nepal Medical Trust (BNMT), a well-established, Nepalese non-governmental organisation. Interventions will be flexible to refine size or frequency of cash or support groups where needed.

STUDY ACTIVITIES. Participants will be surveyed on TB knowledge, stigma, mental health, quality of life, poverty level, costs of TB, and satisfaction with interventions received. Focus groups and interviews with selected participants, project and BNMT team members, and NTP staff will be combined with project costs data to evaluate the feasibility of the interventions.

PRIMARY OUTCOME. To evaluate the feasibility and acceptability of the interventions in order to select the most promising intervention for large-scale trial evaluation.

SECONDARY OUTCOMES. To explore the impact of interventions on TB cure and catastrophic costs of TB-affected households.
Benefits and applications. This research will ensure the most fundable, achievable, and impactful design of a definitive, large-scale trial of socioeconomic support for TB-affected households in Nepal, the findings of which will be the first of their kind in a LIC and will inform regional and international TB policy and practice.

BACKGROUND. Poverty drives TB rates and TB worsens poverty due to catastrophic costs of being ill and seeking care. WHO mandates ending catastrophic costs and providing social and economic (socioeconomic) support to people with TB. This has not been evaluated in low-income countries. With key stakeholders in Nepal, we designed locally-appropriate socioeconomic support packages for TB-affected households, which are ready to be tested.

OBJECTIVES
1. Identify the most feasible and acceptable support package
2. Inform definitive trial design
3. Optimise future chances of funding and trial success

METHODS

DESIGN. An adaptive randomised-controlled pilot trial and process evaluation

POPULATION. 100 people with TB registered at National TB Program (NTP) clinics in Chitwan, Mahottari, Morang, and Pyuthan districts of Nepal

INTERVENTIONS. Tablet-based software will randomly allocate participants equally to:
i) Standard of care (e.g. control)
ii) Social Support through home-based peer-led mutual support groups to reduce stigma
iii) Economic Support with monthly cash transfers to mitigate costs and meet NTP goals
iv) Socioeconomic Support integrating economic and social support

Interventions will be adaptive and delivered by the Nepal NGO, BNMT

ACTIVITIES. Poverty and TB costs will be measured by survey. TB treatment outcomes will be extracted from NTP registers. MRC process evaluation techniques will evaluate feasibility and acceptability by qualitative focus groups and interviews with participants and project staff to examine perceptions of the interventions; and quantitative data on intervention uptake, fidelity, and costs.

PRIMARY OUTCOME. Feasibility and acceptability of support packages

EXPLORATORY OUTCOMES. Impact of support on TB cure and catastrophic costs

APPLICATIONS. This work will ensure fundable, achievable, and impactful design of the first definitive trial of socioeconomic support for TB-affected households in Nepal.

This Impact Summary gives an overview of the key pathways to and beneficiaries of impact. For clarity, the Impact Summary is divided by specific Pathways to Impact.

i) RESEARCH METHODS AND FINDINGS.
The adaptive trial design and rigorous process evaluation in this proposal are innovative and a world-first in this particular research field and low-income setting. To maximise impact, we will publish the research protocol on an open-access platform and write perspectives pieces on the process evaluation outcomes with a focus on barriers to implementation. We will also produce a practical manual on implementing socioeconomic interventions in LMICs. The health and other outcomes of the definitive trial and the resultant publications in high-impact journals will be ground-breaking (e.g. the first robust evidence from LICs in this field) and vital for other researchers.
BENEFICIARIES: research groups working in the same field in other LMICs; mixed-methods researchers and triallists; and intervention implementation teams.

ii) POLICY.
We involve national (NTP and Nepal government) and international (WHO) policy- and decision-makers throughout all stages of our research. We have worked with these collaborators to include catastrophic costs mitigation and socioeconomic support in the current National Strategic Plan 2020-2025. We have also forged collaborations with the Nepal Ministry for Health and Population including those working on social protection programs. We will continue to involve these colleagues and provide them with policy briefs detailing our ongoing research and findings. The PI and Co-I (Lonnroth) continue to work with WHO's Task Force for Catastrophic Costs of TB and will contribute to annual meetings and updates of the TB Patient Costs Survey Handbook 2017 (https://www.who.int/tb/publications/patient_cost_surveys/en/). They also co-lead the international Social Protection Action Research and Knowledge Sharing (SPARKS) network. SPARKS includes many policy makers from within and without the TB sphere (e.g. UNAIDS, UNICEF). This is a superb platform by which to influence policy through presentations at annual meetings, SPARKS mailing list, and depositing our papers in the SPARKS open-access depository.
BENEFICIARIES: Nepal NTP and government decision makers; WHO; SPARKS; multi-sectoral policy makers in poverty alleviation and social protection.

iii) RESEARCH INFRASTRUCTURE AND CAPACITY BUILDING.
A key theme within our four years of collaboration as a team has been to devise and execute a multi-stage collaborative plan to increase research infrastructure and capacity build in Nepal. At BNMT, this has been evidenced by comprehensive additional training for BNMT staff in in research methods and good research practice. Multiple BNMT team members have since published first author papers, won travel scholarships to international conferences, and registered for PhDs. Strengthening capacity at BNMT and collaboration with the NTP will be vital for the future, definitive trial and translation of our research into policy change in Nepal.
BENEFICIARIES: multi-disciplinary team BNMT members and NTP staff.

iv) ADVOCACY AND AWARENESS.
Our involvement of people with TB from study site communities in this work since its inception has driven the community-led design of potential socioeconomic support packages. We hope to formalise this collective of TB-affected people by registering an autonomous TB Civil Society group in Nepal. The PI and Sponsor Prof Squire of LSTM are part of the UK Academics and Professionals Against TB (www.ukaptb.org) UK network, which interacts with advocacy groups like TB Alert and Results UK and lobbies UK government. We continue to make in-roads into supporting other countries to form similar bodies.
BENEFICIARIES: TB Civil Society in Nepal/UK, TB Advocacy groups including UKAPTB and Results UK, and the general public.