Cost of digital technologies and family-observed DOT for a shorter MDR-TB regimen: a modelling study in Ethiopia, India and Uganda.

BACKGROUND: In 2017, the WHO recommended the use of digital technologies, such as medication monitors and video observed treatment (VOT), for directly observed treatment (DOT) of drug-susceptible TB. The WHO's 2020 guidelines extended these recommendations to multidrug-resistant tuberculosis (MDR-TB), based on low evidence. The impact of COVID on health systems and patients underscored the need to use digital technologies in the management of MDR-TB. METHODS: A decision-tree model was developed to explore the costs of several potential DOT alternatives: VOT, 99DOTS (Directly-observed Treatment, Short-course) and family-observed DOT. Assuming a 9-month, all-oral regimen (as evaluated within the STREAM trial), we constructed base-case cost models for the standard-of-care DOTs in Ethiopia, India, and Uganda, as well as for the three alternative DOT approaches. The models were populated with STREAM Stage 2 clinical trial outcome and cost data, supplemented with market prices data for the digital DOT strategies. Sensitivity analyses were conducted on key parameters. RESULTS: Modelling suggested that the standard-of-care DOT approach is the most expensive DOT strategy from a societal perspective in all three countries evaluated (Ethiopia, India, Uganda), with considerable direct- and indirect-costs incurred by patients. The second most expensive DOT approach is VOT, with high health-system costs, largely caused by up-front technology expenditure. Each of VOT, 99DOTS and family-observed DOT would reduce by more than 90% patients' direct and indirect costs compared to standard of care DOT. Results were robust to the sensitivity analyses. CONCLUSIONS: While data on the costs and efficacy of alternative DOT approaches in the context of shorter MDR-TB treatment is limited, our modelling suggests alternative DOT approaches can significantly reduce patient costs in all three countries. Health system costs are higher for VOT and lower for 99DOTS and family-observed therapy when compared to standard of care DOT, as low smartphone penetration and internet availability requires the VOT health system to fund the cost of making them available to patients.

Economic evaluation protocol of a short, all-oral bedaquiline-containing regimen for the treatment of rifampicin-resistant tuberculosis from the STREAM trial.

INTRODUCTION: A December 2019 WHO rapid communication recommended the use of 9-month all-oral regimens for treating multidrug-resistant tuberculosis (MDR-TB). Besides the clinical benefits, they are thought to be less costly than the injectable-containing regimens, for both the patient and the health system. STREAM is the first randomised controlled trial with an economical evaluation to compare all-oral and injectable-containing 9-11-month MDR-TB treatment regimens. METHODS AND ANALYSIS: Health system costs of delivering a 9-month injectable-containing regimen and a 9-month all-oral bedaquiline-containing regimen will be collected in Ethiopia, India, Moldova and Uganda, using 'bottom-up' and 'top-down' costing approaches. Patient costs will be collected using questionnaires that have been developed based on the STOP-TB questionnaire. The primary objective of the study is to estimate the cost utility of the two regimens, from a health system perspective. Secondary objectives include estimating the cost utility from a societal perspective as well as evaluating the cost-effectiveness of the regimens, using both health system and societal perspectives. The effect measure for the cost-utility analysis will be the quality-adjusted life years (QALY), while the effect measure for the cost-effectiveness analysis will be the efficacy outcome from the clinical trial. ETHICS AND DISSEMINATION: The study has been evaluated and approved by the Ethics Advisory Group of the International Union Against Tuberculosis and Lung Disease and also approved by ethics committees in all participating countries. All participants have provided written informed consent. The results of the economic evaluation will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ISRCTN18148631.

Study protocol for a single-centre observational study of household wellbeing and poverty status following a diagnosis of advanced cancer in Blantyre, Malawi - 'Safeguarding the Family' study.

Background: Many households in low-and-middle income countries face the additional burden of crippling out-of-pocket expenditure when faced with a diagnosis of life-limiting illness. Available evidence suggests that receipt of palliative care supports cost-savings for cancer-affected households. This study will explore the relationship between receipt of palliative care, total household out-of-pocket expenditure on health and wellbeing following a first-time diagnosis of advanced cancer at Queen Elizabeth Central Hospital in Blantyre, Malawi. Protocol: Patients and their primary family caregivers will be recruited at the time of cancer diagnosis.  Data on healthcare utilisation, related costs, coping strategies and wellbeing will be gathered using new and existing questionnaires (the Patient-and-Carer Cancer Cost Survey, EQ-5D-3L and the Integrated Palliative Care Outcome Score). Surveys will be repeated at one, three and six months after diagnosis. In the event of the patient's death, a brief five-item questionnaire on funeral costs will be administered to caregivers not less than two weeks following the date of death. Descriptive and Poisson regression analyses will assess the relationship between exposure to palliative care and total household expenditure from baseline to six months. A sample size of 138 households has been calculated in order to detect a medium effect (as determined by Cohen's f 2=0.15) of receipt of palliative care in a regression model for change in total household out-of-pocket expenditure as a proportion of annual household income. Ethics and dissemination: The study has received ethical approval. Results will be reported using STROBE guidelines and disseminated through scientific meetings, open access publications and a national stakeholder meeting.  Conclusions: This study will provide data on expenditure for healthcare by households affected by advanced cancer in Malawi. We also explore whether receipt of palliative care is associated with a reduction in out-of-pocket expenditure at household level.

Delivery of long-term-injectable agents for TB by lay carers: pragmatic randomised trial.

BACKGROUND: People with recurrent or drug-resistant TB require long courses of intramuscular injections. We evaluate a novel system in which patient-nominated lay carers were trained to deliver intramuscular injections to patients in their own homes. METHODS: A pragmatic, individually randomised non-inferiority trial was conducted at two hospitals in Malawi. Adults starting TB retreatment were recruited. Patients randomised to the intervention received home-based care from patient-nominated lay people trained to deliver intramuscular streptomycin. Patients receiving standard care were admitted to hospital for 2 months of streptomycin. The primary outcome was successful treatment (alive and on treatment) at the end of the intervention. RESULTS: Of 456 patients screened, 204 participants were randomised. The trial was terminated early due to futility. At the end of the intervention, 97/101 (96.0%) in the hospital arm were still alive and on treatment compared with 96/103 (93.2%) in the home-based arm (risk difference -0.03 (95% CI -0.09 to 0.03); p value 0.538). There were no differences in the proportion completing 8 months of anti-TB treatment; or the proportion experiencing 2-month sputum culture conversion. The mean cost of hospital-based management was US$1546.3 per person, compared to US$729.2 for home-based management. Home-based care reduced risk of catastrophic household costs by 84%. CONCLUSIONS: Although this trial failed to meet target recruitment, the available data demonstrate that training patient-nominated lay people has potential to provide a feasible solution to the operational challenges associated with delivering long-term-injectable drugs to people with recurrent or drug-resistant TB in resource-limited settings, and substantially reduce costs. Further data under operational conditions are required. TRIAL REGISTRATION NUMBER: ISRCTN05815615.

The Malawi National Tuberculosis Programme: an equity analysis.

BACKGROUND: Until 2005, the Malawi National Tuberculosis Control Programme had been implemented as a vertical programme. Working within the Sector Wide Approach (SWAp) provides a new environment and new opportunities for monitoring the equity performance of the programme. This paper synthesizes what is known on equity and TB in Malawi and highlights areas for further action and advocacy. METHODS: A synthesis of a wide range of published and unpublished reports and studies using a variety of methodological approaches was undertaken and complemented by additional analysis of routine data on access to TB services. The analysis and recommendations were developed, through consultation with key stakeholders in Malawi and a review of the international literature. RESULTS: The lack of a prevalence survey severely limits the epidemiological knowledge base on TB and vulnerability. TB cases have increased rapidly from 5,334 in 1985 to 28,000 in 2006. This increase has been attributed to HIV/AIDS; 77% of TB patients are HIV positive. The age/gender breakdown of TB notification cases mirrors the HIV epidemic with higher rates amongst younger women and older men. The WHO estimates that only 48% of TB cases are detected in Malawi. The complexity of TB diagnosis requires repeated visits, long queues, and delays in sending results. This reduces poor women and men's ability to access and adhere to services. The costs of seeking TB care are high for poor women and men - up to 240% of monthly income as compared to 126% of monthly income for the non-poor. The TB Control Programme has attempted to increase access to TB services for vulnerable groups through community outreach activities, decentralising DOT and linking with HIV services. CONCLUSION: The Programme of Work which is being delivered through the SWAp is a good opportunity to enhance equity and pro-poor health services. The major challenge is to increase case detection, especially amongst the poor, where we assume most 'missing cases' are to be found. In addition, the Programme needs a prevalence survey which will enable thorough equity monitoring and the development of responsive interventions to promote service access amongst 'missing' women, men, boys and girls.