Economic evaluation of short treatment for multidrug-resistant tuberculosis, Ethiopia and South Africa: the STREAM trial.

OBJECTIVE: To investigate cost changes for health systems and participants, resulting from switching to short treatment regimens for multidrug-resistant (MDR) tuberculosis. METHODS: We compared the costs to health systems and participants of long (20 to 22 months) and short (9 to 11 months) MDR tuberculosis regimens in Ethiopia and South Africa. Cost data were collected from participants in the STREAM phase-III randomized controlled trial and we estimated health-system costs using bottom-up and top-down approaches. A cost-effectiveness analysis was performed by calculating the incremental cost per unfavourable outcome avoided. FINDINGS: Health-care costs per participant in South Africa were 8340.7 United States dollars (US$) with the long and US$ 6618.0 with the short regimen; in Ethiopia, they were US$ 6096.6 and US$ 4552.3, respectively. The largest component of the saving was medication costs in South Africa (67%; US$ 1157.0 of total US$ 1722.8) and social support costs in Ethiopia (35%, US$ 545.2 of total US$ 1544.3). In Ethiopia, trial participants on the short regimen reported lower expenditure for supplementary food (mean reduction per participant: US$ 225.5) and increased working hours (i.e. 667 additional hours over 132 weeks). The probability that the short regimen was cost-effective was greater than 95% when the value placed on avoiding an unfavourable outcome was less than US$ 19 000 in Ethiopia and less than US$ 14 500 in South Africa. CONCLUSION: The short MDR tuberculosis treatment regimen was associated with a substantial reduction in health-system costs and a lower financial burden for participants.

Rethinking Tuberculosis Morbidity Quantification: A Systematic Review and Critical Appraisal of TB Disability Weights in Cost-Effectiveness Analyses.

BACKGROUND: The disability-adjusted life year (DALY), a key metric for health resource allocation, encompasses morbidity through disability weights. Widely used in tuberculosis cost-effectiveness analysis (CEAs), DALYs play a significant role in informing intervention adopt/reject decisions. This study reviews the values and consistency of disability weights applied in tuberculosis-related CEAs. METHODS: We conducted a systematic review using the Tufts CEA database, updated to July 2023 with searches in Embase, Scopus and PubMed. Eligible studies needed to have included a cost-per-DALY ratio, and additionally either evaluated a tuberculosis (TB) intervention or included tuberculosis-related weights. We considered all tuberculosis health states: with/without human immunodeficiency virus (HIV) coinfection, TB treatments and treatment side effects. Data were screened and extracted independently by combinations of two authors. FINDINGS: A total of 105 studies spanning 2002-2023 across 50 countries (mainly low- and middle-income countries) were extracted. Disability weights were sourced primarily from the Global Burden of Disease (GBD; 100/165; 61%), with 17 non-GBD studies additionally referenced, along with primary derivation. Inconsistencies in the utilisation of weights were evident: of the 100 usages of GBD-sourced weights, only in 47 instances (47%) had the weight value been explicitly specified with an appropriate up-to-date reference cited (constituting 28% of all weight usages, 47/165). Sensitivity analyses on weight values had been conducted in 30% of studies (31/105). Twelve studies did not clearly specify weights or their sources; nine further calculated DALYs without morbidity. The review suggests methodological gaps in current approaches for representing important aspects of TB, including TB-HIV coinfection, treatment, drug-resistance, extrapulmonary TB and psychological impacts. We propose a set of best practice recommendations. INTERPRETATION: There is a need for increased rigour in the application, sensitivity testing and reporting of TB disability weights. Furthermore, there appears a desire among researchers to reflect elements of the tuberculosis experience beyond those allowed for by GBD disability weights.

Cost of treatment support for multidrug-resistant tuberculosis using patient-centred approaches in Ethiopia: a model-based method.

BACKGROUND: Patient and health system costs for treating multidrug-resistant tuberculosis (MDR-TB) remain high even after treatment duration was shortened. Many patients do not finish treatment, contributing to increased transmission and antimicrobial resistance. A restructure of health services, that is more patient-centred has the potential to reduce costs and increase trust and patient satisfaction. The aim of the study is to investigate how costs would change in the delivery of MDR-TB care in Ethiopia under patient-centred and hybrid approaches compared to the current standard-of-care. METHODS: We used published data, collected from 2017 to 2020 as part of the Standard Treatment Regimen of Anti-Tuberculosis Drugs for Patients with MDR-TB (STREAM) trial, to populate a discrete event simulation (DES) model. The model was developed to represent the key characteristics of patients' clinical pathways following each of the three treatment delivery strategies. To the pathways of 1000 patients generated by the DES model we applied relevant patient cost data derived from the STREAM trial. Costs are calculated for treating patients using a 9-month MDR-TB treatment and are presented in 2021 United States dollars (USD). RESULTS: The patient-centred and hybrid strategies are less costly than the standard-of-care, from both a health system (by USD 219 for patient-centred and USD 276 for the hybrid strategy) and patient perspective when patients do not have a guardian (by USD 389 for patient-centred and USD 152 for the hybrid strategy). Changes in indirect costs, staff costs, transport costs, inpatient stay costs or changes in directly-observed-treatment frequency or hospitalisation duration for standard-of-care did not change our results. CONCLUSION: Our findings show that patient-centred and hybrid strategies for delivering MDR-TB treatment cost less than standard-of-care and provide critical evidence that there is scope for such strategies to be implemented in routine care. These results should be used inform country-level decisions on how MDR-TB is delivered and also the design of future implementation trials.

Economic evaluation of shortened, bedaquiline-containing treatment regimens for rifampicin-resistant tuberculosis (STREAM stage 2): a within-trial analysis of a randomised controlled trial.

BACKGROUND: The STREAM stage 2 trial assessed two bedaquiline-containing regimens for rifampicin-resistant tuberculosis: a 9-month all-oral regimen and a 6-month regimen containing an injectable drug for the first 2 months. We did a within-trial economic evaluation of these regimens. METHODS: STREAM stage 2 was an international, phase 3, non-inferiority randomised trial in which participants with rifampicin-resistant tuberculosis were randomly assigned (1:2:2:2) to the 2011 WHO regimen (terminated early), a 9-month injectable-containing regimen (control regimen), a 9-month all-oral regimen with bedaquiline (oral regimen), or a 6-month regimen with bedaquiline and an injectable for the first 2 months (6-month regimen). We prospectively collected direct and indirect costs and health-related quality of life data from trial participants until week 76 of follow-up. Cost-effectiveness of the oral and 6-month regimens versus control was estimated in four countries (oral regimen) and two countries (6-month regimen), using health-related quality of life for cost-utility analysis and trial efficacy for cost-effectiveness analysis. This trial is registered with ISRCTN, ISRCTN18148631. FINDINGS: 300 participants were included in the economic analyses (Ethiopia, 61; India, 142; Moldova, 51; Uganda, 46). In the cost-utility analysis, the oral regimen was not cost-effective in Ethiopia, India, Moldova, and Uganda from either a provider or societal perspective. In Moldova, the oral regimen was dominant from a societal perspective. In the cost-effectiveness analysis, the oral regimen was likely to be cost-effective from a provider perspective at willingness-to-pay thresholds per additional favourable outcome of more than US$4500 in Ethiopia, $1900 in India, $3950 in Moldova, and $7900 in Uganda, and from a societal perspective at thresholds of more than $15 900 in Ethiopia, $3150 in India, and $4350 in Uganda, while in Moldova the oral regimen was dominant. In Ethiopia and India, the 6-month regimen would cost tuberculosis programmes and participants less than the control regimen and was highly likely to be cost-effective in both cost-utility analysis and cost-effectiveness analysis. Reducing the bedaquiline price from $1·81 to $1·00 per tablet made the oral regimen cost-effective in the provider-perspective cost-utility analysis in India and Moldova and dominate over the control regimen in the provider-perspective cost-effectiveness analysis in India. INTERPRETATION: At current costs, the oral bedaquiline-containing regimen for rifampicin-resistant tuberculosis is unlikely to be cost-effective in many low-income and middle-income countries. The 6-month regimen represents a cost-effective alternative if injectable use for 2 months is acceptable. FUNDING: USAID and Janssen Research & Development.

Identifying actions to foster cross-disciplinary global health research: a mixed-methods qualitative case study of the IMPALA programme on lung health and tuberculosis in Africa.

OBJECTIVES: To identify actions for fostering cross-disciplinary research (CDR) skills and collaborations in global health, and to produce recommendations for improving the design, implementation and management of cross-disciplinary global health research programmes. DESIGN: Using a North-South global health research programme as a case study-and following an adapted framework-we conducted qualitative research using document reviews, semi-structured interviews (purposive sampling) and participatory observation. We used baseline survey findings to identify potential interviewees and tailor interview guides. SETTING: Our case study was a 4.5-year (2017-2021) programme, namely, the International Multidisciplinary Programme to Address Lung Health and Tuberculosis in Africa (IMPALA). Led by a UK research institute, IMPALA spanned 22 partner organisations from 13 countries (10 in sub-Saharan Africa), and involved five research discipline groups: clinical science, social science, health systems, health economics and policy/research capacity. PARTICIPANTS: Thirty-one IMPALA members were interviewed (July 2018-November 2019), with interviewees evenly split by gender (16 female and 15 male) and by Global North/South institution (15 non-African and 16 African). Twenty-five (81%) were researchers, comprising 18 senior researchers (professors, readers, associate professors and senior lecturers) and seven early career researchers (assistant professors, lecturers, research fellows, postdocs, research assistants and PhD students). Twenty-four programme events were observed (September 2018-April 2020) and 49 documents were reviewed (December 2017-April 2020). All 66 IMPALA staff were sent the baseline survey, receiving 51 responses (43/56 researchers and 8/10 non-researchers). RESULTS: Fourteen themes emerged, which suggested that CDR-while valued by many-is not universally understood, and the time it requires is often underestimated. We found that fostering CDR and managing tensions needs planning and continuous discussions and interactions. A shared vision with explicitly agreed goals and roles and active management of cross-disciplinary activities is essential. CONCLUSIONS: Active planning, implementation and management of cross-disciplinary activities are essential for the success of cross-disciplinary global health research and should be separate from the primary research activities.

Stakeholder perspectives around post-TB wellbeing and care in Kenya and Malawi.

BACKGROUND: There is growing awareness of the burden of post-TB morbidity, and its impact on the lives and livelihoods of TB affected households. However little work has been done to determine how post-TB care might be delivered in a feasible and sustainable way, within existing National TB Programmes (NTPs) and health systems, in low-resource, high TB-burden settings. In this programme of stakeholder engagement around post-TB care, we identified actors with influence and interest in TB care in Kenya and Malawi, including TB-survivors, healthcare providers, policy-makers, researchers and funders, and explored their perspectives on post-TB morbidity and care. METHODS: Stakeholder mapping was completed to identify actors with interest and influence in TB care services in each country, informed by the study team's local, regional and international networks. Key international TB organisations were included to provide a global perspective. In person or online one-to-one interviews were completed with purposively selected stakeholders. Snowballing was used to expand the network. Data were recorded, transcribed and translated, and a coding frame was derived. Data were coded using NVivo 12 software and were analysed using thematic content analysis. Online workshops were held with stakeholders from Kenya and Malawi to explore areas of uncertainty and validate findings. RESULTS: The importance of holistic care for TB patients, which addresses both TB comorbidities and sequelae, was widely recognised by stakeholders. Key challenges to implementation include uncertainty around the burden of post-TB morbidity, leadership of post-TB services, funding constraints, staff and equipment limitations, and the need for improved integration between national TB and non-communicable disease (NCD) programmes for care provision and oversight. There is a need for local data on the burden and distribution of morbidity, evidence-informed clinical guidelines, and pilot data on models of care. Opportunities to learn from existing HIV-NCD services were emphasised. DISCUSSION: This work addresses important questions about the practical implementation of post-TB services in two African countries, exploring if, how, where, and for whom these services should be provided, according to a broad range of stakeholders. We have identified strong interest in the provision of holistic care for TB patients in Kenya and Malawi, and key evidence gaps which must be addressed to inform decision making by policy makers, TB programmes, and funders around investment in post-TB services. There is a need for pilot studies of models of integrated TB care, and for cross-learning between countries and from HIV-NCD services.

TB morbidity estimates overlook the contribution of post-TB disability: evidence from urban Malawi.

INTRODUCTION: Despite growing evidence of the long-term impact of tuberculosis (TB) on quality of life, Global Burden of Disease (GBD) estimates of TB-related disability-adjusted life years (DALYs) do not include post-TB morbidity, and evaluations of TB interventions typically assume treated patients return to pre-TB health. Using primary data, we estimate years of life lost due to disability (YLDs), years of life lost due to premature mortality (YLL) and DALYs associated with post-TB cardiorespiratory morbidity in a low-income country. METHODS: Adults aged ≥15 years who had successfully completed treatment for drug-sensitive pulmonary TB in Blantyre, Malawi (February 2016-April 2017) were followed-up for 3 years with 6-monthly and 12-monthly study visits. In this secondary analysis, St George's Respiratory Questionnaire data were used to match patients to GBD cardiorespiratory health states and corresponding disability weights (DWs) at each visit. YLDs were calculated for the study period and estimated for remaining lifespan using Malawian life table life expectancies. YLL were estimated using study mortality data and aspirational life expectancies, and post-TB DALYs derived. Data were disaggregated by HIV status and gender. RESULTS: At treatment completion, 222/403 (55.1%) participants met criteria for a cardiorespiratory DW, decreasing to 15.6% after 3 years, at which point two-thirds of the disability burden was experienced by women. Over 90% of projected lifetime-YLD were concentrated within the most severely affected 20% of survivors. Mean DWs in the 3 years post-treatment were 0.041 (HIV-) and 0.025 (HIV+), and beyond 3 years estimated as 0.025 (HIV-) and 0.010 (HIV+), compared with GBD DWs of 0.408 (HIV+) and 0.333 (HIV-) during active disease. Our results imply that the majority of TB-related morbidity occurs post-treatment. CONCLUSION: TB-related DALYs are greatly underestimated by overlooking post-TB disability. The total disability burden of TB is likely undervalued by both GBD estimates and economic evaluations of interventions, particularly those aimed at early diagnosis and prevention.

Palliative care and catastrophic costs in Malawi after a diagnosis of advanced cancer: a prospective cohort study.

BACKGROUND: Inclusive universal health coverage requires access to quality health care without financial barriers. Receipt of palliative care after advanced cancer diagnosis might reduce household poverty, but evidence from low-income and middle-income settings is sparse. METHODS: In this prospective study, the primary objective was to investigate total household costs of cancer-related health care after a diagnosis of advanced cancer, with and without the receipt of palliative care. Households comprising patients and their unpaid family caregiver were recruited into a cohort study at Queen Elizabeth Central Hospital in Malawi, between Jan 16 and July 31, 2019. Costs of cancer-related health-care use (including palliative care) and health-related quality-of-life were recorded over 6 months. Regression analysis explored associations between receipt of palliative care and total household costs on health care as a proportion of household income. Catastrophic costs, defined as 20% or more of total household income, sale of assets and loans taken out (dissaving), and their association with palliative care were computed. FINDINGS: We recruited 150 households. At 6 months, data from 89 (59%) of 150 households were available, comprising 89 patients (median age 50 years, 79% female) and 64 caregivers (median age 40 years, 73% female). Patients in 55 (37%) of the 150 households died and six (4%) were lost to follow-up. 19 (21%) of 89 households received palliative care. Catastrophic costs were experienced by nine (47%) of 19 households who received palliative care versus 48 (69%) of 70 households who did not (relative risk 0·69, 95% CI 0·42 to 1·14, p=0·109). Palliative care was associated with substantially reduced dissaving (median US$11, IQR 0 to 30 vs $34, 14 to 75; p=0·005). The mean difference in total household costs on cancer-related health care with receipt of palliative care was -36% (95% CI -94 to 594; p=0·707). INTERPRETATION: Vulnerable households in low-income countries are subject to catastrophic health-related costs following a diagnosis of advanced cancer. Palliative care might result in reduced dissaving in these households. Further consideration of the economic benefits of palliative care is justified. FUNDING: Wellcome Trust; National Institute for Health Research; and EMMS International.

A Transparent Universal Health Coverage Index with Decomposition by Socioeconomic Groups: Application in Asian and African Settings.

BACKGROUND: Health and wellbeing as one of the Sustainable Development Goals requires all countries to achieve Universal Health Coverage (UHC). That is, all people must have access to healthcare when needed at an affordable price. While several indices were developed recently to assess UHC status, these indices appeared to be difficult for practitioners to apply without statistical knowledge. OBJECTIVE: This paper presents a transparent and step-by-step practical calculation method of such an index using Excel spreadsheets, applied to some Asian and African countries. We also decompose the contribution of socioeconomic groups to UHC index values. METHODS: We utilized the well known UHC illustration (three-dimensional box, showing population coverage, service coverage and financial protection) to calculate the UHC index. We also broke down the index into socioeconomic groups. For validation, correlation coefficients between our index and other UHC indices were calculated and the relationship of our index with out-of-pocket (OOP) payments was estimated. RESULTS: World Bank data from six Asian and 15 African countries on health-service coverage of people in five socioeconomic quintiles with financial protection were used to calculate our UHC index. Among the Asian countries, indices ranged between 26.0% (Nepal) and 58.7% (Kazakhstan), while in African countries indices ranged between 8.9% (Chad) and 55.3% (Namibia). Decomposition of the UHC index showed a higher contribution to the index by richer socioeconomic groups. The correlation coefficients between our estimated UHC index values and those of others ranged between 0.774 and 0.900. Our index reduced by 1.4% in response to a 1% increase in OOP payments. CONCLUSIONS: This spreadsheet approach for calculating the UHC index appeared to be useful, where the interrelation of UHC dimensions was easily observed. Decomposition of the index could be useful for policy-makers to identify the subpopulations and health services with need for further interventions towards UHC achievement.