Economic evaluation of short treatment for multidrugresistant tuberculosis, Ethiopia and South Africa : the STREAM trial

OBJECTIVE STREAM was a phase-III non-inferiority randomised controlled trial (RCT) to evaluate a shortened regimen for multi-drug resistant tuberculosis (MDR-TB), and included the first-ever within-trial economic evaluation of such regimens, reported here. METHODS We compared the costs of ‘Long’ (20-22 months) and ‘Short’ (9-11 months) regimens in Ethiopia and South Africa. Cost data were collected from trial participants, and health system costs estimated using ‘bottom-up’ and ‘top-down’ costing approaches. A cost-effectiveness analysis was conducted with the trial primary outcome as the measure of effectiveness, including a probabilistic sensitivity analysis (PSA) to illustrate decision uncertainty. FINDINGS The Short-regimen reduced healthcare costs per case by 21% in South Africa (US$8,341 Long vs US$6,619 Short) and 25% in Ethiopia (US$6,097 Long vs US$4,552 Short). The largest component of this saving was medication in South Africa (67%) and social support in Ethiopia (35%). In Ethiopia, participants on the Short-regimen reported reductions in dietary supplementation expenditure (US$225 per case (95$13 (95%CI 11-14), South Africa US$64 (95$19,000 (Ethiopia) or <US$14,500 (South Africa). CONCLUSION The Short-regimen provided substantial health system cost savings and reduced financial burden on participants. Shorter regimens are likely to be cost-effective in most settings, and an effective strategy to support the WHO goal of eliminating catastrophic costs in T

Patient-cost survey for tuberculosis in the context of patient-pathway modelling.

ETTING: Eight tuberculosis treatment sites in Cavite Province, the Philippines, including two sites specialising in management of multidrug-resistant tuberculosis (MDR-TB).OBJECTIVE: To evaluate costs incurred by TB patients and to determine the proportion of households that faced catastrophic costs, then to consider cost survey responses alongside results of detailed patient-pathway modelling.DESIGN: Clustered cross-sectional survey using a field testing version of the WHO TB patient-costing tool and protocol; face-to-face interviews with 194 patients conducted in May-August 2016. Costs included direct-medical, direct non-medical and indirect costs using the human capital approach. Patients were deemed to incur catastrophic expenditure if TB-related costs exceeded 20% of annual household income. Patient pathways were modelled following multiple health staff interviews.RESULTS: Estimated mean cost incurred by patients with drug-susceptible TB was US$321 vs.$2356 for MDR-TB patients. Catastrophic costs were suffered by 28% of drug-susceptible and 80% of MDR-TB patients, with lost income being the largest contributor. Patient-pathway modelling suggested most patients had under-reported health visits.CONCLUSION: Survey results indicate that patient costs are large for all patients in Cavite, particularly for MDR-TB patients. Patient-pathway modelling suggests these costs are an underestimate due to poor recollection of health visits, suggesting that the WHO instrument and protocol could be improved to better capture the diagnostic journey

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

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

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

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

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. Graphical Abstract

Modelling the impact of chest X-ray and alternative triage approaches prior to seeking a tuberculosis diagnosis

Abstract Background Tuberculosis is a major challenge to health in the developing world. Triage prior to diagnostic testing could potentially reduce the volume of tests and costs associated with using the more accurate, but costly, Xpert MTB/RIF assay. An effective methodology to predict the impact of introducing triage prior to tuberculosis diagnostic testing could be useful in helping to guide policy. Methods The development and use of operational modelling to project the impact on case detection and health system costs of alternative triage approaches for tuberculosis, with or without X-ray, based on data from Porto Alegre City, Brazil. Results Most of the triage approaches modelled without X-ray were predicted to provide no significant benefit. One approach based on an artificial neural network applied to patient and symptom characteristics was projected to increase case detection (82% vs. 75%) compared to microscopy, and reduce costs compared to Xpert without triage. In addition, use of X-ray before diagnostic testing for HIV-negative patients could maintain diagnostic yield of using Xpert without triage, and reduce costs. Conclusion A model for the impact assessment of alternative triage approaches has been tested. The results from using the approach demonstrate its usefulness in informing policy in a typical high burden setting for tuberculosis

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

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

ObjectiveTo investigate cost changes for health systems and participants, resulting from switching to short treatment regimens for multidrug-resistant (MDR) tuberculosis.MethodsWe compared the costs to health systems and participants of long (20 to 22&nbsp;months) and short (9 to 11&nbsp;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.FindingsHealth-care costs per participant in South Africa were 8340.7 United States dollars (US$) with the long and US$&nbsp;6618.0 with the short regimen; in Ethiopia, they were US 6096.6 and US&nbsp;4552.3, respectively. The largest component of the saving was medication costs in South Africa (67%; US 1157.0 of total US&nbsp;1722.8) and social support costs in Ethiopia (35%, US 545.2 of total US&nbsp;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&nbsp;19 000 in Ethiopia and less than US$&nbsp;14 500 in South Africa.ConclusionThe short MDR tuberculosis treatment regimen was associated with a substantial reduction in health-system costs and a lower financial burden for participants