Impact and cost-effectiveness of the 6-month BPaLM regimen for rifampicin-resistant tuberculosis in Moldova: A mathematical modeling analysis.

BACKGROUND: Emerging evidence suggests that shortened, simplified treatment regimens for rifampicin-resistant tuberculosis (RR-TB) can achieve comparable end-of-treatment (EOT) outcomes to longer regimens. We compared a 6-month regimen containing bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) to a standard of care strategy using a 9- or 18-month regimen depending on whether fluoroquinolone resistance (FQ-R) was detected on drug susceptibility testing (DST). METHODS AND FINDINGS: The primary objective was to determine whether 6 months of BPaLM is a cost-effective treatment strategy for RR-TB. We used genomic and demographic data to parameterize a mathematical model estimating long-term health outcomes measured in quality-adjusted life years (QALYs) and lifetime costs in 2022 USD ($) for each treatment strategy for patients 15 years and older diagnosed with pulmonary RR-TB in Moldova, a country with a high burden of TB drug resistance. For each individual, we simulated the natural history of TB and associated treatment outcomes, as well as the process of acquiring resistance to each of 12 anti-TB drugs. Compared to the standard of care, 6 months of BPaLM was cost-effective. This strategy was estimated to reduce lifetime costs by $3,366 (95% UI: [1,465, 5,742] p < 0.001) per individual, with a nonsignificant change in QALYs (-0.06; 95% UI: [-0.49, 0.03] p = 0.790). For those stopping moxifloxacin under the BPaLM regimen, continuing with BPaL plus clofazimine (BPaLC) provided more QALYs at lower cost than continuing with BPaL alone. Strategies based on 6 months of BPaLM had at least a 93% chance of being cost-effective, so long as BPaLC was continued in the event of stopping moxifloxacin. BPaLM for 6 months also reduced the average time spent with TB resistant to amikacin, bedaquiline, clofazimine, cycloserine, moxifloxacin, and pyrazinamide, while it increased the average time spent with TB resistant to delamanid and pretomanid. Sensitivity analyses showed 6 months of BPaLM to be cost-effective across a broad range of values for the relative effectiveness of BPaLM, and the proportion of the cohort with FQ-R. Compared to the standard of care, 6 months of BPaLM would be expected to save Moldova's national TB program budget $7.1 million (95% UI: [1.3 million, 15.4 million] p = 0.002) over the 5-year period from implementation. Our analysis did not account for all possible interactions between specific drugs with regard to treatment outcomes, resistance acquisition, or the consequences of specific types of severe adverse events, nor did we model how the intervention may affect TB transmission dynamics. CONCLUSIONS: Compared to standard of care, longer regimens, the implementation of the 6-month BPaLM regimen could improve the cost-effectiveness of care for individuals diagnosed with RR-TB, particularly in settings with a high burden of drug-resistant TB. Further research may be warranted to explore the impact and cost-effectiveness of shorter RR-TB regimens across settings with varied drug-resistant TB burdens and national income levels.

Catastrophic costs incurred by tuberculosis affected households from Thailand's first national tuberculosis patient cost survey.

Tuberculosis (TB) causes an economic impact on the patients and their households. Although Thailand has expanded the national health benefit package for TB treatment, there was no data on out-of-pocket payments and income losses due to TB from patients and their household perspectives. This national TB patient cost survey was conducted to examine the TB-related economic burden, and assess the proportion of TB patients and their households facing catastrophic total costs because of TB disease. A cross-sectional TB patient cost survey was employed following WHO methods. Structured interviews with a paper-based questionnaire were conducted from October 2019 to July 2021. Both direct and indirect costs incurred from the patient and their household perspective were valued in 2021 and estimated throughout pre- and post-TB diagnosis episodes. We assessed the proportion of TB-affected households facing costs > 20% of household expenditure due to TB. We analyzed 1400 patients including 1382 TB (first-line treatment) and 18 drug-resistant TB patients (DR-TB). The mean total costs per TB episode for all study participants were 903 USD (95% confident interval; CI 771-1034 USD). Of these, total direct non-medical costs were the highest costs (mean, 402 USD, and 95%CI 334-470 USD) incurred per TB-affected household followed by total indirect costs (mean, 393 USD, and 95%CI 315-472 USD) and total direct medical costs (mean, 107 USD, and 95%CI 81-133 USD, respectively. The proportion of TB-affected households facing catastrophic costs was 29.5% (95%CI 25.1-34.0%) for TB (first-line), 61.1% (95%CI 29.6-88.1%) for DR-TB and 29.9% (95%CI 25.6-34.4%) overall. This first national survey highlighted the economic burden on TB-affected households. Travel, food/nutritional supplementation, and indirect costs contribute to a high proportion of catastrophic total costs. These suggest the need to enhance financial and social protection mechanisms to mitigate the financial burden of TB-affected households.

Economic implications of novel regimens for tuberculosis treatment in three high-burden countries: a modelling analysis.

BACKGROUND: With numerous trials investigating novel drug combinations to treat tuberculosis, we aimed to evaluate the extent to which future improvements in tuberculosis treatment regimens could offset potential increases in drug costs. METHODS: In this modelling analysis, we used an ingredients-based approach to estimate prices at which novel regimens for rifampin-susceptible and rifampin-resistant tuberculosis treatment would be cost-neutral or cost-effective compared with standards of care in India, the Philippines, and South Africa. We modelled regimens meeting targets set in the WHO's 2023 Target Regimen Profiles (TRPs). Our decision-analytical model tracked cohorts of adults initiating rifampin-susceptible or rifampin-resistant tuberculosis treatment, simulating their health outcomes and costs accumulated during and following treatment under standard-of-care and novel regimen scenarios. Price thresholds included short-term cost-neutrality (considering only savings accrued during treatment), medium-term cost-neutrality (additionally considering savings from averted retreatments and secondary cases), and cost-effectiveness (incorporating willingness-to-pay for improved health outcomes). FINDINGS: Total medium-term costs per person treated using standard-of-care regimens were estimated at US$450 (95% uncertainty interval 310-630) in India, $560 (350-860) in the Philippines, and $730 (530-1090) in South Africa for rifampin-susceptible tuberculosis (current drug costs $46) and $2100 (1590-2810) in India, $2610 (2090-3280) in the Philippines, and $3790 (3090-4630) in South Africa for rifampin-resistant tuberculosis (current drug costs $432). A rifampin-susceptible tuberculosis regimen meeting the optimal targets defined in the TRPs could be cost-neutral in the short term at drug costs of $140 (90-210) per full course in India, $230 (130-380) in the Philippines, and $280 (180-460) in South Africa. For rifampin-resistant tuberculosis, short-term cost-neutral thresholds were higher with $930 (720-1230) in India, $1180 (980-1430) in the Philippines, and $1480 (1230-1780) in South Africa. Medium-term cost-neutral prices were approximately $50-100 higher than short-term cost-neutral prices for rifampin-susceptible tuberculosis and $250-550 higher for rifampin-resistant tuberculosis. Health system cost-neutral prices that excluded patient-borne costs were 45-70% lower (rifampin-susceptible regimens) and 15-50% lower (rifampin-resistant regimens) than the cost-neutral prices that included patient costs. Cost-effective prices were substantially higher. Shorter duration was the most important driver of medium-term savings with novel regimens, followed by ease of adherence. INTERPRETATION: Improved tuberculosis regimens, particularly shorter regimens or those that facilitate better adherence, could reduce overall costs, potentially offsetting higher prices. FUNDING: WHO.

A systematic review of economic evaluations of pharmacological treatments for active tuberculosis.

Objectives: The continuing spread of tuberculosis (TB) worldwide, especially drug-resistant TB, poses a major challenge to healthcare systems globally. Addressing this requires appraising the cost effectiveness of existing pharmacological interventions against TB to identify key drivers of cost effectiveness and value and guide pharmaceutical innovation and novel drug regimen development. Methods: Studies were identified from a search of six database: MEDLINE MEDLINE-In Process, MEDLINE Epub Ahead of Print, EMBASE, Cochrane Database of Systematic Reviews, and Econlit in July 2022. Two reviewers independently assessed all identified studies and reports using pre-defined inclusion/exclusion criteria. Study methodological quality was assessed, data were extracted in standard tables, and results were narratively synthesized. Results: Overall, 991 studies and 53 HTA reports were identified with 20 studies and 3 HTA reports meeting the inclusion criteria. Quality assessment of the 20 studies identified 4 with minor limitations, while the remainder were assessed as having potentially or very serious limitations. Sixteen studies conducted cost-utility analyses, 6 conducted cost-effectiveness analyses, and 2 conducted cost-comparison analyses with some studies performing multiple analyses. The majority (n = 16) were model-based. Eleven studies analyzed the cost-effectiveness of bedaquiline, 6 compared shorter to longer/standard duration regimens, 2 assessed ethambutol, and 1 assessed delamanid. Key drivers of cost effectiveness were drug costs, the number of TB cases, the portion of cases with sputum culture conversion, treatment delivery costs, and treatment efficacy. Common value elements considered included adverse events, drug resistance, and improving treatment adherence. Conclusion: Our results suggest that out of the pharmacological treatments assessed, bedaquiline is likely a cost-effective addition to existing treatment regimens/background treatment regimens, while ethambutol is not likely to be. Newer shorter regimens, even if more costly, seem to be more cost-effective compared to longer regimens. These results illustrate the limited number of novel cost-effective pharmacological interventions and highlight a need to develop new drugs/regimens against TB to overcome resistance, taking into account the key drivers of cost effectiveness and other value attributes identified from this review.

Effectiveness, cost, and safety of four regimens recommended by WHO for RR/MDR-TB treatment: a cohort study in Eastern China.

BACKGROUND: To compare the effectiveness, cost, and safety of four regimens recommended by the World Health Organization (WHO) for rifampicin resistance/multidrug-resistance tuberculosis (RR/MDR-TB) Treatment in Eastern China. METHODS: We performed a cohort study among patients with RR/MDR between 2020 and 2022 in Jiangsu Province. The treatment success rate, cost, and drug adverse reaction rate were compared. RESULTS: Between 2020 and 2022, 253 RR/MDR-TB patients were enrolled in the study. 37 (14.62%), 76 (30.04%), 74 (29.25%), and 66 (26.09%) patients had the short-term regimens, the new long-term oral regimens, the new long-term injectable regimens, and the traditional long-term regimens, respectively. The treatment success rate was the highest among patients treated with the short-term regimen (75.68%) and was the lowest among patients treated with the traditional long-term regimens (60.61%). The estimated mean cost per favorable outcome was 142.61 thousand Chinese Yuan (CNY), and the short-term regimens showed the lowest cost in the four regimes (88.51 thousand CNY vs. 174.24 thousand CNY, 144.00 thousand CNY, and 134.98 thousand CNY). Incremental cost-effectiveness ratios of the short-term regimens, the new long-term oral regimen, and the new long-term injectable regimens were -3083.04, 6040.09, and 819.68 CNY compared to the traditional long-term regimens. CONCLUSIONS: For RR/MDR-TB patients in China who meet the criteria for short-term regimens, the short-term regimens were proven to be the most cost-effective of the four regimens recommended by WHO. For RR/MDR-TB patients in China who don't meet the criteria for short-term regimens, the new long-term injectable regimens are more cost-effective than the remaining two regimens.

This is the first study to evaluate the effectiveness, cost, and safety of four regimens recommended by the WHO for RR/MDR-TB treatment in China.For RR/MDR-TB patients in China who meet the criteria for the short-term regimens, the short-term regimens were proven to be the most cost-effective of the four regimens recommended by WHO.

Implementation of whole genome sequencing for tuberculosis diagnostics in a low-middle income, high MDR-TB burden country.

Whole genome sequencing (WGS) is revolutionary for diagnostics of TB and its mutations associated with drug-resistances, but its uptake in low- and middle-income countries is hindered by concerns of implementation feasibility. Here, we provide a proof of concept for its successful implementation in such a setting. WGS was implemented in the Kyrgyz Republic. We estimated needs of up to 55 TB-WGS per week and chose the MiSeq platform (Illumina, USA) because of its capacity of up to 60 TB-WGS per week. The project's timeline was completed in 93-weeks. Costs of large equipment and accompanying costs were 222,065 USD and 8462 USD, respectively. The first 174 WGS costed 277 USD per sequence, but this was skewed by training inefficiencies. Based on real prices and presuming optimal utilization of WGS capacities, WGS costs could drop to 167 and 141 USD per WGS using MiSeq Reagent Kits v2 (500-cycles) and v3 (600-cycles), respectively. Five trainings were required to prepare the staff for autonomous WGS which cost 48,250 USD. External assessment confirmed excellent performance of WGS by the Kyrgyz laboratory in an interlaboratory comparison of 30 M. tuberculosis genomes showing complete agreeance of results.

A systematic review of pharmacoeconomic evaluations on oral diarylquinoline-based treatment for drug-resistant tuberculosis: from high to low burden countries.

Introduction: There is a rising global interest in the pharmacoeconomic evaluations of bedaquiline (BDQ), a novel oral diarylquinoline, for treatment of drug-resistant tuberculosis (DR-TB).Areas covered: This article systematically reviewed publications retrieved from Medline, American Psychological Association-Psychology information, Web of Science, Embase, Scopus, Science direct, Center for Reviews and Dissemination, and CINAHL Complete during 2010-2020 on pharmacoeconomic studies on BDQ for DR-TB treatment. Ten Markov model-based cost-effectiveness analyses identified were conducted in high (n = 4), intermediate (n = 2), and low (n = 4) TB burden countries.Expert opinion: The paucity of model-based health economic analyses on BDQ-containing regimens for DR-TB indicated that further pharmacoeconomic research of BDQ-based regimens, on the aspects of duration of BDQ treatment, types of DR-TB indicated, and settings of regions and health-systems, is highly warranted to inform global cost-effective use of BDQ-based regimens for DR-TB treatment.

Cost of multidrug resistant tuberculosis in Germany-An update.

BACKGROUND: In 2019, new therapeutic recommendations for multidrug-resistant (MDR-) and extensively drug-resistant (XDR) tuberculosis (TB) were published by the WHO, advocating the use of oral drugs and stepwise composition of antibiotic regimens. To date, the economic consequences of those recommendations in low incidence settings have not been evaluated. OBJECTIVE: To assess the costs of applying the new recommendations against a set of 86 MDR-TB/XDR-TB strains, each with individual phenotypic drug resistance patterns, identified in 2018/2019 by the German National Reference Center for Mycobacteria. METHODS: Hospitalization costs as covered by German statutory health insurance and the loss of productivity due to illness were calculated using the most recent 2018 statistical data. Costs due to combining five agents in the intensive phase and costs of outpatient monitoring were determined by Monte-Carlo simulation covering all treatment options over an 18-month period. Drug costs were compared to those arising under the approach recommended by the WHO in 2016. RESULTS: Hospitalization costs per MDR-TB patient were €30,152 and the mean costs of antimicrobials over a period of 18 months were €66,854 (range €20,671 to €187,444). Total treatment costs, including outpatient monitoring, were €73,551.56 per patient (range €30,114 to €145.878). In addition, we determined an average cost of €11,410.20 due to productivity loss over a period of 6 months sick leave. Despite a shortened minimum recommended treatment duration (18 versus 20 months), the estimated costs were 24.5% higher based on the 2019 recommendations as compared to the 2016 guideline version. CONCLUSION: Higher costs for treating MDR-TB/XDR-TB in Germany are to be expected under the new WHO regimens. However, it must be determined whether treatment duration and costs associated with sick leave may be further reduced in the future through shorter hospital stays and earlier culture conversion.

Cost comparison of nine-month treatment regimens with 20-month standardized care for the treatment of rifampicin-resistant/multi-drug resistant tuberculosis in Nigeria.

BACKGROUND: Globally, drug resistant tuberculosis (DR-TB) continues to be a public health threat. Nigeria, which accounts for a significant proportion of the global burden of rifampicin/multi-drug resistant-TB (RR/MDR-TB) had a funding gap of $168 million dollars for TB treatment in 2018. Since 2010, Nigeria has utilized five different models of care for RR/MDR-TB (Models A-E); Models A, B and C based on a standardized WHO-approved treatment regimen of 20-24 months, were phased out between 2015 and 2019 and replaced by Models D and E. Model D is a fully ambulatory model of 9-12 months during which a shorter treatment regimen including a second-line injectable agent is utilized. Model E is identical to Model D but has patients hospitalized for the first four months of care while Model F which is to be introduced in 2020, is a fully ambulatory, oral bedaquiline-containing shorter treatment regimen of 9-12 months. Treatment models for RR/MDR-TB of 20-24 months duration have had treatment success rates of 52-66% while shorter treatment regimens have reported success rates of 85% and above. In addition, replacing the second-line injectable agent in a shorter treatment regimen with bedaquiline has been found to further improve treatment success in patients with fluoroquinolone-susceptible RR/MDR-TB. Reliable cost data for RR/MDR-TB care are limited, specifically costs of models that utilize shorter treatment regimens and which are vital to guide Nigeria through the provision of RR/MDR-TB care at scale. We therefore conducted a cost analysis of shorter treatment regimens in use and to be used in Nigeria (Models D, E and F) and compared them to three models of longer duration utilized previously in Nigeria (Models A, B and C) to identify any changes in cost from transitioning from Models A-C to Models D-F and opportunities for cost savings. METHODS: We obtained costs for TB diagnostic and monitoring tests, in-patient and out-patient care from a previous study, inflated these costs to 2019 NGN and then converted to 2020 USD. We obtained other costs from the average of six health facilities and drug costs from the global drug facility. We modeled treatment on strict adherence to two Nigerian National guidelines for programmatic and clinical management of drug-resistant tuberculosis. RESULTS: We estimated that the total costs of care from the health sector perspective for Models D, E and F were $4,334, $7,705 and $3,420 respectively. This is significantly lower than the costs of Models A, B and C which were $14,781, $12, 113, $7,572 respectively. CONCLUSION: Replacing Models A-C with Models D and E reduced the costs of RR/MDR-TB care in Nigeria by approximately $5,470 (48%) per patient treated and transitioning from Models D and E to Model F would result in further cost savings of $914 to $4,285 (21 to 56%) for every patient placed on Model F. If the improved outcomes of patients managed using bedaquiline-containing shorter treatment regimens in other countries can be attained in Nigeria, Model F would be the recommended model for the scale up of RR/MDR-TB care in Nigeria.

First national tuberculosis patient cost survey in Lao People's Democratic Republic: Assessment of the financial burden faced by TB-affected households and the comparisons by drug-resistance and HIV status.

BACKGROUND: Tuberculosis (TB) patients incur large costs for care seeking, diagnosis, and treatment. To understand the magnitude of this financial burden and its main cost drivers, the Lao People's Democratic Republic (PDR) National TB Programme carried out the first national TB patient cost survey in 2018-2019. METHOD: A facility-based cross-sectional survey was conducted based on a nationally representative sample of TB patients from public health facilities across 12 provinces. A total of 848 TB patients including 30 drug resistant (DR)-TB and 123 TB-HIV coinfected patients were interviewed using a standardised questionnaire developed by the World Health Organization. Information on direct medical, direct non-medical and indirect costs, as well as coping mechanisms was collected. We estimated the percentage of TB-affected households facing catastrophic costs, which was defined as total TB-related costs accounting for more than 20% of annual household income. RESULT: The median total cost of TB care was US$ 755 (Interquartile range 351-1,454). The costs were driven by direct non-medical costs (46.6%) and income loss (37.6%). Nutritional supplements accounted for 74.7% of direct non-medical costs. Half of the patients used savings, borrowed money or sold household assets to cope with TB. The proportion of unemployment more than doubled from 16.8% to 35.4% during the TB episode, especially among those working in the informal sector. Of all participants, 62.6% of TB-affected households faced catastrophic costs. This proportion was higher among households with DR-TB (86.7%) and TB-HIV coinfected patients (81.1%). CONCLUSION: In Lao PDR, TB patients and their households faced a substantial financial burden due to TB, despite the availability of free TB services in public health facilities. As direct non-medical and indirect costs were major cost drivers, providing free TB services is not enough to ease this financial burden. Expansion of existing social protection schemes to accommodate the needs of TB patients is necessary.

Household financial burden among multidrug-resistant tuberculosis patients in Guizhou province, China: A cross-sectional study.

Multidrug-resistant tuberculosis (MDR-TB) threatens global public health. Poor access to health care due to financial hardship contributes to further transmission of the disease. The study aimed to:A cross-sectional study was conducted in 2 hospitals designated for MDR-TB from January to August 2018. Data were collected by interviewing eligible MDR-TB outpatients and reviewing the medical records. The magnitude of financial burden was documented by total cost and distribution of cost components. Catastrophic payments were measured by 2 indicators: catastrophic health expenditure (CHE) and catastrophic total costs (CTC), both of which were estimated by incidence and intensity. Their associated factors were determined using logistic regression models.Of 161 households affected by MDR-TB, the average total costs due to MDR-TB treatment in the first year was US$ 8266 and consisted of 72% direct medical costs, 5% direct non-medical costs and 23% indirect costs (income loss). Thirty seven percent of direct medical costs were covered by insurance. Overall, the incidence of CHE and CTC was 68.3% and 87.0%, respectively. Both incidence and intensity for the 2 defined catastrophic costs increased when a households income decreased. Five significant factors of catastrophic costs were low household income, absence of students in a family, hospital length of stay, male gender, and job/productivity loss.Households with MDR-TB patients shouldered a high financial burden which was mainly driven by direct medical costs and income loss in Guizhou. Greater catastrophic payments were associated with hospital length of stay and socioeconomic status, especially had a dose-response relationship with households income. Our findings suggest that financial and social protection of local policies for MDR-TB should be improved by preparing a uniform and comprehensive insurance package to cover sufficiently direct medical costs, and introducing social pro-poor assistance policies for risk families to protect them from financial hardship.

What causes high costs for rural tuberculosis inpatients? Evidence from five counties in China.

BACKGROUND: Tuberculosis (TB) still causes high economic burden on patients in China, especially for rural patients. Our study aims to explore the risk factors associated with the high costs for TB inpatients in rural China from the aspects of inpatients' socio-demographic and institutional attributes. METHODS: Generalized linear models were utilized to investigate the factors associated with TB inpatients' total costs and out-of-pocket (OOP) expenditures. Quantile regression (QR) models were applied to explore the effect of each factor across the different costs range and identify the risk factors of high costs. RESULTS: TB inpatients with long length of stay and who receive hospitalization services cross provincially, in tertiary and specialized hospitals were likely to face high total costs and OOP expenditures. QR models showed that high total costs occurred in Dingyuan and Funan Counties, but they were not accompanied by high OOP expenditures. CONCLUSIONS: Early diagnosis, standard treatment and control of drug-resistant TB are still awaiting for more efforts from the government. TB inpatients should obtain medical services from appropriate hospitals. The diagnosis and treatment process of TB should be standardized across all designated medical institutions. Furthermore, the reimbursement policy for migrant workers who suffered from TB should be ameliorated.

Cost-effectiveness of treating multidrug-resistant tuberculosis in treatment initiative centers and treatment follow-up centers in Ethiopia.

BACKGROUND: In Ethiopia, MDR-TB has become a significant public health threat; therefore, the Ministry of Health introduced two treatment approaches for MDR-TB cases: treatment initiative center (TIC) and treatment follow-up center (TFC). TIC is where patients usually are diagnosed and start the treatment. At TFC, we follow MDR-TB patients until they completed the treatment. However, there is no evidence about the cost-effectiveness of the approaches. Therefore, this study aimed to analyze the cost-effectiveness of MDR-TB treatment in TIC and TFC. METHODS: In this study, we employed a full economic evaluation from a providers' perspective. We followed a hypothetical cohort of individuals from the age of 15 for a lifetime using a Markov model with five mutually exclusive health states. We used both primary and secondary data sources for the study. Ingredient-based costing approach was used. The costs include healthcare provider costs (recurrent and capital cost) and patient-side costs (direct and indirect). We use a human capital approach to estimate the indirect cost. The cost estimates were reported in the 2017 United States Dollar (US$), and effectiveness was measured using disability-adjusted life-years (DALYs) averted. Both costs and health benefits were discounted using a 3% discount rate. Both average and incremental cost-effectiveness ratios (ICER) were reported calculated. One-way and probabilistic sensitivity analyses were reported to determine the robustness of the estimates. RESULTS: The cost per HIV negative patient successfully treated for MDR-TB was $8,416 at TIC and $6,657 at TFC. The average cost-effectiveness ratio per DALY averted at TFC was $671 and $1,417 per DALY averted at TIC. The incremental cost-effectiveness ratio (ICER) of MDR-TB treatment at TIC was $1,641 per DALYs averted. CONCLUSION: This study indicates that the treatment of MDR-TB at both TIC and TFC are cost-effective interventions compared with the willingness to pay threshold of three-times the GDP per capita in Ethiopia.

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.

Direct and indirect patient costs of tuberculosis care in India.

OBJECTIVE: To synthesise the evidence for estimating the direct and indirect patient costs of drug-sensitive and drug-resistant tuberculosis care in India. METHOD: PubMed, Embase, Web of Science, IndMED and Google Scholar were searched for studies conducted in India between 2000 and 2018 and published in English. The search terms were "tuberculosis" AND "costs" (cost Analysis, economics, cost of illness, health care costs, health expenditures, direct service costs, catastrophic cost) AND "India". The cost of TB care was from the patient's perspective. Data regarding costs were extracted, indexed to the year 2018 using cumulative inflation rate and converted to US dollars at the exchange rate of 2018. RESULTS: Thirteen studies were included in this review. The mean (unweighted) total cost incurred by patients being treated for drug-sensitive TB in a public health facility was $ 235.00 (SD- 222.10), and the median of means was $ 170.60 (range - 43.70-718.40). The mean direct cost was 45.5% of the total cost. Only one study, which was conducted in a private facility, reported the mean total cost for drug-resistant TB as $ 7778.04. Catastrophic cost (total cost ≥ 20% of the total annual household income) was experienced by 7% to 32.4% of drug-sensitive TB patients and by 68% of drug-resistant TB patients. CONCLUSION: Despite free diagnostic and treatment services provided under the Revised National Tuberculosis Control Programme, the patient cost of tuberculosis care is high. Relevant studies vary widely in methodology and cost reporting.

OBJECTIF: Synthétiser les données probantes permettant d'estimer les coûts directs et indirects des soins anti-TB pour les patients avec une TB sensible ou résistante aux médicaments en Inde. MÉTHODE: PubMed, Embase, Web of Science, IndMED et Google Scholar ont été recherchés pour des études menées en Inde entre 2000 et 2018 et publiées en anglais. Les termes de recherche étaient 'tuberculose' ET 'coûts' (analyse des coûts, économie, coût de la maladie, coûts des soins de santé, dépenses de santé, coûts directs des services, coût catastrophique) ET 'Inde'. Le coût des soins anti-TB était du point de vue du patient. Les données concernant les coûts ont été extraites, indexées pour l'année 2018 en utilisant le taux d'inflation cumulé et converties en dollars US au taux de change de 2018. RÉSULTATS: Treize études ont été incluses dans cette revue. Le coût total moyen (non pondéré) encouru par les patients traités pour une TB sensible aux médicaments dans un établissement de santé public était de 235,00 USD (SD-222,10), et la médiane des moyennes était de 170,60 USD (intervalle - 43,70 - 718,40). Le coût direct moyen était de 45,5% du coût total. Une seule étude, qui a été menée dans un établissement privé, a rapporté le coût moyen total pour la TB résistante aux médicaments équivalent à 7.778,04 USD. Des coûts catastrophiques (coût total ≥ 20% du revenu annuel total du ménage ) ont été subis par 7% à 32,4% des patients avec une TB sensible aux médicaments et par 68% des patients avec une TB résistante aux médicaments. CONCLUSION: Malgré les services gratuits de diagnostic et de traitement fournis dans le cadre du Programme National Révisé de Lutte contre la TB, le coût des soins anti-TB pour les patients est élevé. Les études pertinentes varient considérablement dans la méthodologie et la communication des coûts.

Prediction of treatment outcomes for multidrug-resistant tuberculosis by whole-genome sequencing.

BACKGROUND: Whole-genome sequencing (WGS) has been proposed to be a powerful tool to predict drug resistance for antitubercular drugs. However, the feasibility of WGS in predicting final treatment outcomes for multidrug-resistant tuberculosis (MDR-TB) patients remains unclear PATIENTS AND METHODS: In this prospective observational study conducted from January 2014 to September 2016, MDR-TB patients were enrolled consecutively. Genotypic drug sensitivity testing was performed via WGS using culture isolates. Patients were followed for two years to determine the treatment outcomes. Multivariate analysis was used to identify the association between information provided by WGS and the final treatment outcomes RESULTS: A total of 123 patients with MDR-TB were included in this study. The overall favorable treatment outcome rate was 60.2%. Multivariate analysis showed that independent risk factors associated with unfavorable treatment outcome including high-level moxifloxacin phenotypic resistance (OR, 4.362; 95%CI, 1.364-13.950; p=0.013), cycloserine phenotypic resistance (OR, 7.457; 95%CI, 1.644-33.819; p=0.009), mutations causing high-level fluoroquinolones resistance (OR, 3.947; 95%CI, 1.195-13.034; p=0.024), and ethA mutation (OR, 3.817; 95% CI, 1.154-12.823; p=0.028). WGS costs for each patient are ¥450 ($63), and the average turnaround time was one week CONCLUSIONS: In summary, WGS showed promising feasibility in predicting treatment outcomes for MDR-TB patients within a clinically relevant time frame.

The cost-effectiveness of a bedaquiline-containing short-course regimen for the treatment of multidrug-resistant tuberculosis in South Africa.

Background: Bedaquiline-containing regimens have demonstrated improved outcomes over injectable-containing regimens in the long-term treatment of multidrug-resistant tuberculosis (MDR-TB). Recently, the World Health Organization (WHO) recommended replacing injectables in the standard short-course regimen (SCR) with a bedaquiline-containing regimen. The South African national TB program similarly recommends a bedaquiline-containing regimen. Here, we investigated the cost-effectiveness of a bedaquiline-containing SCR versus an injectable-containing SCR for the treatment of MDR-TB in South Africa.Methods: A Markov model was adapted to simulate the incidence of active patients with MDR-TB. Patients could transition through eight health states: active MDR-TB, culture conversion, cure, follow-up loss, secondary MDR-TB, extensively DR-TB, end-of-life care, and death. A 5% discount was assumed on costs and outcomes. Health outcomes were expressed as disability-adjusted life years (DALYs).Results: Over a 10-year time horizon, a bedaquiline-containing SCR dominated an injectable-containing SCR, with an incremental saving of US $982 per DALY averted. A bedaquiline-containing SCR was associated with lower total costs versus an injectable-containing SCR (US $597 versus $657 million), of which US $3.2 versus $21.9 million was attributed to adverse event management.Conclusions: Replacing an injectable-containing SCR with a bedaquiline-containing SCR is cost-effective, offering a cost-saving alternative with improved patient outcomes for MDR-TB.

Genotype®MTBDRplus and Xpert®MTB/RIF in the diagnosis of tuberculosis and resistant tuberculosis: cost analysis in a tertiary referral hospital.

INTRODUCTION: The present study sought to assess the mean and activity based cost (ABC) of the laboratory diagnosis for tuberculosis through the application of conventional and molecular techniques-Xpert®MTB/RIF and Genotype®MTBDRplus-in a tertiary referral hospital in Brazil. METHODS: The mean cost and ABC formed the basis for the cost analysis of the TB laboratory diagnosis. RESULTS: The mean cost and ABC were US$ 4.00 and US$ 3.24, respectively, for a bacilloscopy; US$ 6.73 and US$ 5.27 for a Lowenstein-Jensen (LJ) culture; US$ 105.42 and US$ 76.56 for a drug sensitivity test (DST)-proportions method (PM) in LJ; US$ 148.45 and US$ 136.80 for a DST-BACTECTM MGITTM 960 system; US$ 11.53 and US$ 9.89 for an Xpert®MTB/RIF; and US$ 84.21 and US$ 48.38 for a Genotype®MTBDRplus. CONCLUSIONS: The mean cost and ABC proved to be good decision-making parameters in the diagnosis of TB and MDR-TB. The effective implementation of algorithms will depend on the conditions at each location.

Genotype®MTBDRplus and Xpert®MTB/RIF in the diagnosis of tuberculosis and resistant tuberculosis: cost analysis in a tertiary referral hospital

Abstract INTRODUCTION: The present study sought to assess the mean and activity based cost (ABC) of the laboratory diagnosis for tuberculosis through the application of conventional and molecular techniques-Xpert®MTB/RIF and Genotype®MTBDRplus-in a tertiary referral hospital in Brazil. METHODS: The mean cost and ABC formed the basis for the cost analysis of the TB laboratory diagnosis. RESULTS: The mean cost and ABC were US$ 4.00 and US$ 3.24, respectively, for a bacilloscopy; US$ 6.73 and US$ 5.27 for a Lowenstein-Jensen (LJ) culture; US$ 105.42 and US$ 76.56 for a drug sensitivity test (DST)-proportions method (PM) in LJ; US$ 148.45 and US$ 136.80 for a DST-BACTECTM MGITTM 960 system; US$ 11.53 and US$ 9.89 for an Xpert®MTB/RIF; and US$ 84.21 and US$ 48.38 for a Genotype®MTBDRplus. CONCLUSIONS: The mean cost and ABC proved to be good decision-making parameters in the diagnosis of TB and MDR-TB. The effective implementation of algorithms will depend on the conditions at each location.