Incremental Cost Effectiveness of Bedaquiline for the Treatment of Rifampicin-Resistant Tuberculosis in South Africa: Model-Based Analysis
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Nearly 20,000 people were diagnosed with multi-drug and rifampicin-resistant tuberculosis (MDR/RR-TB) in South Africa in 2015, yet only one-half of the patients who start treatment are expected to have a successful outcome. There is increasing evidence of the effectiveness and safety of new drug regimens containing bedaquiline for MDR/RR-TB; however, whether they are affordable for high-burden, limited-resource settings is uncertain.
Our objective was to determine the incremental cost effectiveness of a bedaquiline-based regimen for MDR/RR-TB treatment in South Africa compared with the standard kanamycin-based regimen.
We established a Markov model for ambulatory treatment of MDR/RR-TB in a high-HIV prevalence setting, parameterized using clinical outcomes from the South African National TB Programme (SA NTP) before (2012–2014) and after (2015–2016) bedaquiline roll-out. The effectiveness of treatment was evaluated in disability-adjusted life-years (DALYs). Ingredient costs from the provider’s perspective were collected in 2016 South African Rand and converted to $US, including bedaquiline at $US675.23 per 6-month treatment course. Culture conversion rates were derived from the phase IIb trial of bedaquiline, and disability adjustments were adapted from published literature. Costs and effectiveness were discounted at 3%.
For non-bedaquiline regimens, the total expected cost over the 10-year time horizon for a patient with MDR/RR-TB was $US4439 with disability-adjusted survival of 5.1 years. Replacing capreomycin with bedaquiline in patients who failed MDR/RR-TB treatment and required treatment for extensively drug-resistant (XDR-TB) resulted in cost savings ($US4356; 1.8% less) and similar effectiveness (0.02 DALYs averted). As a result, the standard regimen (no bedaquiline) was dominated. Replacing kanamycin with bedaquiline to provide all patients with MDR/RR-TB access to bedaquiline cost $US4647 (4.3% more) and averted 0.17 DALYs compared with the no bedaquiline regimen. The incremental cost-effectiveness ratio was $US1242/DALY averted.
Markov modelling indicates providing bedaquiline for all patients with MDR/RR-TB could increase the 24-month treatment success rate in South Africa from 56.3% using the current regimen to 60.6%, at a cost $US2.6 million over a 10-year horizon, less than 1% of the estimated $US425 million SA NTP annual budget.
This work would not have been possible without the dedication of the clinicians and specialists of the Bedaquiline Clinical Access Programme Clinical Advisory Committee. Special thanks also to each of the RR TB units rolling out bedaquiline and to all of the patients at these units. This analysis is of work led by the South African National Department of Health and collected through the SA NTP, with thanks to Y Pillay, LD Mametja, S Dlamini, and P Richards. Thank you to R Laubscher from the Medical Research Council for matching to the vital statistics register.
KS conceptualized the analysis, built and parameterized the cost-effectiveness model, drafted the manuscript and incorporated all author comments and revisions. CF and ES advised on the analysis design and methods, reviewed the analysis results, and reviewed and critically revised the manuscript. FC and NN assisted in providing access to the data, supported interpretation and understanding of the model parameters, and reviewed the manuscript. All authors approved the manuscript submitted for publication.
Compliance with Ethical Standards
This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.
Conflict of Interest
KS, CF, FC, NN and ES have no conflicts of interest. NN is an official at the South African National Department of Health and therefore has responsibility for establishing and implementing national treatment guidelines for drug-resistant TB.
All procedures performed in the study involving human participants (i.e. analysis of transition probabilities from the EDRweb case register) were in accordance with the 1964 Helsinki declaration and its later amendments and the ethical standards the Human Research Ethics Committee of the University of Cape Town (#490/2015, July 2015) and the Human Research Ethics Committee of the University of Witwatersrand (#M150340, March 2015). For this type of secondary retrospective analysis of routinely collected data, formal consent is not required. A data-sharing agreement was submitted to the Research Information Monitoring, Evaluation and Surveillance Directorate within the South African National Department of Health for access to the EDRweb. Methods and results are presented according to the CHEERS checklist for economic evaluations .
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