Patient and provider costs of the new BPaL regimen for drug-resistant tuberculosis treatment in South Africa: A cost-effectiveness analysis

BACKGROUND: Drug-resistant (DR) tuberculosis (TB) is typically characterized by resistance to a single or combination of first- and/or second-line anti-TB agents and commonly includes rifampicin-resistant (RR) -TB, multidrug-resistant (MDR) -TB, pre-extensively drug-resistant (pre-XDR) -TB and XDR-TB. Historically, all variations of DR-TB required treatment with second-line drugs which are less effective and more toxic than first-line options, have a longer treatment duration and are more expensive to both patients and providers. The World Health Organization (WHO) now recommends a new second-line 3-drug 6-month all-oral regimen consisting of bedaquiline, pretomanid, and linezolid referred to as BPaL. We estimate patient and provider costs of DR-TB treatment with BPaL compared to the current standard of care in South Africa. METHODS AND FINDINGS: In coordination with South Africa's BPaL clinical access programme (CAP) we conducted an economic evaluation of A) patient costs through a cross-sectional patient cost survey and B) provider costs through a bottom-up costing analysis consisting of a retrospective medical record review (patient resource-use) and top-down financial record review (fixed/shared costs such as overhead). Across both costing perspectives, we compare costs of 1) BPaL, to current standard of care options including the 2) 9-11-month standard short oral regimen (SSOR) and 3) 18-21-month standard long oral regimen (SLOR). Eligible patients included those ≥14 years old with confirmed sputum pulmonary RR/MDR-TB, pre-XDR or XDR-TB. All costs are reported in 2022 United States Dollar (US). A total of 72 patients were enrolled and completed the patient cost survey (41. 7% on BPaL, 16. 7% on the SSOR and 41. 7% on the SLOR). Mean on-treatment patient costs were lowest among those on BPaL (56. 6) and increased four-fold among those on the SSOR (228. 1) and SLOR (224. 7). Direct medical patient costs were negligible across all treatment regimens, while direct non-medical patient and guardian costs for travel, food and nutritional supplementation accounted for the largest proportion of total costs (54. 6, 227. 8 and 224. 3 for BPaL, the SSOR and SLOR respectively). In assessing provider costs, a total of 112 medical records were reviewed (37. 5%, 41. 1% and 21. 4% on BPaL, the SSOR and SLOR respectively). Total provider costs for producing a favorable treatment outcome (cured/completed treatment) were similar among those on BPaL (4, 948. 7 per patient) and the SSOR (4, 905. 6 per patient) with costs increasing substantially among those on the SLOR (8, 919. 9 per patient). Based on incremental cost-effectiveness ratios (ICERs), at even the lowest willingness to pay (WTP) threshold, treatment with the new BPaL regimen was more cost-effective than current standard of care treatment options (ICER: 311. 4 < WTP: 3, 341). CONCLUSIONS: When using the newly recommended BPaL regimen, cost to patients decreased by 75% compared to current standard of care treatment options in South Africa. Due in part to higher resource-use within the BPaL CAP offsetting the shorter treatment duration, cost of treatment provision through BPaL and the 9-11-month SSOR were similar. However, when considering cost and treatment outcomes, BPaL was more cost-effective than other standard of care regimens currently available for DR-TB in South Africa.