Pharmaceutical cost dynamics for the treatment of rifampicin-resistant tuberculosis in children and adolescents in South Africa, India, and the Philippines

Rifampicin-resistant (RR) tuberculosis (TB) in children is a major global health concern but is often neglected in economics research. Accurate cost estimations across the spectrum of paediatric RR-TB treatment regimens are critical inputs for prioritisation and budgeting decisions, and an existing knowledge gap at local and international levels. This normative cost analysis was nested in a Phase I/II pharmacokinetics, safety, tolerability, and acceptability trial of TB medications in children in South Africa, the Philippines and India. It assessed the pharmaceutical costs of 36 childhood RR-TB regimens using combinations from 16 different medicines in 34 oral formulations (adult and child-friendly) in 11 weight bands in children <15 years of age. The analysis used local and Global Drug Facility pricing, and local and international guideline recommendations, including adaptions of BPaL and BPaLM regimens in adults. Costs varied significantly between regimen length, age/weight banding, severity of disease, presence of fluroquinolone resistance, and different country guideline recommendations. WHO recommended regimen costs ranged 12-fold: from US$232 per course (short regimen in non-severe disease) to US$2,761 (long regimen in severe, fluroquinolone-resistant disease). Regimen treating fluoroquinolone-resistant infection cost US$1,090 more than comparable WHO-recommended regimen. Providing child-friendly medicine formulations in <5-year-olds across all WHO-recommended regimens is expected to cost an additional $380 (range $212-$563) per child but is expected to have wider benefits including palatability, acceptability, adherence, tolerability, and dose accuracy. There were substantial differences in regimen affordability between countries when adjusted for purchasing power and domestic spending on health. Appropriate, effective, and affordable treatment options are an important component of the fight against childhood RR-TB. A comprehensive understanding of the cost and affordability dynamics of treatment options will enable national TB programs and global collaborations to make the best use of limited healthcare resources for the care of children with RR-TB.

儿童利福平耐药（RR）结核病（TB）是全球重大健康关切，但在经济学研究中常被忽视。儿童利福平耐药结核病（RR-TB）全治疗方案谱系的准确成本估算，是优先级设定与预算决策的关键依据，同时也是地方及国际层面现存的知识空白。本规范性成本分析嵌套于南非、菲律宾及印度开展的一项儿童结核病药物I/II期药代动力学、安全性、耐受性及可接受性试验中。该分析评估了针对15岁以下儿童的36种RR-TB治疗方案的药品成本，这些方案由16种不同药物的34种口服剂型（成人及儿童友好型）组合而成，覆盖11个体重分组。分析采用了地方及全球药品基金（Global Drug Facility）定价，以及地方与国际指南建议，包括成人BPaL及BPaLM方案的儿童适应性调整。成本因治疗方案时长、年龄/体重分组、疾病严重程度、氟喹诺酮耐药性存在与否及不同国家指南建议而显著差异。世界卫生组织（WHO）推荐方案的成本跨度达12倍：单疗程费用从232美元（非重症疾病的短方案）至2761美元（重症、氟喹诺酮耐药疾病的长方案）不等。针对氟喹诺酮耐药感染的治疗方案，其成本较可比的WHO推荐方案高出1090美元。在所有WHO推荐方案中为5岁以下儿童提供儿童友好型药物剂型，预计每名儿童将额外增加380美元成本（范围212-563美元），但有望带来更广泛的益处，包括适口性、可接受性、依从性、耐受性及剂量准确性。经购买力及国内卫生支出调整后，各国治疗方案的可负担性存在显著差异。适宜、有效且可负担的治疗方案，是抗击儿童RR-TB的重要组成部分。全面理解治疗方案的成本与可负担性动态，将助力国家结核病项目及全球合作，为RR-TB儿童患者的照护优化利用有限的卫生资源。