Centre for Health Economics Research & Modelling Infectious Diseases, Vaccine & Infectious Disease Institute, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, Antwerp, Belgium.
Swiss Tropical and Public Health Institute, Socinstrasse 57, Basel, Switzerland.
BMC Med. 2020 Apr 6;18(1):82. doi: 10.1186/s12916-020-01537-6.
Respiratory syncytial virus (RSV) frequently causes acute lower respiratory infection in children under 5, representing a high burden in Gavi-eligible countries (mostly low-income and lower-middle-income). Since multiple RSV interventions, including vaccines and monoclonal antibody (mAb) candidates, are under development, we aim to evaluate the key drivers of the cost-effectiveness of maternal vaccination and infant mAb for 72 Gavi countries.
A static Multi-Country Model Application for RSV Cost-Effectiveness poLicy (MCMARCEL) was developed to follow RSV-related events monthly from birth until 5 years of age. MCMARCEL was parameterised using country- and age-specific demographic, epidemiological, and cost data. The interventions' level and duration of effectiveness were guided by the World Health Organization's preferred product characteristics and other literature. Maternal vaccination and mAb were assumed to require single-dose administration at prices assumed to align with other Gavi-subsidised technologies. The effectiveness and the prices of the interventions were simultaneously varied in extensive scenario analyses. Disability-adjusted life years (DALYs) were the primary health outcomes for cost-effectiveness, integrated with probabilistic sensitivity analyses and Expected Value of Partially Perfect Information analysis.
The RSV-associated disease burden among children in these 72 countries is estimated at an average of 20.8 million cases, 1.8 million hospital admissions, 40 thousand deaths, 1.2 million discounted DALYs, and US$611 million discounted direct costs. Strategy 'mAb' is more effective due to its assumed longer duration of protection versus maternal vaccination, but it was also assumed to be more expensive. Given all parameterised uncertainty, the optimal strategy of choice tends to change for increasing willingness to pay (WTP) values per DALY averted from the current situation to maternal vaccination (at WTP > US$1000) to mAB (at WTP > US$3500). The age-specific proportions of cases that are hospitalised and/or die cause most of the uncertainty in the choice of optimal strategy. Results are broadly similar across countries.
Both the maternal and mAb strategies need to be competitively priced to be judged as relatively cost-effective. Information on the level and duration of protection is crucial, but also more and better disease burden evidence-especially on RSV-attributable hospitalisation and death rates-is needed to support policy choices when novel RSV products become available.
呼吸道合胞病毒(RSV)经常导致 5 岁以下儿童急性下呼吸道感染,在符合 Gavi 资格的国家(主要是低收入和中低收入国家)造成了沉重负担。由于包括疫苗和单克隆抗体(mAb)候选药物在内的多种 RSV 干预措施正在开发中,我们旨在评估母体疫苗接种和婴儿 mAb 对 72 个 Gavi 国家成本效益的关键驱动因素。
开发了静态多国家 RSV 成本效益政策应用模型(MCMARCEL),以每月一次的方式从出生到 5 岁的时间跟踪与 RSV 相关的事件。MCMARCEL 是使用国家和年龄特异性人口统计学、流行病学和成本数据进行参数化的。干预措施的有效性水平和持续时间以世界卫生组织的首选产品特征和其他文献为指导。假设母体疫苗接种和 mAb 需要以与其他 Gavi 资助技术相匹配的价格进行单次给药。在广泛的情景分析中,同时改变干预措施的有效性和价格。残疾调整生命年(DALY)是成本效益的主要健康结果,与概率敏感性分析和部分完美信息分析的预期价值相结合。
这些 72 个国家儿童的 RSV 相关疾病负担估计平均为 2080 万例病例、180 万例住院治疗、4 万例死亡、120 万残疾调整生命年(DALY)和 6.11 亿美元贴现直接成本。与母体疫苗接种相比,由于假设的保护持续时间更长,“mAb”策略更有效,但也假设更昂贵。考虑到所有参数化的不确定性,随着从当前情况到母体疫苗接种(在 WTP>1000 美元/每 DALY)到 mAB(在 WTP>3500 美元/每 DALY)的每 DALY 避免成本的意愿支付(WTP)值的增加,最佳策略的选择往往会发生变化。导致最优策略选择不确定性的主要因素是住院和/或死亡的病例比例。各国的结果大致相似。
母体和 mAb 策略都需要具有竞争力的价格,才能被认为具有相对成本效益。关于保护水平和持续时间的信息至关重要,但在新型 RSV 产品上市时,还需要更多和更好的疾病负担证据,特别是关于 RSV 引起的住院和死亡率的证据,以支持政策选择。