Public health impact and cost-effectiveness of the RTS,S/AS01 malaria vaccine: a systematic comparison of predictions from four mathematical models.
Public health impact and cost-effectiveness of the RTS,S/AS01 malaria vaccine: a systematic comparison of predictions from four mathematical models.
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DOI：
10.1016/s0140-6736(15)00725-4
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发表时间：
2016-01-23
期刊：
影响因子：
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通讯作者：
Ghani AC
中科院分区：
文献类型：
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作者：
Penny MA;Verity R;Bever CA;Sauboin C;Galactionova K;Flasche S;White MT;Wenger EA;Van de Velde N;Pemberton-Ross P;Griffin JT;Smith TA;Eckhoff PA;Muhib F;Jit M;Ghani AC
RTS，S/AS 01疟疾候选疫苗的3期试验显示，该疫苗对恶性疟原虫疟疾的有效性中等，但不足以评估死亡率终点。需要对比试验后续行动更长的时间范围和各种情况下的影响预测和成本效益估计，以便为政策建议提供信息。我们的目的是评估在非洲环境中常规使用RTS，S/AS 01疫苗的公共卫生影响和成本效益。我们比较了四种疟疾传播模型及其预测，以评估疫苗的成本效益和影响。我们使用了32个月或更长时间的随访试验数据，以参数化5-17个月组的疫苗保护。在2-10奥尔兹恶性疟原虫寄生虫患病率水平范围内，计算了15年时间范围内的病例、死亡和避免的残疾调整生命年（DIMs）估计值（PfPR 2 -10;范围3-65%）。我们考虑了两种疫苗接种方案：在6、7、5和9个月大时接种三剂疫苗（三剂方案，覆盖率为90%），在27个月大时接种第四剂疫苗（四剂方案，覆盖率为72%）。我们估计了现有疟疾干预措施的成本效益，疫苗价格为每剂2 -10美元。在PfPR 2 -10为10- 65%的地区，RTS，S/AS 01预计可避免三剂方案中的中位数93 940例（范围20 490-126 540）临床病例和394例（127-708）死亡，或四剂方案中的中位数116 480例（31 450-160 410）临床病例和484例（189-859）死亡（每100 000名完全接种儿童）。 在PfPR 2 -10为5- 10%时也预测有积极影响，但在患病率低于3%时几乎没有影响。在每剂5美元和PfPR 2 -10为10- 65%的情况下，我们估计与目前的干预措施30美元相比，（范围18-211）和80美元（44-279）每DALY避免三剂方案，分别为25美元（16-222）和87美元（48-244），四剂的时间表在低PfPR 2 -10水平下估计ICER较高。我们预测RTS，S/AS 01疫苗在广泛的环境中具有显著的公共卫生影响和高成本效益。关于执行的决定需要考虑疟疾负担水平、其他疟疾干预措施的成本效益和覆盖面、卫生优先事项、筹资以及卫生系统提供疫苗的能力。适宜卫生技术组织疟疾疫苗倡议;比尔和梅林达盖茨基金会;全球良好基金;医学研究理事会;英国国际发展部; GAVI，疫苗联盟;世卫组织。
The phase 3 trial of the RTS,S/AS01 malaria vaccine candidate showed modest efficacy of the vaccine against Plasmodium falciparum malaria, but was not powered to assess mortality endpoints. Impact projections and cost-effectiveness estimates for longer timeframes than the trial follow-up and across a range of settings are needed to inform policy recommendations. We aimed to assess the public health impact and cost-effectiveness of routine use of the RTS,S/AS01 vaccine in African settings. We compared four malaria transmission models and their predictions to assess vaccine cost-effectiveness and impact. We used trial data for follow-up of 32 months or longer to parameterise vaccine protection in the group aged 5–17 months. Estimates of cases, deaths, and disability-adjusted life-years (DALYs) averted were calculated over a 15 year time horizon for a range of levels of Plasmodium falciparum parasite prevalence in 2–10 year olds (PfPR2–10; range 3–65%). We considered two vaccine schedules: three doses at ages 6, 7·5, and 9 months (three-dose schedule, 90% coverage) and including a fourth dose at age 27 months (four-dose schedule, 72% coverage). We estimated cost-effectiveness in the presence of existing malaria interventions for vaccine prices of US$2–10 per dose. In regions with a PfPR2–10 of 10–65%, RTS,S/AS01 is predicted to avert a median of 93 940 (range 20 490–126 540) clinical cases and 394 (127–708) deaths for the three-dose schedule, or 116 480 (31 450–160 410) clinical cases and 484 (189–859) deaths for the four-dose schedule, per 100 000 fully vaccinated children. A positive impact is also predicted at a PfPR2–10 of 5–10%, but there is little impact at a prevalence of lower than 3%. At $5 per dose and a PfPR2–10 of 10–65%, we estimated a median incremental cost-effectiveness ratio compared with current interventions of $30 (range 18–211) per clinical case averted and $80 (44–279) per DALY averted for the three-dose schedule, and of $25 (16–222) and $87 (48–244), respectively, for the four-dose schedule. Higher ICERs were estimated at low PfPR2–10 levels. We predict a significant public health impact and high cost-effectiveness of the RTS,S/AS01 vaccine across a wide range of settings. Decisions about implementation will need to consider levels of malaria burden, the cost-effectiveness and coverage of other malaria interventions, health priorities, financing, and the capacity of the health system to deliver the vaccine. PATH Malaria Vaccine Initiative; Bill & Melinda Gates Foundation; Global Good Fund; Medical Research Council; UK Department for International Development; GAVI, the Vaccine Alliance; WHO.