The Lancet
Jan 23, 2016 Volume 387 Number 10016 p311-402 e9-e12
http://www.thelancet.com/journals/lancet/issue/current
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Comment
Implementation of the malaria candidate vaccine RTS,S/AS01
Brian Greenwood, Ogobara K Doumbo
Published Online: 05 November 2015
Summary
As vaccine manufacturers tackle increasingly intractable pathogens, vaccines will be developed that show efficacy, but that are less efficacious than established vaccines. Consequently, regulatory and public health authorities will be faced with difficult decisions about whether such vaccines should be recommended for implementation and, if so, under what circumstances. The RTS,S/AS01 malaria candidate vaccine provides an important example of such a challenge.

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Public health impact and cost-effectiveness of the RTS,S/AS01 malaria vaccine: a systematic comparison of predictions from four mathematical models
Melissa A Penny, Robert Verity, Caitlin A Bever, Christophe Sauboin, Katya Galactionova, Stefan Flasche, Michael T White, Edward A Wenger, Nicolas Van de Velde, Peter Pemberton-Ross, Jamie T Griffin, Thomas A Smith, Philip A Eckhoff, Farzana Muhib, Mark Jit, Azra C Ghani
367
Open Access
Summary
Background
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.
Methods
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.
Findings
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.
Interpretation
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.
Funding
PATH Malaria Vaccine Initiative; Bill & Melinda Gates Foundation; Global Good Fund; Medical Research Council; UK Department for International Development; GAVI, the Vaccine Alliance; WHO.