# Initial thoughts on malaria vaccine approval

The World Health Organization (WHO) recently recommended the widespread use of the malaria vaccine RTS,S/AS011We’ll use “RTS,S” as shorthand in this post. for children. It provides an additional, effective tool to fight malaria. This is great news!

We’ve been following this vaccine’s development for years and, in the last few months, have been speaking with organizations involved in its development and potential wider rollout.

Our work on RTS,S (and other malaria vaccines) is ongoing, and we might significantly update our views in the near future. But because we’ve been following its progress, we’re sharing some initial thoughts.

## In brief

• This vaccine is a promising addition to the set of tools available to fight malaria, but it’s not a panacea. We expect long-lasting insecticide-treated nets (LLINs) and seasonal malaria chemoprevention (SMC)—interventions provided through two of the programs we currently recommend—to continue to be important in the fight against malaria in the near term.2
• The parts of the WHO news release that we have bolded indicate that RTS,S should be used with existing malaria control interventions:
• “WHO Director-General Dr Tedros Adhanom Ghebreyesus [said,] ‘Using this vaccine on top of existing tools to prevent malaria could save tens of thousands of young lives each year.'”
• “WHO recommends that in the context of comprehensive malaria control the RTS,S/AS01 malaria vaccine be used for the prevention of P. falciparum malaria in children living in regions with moderate to high transmission as defined by WHO.”
• Similarly, Gavi’s news release states: “The vaccine will be a complementary malaria control tool to be added to the core package of WHO-recommended measures for malaria prevention. This includes the routine use of insecticide-treated bed nets, indoor spraying with insecticides, malaria chemoprevention strategies, and the timely use of malaria testing and treatment.”

• Simple comparisons of potential costs and effectiveness of RTS,S and SMC suggest that SMC could be more cost-effective (see below). But there are lots of unknowns about RTS,S that could change that.
• We are actively looking into whether there are promising funding opportunities in this space.
• So:
• For the time being, this news does not affect our recommendations to donors. We do not know of a current option for individuals to donate to scale up RTS,S. We continue to believe that LLIN distribution and SMC are highly cost-effective, and some of the best giving opportunities available for donors who want to prevent deaths from malaria today.
• We aren’t sure whether we’ll recommend funding of RTS,S in the future. That will depend on how cost-effective we estimate particular opportunities to be, which depends on the answers to the open questions listed below.

• Cost.​​ SMC costs about $7 per child fully covered per year,3This is the average estimated cost per child in the four countries where we currently recommend funding for SMC. See here in the current version of our cost-effectiveness analysis. so it would cost$28 to cover a child for four years. Costs for RTS,S are far less certain. Two studies that seem like reasonable starting points suggest costs per child of between $304See Sauboin et al. 2019, Table 2. The average cost across five countries for administering doses to children is ~$30. and $40.5See Winskill et al. 2017, Table 1, row “RTS,S.” • Effectiveness. Our rough estimate is that RTS,S would avert 36%6“Children were followed up for a median of 48 months (IQR 39–50) and young infants for 38 months (34–41) after dose 1. From month 0 until study end, compared with 9585 episodes of clinical malaria that met the primary case definition in children in the C3C [control] group, 6616 episodes occurred in the R3R [4 doses of RTS,S/AS01] group (VE 36·3%, 95% CI 31·8–40·5)…” RTS,S Clinical Trials Partnership 2015, “Findings” section of malaria cases over four years.7We use four years because that’s the time period used in the trials (see the quote in footnote 6 above), and it presents an easy comparison with SMC and other child health programs we support that have annual costs. By way of comparison, we estimate that annual SMC would avert 53% of cases over the same time period.8In particular, we assume SMC averts 75% of cases during peak transmission season and that 70% of malaria deaths occur during this period. Because we also assume a 1:1 ratio between cases and deaths averted, this is equivalent to averting ~53% of cases in a year. Taken at face value, these figures could imply that SMC is 1.5 to 2 times more cost-effective than RTS,S. But these naive comparisons aren’t conclusive.9These comparisons are not equivalent to our full cost-effectiveness analyses (CEAs). In complete CEAs, we use country-specific figures instead of averages, try to adjust for internal and external validity, and try to account for the counterfactual funding decisions of all contributors and the value of their funds (which we call leverage and funging adjustments). These adjustments can make decision-relevant differences to our funding recommendations. ## Open questions There are many open questions whose answers could have a big impact on the cost-effectiveness of a particular opportunity to support RTS,S. Some questions that seem important to us are: • What will it cost to deliver RTS,S? The cost estimates we’ve seen vary widely, and we expect delivery costs to vary from country to country. • Will RTS,S be delivered via routine immunization systems or targeted immediately before seasonal malaria transmission? Routine immunization systems might be less costly, but seasonal delivery could increase effectiveness. • How will RTS,S be layered with other malaria interventions in new implementation areas? We haven’t thoroughly investigated how the presence of LLINs and SMC in addition to RTS,S affect its efficacy in trial contexts, and we’re unsure how layering would affect the cost-effectiveness of delivering RTS,S in new areas. ## In conclusion We’re excited to have another effective tool in the fight against malaria! We’re working to understand whether there are cost-effective opportunities to support wider-scale implementation of RTS,S. Our research team is also keeping an eye on other potential malaria vaccines and malaria control strategies more generally. In the meantime, we anticipate continuing to recommend funding for LLINs and SMC. Notes ↑1 We’ll use “RTS,S” as shorthand in this post. The parts of the WHO news release that we have bolded indicate that RTS,S should be used with existing malaria control interventions: “WHO Director-General Dr Tedros Adhanom Ghebreyesus [said,] ‘Using this vaccine on top of existing tools to prevent malaria could save tens of thousands of young lives each year.'” “WHO recommends that in the context of comprehensive malaria control the RTS,S/AS01 malaria vaccine be used for the prevention of P. falciparum malaria in children living in regions with moderate to high transmission as defined by WHO.” Similarly, Gavi’s news release states: “The vaccine will be a complementary malaria control tool to be added to the core package of WHO-recommended measures for malaria prevention. This includes the routine use of insecticide-treated bed nets, indoor spraying with insecticides, malaria chemoprevention strategies, and the timely use of malaria testing and treatment.” This is the average estimated cost per child in the four countries where we currently recommend funding for SMC. See here in the current version of our cost-effectiveness analysis. See Sauboin et al. 2019, Table 2. The average cost across five countries for administering doses to children is ~$30. See Winskill et al. 2017, Table 1, row “RTS,S.” “Children were followed up for a median of 48 months (IQR 39–50) and young infants for 38 months (34–41) after dose 1. From month 0 until study end, compared with 9585 episodes of clinical malaria that met the primary case definition in children in the C3C [control] group, 6616 episodes occurred in the R3R [4 doses of RTS,S/AS01] group (VE 36·3%, 95% CI 31·8–40·5)…” RTS,S Clinical Trials Partnership 2015, “Findings” section We use four years because that’s the time period used in the trials (see the quote in footnote 6 above), and it presents an easy comparison with SMC and other child health programs we support that have annual costs. In particular, we assume SMC averts 75% of cases during peak transmission season and that 70% of malaria deaths occur during this period. Because we also assume a 1:1 ratio between cases and deaths averted, this is equivalent to averting ~53% of cases in a year. These comparisons are not equivalent to our full cost-effectiveness analyses (CEAs). In complete CEAs, we use country-specific figures instead of averages, try to adjust for internal and external validity, and try to account for the counterfactual funding decisions of all contributors and the value of their funds (which we call leverage and funging adjustments). These adjustments can make decision-relevant differences to our funding recommendations.

• Thecommexokid on October 9, 2021 at 2:17 am said:

Is it possible that in the future, the widespread distribution of this vaccine could decrease the cost-effectiveness of LLINs and SMC by a noticeable margin? (Naively, I’m imagining e.g. 1000 bednets save fewer counterfactual lives when lots of their recipients are also vaccinated, but I could also imagine mitigating factors that could perhaps negate that effect.)

• Julie (GiveWell) on October 12, 2021 at 11:41 am said:

Hi Thecommexokid,

Yes, it is possible that the widespread rollout of a malaria vaccine could decrease the cost-effectiveness of LLINs and SMC in the future.

As we get more information about how an RTS,S rollout might proceed, we would expect to consider how these interventions could interact with one another and what that means for their cost-effectiveness. In the near term (before it is clear how an RTS,S rollout would occur), we’re planning to incorporate lower expected malaria rates in some locations in our SMC cost-effectiveness analysis due to the expectation of higher LLIN coverage in the future than the past. We’re doing the same where we’re funding LLINs to be delivered in areas where SMC is expanding.

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