Initial thoughts on malaria vaccine approval

GiveWell

Initial thoughts on malaria vaccine approval

GiveWell

2 min readOct 8, 2021

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freedomandutility

Apologies if I’ve missed this in the post, but I don’t think it discusses a potential decrease in the marginal value of LLINs and SMC due to RTS,S, instead focusing on a comparison between LLIN and SMC vs RTS,S.

Do GiveWell intend to explore the effect on marginal value at a later point in time / in more detail? It seems plausible to me that despite LLIN and SMC being more cost effective than RTS,S, a decrease in their marginal value could mean that donors would prefer to donate to other GiveWell top charities over AMF.

CatherineHollander

Thanks for your question! I work at GiveWell.

The initial calculation we shared in the blog post is a simple one, intended to give a rough sense of the cost-effectiveness of each opportunity given the current limited investigation we’ve done of RTS,S. You're correct that it doesn't account for how RTS,S might interact with LLINs and SMC and the funding needs for those interventions; it's possible that interventions will be layered atop one another, rather than an "either/or" situation.

We expect we would estimate the marginal value if we were deeply investigating an opportunity to fund RTS,S or if it seemed likely that the rollout of RTS,S was going to impact the cost-effectiveness of LLINs or SMC. Going forward, we're also incorporating 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.

freedomandutility

Thanks for the reply, that answers my question perfectly :)

Comments

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]

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.

Simple estimates of cost and effectiveness

Cost. SMC costs about $7 per child fully covered per year,^[3] 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 $30^[4] and $40.^[5]

Effectiveness. Our rough estimate is that RTS,S would avert 36%^[6] of malaria cases over four years.^[7] By way of comparison, we estimate that annual SMC would avert 53% of cases over the same time period.^[8] Taken at face value, these figures could imply that SMC is 1.5 to 2 times more cost-effective than RTS,S. But these naïve comparisons aren’t conclusive.^[9]

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.

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. ↩︎