Thanks SoGive for the post! We wanted to share some of GiveWell’s current thinking around malaria vaccines in case it’s helpful. We also wrote a report on RTS,S in 2022 here and have recommended a couple grants for vaccine rollout and research.
On a cost-per-person-reached basis, we agree ITNs and SMC are superior to either of the two WHO-approved malaria vaccines. However, we think there’s less of a differential in cost-effectiveness than this post implies, for a number of reasons:
The difference in all-in delivery costs is probably less substantial: We think it roughly costs $6 to deliver an ITN to a household[1], and roughly $7 to provide a child with a full course of SMC. (See also impact metrics here). We estimate the total costs for fully immunizing a child range from $23-$43, depending on the choice of vaccine.[2]
We would approach the comparison for the reduction in malaria incidence differently: Using the effect size from the Pryce et al meta-analysis for ITNs (which consists mostly of trials that lasted one year) and comparing it with the incidence reduction observed after 12 months in RTS,S/R21 trials is not as straightforward as is seems:
The reduction found in Pryce et al has to be considerably updated in light of recent developments, notably new types of nets (PBO, dual active ingredient) and increased insecticide resistance.
The RTS,S Clinical Partnership trial includes results from a follow-up four years after the start of the intervention and finds a reduction in clinical malaria from 28% (3 dose group) to 36% (4-dose group) at endpoint. Our malaria team recommends these results rather than the earlier snapshots, as they are less noisy.
Our best guess is that R21 and RTS,S are similarly effective at preventing malaria. Available evidence suggests that short-term effectiveness is broadly similar between RTS,S and R21. No data has been published for the impact of R21 on malaria incidence over the long run (>20 months after the first dose). Because the short-term outcomes are broadly similar, and both vaccines employ the same mechanism to induce an immune response in the vaccinated person[3], our best guess is that four doses of R21 probably offer similar levels of protection as four doses of RTS,S over the long run.
We believe the apparent difference cited in the post is most likely due to the different setup between trials (Datoo 2022, unlike the RTS,S trial, was carried out in a seasonal setting). Note also that results from a phase III trial on R21 are now available (Datoo 2023 (preprint)).
The duration of protection differs: Due to factors such as attrition and physical decay, we currently estimate an ITN to provide between 1.2 − 2.0 years of effective protection. As indicated above, we estimate that malaria vaccines offer around 30% protection over four years.
There are, of course, additional factors that need to be taken into account to get a full picture (for example, what coverage levels are achievable for each intervention?). However, our current best guess is that even with those included, nets (and SMC) will be more cost-effective than malaria vaccines—just not by an order of magnitude.
The price per dose of RTS,S was $9.30 in 2022, and estimates for R21 indicate a price per dose of $3.90. We expect that, on average, 70% of children who received three doses will also get a booster shot, which implies vaccine costs per child between $14-$37. The best costing estimates for the delivery of the doses suggest around $9 per child.
“The leading malaria vaccine in development is the circumsporozoite protein (CSP)-based particle vaccine, RTS,S, which targets the pre-erythrocytic stage of Plasmodium falciparum infection. It induces modest levels of protective efficacy, thought to be mediated primarily by CSP-specific antibodies. We aimed to enhance vaccine efficacy by generating a more immunogenic CSP-based particle vaccine and therefore developed a next-generation RTS,S-like vaccine, called R21. The major improvement is that in contrast to RTS,S, R21 particles are formed from a single CSP-hepatitis B surface antigen (HBsAg) fusion protein, and this leads to a vaccine composed of a much higher proportion of CSP than in RTS,S.” Collins et al. 2017, “Abstract”
Thanks very much for this, much appreciated. Your best guess of vaccines being less cost-effective than bednets and SMC, but not by an order of magnitude, sounds sensible.
Thanks SoGive for the post! We wanted to share some of GiveWell’s current thinking around malaria vaccines in case it’s helpful. We also wrote a report on RTS,S in 2022 here and have recommended a couple grants for vaccine rollout and research.
On a cost-per-person-reached basis, we agree ITNs and SMC are superior to either of the two WHO-approved malaria vaccines. However, we think there’s less of a differential in cost-effectiveness than this post implies, for a number of reasons:
The difference in all-in delivery costs is probably less substantial: We think it roughly costs $6 to deliver an ITN to a household[1], and roughly $7 to provide a child with a full course of SMC. (See also impact metrics here). We estimate the total costs for fully immunizing a child range from $23-$43, depending on the choice of vaccine.[2]
We would approach the comparison for the reduction in malaria incidence differently: Using the effect size from the Pryce et al meta-analysis for ITNs (which consists mostly of trials that lasted one year) and comparing it with the incidence reduction observed after 12 months in RTS,S/R21 trials is not as straightforward as is seems:
The reduction found in Pryce et al has to be considerably updated in light of recent developments, notably new types of nets (PBO, dual active ingredient) and increased insecticide resistance.
The RTS,S Clinical Partnership trial includes results from a follow-up four years after the start of the intervention and finds a reduction in clinical malaria from 28% (3 dose group) to 36% (4-dose group) at endpoint. Our malaria team recommends these results rather than the earlier snapshots, as they are less noisy.
Our best guess is that R21 and RTS,S are similarly effective at preventing malaria. Available evidence suggests that short-term effectiveness is broadly similar between RTS,S and R21. No data has been published for the impact of R21 on malaria incidence over the long run (>20 months after the first dose). Because the short-term outcomes are broadly similar, and both vaccines employ the same mechanism to induce an immune response in the vaccinated person[3], our best guess is that four doses of R21 probably offer similar levels of protection as four doses of RTS,S over the long run.
We believe the apparent difference cited in the post is most likely due to the different setup between trials (Datoo 2022, unlike the RTS,S trial, was carried out in a seasonal setting). Note also that results from a phase III trial on R21 are now available (Datoo 2023 (preprint)).
The duration of protection differs: Due to factors such as attrition and physical decay, we currently estimate an ITN to provide between 1.2 − 2.0 years of effective protection. As indicated above, we estimate that malaria vaccines offer around 30% protection over four years.
There are, of course, additional factors that need to be taken into account to get a full picture (for example, what coverage levels are achievable for each intervention?). However, our current best guess is that even with those included, nets (and SMC) will be more cost-effective than malaria vaccines—just not by an order of magnitude.
Costs per child reached are much higher, roughly $15-$26.
The price per dose of RTS,S was $9.30 in 2022, and estimates for R21 indicate a price per dose of $3.90. We expect that, on average, 70% of children who received three doses will also get a booster shot, which implies vaccine costs per child between $14-$37. The best costing estimates for the delivery of the doses suggest around $9 per child.
“The leading malaria vaccine in development is the circumsporozoite protein (CSP)-based particle vaccine, RTS,S, which targets the pre-erythrocytic stage of Plasmodium falciparum infection. It induces modest levels of protective efficacy, thought to be mediated primarily by CSP-specific antibodies. We aimed to enhance vaccine efficacy by generating a more immunogenic CSP-based particle vaccine and therefore developed a next-generation RTS,S-like vaccine, called R21. The major improvement is that in contrast to RTS,S, R21 particles are formed from a single CSP-hepatitis B surface antigen (HBsAg) fusion protein, and this leads to a vaccine composed of a much higher proportion of CSP than in RTS,S.” Collins et al. 2017, “Abstract”
Thanks very much for this, much appreciated. Your best guess of vaccines being less cost-effective than bednets and SMC, but not by an order of magnitude, sounds sensible.