How cost-effective is the new R21 vaccine compared to existing malaria interventions?

Karam Elabd and Ryan Duncombe, PhD

Summary

This post evaluates the cost-effectiveness of two malaria vaccines, RTS,S and R21, compared to existing malaria interventions: insecticide-treated bed nets (ITNs), seasonal malaria chemoprevention (SMC, where antimalarial drugs that prevent infection are given to healthy children during malaria season), and mosquito control (vector control). We analyzed available research on these methods that quantified cost-effectiveness using dollars per disability-adjusted life-year averted (DALYs) and converted the findings to 2024 US dollars to allow for a rough comparison between studies and interventions. 

Our findings show that the R21 vaccine is nearly as cost-effective as bed nets, the most efficient intervention ($39/DALY for R21 vs. $38/DALY for bed nets). The RTS,S vaccine is more expensive at $129/DALY, but is still cheaper than mosquito control ($296/DALY), the least cost-effective strategy. Despite some uncertainties in this analysis, the available evidence suggests that the R21 vaccine is competitive with the best available malaria interventions. Given the current funding and manufacturing gap for the R21 vaccine, accelerating the funding and distribution of this vaccine could be a cost-effective method of saving hundreds of thousands of lives.

Background and justification

Malaria remains a significant global health issue, with an estimated 249 million cases and 608,000 deaths worldwide in 2022. Sub-Saharan Africa in particular experiences about 95% of malaria cases and deaths. Given that many African countries are classified as low- and middle-income countries (LMICs), affordability is a crucial factor in the fight against malaria. The WHO recommends several malaria prevention measures, but they make clear that none of these disease control interventions are sufficient to serve as a stand-alone intervention. Despite these various cost-effective prevention methods, progress in reducing Africa’s malaria burden has stalled since 2015 due to factors such as insecticide and drug resistance, funding gaps, health system challenges, political instability, and rapid population growth, among others. The new malaria vaccines present an extraordinary opportunity to make progress in the fight against malaria and save potentially hundreds of thousands of lives in the next couple of years.

Recent modeling studies have estimated the cost-effectiveness of the R21 malaria vaccine in different scenarios, and previous work has covered the RTS,S and conventional malaria interventions, but to our knowledge, no public research has yet compared the cost-effectiveness of the R21 malaria vaccine with other malaria interventions.

Importance of the R21 Vaccine Rollout

The introduction of the R21 vaccine represents a pivotal moment in the fight against malaria. Here’s why the focus on R21 is critical:

1. Production and Delivery Gap: By the end of 2025, around 200 million doses of R21 could be produced, sufficient to vaccinate 50 million children. However, current delivery plans only account for ~25 million doses. Bridging this gap could save approximately 250,000 lives, given that every 1 million vaccinations could save more than 6,000 lives. This gap contrasts with the RTS,S vaccine, which is being delivered near its maximum production capacity for the next two years (~7 million doses per year), underscoring the potential of R21 to scale up the global malaria vaccination efforts dramatically.
2. Cost-Effectiveness: At $3.90/dose (R21) vs. ~$10.90/dose (RTS,S) and with similar or better efficacy than the RTS,S vaccine, R21 represents a more affordable and practical option for widespread immunization in African nations. 
3. Saturation of interventions: SMC, ITNs, and vector control have all been used for years. While advancements in technology and distribution continue to improve their effectiveness, the benefits of additional investments in each may be diminishing due to factors such as insecticide resistance and high existing coverage levels. This suggests that these methods are nearing their maximum potential in the fight against malaria.  Vaccines, however, are a newly introduced intervention with significant unrealized potential.

Methods

We reviewed existing studies on the cost-effectiveness of malaria interventions, adjusting all financial data to 2024 USD for consistency. Our analysis focused on cost per Disability-Adjusted Life Year (DALY) averted, a standard metric in health economics that considers both mortality and morbidity impacts, though it excludes some additional factors such as economic benefits and reduced healthcare costs. Importantly, this analysis is not intended to be a rigorous economic study and the numbers presented should not be considered definitive.

This Google sheet (first tab) contains the full dataset used in this analysis of various malaria prevention and treatment interventions, categorized by their approach to combating malaria. The dataset spans different geographical regions and age groups, with cost-effectiveness measured in terms of the Cost-Effectiveness Ratio (CER), quantified by the cost per DALY averted. For this analysis, we compiled 12 studies and meta-studies on malaria interventions in sub-Saharan Africa, ensuring data uniqueness in cases involving meta-studies. Key details from each study, including the intervention type, category, publishing and costing years, targeted age group, and CER, were documented. To improve the relevance and accuracy of the financial comparisons, the costing year used in the studies was noted in US dollars, and the Federal Reserve Consumer Price Index was used to adjust to 2024 USD figures. 

The full list of interventions evaluated is:

1. Bed nets: both LLINs (long-lasting insecticide-treated nets) and ITNs (insecticide-treated nets)
2. Vector control: larviciding and IRS (indoor residual spraying)
3. Vaccines: both the RTS,S and R21 malaria vaccines
4. Chemoprevention: IPTi (intermittent preventive treatment for malaria in infants, now rebranded PMC) and SMC (seasonal malaria chemoprevention)

Results and discussion

After comparing the available data, bed nets emerge as the most cost-effective malaria intervention at $38 per DALY averted, with the R21 vaccine close behind at approximately $39 per DALY (Fig. 1). SMC is marginally less cost-effective at $82 per DALY, though it can outperform bed nets in certain contexts (see sheet 2 of the CEA spreadsheet linked above, where we plot separate study results for SMC). The RTS,S vaccine, while more expensive at $129 per DALY, remains cost-effective but costs 3-4 times more than bed nets. This is primarily due to its higher price and marginally worse performance in currently available studies compared to R21. Vector control methods, costing around  $296 per DALY, are the least cost-effective but remain a crucial malaria prevention strategy. The R21 vaccine’s favorable cost profile and substantially larger manufacturing capacity than the RTS,S vaccine make it a practical choice for widespread immunization efforts. Importantly, the efficacy of both vaccines is greater in younger children, so if the vaccines are administered in 5-8-month-olds instead of 5-36-month-olds the cost-effectiveness of both vaccines could improve substantially.

Notably, our analysis did not group both R21 and RTS,S vaccines into a ‘vaccines’ category, similar to how we did with other interventions (e.g. grouping IRS and larviciding into vector control). Our reasoning for this was to direct the focus of the post on the R21 vaccine specifically, however, if we were to group all studies examining the R21 and RTS,S vaccines, the average CER for the vaccines category is found to be approximately $83 per DALY, similar to chemoprevention.

Each intervention carries unique advantages (e.g. a single ITN is often used by more than one person, and in some cases, whole families) and limitations (e.g. the emerging insecticide resistance to pyrethroids, which is compromising the effectiveness of pyrethroid-based ITNs and IRS programs), emphasizing the necessity for integrating multiple strategies for a comprehensive approach to malaria prevention. The R21 vaccine’s favorable cost-effectiveness profile and wider age range for administration¹The manufacturer of RTS,S/AS01 recommends that the first dose of the vaccine is given to children aged 5 months to 17 months, whereas the manufacturer of R21/Matrix-M recommends that the first dose of the vaccine is given to children aged 5 months to 36 months of age.  compared to the RTS,S vaccine makes it a more accessible option for large-scale immunization programs.

ITNs, vaccines, and chemoprevention can target children under five years and pregnant women as a strategy that may be more cost-effective than attempting to protect the whole population. Vaccines can be incorporated into national immunization programs, though the four doses required of both RTS,S and R21 will likely require an additional visit or two outside the existing schedule. The WHO recommends capitalizing on these visits to also provide ITNs and address any missed vaccinations, distribute vitamin A, conduct deworming, and other preventative measures.

The cost-effectiveness of different malaria prevention programs can vary widely depending on the specific context and implementation strategies used. Integration and last-mile delivery programs, for example, can greatly influence the cost-effectiveness of a given intervention. A Swiss Tropical Institute study supported by USAID compared five insecticide-treated net programs across five countries. They found that, for conventional ITNs, the average cost per DALY averted varied by about a factor of 2.5 across sites ($37 to $89), and this variation factor increases to ~4 when net re-treatments, a highly country-dependent variable, are taken into account. Since 2007, the WHO has recommended the exclusive use of LLINs over conventional ITNs. Consequently, LLINs have been increasingly adopted because they maintain effective insecticide levels and remain physically intact for at least three years. Conventional ITNs might still be in use in some areas, particularly where LLINs are not available or where older stocks of ITNs are being used up.

The incidence rate of malaria can vary significantly depending on the level of transmission in the area and the efficacy of existing interventions which can significantly impact the cost-effectiveness of a given intervention. For instance, a study on the cost-effectiveness of larviciding, a form of vector control, in Tanzania found that the cost per DALY averted was highly dependent on the assumed baseline malaria incidence rate. In a high transmission scenario with ~900 infections per 1,000 people per year, the cost per DALY averted was estimated to be 12 times lower than in a low transmission scenario with ~100 infections per 1,000 people per year. The scenarios used to model the malaria incidence rate were based on fluctuations in malaria occurrence in Tanzania between 2005 and 2008.

There is a clear need for further research to guide the development of implementation and other policy recommendations. RCTs should be supplemented with well-defined research questions and additional trials that go beyond answering efficacy and safety data, powering the studies to consider comparative effectiveness against, and in combination with, other relevant technologies.

Uncertainties in this analysis

Several factors contribute to uncertainty in the final values, including the following: 

1. Studies were conducted in different countries, which may have different malaria burdens, malaria seasonality, logistical costs, public health infrastructure, and other factors that add considerable uncertainty to this analysis. In particular, interventions are less cost-effective where background malaria prevalence is lower. The figures for R21 and RTS,S vaccines are based on malaria prevalence (PfPR2-10) of 20%, which is about average for malarial regions of Sub-Saharan Africa. Seasonal malaria chemoprevention is tested in scenarios where malaria has significant seasonal characteristics and can be assumed to be less cost-effective elsewhere.
2. Costs of delivering the solutions also vary significantly between and within countries, and the long-term delivery costs are likely lower than the costs of introducing a new program. Some studies have slightly different approaches to costing (e.g. provider cost vs. societal cost) and some studies factor in assumed savings on treatment costs to their overall CER.
3. The long-term performance of the RTS,S and R21 vaccines is estimated by modeling initial clinical trial data and assumes the protective effect of the vaccine wears off in the following years. There is still significant uncertainty around the longevity of protection, and the vaccines will be more cost-effective if some degree of protection is more durable than expected.
4. Most interventions, such as chemoprevention and certain ITN studies, target children, but broader interventions like vector control benefit all age groups. This complicates direct DALY comparisons, as saving the life of a child averts more lost DALYs than saving the life of an adult, though children are by far the most at-risk population from malaria, so this is a minor source of uncertainty.
5. We used average CER values (not a range of CER values) as a starting point and have not incorporated confidence intervals in our analysis. Not all studies reported CER ranges using the same method, making it difficult to assimilate data. We limited this analysis to average values to include more studies. 
6. Some of the studies used are from the late 2000s. In the absence of more detailed figures on local healthcare costs, we have adjusted reported USD costs for inflation based on US CPI.

Despite these limitations, we are confident in our key finding: the R21 malaria vaccine is cost-effective compared to existing malaria countermeasures. This aligns with the overall cost-effectiveness of malaria prevention efforts, as a recent report by Policy Cures Research suggests an over 400x return on investment for malaria prevention efforts. The RTS,S vaccine is competitive as well, so these vaccines should be considered crucial new additions to existing strategies like bed nets and chemoprevention. It is important to note that the optimal mix of interventions will vary based on factors such as the local malaria burden, transmission dynamics, and available resources.

Our Takeaways

The R21 malaria vaccine is a cost-effective and promising new tool in the fight against malaria, comparable to the best existing interventions, and accelerating its deployment could save hundreds of thousands of lives in the coming years. To achieve this, increased financial support is essential to close the production-delivery gap, reduce costs for LMICs, and streamline distribution logistics.

International organizations like Gavi, the Gates Foundation, and UNICEF should enhance transparency regarding their plans for the R21 rollout and address existing roadblocks. The Serum Institute of India, the manufacturer, along with multiple African nations, are calling for increased doses of R21 to be purchased and delivered, indicating that supply and demand are present but funding remains a bottleneck.

Treating the R21 rollout with proper urgency requires coordinated global transparency and communication, ensuring that all stakeholders can contribute effectively to this critical public health effort.

More information can be found in our latest status report available here.

Acknowledgments: Revisions,  discussions, and support provided by Mitch Laughlin and David Tellett from the 1Day Sooner Malaria Research Pool. Alyssa Bilinski, PhD from Brown University, Justin Sandefur, PhD from the Center for Global Development, and Daniel Issing from GiveWell.