Note: This page summarizes the rationale behind a GiveWell grant to PATH. PATH staff reviewed this page prior to publication.
In a nutshell
In September 2025, GiveWell recommended a $250,000 grant to PATH to fill a budget shortfall for a clinical trial in Ghana assessing co-administration of the RTS,S malaria vaccine and perennial malaria chemoprevention (PMC). This grant is a follow-up to our initial $1.6 million in funding for this trial in 2023, which was co-funded by the President's Malaria Initiative (PMI) and the Gates Foundation.
We are recommending this grant because:
- We think the study is likely to be valuable. It aims to provide the first empirical evidence on combining a malaria vaccine with PMC, while also comparing two different drug regimens for PMC.
- This funding makes it more likely that trial results get seen and used. Our understanding is that the budget shortfall would primarily impact the write-up and dissemination of the trial results, which we see as important steps for the findings to potentially influence policy.
Our main reservations about this grant are:
- PATH might have found this funding from another source. We believe this is a high-priority gap for PATH, so it's possible they would have eventually secured funding from another source without our involvement.
- The study's findings may not be as influential as we hope. Changes in the funding landscape and priorities may mean a decreased appetite for PMC among global funders, in which case the evidence generated by this study may be less useful.
Published: October 2025
The organization
PATH is a global nonprofit organization that works to advance health equity through innovation and partnerships. GiveWell has partnered with PATH on multiple occasions; we recommended our initial grant for this clinical trial in February 2023.
The intervention
This grant supports a clinical trial studying the combination of two malaria interventions: the RTS,S malaria vaccine and perennial malaria chemoprevention (PMC). PMC involves administering preventative antimalarial drugs to children at regular intervals in areas where malaria is a year-round threat.1
The grant
The study is a three-arm, individually randomized, placebo-controlled trial. It compares the RTS,S vaccine given alone vs. the vaccine given with one of two different drug regimens for PMC: sulfadoxine-pyrimethamine (SP) or a combination of SP and amodiaquine (SPAQ). The trial aims to measure the incidence of clinical malaria, severe malaria, and all-cause hospital admissions, among other secondary outcomes.2 Our 2023 grant represented about one-third of the total original study budget of $4.8m (with PMI and the Gates Foundation funding the rest).
This $250,000 grant to PATH will be used to fill a budget shortfall for the clinical trial described above, together with the Ares Pathfinder charitable initiative within the Alternative Credit group (Ares), which has committed funding for the remainder of the roughly $520,000 overall gap. Our understanding is that this shortfall stems from a combination of delays in start-up activities and recruitment, and the cancellation of the trial’s USAID award. This top-up funding will support the final stages of the trial, including field oversight and the write-up and dissemination of the study's results.3 The funds will support the three research partners on the study: PATH, the London School of Hygiene & Tropical Medicine, and the Kintampo Health Research Centre in Ghana.4
The case for the grant
We recommended this grant for the following reasons:
- We think the study is likely to be valuable. It aims to provide the first empirical evidence on combining a malaria vaccine with PMC, which partners like WHO have pointed to as a key evidence gap.5 It also compares PMC with SP against PMC with SPAQ; given concerns about growing resistance to SP, we see policy relevance in understanding the potential added benefit from amodiaquine (the "AQ" in SPAQ). While the study is being conducted with the RTS,S vaccine, our expectation based on conversations with the study team and the WHO is that the findings on co-administration will be applicable to the R21 vaccine as well.6
- This funding makes it more likely that trial results get seen and used. Our understanding is that this budget shortfall would primarily impact the write-up and dissemination phase of the trial, which we see as key to the case for the original grant. The main impact pathway we saw for that grant was through the dissemination of findings that could influence the standard of care in malaria-endemic regions with perennial transmission.7 While it’s not certain this will happen in any case, we think leaving this gap unfilled would make it less likely.
Risks and reservations
Our main reservations about this grant are:
- PATH might have found this funding elsewhere. It's possible that PATH could have raised the remaining $250,000 from another source. Our sense is that this is a high-priority gap for them, so they have a strong incentive to search for funding. That said, the funding landscape is tight, and we worry that a continued search for funding would be a drain on the study team’s attention. We also think that PATH has made good-faith efforts to find other funding where they could, resulting in their securing a commitment from Ares to cover half of the original ~$520,000 budget shortfall.8
- The study's findings may be less influential than we’d hope.
- There's a chance that the global health community's appetite for funding PMC may decrease in the coming years due to shifts in funder priorities.9 If that's the case, evidence on how to best implement PMC might not be a high priority for policymakers. That said, the results from this study won't be available until 2027, and we have lots of uncertainty around what the malaria funding landscape will look like in a few years.
- We're also unsure how much we’ll be able to generalize from the SP vs. SPAQ comparison. Our understanding is that Ghana is a relatively low-SP-resistance setting.10 The places where we'd be most interested in the potential added protection from AQ are likely high-SP-resistance settings, and it's not clear to us how applicable the findings from these two arms will be in those contexts.
Our process
We first learned about a potential funding gap for this trial in late 2024. We had a series of phone and email conversations with the PATH study team about this gap over the first half of 2025. We also spoke with Ares to discuss the study after PATH noted that Ares had expressed interest in co-filling the budget shortfall with us.
Sources
- 1
“Perennial malaria chemoprevention (PMC) is the administration of a full treatment course of an antimalarial medicine at predefined intervals, regardless of whether the child is infected with malaria, in order to prevent illness in moderate to high perennial malaria transmission settings. … The Expanded Programme on Immunization (EPI) platform remains important for delivering PMC. Other methods of delivery can be explored to optimize access to PMC and integration with other health interventions.” World Health Organization, “WHO Guidelines for malaria," March 2023
- 2
PATH, MALVAC-PMC Trial Overview slide deck, September 2024 (unpublished)
- 3
PATH, email to GiveWell, July 3 2025 (unpublished)
- 4
See PATH's budget for this grant.
- 5
World Health Organization, Conversation with GiveWell and other stakeholders, September 4, 2024 (unpublished).
- 6
World Health Organization, Conversation with GiveWell and other stakeholders, September 4, 2024 (unpublished).
- 7
See the grant page from our 2023 grant: “From GiveWell’s perspective, this study’s main expected impact is through providing evidence that may inform governments’ decisions to adopt coadministration of malaria vaccines and chemoprevention in perennial settings. Assuming that enough children end up being treated through coadministration as a result of this study, it’s plausible that the whole of the study could far exceed our cost-effectiveness threshold for directing funding.”
- 8
PATH, Conversation with GiveWell and other stakeholders, June 26, 2025 (unpublished)
- 9
An example of this is revised guidance from the Global Fund in the face of US government aid cuts. A revised prioritization framework shows case management first, then prevention – broken down into vector control as top priority, then SMC for children under 5, and then noting “IPTp and other chemoprevention deployed through routine services [like PMC] should be fully integrated and covered by national funding, where possible.” undefinedGlobal Fund, GC7 Programmatic Reprioritization Approach, June 2025, P. 8
- 10
See Amimo et al. 2020 “Plasmodium falciparum resistance to sulfadoxine-pyrimethamine in Africa: a systematic analysis of national trends,” Table 1.