PATH — Perennial Malaria Chemoprevention Pilot in the Democratic Republic of the Congo (November 2022)

Note: This page summarizes the rationale behind a GiveWell grant to PATH. PATH staff reviewed this page prior to publication.

Summary

In a nutshell

In November 2022, GiveWell made a two-year, $6,226,000 grant to PATH to conduct an implementation pilot of perennial malaria chemoprevention (PMC) in the Democratic Republic of the Congo (DRC).

We made this grant because we think it’s highly cost-effective. We estimate PMC is an inexpensive way to reduce deaths due to malaria, a key driver of child deaths in DRC. We think this pilot, by demonstrating the feasibility of implementing in DRC, could accelerate the timeline for other funders supporting PMC, leading to many more children in DRC receiving PMC over the next decade. We’re uncertain about this, though, and think it’s possible we’re overestimating the chance that this pilot accelerates the timeline on which other funders support the scale-up of PMC in DRC.

What we think this grant will do

PMC is the provision of preventive antimalarial medicine to children under two years of age at routine vaccination visits. (more) PMC is not currently implemented in DRC. (more)

This grant will cover PATH’s personnel, commodity, and survey costs for conducting an implementation pilot of PMC in DRC. With this funding, PATH will work together with the DRC Ministry of Health to develop a plan for and oversee the implementation of PMC in four health zones in DRC, including training health care workers and ensuring that an adequate supply of PMC is delivered to clinics. PATH also plans to evaluate the impact of this program through facility and household surveys to assess coverage of PMC and a case-control study to assess the impact of PMC on clinical malaria. (more)

  • Given the direct impact of implementation of PMC during the pilot and the potential to accelerate the adoption of PMC in DRC, we think this grant is highly cost-effective.

    This is because we think:

    • PMC is unlikely to be adopted in DRC without implementation pilots. Based on several conversations with experts and funders of antimalarial programs, our impression is that other funders want to see context-specific evidence on the feasibility of implementation before directing funding into implementation of PMC at a larger scale. (more)
    • An implementation pilot is unlikely to happen in DRC without our funding. Based on conversations we’ve had with PATH and other funders, our impression is that other funders are unlikely to support an implementation pilot of PMC in DRC in the immediate term, and that DRC is unlikely to implement the program on its own without funding for implementation or outside technical assistance to oversee adoption of a new program like PMC. (more)
    • We think this pilot is likely to be successful. We think PATH has the experience to successfully oversee implementation of PMC in DRC. (more)
    • If the pilot is successful at crowding in other funders, PMC is likely to reach many more children over the next 10 years. We roughly estimate an additional 200,000 children will receive PMC during the two-year pilot and 900,000 will receive PMC over the following eight years, compared to what would happen without this pilot. This is based on estimates of population of infants in DRC, feasible coverage if the program were scaled up according to estimates from PATH, and our subjective guess at how much the pilot speeds up roll-out of PMC. (more)
    • PMC is a highly cost-effective program. Malaria is a major driver of deaths among children in DRC, and there is strong evidence that PMC reduces malaria incidence. PMC is cheap to deliver because it relies on inexpensive commodities and delivery through existing infrastructure through routine health visits. (See our intervention report for more details.)

    We have developed a rough model to quantify these drivers of cost-effectiveness. Our best guess is that this grant is ~24 times as cost-effective as cash transfers to GiveDirectly, which is higher than our current bar of 10x cash. However, this analysis is especially uncertain, so we put less weight on it and more on the arguments above.

    Best guess 25th-75th percentile range for key parameters Cost-effectiveness over that range
    Grant size $6,226,000
    Child mortality benefits
    Expected number of infants receiving PMC during the pilot (years 1-2) 183,476 100,000-300,000 22x-27x
    Expected number of additional infants reached beyond the pilot (years 3-10) 918,821 200,000-1,800,000 8x-43x
    Annual malaria mortality rate for children in DRC 1% 0.5%-1.5% 13x-38x
    Effect of PMC on annual mortality rate 49% 25%-75% 12x-37x
    Number of deaths averted 5,115
    $ / death averted $1,217
    Moral weight for each death averted 101
    Initial cost-effectiveness estimate (x cash) 25
    Additional modeled benefits beyond child mortality +10%
    Additional unmodeled upsides and downsides -10%
    Overall cost-effectiveness (x cash) 24
    % of benefits from years 1-2 17%
    % of benefits from years 3-10 83%
  • We think this grant may have additional benefits that we have not tried to quantify. This includes learning value to GiveWell (providing updates on inputs informing cost-effectiveness, such as the percentage of children at different routine immunization visits receiving PMC) and learning value to others (findings from implementation of PMC could inform implementation of rollout of a malaria vaccine). In addition, if the pilot is successful, it could open up the opportunity for GiveWell to support the scale-up of PMC across eligible geographies in DRC and other settings. (more)

Main reservations

  • We may be overestimating the chance that, if the pilot is successful, other funders will support scale-up of PMC. We have heard that the Global Fund and other malaria funders have not prioritized funding PMC in DRC, and it’s possible that may persist, even after these pilots, due to limited funding. We guess that there’s a 35% chance that this does not lead to speed-up of roll-out at all, either through GiveWell funding or crowding in other funders, in which case cost-effectiveness would be 4x. We expect to be able to assess whether our funding was successful at crowding in funding after the pilot by speaking to other funders. We view this as worth the risk, given the potential for high cost-effectiveness if this does lead to speed-up. (more)
  • We’re uncertain about other factors feeding into our estimates of scale-up of the program. This includes not just the chance other funders would support scale-up after a successful pilot but also how feasible it is to reach a large number of children with PMC and how likely it is this scale-up would occur on its own. Our 25th-75th percentile on number reached is 200,000 to 1,800,000, which implies a range in cost-effectiveness of 8x-43x. We expect to at least partially learn about this value after the pilot occurs by assessing program reach under any scale-up, though it will be difficult to know what would have happened counterfactually.
  • It’s possible that ongoing implementation research on PMC in other countries makes this pilot in DRC less useful. We are aware of other studies from the Bill and Melinda Gates Foundation and Unitaid that are also aimed at assessing the feasibility of implementing PMC. This may be duplicative with the pilot study we’re funding. However, that other research does not focus specifically on DRC, and we think context-specific factors are likely to be very important for this type of work. We expect to at least partially learn about this by having conversations with experts in DRC and other funders following the pilot. (more)

Published: September 2023

Table of Contents

The organization

PATH is a global non-profit launched in 1977 that works in a number of health areas, including malaria, with the goal of promoting health equity.1 GiveWell has previously supported a number of PATH malaria programs. In September 2021, GiveWell recommended a $120,000 grant to Malaria Consortium and PATH to scope opportunities for implementing perennial malaria chemoprevention (PMC), formerly known as intermittent preventive treatment in infants (IPTi), for malaria.2 The proposal for this implementation pilot came out of the scoping work supported by that grant.

Additionally, GiveWell recommended an approximately $5 million grant to PATH in January 2022 to support ministries of health in Ghana, Kenya, and Malawi in the implementation of the RTS,S malaria vaccine through the end of 2023.

The intervention

PMC, formerly known as IPTi, is the provision of a preventive antimalarial medication, generally sulfadoxine-pyrimethamine (SP), to children, often during their routine immunization visits in the first two years of life.3 This medication is given whether or not a child is infected with malaria.4 It is different from seasonal malaria chemoprevention (SMC), which is only delivered during the peak season of malaria transmission, as PMC is administered in areas of perennial malaria transmission at regular intervals (regardless of season) to protect children up to 24 months.5

Does PMC work?

There is strong evidence showing that PMC is effective in substantially reducing cases of malaria in the treated population: a Cochrane meta-analysis of 12 randomized controlled trials (RCTs)6 found that PMC reduced cases of clinical malaria by 30%.7 See here for our review of this evidence.8

The World Health Organization (WHO) has recommended PMC since 2010,9 but it has been implemented at a national scale in only one country.10 The WHO updated its malaria recommendations in 2022 to give more flexibility on the number of recommended doses and to expand the age range suitable for PMC from 12 months to 24 months.11

The grant

Planned activities

The implementation pilot supported by this grant will build on PATH’s and Malaria Consortium’s scoping work on PMC (see their scoping report for their learnings in DRC and Nigeria). In coordination with the DRC Ministry of Health and other partners, the pilot will aim to support the government to assess the program’s operational feasibility and to design an optimal PMC dosing schedule, including both timing and number of doses administered, for children in high-burden areas of DRC.12 They will be testing delivery of PMC at 10 weeks, 14 weeks, 6 months, 9 months, 12 months, and 15 months of age.13

During the two-year grant period, PATH will conduct a case-control study at the health facility level. This will involve recruiting patients seen at health facilities in study health zones. The PMC status of patients with confirmed malaria cases and patients without malaria (controls) will be compared to assess the impact of PMC on clinical malaria. Blood samples will also be collected to test for SP resistance.14 PATH will use existing health facility surveillance data and validate the data through audits to measure the impact of PMC on the incidence of malaria and severe anemia.15

PATH will also conduct cross-sectional surveys at the facility and household levels to assess PMC coverage, access, acceptability, awareness, and operational feasibility.16

Budget for grant activities

The budget for this grant is $6,226,000 over two years. It breaks down as follows:17

  • Personnel, consultants, and travel (41%): $2,576,000
  • Equipment and commodity procurement (8%): $486,000
  • Sub-awards (2%): $136,000
  • Other direct costs (33%): $2,081,000
  • Indirect costs (15%): $947,000

Geography

We think DRC is a particularly promising setting in which to implement PMC, for several reasons:

  • The DRC Ministry of Health has demonstrated interested in PMC, but funding has been the limiting factor to adoption18
  • High cost-effectiveness and room for more funding due to:
    • High malaria burden among children19
    • Relatively low levels of parasitic resistance to SP, the drug used for PMC20
    • Large target population, which could lead to higher cost-effectiveness if there are fixed costs to scaling up the program in each country21
  • PATH’s deep experience in implementing and scaling malaria and other health programs in DRC (see next section)

The case for the grant

We made this grant for the following reasons:

  • We think this grant may open up cost-effective room for more funding to implement PMC at national scale in DRC.
    • We estimate that supporting the scale-up of PMC across eligible geographies of DRC is within the range of cost-effectiveness of programs we would recommend funding, but we are very uncertain about the number of doses it would be feasible to deliver and the achievable coverage for each dose, both of which greatly affect the cost-effectiveness of the program.22 A high-quality implementation pilot of PMC in DRC could update us substantially on the cost-effectiveness of implementing the program in DRC and open up significant room for more funding to scale-up PMC across eligible geographies in DRC and other settings.
    • We estimate that there is approximately $30 million in additional room for more funding for PMC in DRC and approximately $40 million in the five highest-burden countries outside of DRC.23
  • The implementation pilot could crowd in funding for scale-up of PMC. Our impression is that other funders want to see context-specific evidence on the feasibility of implementation before directing funding into implementation of PMC at a larger scale.24 If the pilot demonstrates successful implementation of PMC in DRC with six doses, it could increase the likelihood that other funders support the implementation of PMC at national scale in DRC or accelerate the timeline for other funders doing so. PATH is aiming to implement the pilot with the explicit goal of trying to secure funding for scale-up from the Global Fund and other large malaria funders.25
  • We think this grant is likely to be a cost-effective use of funds. We estimate the cost-effectiveness of this grant to be 24 times as cost-effective as unconditional cash transfers.26 Our model includes the direct impact on infants we expect to be covered in the implementation pilot, plus the impact from increasing the likelihood of other funders supporting the scale-up of PMC in DRC and accelerating the timeline on which that would happen. We estimate that this combined impact could lead on expectation to approximately 5,000 lives being saved.27 We are highly uncertain about the assumptions we make in our model, and, as such, we rely mainly on the qualitative case outlined in this section and use the cost-effectiveness analysis as a rough quantitative check (more below).
    • In our cost-effectiveness analysis, we assume:
      • The implementation pilot will directly cover PMC for 62,660 children under the age of two across four health zones of DRC.28
      • The pilot will lead to a 10 percentage point increase in the likelihood that the program is scaled up with funding from another donor. Conditional on the program being scaled up with funding from another donor, the program’s scale-up will be accelerated by one year. We are especially uncertain about these assumptions.
  • We think PATH has the organizational experience to successfully implement this pilot. PATH has a strong track record scaling other interventions through the routine health system, including rolling out the RTS,S malaria vaccine.29 They also have a strong working relationship with the DRC Ministry of Health;30 we think strong relationships with ministries of health are important for the success of interventions implemented within government health systems. Moreover, during the course of the PMC scoping period and the subsequent grant investigation, PATH's team demonstrated knowledge of scientific and practical considerations relevant to implementing malaria chemoprevention and vaccine strategies, as well as thoughtful and transparent reasoning.
  • We believe this pilot is relatively unlikely to be funded in the absence of GiveWell’s recommendation. The DRC Ministry of Health has been interested in PMC for several years but has not been able to implement the program due to funding constraints.31 DRC included PMC in its previous Global Fund application, but the Global Fund did not fund it due to competing priorities. It is also not part of the U.S. President’s Malaria Initiative (PMI) implementation strategy.32 From our conversations with other funders, it doesn’t seem likely that they have plans for expanding their investments in PMC in the next couple years, before results from ongoing PMC implementation research that they are currently supporting become available.33
  • There is momentum to continue to implement PMC in DRC. The DRC Ministry of Health is keen to continue its work to scale-up PMC across DRC, working on momentum and interest from the scoping project there.34
  • We think there could be additional unaccounted for benefits from supporting PATH in DRC specifically. For example, work to generate evidence on and to develop the infrastructure for PMC now could later be leveraged for rolling out a malaria vaccine through the same platform and in similar target areas in DRC and Nigeria. PATH has told us it is interested in assessing the impact and interaction of PMC and RTS,S.35

Risks and reservations

We have the following risks and reservations about this grant:

  • We are uncertain about the actual effect the pilot will have on crowding in funding or accelerating scale-up. We are highly uncertain about the likelihood of the program being scaled up through other sources of funding, either with or without this implementation pilot, and about how much this pilot would actually accelerate scale-up of PMC in DRC. On this point, we rely heavily on the qualitative case for this grant and consider the CEA as a quantitative check rather than the main reason for making the grant.
  • It’s possible that the information value added from this pilot will be negligible because of other ongoing research. We are aware of other implementation research currently underway, funded by the Bill and Melinda Gates Foundation36 and Unitaid.37 It’s possible that this pilot will ultimately be redundant with those efforts. However, we think there may be value in generating context-specific evidence in order for funders such as the Global Fund to be willing to support implementation in DRC.
  • Funding this pilot might actually slow down the scale-up of PMC. It’s possible that in the counterfactual of funding this pilot, implementation in DRC might have happened without needing to first conduct a pilot. However, we think the risk of this is fairly low, as our impression from conversations with PATH and malaria funders is that following the more flexible WHO guidelines released in June 2022,38 countries and funders are mainly interested in PMC with an expanded set of touchpoints (e.g., four to seven doses rather than three), which would necessitate more evidence generation in specific contexts.39
  • There may be a risk of funging other investments or leaving DRC without funding for PMC if we fund this pilot but don’t fund the scale-up of PMC following this pilot. There may be a risk to making a small grant and then not following up with additional funding for PMC in DRC if other funders view GiveWell’s commitment as ongoing and choose not to make investments they otherwise would have made in DRC. However, we view this as a relatively small risk because of the ongoing interest in PMC, as well as our transparency with PATH about our hope to crowd in other funders.

Plans for follow-up

We plan to check in with PATH at six-month intervals, and will schedule additional meetings as necessary to discuss program developments.

At the end of the grant period, in late 2024, PATH will produce a report including:

  • Results from the implementation pilot and case-control study on effectiveness and operational feasibility
  • A plan for scale-up in DRC
  • Support requirements for scale-up

GiveWell and PATH plan to ensure that this report is available to key stakeholders who will benefit from the information gathered during the implementation pilot phase.

Internal forecasts

For this grant, we are recording the following forecasts:

Confidence Prediction By time​​
85% PATH will have written an implementation pilot report that will be sufficient for our cost-effectiveness analyses and be disseminated to global stakeholders of PMC. May 2025
70% We will estimate the cost-effectiveness of scaling up PMC in DRC to be >10x cash. May 2025
40% GiveWell will make at least one grant worth more than $10 million to PMC programs.. December 2025
40% The Global Fund or another funder will fully fund scale-up of PMC in DRC, conditional on GiveWell not funding scale-up of PMC in DRC. December 2025

Our process

Calculated as: (180,000 + 920,000) x 1% x 49%
Calculated as: $6,226,000 / 5,115
Calculated as: 101 / $1,217 / 0.00335
Calculated as: 25 x (1 + 10%) x (1 - 10%)