Containment of Artemisinin Resistance in Eastern Myanmar

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A retailer in rural Myanmar offers a customer a package of Supa Arte, a high-quality antimalarial medication which was procured and subsidized by Population Services International to help slow the spread of drug-resistant malaria. (Photo courtesy of PSI)

Note: This page was created using content published by Good Ventures and GiveWell, the organizations that created the Open Philanthropy Project, before this website was launched. Uses of “we” and “our” on this page may therefore refer to Good Ventures or GiveWell, but they still represent the work of the Open Philanthropy Project.

Good Ventures awarded a $1 million grant to Population Services International in August 2012 to support a project aimed at slowing the spread of drug resistance to the highly effective antimalarial artemisinin in Myanmar. The project was recommended to us by the Gates Foundation and is the first project we’re co-funding with another foundation. We expect this grant to help us learn how a major funder like the Gates Foundation monitors the progress and asseses the impact of a large-scale global health project.

The purpose of the project is to prevent the emergence of drug-resistant malarial parasites in Myanmar by replacing artemisinin monotherapies (AMTs) with artemisinin combination therapies (ACTs) as the primary mode of treatment available for individuals to purchase in the private sector, and by promoting the proper diagnosis and treatment of malaria. The project was estimated to cost $35 million over three years, with approximately $27.5 million previously committed by the Gates Foundation and the UK Department for International Development.

The goal of co-funding with other foundations is twofold: to support promising projects and, most importantly, to learn how experienced foundations find, monitor and assess the impact of projects. Read more about our rationale for co-funding and how we selected this project.

We’ve published updates on this project in April 2013 and November 2013.

About the project

PSI aims to improve malaria treatment in Myanmar with the primary aim of preventing the spread of drug resistance to the highly effective antimalarial drug artemisinin. PSI states that drug resistance is minimized when patients complete full treatment regimens and when treatment regimens contain combinations of drugs that attack the parasite in multiple ways.1 PSI’s project focuses on replacing therapies that contain a single antimalarial drug (artemisinin monotherapies, or AMTs) with therapies that contain artemisinin in combination with other antimalarials (artemisinin combination therapies, or ACTs),2 and on ensuring that malaria patients receive and complete a full course of ACT and that only patients with malaria receive antimalarials.3

The project will include the following primary activities:4

  • Subsidizing ACTs sold through the private sector. To date, PSI has agreed to work with a single supplier that provides over 70% of the AMT delivered through private sector suppliers in Myanmar.5 PSI aims to provide a subsidy that results in the price of a full course of ACT being equal to what patients previously paid to treat malaria with AMT (which in many cases was only part of a recommended course).6 PSI has budgeted $14.4 million to purchase ACTs over three years, $12.5 million of which will treat adult patients.7
  • Advocating to drug providers to improve prescription practices. PSI will use mass media, targeted media, and visits to providers (pharmaceutical detailing) to promote use of ACTs and rapid diagnostic tests and to encourage providers to prescribe recommended drug regimens.8
  • Advocating to the national government for legal restrictions on selling AMTs. As of mid-2012, the government had agreed to institute an importation and marketing ban on AMTs by the end of 2012.9
  • Promoting PSI-branded ACTs and other behavior change communications. PSI will launch a campaign to promote demand for high-quality ACTs, prompt treatment seeking, use of diagnostic tests, and completion of full treatment courses.10
  • Training informal drug providers in the use of rapid diagnostic tests (RDTs), and supplying RDTs to these providers. In order to reduce the number of patients receiving antimalarials for fevers not caused by malaria, PSI aims to motivate drug providers to conduct regular testing of patients for malaria before prescribing drugs.11

The project is expected to have national reach with a particular focus on a high-risk area in the eastern part of the country.12

Potential project impact

PSI’s project, if it succeeds in helping to stop the spread of artemisinin resistance, has the potential to have a very high impact. A World Health Organization report states that artemisinin is the most effective antimalarial and that “there is currently no practical alternative treatment” for P. falciparum,13 the most deadly form of malaria.14 Artemisinin resistance has been found in countries neighboring Myanmar in the Greater Mekong region,15 and signs of resistance have been detected near Thailand’s border with Myanmar.16

There is an extensive history of the development and spread of drug resistance to other classes of antimalarial drugs. This, in turn, is thought to have led to rising child mortality rates as available drugs became ineffective.17 In particular, resistance to two types of antimalarial drugs emerged in the Greater Mekong region and likely spread from there to Africa,18 where the malaria burden is highest.19 Myanmar has by far the highest malaria burden in the region, and therefore, resistance, once in Myanmar, may be more likely to spread quickly.20 PSI reports that a high proportion of malaria treatments in Myanmar are supplied through the private sector,21 and over 70% of private sector treatments are supplied through a supplier that has agreed to work with PSI.22 A recent household survey conducted in regions at high risk of drug resistance, found that 30-47% reported that they used a private healthcare provider for their most recent case of fever.23

The project is also high risk, as the development and spread of drug resistance is not well understood and the project is has not been tried and tested previously.24

Risks to the success of the project

As discussed above, this is a high-risk project because it is an unproven approach to a problem that is not well understood. In addition to the risk of PSI’s project being an ineffective approach, there are risks that could prevent PSI from executing the project as planned. These include:

  • Operating environment: The government of Myanmar has in the past restricted the movement and activities of charitable organizations. It has recently begun to ease these restrictions.25
  • Targeting of subsidies: PSI will subsidize ACTs through a national supplier and will not have direct control over the supply chain of the drugs.26 There is therefore a risk that the price reduction will not reach consumers and will instead be captured by suppliers or retailers. There is also a risk of the subsidized drugs being misappropriated by the government, military, or other powerful interests.27
  • Patient compliance with full treatment course of ACT: The success of the project will be dependent on patients choosing to buy and complete a full course of ACT. PSI believes that patients are often highly sensitive to price, and many purchase partial courses of AMT. If they chose to purchase partial courses of ACT, as they do AMT, or to continue to purchase AMTs, the project is likely to have a smaller impact on controlling drug resistance. Helping to mitigate this risk, the ACT treatment course PSI plans to use is only three days long, compared to seven days for a full course of AMT. Also, PSI aims to keep the price of a full course of ACT at approximately the same price patients pay for a typical partial course of AMT.28
  • Partnership with large supplier: A single supplier provides over 70% of AMT treatments nationwide. The success of the project is highly dependent on a successful partnership with this single supplier.
  • Inherent challenges of behavior change: many of PSI’s planned interventions revolve around advocacy to change behavior; this sort of work seems inherently difficult to us. However, we note that this project, unlike behavior change projects that rely exclusively on communications, aims to increase the use of an inexpensive, high-quality product by subsidizing that product, and the country has agreed to ban the product it aims to replace. Therefore, this project relies less on convincing people to behave in a way that causes them to incur costs in the near term (as campaigns to exercise more or use condoms do, for example).

Monitoring and evaluation

PSI plans to use the following tools to monitor and evaluate the program:

  1. Private outlet surveys: PSI will randomly select areas in which to conduct the surveys and will visit all private antimalarial providers and sellers in the area (government-run facilities will not be surveyed). During the visits, PSI will directly observe availability of different types of antimalarials, as well as rapid diagnostic tests, and interview the provider to collect information on prices, sales volume, and knowledge of correct prescription practices.29 PSI has provided details of the survey methodology,30 and plans to conduct the surveys annually throughout the project.31 PSI has completed a baseline outlet survey and shared preliminary results.32
  2. Household surveys: PSI will conduct nationally-representative baseline and three-year follow up surveys to question households33 on their access to and use of different antimalarials. PSI will also ask households about the prices they paid for the medicines and test their basic knowledge about malaria and its treatment.34 PSI has provided details of the survey methodology.35
  3. Baseline supply chain assessment: PSI will conduct interviews with suppliers and key informants to map the supply chain for antimalarials in the country and determine the pricing structure.36 PSI also plans to conduct “routine monitoring of the supply chain to ensure consistent availability of stock at all levels.”37
  4. Mystery client surveys, exit interviews, and focus group discussions: PSI will “use actors who pretend to seek treatment for fever at a variety of outlets” to check drug providers prescription practices. Mystery client surveys will be conducted on an annual basis and ad hoc basis during the year.38 It will also interview patients after they visit drug sellers “to find out what advice they were given, what they bought and their views of the experience.”39
  5. Monthly sales data of subsidized antimalarials.

PSI has used this set of tools to collect data on anti-malarial markets in seven countries in Africa and Asia as part of an initiative called “ACTwatch.”40

In addition, the World Health Organization collects data on parasite clearance rates, a measure of the prevalence of drug resistance.41 We have not seen details of where or when this data will be collected in Myanmar. PSI notes, “the project contributes to, but wouldn’t be solely responsible for, any goal-level impact observed. Lastly, many aspects determining the nature of artemisinin resistance spread remain unclear, thus further complicating evaluation of impact at this level.”42

Use of additional funding and room for more funding

The project is projected to cost about $35 million over three years. The UK’s Department for International Development (DFID) and the Bill and Melinda Gates Foundation have committed approximately $27.5 million to the project.43

PSI told us, “At current levels of funding, PSI will conduct the planned surveys, run social mobilization campaigns, and purchase some commodities. The additional $7.5 million would allow for the purchase of additional ACTs and malaria diagnostic tests, and therefore scale up the replacement program more quickly.”44

Assuming that non-drug costs do not vary with the quantity of drugs sold (this is an aggressive assumption that likely understates the full costs of providing additional drugs),45 the cost to PSI of an average ACT treatment46 is about $1.78, which includes the cost of drugs and packaging.47 PSI estimates the cost of an additional RDT, including packaging, at $0.74.48 Thus an additional $1 million donation purchases up to 561,000 ACT treatments or 1.3 million RDTs, or a combination of the two.

Good Ventures has committed an additional $1 million for the project, leaving a funding gap of about $6.5 million. PSI hopes to secure the remaining funding for the project through new donors by the end of 2012; it does not believe that existing donors will fill the gap.49

Sources

Expand Footnotes Collapse Footnotes

1.“Resistance to antimalarial medicines has been documented in all classes of antimalarials, including the artemisinin derivatives, and it is a major threat to malaria control. Widespread and indiscriminate use of antimalarials exerts a strong selective pressure on malaria parasites to develop high levels of resistance. Resistance can be prevented, or its onset slowed considerably, by combining antimalarials with different mechanisms of action and ensuring very high cure rates through full adherence to correct dose regimens.” World Health Organization, “Guidelines for the Treatment of Malaria (Second Edition),” Pg 6.

“The use of monotherapy selects for resistance—susceptible parasites are killed, leaving resistant parasites to reproduce and spread (the science behind this is described in more detail in Annex N.) The widespread use of AMT is the single most important factor in the de novo development and spread of parasite drug resistance.” PSI, “Proposal for Containment of Artemisinin Resistance in Eastern Myanmar (Revision 1),” Pg 7.

2.“PSI will work with private sector suppliers and providers throughout Myanmar to rapidly replace widely available AMT with highly subsidized, quality assured ACTs. Broad reaching behavior change communications (BCC) targeting both consumers and providers will support supply chain activities and together will halt the spread artemisinin resistance in the region.” PSI, “Proposal for Containment of Artemisinin Resistance in Eastern Myanmar (Revision 1),” Pg 1.

3.“PSI will complement this with a behavior change communications (BCC) campaign targeting both providers and consumers, emphasizing the importance of testing and the need to complete a full course of ACT.” PSI, “Proposal for Containment of Artemisinin Resistance in Eastern Myanmar (Revision 1),” Pg 2.

4.PSI, “Proposal for Containment of Artemisinin Resistance in Eastern Myanmar (Revision 1),” Pgs 11-20.

5.“To that end, PSI has engaged the major private sector supplier of AMT, [which has] agreed to purchase highly subsidized, pre-packaged, quality-assured ACTs from PSI, rapidly replacing AMT in at least 70% of all private sector malaria treatment in Myanmar.” PSI, “Proposal for Containment of Artemisinin Resistance in Eastern Myanmar (Revision 1),” Pg 1.

6.“The root cause of the sale of incomplete treatment regimens is most often cost—patients cannot afford a full course. Countering this price disparity between ACT and partial AMT will be the most critical factor in increasing the proportion of malaria suspects who receive and take a full course of treatment…
Determining correct pricing for a complete course of quality ACTs through this channel and pricing it at or below what consumers are currently willing to pay will be a critical factor in increasing adherence.” PSI, “Proposal for Containment of Artemisinin Resistance in Eastern Myanmar (Revision 1),” Pg 6 and 11.

7.PSI, “Controlling the Spread of Artemisinin Resistance: Detailed Budget,” Pgs 2-3. The total budget for “commodities” is $15,793,643, which includes the cost of rapid diagnostic tests. Subtracting the cost of the tests, PSI plans to spend $14,419,860 on anti-malarials, including both ACTs and primaquine which will be co-packaged with the ACTs. Of this, PSI plans to spend $12,454,723 on anti-malarials for adults.

8.“The campaign will leverage three communication channels to influence correct clinical practice among healthcare providers. These channels will include: national airing of a media campaign, targeted placement of mid-media materials/activities within endemic areas, and targeted deployment of pharmaceutical detailing teams in eastern Myanmar.” PSI, “Proposal for Containment of Artemisinin Resistance in Eastern Myanmar (Revision 1),” Pg 14.

9.“Until recently, Myanmar had not banned monotherapies, but, following a recent political transition, the Ministry of Health has decided to institute an importation and marketing ban by the end of 2012.” GiveWell, “Summary of Phone Conversation Regarding ‘Artemisinin Monotherapy Replacement Project’ in Myanmar (May 31, 2012).”

10.“To address negative consumer behaviors related to treatment of malaria, PSI will develop and launch a campaign that motivates the target populations to:

  • promptly seek treatment when they have a fever;
  • demand correct diagnosis through malaria testing;
  • demand the brand name of the quality assured ACT;
  • recognize and demand a full course of treatment and take all the medicines purchased/prescribed in the correct way;
  • believe the quality assured ACT brand is a superior drug to their previous drug/s of choice; and
  • be aware of the potential dangers of using counterfeit and substandard medicines.”

PSI, “Proposal for Containment of Artemisinin Resistance in Eastern Myanmar (Revision 1),” Pg 18.

11.“Problem: Treating malaria suspects without previously confirming malaria infection results in significant overtreatment. Current estimates suggest that in Myanmar, only 42% of malaria suspects are actually infected, and this proportion is likely to decrease as malaria incidence declines. Not only will overtreatment delay the correct diagnosis and treatment of the cause of fever but it may also potentially promote drug resistance, particularly in the ACT partner drug. Long half-lives of partner drugs mean that traces may be present long after taking treatment, increasing the potential that a new infection of malaria parasites will be subjected to sub-therapeutic levels, and selection for resistance promoted…
PSI will ask detailers to identify informal providers who might be interested in, and capable of, conducting a rapid diagnostic test (RDT) for malaria. Selected providers will be trained in RDT and supplied with test kits through the Detailers, who will also be responsible for monitoring the program and collecting testing data.” PSI, “Proposal for Containment of Artemisinin Resistance in Eastern Myanmar (Revision 1),” Pg 19.

12.“As with drug sales, mass media BCC will be nationwide. However, a more intensive campaign, including PSI staff working as Pharmaceutical Detailers to influence the behavior of local drug sellers, will work only with a defined Target Area. This Target Area follows the length of the eastern border of Myanmar, where a combination of high malaria incidence and evidence of emerging artemisinin resistance make the need for AMT replacement most critical.” PSI, “Proposal for Containment of Artemisinin Resistance in Eastern Myanmar (Revision 1),” Pg 2.

13.“With the emergence and spread of resistance to a number of anti-malarial drugs since the 1950s and as a result of continuous research efforts to find alternative drugs, standard treatment for uncomplicated P. falciparum malaria worldwide has now shifted to the use of artemisinin-based combination therapy (ACT). Preservation of ACT as the effective first-line treatment for uncomplicated malaria is critical in part because there is currently no practical alternative treatment. Development and spread of resistance of malaria to artemisinin could be disastrous for global efforts to control and eliminate malaria.” Christophel et al. 2012, Pg 11.

“The emergence and potential spread of resistance to artemisinins means that artemisinins, and consequently ACTs, could be lost as an effective treatment for P. falciparum malaria. At present, no other antimalarial medicines are available that offer the same level of efficacy and tolerability as ACTs, and there are few promising candidates in the pipeline.” World Health Organization, “Global Plan for Artemsinin Resistance Containment (2011),” Pg 52.

14.“Plasmodium falciparum is the most deadly.” World Health Organization, “Malaria.”

15.“Evidence of resistance to artemisinins has been identified and confirmed on the Cambodia-Thailand border. Other suspected foci have been identified in the Greater Mekong subregion, but are not yet confirmed.” World Health Organization, “Global Plan for Artemsinin Resistance Containment (2011),” Pg 5.

16.“Until 2009, there were no clear signs of artemisinin resistance in Myanmar. In 2009, TES studies with ACTs showed the following main results…In principle, these results, seen in isolation, only raise a suspicion. However, when considered together with elevated day 3 positivity rates in Kanchanaburi, Tak and Ranong on the Thai side of the border (Fig.1), there is no doubt that artemisinin resistance has emerged in eastern Myanmar. As mentioned, worrying results have also been found on the border to China in Kachin State, but these need further investigation. Unpublished results from Myanmar in 2010 suggest that so far, there are no signs of artemisinin resistance in the Shan States (2 sites), in Myitkyina, Kachin State, or in Rakhine State. In contrast, results from Mon and Kayin States close to areas of suspected resistance in Thailand, give rise to concern, but no final conclusions can be drawn until the results have been PCR corrected. A study with artesunate monotherapy is to take place in Kawthaung in 2011. So far, there is no indication of artemisinin resistance in Bangladesh or in India.” World Health Organization, “Strategic Framework for Artemisinin Resistance Containment in Myanmar (MARC) 2011‐2015 (April 2011),” Pgs 13-14.

“The study entitled Emergence of artemisinin-resistant malaria on the western border of Thailand: a longitudinal study by Nosten and colleagues (Lancet, 5 April 2012) contains important evidence about the existence of artemisinin-resistant P. falciparum parasites in parts of western Thailand. The findings further deepen the concern WHO and other partners have had about emerging artemisinin resistance along the Thailand-Myanmar border… In Myanmar, the three registered ACTs are still highly effective in all the sentinel sites where their efficacy was monitored (>95%). However, the emergence of resistance at new locations in the Greater Mekong sub-region is disconcerting.” World Health Organization, “The Status of Drug-Resistant Malaria Along the Thailand-Myanmar Border (May 2012),” Pg 1.

17.“Resistance has developed to every antimalarial medicine used so far (see Global report on antimalarial drug efficacy and drug resistance, 2000–2010, section 1.2 for details), and the malaria burden rebounded due to consequent treatment failures. For example, the spread of P. falciparum resistance to chloroquine in the 1970s and 1980s was linked to a subsequent increase in child mortality in Africa (Trape, 2001; Dondorp et al., 2010).” World Health Organization, “Global Plan for Artemsinin Resistance Containment (2011),” Pg 19.

18.“It is noteworthy that resistance to chloroquine, sulfadoxine–pyrimethamine and mefloquine all first emerged in this area. Resistance to chloroquine and sulfadoxine–pyrimethamine then spread from the Greater Mekong subregion to Africa and also emerged in and spread through other regions. We cannot be certain that the pattern of spread of artemisinin resistance will be similar to that of other antimalarial medicines.” World Health Organization, “Global Plan for Artemsinin Resistance Containment (2011),” Pg 19.

“By contrast with pyrimethamine resistance, chloroquine-resistant falciparum malaria seemed to have emerged just twice (Figure 1). Resistance was first reported in the late 1950s along both the Panama-Colombian and Thai-Cambodian borders and radiated slowly and inexorably outward from these two foci, taking 10 years to advance across Thailand to Burma, reaching central India by the late 1970s. Resistance more rapidly disseminated throughout the Amazon region, crossing southwards across Bolivia in the early 1960s and extending to the Atlantic coast of French Guiana and Surinam by the early 1970s. Chloroquine resistance appeared in East Africa in 1978 and moved westward across the continent in a less well-documented pattern owing to limited surveillance in Central and West Africa…
In a striking parallel to the pattern of emergence and spread of chloroquine resistance, it was the Southeast Asian DHFR triple-mutant form that had spread to Africa, bringing with it clinically significant resistance to pyrimethamine that contributed to sulfadoxine-pyrimethemine treatment failure. These molecular epidemiological studies thus finally demonstrated that clinically important forms of drug-resistant malaria had very limited origins and then spread globally.” Plowe 2009, Pg 3.

19.“Most malaria cases and deaths occur in sub-Saharan Africa.” World Health Organization, “Malaria.”

20.“The four countries most affected by the emergence of artemisinin resistance are Cambodia, Thailand, Viet Nam and Myanmar. Of these, Myanmar has by far the greatest malaria burden. Over 40 million people, or an estimated 69% of the Myanmar population, reside in malaria- endemic areas, and 24 million live in high-transmission areas. For 2010, Myanmar reported 650,000 malaria cases and 788 malaria-related fatalities in the public sector. Given its extensive migrant population, the widespread use of oral artemisinin-based monotherapies, and its geographical proximity to India, Myanmar is critical to the success of efforts to prevent the emergence of artemisinin resistance globally.” World Health Organization, “The Status of Drug-Resistant Malaria Along the Thailand-Myanmar Border (May 2012),” Pg 1.

“Myanmar accounts for 78% of malaria cases and 75% of malaria deaths in the GMS, has the most under-resourced health system and is a potential conduit for amplification and spread of resistance to the West.” Christophel et al. 2012, Pg 6.

21.“Evidence from PSI’s rapid supply chain analysis also indicates that the private sector plays a major role in malaria treatment in Myanmar. Self treatment via drug purchases at unregulated private sector local outlets is the norm.” PSI, “Proposal for Containment of Artemisinin Resistance in Eastern Myanmar (Revision 1),” Pg 6.

22.“PSI’s Rapid Supply Chain Assessments found that one company, AA Pharmaceuticals, dominates the market, with at least 70% of national sales.” PSI, “Proposal for Containment of Artemisinin Resistance in Eastern Myanmar (Revision 1),” Pg 6.

23.Malaria Consortium, “MARC Baseline Survey Preliminary Results of Household and Drug Outlet Surveys,” Pg 24.

24.“Much remains to be elucidated about the emergence and spread of artemisinin resistance. Scientists do not know the mechanism of resistance nor what definitively contributes to the emergence and spread of resistant parasites. The extent of artemisinin resistance today – and specifically whether it has spread beyond the Greater Mekong subregion – is unknown, and scientists are unable to predict whether it will emerge in new foci or how quickly it could spread from current foci. There are also unanswered questions about which tools and methods will be most effective in addressing artemisinin resistance (see Global report on antimalarial drug efficacy and drug resistance, 2000–2010, chapter 2 for details). Much of the information contained in the GPARC is based on knowledge and experience gained with resistance to other antimalarial medicines.” World Health Organization, “Global Plan for Artemsinin Resistance Containment (2011),” Pg 19.

25.“NGOs in Burma are only allowed to operate with in areas agreed in their MOU with the government. NGOs are not allowed to operate in many of the areas where the most vulnerable reside.” Department for International Development, “Business Case and Summary of PSI Replacement of Malaria Monotherapy,” Pg 21.

“Risk: Restrictive operating environment;
Description: Lengthy approval processes for drug import clearances, permission for local programming;
Response: PSI Myanmar’s procurement processes ensure careful advance planning for importation of critical materials and drugs. Transparent advocacy at all levels to ensure access for program activities ensures that adequate staff levels to maintain effective monitoring, and monitoring plans are considered and crafted far in advance.” Department for International Development, “Business Case and Summary of PSI Replacement of Malaria Monotherapy,” Pg 39.

“In its pre-funding report on the project, DFID assessed the risks involved in the project as high. The Gates Foundation noted that this report was written before Myanmar’s political situation ‘opened up,’ and that they believe the chances of success have improved since then.” PSI, “Summary of Phone Conversation Regarding ‘Artemisinin Monotherapy Replacement Project’ in Myanmar (June 18, 2012),” Pg 3.

26.“Nevertheless, we hope and expect that we will succeed in maintaining, and even expanding, AA’s dominant position. In the short term, this is certainly to be wished for. In the longer term, the risk of this dominance is that price competition fails and AA’s monopoly allows them (and other market players) to increase margins to the detriment of patients.
This risk will be mitigated by three factors;

  1. PSI will set selling prices to different levels of the supply chain as part of distributor contracts.
  2. AA does not control the full supply chain – wholesalers and pharmacies down the supply chain will buy at set prices from AA, but will compete against each other for re-sale business, just as outlets in the village will compete.
  3. PSI will reserve the right to offer subsidized product to other distributors following the planned mid-term review.
    PSI monitoring system will identify price fluctuations, and if price gouging is identified in specific locations, PSI will consider working with distributors to bypass that part of the supply chain, for example by supplying drugs directly to local suppliers.”

PSI, “Proposal for Containment of Artemisinin Resistance in Eastern Myanmar (Revision 1),” Pg 12.

27.“Risk of drugs being misappropriated by the military: Through its outlet and household surveys and routine monitoring, PSI expects that it will be able to detect if large quantities of drugs are missing. However, it does not expect to be able to detect whether individuals employed by the military benefit from accessing subsidized antimalarials.” PSI, “Summary of phone conversation regarding ‘Artemisinin Monotherapy Replacement Project’ in Myanmar (June 18, 2012),” Pg 3.

28.“The full regimen of ACTs is three days long with two doses per day and multiple tablets at each dose (number dependent on age/weight category), compared with a 7 day full regimen for the most common current treatment, monotherapy. Currently, patients often buy only enough pills for a few days of treatment (with cost being the most likely barrier to full course purchases). PSI plans to try to set prices such that a full regimen of ACT costs about what patients currently pay for a partial course of monotherapy (around 500 Kyat).” PSI, “Summary of Phone Conversation Reegarding ‘Artemisinin Monotherapy Replacement Project’ in Myanmar (June 18, 2012),” Pgs 3-4.

29.“These surveys are multi-round and cross-sectional, utilizing a multi-staged cluster sampling technique. Within clusters, a census of ALL outlets with the potential to sell or provide antimalarials is completed. Outlet types include: (1) private clinics and hospitals, (2) private pharmacies, (3) itinerant drug vendors, (4) general retailers, and (5) community-level providers.

These outlets are then screened to ascertain which meet study inclusion criteria. Data are weighted to ensure results are nationally representative. Two tools are used for these surveys in every outlet included in the study: A physical audit of ALL antimalarials in stock on the day of the visit and a provider interview to assess knowledge.” PSI, “Summary of Phone Conversation Regarding ‘Artemisinin Monotherapy Replacement Project’ in Myanmar (June 18, 2012),” Pgs 1-2.

30.PSI, “ACTwatch Methodologies: Outlet Survey Study Design.”

31.“The first annual (and therefore baseline) outlet survey has already been completed.” PSI, “Summary of Phone Conversation Regarding ‘Artemisinin Monotherapy Replacement Project’ in Myanmar (June 18, 2012).”

32.Shared data includes:

  • Distribution of outlets stocking antimalarials
  • How easy is it to find any antimalarial among private sector outlets?
  • Among all outlets, what antimalarials are available?
  • Where we find antimalarials, which are available?
  • What is the market share among outlet types?
  • What is the market share of different antimalarials within each outlet type?
  • What is the median price with interquartile range for 1 adult equivalent treatment dose?
  • Of the private outlets with antimalarials, what was the availability of diagnostic tools?
  • Private outlets that did not cut blisters (i.e. pill packets) or provide partial courses in the previous month
  • Private outlet providers that know the first-line treatment

PSI, “MARC Annual Review Meeting: Artemisinin Monotherapy Replacement (June 2012),” Pgs 18-27.

33.“Nationally representative household surveys capture treatment-seeking behavior and use of antimalarial drugs, as well as respondent knowledge of antimalarials. The design mirrors that typically used in population-based surveys and follows standard Demographic Health Survey (DHS) sampling procedures. Eligibility for household inclusion in the Myanmar epidemiological context is determined by the presence of any family member with fever in the past two weeks. As a result of relatively low malaria transmission (and therefore lower fever incidence rates) compared to sub-Saharan Africa, the survey planned for August 2012 will include over 4,000 households. The survey will serve as the baseline, with a second end point survey occurring in year three at a similar point in time (i.e. towards the end of the monsoon season).” PSI, “Summary of Phone Conversation Regarding ‘Artemisinin Monotherapy Replacement Project’ in Myanmar (June 18, 2012),” Pg 2.

34.PSI, “ACTwatch Methodologies: Household Survey Study Design,” Pgs 30-34.

35.PSI, “ACTwatch Methodologies: Household Survey Study Design.”

36.“The Supply chain assessment is a structured survey of wholesalers and a series of in-depth interviews with wholesalers and other key informants. The aim is to get a picture of the supply chain serving various types of outlet and measure the mark-ups at each supply chain level.” PSI, “Summary of Phone Conversation Regarding ‘Artemisinin Monotherapy Replacement Project’ in Myanmar (June 18, 2012),” Pg 2.

37.PSI, “Summary of Phone Conversation Regarding ‘Artemisinin Monotherapy Replacement Project’ in Myanmar (June 18, 2012),” Pg 3.

38.“Annual quantitative Mystery Client Surveys that will enable PSI to monitor indicators of provider practices (esp. in relation to partial dose provision and price setting). Mystery Client Surveys use actors who pretend to seek treatment for fever at a variety of outlets. Qualitative spot checks will be conducted on a more ad hoc basis throughout the year. The audits will target all outlets, regardless of whether they are supplied by AA Medical Products Ltd.” PSI, “Summary of Phone Conversation Regarding ‘Artemisinin Monotherapy Replacement Project’ in Myanmar (June 18, 2012),” Pg 3.

39.“Exit interviews and focus group discussions will be conducted with patients after going to drug sellers to find out what advice they were given, what they bought and their views of the experience. ‘Mystery’ clients, enumerators who portray a set of malaria symptoms to the drug sellers to see what advice is given, will also be used to check adherence of drug sellers to the programme.” Department for International Development, “Business Case and Summary of PSI Replacement of Malaria Monotherapy,” Pg 16.

40.“The project is being conducted in seven malaria-endemic countries: Benin, Cambodia, the Democratic Republic of Congo, Madagascar, Nigeria, Uganda and Zambia from 2008 to 2012.” Shewchuk et al. 2011, Pg 2.

41.“WHO defines resistance as ‘the ability of a parasite strain to survive and/or multiply despite the administration and absorption of a drug given in doses equal to or higher than those usually recommended but within tolerance of the subject’ (WHO, 1967). For the purposes of the GPARC, we consider that a significant increase in parasite clearance time is an early warning sign of artemisinin resistance and deserving of a response similar to that for confirmed resistance. In this document, the term ‘artemisinin resistance’ is a working definition used to refer to:

  • an increase in parasite clearance time, as evidenced by 10% of cases with parasites detectable on day 3 after treatment with an ACT (suspected resistance); or
  • treatment failure after treatment with an oral artemisinin-based monotherapy with adequate antimalarial blood concentration, as evidenced by the persistence of parasites for 7 days, or the presence of parasites at day 3 and recrudescence within 28/42 days (confirmed resistance).”

World Health Organization, “Global Plan for Artemsinin Resistance Containment (2011),” Pg 16.

42.PSI, “Summary of Phone Conversation Regarding ‘Artemisinin Monotherapy Replacement Project’ in Myanmar (June 18, 2012),” Pgs 2-3.

43.“The budget for the program is $35 million over three years. To date, PSI has raised $27.5 million from the Gates Foundation and DFID.” GiveWell, “Summary of Phone Conversation Regarding ‘Artemisinin Monotherapy Replacement Project’ in Myanmar (May 31, 2012),” Pg 4.

44.GiveWell, “Summary of Phone Conversation Regarding ‘Artemisinin Monotherapy Replacement Project’ in Myanmar (May 31, 2012),” Pg 4.

45.We have examined the budget and have not found costs that we felt confident would vary with the quantity of drugs produced. It seems reasonable that management costs and monitoring and evaluation costs (which rely on nationally representative surveys) would remain roughly the same as the number of drugs purchased increased. Communications costs could vary, though PSI has stated that it would go forward with its social mobilization campaign at current budget levels.

One component that might vary is the costs associated with pharmaceutical detailing teams and “additional warehouse” costs. These costs comprise $6.2 million. Assuming these costs vary proportionally with drug costs (a conservative assumption), the average cost of an additional ACT treatment would rise from $1.78 to $2.40.

46.PSI’s project budget contains four types of ACT treatments: adult, youth, child, and young child. Our average is the total budgeted cost for all types divided by the total number of treatments of all types. We also include the cost of primaquine, a drug PSI plans to co-package with ACT, though we note that the number of primaquine treatments is only a fraction of the number of ACT treatments and it is not clear why these differ. GiveWell, “Marginal Cost Analysis for PSI Myanmar Project.”

47.Total budgeted cost of all types of ACTs with primaquine: $14,419,860

Total budgeted cost of packaging for ACTs: $1,571,813

Potential budget increase for ACTs and primaquine noted in February 2012: $1,900,000

Total budgeted treatments: 10,047,058

Cost per treatment: ($14,419,860 + $1,571,813 + $1,900,000) / 10,047,058 = $1.78

48.Total budgeted cost of RDTs: $1,373,774

Total budgeted cost of packaging for RDTs: $130,680

Total budgeted RDTs: 2,019,797

Cost per RDT: ($1,373,774 + $130,680) / 2,019,797 = $0.74

49.Tom Kanyok, phone conversation with GiveWell, June 29, 2012.