Linking Research to Global Health Equity: The Contribution of Product Development Partnerships to Access to Medicines and Research Capacity Building

Abstract

Certain product development partnerships (PDPs) recognize that to promote the reduction of global health disparities they must create access to their products and strengthen research capacity in developing countries.

We evaluated the contribution of 3 PDPs—Medicines for Malaria Venture, Drugs for Neglected Diseases Initiative, and Institute for One World Health—according to Frost and Reich’s access framework. We also evaluated PDPs’ capacity building in low- and middle-income countries at the individual, institutional, and system levels.

We found that these PDPs advance public health by ensuring their products’ registration, distribution, and adoption into national treatment policies in disease-endemic countries. Nonetheless, ensuring broad, equitable access for these populations—high distribution coverage; affordability, particularly for the poor; and adoption at provider and end-user levels—remains a challenge.

PRODUCT DEVELOPMENT partnerships (PDPs) are not-for-profit organizations that build partnerships between the public, philanthropic, academic, and private sectors to drive the development of new products for underserved markets and thereby improve health in low- and middle-income countries (LMICs). The PDP mission differs from that of the pharmaceutical industry, whose main objective is to maximize profits for shareholders by creating interventions for lucrative markets. Key features of the PDP model are a public health objective, use of the portfolio management approach, focus on a neglected disease target, and development of technical interventions (vaccines, drugs, or diagnostics). Yet PDPs vary on several parameters, including their core choice of disease and product targets, scope or breadth of activities (basic research, clinical research, access activities, capacity building), financial model, and operations model.¹

The World Health Organization recognizes that PDPs can contribute to the reduction of global health disparities.² This idea has been reiterated by high-income country governments and influential organizations such as the United States’ Institute of Medicine, which identified the PDP platform as “one of the most promising approaches” to combat health disparities between and within countries.^3(p30),4 Accordingly, high-income country aid agencies, such as the US Agency for International Development and the United Kingdom’s Department for International Development, and philanthropic organizations have increasingly supported the PDP platform.⁵ Of the more than 60 existing drug projects for neglected diseases, three quarters are being performed by PDPs.⁶

Despite their capacity to generate much-needed interventions for neglected diseases, PDPs are not without their critics. It has been suggested that the paradigm perpetuates research disparities and power inequities between high-income countries and LMICs. Financial control and decision-making power within PDPs rest with first-world head offices and senior staff primarily from the United States and Europe.⁷ We recently contended that because the majority of PDPs’ investment in research infrastructure and personnel goes to high-income countries, their ability to promote global health equity may be impaired.⁸

For PDPs to improve the health of LMIC populations, it has been argued that they must not only develop new products for diseases identified as a priority by these countries but also, at a minimum, help to create access to their products and make meaningful efforts to strengthen research capacity.^9,10 PDPs have expertise in the conduct of clinical research, making them an appropriate vehicle for capacity building in that area. PDPs can thus promote LMICs’ ability to one day conduct their own research to develop products for neglected diseases and to improve their health systems.

Some PDPs appear to have recognized this and have expanded their scope to include access and capacity building. The access strategy of the Drugs for Neglected Diseases Initiative (DNDi) aims to facilitate a consistent and affordable treatment supply of DNDi products to LMICs; this entails ensuring rapid regulatory approval, making agreements with manufacturing partners, forecasting, ensuring supply to LMICs, and updating in-country treatment guidelines. Its strategy involves eventually shifting access activities for products to in-country champions.¹¹ The access approach of the Medicines for Malaria Venture (MMV) is similar but involves an element—expanding reach—that could extend its role further than DNDi’s. Expanding reach means working with partners to achieve availability not just at the country level but also at the clinic level (point of use) and to ensure uptake by patients. Unlike DNDi, MMV’s strategy does not discuss an endpoint of involvement.¹² In 2010, DNDi and MMV spent € 2.9 million (10.6% of total expenditure) and US $4.78 million (8.6% of total expenditure) on access and delivery, respectively.^13,14 The Institute for One World Health (OWH) is undertaking access activities as well, although it does not have a formal access strategy. Both MMV and DNDi are involved in building research capacity in LMICs, but OWH is not. Even so, different objectives underlie DNDi and MMV’s research capacity–strengthening efforts. MMV sees capacity building as necessary for its performance of high-quality clinical trials; DNDi aims to contribute to the development of sustainable health research systems in LMICs.^12,13

Although MMV, DNDi, and OWH have expanded their scope to access and capacity building, some funders and even PDP board members have questioned the appropriateness and effectiveness of PDPs’ role in these areas, suggesting that they should focus solely on product development.^15,16 Because most PDP products have only recently been launched, little investigation has been conducted into PDP achievements beyond product development to indicate whether such claims have substance. So far, PDPs have been evaluated against their success in financing and developing new vaccines and drugs, with their recent product approvals highlighted.^5,6 Aside from acknowledging that listing these products on the World Health Organization’s Essential Medicine List does not amount to access,¹⁷ PDPs’ contribution to product accessibility or to research capacity strengthening in LMICs has undergone limited assessment.

We examined the progress MMV, DNDi, and OWH have made in creating access to 8 of their recently launched products (Coartem Dispersible, Eurartesim, Pyramax, artesunate–amodiaquine [ASAQ], and artesunate–mefloquine [ASMQ] for malaria; nifurtimox–eflornithine combination therapy [NECT] for human African trypanosomiasis [HAT]; and paromomycin and sodium stibogluconate–paromomycin combination therapy for leishmaniasis). We selected these PDPs as the focus of our assessment because they are the first PDPs to have brought products to market.¹⁸ Relying on information derived from publicly available sources, we used the access framework developed by Frost and Reich to evaluate the 8 products for availability, affordability, and adoption.⁹ We assessed DNDi's and MMV's approaches to research capacity strengthening in LMICs for individual, institutional, and system achievements. This accords with a growing consensus that research capacity building at the country level requires strategies to be directed at these 3 distinct but complementary levels.^10,19 We also compared PDPs’ access activities to those of the pharmaceutical industry to determine whether the 2 types of drug development organizations’ differing missions affected their access approaches.

Because we only selected drug development PDPs for analysis, our conclusions may not reflect the approaches and achievements of vaccine development PDPs. Herman and Oudin argue that public health systems in LMICs are an adequate means of vaccine distribution to target populations.¹⁶ For certain vaccine PDPs, the GAVI Alliance also provides a centralized financing mechanism. As a result, access planning processes for new vaccines are potentially less complex and may require vaccine PDPs to take on fewer activities than do drug development PDPs.

CONTRIBUTIONS OF PRODUCT DEVELOPMENT PARTNERSHIPS

As shown in Table 1, aside from Eurartesim and Pyramax, which have only recently been approved by the European Medicines Agency, PDP products have been registered in most of the countries that hosted their efficacy trials. Pyramax, however, is likely to be an exception to this trend. It was tested in 18 countries in Africa, Southeast Asia, and India, but MMV’s registration strategy focuses on countries with areas of reported artemisinin resistance and reduced efficacy of other artemisinin-based combination therapies. So far, registration dossiers have been submitted to Myanmar and Vietnam, and future submissions are planned for Cambodia and Thailand. MMV, DNDi, and OWH are also making considerable progress toward registering their products in other countries endemic for HAT, malaria, and leishmaniasis, although progress in licensing specific products is often biased toward particular malaria-endemic regions. MMV’s Coartem Dispersible and DNDi’s ASAQ are primarily registered in African countries, whereas MMV’s Pyramax and DNDi’s ASMQ are registered or soon to be registered mainly in Southeast Asian countries. For leishmaniasis, 90% of cases occur in 7 countries.³¹ Paromomycin is registered or in the process of being registered in India, Nepal, and Bangladesh, with registration still required for Brazil, Ethiopia, Kenya, and Sudan. In the latter 3 countries, however, DNDi’s registration of sodium stibogluconate–paromomycin combination therapy is pending. (Trials showed that this combination was more effective than paromomycin at treating leishmaniasis in East Africa.¹¹) This commitment to broad registration is a particular strength of DNDi's and MMV's access approaches.

TABLE 1—

Availability and Affordability of Product Development Partnership Products in Disease-Endemic Countries

PDP (Partners)	Drug (Disease)	Trial Locations in LMICsa	Countries of Registration	Manufacturing Company	Distribution	Costb
MMV (Novartis)	Coartem Dispersible (malaria)	Benin, Kenya, Mali, Tanzania, Mozambique20,c	17 African countries,12 SwissMedic,21 on WHO’s Model Essential Medicines List for Children and in WHO’s 2010 Standard Treatment Guidelines12	Novartis (Switzerland)	As of June 2012, 152 million treatments delivered to 35 countries11	Price/full treatment = US $0.36d for patients 5–15 kg, US $0.72e for patients 15–25 kg12
MMV (Sigma-Tau Pharmaceuticals)	Eurartesim (malaria)	Burkina-Faso, Uganda, Zambia, Kenya, Mozambique, Thailand, Laos, India12,22,f	Approved by European Medicines Agency12	Pfizer (United States), Sigma-Tau Pharmaceuticals (Italy), Holleykin (China)12,23	Distributed only to Cambodia thus far; 160 000 treatments delivered in July 201212	Holleykin’s product costs ∼US $1–2g/2-d treatment course24
MMV (Shin Poong Pharmaceutical Company)	Pyramax (malaria)	18 countries in sub-Saharan Africa, Southeast Asia, and India, including Cambodia, Thailand, and Indonesia12,h	Approved by European Medicines Agency and Korea FDA; WHO has granted Pyramax prequalified status12 (Dossiers for registration submitted to Myanmar and Vietnam; Cambodia and Thailand to follow)	Shin Poong Pharmaceutical Company (South Korea)12	Product not distributed yet	Price/full treatment < US $1i for adults and US $0.50j for children25
DNDi (MSF Epicentre, HAT platform, Swiss TPH, National Control Programmes of the DRC and Republic of Congo, with support of WHO)	NECT (HAT)	Republic of Congok and DRC21	10 African countries, on WHO’s Model Essential Medicines List since 200911	Sanofi-Aventis (France), Bayer Schering Pharma (Germany)11	> 4000 treatments distributed in 2011 in 12 African countries that account for 99% of HAT cases11,13	Donated by manufacturers through 201426
DNDi (Sanofi-Aventis)	ASAQ (malaria)	16 African countries, India, Columbia, Malaysia27,l	30 African countries and India,13 WHO has granted ASAQ prequalified status11	Produced in Morocco,11 technology transfer planned to Zenufa (Tanzania) in 201113	By late 2010, 80 million treatments distributed in 21 countries,27 by 2012, 120–150 million treatments distributed11	Price/full treatment = US $0.50m for children and US $1n for adults11
DNDi (Farmanguinhos, Cipla, FACT project consortium, WHO-TDR)	ASMQ (malaria)	Thailando, India, Brazil, Tanzania (planned)28	Brazil, India, Malaysia, and soon Myanmar,11 submitted to WHO for prequalified status13	Farmanguinhos/Fiocruz (Brazil), and Cipla Ltd (India)11	100 000 treatments distributed to Brazil, India, Myanmar, and Malaysia11	$2.50p/adult treatment29
DNDi (LEAP, MSF, WHO, and National Control Programmes in Kenya, Ethiopia, Sudan, and Uganda)	SSG and PM combination therapy (leishmaniasis)	Kenya, Ethiopia, Sudan, Uganda13	Registration efforts under way in East African countries11	Albert David (India), GlaxoSmithKline (UK) (SSG), Gland Pharma Limited (India; PM)11	Distribution in Sudan and South Sudan under way11	∼US $44q/17-d adult course11
OWH (Gland Pharma Limited, WHO-TDR)	PM (leishmaniasis)	India30	India, Nepal, and soon Bangladesh,18 on WHO’s Model Essential Medicines List31	Gland Pharma Limited (India)31	Deployed in Bihar, India, > 50 000 vials (1 injection/vial) supplied to Africa in 2010–201131	∼US $20r/adult course of 21 injections, 1/d32

Note. ASAQ = artesunate–amodiaquine; ASMQ = artesunate–mefloquine; DNDi = Drugs for Neglected Disease Initiative; DRC = Democratic Republic of Congo; FACT = fixed-dose artesunate combination therapy; FDA = Food and Drug Administration; HAT = human African trypanosomiasis; LEAP = Leishmaniasis East Africa Platform; LMICs = low- and middle-income countries; MMV = Medicines for Malaria Venture; MSF = Médecins Sans Frontières; NECT = nifurtimox–eflornithine combination therapy; OWH = Institute for One World Health; PDP = product development partnership; PM = paromomycin; SSG = sodium stibogluconate; TPH = Tropical and Public Health Institute; UK = United Kingdom; WHO-TDR = World Health Organization Special Programme for Research and Training in Tropical Diseases.

Source. For wage comparisons, CIA World Factbook.³³

^aSites of efficacy trials involving MMV, DNDi, or OWH.

^bProduct costs not necessarily actual sale prices.

^cCoartem Dispersible has not yet been registered in Mozambique.

^dRoughly 8.6%–17% of a day’s wage in Mozambique.

^eRoughly 17% of a day’s wage in Mozambique.

^fEuratesim has not been registered in any of these countries yet.

^gRoughly 24%–48% of a day’s wage in Mozambique.

^hPyramax has not been registered in any of these countries yet.

ⁱRoughly 43% of a day’s wage in DRC.

^jRoughly 87% of a day’s wage in DRC.

^kNECT has not yet been registered in the Republic of Congo.

^lASAQ has not yet been registered in Columbia or Malaysia.

^mRoughly 22% 43% of a day’s wage in Liberia.

ⁿRoughly 43% of a day’s wage in Liberia.

^oASMQ has not yet been registered in Thailand.

^pRoughly 41% of a day’s wage in Tanzania.

^qRoughly 4.3 days’ wages in Sudan.

^rRoughly 1.4 days’ wages in India.

Manufacturing and Distribution

As shown in Table 1, MMV typically partners with high-income country pharmaceutical companies; aside from NECT, DNDi and OWH products are manufactured in LMICs. Partnering with high-income country firms means that MMV does not strongly build the capacity of LMIC manufacturers.

Manufacturers of Coartem Dispersible and NECT are located in all malaria- and HAT-endemic regions of the world. However, the manufacturers of the other 6 products are not necessarily located in all regions endemic for malaria and leishmaniasis. For example, Pfizer and Sigma-Tau will ensure access to Eurartesim in Africa in collaboration with various local stakeholders, but manufacturing partners in other malaria-endemic regions are not identified.²³ Shin Poong Pharmaceuticals has affiliations in Vietnam and Sudan for manufacturing but not in South America.¹² This may have implications for product availability in other regions. A means of avoiding overreliance on manufacturers from a single region is reflected in DNDi’s South–South technology transfer platform and could be employed by other PDPs.

As shown in Table 1, NECT (for HAT) and Coartem Dispersible and ASAQ (for malaria) have been delivered to a significant proportion of disease-endemic countries. Even so, it is unclear whether the volume of the 8 products delivered to countries aligns with population need (or demand, though MMV’s access strategy identifies a forecasting role for the PDP). The limited information available on product distribution generally gives an aggregate amount (i.e., the total number of treatments distributed to the total number of countries) rather than detailing amounts by year and by country. The little disaggregated information we could find indicates that distribution of Eurartesim to Cambodia may exceed the population’s need and that distribution of paromomycin and NECT to Africa may fall short of what is needed (Table 1). A lack of correspondence between need and distribution may be a weakness of the PDP approach, but more information is required to verify this.

Existing evidence suggests that levels of product distribution may be higher in the public sector and vary considerably by country. In Cambodia, where ASMQ is the first-line treatment for malaria, only 6.5% of all outlets stock the drug.³⁴ In the Democratic Republic of Congo and Madagascar, where ASAQ is the first-line treatment, 20.2% and 85.6%, respectively, of public and 8.6% and 20% of private facilities have the drug.^35,36 In Burundi, 90% of public and nongovernmental organization outlets and 33% of private outlets stock ASAQ.³⁷ Further work is needed to increase distribution, particularly in private markets, because a significant proportion of people access medicines primarily through this sector.³⁸ (MMV has done an in-depth survey of Uganda’s antimalarials market, but this provides distribution information for the artemisinin-based combination therapy, artemether–lumefantrine, rather than ASAQ or ASMQ, because artemether–lumefantrine is Uganda’s first-line treatment for malaria.¹²)

Affordability

As shown in Table 1, the cost of most products is quite low, which is a strength of the PDP model. Only limited information is available about the prices at which they are sold (which may be higher or lower than the product cost) and their affordability within countries. Evidence from Burundi shows that a course of ASAQ is US $0.16 in the public sector, or 40% of a day’s wage. However, its price in the private sector is higher (US $0.56), amounting to a day and a half’s wages.³⁷ In the Democratic Republic of Congo and Madagascar, 90% and 92.5%, respectively, of ASAQ treatments are distributed for free. Among outlets that sell ASAQ in the Democratic Republic of Congo, the median price is US $2.72 (roughly 2.4 days' wages) in public facilities and US $3.43 (roughly 3 days' wages) in private facilities.^35,36 (To determine this, we calculated a rough daily wage derived from the gross domestic product per capita of the Democratic Republic of Congo [US $300]. We assumed a 5-day work week [although 7 days may be more accurate], dividing 300 by 261, to generate a likely daily wage [US $1.15].) In Cambodia, 61.2% of ASMQ treatments are distributed free of cost. Among outlets that sell ASMQ, the median price is US $1.18 (roughly 15% of a day’s wage).³⁴ (We based our calculation on Cambodia's gross domestic product per capita of US $2100.) In these 4 countries, then, ASAQ and ASMQ are either free or moderately affordable, particularly in the public sector. More information is needed regarding the price and affordability of Coartem Dispersible and paromomycin in countries of registration and of ASAQ and ASMQ in other countries where they are first-line treatments. MMV has developed a survey method that can be used to gather this information.¹²

Higher costs of artemisinin-based combination therapies in the private sector probably affect their accessibility. To lower prices, the Global Fund has set up the Affordable Medicines Facility for Malaria. This financing mechanism provides significant subsidies to the private sector to procure these therapies, which are then sold at much-reduced prices, leading to rapid uptake. Two pilot studies conducted by MMV in Uganda have demonstrated that this mechanism can work, which may inform the wider implementation of this approach.¹²

Adoption

As shown in Table 2, DNDi has done an excellent job of ensuring that its products are listed in national treatment guidelines for HAT and malaria in disease-endemic countries. In keeping with the locations of DNDi's manufacturers, ASAQ is the first-line treatment in the national guidelines of 20 African countries and Indonesia, and ASMQ is the first-line treatment in the national guidelines of 5 South American countries and 4 Southeast Asian countries.^12,29 This success likely reflects DNDi’s practice of collaborating with national malaria control programs in endemic countries.²⁷

TABLE 2—

Adoption of Product Development Partnership Products in Disease-Endemic Countries

		Adoption Strategies
PDP (Partners)	Drug (Disease)	Global Level	National Level	Provider Level	User Level
MMV (Novartis)	Coartem Dispersible (malaria)		Engaging country policymakers to encourage the revision of national treatment guidelines,39 briefing National Malaria Control Programmes about availability of this new child-friendly product.12	Best-practice workshops sponsored by Novartis.12
MMV (Sigma-Tau Pharmaceuticals)	Eurartesim (malaria)		Adopted in the national treatment policy of Ghana.12 MMV Access helps WHO and country-level decision-makers consider Eurartesim for inclusion in their Standard Treatment Guidelines.12
MMV (Shin Poong Pharmaceuticals)	Pyramax (malaria)		MMV Access helps WHO and country-level decision-makers consider Pyramax for inclusion in their Standard Treatment Guidelines.12
DNDi (MSF Epicentre, HAT platform, Swiss TPH, National Control Programmes of DRC and Republic of Congo, with support of WHO)	NECT (HAT)		Adopted in national treatment policies of 9 endemic countries.28	WHO-sponsored medical training sessions for administering NECT held in DRC for representatives from Cameroon, Central African Republic, Chad, DRC, Guinea, and Republic of Congo, and in Uganda for representatives from Uganda and southern Sudan.21
DNDi (Sanofi-Aventis)	ASAQ (malaria)		Adopted in the national treatment guidelines of 20 African countries and Indonesia; Sanofi-Aventis partnering with National Malaria Control Programmes in 12 African countries.40		Education tools developed for school children.28
DNDi (Farmanguinhos, Cipla, FACT project consortium, WHO-TDR)	ASMQ (malaria)		Adopted into national treatment guidelines of Bolivia, Brazil, Columbia, Peru, Venezuela, Cambodia, Malaysia, Burma, and Thailand,29 malaria-endemic countries (e.g., India, Bangladesh, Laos, Vietnam, Ecuador) have not yet adopted.29
DNDi (LEAP, MSF, WHO, and National Control Programmes in Kenya, Ethiopia, Sudan, and Uganda)	SSG and PM combination therapy (leishmaniasis)	WHO Expert Committee on the Control of Leishmaniasis recommends SSG&PM as first-line treatment for visceral leishmaniasis in East Africa.13	Sudan’s Ministry of Health recommends SSG&PM as first-line treatment for visceral leishmaniasis.13
OWH (Gland Pharma Limited, WHO-TDR)	PM (leishmaniasis)		OWH collaborating with governments of India and Nepal on public sector adoption of PM.41

Note. ASAQ = artesunate–amodiaquine; ASMQ = artesunate-mefloquine; DNDi = Drugs for Neglected Disease Initiative; DRC = Democratic Republic of Congo; FACT = fixed-dose artesunate combination therapy; HAT = human African trypanosomiasis; LEAP = Leishmaniasis East Africa Platform; MMV = Medicines for Malaria Venture; MSF = Médecins Sans Frontières; NECT = nifurtimox–eflornithine combination therapy; OWH = Institute for One World Health; PDP = product development partnership; SSG = sodium stibogluconate; TPH = Tropical and Public Health Institute; WHO-TDR = World Health Organization Special Programme for Research and Training in Tropical Diseases.

MMV has carried out adoption activities at the national level related to Coartem Dispersible, Eurartesim, and Pyramax (Table 2, box on p.1976). Because the latter 2 products have only recently gained European Medicines Agency approval, they are not listed in national treatment guidelines of malaria-endemic countries, aside from Ghana. Paromomycin is not listed in India’s National Vector-borne Disease Control Program’s leishmaniasis treatment guidelines,⁴² but this may change. OWH is working with the Indian government to support the drug’s adoption and distribution.

Other Adoption Activities of the Medicines for Malaria Venture, Drugs for Neglected Diseases Initiative, and Institute for One World Health

Regional and national levels

• Regional scientific symposium with participation of national malaria control program managers and international and regional organizations in South America.29 (DNDi)

• Regional workshop briefing to engage national malaria control program managers and international and regional organizations in India, Africa, and Southeast Asia. 29 (DNDi)

• Country-level dialogues such as subregional meetings of WHO and Roll Back Malaria and, in select cases, day-long workshops (MMV Access Symposia) to give product-specific briefings and to reinforce WHO recommendations on best practice for the development and revision of national treatment guidelines. (MMV, DNDi)

• Representatives from key research organization in endemic counties that make national decisions about adoption on DNDi board of directors.28 (DNDi)

• Engagement of key stakeholders in Indian government, World Bank, and WHO.28 (OWH)

• Field trials, conducted in collaboration with national programs and NGOs, to demonstrate product feasibility and generate data for adoption into national programs.11,21 (DNDi, OWH)

• Support for training programs and policy change to incorporate child-friendly medicines into national treatment guidelines.14 (MMV)

• Engagement with national decision-makers from a cross-section of 6 countries in sub-Saharan Africa to understand national preferences for child-friendly formulations of drugs.14 (MMV)

• Development of training modules and community communication modules for national authorities.28 (OWH)

Provider level

• Training sessions for providers. (DNDi)

Note. DNDi = Drugs for Neglected Disease Initiative; MMV = Medicines for Malaria Venture; NGO = nongovernmental organization; OWH = Institute for One World Health; PDP = product development partnership; WHO = World Health Organization.

Research Capacity Strengthening

MMV allocates 2% of its annual research and development budget to strengthening research capacity in LMICs.^12,15 In 2009, DNDi and MMV invested US $1.3 million and US $886 000, respectively, in building infrastructure at trial sites, providing equipment, and training individuals from LMICs in good clinical practice.^43,44 Although MMV has limited capacity-building objectives compared with DNDi, MMV has a much larger research and development budget than DNDi, so 2% of this budget amounts to nearly a million dollars.

DNDi’s efforts focus solely on Africa; MMV has built capacity at trial sites in Southeast Asia and the Pacific as well. Thus far, 27 functional research sites and 9 sites with basic facilities have been upgraded to good clinical practice standards across 23 countries.¹² Ultimately, DNDi and MMV investment creates trial sites in LMICs that are compliant with these standards, to support the development of their products. This includes countries with very low research capacity, such as Chad, Sudan, and Angola, as well as countries with comparatively stronger research systems, such as Thailand, Tanzania, Kenya, and Uganda.^12,23 Such efforts, however, cannot be considered to be building sustainable capacity for LMIC research systems at the individual, institutional, or system levels. Creating good clinical practice–compliant trial sites does not necessarily strengthen research institutions in LMICs or increase the number of LMIC nationals who are able to carry out their own research studies.

To support its broader capacity-building mission, DNDi also has 2 regional platforms dedicated to HAT and leishmaniasis research that bring together partners from more than half of the endemic countries for each disease.⁴⁴ The platforms’ reported achievements include their members’ participation in clinical trials (primarily for DNDi products), conduct of good clinical practice and postgraduate training for local researchers and technicians, building of infrastructure, and communication between partners.¹³ In 2011, DNDi supported the postgraduate training of 8 individuals from 4 countries, although the conferral of specific degrees was not reported.¹³ It has been suggested that these platforms have made a limited contribution to capacity building, particularly at the individual level, because they have not resulted in any postgraduate degrees or first-author publications for African researchers.⁴⁵ It is difficult to tell from publicly available information whether some trial sites can now perform clinical research independent of researchers from high-income countries or even whether their doing so is a long-term goal. Future capacity-building efforts and evaluation criteria might usefully include building a core nucleus of research faculty (through postgraduate degree training) at LMIC institutions and enhancing those institutions’ ability to train researchers and to be competitive when applying for external grants.

COMPARISONS WITH PHARMA

Comparisons between the health impact of Pharma and PDP products have been based on the criterion of affordability but not on the overall access strategies embraced by their developers.⁶ We compared the access strategy of GlaxoSmithKline with those of MMV, DNDi, and OWH to assess whether their differing organizational missions affect their approaches to creating access. (Although one might assume this to be the case, the question has not been investigated to corroborate such an assumption.) GlaxoSmithKline was ranked first out of 20 pharmaceutical companies in the 2 most recent Access to Medicines Index reports.^46,47 GlaxoSmithKline’s access strategy for its independently developed neglected-disease products has 2 main components: flexible pricing and investment in health care infrastructure. Its priority is contributing to a single aspect of access—affordability—and it considers national governments and the international community to be responsible for achieving the rest.⁴⁸

Accordingly, GlaxoSmithKline has implemented a pricing strategy for antiretrovirals that offers its drugs (10 so far: Combivir, Epivir–lamivudine, Epzicom–kivexa, Lexiva–telzir, Rescriptor, Retrovir–zidovudine, Selzentry–celsentri, Trizivir, Viracept, and Ziagen⁴⁹) at not-for-profit prices to 135 countries and a (royalty-free) voluntary licensing program that allows generic manufacturers to produce and sell its antiretrovirals in least-developed countries, World Bank low-income countries, and sub-Saharan Africa.⁵⁰ This has expanded the number of manufacturers, which in turn has increased the scale of antiretroviral drug supply and lowered prices. The company first issued voluntary licenses for the antiretroviral Combivir (approved by the Food and Drug Administration in 1997) in 2006. Subsequently, supply has more than tripled, and the price of an annual supply has been lowered from US $730 per patient in 2001 to US $110 per patient in 2011, with 5 generic manufacturers entering the market.^4,49 A similar effect has been observed for Abacavir (approved in 1980), after the company implemented not-for-profit prices and issued voluntary licenses in 2009.^49,51 For diseases other than HIV/AIDS, GlaxoSmithKline sells its patented products in LMICs (where they are registered) at 25% of their cost in the United Kingdom. So far, this applies to 11 patented products, only 2 of which (Malarone and Zeffix) combat infectious diseases.^49,50 GlaxoSmithKline also invests 20% of the profits it makes from selling its products in the least-developed countries into improving their health care infrastructure. In 2012, this amounted to £ 3.8 million.⁵²

By contrast with MMV, DNDi, and OWH, GlaxoSmithKline’s access approach does not entail ensuring product registration and distribution to disease-endemic countries or adoption into national treatment guidelines. Furthermore, PDP products are created to be low cost; GlaxoSmithKline’s patented products are not. Even with price reductions, Malarone is still more expensive than ASAQ or Pyramax.

CONCLUSIONS

MMV, DNDi, and OWH are successfully implementing an access strategy with the following components: product registration and distribution to disease-endemic countries, assurance of a comparatively low-cost product, and product adoption into national treatment guidelines. They have achieved considerable improvement in product access in a short period (≤ 5 years since products were launched), which is especially significant in light of the difficulties in gaining regulatory approval for interventions in African countries.⁵³ Nonetheless, the 3 PDPs clearly vary in the magnitude of their activities, with MMV and DNDi pursuing access to their products in many more disease-endemic countries than OWH. DNDi, in particular, appears to be achieving most elements of its access strategy, perhaps aside from affordability. It has announced plans to shift the technology transfer and access activities for its malaria products (ASAQ, ASMQ) to other partners in 2014.¹³

Achieving the next steps toward broad, equitable access—high distribution coverage in the public and private sectors; affordability, particularly for poor populations; and adoption at provider and end-user levels—will be difficult. DNDi and OWH likely do not consider such activities to fall within their mission, although these activities may be part of MMV’s access strategy.³⁸ If MMV aims to create broad, equitable access to its products in LMICs, its progress is difficult to evaluate. Key information gaps remain regarding product distribution, affordability, and adoption (by health providers and end users) within countries. To the extent that it is possible, these criteria should be measured as part of future efforts to evaluate the impact of MMV on access, and these findings should be made public. Methods already exist for these purposes.^12,54

To achieve equitable in-country access, parallel investment in health policy and systems research, which does not necessarily fall within the scope of PDP activities, is likely to be required to overcome health system barriers to high-volume delivery.^55,56 Germinal research is being performed by PDPs in relation to the availability, affordability, and adoption of their products, which might be scaled up in the future. For example, MMV has conducted market research in Malawi to assess the relative affordability and distribution of the various artemisinin-based combination therapies and to identify possible means of addressing any gaps in coverage.¹² OWH is performing stakeholder analyses to determine what South Asian governments require to accept and distribute paromomycin in the public sector.⁴¹ The outputs of this research inform PDPs’ access activities, although available information does not describe how.

Ultimately, MMV and DNDi, in particular, are better than the pharmaceutical industry at developing novel and inexpensive products for neglected diseases and at supporting access to their products. Although this suggests that PDPs should not limit their role to product development, they may need to clarify or redefine the scope of their access activities in relation to other global health partnerships.¹⁵ To assist PDPs to identify where their comparative advantage lies and how far their role in access should extend, their access and delivery achievements should be compared with those of the Global Fund and UNITAID. No existing option is perfect, but it is entirely possible that PDPs are duplicating existing functions of global health partnerships that may be more effective at creating access to medical products in LMICs.

Finally, DNDi needs to better align its activities with its capacity-building objective. If the long-term intention is to promote the development of independent, competitive research institutions and scientists in LMICs, this may require changing the nature of the HAT platform and the Leishmaniasis East Africa Platform and their evaluation indicators. Although MMV appears to be meeting its limited capacity-building goals, it should adopt a broader approach that aims to enhance LMIC research systems.