Are public-private partnerships the solution to tackle neglected tropical diseases? A systematic review of the literature
Introduction
Neglected tropical diseases (NTDs) are a diverse group of communicable diseases that affect more than one billion people, mainly across the developing world. The World Health Organization (WHO) lists 17 NTDs: Buruli Ulcer, Chagas disease, Dengue, Chikungunya, Dracunculiasis (guinea-worm disease), Echinococcosis, Endemic treponematoses, Yaws, Human African trypanosomiasis (sleeping sickness), Leishmaniasis, Leprosy, Hansen disease, Lymphatic filariasis, Onchorcerciasis (river blindness), Rabies, Schistosomiasis, Soil-transmitted helminthiases, Taeniasis, Cysticercosis, Trachoma [1]. It is common for people infected with NTDs to be hit by multiple pathogens; impairing physical and cognitive development, and leading to an estimated 534,000 death yearly [2]. These diseases were associated with 26.06 million disability adjusted-life years (DALYs) [3]. NTDs have a serious impact on work productivity: the largest of which seems to be due to blindness from onchocerciasis and severe manifestations of schistosomiasis [4]. Overall, these 17 diseases have been estimated to cost billions of dollars to developing economies each year [3].
The development of new treatments and vaccines cannot be incentivized through the usual patent system, for the ensuing reasons. First, the patent system grants monopoly power to pharmaceutical companies, usually for a period of 20 years, to encourage investment in research and development (R&D). The resulting lack of competition enables pharmaceutical companies to recoup R&D investment costs by setting a market price well above the marginal cost of production. Pharmaceutical companies are hence reluctant to invest in R&D for diseases that predominantly affect low and middle-income countries (LMICs) because of the health insurance system and consumers’ reduced ability-to-pay. Second, as LMICs are often characterized by poor local infrastructure and sanitation, lack of political commitment and bad governance in the health sector, lack of drug safety harmonization and weak legal frameworks, there can be no guarantee that a developed product will necessarily reach the population in need, thereby discouraging investment in R&D [5], [6], [7].
Translating this market failure into real facts, only five new therapeutic products were approved for NTDs between 2000 and 2011, accounting for less than 1% of the total products approved (i.e. 5 products out of 850). A significant share of the newly approved products instead targeted neuropsychiatric disorders (13%) and cardiovascular diseases (10%) [8]. This issue was pointed out by Bill Gates who, in 2008, called for “creative capitalism” [9], which include push, pull and mixed (push-pull) schemes. Push schemes reduce upfront costs inherent to R&D activities through various grants and subsidies offered prior to product discoveries – examples include R&D grants and direct funding. Pull schemes, on the contrary, offer a variety of rewards that are contingent on successful product discoveries – examples include advance market commitment (AMC) and priority review voucher (PRV). Push, pull and mixed schemes offer avenues for PPPs to overcome the barriers to the development of products for NTDs.
In 2011, half of the 34 new formulations for NTDs in clinical development – of which 85% were in Phase 2 or 3 – were sponsored through PPPs, charities, foundations and philanthropic institutions [8]. PPPs, so far, have mainly used push schemes, with government (e.g. The United Kingdom Department for International Development) or philanthropic (e.g. Bill and Melinda Gates Foundation) bodies providing upfront financing for clinical trials. The role of PPPs mainly lies in product development (PDPs; e.g. The Drug for Neglected Disease Initiative (DNDi)) and in product delivery and uptake (Access PPPs; e.g. The Onchocerciasis Control Program (OCP)). Other types of PPPs include financing and coordinating partnerships [10]. The different types of partnerships are not mutually exclusive: while it is more common for partnerships to dedicate themselves to one particular role, some use a hybrid model [10].
Tackling NTDs has become a major goal subscribed by the international community: the London Declaration – signed in 2012 – aims to reach the control or elimination of at least 10 NTDs by 2020 [11]. Various PPPs, with differing models, have hence been put in place to achieve this objective [12]. These have expanded over the past 20 years, and for some, the impacts are now measurable. Accordingly, we believe that it is now within researchers’ reach to assess the effectiveness and impact of these alliances. We thus conducted this review to respectively: (i) assess the scientific opinion on the adequacy and viability of PPPs; (ii) identify potential best mechanism(s) between push, pull and mixed ones; (iii) map the different partnerships and analyze their role in reaching the globally set goal to control, eliminate or eradicate NTDs.
Section snippets
Search strategy and selection criteria
A systematic literature search on PPPs for NTDs was performed over three databases: a general (Scopus), a bio-medical (PubMed) and an economic (IDEAS – Research Papers in Economics, REPEC) database. The search was conducted over three different databases to capture the multidisciplinary facets of PPPs. The REPEC database, for instance, enabled us to capture the economic perspective – a crucial feature – of PPPs and hence of the push, pull and hybrid mechanisms. In order to not discard any
Results
The search resulted in 198 non-duplicate articles, among which 6 could not be accessed. After abstract screening and full-text review, 74 articles were assessed eligible (cf. Fig. 1 for PRISMA diagram).
Discussion
The scientific literature on PPPs for NTDs is predominantly descriptive. An important part of the literature focuses on narrative descriptions of specific partnerships. A smaller but still significant share of the literature describes the different Schemes – push, pull and mixed Schemes – that can be used in a partnership. The striking point, however, is the small number of empirical studies: only 8 studies out of 74 had a research objective that was assessed through empirical investigation.
Ethical issues
There are no ethical issues.
Conflict of interest
There is no conflict of interest.
Acknowledgment
This project has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement N° 642609.
References (77)
- et al.
Programmes, partnerships, and governance for elimination and control of neglected tropical diseases
The Lancet
(2010) - et al.
Human anthelminthic vaccines: rationale and challenges
The Vaccine
(2016) - et al.
Stimulating pharmaceutical research and development for neglected diseases
Health Policy
(2003) - et al.
WIPO Re:Search: accelerating anthelmintic development through cross-sector partnerships
International Journal for Parasitology
(2014) - et al.
The introduction of new vaccines into developing countries. IV: Global Access Strategies
The Vaccine
(2007) Public-private partnership works to stamp out sleeping sickness in Uganda
Trends in Parasitology
(2007)- et al.
New vaccines for neglected parasitic diseases and dengue
Translational Research
(2013) - et al.
Advancing a vaccine to prevent human schistosomiasis
Vaccine
(2016) - et al.
The biotechnology-value chain: development of Sm14 as a schistosomiasis vaccine
Acta Tropica
(2008) - et al.
Strengthening vaccination policies in Latin America: an evidence-based approach
The Vaccine
(2013)
Measuring progress in neglected disease drug development
Clinical Therapeutics
The role of Product Development Partnerships in research and development for neglected diseases
International Health
Product development public-private partnerships for public health: a systematic review using qualitative data
Social Science & Medicine
The global burden of disease study 2010: interpretation and implications for the neglected tropical diseases
PLoS Neglected Tropical Diseases
Productivity loss related to neglected tropical diseases eligible for preventive chemotherapy: a systematic literature review
PLoS Neglected Tropical Diseases
Public-private partnerships for health: their main targets, their diversity, and their future directions
Bulletin World Health Organization
The role of modern drug discovery in the fight against neglected and tropical diseases
MedChemComm
The drug and vaccine landscape for neglected diseases (2000-11): A systematic assessment
The Lancet Global Health
A new Approach to Capitalism in the 21 st Century
Can medical products be developed on a non-profit basis? Exploring product development partnerships for neglected diseases
Science Public Policy
Perspectives on stimulating industrial research and development for neglected infectious diseases
Bull World Health Organ.
US incentive scheme for neglected diseases: a good idea gone wrong?
The BMJ
Optimal use of donor funding to incentivize vaccine research & development for neglected diseases: an analysis of different R&D incentive mechanisms
The Journal of Public and International Affairs
Financing sustainable drug development for neglected diseases: a case of push-Pull mechanisms and global public goods
The Economic and Social Review (IREL)
Drug discovery and development for neglected diseases: the DNDi model
Drug Drug Design, Development and Therapy
Progress in public-private partnerships to fight neglected diseases
Health Affairs (Millwood)
The human hookworm vaccine: recent updates and prospects for success
Journal of Helminthology
Innovation for the Bottom 100 million: eliminating neglected tropical diseases in the Americas
Advances in Experimental Medicine and Biology
Pharmaceutical innovation and public policy: the case for a new strategy for drug discovery and development
Science and Public Policy
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