An economic perspective on the challenges associated with tackling neglected diseases: from product development to implementation and adoption

Abstract

[eng] The World Health Organization (WHO) has identified over 20 neglected tropical diseases (NTDs), affecting 1.5 billion people worldwide (Uniting to combat neglected tropical diseases, 2017). While being all infectious diseases, many NTDs are chronic, with conditions that progressively become worse if undetected and untreated. Moreover, the damage they cause is often irreversible with important social and economic consequences (Sachs et al., 2007; Lenk et al., 2016). Such diseases are called neglected because they mainly affect the world’s poorest populations, for whom there is no interest from the pharmaceutical industry to invest in research and development (R&D). As a result, most of the drugs currently used to treat NTDs are repurposed drugs that were originally developed for other indications (e.g. miltefosine for leishmaniasis was initially developed for cancer) (Pink et al., 2005; Cheuka et al., 2017; Weng, Chen and Wang, 2018). This is not without repercussions on their adequacy and efficacy, with various limitations including drug resistance, severe adverse-effects, lengthy treatment regimens, toxicity and complicated administration procedures (Cheuka et al., 2017). While some NTDs such as leprosy, lymphatic filariasis (LF), trachoma, dracunculiasis can be eliminated using the currently available drugs, the remaining majority of NTDs truly need safe, effective, low-cost and short-course treatments (Weng, Chen and Wang, 2018). Given the many drawbacks of NTDs drugs, diagnostic tools that are accurate (i.e. good sensitivity and specificity) and field-amenable are particularly needed to decrease the number of untreated cases and ensure that patients are given the right treatment. Yet, since many of these diseases are zoonotic and/or vector-borne, control strategies based only on treating the infected human population are unlikely to be successful, thus leading to the concept of “one health” approach (Weng, Chen and Wang, 2018) (Okello et al., 2011). It is generally agreed that vaccines are powerful and often cost-effective tools to reach elimination. However, vaccine development in the NTDs era has lagged behind: currently, licensed vaccines only exist for yellow fever, dengue and rabies (Hotez, 2018). Unfortunately, the development of products for NTDs cannot rely upon the pharmaceutical industry alone. People affected by NTDs are mainly poor, live in countries with weak health systems that care for them, and will not be able to afford what the pharmaceutical industry will charge – resulting in the so-called market failure. As a result, in 2012, international organizations, partners from donor agencies and the pharmaceutical industry met in London to tackle the situation regarding NTDs and endorse the London Declaration, which specifically targeted the control or elimination of at least 10 NTDs by 2020 (Uniting to combat neglected tropical Diseases, 2012). To comply with this objective, a variety of push and pull mechanisms have been suggested; some of which have been implemented. These include, among others, R&D grants, priority review voucher (PRV) and advance market commitment (AMC). The rationale behind push and pull mechanisms is to delink the cost of research from the price of the product, so that the incentive to invest in the R&D of a particular NTD is not or less contingent on the price at which the product will be sold (Tuttle, 2016). Push mechanisms reduce the costs associated with R&D in advance of investment (ex-ante) whereas pull mechanisms offer rewards that are contingent on successful product discoveries (ex-post). Push and pull mechanisms are not mutually exclusively: they can be combined to form mixed mechanisms. Push, pull and mixed mechanisms provide avenues to public-private partnerships (PPPs) and more specifically to product-development partnerships (PDPs) .Partners of PDPs generally include non-governmental organizations (NGOs), academia, government and industry, with varying expertise that can be used at the appropriate stage to ensure a smooth development process. PDPs for NTDs have proliferated over the last two decades; in 2017, PDPs received 508$ million, accounting for 14% of all neglected disease basic research (Policy Cures Research, 2018). PDPs may focus on single disease and/or product type or alternatively, operate across multiple diseases and/or product types. Yet, the challenges associated with NTDs are not limited to R&D market failure. A product that is developed may not be cost-effective for the country needing it. More precisely, the gain in effectiveness from a new product often comes at a cost, which affordability will depend on the country’s available resources and often represented by the gross domestic product (GDP) per capita. Cost-effectiveness analysis is a unique tool that allows to judge whether new products should be implemented in a country of interest. Yet, this is not a silver bullet: a product judged cost-effective and thus implemented may still not be accessible for diverse reasons, such as high prices, poor infrastructure, weak health systems and non-financial barriers (e.g. wrong beliefs, lack of knowledge and inaccurate perception of the infection’s risk). Dwelling deeper into those non-financial barriers is even more crucial in the context of NTDs since most of these are vector-borne diseases (VBDs). For VBDs, individuals’ demand/behavior about prevention plays a role in infection transmission. Furthermore, since the actual risk of infection is often uncertain, individuals’ demand/behavior is influenced by their perception of the risk. A low risk perception, corresponding or not the actual risk, is likely to diminish the use of preventive measures (behavior). If risk perception is a good indicator of the actual risk of infection, then it has important implication in a context of disease elimination. However, as of now, very little empirical research has been conducted on the topic. Therefore, as one can see, many barriers to the elimination of NTDs – from product development, to implementation and adoption – have economic components that warrant economic analyses. Accordingly, the general objective of this thesis is to improve our understanding of selected obstacles, from product development to their adoption at the individual level.