The challenges of conducting clinical trials for neglected tropical diseases

Abstract

Clinical research involving human subjects is driven mainly by the availability of novel products, devices or interventions that require further investigations to determine their safety and efficacy. The designs of clinical trials are critical to ensuring scientific validity and reproducibility of the results and it is essential that ethical approval is obtained by well-informed ethical committees in all participating countries. The WHO has developed a roadmap for 17 poverty related diseases, collectively called neglected tropical diseases (NTDs) [1]. However, the WHO focus NTDs do not include malaria, HIV/AIDs and tuberculosis which account for nearly two-thirds of all R&D funding associated with poverty related or neglected diseases. According to the 2014 G-FINDER survey report [2], in 2013, US$3.2 billion were invested in R&D for 132 poverty related diseases referred to as ‘neglected diseases’ [2]. The investment targeted 138 products that included drugs, vaccines, diagnostics, microbicides and vector control products. The big three diseases, HIV/AIDS, malaria and TB received 69% of the global neglected disease R&D funding and less than 10% was invested in the WHO focus NTDs. Of the US$2.1 billion contributed by the public sector, over US$2 billion were provided by high income countries (HIC) that influenced the diseases to focus on. This may partly explain the huge disparity between funding for the big three diseases and the 17 WHO focus NTDs. Nevertheless, in 2012 and 2014, 22 partners from the public and private sectors, including WHO, Bill & Melinda Gates Foundation, pharmaceutical companies and the US and UK governments committed through the London Declaration on NTDs ‘to advance R&D through partnerships and provision of funding to find nextgeneration treatments and interventions for neglected diseases’ [3]. Many of the WHO focus NTDs are considered tools ready, and targeted for eradication or elimination by 2020 [1]. These include Guinea worm disease, lymphatic filariasis, leprosy, human African trypanosomiasis and blinding trachoma. Other focus NTDs including schistosomiasis, soil-transmitted helminthiasis (STH), Chagas disease, visceral leishmaniasis and river blindness (onchocerciasis) are targeted for control as a public health problem by 2020. Alternative intervention strategies based on new drugs, vaccines and novel devices have been proposed as additional tools that could fast-track the fight against NTDs [4–7]. However, many challenges exist for the conduct of clinical trials that will determine the safety and efficacy of the proposed new products and interventions. NTDs are diseases of neglected people living in lowand middle-income countries (LMIC) with little influence over the allocation of the substantial R&D funding required for the development of new products for “Making an investment case for the R&D for vaccines of tool ready diseases have been challenging but researchers advocating for new products, including vaccines, are aware of these challenges and the low priority given to diseases that are amenable to the WHO preventive chemotherapy strategy.”