Barriers to innovation in human rabies prophylaxis and treatment: A causal analysis of insights from key opinion leaders and literature

Abstract

SummaryRabies is an essentially 100% fatal, zoonotic disease, caused by Lyssaviruses. Currently, the disease is vaccine-preventable with pre-and post-exposure prophylaxis (PrEP and PEP). Still, rabies virus is estimated to cause up to 60,000 human deaths annually, of which the vast majority occurs in rural Asia and Africa, due to the inaccessibility of prophylaxis and non-existence of treatment. Despite these unmet clinical needs, rabies control mainly focuses on the sylvatic reservoir and drug innovation receives relatively little attention compared to other neglected tropical diseases (NTDs). As such, the lag of innovation in human rabies prophylaxis and treatment cannot be explained by limited return on investment alone. Strategies countering rabies-specific innovation barriers are important for the acceleration of innovation in human rabies prophylaxis and treatment. Barriers throughout society, science, business development and market domains were identified through literature review and 23 semi-structured interviews with key opinion leaders worldwide. A subsequent root cause analysis revealed causal relations between innovation barriers and a limited set of root causes. Finally, prioritization by experts indicated their relative importance. Root causes, which are fundamental to barriers, were aggregated into four types: market and commercial, stakeholder collaboration, public health and awareness, and disease trajectory. These were found in all domains of the innovation process and thus are relevant for all stakeholders. This study identifies barriers that were not previously described in this specific context, for example the competition for funding between medical and veterinary approaches. The results stress the existence of barriers beyond the limited return on investment and thereby explain why innovation in human rabies medication is lagging behind NTDs with a lower burden of disease. A re-orientation on the full spectrum of barriers that hinder innovation in rabies prophylaxis and treatment is necessary to meet unmet societal and medical needs. K E Y W O R D Sbarriers, preventive medicine, public health, rabies, root cause analysis, treatment of diseases † These authors contributed equally to this work.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Overcoming challenges for designing and implementing the One Health approach: A systematic review of the literature

“…Secondly, the geographic-cultural fragmentation is reflected in diverse social and cultural preferences, values and even disparities in knowledge and capacity; which is particularly, but not exclusively, evident in institutions from developed nations adjacent to developing countries. Building upon similar root causes found in the fields of OH data sharing [78] and rabies innovation [14], this study elaborates on fundamental challenges that generate persistent and complex problems for OH initiatives.…”

“…Solutions were classified on their extent of implementation indicating whether they were only recommended or also implemented in specific cases. Thirdly, a causal analysis was conducted, through the construction of a causal tree, to unravel arguments for defining causal relations between challenges [[13], [14], [15]]. Finally, a semi-quantitative analysis was performed to measure the frequency in which challenges and solutions were mentioned by the included papers.…”

A research agenda to reinforce rabies control: A qualitative and quantitative prioritization

“…The variety between KOLs of different disciplines is not surprising considering the general preference of animal rabies control measures, which seems to have caused a protective tendency by the public health sector. The significant importance that more experienced KOLs (>10 years of experience) give to the agent indicates that the limited successes in the past led to disbelief in possible solutions without a better understanding of the pathogenesis of rabies virus [ 34 ]. This finding not only argues for the reintroduction of basic research on research agendas, which has been diminished by ‘impact assessments’ [ 35 ], it also informs funders to shift their expectations for the development of novel medications against rabies from short-term to medium-long term.…”

“…This finding not only argues for the reintroduction of basic research on research agendas, which has been diminished by ‘impact assessments’ [ 35 ], it also informs funders to shift their expectations for the development of novel medications against rabies from short-term to medium-long term. Overcoming these innovation barriers, that can stop research (funding) in a premature phase [ 34 ], should coincide with the implementation of research priorities to optimize societal impact.…”

Lyssavirus Vaccine with a Chimeric Glycoprotein Protects across Phylogroups

“…There are a variety of ways to broaden a vaccine’s protective breadth, some of which have been attempted for lyssaviruses. A straightforward approach is to create multiple vaccine constructs, each expressing a separate lyssavirus G ( Evans et al., 2018b ), but this strategy would multiply the cost of a vaccine already deemed too expensive for the regions that need it most ( van de Burgwal et al., 2017 ). Furthermore, one lyssavirus G might be immunodominant over others.…”