van de Burgwal L H M, Neevel A M G, Pittens C A C M, Osterhaus A D M E, Rupprecht C E, Claassen E
Athena Institute, VU University, Amsterdam, The Netherlands.
Artemis One Health, Utrecht, The Netherlands.
Zoonoses Public Health. 2017 Dec;64(8):599-611. doi: 10.1111/zph.12352. Epub 2017 Mar 20.
Rabies 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.
狂犬病是一种基本上100%致命的人畜共患病，由狂犬病病毒引起。目前，该疾病可通过暴露前和暴露后预防（PrEP和PEP）进行疫苗预防。尽管如此，据估计，狂犬病病毒每年仍导致多达6万人死亡，其中绝大多数发生在亚洲和非洲农村地区，原因是预防措施难以获得且没有治疗方法。尽管存在这些未满足的临床需求，但狂犬病控制主要集中在野生动物宿主方面，与其他被忽视的热带病（NTDs）相比，药物创新受到的关注相对较少。因此，人类狂犬病预防和治疗方面创新的滞后不能仅用投资回报有限来解释。应对狂犬病特定创新障碍的策略对于加速人类狂犬病预防和治疗方面的创新很重要。通过文献综述以及对全球关键意见领袖进行的23次半结构化访谈，确定了社会、科学、商业发展和市场领域的障碍。随后的根本原因分析揭示了创新障碍与一组有限的根本原因之间的因果关系。最后，专家们进行的优先级排序表明了它们的相对重要性。作为障碍基础的根本原因被归纳为四种类型：市场与商业、利益相关者合作、公共卫生与认知以及疾病发展轨迹。这些在创新过程的所有领域都存在，因此与所有利益相关者都相关。本研究确定了在这一特定背景下以前未描述过的障碍，例如医学和兽医方法在资金方面的竞争。结果强调了除投资回报有限之外还存在其他障碍，从而解释了为什么人类狂犬病药物创新落后于疾病负担较低的被忽视热带病。有必要重新关注阻碍狂犬病预防和治疗创新的全方位障碍，以满足未满足的社会和医疗需求。
