Addressing political, economic, administrative, regulatory, logistical, ethical, and social challenges to clinical research responses to emerging epidemics and pandemics: a systematic review

Abstract Background Clinical research generates evidence for improving clinical management and control of emerging epidemics. However, experiences from previous disease outbreaks have identified multiple challenges to undertaking necessary clinical research in a timely way. We aimed to identify how political, economic, administrative, regulatory, logistical, ethical, and social (PEARLES) challenges can be overcome to advance clinical research preparedness and responses to emerging epidemics by searching the literature. Methods In this systematic review, we searched six databases (MEDLINE, Embase, Ovid Global Health, PsycINFO, Scopus, and Epistemonikos) for English language articles published between Jan 1, 2008, and July 31, 2018. We included articles about clinical research responses (ie, responses regarding the safety and effectiveness of medications, treatment regimens [including supportive care], devices, or diagnostic products intended for human use) to epidemics that were declared a public health emergency of international concern and that contained up-to-date information. We did not include studies that only focused on public health responses. Two reviewers screened records for inclusion and extracted and summarised the data using a narrative approach. We included publications reporting PEARLES challenges of, and solutions to, the instigation of clinical research responses to emerging epidemics, or solutions identified through research with health system stakeholders. Findings Of 2678 articles screened for inclusion, 76 articles were included. Most presented clinical research experiences from the 2014–16 Ebola virus disease outbreak (58 [76%]) or the 2009 H1N1 pandemic (20 [26%]), or both. The articles related to studies set in Africa (n=37), Europe (n=8), North America (n=5), Latin America and the Caribbean (n=3), and Asia (n=1); 22 articles covered a global perspective. The publications presented a range of challenges to delivering clinical research. Some were universal, others depended on the context and nature of the outbreak. International agreed frameworks, research protocols and standards, data sharing agreements, ethical publication standards, and incentivised, primed, global clinical research networks were among the solutions recommended, together with national ownership and community engagement from the outset and strengthening of country research capacity. Despite the wide range of recommended solutions, none had been formally evaluated. Interpretation To strengthen global preparedness to emerging epidemics, solutions for rapid clinical research deployment, delivery, and dissemination must be developed, implemented, and evaluated. Improvements are urgently needed to develop and strengthen collaborations, funding mechanisms, global and national research capacity, pre-approved protocols, tools, and frameworks for various contexts and scenarios. Clinical research communities globally need to evaluate their activities and refine and rehearse outbreak research response plans in between epidemics. Funding Global Research Collaboration for Infectious Disease Preparedness for (GLoPID-R) Secretariat (GLOPID-R-Sec), grant agreement 643434.