Preparedness for clinical research during pandemics: a perspective from the Platform for European Preparedness Against (Re-)emerging Epidemics (PREPARE)

Abstract

BackgroundA new or re-emerging infectious disease pandemic ranks among the highest priorities for civic contingency planning. Despite advances in preclinical and clinical research methods, patient-centered clinical research is not effectively embedded in outbreak responses to inform clinical management of patients and public health responses. Prefunded clinical research networks offer a solution but require well-specified processes for rapid response. We aimed to define a model for how a prefunded clinical research network, Platform for European Preparedness Against (Re-)emerging Epidemics (PREPARE), could rapidly respond at the earliest stages of a new or re-emerging infectious disease outbreak. MethodsTo develop and test the operational framework, we consulted with multiple stakeholders and facilitated tabletop simulation exercises in Lisbon (May 3, 2017), Brussels (Oct 3, 2017), and Berlin (May 14, 2018). Delegates simulated clinical research planning and delivery, based on PREPARE's operational capabilities, in response to infectious disease outbreak scenarios. Meeting outcomes informed iteration of an operational framework. FindingsWe developed an operational framework to detail how PREPARE is triggered, and escalates and de-escalates a response. On receipt of a valid trigger signalling an infectious disease outbreak, a rapidly convened expert committee determines the scale and scope of a proportionate clinical research response in one of three outbreak response modes (preparation, mobilisation, response). Modes are defined by the risk to the health and security of European citizens and the need for clinical research contribution. An operational team develops and delivers bespoke outbreak-relevant research plans through research-active clinical research networks across Europe. Simulation exercises have rehearsed the consortium's response to a hypothetical influenza pandemic and estimate it would take up to 3 weeks for existing sites to be open to patient recruitment. A tiered approach and amendment of existing protocols, contracts, and study materials enable a rapid response. However, ethical, regulatory, administrative, laboratory, and logistic bottlenecks present an ongoing challenge to rapid research deployment. Pragmatic solutions have been mapped, including expedited regulatory review, generic contracts, and modified research enrolment procedures. InterpretationPREPARE's outbreak capability is an important step forward in delivering clinical research during an infectious disease pandemic. When properly aligned with public health activities, both patient outcomes and public health responses will benefit from sustained clinical networks. PREPARE's operational framework may be adapted for use by clinical trial networks operating in different global regions. FundingPREPARE is funded by the European Commission's FP7 programme (grant agreement 602525).