A key lesson from a series of recent epidemics of emerging pathogens of global public health importance (e.g., the 2009 H1N1 influenza pandemic) was that implementing clinical research in response to a rapidly emerging ID is extremely challenging and often delayed. We currently do not have European framework for ensuring that clinical research is built into epidemic responses and in fact our present research culture often precludes a rapid clinical response. Because of this, clinical research studies generally miss the initial waves of an epidemic or pandemic and in many cases fail to enroll significant numbers of patients across the clinical spectrum of disease, even during subsequent waves. This in turn means the opportunity is missed to improve patient outcomes and develop high-quality evidence to inform future clinical management strategies at the ‘coalface’. Indeed, in almost all epidemics over the last decades very little research directly aimed at improving clinical management or understanding pathogenesis has been able to be conducted. PREPARE has been designed to change the approach to clinical research, so a next epidemic will not result in a missed opportunity to save lives and advance medical knowledge.