An umbrella protocol for the clinical evaluation of diagnostics in infectious disease

Umbrella protocols have recently come to be widely used in clinical trial designs. However, the value of this approach in public health is less well recognized. The coronavirus disease 2019 (COVID-19) pandemic highlighted the need for rapid, reliable and scalable evaluation of diagnostic technologies. In the United Kingdom of Great Britain and Northern Ireland, this need prompted the development of an umbrella research protocol enabling multiple clinical evaluation studies of similar designs to be undertaken under a single overarching preapproved ethics and governance framework. We describe the development, implementation and evolution of this protocol, which was designed to support timely assessment of the performance of in vitro diagnostic devices and associated testing approaches in various settings. The umbrella protocol allowed studies to be started quickly during the pandemic, reduced administrative burdens, supported regulatory submissions and enabled prospective collection of samples for surveillance. While the system described reflects British governance structures, the principles underpinning this approach, including proportionality (ensuring oversight requirements are appropriate to the risk level), standardization and preapproved flexibility, are applicable to many settings. The protocol now forms part of the United Kingdom's wider pandemic preparedness structure and illustrates how preapproved, adaptable research frameworks can accelerate evidence generation during outbreaks. The world is now assessing lessons from the COVID-19 pandemic and it is timely to consider how research systems can support innovative designs such as umbrella protocols. We therefore summarize lessons learnt and practical considerations to support other countries seeking to adopt similar approaches within their own ethical and regulatory systems.