Full title: Adapt or die: how the pandemic made the shift from EBM to EBM+ more urgent Authors: Trisha Greenhalgh, David Fisman, Danielle J Cane, Matthew Oliver, Chandini Raina Macintyre Open access: https://ebm.bmj.com/content/early/2022/07/19/bmjebm-2022-111952 (Paragraphs mine for legibility) Evidence-based medicine (EBM’s) traditional methods, especially randomised controlled trials (RCTs) and meta-analyses, along with risk-of-bias tools and checklists, have contributed significantly to the science of COVID-19. But these methods and tools were designed primarily to answer simple, focused questions in a stable context where yesterday’s research can be mapped more or less unproblematically onto today’s clinical and policy questions. They have significant limitations when extended to complex questions about a novel pathogen causing chaos across multiple sectors in a fast-changing global context. Non-pharmaceutical interventions which combine material artefacts, human behaviour, organisational directives, occupational health and safety, and the built environment are a case in point: EBM’s experimental, intervention-focused, checklist-driven, effect-size-oriented and deductive approach has sometimes confused rather than informed debate. While RCTs are important, exclusion of other study designs and evidence sources has been particularly problematic in a context where rapid decision making is needed in order to save lives and protect health. It is time to bring in a wider range of evidence and a more pluralist approach to defining what counts as ‘high-quality’ evidence. We introduce some conceptual tools and quality frameworks from various fields involving what is known as mechanistic research, including complexity science, engineering and the social sciences. We propose that the tools and frameworks of mechanistic evidence, sometimes known as ‘EBM+’ when combined with traditional EBM, might be used to develop and evaluate the interdisciplinary evidence base needed to take us out of this protracted pandemic. Further articles in this series will apply pluralistic methods to specific research questions.