Will COVID-19 be evidence-based medicine’s nemesis?
Authors: Trisha Greenhalgh
Journal: PLoS Medicine (2020)

Once defined in rhetorical but ultimately meaningless terms as "the conscientious, judicious and explicit use of current best evidence in making decisions about the care of individual patients" [1], evidence-based medicine rests on certain philosophical assumptions: a singular truth, ascertainable through empirical enquiry; a linear logic of causality in which interventions have particular effect sizes; rigour defined primarily in methodological terms (especially, a hierarchy of preferred study designs and tools for detecting bias); and a deconstructive approach to problem-solving (the evidence base is built by answering focused questions, typically framed as 'PICO'-population-intervention-comparison-outcome) [2].The trouble with pandemics is that these assumptions rarely hold.A pandemic-sized problem can be framed and contested in multiple ways.Some research questions around COVID-19, most notably relating to drugs and vaccines, are amenable to randomised controlled trials (and where such trials were possible, they were established with impressive speed and efficiency [3,4]).But many knowledge gaps are broader and cannot be reduced to PICO-style questions.Were care home deaths avoidable [5]?Why did the global supply chain for personal protective equipment break down [6]?What role does health system resilience play in controlling the pandemic [7]?And so on.Against these-and other-wider questions, the neat simplicity of a controlled, intervention-on versus intervention-off experiment designed to produce a definitive (i.e.statistically significant and widely generalisable) answer to a focused question rings hollow.In particular, upstream preventive public health interventions aimed at supporting widespread and sustained behaviour change across an entire population (as opposed to testing the impact of a short-term behaviour change in a select sample) rarely lend themselves to such a design [8,9].When implementing population-wide public health interventions-whether conventional measures such as diet or exercise, or COVID-19 related ones such as handwashing, social distancing and face coverings-we must not only persuade individuals to change their behavior but also adapt the environment to make such changes easier to make and sustain [10][11][12].Population-wide public health efforts are typically iterative, locally-grown and path-dependent, and they have an established methodology for rapid evaluation and adaptation [9].But evidence-based medicine has tended to classify such designs as "low methodological quality" [13].Whilst this has been recognised as a problem in public health practice for some time [11], the inadequacy of the dominant paradigm has suddenly become mission-critical.Whilst evidence-based medicine recognises that study designs must reflect the nature of question (randomized trials, for example, are preferred only for therapy questions [13]), even senior scientists sometimes over-apply its hierarchy of evidence.An interdisciplinary group of scholars from the UK's prestigious Royal Society recently reviewed the use of face masks by the general public, drawing on evidence from laboratory science, mathematical modelling and