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Greenhalgh et al 1 argue that the COVID-19 pandemic has uncovered a need for a shift in the evidence-based medicine (EBM) paradigm in which mechanistic evidence is also used as a complementary source for decision-making. Their justification is based on limitations of evidence hierarchies, which prioritise meta-analyses and randomised controlled trials (RCTs)1; and the urgency, threat and complexity of a pandemic. However, in defence of EBM, we present a counter argument.
First, mechanistic evidence may be misleading. Textbooks of clinical epidemiology and EBM manuals include numerous examples of mechanistic evidence supporting various treatments that subsequently turned out to be ineffective or harmful.2 A recent example, hydroxychloroquine has antiviral activity in vitro inhibiting viral entry, uncoating, assembly and budding through different molecular mechanisms.3 Yet, trials in thousands of patients have shown that hydroxychloroquine is not effective and is only exposing patients to adverse events.3 When we …
Contributors MHM is a professor of Medicine and director of the Mayo Clinic Evidence-based Practice Centre. SS is postdoctoral research fellow at the Mayo Clinic. They both conceived the idea and critically revised and approved the manuscript. MHM is the guarantor of this work.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests MHM is a member of the GRADE Working Group and cofounder of the US GRADE Network.
Provenance and peer review Not commissioned; internally peer reviewed.