Abstract
RationaleEvidence‐based medicine (EBM), the dominant approach to assessing the effectiveness of clinical and public health interventions, focuses on the results of association studies. EBM+ is a development of EBM that systematically considers mechanistic studies alongside association studies.Aims and objectivesTo explore examples of the importance of mechanistic evidence to coronavirus research.MethodsWe have reviewed the mechanistic evidence in four major areas that are relevant to the management of COVID‐19.Results and conclusions(a) Assessment of combination therapy for MERS highlights the need for systematic assessment of mechanistic evidence. (b) That hypertension is a risk factor for severe disease in the case of SARS‐CoV‐2 suggests that altering hypertension treatment might alleviate disease, but the mechanisms are complex, and it is essential to consider and evaluate multiple mechanistic hypotheses. (c) Confidence that public health interventions will be effective requires a detailed assessment of social and psychological components of the mechanisms of their action, in addition to mechanisms of disease. (d) In particular, if vaccination programmes are to be effective, they must be carefully tailored to the social context; again, mechanistic evidence is crucial. We conclude that coronavirus research is best situated within the EBM+ evaluation framework.
Highlights
Evidence-based medicine (EBM) provides the dominant approach to assessing the effectiveness of clinical and some public health interventions
Mechanistic reasoning, which appeals to features of the mechanisms by which the intervention is hypothesized to lead to the outcome and to the mechanistic studies that investigate these features, is viewed as inferior to association studies by present-day EBM1
We have presented a range of contexts in coronavirus research in which it is beneficial to systematically assess mechanistic studies alongside association studies
Summary
Evidence-based medicine (EBM) provides the dominant approach to assessing the effectiveness of clinical and some public health interventions. Mechanistic reasoning is pertinent when specific hypotheses about key features of the mechanism complex are established (or ruled out) by mechanistic studies (see section 3) Given this more nuanced picture of causal assessment, it can be important to explicitly and systematically scrutinize mechanistic studies when assessing causal claims. In this paper we aim to redress the balance, by showing that there is a need to assess mechanistic studies explicitly and systematically when interrogating the effects of interventions in infections with coronaviruses This need is urgent in diseases such as SARS, MERS, and COVID-19 (due respectively to SARS-CoV-1, MERS-CoV, and SARSCoV-2), because outbreaks are rapid, limiting the opportunity to conduct high-quality RCTs. association studies on their own tend to provide evidence that is too weak to establish causation. We conclude that coronavirus research is best situated within the EBM+ evaluation framework (section 6)
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