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. 2021 Jun;27(3):684-693.
doi: 10.1111/jep.13438. Epub 2020 Jul 15.

The use of mechanistic reasoning in assessing coronavirus interventions

Jeffrey K Aronson  1 , Daniel Auker-Howlett  2 , Virginia Ghiara  2 , Michael P Kelly  3 , Jon Williamson  2
Affiliations

The use of mechanistic reasoning in assessing coronavirus interventions

Jeffrey K Aronson et al. J Eval Clin Pract. 2021 Jun.

Abstract

Rationale: Evidence-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 objectives: To explore examples of the importance of mechanistic evidence to coronavirus research.

Methods: We 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.

Keywords: coronavirus; evidence-based medicine; mechanisms; mechanistic reasoning.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

FIGURE 1
FIGURE 1
Evidential relationships for establishing a causal claim. The existence of an appropriate correlation and an appropriate mechanism together confirm causation—it is not enough to have one without the other. Arrows signify potential positive or negative evidential relationships
FIGURE 2
FIGURE 2
Two conflicting hypotheses about whether to recommend continuing treatment with antihypertensive drugs in the context of COVID‐19. The two hypotheses interpret increased activity of the renin‐angiotensin system (RAS) in different ways, leading to different pieces of advice regarding continuation of antihypertensive drug use (see Aronson and Ferner)2
FIGURE 3
FIGURE 3
Factors that can influence vaccination status, motivated by EBM+ and the WHO's Tailoring Immunization Programmes. Personal, external, and environmental determinants influence belief and behavioural factors, which then bring about different phenomena relevant to vaccination status
See this image and copyright information in PMC

References

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    1. Aronson JK, La Caze A, Kelly MP, Parkkinen V‐P, Williamson J. The use of mechanistic evidence in drug approval. J Eval Clin Pract. 2018;24(5):1166‐1176. - PMC - PubMed

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