Background: Basic science has delivered unprecedented insights into intricate relationships on the smallest scales within well-controlled environments. Addressing pressing societal decision problems requires an understanding of systems on larger scales in real-world situations. Objective: To assess how well the evidence assessors E-Synthesis and EBM+ assess basic science findings to support medical decision making. Method: We demonstrate the workings of E-Synthesis and EBM+ on a case study: the suspected causal connection between the widely-used drug amoxicillin (AMX) and the putative adverse drug reaction: Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). Results: We determine an increase in the probability that AMX can cause DRESS within the E-Synthesis approach and using the EBM+ standards assess the basic science findings as supporting the existence of a mechanism linking AMX and DRESS. Conclusions: While progress is made towards developing methodologies which allow the incorporation of basic science research in the decision making process for pressing societal questions, there is still considerable need for further developments. A continued dialogue between basic science researchers and methodologists, philosophers and statisticians seems to offer the best prospects for developing and evaluating continuously evolving methodologies.
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.
Some philosophers have argued that evidence of underlying mechanisms does not provide evidence for the effectiveness of a medical intervention. One such argument appeals to the unreliability of mechanistic reasoning. However, mechanistic reasoning is not the only way that evidence of mechanisms might provide evidence of effectiveness. A more reliable type of reasoning may be distinguished by appealing to recent work on evidential pluralism in the epistemology of medicine. A case study from virology provides an example of this so‐called reinforced reasoning in medicine. It is argued that in this case study, the available evidence of underlying mechanisms did in fact play a role in providing evidence in favour of a medical intervention. This paper therefore adds a novel and recent case study to the literature in support of evidential pluralism in medicine.
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