This one of the best appraisals of evidence based medicine(EBM):
It highlights one important pitfall of EBM, ie its failure to integrate scientific(biological) plausibility in the pyramid of evidence.
I think the best way to effect a synthesis between evidence from clinical data and biological plausibility is through a Bayesian argument:
– Decide on a standard EBM approach to synthesize the clinical data regarding a hypothesis from multiple sources eg a meta-analysis
– Encode the non-clinical, background knowledge into a prior. This prior encodes the scientific plausibility of the hypothesis under question
A Bayesian analysis of the clinical data under a scientific plausibility prior provides a transparent way to leverage the pyramid evidence of EBM while providing a basic science/disease understanding context for the interpretation of clinical data.