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. 2018 Oct;24(5):1166-1176.
doi: 10.1111/jep.12960. Epub 2018 Jun 11.

The use of mechanistic evidence in drug approval

Jeffrey K Aronson  1 , Adam La Caze  2 , Michael P Kelly  3 , Veli-Pekka Parkkinen  4 , Jon Williamson  4
Affiliations

The use of mechanistic evidence in drug approval

Jeffrey K Aronson et al. J Eval Clin Pract. 2018 Oct.

Abstract

The role of mechanistic evidence tends to be under-appreciated in current evidence-based medicine (EBM), which focusses on clinical studies, tending to restrict attention to randomized controlled studies (RCTs) when they are available. The EBM+ programme seeks to redress this imbalance, by suggesting methods for evaluating mechanistic studies alongside clinical studies. Drug approval is a problematic case for the view that mechanistic evidence should be taken into account, because RCTs are almost always available. Nevertheless, we argue that mechanistic evidence is central to all the key tasks in the drug approval process: in drug discovery and development; assessing pharmaceutical quality; devising dosage regimens; assessing efficacy, harms, external validity, and cost-effectiveness; evaluating adherence; and extending product licences. We recommend that, when preparing for meetings in which any aspect of drug approval is to be discussed, mechanistic evidence should be systematically analysed and presented to the committee members alongside analyses of clinical studies.

Keywords: causality; epistemology; evaluation; evidence-based medicine; philosophy of medicine.

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Figure 1
Figure 1
Classification of adverse drug reactions according to their dose relations (see the text for explanation)
See this image and copyright information in PMC

References

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