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Bridging the efficacy–effectiveness gap: a regulator's perspective on addressing variability of drug response

Abstract

Drug regulatory agencies should ensure that the benefits of drugs outweigh their risks, but licensed medicines sometimes do not perform as expected in everyday clinical practice. Failure may relate to lower than anticipated efficacy or a higher than anticipated incidence or severity of adverse effects. Here we show that the problem of benefit–risk is to a considerable degree a problem of variability in drug response. We describe biological and behavioural sources of variability and how these contribute to the long-known efficacy–effectiveness gap. In this context, efficacy describes how a drug performs under conditions of clinical trials, whereas effectiveness describes how it performs under conditions of everyday clinical practice. We argue that a broad range of pre- and post-licensing technologies will need to be harnessed to bridge the efficacy–effectiveness gap. Successful approaches will not be limited to the current notion of pharmacogenomics-based personalized medicines, but will also entail the wider use of electronic health-care tools to improve drug prescribing and patient adherence.

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Figure 1: Average benefit–risk of drugs as a function of treatment scenario.
Figure 2: Signal-to-noise ratio in clinical trials.
Figure 3: The onion skin model of drug licensing.
Figure 4: The role of electronic drug information in reducing the efficacy–effectiveness gap.

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Eichler, HG., Abadie, E., Breckenridge, A. et al. Bridging the efficacy–effectiveness gap: a regulator's perspective on addressing variability of drug response. Nat Rev Drug Discov 10, 495–506 (2011). https://doi.org/10.1038/nrd3501

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