Opinion

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

  • Nature Reviews Drug Discovery volume 10, pages 495506 (2011)
  • doi:10.1038/nrd3501
  • Download Citation
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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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Author information

Affiliations

  1. Hans-Georg Eichler, Eric Abadie, Bruno Flamion, Hubert Leufkens, Christian K. Schneider and Brigitte Bloechl-Daum are at the European Medicines Agency, London, UK.

    • Hans-Georg Eichler
    • , Eric Abadie
    • , Bruno Flamion
    • , Hubert Leufkens
    • , Christian K. Schneider
    •  & Brigitte Bloechl-Daum
  2. Hans-Georg Eichler is also at the Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

    • Hans-Georg Eichler
  3. Eric Abadie is also at the European Medicines Agency Committee for Medicinal Products for Human Use, London, UK; and the General Directorate Agence Francaise de Securite Sanitaire des Produits de Santé (AFSSAPS), Paris, France.

    • Eric Abadie
  4. Alasdair Breckenridge is at the Medicines and Healthcare Products Regulatory Agency, London, UK.

    • Alasdair Breckenridge
  5. Bruno Flamion is also at the Agence Fédérale des Médicaments et des Produits de Santé, Brussels, Belgium.

    • Bruno Flamion
  6. Lars L. Gustafsson is at the Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.

    • Lars L. Gustafsson
  7. Hubert Leufkens is also at the Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht, The Netherlands.

    • Hubert Leufkens
  8. Malcolm Rowland is at the Centre for Applied Pharmacokinetic Research, School of Pharmacy and Pharmaceutical Sciences, University of Manchester, Manchester, UK.

    • Malcolm Rowland
  9. Christian K. Schneider is also at the Paul-Ehrlich-Institut, Langen, Germany; and the Twincore Centre for Experimental and Clinical Infection Research, Hannover, Germany.

    • Christian K. Schneider
  10. Brigitte Bloechl-Daum is at the Department of Clinical Pharmacology, Medical University Vienna, Vienna, Austria.

    • Brigitte Bloechl-Daum

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Competing interests

The views expressed in this article are the personal views of the authors and may not be understood or quoted as being made on behalf of or reflecting the position of the regulatory agencies, health technology assessment bodies or other organizations that the authors work for.

Corresponding author

Correspondence to Brigitte Bloechl-Daum.