Abstract
Pharmacogenetics, one of the cornerstones of personalized medicine, has the potential to change the way in which health care is offered by stratifying patients into various pretreatment categories, such as likely responders, likely non-responders or likely to experience adverse drug reactions. In order to advance drug development and regulatory science, regulatory agencies globally have promulgated guidelines on pharmacogenetics for nearly a decade. The aim of this article is to provide an overview of new guidelines for the implementation of pharmacogenetics in drug development from a multiregional regulatory perspective — encompassing Europe, the United States and Japan — with an emphasis on clinical pharmacokinetics.
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Acknowledgements
The authors greatly appreciated helpful discussions with I. Kohane (Harvard, USA), R. Diasio (Mayo Clinic, USA) and F. Innocenti (University of North Carolina, Chapel Hill, USA). C.N. is supported by the Lise Meitner stipend of the Fonds zur Förderung der Wissenschaftlichen Forschung (FWF) (M11108-B11). Further support was given by the FWF and the FP-7 to M. Paulmichl (P18608; PIRSES-GA-2008-230661). The authors acknowledge the expert secretarial assistance of E. Mooslechner.
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FURTHER INFORMATION
Committee for Medicinal Products for Human Use
EMA — Qualification of novel methodologies for medicine development
EMA workshop on pharmacogenomics: from science to clinical care
International Conference on Harmonisation — Guidelines
Pharmacogenomics Working Party
Glossary
- Adverse drug reactions
-
(ADRs). Noxious, undesired or unintended responses to pharmacological treatments that occur at dosages used for prophylaxis, diagnosis or therapy of diseases.
- Enrichment studies
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Clinical studies in which patient subsets are enrolled or analysed in order to increase the likelihood for demonstrating a specific treatment effect (if one exists).
- Genetic subpopulations
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Groups of individuals sharing the same genetic variants. Ethnicity is not included in the context here.
- Interactome
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The entire set of protein–protein interactions that occur in a cell.
- Pharmacodynamics
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(PD). The desired or adverse biological (for example, biochemical or physiological) effect of a drug on the body.
- Pharmacogenetics
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According to the definitions set by the International Conference on Harmonisation Topic E15 guideline, pharmacogenetics is a subset of pharmacogenomics that studies variations in DNA sequence as related to drug response.
- Pharmacogenomics
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According to the definitions set by the International Conference on Harmonisation Topic E15 guideline, pharmacogenomics is the study of variations in DNA and RNA characteristics as related to drug response.
- Pharmacokinetics
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(PK). How the body affects a drug over a period of time as a function of absorption, distribution, metabolism and excretion.
- Pharmacovigilance
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A pharmacological science related to the detection, assessment and prevention of adverse drug reactions in the post-marketing period of a drug's life cycle.
- Phenotyping
-
Grouping of individuals based on measurement of an observable characteristic (for example, the extent to which they are able to metabolize a drug or other substrate).
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Maliepaard, M., Nofziger, C., Papaluca, M. et al. Pharmacogenetics in the evaluation of new drugs: a multiregional regulatory perspective. Nat Rev Drug Discov 12, 103–115 (2013). https://doi.org/10.1038/nrd3931
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DOI: https://doi.org/10.1038/nrd3931
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