Pharmacogenetics in the evaluation of new drugs: a multiregional regulatory perspective

1] Medicines Evaluation Board, Utrecht and Radboud University Nijmegen Medical Center, PO Box 8275, 3503 RG Utrecht, The Netherlands. [2].
dressNature Reviews Drug Discovery (Impact Factor: 37.23). 02/2013; 12(2):103-115. DOI: 10.1038/nrd3931
Source: PubMed

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.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Pharmacogenomics (PGx) or biomarker (BM) has the potential to facilitate the development of safer and more effective drugs in terms of their benefit/risk profiles by stratifying population into categories such as responders/non-responders and high-/low-risks to drug-induced serious adverse reactions. In the past decade, practical use of PGx or BM has advanced the field of anti-cancer drug development. To identify the characteristics of the PGx/BM-guided clinical trials for regulatory approval of anti-cancer drugs in Japan, we collected information on design features of 'key trials' in the review reports of anti-cancer drugs that were approved after the implementation of the 'Revised Guideline for the Clinical Evaluation of Anti-cancer drugs' in April 2006. On the basis of the information available on the regulatory review data for the newly approved anti-cancer drugs in Japan, this article aims to explain the limitations and points to consider in the study design of PGx/BM-guided clinical trials.Journal of Human Genetics advance online publication, 9 May 2013; doi:10.1038/jhg.2013.36.
    Journal of Human Genetics 05/2013; DOI:10.1038/jhg.2013.36 · 2.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The FDA emphasizes the role of regulatory science in the fulfillment of its mission to promote and protect public health and foster innovation. With respect to the evaluation of drug effects in the real world, regulatory science plays an important role in drug risk assessment and management. This paper discusses opportunities and challenges with population-based drug risk assessment as well as related regulatory science knowledge gaps in the following areas: (1) population-based data sources and methods to evaluate drug safety issues; (2) evidence-based thresholds to account for uncertainty in postmarket data; (3) approaches to optimize the integration and interpretation of evidence from different sources; and (4) approaches to evaluate real world impact of regulatory decisions. Regulators should continue the ongoing dialogue with multiple stakeholders to strengthen regulatory safety science and address these and other critical knowledge gaps.Clinical Pharmacology & Therapeutics (2013); accepted article preview online 5 June 2013; doi:10.1038/clpt.2013.118.
    Clinical Pharmacology &#38 Therapeutics 06/2013; 94(3). DOI:10.1038/clpt.2013.118 · 7.39 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The utilization of pharmacogenomics (PGx) in drug development is increasing as pharmaceutical companies and regulatory agencies work to understand variation in response to medications. The implementation of PGx in clinical trials requires a number of considerations that begin early at the point of program development for a compound. This article will discuss the issues involved in mobilizing a PGx study during the conduct of a clinical trial, including the development of a PGx hypothesis, the identification of genetic markers for analysis, PGx platform selection and assay development, as well as challenges that arise in relation to global laws and regulations related to genetic research and logistical/timeline concerns in the execution of a PGx analysis.
    Pharmacogenomics 07/2013; 14(10):1227-35. DOI:10.2217/pgs.13.109 · 3.43 Impact Factor
Show more