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Fulfilling the Promise of Personalized Medicine? Systematic Review and Field Synopsis of Pharmacogenetic Studies

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  • Michael V Holmes
  • Tina Shah
  • Christine Vickery
  • Liam Smeeth
  • Aroon D Hingorani
  • Juan P Casas

Abstract

Background: Studies of the genetic basis of drug response could help clarify mechanisms of drug action/metabolism, and facilitate development of genotype-based predictive tests of efficacy or toxicity (pharmacogenetics). Objectives: We conducted a systematic review and field synopsis of pharmacogenetic studies to quantify the scope and quality of available evidence in this field in order to inform future research. Data Sources: Original research articles were identified in Medline, reference lists from 24 meta-analyses/systematic reviews/review articles and U.S. Food and Drug Administration website of approved pharmacogenetic tests. Study Eligibility Criteria, Participants, and Intervention Criteria: We included any study in which either intended or adverse response to drug therapy was examined in relation to genetic variation in the germline or cancer cells in humans. Study Appraisal and Synthesis Methods: Study characteristics and data reported in abstracts were recorded. We further analysed full text from a random 10% subset of articles spanning the different subclasses of study. Results: From 102,264 Medline hits and 1,641 articles from other sources, we identified 1,668 primary research articles (1987 to 2007, inclusive). A high proportion of remaining articles were reviews/commentaries (ratio of reviews to primary research approximately 25∶1). The majority of studies (81.8%) were set in Europe and North America focussing on cancer, cardiovascular disease and neurology/psychiatry. There was predominantly a candidate gene approach using common alleles, which despite small sample sizes (median 93 [IQR 40–222]) with no trend to an increase over time, generated a high proportion (74.5%) of nominally significant (p

Suggested Citation

  • Michael V Holmes & Tina Shah & Christine Vickery & Liam Smeeth & Aroon D Hingorani & Juan P Casas, 2009. "Fulfilling the Promise of Personalized Medicine? Systematic Review and Field Synopsis of Pharmacogenetic Studies," PLOS ONE, Public Library of Science, vol. 4(12), pages 1-14, December.
    • Handle: RePEc:plo:pone00:0007960
    DOI: 10.1371/journal.pone.0007960
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    References listed on IDEAS

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    1. Allen D. Roses, 2000. "Pharmacogenetics and the practice of medicine," Nature, Nature, vol. 405(6788), pages 857-865, June.
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    Cited by:

    1. Marisa Faggini & Silvia Cosimato & Francesco David Nota & Giancarlo Nota, 2018. "Pursuing Sustainability for Healthcare through Digital Platforms," Sustainability, MDPI, vol. 11(1), pages 1-15, December.

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