title: Genotype-guided drug prescribing: a systematic review and meta-analysis of randomized control trials.
abstract: OBJECTIVE
  Adverse drug events lead to increased morbidity, mortality and health care costs. Pharmacogenetic testing that guides drug prescribing has the potential to reduced adverse drug events and increase drug effectiveness. Our aim was to quantify the clinical effectiveness of genotype-guided prescribing.
  
  
  METHODS
  Three electronic databases were searched from January 1980 through December 2013. Studies were eligible if they were RCTs comparing genotype-guided prescribing with non-genetic informed prescribing, reported drug specific adverse drug events and clinical effectiveness outcomes. Two reviewers independently screened titles and abstracts, extracted data and assessed study quality. Meta-analyses of specific outcomes were conducted where data allowed.
  
  
  RESULTS
  Fifteen studies, involving 5688 patients and 19 drugs, met the inclusion and exclusion criteria. Eight studies had statistically significant results for their primary outcome in favour of genotype-guided prescribing. Nine studies evaluated genotype-guided warfarin dosing. Analysis of percentage of time in therapeutic international normalized ratio range (1952 individuals) showed a statistically significant benefit in favour of genotype-guided warfarin dosing (mean difference = 6.67; 95% CI 1.34, 12.0, I(2) = 80%). There was a statistically significant reduction in numbers of warfarin-related minor bleeding, major bleeding and thromboembolisms associated with genotype guided warfarin dosing, relative risk 0.57 (95% CI 0.33, 0.99; I(2) = 60%). It was not possible to meta-analyze genotype-guided dosing for other drugs. Of the six non-warfarin genotype-guided trials, two demonstrated a statistically significant benefit for their primary outcome, odds ratio 0.03 (95% CI 0.00, 0.62, P < 0.001) for abacavir.
  
  
  CONCLUSIONS
  There is evidence of improved clinical effectiveness associated with genotype-guided warfarin dosing.
authors: Department of Family Practice, Faculty of Medicine, University of British Columbia, 3rd Floor David Strangway Building, 5950 University Boulevard, Vancouver, British Columbia, V6T 1Z3, Canada.
authors: Rebecca
authors: R
authors: Goulding
authors: Department of Family Practice, Faculty of Medicine, University of British Columbia, 3rd Floor David Strangway Building, 5950 University Boulevard, Vancouver, British Columbia, V6T 1Z3, Canada.
authors: Diana
authors: D
authors: Dawes
authors: Department of Family Practice and Island Medical Program, University of Victoria, PO Box 1700 STN CSC, Victoria, British Columbia, V8W 2Y2, Canada.
authors: Morgan
authors: M
authors: Price
authors: Department of Family Practice, Faculty of Medicine, University of British Columbia, 3rd Floor David Strangway Building, 5950 University Boulevard, Vancouver, British Columbia, V6T 1Z3, Canada.
authors: Sabrina
authors: S
authors: Wilkie
authors: Department of Family Practice, Faculty of Medicine, University of British Columbia, 3rd Floor David Strangway Building, 5950 University Boulevard, Vancouver, British Columbia, V6T 1Z3, Canada.
authors: Martin
authors: M
authors: Dawes
mesh_terms: D011307:Drug Prescriptions / Q000706:statistics & numerical data*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000235:genetics* / Q000517:prevention & control*; D005838:Genotype; D006801:Humans; D010597:Pharmacogenetics / Q000379:methods*; D016032:Randomized Controlled Trials as Topic
keywords: adverse drug events; genotype-guided; pharmacogenetic; systematic review