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A Systematic Review

Kathryn A. Phillips, PhD; David L. Veenstra, PhD, PharmD; Eyal Oren, BA; Jane K. Lee, BA; Wolfgang Sadee, PhD

JAMA. 2001;286:2270-2279.

Context  Adverse drug reactions are a significant cause of morbidity and mortality. Although many adverse drug reactions are considered nonpreventable, recent developments suggest these reactions may be avoided through individualization of drug therapies based on genetic information, an application known as pharmacogenomics.

Objective  To evaluate the potential role of pharmacogenomics in reducing the incidence of adverse drug reactions.

Data Sources  MEDLINE English-language only searches for adverse drug reaction studies published between January 1995 and June 2000 and review articles of variant alleles of drug-metabolizing enzymes published between January 1997 and August 2000. We also used online resources, texts, and expert opinion.

Study Selection  Detailed inclusion criteria were used to select studies. We included 18 of 333 adverse drug reaction studies and 22 of 61 variant allele review articles.

Data Extraction  All the investigators reviewed and coded articles using standardized abstracting forms.

Data Synthesis  We identified 27 drugs frequently cited in adverse drug reaction studies. Among these drugs, 59% are metabolized by at least 1 enzyme with a variant allele known to cause poor metabolism. Conversely, only 7% to 22% of randomly selected drugs are known to be metabolized by enzymes with this genetic variability (range, P = .006-P<.001).

Conclusions  Our results suggest that drug therapy based on individuals' genetic makeups may result in a clinically important reduction in adverse outcomes. Our findings serve as a foundation for further research on how pharmacogenomics can reduce the incidence of adverse reactions and on the resulting clinical, societal, and economic implications.

Author Affiliations: Department of Clinical Pharmacy (Drs Phillips, Mr Oren, and Ms Lee) and Biopharmaceutics (Dr Sadee) University of California-San Francisco; Department of Pharmacy, University of Washington, Seattle (Dr Veenstra).

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