Authors' recommendations: Focusing on the clinical utility of commercially available pharmacogenomic testing of polymorphisms of Cytochrome P450, UGT1A1 in Irinotecan toxicity, and dihydropyrimidine dehydrogenase (DPD) in fluoropyrimidine toxicity, the questions VATAP sought to address based on evidence from available systematic reviews and scoping reports are as follows:1. What pharmacogenomic tests are available commercially?The FDA-approved tests identified in this report are:• CYP450 AmpliChip® (Roche Molecular Diagnostics, Pleasanton, CA);• Invader® UGT1A1 Molecular Assay (Third Wave Technologies, Madison WI);• Warfarin Target Dose Safety Test (Genelex Corp., Seattle, WA);• PGxPredict: WARFARIN™ (Clinical Data, Inc., New Haven, CT);• Warfarin DoseAdvise (Kimball Genetics, Inc. , Denver, CO);• Verigene System (Nanosphere Inc., Northbrook, IL).2. For which clinical conditions should each pharmacogenomic test be applied?3. What is the quality of evidence for their usefulness?The clinical conditions for which each of the commercially available pharmacogenomic tests listed above have been rigorously reviewed or comprehensively catalogued are organized in Table 1, according to: mental health disorders; neoplasms; cardiovascular disorders; and other (pain management).• The strongest evidence for use of pharmacogenomic testing supports using genotyping to aid in the determination of warfarin dosage along with existing tools such as routine monitoring of the International Normalized Ratio (INR) by a physician. This is based on evidence supporting comparable analytic validity (diagnostic test performance) to that of most genomic tests and evidence supporting a relationship between the genomic variant(s) and the final warfarin dose. Specifically, the American College of Medical Genetics recommends that: “…C9 and VKORC1 genotypes can reasonably be used as part of diagnostic efforts to determine the cause of an unusually low maintenance dose of warfarin or an unusually high INR during standard dosing.” 26 However, significant knowledge gaps regarding clinical utility and the balance between harm, benefit and cost must be resolved before this testing becomes the standard of care for all patients undergoing anticoagulation with warfarin.• None of the existing reviews supported using pharmacogenomic testing alone for routine clinical use. However, although completion of the AHRQ systematic review of Irinotecan for colorectal cancer is still pending, FDA has recommended UGT1A1 testing in patients planned for treatment with Irinotecan to identify individuals who are homozygous for the UGT1A*28 allele. Patient with this mutation are at increased risk for neutropenia following initiation of treatment, and a reduced initial dose should be considered.• For all of the clinical applications reviewed in this report, evidence linking the use of pharmacogenomic testing to improvements in clinical outcomes and clarifying the risks and benefits associated with use of these tests is needed in order to determine the clinical utility of pharmacogenomic testing.

Project Status: Completed

URL for project: http://www4.va.gov/VATAP/docs/PharmacogenomicTesting2008tagm.pdf

Year Published: 2008

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: United States

Organisation Name: VA Technology Assessment Program

Contact Address: Liz Adams, VA Technology Assessment Program, Office of Patient Care Services (11T), VA Boston Healthcare System Room 4D-142, 150 South Huntington Avenue, Boston, MA 02130 USA Tel: +1 617 278 4469; Fax: +1 617 264 6587;

Contact Name: elizabeth.adams@med.va.gov

Contact Email: elizabeth.adams@med.va.gov

Copyright: VA Technology Assessment Program (VATAP)