Genotype and Phenotype Concordance for Pharmacogenetic Tests Through Proficiency Survey Testing

Arch Pathol Lab Med. 2020 Sep 1;144(9):1057-1066. doi: 10.5858/arpa.2019-0478-CP.

Abstract

Context.—: As pharmacogenetic testing is incorporated into routine care, it is essential for laboratories to provide accurate and consistent results. Certified laboratories must successfully complete proficiency testing.

Objectives.—: To understand and examine trends in participation and performance of laboratories participating in the College of American Pathologists pharmacogenetic proficiency testing surveys.

Design.—: Results from College of American Pathologists pharmacogenetic proficiency testing challenges from 2012 through 2017 were reviewed for concordance with expected genotype and phenotype for each sample (intended responses).

Results.—: Laboratories correctly reported results for 96.7% to 100% of samples with no variants. Excluding CYP2D6, laboratories correctly detected and reported variant alleles for each gene (93.7%-99.2% correct). CYP2D6 showed lower concordance, with 83.1% of laboratories reporting the intended genotype across all samples; however, in many cases, the laboratories that did not report a variant allele did not test for that allele. Among laboratories reporting the intended genotype, most successfully reported the intended phenotype (85.9%-99.0%).

Conclusions.—: Although laboratories are generally performing well, there is room for additional improvement, particularly for challenging genes, such as CYP2D6. Efforts in the field of pharmacogenomics to recommend alleles that should be included in clinical tests, identify reference materials, and standardize translation from genotype to phenotype may address some of the remaining variability in results.

MeSH terms

  • Genotype*
  • Humans
  • Laboratories / standards*
  • Laboratory Proficiency Testing
  • Pharmacogenetics*
  • Pharmacogenomic Testing*
  • Phenotype*