Genotype and Phenotype Concordance for Pharmacogenetic Tests Through Proficiency Survey Testing

Area of Science:

• Clinical Laboratory Science
• Pharmacogenomics
• Molecular Diagnostics

Background:

• Pharmacogenetic testing is increasingly integrated into clinical practice, necessitating high accuracy and consistency from testing laboratories.
• Proficiency testing is a critical component for ensuring laboratory quality and reliability in pharmacogenetic diagnostics.

Purpose of the Study:

• To analyze participation and performance trends in pharmacogenetic proficiency testing surveys conducted by the College of American Pathologists.
• To evaluate laboratory concordance with expected genotypes and phenotypes over a six-year period.

Main Methods:

• Review of College of American Pathologists (CAP) pharmacogenetic proficiency testing data from 2012 to 2017.
• Assessment of laboratory concordance for genotype and phenotype results against established intended responses for each sample.

Main Results:

• Laboratories demonstrated high accuracy (96.7%-100%) for samples without variants.
• Excluding CYP2D6, variant allele detection and reporting accuracy ranged from 93.7% to 99.2%.
• CYP2D6 testing showed lower concordance (83.1% for intended genotype), with some laboratories not testing for specific alleles; however, phenotype reporting was generally high (85.9%-99.0%) among those reporting the intended genotype.

Conclusions:

• Laboratories exhibit strong performance in pharmacogenetic proficiency testing, with notable accuracy in genotype and phenotype reporting.
• Areas for improvement exist, particularly for complex genes such as CYP2D6, highlighting the need for standardized guidelines and reference materials in pharmacogenomics.
• Ongoing efforts to standardize allele recommendations, reference materials, and genotype-to-phenotype translation are crucial for reducing variability in pharmacogenetic testing results.