Figure 1

Schematic representation of the Coriell Personalized Medicine Collaborative (CPMC) Pharmacogenomics Appraisal, Evidence-based Scoring and Interpretation System (PhAESIS) Procedure. Candidate drugs for PGx reporting are identified and prioritized for the CPMC study based on a number of criteria (as listed in the Methods section). Once a drug is selected for evaluation, the FDA drug label, the peer-reviewed scientific and clinical literature, and public web-based databases are searched for studies that report drug-related genotype–phenotype associations (see Additional file 1: Table S1 for examples of resources). This initial search identifies genes with a significant influence on response to this drug, with at least one genetic variant that is significantly and consistently associated with a clinically relevant drug-response outcome (altered efficacy or adverse reaction). For each key PGx gene, drug-specific gene variant evidence scoring is carried out (as described in the Methods section) using the scale depicted in Table 1. Genetic variant evidence scores are used to partition variants based on potential clinical relevance. Scores of 7 or lower indicate a defined effect on drug response or clinical outcome, whereas those of 8 or higher represent a lack of or insufficient evidence for an effect. Once all of the genetic variants of potential clinical relevance (those with evidence codes ≤7) have been identified, the anticipated response of the diploid individual (who possesses two copies of the gene, one inherited from each parent) with each combination of inherited variants is defined, based on published clinical outcomes data. A Punnett square is used to represent distinct diploid individuals, each assigned a defined drug response phenotype. Curated data from steps 2 to 6 are prepared as PhAESIS summary documents for review by the CPMC Pharmacogenomics Advisory Group (PAG). If approved by the PAG, drug-specific risk reports are then developed and released to study participants.