Pharmacogenomics
Clinical pharmacogenetics
Watch scope
Actionable drug-gene interactions in clinical practice. Focus on CPIC Level A and B variants (CYP2D6, CYP2C19, DPYD, TPMT, SLCO1B1, HLA-B*57:01, HLA-B*15:02, NUDT15...), preemptive genotyping programs in hospitals, drug phenoconversions (enzyme inhibitors/inducers), dose recommendations and alerts on serious adverse drug reactions with genetic determinism. Includes CPIC and DPWG guideline updates.
Inclusion / exclusion criteria
Included
- ✓CPIC Level A or B variants, or strong DPWG recommendation
- ✓Clinical studies on PGx-guided prescribing
- ✓CPIC/DPWG guideline updates
- ✓Impact on serious adverse drug reactions
- ✓Preemptive genotyping at hospital scale
Excluded
- ✕Purely preclinical PGx (in vitro, animal models)
- ✕Studies without direct clinical implications
- ✕Somatic-only biomarkers
- ✕Drug interactions without a genetic component
- ✕Studies on variants of uncertain significance (VUS)
Scoring methodology
Each article is evaluated out of 10 points. Inclusion threshold: score ≥ 5.
- Clinical impact (0–3)Primary criterion. +3: changes practice immediately (CPIC A dose recommendation, prophylactic surgery, deployable tool). +2: likely impact in the short term. +1: indirect contribution to counselling or understanding. 0: fundamental interest only.
- Strength of evidence (0–3)+3: robust causality — functional + multi-family segregation, large prospective cohort, or RCT. +2: good evidence — quality functional alone, cohort ≥10 families or ≥100 patients. +1: partial evidence. 0: preliminary data or single case report.
- Novelty (0–2)+2: unprecedented element (new gene, new CPIC A/B interaction, breakthrough tool). +1: significant extension (phenotypic expansion, VUS→P/LP reclassification, major replication). 0: minor replication or narrative review.
- Cohort size / robustness (0–1)+1 if ≥5 independent cases, ≥100 genotyped patients, cohort ≥1000, open-source code (bioinformatics), or meta-analysis ≥5 studies. 0 otherwise.
- Journal quality (0–1)+1 for a peer-reviewed journal recognised in the specialty (Nat Genet, AJHG, Genet Med, JCO, Pharmacogenomics J, Nat Methods…). 0 otherwise.
- Preprint penalty (−1)−1 for bioRxiv/medRxiv preprints not yet peer-reviewed. The preprint is still included if it carries major information.
Domain-specific note: In pharmacogenetics, clinical impact is the primary criterion (0–3 pts): an immediately applicable CPIC Level A dose recommendation scores +3. Strength of evidence (0–3 pts) distinguishes a preemptive genotyping RCT from a retrospective study. An article with CPIC A + large prospective cohort can reach 9–10/10.
Sources consulted
- —PubMed — CYP2D6, CYP2C19, DPYD, clinical pharmacogenetics query
- —Pharmacogenomics Journal, Clinical Pharmacology & Therapeutics
- —CPT: Pharmacometrics & Systems Pharmacology
- —British Journal of Clinical Pharmacology
- —CPIC (cpicpgx.org) and DPWG (knmp.nl) guidelines
Author
Informational document — does not constitute medical advice.