{"entity":{"id":"idea-tr1-ancestry-aware-pharmacology-programme","kind":"idea","name":"Ancestry-aware pharmacology: drug-level sub-studies across populations before approval","aka":[],"tldr":"Drugs are processed differently by people with different genetic backgrounds, but doses are set mostly in white and East Asian populations. Every new drug should be studied for how it behaves across ancestries, with dosing advice by genotype rather than by race.","summary":"Registrational programmes include pharmacokinetic and pharmacogenomic sub-studies powered across the main genetic ancestry groups, genotyping known variants (CYP2D6, CYP3A5, UGT1A1, DPYD, NUDT15, HLA alleles) and reporting exposure and toxicity by genotype. Labels carry genotype-based dosing where exposure differs, replacing crude race-based statements. African, South Asian and Indigenous populations are prioritised because they are least represented in existing PK data.","asOf":"2026-09-08","links":[{"label":"CPIC guideline: fluoropyrimidines and DPYD","url":"https://cpicpgx.org/guidelines/guideline-for-fluoropyrimidines-and-dpyd/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["germline-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["germline-vs-somatic"],"trials":[],"people":[],"bottlenecks":["b-trial-diversity","b-dose-optimisation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Ancestry-aware programmes will identify clinically relevant exposure differences for a meaningful fraction of new oral oncology agents, and genotype-guided dosing will reduce grade 3+ toxicity in affected groups without loss of efficacy.","rationale":"Known examples include NUDT15 variants and thiopurine toxicity in East Asian and Hispanic patients, UGT1A1*28 and irinotecan, and DPYD variants and fluoropyrimidines; several were discovered only after approval and harm.","test":"Mandate the sub-study for new oral agents for three years and count label changes attributable to it; run a genotype-guided dosing RCT for one agent with a discovered difference.","maturity":"early-clinical","actor":"regulator","cost":"medium","horizonYears":4},"route":"/ideas/idea-tr1-ancestry-aware-pharmacology-programme/","neighbours":{"technology":[{"id":"germline-testing","kind":"technology","name":"Germline (hereditary) testing","route":"/technologies/germline-testing/"}],"term":[{"id":"germline-vs-somatic","kind":"term","name":"Germline vs somatic mutations","route":"/terms/germline-vs-somatic/"}],"bottleneck":[{"id":"b-trial-diversity","kind":"bottleneck","name":"Trials do not represent the people who get cancer","route":"/bottlenecks/b-trial-diversity/"},{"id":"b-dose-optimisation","kind":"bottleneck","name":"Wrong doses","route":"/bottlenecks/b-dose-optimisation/"}]}}