title: Health regulatory communications of well-established safety-related pharmacogenomics associations in six developed countries: an evaluation of alignment.
abstract: Recommendations on genetic testing are typically conveyed by drug regulatory authorities through drug labels, which are legal requirements for market authorization of drugs. We conducted a cross-sectional study of drug labels focusing on three crucial aspects of regulatory pharmacogenomics communications: (i) intent; (ii) interpretation in the local context; and (iii) implications of the genetic information. Labels of drugs associated with well-established safety-related genetic markers for adverse drug reactions across six developed countries of United States, Canada, United Kingdom, Australia, New Zealand and Singapore were reviewed. We found differing medical advice for genotype-positive HLA-B*15:02, HLA-A*31:01, UGT1A1*28 and CYP2D6 ultra-rapid metabolisers in breastfeeding women. This raises questions on implications to clinical practice between these countries. Varying ways of presenting at-risk population and allele frequencies also raises question in incorporating such information in drug labels. An international guidance addressing these crucial aspects of regulatory pharmacogenomic communications in drug labels is long overdue.
authors.affiliation: Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
authors.forename: W C
authors.initials: WC
authors.lastname: Tan-Koi
authors.affiliation: Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
authors.forename: Evelyn S H
authors.initials: ES
authors.lastname: Lim
authors.affiliation: Saw Swee Hock School of Public Health, National University of Singapore, Singapore.|Life Sciences Institute, National University of Singapore, Singapore.|Department of Statistics and Applied Probability, National University of Singapore, Singapore.|NUS Graduate School for Integrative Science and Engineering, National University of Singapore, Singapore.|Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore.
authors.forename: Y Y
authors.initials: YY
authors.lastname: Teo
mesh_terms: D001315:Australia; D001942:Breast Feeding; D002170:Canada; D032921:Consensus; D003430:Cross-Sectional Studies; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D004348:Drug Labeling / Q000331:legislation & jurisprudence* / Q000592:standards; D064420:Drug-Related Side Effects and Adverse Reactions / Q000201:enzymology / Q000235:genetics* / Q000276:immunology / Q000517:prevention & control; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014453:Glucuronosyltransferase / Q000235:genetics; D015234:HLA-A Antigens / Q000235:genetics; D059910:HLA-B15 Antigen / Q000235:genetics; D006801:Humans; D009520:New Zealand; D061214:Patient Safety / Q000331:legislation & jurisprudence; D010597:Pharmacogenetics / Q000331:legislation & jurisprudence* / Q000592:standards; D000071185:Pharmacogenomic Testing / Q000331:legislation & jurisprudence; D000071184:Pharmacogenomic Variants; D010641:Phenotype; D011237:Predictive Value of Tests; D018570:Risk Assessment; D012307:Risk Factors; D012737:Sex Factors; D012846:Singapore; D006113:United Kingdom; D014481:United States; D000099148:UGT1A1 Enzyme
chemical_list: D019389:Cytochrome P-450 CYP2D6; D014453:Glucuronosyltransferase; D015234:HLA-A Antigens; D059910:HLA-B15 Antigen; D000099148:UGT1A1 Enzyme; C506273:HLA-A*31:01 antigen; C483536:HLA-B*15:02 antigen