The aim of this study was to compare guidance for genetic testing in US Food and Drug Administration (FDA)-approved drug labels in oncology to those of drugs for other therapeutic areas.
We reviewed labels of all the FDA-approved drugs with labels containing pharmacogenomic information. We assessed whether genetic testing was required or recommended before prescription and, if not, the reason for pharmacogenomic labeling.
We included 140 drugs corresponding to 158 drug–biomarker pairs. Overall, 46 (29%) of 158 pairs stated a requirement or recommendation for genetic biomarker testing in the label. This proportion was higher in oncology than in other areas (62 vs. 12%; P < 0.001). For the 112 drug–biomarker pairs (including 20 in oncology) without recommendation or requirement for genetic testing, the main reasons for pharmacogenomic labeling were change in pharmacologic end points (32%) and higher risk of toxicity (30%). For 11 (10%) pairs (including 1 in oncology), a genetic biomarker was mentioned only to inform that it was not relevant. In oncology, the main reasons for pharmacogenomic labeling were higher risk of toxicity (55%) and definition of the mechanism of action (25%).
Inclusion of biomarkers in drug labels does not always correspond to required or recommended genetic testing, especially outside oncology.
Genet Med advance online publication 18 December 2014
Palomaki GE, Bradley LA, Douglas MP, Kolor K, Dotson WD. Can UGT1A1 genotyping reduce morbidity and mortality in patients with metastatic colorectal cancer treated with irinotecan? An evidence-based review. Genet Med2009;11:21–34.
Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group.Recommendations from the EGAPP Working Group: can tumor gene expression profiling improve outcomes in patients with breast cancer?Genet Med2009;11:66–73.
Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group.Recommendations from the EGAPP Working Group: testing for cytochrome P450 polymorphisms in adults with nonpsychotic depression treated with selective serotonin reuptake inhibitors. Genet Med2007;9:819–825.
Sadée W, Dai Z. Pharmacogenetics/genomics and personalized medicine. Hum Mol Genet2005;14 Spec No. 2:R207–R214.
Preskorn SH, Kane CP, Lobello K, et al. Cytochrome P450 2D6 phenoconversion is common in patients being treated for depression: implications for personalized medicine. J Clin Psychiatry2013;74:614–621.
Osnabrugge RL, Head SJ, Zijlstra F, et al. A systematic review and critical assessment of 11 discordant meta-analyses on reduced-function CYP2C19 genotype and risk of adverse clinical outcomes in clopidogrel users. Genet Med2014; e-pub ahead of print 19 June 2014.
Malottki K, Biswas M, Deeks JJ, et al. Stratified medicine in European Medicines Agency licensing: a systematic review of predictive biomarkers. BMJ Open2014;4:e004188.
Trotta F, Leufkens HG, Schellens JH, Laing R, Tafuri G. Evaluation of oncology drugs at the European Medicines Agency and US Food and Drug Administration: when differences have an impact on clinical practice. J Clin Oncol2011;29:2266–2272.
Wang B, Canestaro WJ, Choudhry NK. Clinical evidence supporting pharmacogenomic biomarker testing provided in US Food and Drug Administration drug labels. JAMA Intern Med2014; e-pub ahead of print 13 October 2014.
Tajik P, Zwinderman AH, Mol BW, Bossuyt PM. Trial designs for personalizing cancer care: a systematic review and classification. Clin Cancer Res2013;19:4578–4588.
Le Tourneau C, Paoletti X, Servant N, et al. Randomised proof-of-concept phase II trial comparing targeted therapy based on tumour molecular profiling vs conventional therapy in patients with refractory cancer: results of the feasibility part of the SHIVA trial. Br J Cancer2014;111:17–24.
ver historia personal en: www.cerasale.com.ar [dado de baja por la Cancillería Argentina por temas políticos, propio de la censura que rige en nuestro medio]//
weblog.maimonides.edu/farmacia/archives/UM_Informe_Autoevaluacion_FyB.pdf - //
weblog.maimonides.edu/farmacia/archives/0216_Admin_FarmEcon.pdf - //
www.proz.com/kudoz/english_to_spanish/art_literary/523942-key_factors.html - 65k - // www.llave.connmed.com.ar/portalnoticias_vernoticia.php?codigonoticia=17715 // www.frusculleda.com.ar/homepage/espanol/activities_teaching.htm // http://www.on24.com.ar/nota.aspx?idNot=36331 ||