Abstract
To study the possible genetic associations with adverse drug reactions (ADR), the Singapore Health Sciences Authority (HSA) has piloted a program to collect DNA and phenotype data of ADR cases as part of its pharmacovigilance program. Between 2009 and 2012, HSA screened 158 cases of Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). To assess the association between HLA-B*1502 and carbamazepine (CBZ)-induced SJS/TEN, 13 cases and 26 drug-tolerant controls were analyzed. All 13 CBZ-SJS/TEN cases and 3/26 controls were HLA-B*1502 positive (odds ratio 181, 95% confidence interval: 8.7–3785, P=6.9 × 10−8). Discussions of the finding with the Ministry of Health and an expert panel led to the decision to make HLA-B*1502 testing the standard of care prior to first use of CBZ in Asians and to subsidize the genotyping test at public hospitals. This program illustrates the role of a regulatory authority in advancing the use of pharmacogenetics for drug safety.
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Acknowledgements
We thank the clinical research coordinators (NUH: Ms Seow Lih Jen, Ms Serene Ng and Mr Eric Seow; SGH: Ms Goh Poh Kuan and Ms Ei Mon Soe; CGH: Ms Low Li Fang, Ms Geraldine Lim and Ms Candy Yang) for assistance in patient recruitment and data collection, Dr Mariam Molokhia for sharing the RegiSCAR protocol, Lee Yan Lim and Tzer Jing Seng for assistance with developing the e-CRF and coding protocols, Singapore Tissue Network/Singapore Biobank and National University Health Systems Tissue Repository for sample storage and processing services, and the HSA Pharmacogenetics Expert Panel for valuable suggestions on design and implementation of the study. This study was funded by HSA.
Author contributions
Conceived the project: DT, LLT, CLL and CS; study design and site set up: DT, LLT, DCWA, SMP, TT, HYL, YKT, CL and CS; managed the project and monitored cases: LLT and CL; screened, recruited and consented patients: DCWA, SMP, SHL, HYL, YYT, SKT, AV, AL and YYC; genotyping and data analysis: ECR, ESCK, LLT and CS; wrote the manuscript: CS and DT.
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Toh, D., Tan, L., Aw, D. et al. Building pharmacogenetics into a pharmacovigilance program in Singapore: using serious skin rash as a pilot study. Pharmacogenomics J 14, 316–321 (2014). https://doi.org/10.1038/tpj.2013.46
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DOI: https://doi.org/10.1038/tpj.2013.46
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