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Building pharmacogenetics into a pharmacovigilance program in Singapore: using serious skin rash as a pilot study

The Pharmacogenomics Journal volume 14, pages 316–321 (2014)Cite this article

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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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Author notes

  1. Y Y Chong

    Present address: 17Present address: Raffles Hospital, North Bridge Road, Singapore.,

  2. D S L Toh and L L Tan: These authors contributed equally to this work.

Authors and Affiliations

  1. Vigilance Branch, Health Sciences Authority, Singapore

    D S L Toh, L L Tan, C Loke, C L Chan & C Sung

  2. Dermatology Department, National University Hospital, Singapore

    D C W Aw

  3. Dermatology Department, Singapore General Hospital, Singapore

    S M Pang, T Thirumoorthy & H Y Lee

  4. Neurology Department, Singapore General Hospital, Singapore

    S H Lim

  5. Duke-NUS Graduate Medical School, Singapore

    S H Lim & C Sung

  6. Dermatology Department, Changi General Hospital, Singapore

    Y K Tay & S K Tan

  7. Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore

    Y K Tay & Y C Chan

  8. Rheumatology Department, Changi General Hospital, Singapore

    A Vasudevan

  9. Rheumatology Department, National University Hospital, Singapore

    A Lateef

  10. Rheumatology and Immunology Department, Singapore General Hospital, Singapore

    Y Y Chong

  11. Neurology Department, National University Hospital, Singapore

    Y C Chan

  12. Molecular Diagnosis Centre, National University Hospital, Singapore

    E S C Koay

  13. Pathology Department, Yong Loo Lin School of Medicine, National University of Singapore, Singapore

    E S C Koay

  14. Singapore Immunology Network, Agency for Science, Technology and Research, Singapore

    E C Ren

  15. Pharmacology Department, Yong Loo Lin School of Medicine, National University of Singapore, Singapore

    E J D Lee

Authors
  1. D S L Toh
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  2. L L Tan
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  3. D C W Aw
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  4. S M Pang
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  7. H Y Lee
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  8. Y K Tay
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  9. S K Tan
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  10. A Vasudevan
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  11. A Lateef
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  12. Y Y Chong
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  13. Y C Chan
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  14. C Loke
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  15. C L Chan
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  16. E S C Koay
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  17. E C Ren
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  18. E J D Lee
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  19. C Sung
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Corresponding author

Correspondence to C Sung.

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The authors declare no conflict of interest.

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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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