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Sequence symmetry analysis in pharmacovigilance and pharmacoepidemiologic studies

  • PHARMACO-EPIDEMIOLOGY
  • Published:
European Journal of Epidemiology Aims and scope Submit manuscript

Abstract

Sequence symmetry analysis (SSA) is a method for detecting adverse drug events by utilizing computerized claims data. The method has been increasingly used to investigate safety concerns of medications and as a pharmacovigilance tool to identify unsuspected side effects. Validation studies have indicated that SSA has moderate sensitivity and high specificity and has robust performance. In this review we present the conceptual framework of SSA and discuss advantages and potential pitfalls of the method in practice. SSA is based on analyzing the sequences of medications; if one medication (drug B) is more often initiated after another medication (drug A) than before, it may be an indication of an adverse effect of drug A. The main advantage of the method is that it requires a minimal dataset and is computationally efficient. By design, SSA controls time-constant confounders. However, the validity of SSA may be affected by time-varying confounders, as well as by time trends in the occurrence of exposure or outcome events. Trend effects may be adjusted by modeling the expected sequence ratio in the absence of a true association. There is a potential for false positive or negative results and careful consideration should be given to potential sources of bias when interpreting the results of SSA studies.

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Funding

This study was supported by a grant from the Ministry of Science and Technology of Taiwan (ID: NSC 102-2628-B-006-003-MY).

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Author notes

  1. Nicole Pratt and Edward Chia-Cheng Lai have contributed equally to this work.

Authors and Affiliations

  1. School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, No. 1, University Road, Tainan, 701, Taiwan

    Edward Chia-Cheng Lai, Cheng-Yang Hsieh & Yea-Huei Kao Yang

  2. Health Outcome Research Center, National Cheng Kung University, Tainan, Taiwan

    Edward Chia-Cheng Lai & Yea-Huei Kao Yang

  3. Department of Pharmacy, National Cheng Kung University Hospital, Tainan, Taiwan

    Edward Chia-Cheng Lai

  4. Quality Use of Medicines and Pharmacy Research Centre, Sansom Institute for Health Research, University of South Australia, GPO Box 2471, Adelaide, SA, 5001, Australia

    Nicole Pratt & Elizabeth E. Roughead

  5. Department of Neurology, Tainan Sin-Lau Hospital, Tainan, Taiwan

    Cheng-Yang Hsieh

  6. Department of Pharmacy Systems, Outcomes and Policy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA

    Swu-Jane Lin

  7. Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, 5000, Odense C, Denmark

    Anton Pottegård & Jesper Hallas

Authors
  1. Edward Chia-Cheng Lai
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  2. Nicole Pratt
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  3. Cheng-Yang Hsieh
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  6. Elizabeth E. Roughead
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  7. Yea-Huei Kao Yang
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  8. Jesper Hallas
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Corresponding authors

Correspondence to Elizabeth E. Roughead, Yea-Huei Kao Yang or Jesper Hallas.

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Lai, E.CC., Pratt, N., Hsieh, CY. et al. Sequence symmetry analysis in pharmacovigilance and pharmacoepidemiologic studies. Eur J Epidemiol 32, 567–582 (2017). https://doi.org/10.1007/s10654-017-0281-8

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  • DOI: https://doi.org/10.1007/s10654-017-0281-8

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