A New Drug Safety Signal Detection and Triage System Integrating Sequence Symmetry Analysis and Tree-Based Scan Statistics with Longitudinal Data

Abstract

Miyuki Hsing-Chun Hsieh,1,2,* Hsun-Yin Liang,2,* Chih-Ying Tsai,2 Yu-Ting Tseng,2 Pi-Hui Chao,2 Wei-I Huang,2 Wen-Wen Chen,2 Swu-Jane Lin,3 Edward Chia-Cheng Lai1 1Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 2Taiwan Drug Relief Foundation (TDRF), Taipei, Taiwan; 3Department of Pharmacy Systems, Outcomes & Policy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA*These authors contributed equally to this workCorrespondence: Edward Chia-Cheng Lai, Email [email protected]: Development and evaluation of a drug-safety signal detection system integrating data-mining tools in longitudinal data is essential. This study aimed to construct a new triage system using longitudinal data for drug-safety signal detection, integrating data-mining tools, and evaluate adaptability of such system.Patients and Methods: Based on relevant guidelines and structural frameworks in Taiwan’s pharmacovigilance system, we constructed a triage system integrating sequence symmetry analysis (SSA) and tree-based scan statistics (TreeScan) as data-mining tools for detecting safety signals. We conducted an exploratory analysis utilizing Taiwan’s National Health Insurance Database and selecting two drug classes (sodium-glucose co-transporter-2 inhibitors (SGLT2i) and non-fluorinated quinolones (NFQ)) as chronic and episodic treatment respectively, as examples to test feasibility of the system.Results: Under the proposed system, either cohort-based or self-controlled mining with SSA and TreeScan was selected, based on whether the screened drug had an appropriate comparator. All detected alerts were further classified as known adverse drug reactions (ADRs), events related to other causes or potential signals from the triage algorithm, building on existing drug labels and clinical judgement. Exploratory analysis revealed greater numbers of signals for NFQ with a relatively low proportion of known ADRs; most were related to indication, patient characteristics or bias. No safety signals were found. By contrast, most SGLT2i signals were known ADRs or events related to patient characteristics. Four were potential signals warranting further investigation.Conclusion: The proposed system facilitated active and systematic screening to detect and classify potential safety signals. Countries with real-world longitudinal data could adopt it to streamline drug-safety surveillance.Keywords: drug safety, signal detection, triage, sequence symmetry analysis, tree-based scan statistics

Keywords

• drug safety
• signal detection
• triage
• sequence symmetry analysis
• tree-based scan statistics