Developing a signal triage algorithm for Thai national adverse drug reaction database

Abstract

There has been increasing adverse drug reaction (ADR) reports submitted to the Health Product Vigilance Center under the Thai Food and Drug Administration. To find some signals, the Thai Signal Detection Program was developed to identify and filter the potential signals, called signals of disproportionate reporting (SDRs). A large number of SDRs cannot be in-depth assessed by the Signal Detection Advisory Working Group (SDAWG) in time. The prioritized SDRs with concentrated in-depth assessment might help in finding some true signals. This preliminary study aimed at developing a signal triage algorithm that can prioritize SDRs to assign an in-depth assessment for true signals and to test the proposed triage algorithm and compare against the traditional method by the SDAWG. Multi-criteria decision analysis was chosen for proposing a triage algorithm by generating scores for priority rankings of the clinical importance of SDRs. This study had three main steps. Key attributes for a triage decision were first identified and followed by the development of a signal triage algorithm. After that, the triage algorithm was tested by comparing the triage results of the proposed algorithm with triaging by experts in the SDAWG. Six factors were selected as key attributes, i.e., fatal outcome, serious ADRs, positive rechallenge, new drug, change in number of ADR reports, and source of reports. Four attributes used in the Thai Signal Detection Program were excluded, i.e., the drug-ADR associations, WHO-ART critical term, disproportionality, and volume of reports. Six experts gave the weight for the six key attributes using their experiences, and score criteria were set. To test the proposed triage algorithm, systemic antibiotics with 86 SDRs in total were triaged by the SDAWG, and eight SDRs were chosen for further assessment. Six of them were consistent with the result of the proposed signal triage algorithm (75% agreement) and were the top of the priority ranking. The other two SDRs were selected only by the SDAWG because they were high-concerned and serious ADRs and unfamiliar cases. These could be because of the drug or ADRs of current interest, the level of being key attributes, comorbidity and concurrent medication use, and characteristics of experts’ opinions. The signal triage algorithm can enhance the efficiency of the triage method by experts as it is systematic, transparent, timely, repeatable, and also scientifically based. More research is necessary to evaluate and/or improve this triage algorithm.