Abstract
A primary aim in pharmacovigilance is the timely detection of either new adverse drug reactions (ADRs) or a relevant change of the frequency of ADRs that are already known to be associated with the drugs involved, i.e. signal detection. Adequate signal detection solely based on the human intellect (case-by-case analysis or qualitative signal detection) has proven its value. However, it is becoming increasingly time consuming given the growing volume of data, as well as less effective, especially in more complex associations, such as drug-drug interactions, syndromes and when various covariates are involved. In quantitative signal detection, measures that express the extent in which combinations of drug(s) and clinical event(s) are disproportionately present in the database of reported suspected ADRs are used to reveal associations of interest. Although the rationale and the methodology of the various quantitative approaches differ, they all share the characteristic in that they express to what extent the number of observed cases differs from the number of expected cases.
Recent years have shown that the use of quantitative measures in addition to qualitative analysis is a step forward in signal detection in pharmacovigilance.
This paper uses historical, classic examples and studies to illustrate the principles, pros and cons of especially quantitative methods in signal detection and adds a flavour of future perspective.
References
Edwards IR, Lindquist M, Wiholm B-E, et al. Quality criteria for early signals of possible adverse drug reactions. Lancet 1990; 336(8708): 156–8
Venning GR. Identification of adverse reactions to new drugs. I: what have been the important adverse reactions since thalidomide? Br Med J (Clin Res Ed) 1983; 286(6360): 199–202
Venning GR. Identification of adverse reactions to new drugs. II: how were 18 important adverse reactions discovered and with what delays? Br Med J (Clin Res Ed) 1983; 286(6361): 289–92
Venning GR. Identification of adverse reactions to new drugs. II (continued): how were 18 important adverse reactions discovered and with what delays? Br Med J (Clin Res Ed) 1983; 286(6362): 365–8
Venning GR. Identification of adverse reactions to new drugs. III: alerting processes and early warning systems. Br Med J (Clin Res Ed) 1983; 286(6363): 458–60
Venning GR. Validity of anecdotal reports of suspected adverse drug reactions: the problem of false alarms. Br Med J (Clin Res Ed) 1982; 284(6311): 249–52
Venning GR. Identification of adverse reactions to new drugs. IV: verification of suspected adverse reactions. Br Med J (Clin Res Ed) 1983; 286(6364): 544–7
Finney DJ. The design and logic of a monitor of drug use. J Chronic Dis 1965; 18: 77–98
Mcbride WG. Thalidomide and congenital abnormalities. Lancet 1961; 278(7216): 1358
Napke E. Canada. In: Inman WHW, editor. Monitoring for drug safety. Lancaster: MTP Press, 1986: 65–6
van Puijenbroek EP, Bate A, Leufkens HG, et al. A comparison of measures of disproportionality for signal detection in spontaneous reporting systems for adverse drug reactions. Pharmacoepidemiol Drug Saf 2002; 11(1): 3–10
De Bruin ML, Pettersson M, Meyboom RHB, et al. Anti-HERG activity and the risk of drug-induced arrhythmias and sudden death. Eur Heart J 2005; 26(6): 590–7
Egberts TCG, Smulders M, De Koning FHP, et al. Can adverse drug reactions be detected earlier? A comparison of reports by patients and professionals. Br Med J 1996; 313(7056): 530–1
Russmann S, Kaye J, Jick S, et al. Risk of cholestatic liver disease associated with flucloxacillin and flucloxacillin prescribing habits in the UK: Cohort study using data from the UK General Practice Research Database. Br J Clin Pharmacol 2005; 60(1): 76–82
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No sources of funding were used to assist in the preparation of this paper. The author has no conflicts of interest that are directly relevant to the content of this paper.
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Egberts, T.C.G. Signal Detection. Drug-Safety 30, 607–609 (2007). https://doi.org/10.2165/00002018-200730070-00006
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DOI: https://doi.org/10.2165/00002018-200730070-00006