28 SECTION II Safety Data and Real World Evidence

4. Hauben M, Madigan D, Gerrits CM, Walsh L, Van

Term Definition
Puijenbroek EP. The role of data mining in phar-
Safety Activities, both qualitative and quantitative, macovigilance. Expert Opin Drug Saf. 2005;4(5):929e948.
surveillance designed to identify previously unknown 5. Chan KA, Hauben M. Signal detection in pharmacovigi-
effects of a compound, or new aspects of lance: empirical evaluation of data mining tools. Pharma-
known effects, in order to harness such effects coepidemiol Drug Saf. 2005;14(9):597e599.
(if beneficial) or prevent or mitigate them (if 6. Bate A, Evans SJ. Quantitative signal detection using
harmful). spontaneous ADR reporting. Pharmacoepidemiol Drug Saf.
Signal Evaluating the totality of available scientific 2009;18(6):427e436.
assessment evidence across all developmental phases of a 7. Quattrini G, Zambon A, Simoni L, Fiori G. Disproportion-
drug product and from multiple sources. ality measures used in signal detection: an assessment on
Signal A set of activities performed to determine pharmacovigilance adverse event reporting system data.
management whether there are new risks causally Value Health. 2015;18(7):A720.
associated with an active substance or 8. Hauben M, Zhou X. Quantitative methods in pharmacovi-
medicinal product or whether known risks gilance: focus on signal detection. Drug Saf. 2003;26(3):
have changed. This includes signal detection, 159e186.
signal validation, signal assessment, and 9. Almenoff JS, LaCroix KK, Yuen NA, Fram D, DuMouchel W.
recommendation for action. Comparative performance of two quantitative safety signal-
Signal Signals may come from various sources that ling methods: implications for use in a pharmacovigilance
sources include, but are not limited to, department. Drug Saf. 2006;29(10):875e887.
• spontaneous reporting 10. Jokinen JD. Determination of Change in Online Monitoring of
• solicited reporting Longitudinal Data: An Evaluation of Methodologies [Disserta-
• published literature tion]. Athens, OH: Ohio University; 2015.
• clinical trials 11. Jokinen JD, Lievano F, Truffa M. A Frequency-Based Method
• product quality/manufacturing for Safety Signal Detection Data Mining. 2017.
12. European Medicines Agency. Guideline on Good Pharmacovi-
• toxicology
gilance Practices (GVP) Module IX Addendum I e Methodolog-
• legal
ical Aspects of Signal Detection from Spontaneous Reports of
• regulatory authorities Suspected Adverse Reactions 2016; 2016. Available from:
• Internet and digital, including social media http://www.ema.europa.eu/docs/en_GB/document_library
• independent organizations /Regulatory_and_procedural_guideline/2016/08/WC5002
• academia 11715.pdf.
Signal Process of evaluating the data supporting a 13. Pinheiro LC, Candore G, Zaccaria C, Slattery J, Arlett P.
validation detected signal in order to verify that the An algorithm to detect unexpected increases in frequency
available documentation contains sufficient of reports of adverse events in EudraVigilance. Pharmacoe-
evidence demonstrating the existence of a new pidemiol Drug Saf. 2017.
potentially causal association, or a new aspect 14. Banks PA, Bollen TL, Dervenis C. Acute Pancreatitis
of a known association, and therefore justifies Classification Working Group. Classification of acute
further assessment of the signal. pancreatitisd2012: revision of the Atlanta classification
and definitions by international consensus. Gut. 2013;62:
102e111. https://doi.org/10.1136/gutjnl-2012-302779.
15. Heath A, Manolopoulou I, Baio G. A review of methods for
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