title: Factors Affecting the Timing of Signal Detection of Adverse Drug Reactions.
abstract: We investigated factors affecting the timing of signal detection by comparing variations in reporting time of known and unknown ADRs after initial drug release in the USA. Data on adverse event reactions (AERs) submitted to U.S. FDA was used. Six ADRs associated with 6 drugs (rosuvastatin, aripiprazole, teriparatide, telithromycin, exenatide, varenicline) were investigated: Changes in the proportional reporting ratio, reporting odds ratio, and information component as indexes of signal detection were followed every 3 months after each drugs release, and the time for detection of signals was investigated. The time for the detection of signal to be detected after drug release in the USA was 2-10 months for known ADRs and 19-44 months for unknown ones. The median lag time for known and unknown ADRs was 99.0-122.5 days and 185.5-306.0 days, respectively. When the FDA released advisory information on rare but potentially serious health risks of an unknown ADR, the time lag to report from the onset of ADRs to the FDA was shorter. This study suggested that one factor affecting signal detection time is whether an ADR was known or unknown at release.
authors.affiliation: Division for Evaluation and Analysis of Drug Information, Faculty of Pharmacy, Keio University, Shibakoen, Minato-ku, Tokyo, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hashiguchi
authors.affiliation: Division for Evaluation and Analysis of Drug Information, Faculty of Pharmacy, Keio University, Shibakoen, Minato-ku, Tokyo, Japan.
authors.forename: Shungo
authors.initials: S
authors.lastname: Imai
authors.affiliation: Japan Pharmaceutical Information Center (JAPIC), Shibuya, Shibuya-ku, Tokyo, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Uehara
authors.affiliation: Division for Evaluation and Analysis of Drug Information, Faculty of Pharmacy, Keio University, Shibakoen, Minato-ku, Tokyo, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Maruyama
authors.affiliation: Department of Hygienic Chemistry, Faculty of Pharmacy, Keio University, Shibakoen, Minato-ku, Tokyo, Japan.
authors.forename: Mikiko
authors.initials: M
authors.lastname: Shimizu
authors.affiliation: Division for Evaluation and Analysis of Drug Information, Faculty of Pharmacy, Keio University, Shibakoen, Minato-ku, Tokyo, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Mochizuki
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems / Q000706:statistics & numerical data; D000068180:Aripiprazole / Q000009:adverse effects; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D057225:Data Mining; D016208:Databases, Factual; D004348:Drug Labeling; D064420:Drug-Related Side Effects and Adverse Reactions; D000077270:Exenatide; D006801:Humans; D006934:Hypercalcemia / Q000139:chemically induced; D048628:Ketolides / Q000009:adverse effects; D010195:Pancreatitis / Q000139:chemically induced; D010455:Peptides / Q000009:adverse effects; D012206:Rhabdomyolysis / Q000139:chemically induced; D000068718:Rosuvastatin Calcium / Q000009:adverse effects; D013405:Suicide; D019379:Teriparatide / Q000009:adverse effects; D013997:Time Factors; D014481:United States; D014486:United States Food and Drug Administration; D000068580:Varenicline / Q000009:adverse effects; D014688:Venoms / Q000009:adverse effects
chemical_list: D048628:Ketolides; D010455:Peptides; D014688:Venoms; D019379:Teriparatide; D000068180:Aripiprazole; D000068718:Rosuvastatin Calcium; D000077270:Exenatide; C106791:telithromycin; D000068580:Varenicline