Background: Notoriety bias is defined as “a selection bias in which a case has a greater chance of being reported if the subject is exposed to the studied factor known to cause, thought to cause, or likely to cause the event of interest.” This study aimed to determine the existence of notoriety bias in the FDA Adverse Event Reporting System (FAERS) database and estimate the impact of potential notoriety bias induced by safety alerts on signal estimation using disproportionality analysis. Methods: Publicly available FAERS data were downloaded and used for analysis. Thirty-one drugs which had label change/safety alert issued by FDA from 2009 to 2013 were considered. These drugs were reviewed 4 quarters before and after the safety alert notification for the existence of notoriety bias. The impact of notoriety bias induced by safety alerts was analyzed by comparing the signal strength using reporting odds ratio (ROR) and proportional reporting ratio (PRR), 2 years before and after the safety alert. Wilcoxon signed rank test was used to determine whether there were a statistically significant difference before and after the safety alert. Results: There was increased reporting for 11 drugs after the safety alert/label change by the FDA. The reporting of 20 drugs decreased or remained unchanged after the safety alert/label change by the FDA. Wilcoxon signed rank test showed that there is no statistically significant difference with respect to the number of reports before and after the safety alert (P = .330, Z = −0.974). Fourteen (45.16%) drugs had an increase in ROR, while 17 (54.83%) drugs had a decrease in ROR after safety alert issued by FDA (P = .953, Z = −0.059). Fourteen (45.16%) drugs had an increase in PRR, while 17 (54.83%) drugs had a decrease in PRR after safety alert issued by the FDA (P = .914, Z = −0.108). Conclusion: Although few FDA safety alert/warnings had a strong and immediate impact, many had no impact on reporting of AE and signal strength. This study found that overreporting due to notoriety bias does not exist in the FAERS database and the overall disproportionality in signal estimates is not altered by the safety alert.
AhmadSR. Adverse drug event monitoring at the Food and Drug Administration. J Gen Intern Med. 2003;18(1):57-60.
2.
CharatanF. Bayer decides to withdraw cholesterol lowering drug. BMJ. 2001;323(7309):359.
3.
QureshiZPSeoane-VazquezERodriguez-MonguioRStevensonKBSzeinbachSL. Market withdrawal of new molecular entities approved in the United States from 1980 to 2009. Pharmacoepidemiol Drug Saf. 2011;20(7):772-777.
4.
McBrideWG. Thalidomide and congenital abnormalities. Lancet. 1961;278(7216):1358.
5.
PoluzziERaschiEPiccinniCDe PontiF. Data mining techniques in pharmacovigilance: analysis of the publicly accessible FDA Adverse Event Reporting System (AERS). In: KarahocaA, ed. Data Mining Applications in Engineering and Medicine. Rijeka, Croatia: InTech; 2012:265-302.
Alvarez-RequejoACarvajalABegaudBMorideYVegaTAriasLM. Under-reporting of adverse drug reactions. Estimate based on a spontaneous reporting scheme and a sentinel system. Eur J Clin Pharmacol. 1998;54(6):483-488.
10.
BeulahEReddyNSubeeshVMaheswariEPudiC. Weber effect: an extended analysis for ten years of reporting trends in FDA Adverse Event Reporting System (FAERS). Value Health. 2018;21:S369.
11.
HarringtonCAGarciaASSircar-RamsewakF. Evaluation of adverse drug event information in US manufacturer labels. Curr Drug Saf. 2011;6(1):30-35.
12.
PieningSHaaijer-RuskampFMde VriesJT, et al. Impact of safety-related regulatory action on clinical practice: a systematic review. Drug Saf. 2012;35(5):373-385.
13.
BuschSHFrankRGLeslieDL, et al. Antidepressants and suicide risk: how did specific information in FDA safety warnings affect treatment patterns?Psychiatr Serv. 2010;61(1):11-16.
14.
CluxtonRJLiZHeatonPC, et al. Impact of regulatory labeling for troglitazone and rosiglitazone on hepatic enzyme monitoring compliance: findings from the state of Ohio Medicaid program. Pharmacoepidemiol Drug Saf. 2005;14(1):1-9.
15.
ShrankWHChoudhryNKTongA, et al. Warnings without guidance: patient responses to an FDA warning about ezetimibe. Med Care. 2012;50:479-484.
16.
ValluriSZitoJMSaferDJZuckermanIHMullinsCDKorelitzJJ. Impact of the 2004 Food and Drug Administration pediatric suicidality warning on antidepressant and psychotherapy treatment for new-onset depression. Med Care. 2010;48:947-954.
17.
OlfsonMMarcusSCDrussBG. Effects of Food and Drug Administration warnings on antidepressant use in a national sample. Arch Gen Psychiatry. 2008;65(1):94-101.
18.
SubeeshVSinghHMaheswariEBeulahE. Novel adverse events of vortioxetine: a disproportionality analysis in USFDA Adverse Event Reporting System database. Asian Journal of Psychiatry. 2017;30:152-156.
19.
SubeeshVMaheswariESinghHBeulahTESwaroopAM. Novel adverse events of iloperidone: a disproportionality analysis in US Food and Drug Administration Adverse Event Reporting System (FAERS) database. Curr Drug Saf. 2019;14(1):21-26.
20.
HoffmanKBDemakasARDimbilMTatonettiNPErdmanCB. Stimulated reporting: the impact of US Food and Drug Administration-issued alerts on the adverse event reporting system (FAERS). Drug Saf. 2014;37(11):971-980.
21.
ParienteAGregoireFFourrier-ReglatAHaramburuFMooreN. Impact of safety alerts on measures of disproportionality in spontaneous reporting databases: the notoriety bias. Drug Saf. 2007;30(10):891-898.
22.
FaasseKGambleGCundyTPetrieKJ. Impact of television coverage on the number and type of symptoms reported during a health scare: a retrospective pre-post observational study. BMJ Open. 2012;2(4):e001607.
23.
CasselsAHughesMAColeCMintzesBLexchinJMcCormackJP. Drugs in the news: an analysis of Canadian newspaper coverage of new prescription drugs. CMAJ. 2003;168(9):1133-1137.
24.
MorratoEHLibbyAMOrtonHD, et al. Frequency of provider contact after FDA advisory on risk of pediatric suicidality with SSRIs. Am J Psychiatry. 2008;165(1):42-50.
25.
GoldmanSA. Communication of medical product risk. Drug Saf. 2004;27(8):519-534.
26.
IsacssonGRichCL. Antidepressant drugs and the risk of suicide in children and adolescents. Pediatr Drugs. 2014;16(2):115-122.
27.
GibbonsRDBrownCHHurK, et al. Early evidence on the effects of regulators’ suicidality warnings on SSRI prescriptions and suicide in children and adolescents. Am J Psychiatry. 2007;164(9):1356-1363.
28.
LasserKESegerDLYuDT, et al. Adherence to black box warnings for prescription medications in outpatients. Arch Intern Med. 2006;166(3):338-344.
