How are safety signals detected, evaluated, and managed?

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Data spontaneously reported to sponsor company may be incomplete or confounded10,14
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It can be challenging to determine causality if limited information is reported10
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Signal evaluation can include assessment of pre-clinical, clinical, post-marketing, and epidemiology data10,17

Sponsor companies communicate individual AEs and signals to regulatory agencies via individual case study reports and periodic aggregate safety reports according to timelines specified by regulatory guidelines1,9,10,12

Regulatory authorities have the final decision on the content and language included in the product label and what subsequent action may be required if signals are identified post-approval8,9,17,19,20

References

1. Beninger P. Clin Ther. 2018;40:1991-2004. 2. Singh S, Loke YK. Trials. 2012;13:138. 3. WHO. Safety of Medicines. A guide to detecting and reporting adverse drug reactions. 2002. 4. Ioannidis JPA, et al. Ann Intern Med. 2004;141:781-788. 5. Lineberry N, et al. BMJ. 2016;355:i5078. 6. Berlin JA, et al. Am J Public Health. 2008;98:1366-1371. 7. FDA. Guidance for Clinical Trial Sponsors. Establishment and Operation of Clinical Trial Data Monitoring Committees. 2006. 8. FDA. Guidance for Industry. Safety Labeling Changes. 2013. 9. Kumar A. Am J Health-Syst Pharm. 2017;74:606-612. 10. FDA. Guidance for Industry. Good Pharmacovigilance Practices and Pharmacoepidemiologic Assessment. 2005. 11. FDA. Questions and Answers on FDA's Adverse Event Reporting System (FAERS). https://www.fda.gov/drugs/surveillance/questions-and-answers-fdas-adverse-event-reporting-system-faers. Accessed October 14, 2019. 12. FDA. Guidance for Industry. Providing Submissions in Electronic Format. Postmarketing Safety Reports. 2014. 13. WHO. Open Access to the WHO Global Pharmacovigilance Database. https://www.who.int/medicines/news/glob_pharmvig_database_qa/en/. Accessed October 14, 2019. 14. EMA. Guideline on good pharmacovigilance practices (GVP). 2017. 15. Koutkias VG, Jaulent MC. Drug Saf. 2015;38:219-232. 16. EMA. Guide on the interpretation of spontaneous case reports of suspected adverse reactions to medicines. 2017. 17. Council for International Organizations of Medical Sciences Working Group IV. Benefit-Risk Balance for Marketed Drugs: Evaluating Safety Signals. 1998. 18. FDA. Guidance for Industry. Development of a Shared System REMS. 2018. 19. FDA. Guidance for Industry and Investigators. Safety Reporting Requirements for INDs and BA/BE Studies. 2012. 20. FDA. Guidance. Classifying Significant Postmarketing Drug Safety Issues. 2012.