PharmacoVigilance

How adverse events are detected, assessed, and understood throughout a product's lifecycle1

Overview of safety in clinical trials ... *

... the real-world setting

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  • Pre-specified patient poolTrial participants are selected according to
    pre-specified eligibility criteria2,3
  • Controlled trialsIn randomized controlled trials (RCTs), incidence of AEs with a product is compared with a control (eg, placebo)4-6
  • Types of adverse events (AEs) reportedIn clinical trials, all AEs are reported for the study duration (including controlled and open-label phases) regardless of causality2,3,5,6-8
Doctors & Nurses
  • Heterogeneous patient populationA larger and more heterogenous patient population use the approved/marketed product in the real-world setting (eg, patients with more complex comorbidities)9,10
  • Challenges in assessing causalityEstablishing whether a causal relationship exists between real-world AEs and the drug is challenging because:
    • There may be unidentified or unaccounted for confounding factors10
    • The incidence of real-world AEs includes background rates of the affected population10
  • Types of AEs reportedIn the post-marketing setting, the manufacturer must communicate all AEs that are reported to them to regulatory agencies regardless of causality11
  • Regulatory agency reporting timelinesAEs are communicated to regulatory agencies according to specified timelines11,12

Although AEs reported in the real world may differ from those in clinical trials,
together these help reflect the product safety profile13

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.