The workshop is designed to introduce pharmacovigilance to graduate students and working professionals interested in drug safety as a career field. After a brief introduction of publicly available data sources, each team received a case study that detailed a specific safety concern that resulted in a significant safety update of product labeling or product withdrawal. Medicines may be withdrawn from markets because of risks to patients or business reasons. Change of benefit: risk profile is usually prompted by adverse effects that were either not previously detected, are more frequent, or more severe than anticipated based on the results of Phase III clinical trials. Market withdrawals are triggered by adverse events that were only made apparent from postmarketing surveillance data collected from population-wide use over more extended periods of time. The sources of information the regulatory agencies use when deciding on market withdrawal include meta-analyses and pooled analyses of data from clinical trials, clinical trials, spontaneous case reports, laboratory studies, observational studies, animal studies, and reviews of existing safety data. In the U.S., individual case safety reports are collected in the FDA Adverse Event Reporting System (FAERS). In Europe, medication side effects are sent to national regulatory authorities and in the EU pharmacovigilance database EudraVigilance. The participants learned where to find clinical trials, market authorizations, and product labeling. After the introductory presentation, each team received a case study that detailed a specific safety issue that resulted in a significant safety update of product labeling or product withdrawal. Each case study received product labeling and several scientific publications that discussed the safety concern in depth. Each team prepared a presentation with detailed overview of their assigned case study. Are you interested in drug safety? Try this for yourself! https://www.aretezoe.com/pharmacovigilance-workshop

1. PHARMACOVIGILANCE
WORKSHOP
Veronika Valdova
ARETE-ZOE, LLC
9/7/2022
PV WORKSHOP: EXPLORE PUBLICLY AVAILABLE
DATA SOURCES IN DRUG SAFETY
1

2. Agenda
Safety withdrawals
PV System Overview
• USA, EU
Publicly available sources
• PV Databases
• Clinical Trial Registries
• Product Authorization
• Product Labeling
9/7/2022
PV WORKSHOP: EXPLORE PUBLICLY AVAILABLE DATA SOURCES
IN DRUG SAFETY 2

3. Significant Safety Withdrawals
​Medicines may be withdrawn from markets because
of risks to patients or for business reasons. Change
of benefit:risk profile to unfavorable is usually
prompted by adverse effects that were either not
previously detected, are more frequent or more
severe than anticipated based on Phase III clinical
trials. Market withdrawals are triggered by adverse
events that were only made apparent
from postmarketing surveillance data collected from
population-wide use over longer periods of time.
9/7/2022 P V W O R K S H O P : E X P L O R E P U B L I C L Y A V A I L A B L E D A T A S O U R C E S I N D R U G S A F E T Y 3

4. Sources of information leading to market withdrawal
PV WORKSHOP: EXPLORE PUBLICLY AVAILABLE
DATA SOURCES IN DRUG SAFETY
9/7/2022 4
Craveiro NS, Lopes BS, Tomás L, Almeida SF. Drug Withdrawal Due to Safety: A Review of the Data
Supporting Withdrawal Decision. Curr Drug Saf. 2020;15(1):4-12. doi:
10.2174/1574886314666191004092520. PMID: 31584381.

5. Cardiovascular drugs withdrawn for safety reasons
PV WORKSHOP: EXPLORE PUBLICLY AVAILABLE
DATA SOURCES IN DRUG SAFETY
9/7/2022 5
Kocadal
K,
Saygi
S,
Alkas
FB,
Sardas
S.
Drug-
associated
cardiovascular
risks:
A
retrospective
evaluation
of
withdrawn
drugs.
North
Clin
Istanb
2019;6(2):196–202.

6. Pharmacovigilance Databases
PV WORKSHOP: EXPLORE PUBLICLY AVAILABLE
DATA SOURCES IN DRUG SAFETY
9/7/2022 6
EudraVigilance
FAERS

7. DRUG SAFETY
SURVEILLANCE
IN EUROPE
Adverse Drug Events in
• Clinical Trials
• Post-Market Use
PV WORKSHOP: EXPLORE PUBLICLY AVAILABLE DATA SOURCES IN DRUG SAFETY

8. EudraVigilance System Components
9/7/2022
PV WORKSHOP: EXPLORE PUBLICLY AVAILABLE DATA
SOURCES IN DRUG SAFETY 8

9. HTTP://WWW.ADR
PV WORKSHOP: EXPLORE PUBLICLY AVAILABLE
DATA SOURCES IN DRUG SAFETY 9/7/2022 9
HTTP://WWW.ADRREPORTS.EU/
EudraVigilance
European database of suspected
adverse drug reaction reports

10. PV WORKSHOP: EXPLORE PUBLICLY AVAILABLE DATA SOURCES IN DRUG SAFETY 10
HTTP://WWW.ADRREPORTS.EU/

11. PV WORKSHOP: EXPLORE PUBLICLY AVAILABLE DATA SOURCES IN DRUG SAFETY 11
H
T
T
P
:/
/
W
W
W.
A
D
RR
EP
O
RTS.
EU
/

12. DRUG SAFETY
SURVEILLANCE
IN THE USA
Adverse Drug Events in
• Clinical Trials
• Post-Market Use
PV WORKSHOP: EXPLORE PUBLICLY AVAILABLE DATA SOURCES IN DRUG SAFETY

13. PV WORKSHOP: EXPLORE PUBLICLY AVAILABLE DATA SOURCES IN DRUG SAFETY 13
https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformatio
n/Surveillance/AdverseDrugEffects/ucm070093.htm

14. PV WORKSHOP: EXPLORE PUBLICLY AVAILABLE DATA SOURCES IN DRUG SAFETY 14
MedWatch Alerts

15. PV WORKSHOP: EXPLORE PUBLICLY AVAILABLE DATA SOURCES IN DRUG SAFETY 15
https://fis.fda.gov/sense/app/d10be6bb-494e-4cd2-82e4-0135608ddc13/sheet/7a47a261-d58b-4203-a8aa-
6d3021737452/state/analysis

16. PV WORKSHOP: EXPLORE PUBLICLY AVAILABLE DATA SOURCES IN DRUG SAFETY 16
https://fis.fda.gov/sense/app/d10be6bb-494e-4cd2-82e4-0135608ddc13/sheet/7a47a261-d58b-4203-a8aa-
6d3021737452/state/analysis

17. PV WORKSHOP: EXPLORE PUBLICLY AVAILABLE DATA SOURCES IN DRUG SAFETY 17
https://fis.fda.gov/sense/app/d10be6bb-494e-4cd2-82e4-0135608ddc13/sheet/7a47a261-d58b-4203-a8aa-
6d3021737452/state/analysis

18. CLINICAL TRIAL
REGISTRIES
• ClinicalTrials.gov
• EU CT REGISTER
• WHO ICTRP
PV WORKSHOP: EXPLORE PUBLICLY AVAILABLE DATA SOURCES IN DRUG SAFETY

19. PV WORKSHOP: EXPLORE PUBLICLY AVAILABLE DATA SOURCES IN DRUG SAFETY 19
https://clinicaltrials.gov/

20. PV WORKSHOP: EXPLORE PUBLICLY AVAILABLE DATA SOURCES IN DRUG SAFETY 20
https://clinicaltrials.gov/
Clinical trails with bevacizumab

21. PV WORKSHOP: EXPLORE PUBLICLY AVAILABLE DATA SOURCES IN DRUG SAFETY 21
https://www.clinicaltrialsregister.eu/

22. PV WORKSHOP: EXPLORE PUBLICLY AVAILABLE DATA SOURCES IN DRUG SAFETY 22
https://www.clinicaltrialsregister.eu/

23. PV WORKSHOP: EXPLORE PUBLICLY AVAILABLE DATA SOURCES IN DRUG SAFETY 23
https://trialsearch.who.int/Default.aspx

24. PV WORKSHOP: EXPLORE PUBLICLY AVAILABLE DATA SOURCES IN DRUG SAFETY 24
https://trialsearch.who.int/Default.aspx

25. PV WORKSHOP: EXPLORE PUBLICLY AVAILABLE DATA SOURCES IN DRUG SAFETY 25
https://trialsearch.who.int/Default.aspx

26. PRODUCT
AUTHORIZATION
• EU ARTICLE 57 DATABASE
• NDC DIRECTORY
• EU NATIONAL REGISTRIES
PV WORKSHOP: EXPLORE PUBLICLY AVAILABLE DATA SOURCES IN DRUG SAFETY

27. PV WORKSHOP: EXPLORE PUBLICLY AVAILABLE DATA SOURCES IN DRUG SAFETY 27
https://www.ema.europa.eu/en/human-regulatory/post-authorisation/data-
medicines-iso-idmp-standards/public-data-article-57-database

28. PV WORKSHOP: EXPLORE PUBLICLY AVAILABLE DATA SOURCES IN DRUG SAFETY 28
https://www.ema.europa.eu/en/medicines/national-registers-authorised-medicines

29. PV WORKSHOP: EXPLORE PUBLICLY AVAILABLE DATA SOURCES IN DRUG SAFETY 29
https://www.accessdata.fda.gov/scripts/cder/ndc/index.cfm

30. PRODUCT
LABELING
• DAILYMED
• UK eMC
• UNION REGISTER OF MPs
• EU NATIONAL REGISTRIES
PV WORKSHOP: EXPLORE PUBLICLY AVAILABLE DATA SOURCES IN DRUG SAFETY

31. PV WORKSHOP: EXPLORE PUBLICLY AVAILABLE DATA SOURCES IN DRUG SAFETY 31
https://dailymed.nlm.nih.gov/dailymed/

32. PV WORKSHOP: EXPLORE PUBLICLY AVAILABLE DATA SOURCES IN DRUG SAFETY 32
https://www.medicines.org.uk/

33. PV WORKSHOP: EXPLORE PUBLICLY AVAILABLE DATA SOURCES IN DRUG SAFETY 33
https://ec.europa.eu/health/documents/community-register/html/index_en.htm

34. PV WORKSHOP: EXPLORE PUBLICLY AVAILABLE DATA SOURCES IN DRUG SAFETY 34
https://ec.europa.eu/health/documents/community-register/html/index_en.htm

35. PV WORKSHOP: EXPLORE PUBLICLY AVAILABLE DATA SOURCES IN DRUG SAFETY 35
https://ec.europa.eu/health/documents/community-register/html/index_en.htm

36. PV WORKSHOP: EXPLORE PUBLICLY AVAILABLE DATA SOURCES IN DRUG SAFETY 36
https://ec.europa.eu/health/documents/community-register/html/index_en.htm

37. PV WORKSHOP: EXPLORE PUBLICLY AVAILABLE DATA SOURCES IN DRUG SAFETY 37
https://www.ema.europa.eu/en/medicines/national-registers-authorised-medicines

38. PV WORKSHOP: EXPLORE PUBLICLY AVAILABLE DATA SOURCES IN DRUG SAFETY 38
https://www.sukl.eu/modules/medication/search.php?lang=2

39. ADDITIONAL
RESOURCES
• CPIC
• DRUGBANK
• PUBMED
PV WORKSHOP: EXPLORE PUBLICLY AVAILABLE DATA SOURCES IN DRUG SAFETY

40. PV WORKSHOP: EXPLORE PUBLICLY AVAILABLE DATA SOURCES IN DRUG SAFETY 40
https://cpicpgx.org/genes-drugs/

41. PV WORKSHOP: EXPLORE PUBLICLY AVAILABLE DATA SOURCES IN DRUG SAFETY 41
https://go.drugbank.com/drugs/DB00178

42. PV WORKSHOP: EXPLORE PUBLICLY AVAILABLE DATA SOURCES IN DRUG SAFETY 42
https://www.ncbi.nlm.nih.gov/pubmed

43. THANK YOU
Veronika Valdova
veronikav@arete-zoe.com
https://www.aretezoe.com /
PV WORKSHOP: EXPLORE PUBLICLY AVAILABLE
DATA SOURCES IN DRUG SAFETY
9/7/2022 43