An agency of the European Union
Presented by: Cosimo Zaccaria Signal Management Pharmacovigilance Department
EMA Statistical Signal Detection in practice PROTECT symposium 18 February 2015
Presentation contents
• Signal management (EMA perspective)
• Legal requirements
• eRMR
• Priorities
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Presented by: Cosimo Zaccaria – PROTECT symposium
The EU signal management process at a
glance…
Detection Validation Confirmation Analysis &
prioritisation Assessment Recommendation for action
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Detection
30 days 30/60 days
Signal Manag. Legal Requir eRMR Priorities
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Statistical approach:
SDRs/PRR
Clinical approach:
• Temporal association
• Biological plausibility
• De-Rechallenge
Signal Detection
PRAC
Signal Management
Signal Validation
Causality assess: •Very likely/certain •probable/possible •unlikely •Unrelated •Unassessable…
Signal Manag. Legal Requir eRMR Priorities
Sources of information
Clinical trials
Scientific literature
Spontaneous ADR reporting
systems Non-interventional
studies
PE studies
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91%
5%3%
1%
EV Literature Other RAs Other
Signal Manag. Legal Requir eRMR Priorities
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LEGAL BACKGROUND
Signal Manag. Legal Requir eRMR Priorities
Why an electronic tool for Signal detection?
• More products authorised
~4500 ICSRs per day
• Several Sources of information (SmPC, RMP, PSUR, EPITT etc.)
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~800 CAPs
Signal Manag. Legal Requir eRMR Priorities
Monitoring
• MedDra Built-in dictionary
• Historical of ADRs
• Reminder for SDR
Tracking
• Signal Status
• Comment field
eRMR = electronic Reaction Report
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Activ
e s
ub
sta
nces
MedDRA Structure
SO
Cs
HLG
Ts
HLTs
SM
Qs (
narro
w)
PTs
eRMR structure Use of agreed terminology
Signal Manag. Legal Requir eRMR Priorities
eRMR structure
EV data and different categories
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EV
Cases
Fata
l cases
EV
Paedia
tric c
ases
Geria
tric c
ases
EEA c
ases
HCP c
ases
Serio
us c
ases
Sponta
neous c
ases
PR
R(-)
/P
RR
Lite
ratu
re c
ases
Observ
atio
nal s
tudie
s
CT c
ases
Med. E
rr./Abuse
Electronic reaction monitoring report Confidential - © EMA 2014
Signal Manag. Legal Requir eRMR Priorities
DME
IME/SDR
Fatal
Literature
Criteria for prioritisation in Screening
the eRMR:
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Use of statistical and clinical principles
Pr1 = Designated Medical Events
Pr2 = Important Medical Events with a Signal Of Disproportionate Reporting
Pr3 = Important and non Important Medical Events with a Fatal outcome or Paediatric Cases
Signal Manag. Legal Requir eRMR Priorities
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Operational columns
Med
DR
A P
T c
od
e
IM
E/
DM
E
Prio
rity
Ch
an
ges
SD
R (
n)
Sig
nal S
tatu
s
Co
mm
en
ts
eRMR – Operational Functionalities
Signal Manag. Legal Requir eRMR Priorities
Monitoring Tracking
Assigning the Signal Status
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• Listed
• Linked
• Check
• Closed
• Monitor
• PSUR
• RMP
• Disease
SmPC 4.8/4.4
Synonymous or more severe medical concept
Review cases
Cases reviewed
PT under monitoring
Rapporteur’s conclusion
Potential/Identified Risk
Indication/Symptoms
Signal Status
Signal Manag. Legal Requir eRMR Priorities
Message to take home
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4 - Assess EV data
3 - Differentiate ICSRs
2 - Prioritise ICSRs
1 - Read EV data
eRMR
priority column (DME, SDR, fatal etc.)
assigning signal status
check previous awareness (PSUR, RMP), review cases, review literature
e-RMR GOAL
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