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

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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

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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

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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

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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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