Overview of the new process for Signal Detection and Managem ent - - PowerPoint PPT Presentation

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Overview of the new process for Signal Detection and Managem ent - - PowerPoint PPT Presentation

May 21, 2023 9 likes •294 views

Overview of the new process for Signal Detection and Managem ent PCW P and HCPW P joint m eeting 2 5 February 2 0 1 4 Presented by: Georgy Genov EMA/ Inspections & Human Medicines Pharmacovigilance Division An agency of the European

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An agency of the European Union

Overview of the new process for Signal Detection and Managem ent

PCW P and HCPW P joint m eeting 2 5 February 2 0 1 4

Presented by: Georgy Genov EMA/ Inspections & Human Medicines Pharmacovigilance Division

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EMA Human Scientific Committees' Working Party with PCWP & HCPWP 1

Agenda for presentation

  • EU Pharmacovigilance Legislation
  • Overview of Signal Management Process
  • Pharmacovigilance Risk Assessment Committee
  • Trends in requests for access to information/ documents
  • Transparency
  • Summary
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Main pillars of the new EU PV Legislation

EMA Human Scientific Committees' Working Party with PCWP & HCPWP 2

Proactive and proportionate risk m anagem ent Higher quality of safety data Strengthened transparency, com m unication and patient involvem ent Stronger link betw een safety assessm ents and regulatory action Clear tasks and responsibilities for all parties ( m arketing authorisation holders, com petent authorities, EMA) I m proved EU decision-m aking procedures ( harm onised decisions and efficient use of resources) Establishm ent of the Pharm acovigilance Risk Assessm ent Com m ittee

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New EU PV Legislation: four topic areas

EMA Human Scientific Committees' Working Party with PCWP & HCPWP 3

1 . Collection of key inform ation on m edicines:

  • Risk Management Plans (RMPs)
  • Periodic Safety Update Reports (PSURs)
  • Post-authorisation safety and efficacy studies

(PASS/ PAES)

  • Electronic submission of core medicine

information by pharmaceutical industry

  • Reporting by patients

2 . Better analysis and understanding of data and inform ation:

  • EudraVigilance and signal detection
  • Additional Monitoring
  • IT systems to support processing and

analysis of data 3 . Regulatory Action to safeguard public health:

  • Scientific committees and decision-making
  • Strengthening referral procedures

4 . Com m unication w ith stakeholders:

  • Online publishing of information
  • Coordination of safety messages
  • Public hearings
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Those directly involved in Pharm acovigilance

EMA Human Scientific Committees' Working Party with PCWP & HCPWP 4

Patients who use the medicines Healthcare professionals working with medicines Regulatory Authorities and Member States responsible for monitoring the medicines Pharmaceutical companies and companies importing and/ or distributing the medicines European Medicines Agency coordinating the EU's safety-monitoring and Pharmacovigilance for medicines

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Definition of a Signal

EMA Human Scientific Committees' Working Party with PCWP & HCPWP 5

“Information that arises from one or multiple sources (including observations and experiments), which suggest a new potentially causal association, or a new aspect

  • f

a know n association, between an intervention and an event or set of related events, either adverse or beneficial, that is judged to be of sufficient likelihood to justify verificatory action”

Report of Council for International Organisations of Medical Sciences WG VIII Practical Aspects of Signal Detection in Pharmacovigilance (CIOMS, Geneva 2010)

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Sources of inform ation

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Spontaneous ADR reporting systems Clinical trials data Scientific literature Pharmacoepidemiological studies Non clinical trial data e.g non- interventional studies

Pharm acovigilance

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EMA Human Scientific Committees' Working Party with PCWP & HCPWP 7

I CSR reporting pre- and post new PV legislation

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EMA Human Scientific Committees' Working Party with PCWP & HCPWP 8

Proportion of I CSR reporting pre- and post new PV legislation

Pre Leg After Leg

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EMA Human Scientific Committees' Working Party with PCWP & HCPWP 9

How do we review EudraVigilance data?

Statistical analysis Clinical review

  • f individual

case safety reports Validation m eeting

  • Clinical relevance: exposure, temporal

association, plausible mechanism, de/ re- challenge, severity of reaction and outcome; novelty of reaction

  • Previous awareness (SmPCs/ PL; PSURs)
  • Other relevant sources (literature, experimental

findings)

Signal Detection, Validation & Confirm ation

Signal Confirm ation

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EMA Human Scientific Committees' Working Party with PCWP & HCPWP 10

European Pharm acovigilance I ssues Tracking Tool ( EPI TT)

  • All validated signals are entered into EPITT by the authority

who detected and validated it

  • Validated signals undergo further analysis and are either:

CONFI RMED NOT CONFI RMED

Added to agenda for the Pharmacovigilance Risk Assessment Committee (PRAC) Justification to be provided as to why signal is not confirmed

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EMA Human Scientific Committees' Working Party with PCWP & HCPWP 11 Signal Detection Signal Validation Signal Confirm ation Signal Analysis and Prioritisation Signal Assessm ent Signal Recom m endation for action Exchange of inform ation and im plem entation

EMA MAHs MSs PRAC All stakeholders EMA MSs

Signal Managem ent Process

Exchange of inform ation

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EMA Human Scientific Committees' Working Party with PCWP & HCPWP 12

(# signals discussed at PRAC; 43 detected by EMA) (# of signal evaluated and discussed yearly at P-PH-SMA team level) (# of medical terms reviewed yearly by P-PH-SMA) (# of ICSRs received per year in EV – European database of suspected adverse drug reaction reports)

  • Update SmPC/ PIL
  • Referral
  • PASS
  • MA varied, suspended…

100 2,449 980,000 1,200,000 Adverse Reactions reported by: Patients, HCPs, Pharmaceutical companies

Trends in Adverse Event reports and signals in 2 0 1 3 ( Jan – Dec)

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EMA Human Scientific Committees' Working Party with PCWP & HCPWP 13

Source of all signals evaluated by EMA in 2 0 1 3 ( n= 2 4 4 9 )

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EMA Human Scientific Committees' Working Party with PCWP & HCPWP 14

Therapeutic area of all 2 0 1 3 PRAC signals ( n= 1 0 0 )

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EMA shall make public on the European medicines web-portal a list of active substances/ medicinal products and the authority (lead Member State, co-lead Member State or the Agency) responsible for their monitoring in EudraVigilance

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EMA Human Scientific Committees' Working Party with PCWP & HCPWP 16

Pharm acovigilance Risk Assessm ent Com m ittee ( PRAC)

Responsible for assessing and monitoring safety issues for human medicines

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Presentation title (to edit, click View > Header and Footer) 17

HCP and patient representatives

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 No need for further evaluation or action at this point in time  Request for additional data to be submitted:

  • Monitor any relevant emerging information on the signal as it becomes available
  • Address the signal in the following PSUR or submit an ad-hoc PSUR
  • Submit additional data (such as cumulative review)
  • Collect further information or perform additional analyses in EudraVigilance or other

data sources

  • Conduct a post-authorisation safety study

 Need for regulatory action:

  • The product information and/ or RMP should be updated through a variation
  • The Member States or the Commission, should initiate a referral procedure
  • Urgent safety restrictions should be imposed

 A Pharmacovigilance inspection should take place

EMA Human Scientific Committees' Working Party with PCWP & HCPWP 18

PRAC recom m endations for action

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EMA Human Scientific Committees' Working Party with PCWP & HCPWP 19

Outcom es of signals validated by EMA in 2 0 1 3 ( n= 4 3 )

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EMA Human Scientific Committees' Working Party with PCWP & HCPWP 20

Exam ple of signal analysis, prioritisation and assessm ent of recent signal discussed at PRAC

4.1.9. Sunitinib - SUTENT (CAP)

  • Signal of cholecystitis

Status: for initial discussion Regulatory details: PRAC Rapporteur: Carmela Macchiarulo (IT) 4 . Signals assessm ent and prioritisation 4 .1 . New signals detected from EU spontaneous reporting system s Recom m endation( s) :

Labelling change w ith Sections 4 .4 and 4 .8 of Sm PC updated

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EMA Human Scientific Committees' Working Party with PCWP & HCPWP 21

Som e exam ples of signals discussed at PRAC

Adalimumab - Missed dose due to m alfunction of the pre-filled pen device Leuprorelin - Medication errors (wrong technique in drug usage process) Clopidogrel - Eosinophilic pneum onia * Docetaxel - Serious/ fatal drug interactions * Bevacizumab - Anaphylactic shock Roxithromycin - Hearing disorders * Temozolomide - Hepatic failure * Ticagrelor - I nteraction with grapefruit juice * Cinacalcet - QT prolongation/ ventricular arrhythm ias * * Represents those resulting in labelling changes

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EMA Human Scientific Committees' Working Party with PCWP & HCPWP 22

Requests for EudraVigilance data analyses: Type

  • f requester ( 2 0 1 1 - 2 0 1 3 )
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Transparency

  • Publication of data on ADRs
  • Currently only for CAPs
  • Aim to extend to NAP
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wk1 wk2 wk3 wk4 wk1

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Highlights PRAC Highlights CHMP Agenda PRAC Minutes from previous PRAC PRAC CHMP Publication of PRAC recommendations

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Publication of PRAC agendas and m inutes

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EMA Human Scientific Committees' Working Party with PCWP & HCPWP 26

Publication of PRAC recom m endations – first publication October 2 0 1 3

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EMA Human Scientific Committees' Working Party with PCWP & HCPWP 27

Sum m ary

  • New process for signal management in line with the new EU

Pharmacovigilance legislation

  • Harmonised process for both CAPs and NAPs
  • Increased transparency through communication of information/ evidence

(EU database on ADR reports, publications of PRAC minutes, recommendations etc.)

  • Continued improvement in monitoring the safety of medicines, making it

more robust and transparent

  • Helping to ensure greater patient safety and improved public health

through better detection, assessment, understanding and prevention of adverse reactions.

Thank you!