Three years of the Pharmacovigilance Risk Assessment Committee Where are we now?

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1 Three years of the Pharmacovigilance Risk Assessment Committee Where are we now? June M Raine Chair, PRAC MEB College Day Workshop 3 rd June 2015 An agency of the European Union

2 The Pharmacovigilance Risk Assessment Committee is the committee at the European medicines Agency that is responsible for assessing and monitoring safety issues for human medicines

3 Outline of presentation Why is there the need for a pharmacovigilance committee in EU? What has PRAC delivered via the new legislative public health tools in its first three years? Where next? What is still to be done to fully realise the potential of the new legislation to achieve excellence in public health protection? Brussels, 19 July 2012

4 Why need for pharmacovigilance? Duijnhoven et al PLoS March 2013 Patients studied prior to approval of new medicine For 200 new standard medicines between 2000 and 2010, median total no patients= 1708, for orphan drugs = 438 patients studied For 84 medicines for chronic use 79.8% met guidelines for 12 months (at least 100 participants)

5 Pharmacovigilance cycle Monitor risk minimisation effectiveness Signal detection in real world use Risk minimisation, communication, maintain favourable benefit risk Better characterised risks of medicine Ongoing evaluation of benefit risk

6 New EU legislation in 2012 Clear legal framework for drug safety monitoring Patient reporting of adverse drug reactions Timely review of new safety issues Risk management plans for all new medicines Post-authorisation studies - regulatory oversight Greater transparency

7 PRAC s mandate All aspects of the risk management of the use of medicinal products including the detection, assessment, minimisation and communication relating to the risk of adverse reactions, having due regard to the therapeutic effect of the medicinal product, the design and evaluation of post-authorisation safety studies and pharmacovigilance audit

8 PRAC s main goals Proactively investigating drug safety - continuous signal detection, filling knowledge gaps via post-authorisation studies Responding to safety and benefit risk issues risk-proportionate decisions to rigorous timescales, effectiveness of risk minimisation Driving forward the new era in transparency - real time access to information on PRAC activities Increasing involvement of stakeholders - health professionals, patients and public

9 European Commission experts Pharmacoepidemiology Marieke de Bruin Stephen Evans Pharmacovigilance Hervé Le Louët Signal detection Lennart Waldenlind Biologicals and vaccines Brigitte Keller Stanislawski Risk Communication Jane Ahlqvist Rastad

10 HCP and patient representatives

11 Over 600 risk management plans Over 1000 PSURs 32 meetings 33 safety referrals Over 150 protocol reviews Over 300 signals

12 PRAC monthly activities

13 Patient ADR reporting

14 Strengthened ADR reporting Pre Legislation 02/07/11-01/07/12 After Legislation 02/07/12-01/07/13 After Legislation 02/07/13-01/07/14 * Number of ICSRs received in EudraVigilance before de-duplication

15 Additional monitoring list Monthly review by PRAC of proposed additions to the list of new medicines for additional monitoring

16 Strengthened ADR reporting EudraVigilance database provides common signal detection tools for all member states >54% serious safety issues detected earlier if EV used in addition to other resources Drug Safety 33(6)

17 Signal of medication error

18 Signal management review PRAC s Signal Management Review Team meets monthly under Dr Sabine Straus leadership to work on: - Tools and processes - Methodological guidance - Signal detection methods Implementing Regulation requires that the Pharmacovigilance Risk Assessment Committee shall regularly review the methodology(ies) used and publish recommendations, as appropriate

19 Signals & drug lifecycle Pacurariu et al Drug Safety 15 Nov 2014

20 PRAC safety referrals 19

21 Referrals started and finalised

22 Rapporteurs for referrals 6 (Co) Rapporteurship per Member State *3 procedures have multiple co-rapporteurs (SABA-HU, BE, CS, IT; RAS - UK, IT, SV, DE, NL, PT, SK, IE, ES, Ambroxol/Bromhexine PT, AT, BE) Rapp Co-Rapp

23 Combined hormonal contraceptives VTE Review of all available data on known risk of VTE associated with combined hormonal contraceptives Full information on risk of VTE to support decisions by women and their healthcare professionals HCPs and women reminded to be watchful for symptoms and signs

24 Valproate & developmental disorders Teratogenicity known since time of market authorisation Assessment of latest evidence on risk of developmental disorder in infants following pregnancy exposure of mother Strengthened warnings in product information to support decisions by women Patient representatives involved in advising on risk minimisation measures

25 Ivabradine & cardiovascular risk Small but significant increase of cardiovascular death, MI and heart failure in SIGNIFY study in ivabradine arm Risk Minimisation Measures to include initiation heart rate, dose, monitoring for atrial fibrillation & stopping within 3 months if no benefit Drug utilisation study to monitor RMM effectiveness

26 Proactive pharmacovigilance Shift from reactive vigilance to proactive investigation of drug safety To fill in gaps in knowledge, Risk Management Plans and PASS protocols are PRAC s major priority PRAC experts in pharmacoepidemiology provide specialist contributions on design and methodology Better evidence on which to base regulatory decisions

27 Types of PASS reviewed by PRAC Registries (prospective cohorts) - Eg assess safety profile, health outcomes in clinical use, consider existing infrastructure consider comparator Database studies - Eg risk characterisation, investigation of targeted AEs Drug utilisation studies Eg to assess effectiveness of risk minimisation measures or help plan PAS Special populations - Pregnancy registries, paediatrics, elderly Medication errors - Human factors studies

28 Strontium ranelate PASS imposed after PSUR raised concerns about cardiovascular safety and further in-depth evaluation of benefit risks under Article 20 referral MAH`s proposal: descriptive study using retrospective healthcare databases Main methodological issues related to ability of proposed algorithms to extract reliable information on variables and endpoints from proposed data sources

29 Isotretinoin pregnancy prevention

30 Driving forward transparency

31 PRAC s work moving forward Information technology Innovative science Innovative methodologies Involvement of patients Impact evaluation

32 Innovative science Using pharmacogenomics to define populations at risk of ADRs

33 Innovative methodologies Incorporating new methodologies in signal detection, benefit risk evaluation and risk communication based on research and best evidence

34 Impact evaluation

35 Information technology Innovative Medicines Initiative WEB-RADR project Development of a mobile app for ADR reporting Provision of information to users Evaluation of using social media data to identify ADRs

36 Involving patients & public Interaction with patient and health professional organisations so far during formal reviews Input to setting goals for RMMs, reviewing thresholds and decisions on effectiveness of RMMs Opportunity of public hearings to be introduced later in 2015

37 Reflections on 3 years of PRAC Real-time signal detection and signal prioritisation every month at PRAC Rapid action to manage risk with binding outcomes Benefit risk monitoring throughout a medicine s life cycle in clinical use New era of transparency and openness in place Current initiatives based on best evidence, effectiveness evaluation, and stakeholder engagement PRAC s goal is measurable impact of what we do: demonstrable excellence in public health protection

38 Hartelijk dank!