Regulatory Science: Are regulators leaders or follow ers? Health - PowerPoint PPT Presentation

Regulatory Science: Are regulators leaders or follow ers? Health data to support m edicines regulation: - identifying the opportunities - im proving the m ethods - building the capacity Presented by: Dr Peter Arlett Head, Pharm acovigilance and Risk Managem ent, European Medicines Agency An agency of the European Union

Health data to support medicines regulation In this talk: • Introduction • Case histories • Health data and pharmacoepidemiology through the product lifecycle • Resources and capacity building • Improving methods • New law: an opportunity for the pharmacoepidemiologist, statistician and programmer • Conclusions 2

Introduction Are medicines regulators leaders or followers? Both: • Followers - as science and scientific evidence should underpin medicines regulation • Leaders – as sometimes science needs a guide But you decide… .. 3

Introduction Old model vs. new vision Old model – regulator places obligations on industry and then assesses the results of industry studies New vision – regulatory decision-making is based on assessment of all available data including: • industry studies • academic studies • public authority studies (including by regulators) • use of data from real-life health outcomes 4

Introduction Enabling the vision requires: Science Law Resource 5

Introduction Health data and epidemiology: Resources that should support decision-making throughout the lifecycle of a medicine… . … . More later 6

Working Model for Excellence in Pharmacovigilance and Medicines Regulation Best Evidence Culture of Robust scientific Outcome scientific decision-making measures development and audit Tools for protecting public health Measurable excellence in terms of public health benefit Waller & Evans. Pharmacoepidemiology & Drug Safety 2003;12:17- 7 7

Introduction If we accept the evidence hierarchy we should embracing the entire spectrum of evidence… … … • Meta-analysis Lower degree of uncertainty • Clinical trial (e.g. causality, incidence) • Prospective cohort (with controls) • Case control study • Observational cohort (no controls) • Individual case report / case series 8

Introduction ‘high’ evidence may be of limited relevance to real world use. • Meta-analysis Lower degree of uncertainty • Clinical trial (e.g. causality, incidence) • Prospective cohort (with controls) • Case control study • Observational cohort (no controls) • Individual case report / case series 9

Introduction Brave new world – a call to arms for medicines regulators! Ensuring that health protection and promotion are effective, through study of effects of medicines in real life situations: • New pharmacovigilance legislation ‘EMA / MSs shall monitor the outcome of risk minimisation measures contained in risk management plans… ’ 10

Health data to support medicines regulation In this talk: • Introduction • Case histories • Health data and pharmacoepidemiology through the product lifecycle • Resources and capacity building • Improving methods • New law: an opportunity for the pharmacoepidemiologist, statistician and programmer • Conclusions 11

European Medicines Agency recommends suspension of Avandia, Avandamet and Avaglim Anti-diabetes medication to be taken off the market September 2010 EMA recommended the suspension of the marketing authorisations for the rosiglitazone-containing anti-diabetes medicines Avandia, Avandamet and Avaglim. These medicines will stop being available in Europe within the next few months. Patients who are currently taking these medicines should make an appointment with their doctor to discuss suitable alternative treatments. Patients are advised not to stop their treatment without speaking to their doctor. Doctors should stop prescribing rosiglitazone-containing medicines. Patients taking rosiglitazone-containing medicines should be reviewed in a timely manner 12 to amend their treatment.

Case histories: Avandia Avandia - PhV data to support decision making Aug 2 0 1 0 THIN database drug utilisation study conducted to investigate off-label use Aim: Measure the proportion of patients treated with rosiglitazone with concomitant cardiac disorder listed as contraindicated conditions in the SPC. Ref: ENCePP Studies databases 2 3 Sep 2 0 1 0 EMA Launch call for tender Aim: Evaluate the impact of regulatory decisions taken by the EMA regarding rosiglitazone on drug utilisation data (e.g., switch to other therapies, compliance with therapeutic indications) and new potential and identified risks (possible new acute ADRs in diabetic patients, and modifications on objective chemical parameters of disease). Contract signed. 13

Post-authorisation activities for A/ H1N1 vaccines during the influenza pandemic 14 14

• Strengthening Strengthening of the of the spontaneous spontaneous reporting reporting system system at at national national • and European European levels levels (EudraVigilance) (EudraVigilance) and • • Monthly Monthly simplified simplified Periodic Periodic Safety Safety Update Update Reports Reports • List of List of Adverse Adverse events events of special of special interests interests to to be be closely closely monitored monitored • • • Weekly Weekly collection collection of vaccine of vaccine exposure exposure data data through through survey survey of of Member States Member States • Pandemic Pandemic Pharmacovigilance Pharmacovigilance Rapid Rapid Response Response Expert Expert Group Group • ( PREG PREG) ) ( • Rapid response to concerns raised by Member States • Identification Identification of research of research projects projects relevant relevant for for A/ H1N1 vaccine A/ H1N1 vaccine • B/ R monitoring monitoring B/ R • 43 projects, 8 multicountry, 35 national (14 countries) • • Communication Communication: : weekly weekly pandemic pandemic pharmacovigilance updates pharmacovigilance updates • published on on EMA website EMA website from published from December 5, 2010 December 5, 2010 15 15

Spontaneous Spontaneous reports reports were were the the main main source source of data of data on on vaccine vaccine safety safety during during the the vaccination vaccination campaign campaign… … AR reports Exposure 16000 40000000 As compared to Number of vaccinated individuals 14000 35000000 other vaccines in Number of reports 12000 30000000 pre-pandemic period: 10000 25000000 8000 20000000 • less missing values in AR reports 6000 15000000 4000 10000000 • faster reporting of AR by health care 2000 5000000 professionals 0 0 Oct Nov Dec Jan Feb Mar Apr • faster reporting to EudraVigilance, 2009 2010 thereby facilitating signal detection 16 16

…but the pandemic highlighted avenues to improve benefit … but the pandemic highlighted avenues to improve benefit - - risk risk monitoring for all vaccines and drugs. monitoring for all vaccines and drugs. • Capacity Capacity building building for for post post - - authorisation authorisation studies studies • • Pregnancy Pregnancy outcomes outcomes: : network network for for sharing sharing information information, , • pooling of data or or combining combining results results – – EMA EMA funded funded study study pooling of data • Infrastructure Infrastructure for for observed observed- - to to- - expected expected analysis analysis • • Vaccination coverage/ exposure data – age and sex stratified • System for collection of EU-wide background incidence rates of events • European European vaccine vaccine health health outcome outcome resource resource • • Prompt evaluation of signals detected in EudraVigilance • Benefit-risk studies The EMA is working on it … ….with our partners ! .with our partners ! The EMA is working on it 17 17

Case histories: Progressive multifocal leucoencephalopathy (PML) Normal brain PML 18

Drug-related PML Research Agenda Aim s of the Project: Background: • PML is a severe disease. • Define researchable questions that will help • Reported as an ADR of regulatory agencies to protect public health some immunosuppressive drugs (few Mabs). • There is no effective • Communicate to stakeholders about the initiative. treatment. Tools for this: a paper in a medical/ scientific • Regulatory actions were journal and an international w orkshop . taken regarding this ADR (* Tysabri, Raptiva and Mabthera). • Stimulate partnerships and funding to fill • PML Research Agenda knowledge and research gaps in the area. developed since December 2009. • Initiative led by EMA, in • Ensure regular stocktaking of the project in the collaboration with FDA. knowledge and knowledge gaps in this field. • PML Research Agenda was adopted by the PhVWP and CHMP. 19

Use of epidem iological m odels to investigate efficacy of Bluetongue vaccination � 2 epidem iological m odels investigated the reduction of bluetongue ( BT) transm ission in cattle � Basic reproduction num ber R 0 prem ise: For vaccination to be effective it m ust reduce R 0 below one � R 0 in vaccinated population w as found below 1 � CVMP concluded that the dem onstrated reduction in BT viraem ia, although not com plete, w as sufficient for the vaccine to be effective at a population level