PROTECT: Work Package 6 PROTECT: An Innovative Public-Private Partnership for New Methodologies in Pharmacovigilance and Pharmacoepidemiology

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1 PROTECT: Work Package 6 PROTECT: An Innovative Public-Private Partnership for New Methodologies in Pharmacovigilance and Pharmacoepidemiology ICPE presentation, Barcelona 2012

2 Acknowledgments The research leading to these results was conducted as part of the PROTECT consortium (Pharmacoepidemiological Research on Outcomes of Therapeutics by a European ConsorTium, which is a public-private partnership coordinated by the European Medicines Agency. The PROTECT project has received support from the Innovative Medicine Initiative Joint Undertaking ( under Grant Agreement n , resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/ ) and EFPIA companies in kind contribution. 2

3 WP6 Participants Institutions Names L.A. Sante Epidémiologie Evaluation Recherche Lucien Abenhaim (WP Co-leader), Lamiae Grimaldi (WP co-leader alternate) Sanofi-Aventis Research and Development European Medicines Agency Takeda Global Research and Development Centre (Europe) Ltd GlaxoSmithKline Research and Development LTD Universiteit Utrecht Aarhus University Laurent Auclert (WP Co-leader), Juhaeri Juhaeri (WP co-leader alternate), Nathalie Piton (WP Project Manager), Stéphanie Tcherny-Lessenot, Xavier Kurz Lesley Wise, Gemma Hogdson, David Irvine Jeanne Pimenta, John Logie Marieke De Bruin, Ines Teixidor Christiane Gasse 3

4 BACKGROUND ICPE presentation, August 2012

5 PROTECT Overall Goal To strengthen the monitoring of benefit-risk of medicines in Europe by developing innovative methods to enhance early detection and assessment of adverse drug reactions from different data sources (clinical trials, spontaneous reporting and observational studies) to enable the integration and presentation of data on benefits and risks These methods will be tested in real-life situations. 5

6 PROTECT Work Packages Data collection from consumers WP4 Clinical trials Observational studies Electronic health records Spontaneous ADR reports Benefits Risks Signal detection WP3 Signal evaluation WP2 Validation studies WP6 Benefit-risk integration and representation WP5 Training and education WP7 6

7 OBJECTIVES OF WP6 ICPE presentation, August 2012

8 Work Package 6 Specific objectives To validate and test the transferability and feasibility of methods developed in PROTECT (WP2 & 5) to other data sources and population groups To determine the added value of using other data sources as a supplement or alternative to those generally used for drug safety studies, in order to investigate specific aspects or issues. Started in September 2010 (Year 2) 8

9 MATERIAL & METHODS ICPE presentation, August 2012

10 WP2 Replicability research plan: Study Objectives, Rationale and Design Defined Study Objective Objective 1 Replication study in same database Scientific Question Is the study replicable when conducted independently in the same database? DB identification GPRD Danish Psychiatric, Somatic Hospital Discharge & Mortality Registers (DKMA) Study design Population case control Objective 2 Replication study in different database Do the results have external validity? LabRx/Premier MarketScan and Medicare E3N PGRx UPOD Nested case control Population case control Cohort Descriptive study 10

11 WP2 Replicability research plan: Study Objectives, Rationale and Design Defined Study Objective Objective 3 Negative control study Objective 4 Use of alternative outcome definition Scientific Question Does a study using the same protocol provide absence of evidence of an association where the exposure is such that the expected result is one of no association? What is the impact of different levels of certainty of the outcome (e.g. definite, probable, possible) on the effect estimate? DB identification LabRx/Premier GPRD PGRx GPRD PGRx DKMA Study design Nested case control (AMI) Selfcontrolledseries (hip fracture) Population case control Population case control 11

12 WP2 Replicability research plan: Study Objectives, Rationale and Design Defined Study Objective Scientific Question DB identification Study design Objective 5 Validation of outcome Objective 6 Assessment of confounders Has the outcome of interest been validated through clinical record review? What is the impact of validation on the effect estimate? Has confounding been adequately taken into consideration? Are there additional confounders that need to be assessed? How does better control for confounding impact the effect estimate? GPRD LabRx/Premier UPOD DKMA GPRD UPOD PGRx DKMA Population case control Nested case control Descriptive study Descriptive study Population case control 12

13 PROJECT STATUS ICPE presentation, August 2012

14 WP 6 Project status Inventory of data sources Review of a comprehensive list of data sources owned or managed by Consortium Partners, including EFPIA companies Participants in the Extended Audience (EAp): were contacted on behalf of the PROTECT programme to gauge interest and explore the availability and suitability of data sources Other centres not identified in the original EAp list, using ENCePP ressource or litterature. Definition of the validation approach Focus on the outcomes of Work Packages 2 and 5, to evaluate them in light of the inventory of data sources (e.g. type of data, covariate information, mode of collection, type of prescription data, etc) 14

15 WP6 Status in August 2012: WP2 validation protocols Antibiotics & ALI Status Start of analysis Labrx premier Final protocol Sanofi approval April 2012 UPOD Final protocol UPOD approval + review April 2012 GPRD Final protocol Wait for ISAC approval July 2012 Antibiotics and AMI LabrX premier Final protocol Complete End of march 2012 PGRx Final protocol Complete May 2012 Antidepressants/BZD & hip/femur fracture GPRD April 2012 Beta2 agonists & AMI PGRx Final protocol complete End of march 2012 Labrx premier Not yet released timelines to be provided August 2012 Calcium Channel Blocker & Cancer E3N Not yet released timelines to be provided August 2012 Marketscan/Medicaid Not yet released timelines to be provided April-May Antiepileptic & Suicidality Danish register (Validation) Final protocol complete, coding started March PGRx Final protocol complete May 2012 GPRD Not yet released delay, wait for WP2 April

16 Validation of WP5 WP5: methods in risk-benefit balance assessment Wave 1: comparative screening and benchmarking of methods using 4 case-studies (Tysabri, Acomplia, Ketek, Raptiva) Wave 2: Methodology refinement and inclusion of visualisation interface WP6: Wave 3 : Validation studies to test the robustness of the wave 2 methods eg in specific situations (no comparator, different perspectives...) 16

17 Validation of WP5 Planned priority activities: Testing the visualisation tools on group of patients Account for time dependency of long-term outcomes using more advanced modeling (Raptiva) Evaluating the impact of the variability between patients/group of patients perspective (Raptiva, Tysabri) on the benefit-riks balance. 17

18 WP6 Perspectives Wide and proactive dissemination of the results of WP6 should ultimately bring maximum benefits to patients; and the presence of patients associations as Partner and Member of the External Advisory Board will help achieve this objective. 18