Epidem iology as an enabler for Health Tenth Stakeholder forum on the Pharmacovigilance legislation 21 st September 2016 European Medicines Agency London Presenter: Dr Alison Cave Pharmacovigilance and Epidemiology Department, EMA An agency of the European Union
Disclaimer I am a full time employee of the European Medicines Agency 1
Epidem iology as an enabler for health In this talk: • What are the data needs across the life of a product? • Data subtypes • Power of data integration to drive innovation • Initiatives to build capacity • Key messages 2
W hat are the data needs across the life of a product? Developm ent Grow th phase Mature phase Post m arketing PROs Budget com m itm ents im pact Head to head Evidence required ( safety etc.) com parative Effects of Unm et need Adherence Usage effectiveness sw itching on / disease Difference Differentiation outcom es burden Utilization in sub- Effectiveness Patient Differentiate / prescribing populations recruitm ent w ith or vs. patterns protected Target galenics populations Understand standard of Now care and NHD Trial Past design Com petitor Launch Conditional New New form ulation/ goes generic pricing review com petition indication 3 3 3 Source: I MI GetReal
Medicines Developm ent • Population-based databases to characterize frequency and distribution of disease • Identify the population to be treated • Identify whether the disease effects high risk populations e.g. paediatrics • Identify unmet medical need • Identifying prevalence of disease (orphan medicines) • Current standard of care • Clinical trial recruitment • Real World clinical trials 4
Medicines Developm ent Salford Lung Study – Real W orld Trial Disease Epidem iology 5
At and Follow ing Authorisation • The EU Risk Management Plan is key to driving proactivity and promoting better targetted studies • Safety Specification – important known and potential risks + missing information • Pharmacovigilance Plan – routine PhV + additional studies • + / - Risk Minimisation Plan – including effectiveness measures • Future – Benefit risk management plans 6
At and Follow ing Authorisation 7
Post-authorisation safety • The entire evidence hierarchy • Detecting signals (new or changing safety issues) • Confirming signals e.g: observed vs. expected; impact / burden • Continuous safety monitoring in real world • Formal association studies in case control, cohort, etc • Assessing rare, delayed or chronic exposure adverse reactions • Effectiveness studies • Health outcome and HTA studies 8
Post-authorisation safety RALES: RCT 25mg spironolactone + usual treatment v placebo + usual treatment 9
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W hat are the available datasources? Epigenetics Transcriptomics Genomics Proteomics Functional RCTs Phenotypes Metabolomics Lipodomics In silico Social Pharmaco modelling Media genomics Structural biology Electronics Surveys health records RWE Digital Data Environmental Claims data Registries databases 11
Looking to the future: Data Linkage to Provide Additional I nsight Exam ple – System s pharm acology • Using data on drug’s target proteins and pathways to guide ADR detection Lorberbaum T, Nasir M, Keiser M, Vilar S, Hripsak G, Tatonetti N. Systems pharmacology augments drug safety surveillance. Clin Pharm & Ther 2015: 97(2): 151-158 12
Looking to the future: Data Linkage to Provide Additional I nsight 13
But There is lim ited access to RW E across the EU to support decision m aking Lack of a fram ew ork to facilitate rapid access to and analysis of relevant data Lack of sustained Fragm entation of sources funding m echanism s resources, lack of to secure access to interoperability and analysis of RW D Lack of cross border Governance and collaborations to privacy concerns leverage existing data and know ledge Underuse of Need to im plem ent technological advances m ethods to integrate to exploit innovative and analyse data sets heterogeneous data 14
W hat is the current European landscape? 15
Looking to the future Collaboration betw een stakeholders can support access to and analysis of an extensive range of m ulti-national real w orld data to optim ise m edicines developm ent and decision m aking 16
Patient Registry I nitiative 17
Benefits of planning and em bracing epidem iology Optim ising use of I m proved access m edicines through HTA to real w orld ongoing m onitoring data Ability to define the im pact of Reducing cost of regulatory/ HTA developm ent decisions Determ ining safety Enabling and efficacy in high innovation risk groups Faster identification Optim ise and assessm ent of indications safety issues Safe, New outcom e Effectiveness I m proved EMA Patient accelerated m easures data and HTA decision stratification for access to m aking benefit and risk m edicines 18
Key m essages • Pharmacoepidemiology and pharmacovigilance play critical roles in medicines regulation • Planning data collection and integrating knowledge starts in early development and is life-long • It is critical to embrace the evidence spectrum: different data and methods are best to address different questions • Use of real world evidence holds great promise to support drug development and in the fulfilment of unmet needs • Further integration of big datasets with real world data holds further promise for the future. 19
Thank you Registries w orkshop 2 8 th October Big Data W orkshop 1 4 -1 5 th Novem ber 20
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Post-authorisation safety Fluoroquinolones + Retinal Detachm ent Alves C, Penedones A, Mendes D, Marques F. A system atic review and m eta-analysis of the association betw een system fluoroquinolones and retinal detachm ent. Acta Ophthalm ol. 2 0 1 6 : 1 9 : e2 5 1 -e2 5 9 22
Patient Registries A key RW E platform for efficacy/ safety studies • Use of existing disease registries to identify natural history of the disease, current SoC, resource utilisation, adherence to treatment. • Potential to support single arm studies for rare diseases compared with outcomes inferred from disease registries • Open label salvage studies in patients with no remaining therapeutic options, with the purpose of obtaining an expansion of the indication; • Collection of efficacy and safety data from early access/ compassionate use programs to supplement RCTs in small populations; • Post-authorisation drug registries for effectiveness, long-term outcomes, drug utilisation, time to treatment failure and diagnosis confirmation 23
W hat is Available Data? Spontaneous reports Digital phenotypes Electronic Health Health I nsurance Records Data Biobanks Patient and physician Registries surveys Hospital data Genom es Term ed Real W orld Evidence w hich is defined as data that are collected outside the constraints of conventional random ised clinical trials . 24
Opportunities for unm et m edical need • Product development can fulfil unmet medical need. This is supported by robust planning of evidence generation where epidemiology is key: – Scientific advice for products in development – Risk management planning at authorisation and post-authorisation • Hypothesis generation – Signalling safety issues – Creating new directions for research • Supporting assumptions – Validation of surrogate outcomes – Validation of modelling and simulation – Extending clinical trial data • Longer term outcomes • Clinical pathways for HTA analyses • Outcome evaluation of regulatory interventions • Evaluation of safety concerns 25 • Evaluation of efficacy
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