Epidem iology as an enabler for Health Tenth Stakeholder forum on - - PowerPoint PPT Presentation

An agency of the European Union

Epidem iology as an enabler for Health

Tenth Stakeholder forum on the Pharmacovigilance legislation 21st September 2016 European Medicines Agency London

Presenter: Dr Alison Cave Pharmacovigilance and Epidemiology Department, EMA

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Disclaimer

I am a full time employee of the European Medicines Agency

Epidem iology as an enabler for health

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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

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W hat are the data needs across the life of a product?

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Past Now Evidence required

Developm ent

Grow th phase Mature phase

Launch Understand standard of care and NHD Trial design Patient recruitm ent Unm et need / disease burden PROs Budget im pact Post m arketing com m itm ents ( safety etc.) Conditional pricing review Utilization / prescribing patterns Adherence New com petition New form ulation/ indication Com petitor goes generic Effectiveness Differentiation in sub- populations Head to head com parative effectiveness Target populations Usage Difference Effects of sw itching on

• utcom es

Differentiate w ith or vs. protected galenics

Source: I MI GetReal

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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

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Salford Lung Study – Real W orld Trial

Disease Epidem iology Medicines Developm ent

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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

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At and Follow ing Authorisation

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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

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RALES: RCT 25mg spironolactone + usual treatment v placebo + usual treatment

Post-authorisation safety

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W hat are the available datasources?

11 Environmental data Electronics health records Digital Data Epigenetics Structural biology Pharmaco genomics Registries Genomics Social Media In silico modelling Transcriptomics Proteomics RCTs Surveys Claims databases

RWE

Functional Phenotypes Metabolomics Lipodomics

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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

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Looking to the future: Data Linkage to Provide Additional I nsight

Lack of a fram ew ork to facilitate rapid access to and analysis of relevant data sources

There is lim ited access to RW E across the EU to support decision m aking

But

Lack of cross border collaborations to leverage existing data and know ledge Underuse of technological advances to exploit innovative data sets Need to im plem ent m ethods to integrate and analyse heterogeneous data Lack of sustained funding m echanism s to secure access to and analysis of RW D Governance and privacy concerns Fragm entation of resources, lack of interoperability

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W hat is the current European landscape?

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

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Patient Registry I nitiative

Benefits of planning and em bracing epidem iology

I m proved EMA and HTA decision m aking Patient stratification for benefit and risk Faster identification and assessm ent of safety issues I m proved access to real w orld data Effectiveness data Safe, accelerated access to m edicines New outcom e m easures Ability to define the im pact of regulatory/ HTA decisions Determ ining safety and efficacy in high risk groups

HTA

Optim ise indications Optim ising use of m edicines through

• ngoing m onitoring

Enabling innovation Reducing cost of developm ent

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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.

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Big Data W orkshop 1 4 -1 5 th Novem ber Registries w orkshop 2 8 th October

Thank you

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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

Post-authorisation safety

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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

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W hat is Available Data?

Term ed Real W orld Evidence w hich is defined as data that are collected

• utside the constraints of conventional random ised clinical trials.

Biobanks Digital phenotypes Genom es Electronic Health Records Registries Patient and physician surveys Hospital data Health I nsurance Data Spontaneous reports

Opportunities for unm et m edical need

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• Product development can fulfil unmet medical need. This is supported by robust planning
• f 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
• Evaluation of efficacy