RWE – What are the Opportunities across the product life cycle?

• Medicines Development
  • 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

• At and Following 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

• 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

Data – Which data and when?

• Registry roles
  • Describe natural history of a disease
  • Determine clinical effectiveness of healthcare products /services
  • Measure / monitor safety / harm
  • Measure quality of care
  • All may inform research and medicines approval & monitoring
• Current Challenges with Registries
  • Majority of imposed registries are for orphan products and/or products approved under exceptional circumstances and imposed for safety reasons.
  • Registries face challenges around:
    • Recruitment: lack of physician engagement due to administrative burdens, patient consent, low product usage and competing registries
    • Data Quality: compliance, study design, representativeness of registry population
    • Companies predominantly choose to establish individual product registries rather than utilise existing disease registries.
  • This often results in duplication of effort, a likely slower resolution of the initial concern and multiple, relatively inflexible registries with limited application in the future
  • Lack of sustainability of current disease registries
• Summary of the challenges
  • Financial stability and sustainability of the registry
  • Clarity of data ownership including linked data
  • Data access
  • Mismatch between the required standards for industry and registry
  • Regulatory guidance to increase understanding among registries around MAH obligations and required data standards
• Summary of the key success factors
  • Need for guidance on standardised data collection and coding
  • Recoding of medicines information, response to treatment, changes in disease state etc
  • Flexibility and capacity to accommodate methodological differences across multiple studies
  • Defined contact points to facilitate communication
  • Appropriate approvals/established governance to allow data access and sharing
  • Feedback to healthcare professionals and participating families
• Possible solutions……..to facilitate the consistent use of registry data for post-marketing evaluation of medicines
  • Sustainable funding
  • Need to establish common infrastructure/platform, consistent ontologies and common data elements
  • European inter-operability framework principles
  • Need for good governance and data management
  • Need for bioinformatics and statistical skills
  • Sharing of collaborative experiences

EMA Strategy on Registries

• Status of Pilot Phase
  • Creation of a taskforce composed of representatives of EMA Scientific committees and working parties, the European Commission, experts from national competent authorities and EMA staff
  • Currently >12 expressions of interest received (pharmaceutical companies and registry managers)
  • Suitability of candidates discussed within the Cross-Committee Task Force
  • Four case studies have been identified which together represent the need to
    • Establish a new registry
    • Use of an existing disease registry
    • Switching from product registry to disease registry
• Learnings to date
  • Early dialogue between the MAHs and registry owners
  • Clear lines of communication between the stakeholders
  • Definition of a clear protocol at an early stage in order that the registry can establish the feasibility of any collaboration
  • Clear governance models to address issues such as consent and data ownership
  • Clear information from the registry on the model of collaboration, structure, governance, data collection mechanisms and points of contact.

Conclusions

• Planning the collection of data and information is a critical success factor for product development throughout the lifecycle.
• Planning for the post-authorisation phase and for real-world evidence collection is as important as pre-authorisation and clinical trials.
• Scientific Advice provides a vehicle to bring stakeholders together and ensure expert input on planning data collection
• The EMA initiative on patient registries was initiated based on the observation that 75% of all registries requested by regulators to industry were product registries. While we see increased interest from companies to collaborate with patient registries, registries coordinators will also need to raise to the challenge to establish mechanisms to facilitate such collaborations.
• Together with the EU regulatory network, the EMA is committed to play a role in this critical development. The workshop demonstrated that this involvement will include supporting initiatives to deliver maximum utility of registries for the benefit of all patients through better governance principles, better access to high quality data, facilitation of collaborations and mechanisms for sustainable funding.
• This will require a concerted effort from all stakeholders

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