Best practices and considerations for conduct of Late Phase Studies.

1. FOCUSED. TRUSTED. GLOBAL.
Planning and Executing a Late
Phase Trial: Setting Expectations
and Maximizing Outcomes
Alexander Artyomenko MD PhD
3rd Annual Outsourcing in Clinical Trials Europe
Zurich, 14 May 2013

2. FOCUSED. TRUSTED. GLOBAL.
o Key objectives and critical
differences of Late Phase research
o Early planning: maximizing
product potential
o Selecting a strategic partner:
benefits and considerations

3. FOCUSED. TRUSTED. GLOBAL.
Example definitions
Late Phase Studies
o Any study conducted on a marketed, fully approved
product
o Studies capturing clinical data and addressing real world
issues of safety, effectiveness, health outcomes,
reimbursement and risk management

4. FOCUSED. TRUSTED. GLOBAL.
Late Phase Research Objectives
o Long-term real-world safety data and risk
management
 FDA/EMA mandated
 Adverse claims
 New endpoints, health outcomes, effectiveness
o Maximize market penetration
 New comparators and dosage forms
 Label extension
o Provide access to yet unregistered drugs
 EAP/Named Patient/Compassionate use studies
o Health economics and Patient Reported Outcomes
 Reimbursement

5. FOCUSED. TRUSTED. GLOBAL.
Interventional/Non-interventional
Late Phase Study Types
o Randomized Clinical Trials
o Observational epidemiologic studies
o Expanded Access Programs
o Post-Authorization Safety/Efficacy studies
o Health Economics and Patient-Reported Outcomes
o Product and disease registries

6. FOCUSED. TRUSTED. GLOBAL.
Regulatory Framework
o GCP and GPP
o ISPE Guidelines for GPP
o CIOMS International Ethical Guidelines for Epidemiological
Studies
o Eudralex Volume 9A: Guidelines on Pharmacovigilance for
Medicinal Products for Human Use
o GRACE Principles
o Country-specific HEOR guidelines
o No harmonized legal framework across countries due to a
lower risk to subjects
o High emphasis on scientific credibility and data protection

7. FOCUSED. TRUSTED. GLOBAL.
Phase II/III vs. Late Phase
o Objectives
o Protocol design
o Study Population
o Sites outreach
o Data collection
o Regulatory documents and submissions
o Site agreements
o Monitoring

8. FOCUSED. TRUSTED. GLOBAL.
Late Phase Studies/Non-interventional
o Capture real-world data/standard of care
o Analyse data from a large number of patients
o Less per patient costs than in a clinical trial
o Increase disease and/or drug awareness
o Hypotheses generation and academic
research support
o Create and support stakeholder relationships

9. FOCUSED. TRUSTED. GLOBAL.
Challenges
Late Phase Studies/Non-interventional
o Attributing causality to outcomes
o Retrospective and prospective data
collection
o Diversity of regulation, standards of care
and cultures

10. Maximizing
Product Potential

11. FOCUSED. TRUSTED. GLOBAL.
Early Planning for Late Phase

12. FOCUSED. TRUSTED. GLOBAL.
Clinical to Commercial
o Know the Stakeholders
o Research unmet needs
o Understand diverse objectives
o Consider industry advances

13. FOCUSED. TRUSTED. GLOBAL.
Engaging Broader Audience
o Phase I/II Safety vs. Long-term Safety
 Outcomes
o Efficacy vs. Effectiveness
 Real-World Data
o Cost and Value
 Compliance
 Health Economics

14. FOCUSED. TRUSTED. GLOBAL.
Maximize Study Potential
o Focus on key objectives
 Impact on design, timelines, risks and costs
o Consider designs
 Follow-up extensions
 Health Economics and Patient-reported outcomes
 Genetic/biomarker testing
o Target geographies
 Market access
 KOL support
 Product launch

15. FOCUSED. TRUSTED. GLOBAL.
Starting Up
o Feasibility
o Start-up timelines
o Product approval status
o Submission requirements
o Site communication and training

16. FOCUSED. TRUSTED. GLOBAL.
Monitoring
o Risk assessment during
protocol development
o Focus on patient safety and
data quality
o Targeted on-site activities
o Timely data entry
o Remote site management
o Patient recruitment…and
retention!

17. FOCUSED. TRUSTED. GLOBAL.

18. FOCUSED. TRUSTED. GLOBAL.
Data Management
o Electronic Data Capture
o Electronic Health Records
o Direct Data Entry by patients
o Multiple data sources
o Large data volumes

19. FOCUSED. TRUSTED. GLOBAL.
Safety Reporting
o Increased demand for real-world safety data
o Focus on the events of special interest, SAEs
and SUSARs
o Data mining beyond trials

20. FOCUSED. TRUSTED. GLOBAL.
Selecting a Service Provider

21. FOCUSED. TRUSTED. GLOBAL.
Selecting a Strategic Research Partner
o Therapeutic expertise
o Local knowledge and global reach
o Broad scope of services
o Prior positive experience
o Operational expertise and efficiencies
o Market access expertise
o Greater flexibility

22. FOCUSED. TRUSTED. GLOBAL.
Continuous Collaboration
o Facilitates early planning
o Leverages previous learning
o Ensures process clarity
o Utilizes innovative technologies
o Streamlines project execution
o Maintains organizational focus
Saves time and money!

23. FOCUSED. TRUSTED. GLOBAL.
Late Phase Research
o Therapeutic, regulatory and operational
expertise is essential
o Diverse objectives require early planning
o Strategic partnership brings significant
efficiencies to all stakeholders

24. Thank you!
Dr Alexander Artyomenko MD PhD
a.artyomenko@medpace.com
www.medpace.com