Strategies for Site Placement

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Strategies for Site Placement

• Francois Le Barbenchon
• Client Relationship Director
• Covance Canada Inc.

2
Site Performance Is the Center of Clinical Trial
Value Chain
Clinical/ medical monitoring
Site Selection, Agreements
Site Performance enrollment, dosing,
evaluating, subject care provision data recording
Data Flow Management, refinement
Design
Packaging/ shipping of study materials
Analysis/ Reporting
Central Labs ECGs
3
Site Performance Economically Driven
Distorted Economics - Escalating Cost
of Production

• Increased study complexity/ procedures
• Global nursing shortage
• Nursing salary inflation 10
• Increased administrative burden
• Legal indemnification, privacy protection
• Ethical committee/ IRB reviews

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Informative Site Selection

• Past performance analysis
• Variability and predictability
• Key success indicators
• Epidemiology/ demographic review
• Population density
• Disease prevalence
• Competitive factors
• Healthcare environment
• Referral rates

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Traditional Site Placement Trilogy
Where to go?
How well will site perform?
Which sites to choose?
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Traditional Site Selectionand Enrollment
Number of sites
subjects per month
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Traditional Site Selectionand Enrollment
Number of sites
subjects per month
8
Traditional Site Selectionand Enrollment
Number of sites
subjects per month
9
Empirical Data Defines Preliminary Cross Center
Variability Presumption
10
Site Placement Trilogy Adaptive
Where to go?
How well will site perform?
Which sites to choose?
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Factors Affecting Country Site Selection
Tumor Epidemiology Demography
1
Current Competition
5
Treatment Practices
2
Care Systems Referral Patterns
Investigator Feedback
4
3
Past Site Performance Variability
12
Factors Affecting Country Site Selection
Tumor Epidemiology Demography
Current Competition
Treatment Practices
1
Care Systems Referral Patterns
Investigator Feedback
Past Site Performance Variability
13
Country and Site Selection

• When you can measure what you are speaking about
  and express it in numbers, you know something
  about it but when you cannot measure it, when
  you cannot express it in numbers, your knowledge
  is of the meager and unsatisfactory kind.
• - Lord Kelvin (British physicist)

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Demography Advanced Breast Cancer
Mortality Data WHO Mortality Database, 1998
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Demography (2) Advanced Breast Cancer
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Demography Rare Tumor
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Factors Affecting Country Site Selection
Tumor Epidemiology Demography
Treatment Practices
Current Competition
2
Care Systems Referral Patterns
Investigator Feedback
Past Site Performance Variability
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Factors Affecting Country Site Selection

• Treatment Practices
• Standards of care
• Availability of appropriate equipment
• Care Systems/Referral Patterns
• Varies by and within countries
• Centralized tertiary care
• Comprehensive referrals networks

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Factors Affecting Country Site Selection
Tumor Epidemiology Demography
Treatment Practices
Current Competition
Care Systems Referral Patterns
Investigator Feedback
3
Past Site Performance Variability
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Predicting Country Performance through
Variability
North America/ W. Europe
Central and E. Europe
South Asia and Latin America
Pts. Per Site Per Month
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Site Selection/ Activation
High Potential Variability
(e.g. left skew)
Sites evaluated
Sites activated
Sites kept open after
evaluation
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Predicting Country Performance through
Variability
North America / W. Europe
Central E. Europe
South Asia Latin America
Pts. Per Site Per Month
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Logistics Variability

• Trade-off country yield vs. set-up
• time and effort
• Regulatory submissions
• Drug importation
• Contract negotiations
• Investigator payment mechanisms
• Laboratory infrastructure

Typical Site Activation Lag
Pts. / site /month by country
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Enrollment USA vs. Eastern Europe
Number of subjects
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US only Optimum
Number of subjects
26
Balanced USPoland Optimum
Number of subjects
27
Predominantly Poland Optimum
Number of subjects
28
Effort vs. Yield
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Advantages for Expanded Selection

• Centralized health care - larger patient pools
• Highly motivated
• Treatment naive patients
• Investigators site staff
• Predictable consistent enrollment
• overall performance quality

30
Factors Affecting Country Site Selection
Tumor Epidemiology Demography
Treatment Practices
Current Competition
Care Systems Referral Patterns
Investigator Feedback
4
Past Site Performance Variability
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Factors Affecting Site Placement

• Investigator Feedback
• Relative enthusiasm scientific interest
• Feasibility of study design
• Preliminary patient recruitment projections

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Factors Affecting Country Site Selection
Tumor Epidemiology Demography
Treatment Practices
Current Competition
5
Care Systems Referral Patterns
Investigator Feedback
Past Site Performance Variability
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Factors Affecting Site Placement

• Current Competition
• Consider number of studies competing for limited
  number of patients
• Expand country selection non-traditional

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Emerging Global Distributions
Emergent
Past

• US/Canada 64 ? 30
• Western Europe 28 ? 20
• Central E. Europe 2 ? 25
• Latin America 5 ? 8
• South Asia lt1 ? 17

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Considerations of Expanded Site Selection

• Study conduct
• Start up process
• Finances ( savings?)
• Site GCP capabilities technology
• Study outcomes
• Limited insight on drug-drug interaction
• Regulatory agency acceptance
• Market acceptance
• Ongoing commitments supported by US Western
  Europe organizations

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In Summary

• Site selection adaptive, dynamic process
  systematically blending fact, opinion and
  speculation
• Evaluation applying statistical models predict
  study challenges and success with robustness
• Reiterative process enhances country and site
  selection
• Operational constraints gtgtgt scientific
  opportunities