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Clinical Trials Conduct and Protocol Compliance in Asia
James M. Pusey MD, MBA
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New Zealander
Confidential Dr. James M. Pusey2
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“‟Pharma Valley”
Shanghai, Cincinnati & Philadelphia
Confidential Dr. James M. Pusey 3
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James Pusey Profile
o Serial Global & China CEO
o Eternal Optimist
o No Sales Pitch Today!!
Confidential Dr. James M. Pusey 4
® ®
®
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Globalization & Population Trends
Has Asia Pacific taken a higher share of pivotal Phase II & III
Global Clinical Trials?
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Registered 1572 Investigators*
6
Country 2009 2013 % Change
Argentina 364 329 -10%
Brazil 371 343 -8%
China 186 177 -5%
UK 875 964 +10%
Hungary 439 488 +11%
Japan 521 658 +26%
Ukraine 466 514 +10%
Circa 60% of 1572 Investigators in USA, & 20% in Europe (no
change)
Several researchers report declines in Asia/Pacific Phase II & III trials
“Globalization” of Clinical Trials has not yet matched population trends
* Tufts Center for the Study of Drug Development (CSDD)
Confidential Dr. James M. Pusey
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China Case Study
• Healthcare Priorities
• Conducting China Trials
• Improving Data Quality
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Healthcare Priorities
Where we are today, Clinical Trials and Disease Prevalence in China
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Healthcare Priorities
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• 30% of World’s smokers live in
China
• 60% of male Chinese doctors
smoke
Smoker Presence
Confidential Dr. James M. Pusey10
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Non-Small Cell Lung Cancer
o High smoking rates
o +ve EGFR rates higher vs ROW
o Only 50% of patients have routine EGFR
o Late presentations
o Many competing trials
o Clinics have administrative overload
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Country Prevalence # Pts million Pediatric thousands
USA 6.4% 17.0 5,000
Australia 6.5% 1.3 430
NZ 6.6% 0.3 85
China 2.1 – ??6.4% 27- ??83 9,000- ??27,000
Thailand 6.5% 4.2 1,400
S Korea 6.4% 3.1 1,000
Prevalence is converging due to ↑ spirometry & education; KOLs
& ICF management is key
Prevalence of Asthma
Confidential Dr. James M. Pusey12
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Causes of Death 1. Cancer2. Stroke3. Heart Attacks4. COPD5. Trauma & Poison
Ministry of Health Priorities 2007 -2022
1. Hypertension2. Diabetes 3. Heart disease 4. Malignant tumor5. Chronic respiratory disease
Government COPD Initiatives1. Risk factors
• Smoking cessation• Reduction of air pollution
2. Early Intervention with Rx3. Development of effective and
affordable medication
China Deaths & COPD Example
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Conducting China Trials
Protocol Compliance in China
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Hospital Admissions Area EU
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Hospital Admissions Area - China
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Resourcing Sites
o Trial funding
Access difficulties …. Institutions receive $$ not clinic
Considered income & not resource building
o Site staff availability & “dedication”
Dedicated research personnel rare
Motivation highly variable due to workload
Inexperience in clinical trials
High workload
• > 70 patients per clinician per session
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Site Number (2 Year study) 20 sites in Mainland China
FTE during start up & closeout 0.5 per site
FTE during recruitment 1.0 per site
Service Cost $108,108
Product Manager Cost $144,963
Pass through cost $4,425
Total Cost for 100% of sites $2,395,623
Total Cost for 50% of sites $1,270,293
Cost of Providing CRCs in China (from SMO)
o More cost effective than Study Nurses or Managers
o Managed independently of Trial Staff
o Can focus on larger site databases >1,000 pts
o Accelerate study start-up
o Increase recruitment (randomization) significantly
o Improved SD administration & data quality
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Protocol Compliance in China
o Protocol design
Healthcare priorities are different to West
Clinical care ≠ to US & Europe clinical care
Different screening & Rx approaches
o Healthcare culture at sites
Inter-disciplinary & Institutional care constraints
Resourcing at sites
Inexperience in clinical trials: rural > urban
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Large cities e.g. Beijing,
Shanghai, Guangzhou,
Wuhan, and Hong Kong
17 cities have the best
centers including HKG
Many Cities > 20 Million
Strategically place trial
centers to cover best sites
for recruitment and data
quality (i.e., urban areas)
Circa 2,500 CFDA certified
sites including HKG
Deciding on a Footprint in China: Urban Trial Centers
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Success Factors & Site Compliance
o Address clinical practice during protocol development (KOL Steering Committee) Take into account healthcare priorities
o Establish close CRA & independent CRC relationships at sites (ensuring protocol compliance) Very high site visit frequency Pro-active site issue identification & resolution Constant education of site staff (SDV, GCP, ICH
etc) Providing resource (CRCs from independent SMO)
• Improves patient recruitment
• Quality of source documentation
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Latest Approaches to Improve Data
Quality
Risk Based Monitoring improves
Quality, but does not directly lower
cost
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Risk
Protocol
• TA
• Safety profile
• Endpoints
• Population
• Vendors
Dynamic
• Turnover
• Recruitment
• SAE
• Deviations
• Site errors
• Queries
• Entry lag
• Misconduct
• Fraud
Site
• Experience
• CRA
seniority
• Location
• CRCs
• Focus
Risk Assessment and Plan Development
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Centralized Data Analytics
• Individual patient data
• Across patient data
• Across site & study data
Central Monitoring
Site Management
Associate (SMA)
Study Site
Project Team
• On-going Risk Assessment & Iterative Operational Strategy
On-Site Monitoring (CRA)
• SDV
• Patient & Site triggers & alerts24
Central Monitoring
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Regulatory &
Safety
• Regulatory Documents
• Status of IRB/EC
• Informed Consents
• CTA Initial/ Amendments
• Safety Events Reporting
Site Performance
• Training
• Motivation
• Activation
• Availability
• Retention
• Identification of new staff
• Metrics Analysis (data entry lag, query resolution)
Enrollment
• Rates
• Eligibility
• Randomize
• IMP Inventory, dispensation
Data
• EDC System
• Data entry review
• Scales completion
• Sample collection and shipment
• Adjudication Documents
Site Management Associate (SMA)Central Monitoring Activities
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Central Monitoring DashboardExample
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China is the largest patient event HealthCare
Market in the World
Case Study Summary
o Global systems & processes are increasing in China
o Investigator & site staff sophistication is increasing
But inadequate resources threaten data quality
o Technical & therapeutic expertise
Use of risk based monitoring techniques to spot sites at risk
o Administrative resources at site: CRCs & quality control staff
Improves SDV and supports sites at risk
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Takeaways for Asia Clinical Trials
o Protocol design
Healthcare priorities are different to West
Clinical care ≠ to US & Europe clinical care
Different screening & Rx approaches
o Healthcare culture at sites
Inter-disciplinary & institutional care constraints
Resourcing at sites
Inexperience in clinical trials: Rural > Urban
o Immense clinical trial markets remain
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谢谢Thank You