clinical trials conduct and protocol compliance in asia
TRANSCRIPT
Clinical Trials Conduct and Protocol Compliance in Asia
James M. Pusey MD, MBA
New Zealander
Confidential Dr. James M. Pusey2
“‟Pharma Valley”
Shanghai, Cincinnati & Philadelphia
Confidential Dr. James M. Pusey 3
James Pusey Profile
o Serial Global & China CEO
o Eternal Optimist
o No Sales Pitch Today!!
Confidential Dr. James M. Pusey 4
® ®
®
Globalization & Population Trends
Has Asia Pacific taken a higher share of pivotal Phase II & III
Global Clinical Trials?
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
China Case Study
• Healthcare Priorities
• Conducting China Trials
• Improving Data Quality
Healthcare Priorities
Where we are today, Clinical Trials and Disease Prevalence in China
Healthcare Priorities
Confidential Dr. James M. Pusey9
• 30% of World’s smokers live in
China
• 60% of male Chinese doctors
smoke
Smoker Presence
Confidential Dr. James M. Pusey10
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
Confidential Dr. James M. Pusey 11
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
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
Confidential Dr. James M. Pusey13
Conducting China Trials
Protocol Compliance in China
Hospital Admissions Area EU
Confidential Dr. James M. Pusey 15
Hospital Admissions Area - China
Confidential Dr. James M. Pusey16
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
Confidential Dr. James M. Pusey17
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
Confidential Dr. James M. Pusey18
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
Confidential Dr. James M. Pusey19
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
Confidential Dr. James M. Pusey20
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
Confidential Dr. James M. Pusey21
Latest Approaches to Improve Data
Quality
Risk Based Monitoring improves
Quality, but does not directly lower
cost
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
Confidential Dr. James M. Pusey23
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
Confidential Dr. James M. Pusey24
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
Confidential Dr. James M. Pusey 25
Central Monitoring DashboardExample
Confidential Dr. James M. Pusey26
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
Confidential Dr. James M. Pusey27
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
Confidential Dr. James M. Pusey28
谢谢Thank You