Appendix w — Pragmatic vs Explanatory Trials: A Quantitative Analysis

Pragmatic vs Explanatory Trials: A Quantitative Analysis

What are Pragmatic Trials?

Pragmatic trials are designed to test interventions in real-world conditions, focusing on:

• Real-world effectiveness rather than controlled efficacy
• Broad patient populations with minimal exclusion criteria
• Routine clinical settings rather than specialized research environments
• Practical outcomes that matter to patients and clinicians
• Rapid implementation of findings into clinical practice

Key Differences at a Glance

Metric	Pragmatic Trials (e.g., RECOVERY)	Traditional Explanatory Trials
Cost per Trial	Lower due to existing infrastructure	$48-225 million
Time to Results	Weeks to months	5-7 years average
Participants	Large (e.g., 47,000+ in RECOVERY)	Typically 500-3000
Implementation Speed	Hours to days	Months to years
Patient Population	Diverse, real-world	Highly selected
Setting	Routine clinical practice	Specialized research centers
Generalizability	High	Limited

Cost Analysis

Traditional Explanatory Trials

• Average phase costs (source):
  • Phase 1: $4 million
  • Phase 2: $13 million
  • Phase 3: $20 million
• Per-patient costs vary by therapeutic area:
  • Blood disorders: $200,000-422,000
  • Average across areas: $41,117

Pragmatic Trials (RECOVERY Example)

• Cost savings of 68-78% compared to traditional trials
• Utilized existing healthcare infrastructure
• Minimal additional staff costs
• Reduced monitoring costs
• Simple data collection systems

Speed and Efficiency

RECOVERY Trial Metrics

• 9 days: Concept to first patient enrollment
• 10 weeks: First life-saving treatment identified
• 3 hours: Results to policy implementation
• 47,000+ participants across 6 countries
• 200+ hospital sites
• 10 major results obtained
• 4 effective COVID-19 treatments identified

Traditional Trial Metrics

• Average time from phase 1 to approval: 7.2 years
• 80% of trials fail to meet enrollment timelines
• Up to 50% of research sites enroll one or no patients

Clinical Impact

RECOVERY Trial

• Dexamethasone findings:
  • 35% reduction in mortality for ventilated patients
  • Estimated 1 million lives saved globally
• Implementation within hours of results
• Real-world effectiveness immediately apparent

Traditional Trials

• 14% success rate from phase 1 to approval
• Average 7 years from discovery to clinical practice
• Limited real-world applicability due to strict inclusion criteria

Advantages of Pragmatic Trials

1. Better Generalizability

   • Results apply to broader patient populations
   • Findings directly relevant to routine clinical practice
   • Higher external validity

2. Resource Efficiency

   • Uses existing healthcare infrastructure
   • Lower per-patient costs
   • Faster recruitment and completion

3. Implementation Speed

   • Rapid translation to clinical practice
   • Immediate real-world validation
   • Reduced lag between evidence and practice

4. Statistical Power

   • Larger sample sizes possible
   • More diverse patient populations
   • Better representation of real-world outcomes