Clinical trials basics

Four phases in clinical trials

Phase 1:

• Purpose: safety and dosage; refine phase 2 design
• 20-100 healthy volunteers or patients with disease condition
• Approximately 70% of drugs move to the next phase

Phase 2:

• Purpose: efficacy and side effects, refine research questions and design phase3.
• Up to severalhundredspatients
• ~33% move to the nextphase

Phase 3:

• Purpose: efficacy and adverse reactions
• 300~3000 patients
• ~50% move to the next phase

Phase 4:

• Purpose: efficacy and safety
• Phase 4 trials are carried out once the drug or device has been approved by FDA during the Post-Market SafetyMonitoring

Handling intercurrent events (ICE)

1. Treatment policy strategy: Use the observed data even it is after an ICE.
2. Composite strategy: Occurrence of ICEs is considered as non-responder/failure
3. While-on-treatment strategy: Only use the data while they are on treatment
4. Hypothetical strategy: Discard data after ICE, and estimate what would have happened in the absence of the ICE via appropriate model.
5. Principal stratum strategy: Find a subset of population where the ICE would (or would not) occur in both treatments

Types of missing data

1. Missing at Random (MAR): The probability of missingness does NOT depend on the unobserved outcomes of the variable being analyzed