Table of Contents
Statistical Issues in Specification of D
Outline
The Problem
What is D?
Non-inferiority Trials
Estimation of treatment effect & Confidence Interval
Example 1: Non-inferiority demonstrated
Example 2: Non-inferiority not demonstrated
Goals of non-inferiority trials:
History of D Selection
PPT Slide
Concerns about 1992 PTC approach
Concern of Potential “Bio-Creep”
July 1998 AC Meeting
July 1998 AC Meeting: Proposal
Committee for Proprietary Medicinal Products (CPMP)
Transition
Now what?
Road Map
To demonstrate efficacy:
ICH-E10 says
Translation
Principles from E10
Possible Choices for D
General approach to D
Estimation of benefit of AC over placebo (D1)
Estimating benefit of AC (D1): Be Conservative
Estimating benefit of AC(D1 ): What is best information?
Estimating benefit of AC(D1): Placebo Control Trial Data
Estimating D1: Bottom Line
D: Step 2
Selection of clinically acceptable loss (D2)
Selection of clinically acceptable loss (D2)
Clinically Acceptable Loss (D2): Consider consequence to patients
Clinically Acceptable Loss (D2): Consider Clinical Trial Realities
Selection of clinically acceptable loss (D2)
General Approach: D for each indication
Consequence to Sample Size
BIGGEST CHALLENGES
Early Escape: Ethical?
Other Superiority Designs
Selection of D: BIG PICURE
Choice of D impacts patients
Take Home Message
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