Selection of Delta to Determine Efficacy in Noninferiority Trials of Antibacterial Drugs

2/25/02


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Table of Contents

Selection of Delta to Determine Efficacy in Noninferiority Trials of Antibacterial Drugs

PhRMA’s Antimicrobial Working Group

Antimicrobial Working Group

Outline of Today’s Remarks

PhRMA’s Key Messages

Clinical Trials with Anti-infective Drugs: Unique Considerations

FDA’s Approach Throughout the 1990s

“Step-Function” Delta and Clinical/Statistical Issues

Merits of Existing Step-Function Approach -“One size” does not fit all

Many Effective Antibacterial Products Have Been Developed Since the Early 1990s Using This Approach

Implications of A Smaller Delta

Actual Example : Pediatric Meningitis Trial Investigational Drug vs. Active Control

What is Gained by Reducing Delta ?

Potential Disadvantages of a Fixed Margin Approach Regardless of the Response Rate of the Comparator

Unintended Consequences of Smaller Delta

Investigational Antibacterial Drugs are Already Disadvantaged in an R&D Portfolio

Suggested Principles for Selection of Delta

Specific Options for Delta: Options for Various Development Programs

Specific Options for Delta: Options for Various Development Programs

Example of “General Equivalence” Approach: Nosocomial Pneumonia (in 1992 FDA Points to Consider)

Study Design Options: Non-Life Threatening Infections with Spontaneous Cure (eg, acute bronchitis, AECB, acute otitis media)

Summary

Author: dmc3317