Topic: Reference-Scaled Approaches for Highly Variable Drugs

Why High Variability Undermines Conventional Average Bioequivalence

Why Total Variability Cannot Replace Reference Variability

Within-Subject Reference Variance in Replicate Data

Worked EMA Analysis With Expanded Limits

Worked FDA Analysis With the Linearized Criterion

Variance Components for Reference-Scaled Analysis

What Replicate Observations Identify

The FDA Linearized Reference-Scaled Criterion

The Point-Estimate Constraint in Scaled Bioequivalence

The Reference-Scaled Average Bioequivalence Estimand