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IBE Criteria Flaw

IBE Criteria Flaw. Development of the Criterion E(T-R) 2 / E(R-R ) 2 Ratio of the expected squared difference between T and R administered to the same individual and the expected squared difference of two administrations of the Reference to the same individual. IBE Criteria Flaw.

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IBE Criteria Flaw

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  1. IBE Criteria Flaw Development of the Criterion E(T-R)2 / E(R-R)2 Ratio of the expected squared difference between T and R administered to the same individual and the expected squared difference of two administrations of the Reference to the same individual.

  2. IBE Criteria Flaw Development of the Criterion Aggregate Criterion • Difference in Means • Difference in Variances • Subject-by-Formulation Term • Scaled by Reference Variance • Added without justification: T/R within 0.80-1.25

  3. IBE Criteria Flaw Development of the Criterion Restrictions on Individual Terms • Not supported by the mathematics • Not supported by clinical/scientific considerations • Has undesirable consequences

  4. IBE Criteria Flaw Immediate-release, Coated Oral Tablet FDA approval early 1980s Two-way 10-subject crossover study Single one-tablet fasted dose Generic vs. Brand

  5. IBE Criteria Flaw

  6. IBE Criteria Flaw

  7. IBE Criteria Flaw

  8. IBE Criteria Flaw

  9. IBE Criteria Flaw

  10. IBE Criteria FlawTest-to-Reference Ratios

  11. IBE Criteria FlawSimulation (100,000 trials) T/R=1.05 for 80% of Brand tablets T/R=3.50 for 20% of Brand tablets Generic within-subject cv = 20% Brand within-subject cv = 30% Replicated study in 30 subjects Only 30% of the time T/R was within 0.80-1.25 Only recourse is make a more variable generic

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