Bioequivalence and Bioavailability Forum • Groups: (Hardly‽) overlapping CIs

Groups: (Hardly‽) overlapping CIs [Design Issues]

posted by Helmut – Vienna, Austria, 2024-11-21 14:20 (235 d 17:37 ago) – Posting: # 24286
Views: 6,156

Hi BEQool,

an example. Study powered to 90%, n=65, n₁=31, n₂=34, groups separated by 1 (one!) day. Evaluation per protocol with group model II. C_max and AUC passed with ease. A deficiency letter one week before M13A was published:

Due to the significant Group × Formulation effect (p<0.05) for ln-transformed C_max observed in model I, a separate exploratory analysis of each group was performed and produced the following outcomes:

Group 1: The 90% CI for C_max (108.5–126.38%) fell outside the bioequivalence limits, while the CI for AUC (99.31–117.47%) remained within the limits.
Group 2: Both the 90% CIs for C_max (90.01–109.2%) and AUC (85.43–106.39%) fell within the bioequivalence limits.

The finding from model I suggests heterogeneity of treatment effect across groups, with 90% CIs for C_max hardly overlapped as demonstrated with model III submitted by the applicant. Therefore, the applicant should provide a justification for this difference and discuss its potential impact on the conclusion of bioequivalence.

A new term: Hardly overlapping CIs. Again: So what? Justification?

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Helmut Schütz

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Complete thread:

Possible reasons for group effect GM 2019-07-20 07:36 [Design Issues]
- Group “effect” Helmut 2019-07-20 14:02
- Possible reasons for group effect ElMaestro 2019-07-20 19:20
  - Possible reasons for group effect GM 2019-07-23 06:23
    - “Group-by-Treatment Interaction” Helmut 2019-07-23 10:32
      - “Group-by-Treatment Interaction” BEQool 2024-10-22 12:39
        
        “Group-by-Treatment Interaction” Helmut 2024-10-22 12:47
        
        OT: A choice between mittyri 2024-10-22 16:03
        
        OT: A choice between BEQool 2024-10-23 11:02
        
        OT: A choice between Helmut 2024-10-23 11:58
        
        OT: A choice between BEQool 2024-10-23 13:17
        
        OT: A choice between Helmut 2024-10-23 13:22
        Groups: Overlapping CIs Helmut 2024-11-03 11:36
        
        Groups: Overlapping CIs BEQool 2024-11-05 09:14
        
        Groups: Overlapping CIs Helmut 2024-11-05 10:12
        
        Groups: Overlapping CIs BEQool 2024-11-06 07:44
        
        Groups: (Hardly‽) overlapping CIsHelmut 2024-11-21 13:20
        
        Groups: (Hardly‽) overlapping CIs BEQool 2024-11-22 12:32
        
        Groups: (Hardly‽) overlapping CIs Helmut 2024-11-22 12:58
        Multiplicity? Helmut 2024-11-23 13:05
        
        Groups BEQool 2024-11-26 08:15