Bioequivalence and Bioavailability Forum • Loss in power

Loss in power [Regulatives / Guidelines]

posted by Helmut – Vienna, Austria, 2017-05-14 19:22 (2531 d 06:42 ago) – Posting: # 17352
Views: 29,316

Hi mittyri,

continuing the evaluation of the data sets of this post.
Background: Some studies are quite dated (the oldest performed in October 1992!). In those days a pre-specified acceptance range of 75.00–133.33% (or even 70.00–142.86%) was acceptable for C_max. However, I evaluated all data sets for the common 80.00–125.00%. This explains why more than the expected 20% failed (no, I didn’t screw up the design ;-)

). If ever possible I tried to avoid equal group sizes but kept one as large as possible. Didn’t succeed sometimes. Working in a CRO, the sponsor is always right…
All data sets were evaluated by model 3 for pooled data (like in the reports – I never cared about groups) and by model 1 to get the p value of the Group-by-Treatment interaction.

If p (G×T) ≥0.1 the pooled data was evaluated by model 2.
If p (G×T) <0.1 the largest group(s) were evaluated by model 3.
If there were more than one large group with equal sizes, both had to pass since I expect assessors will ask for it.

Here the results:

86 studies, 60 analytes, data sets: 85 (AUC), 86 (Cmax). Evaluated by model 1 (all effects fixed); p (G×T) <0.1: AUC : 8.24% ( 7/85) Cmax: 12.79% (11/86) Summary of passing results. AUC : model 2 (pooled) : 84.62% (66/78) model 2 (pooled without pre-test) : 84.71% (72/85) loss (compared to pooled model 3) : 1.18% ( 1/85) model 3 (largest group) : 85.71% ( 6/ 7) model 2 (pooled) or model 3 (largest group): 84.71% (72/85) loss (compared to pooled model 3) : 1.18% ( 1/85) model 3 (pooled) : 85.88% (73/85) CV (range) : 21.36% (4.59–61.73%) Cmax: model 2 (pooled) : 62.67% (47/75) model 2 (pooled without pre-test) : 63.95% (55/86) loss (compared to pooled model 3) : 0.00% ( 0/86) model 3 (largest group) : 27.27% ( 3/11) model 2 (pooled) or model 3 (largest group): 58.14% (50/86) loss (compared to pooled model 3) : 5.81% ( 5/86) model 3 (pooled) : 63.95% (55/86) CV (range) : 27.88% (6.82–76.99%)

The loss in power if we follow the FDA’s procedure (compared to the pooled model 3) is lower than I expected. Surprise. A possible explanation is that studies were usually powered for C_max. Therefore, already the largest groups passed AUC.
On another note: If we apply model 2 without a pre-test (maybe the best way to go for regulators insisting in a group-term) the loss in power compared to the pooled model 3 is negligible. Reasonable, since we lost only few residual degrees of freedom:
pooled model 3: DF=n₁+n₂–2
pooled model 2: DF=n₁+n₂-(N_groups–1)–2

—
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz

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Complete thread:

Russian «Экспертами» and their hobby Helmut 2017-04-29 00:46 [Regulatives / Guidelines]
- Low power of Group-by-Treatment interaction mittyri 2017-04-29 22:57
  - Let’s forget the Group-by-Treatment interaction, please! Helmut 2017-04-30 13:54
    - Let’s forget the Group-by-Treatment interaction, please! ElMaestro 2017-05-01 16:19
      - Some answers Helmut 2017-05-02 01:10
        
        Some answers ElMaestro 2017-05-02 09:04
        
        Example Helmut 2017-05-02 12:35
        
        Sensitivity of term? mittyri 2017-05-02 18:29
        
        Simulations Helmut 2017-05-05 14:38
        
        loosing specificity due to low sensitivity mittyri 2017-05-08 23:28
        
        loosing specificity due to low sensitivity Helmut 2017-05-09 00:55
        
        Loss in power Helmut 2017-05-06 17:31
        Interval between groups Helmut 2017-05-08 19:02
        
        IMP handling mittyri 2017-05-08 23:40
        
        IMP handling Helmut 2017-05-09 01:08
        
        Loss in powerHelmut 2017-05-14 17:22
      - No convergence in JMP and Phoenix WinNonlin Helmut 2017-05-25 15:26
        
        Ouch?!??? ElMaestro 2017-05-25 16:24
- Russian «Экспертами» and their hobby Artem Gusev 2017-05-02 16:13
  - be careful with mixed models mittyri 2017-05-02 17:53
    - be careful with mixed models Artem Gusev 2017-05-03 11:02
  - p-value(s) in model 2 Helmut 2017-05-05 14:48
- Russian «Экспертами» following the EEU GLs Helmut 2017-05-24 20:17
  - Russian «Экспертами» following the EEU GLs Beholder 2017-05-24 22:37
    - Penalty for carelessness mittyri 2017-05-25 08:52
    - Russian «Экспертами» following the EEU GLs Beholder 2017-05-25 10:43
  - Russian «Экспертами» following the EEU GLs Mikalai 2018-01-04 10:43
    - Belarus = member of the EEU Helmut 2018-01-04 13:08
      - Belarus = member of the EEU Mikalai 2018-01-04 19:49
      - Trying your model for EEU mittyri 2018-01-04 22:04
        
        Trying your model for EEU Helmut 2018-01-05 00:06
        
        help us to stop it, please... Astea 2018-01-10 12:09
        
        help us to stop it, please... Beholder 2018-01-10 12:49
        regulators convinced by science? d_labes 2018-01-10 15:15
        
        regulators convinced by science? Beholder 2018-01-10 17:14
        
        Чёрт побери! d_labes 2018-01-10 18:53
        
        regulators convinced by science? Astea 2018-01-10 19:10
        
        Excuse me d_labes 2018-01-10 20:18
        
        Excuse me Astea 2018-01-10 20:38