Bioequivalence and Bioavailability Forum • Bias?

Bias? [Regulatives / Guidelines]

posted by ElMaestro – Denmark, 2010-02-04 12:27 (5568 d 00:35 ago) – Posting: # 4707
Views: 23,803

Dear d_labes,
(and HS who made similar arguments)

❝ What if we have period effects? In the '2x2 extracted evaluation' we are then mixing periods (for instance in T1T2R for the pair T1/R T1 comes from period 1, in sequence T2T1R from period 2).

❝

❝ And what about sequences? For the above example T1T2R and T2T1R are the same in evaluating T1/R?

❝

❝ And what about the error (MSE). In the 3x3 cross-over we have then two (distinct) MSE's and also CV's?

❝

❝ Questions over questions. With the simple answer: This is statistically not so very sound, to be political correct (and not saying nonsense).

These are relevant and important points to make. I do not have a good reply and I am not a regulator. To make matters worse, I have not read any literature.
I could easily be 120% wrong, but ... All in all, I would think that whether something or not is wrong in this game comes down to whether or not the parameter on which a decision is based, is biased (sorry about this terrible sentence, I could not formulate myself better). Wrong is not the same as sub-optimal in the sense that 'minimum variance unbiased' and just plain 'unbiased' can be both correct although one may be more practical (some would say optimal) than the other. If it can be proven that some approach like the one discussed here biases the estimate of T/R then I think that could weigh in heavily. I am incompetent to tell if this is the case here.

Best regards,
EM.

Complete thread:

EMA BE guideline - final version Ohlbe 2010-01-28 18:31 [Regulatives / Guidelines]
- Final version published Helmut 2010-01-29 14:29
  - Final version published ElMaestro 2010-01-29 17:02
    - Statistix Helmut 2010-01-29 17:30
      - Statistix ElMaestro 2010-01-29 18:11
    - Calories ;-) Helmut 2010-01-29 19:22
      - Calories ;-) ElMaestro 2010-01-29 20:43
        
        Calories ;-) Helmut 2010-01-29 21:08
      - Variable calories d_labes 2010-02-01 12:05
    - ANOVA only - no doubts Helmut 2010-02-10 23:41
      - ANOVA only - no doubts ElMaestro 2010-02-12 21:09
  - Final EMA oracle d_labes 2010-02-01 11:53
    - Final EMA oracle Helmut 2010-02-01 12:28
    - Final EMA oracle ElMaestro 2010-02-01 12:50
      - More then two EMA oracles d_labes 2010-02-01 13:30
        
        Less of an issue ElMaestro 2010-02-01 15:29
        
        Less or More of an issue d_labes 2010-02-01 16:53
        
        Less or More of an issue ElMaestro 2010-02-01 17:22
        
        Effective with 1 Aug 2010 Helmut 2010-02-02 00:55
        Bias?ElMaestro 2010-02-04 11:27
        
        Bias? Helmut 2010-02-05 02:03
        
        Bias? ElMaestro 2010-02-05 09:33
        
        Bias? Helmut 2010-02-05 10:21
        
        Bias? d_labes 2010-02-05 13:59
        Bias? ElMaestro 2010-02-05 16:00
        
        Bias? Helmut 2010-02-05 19:14
      - Final EMA oracle Helmut 2010-02-01 13:43
        
        Final EMA oracle ElMaestro 2010-02-01 14:54
        
        Final EMA oracle d_labes 2010-02-01 15:20
        
        Teaching Helmut 2010-02-01 16:07
  - Cmin really gone? tmax reappeared? d_labes 2010-02-01 14:02
    - Cmin really gone. tmax reappeared - but how? Helmut 2010-02-01 23:30
  - Interpol or not d_labes 2010-02-01 14:52
    - Interpol! Helmut 2010-02-02 00:02
      - Interpol! ray_be 2010-02-03 18:31
        
        WinNonlin/Phoenix extrapolation to t=tau Helmut 2010-02-03 20:26
  - Meta-analysis Helmut 2010-02-07 17:41
  - Final version published Panks.79 2010-03-08 07:22
    - Cmin for MR-formulations? Helmut 2010-03-08 18:16
      - Cmin for MR-formulations? Marcel 2010-04-23 10:09
        
        MR-Guideline? Helmut 2010-04-23 12:34
- Overview of comments published Helmut 2010-02-10 18:33
  - Comments commented d_labes 2010-02-11 08:19
  - Definition of Cmin by EMEA Ravi 2010-03-13 12:05
    - The EMA’s Cmin & WinNonlin Helmut 2010-03-13 12:52