Bioequivalence and Bioavailability Forum • Yes but no but yes but no but…

Yes but no but yes but no but… [RSABE / ABEL]

posted by Helmut – Vienna, Austria, 2013-03-29 17:10 (4039 d 03:09 ago) – Posting: # 10312
Views: 20,058

Hi Martin!

❝ what about defining the extent of scaling after interim analysis of the first stage data (CV estimated in 1st stage) within a group-sequential adaptive design?

Theoretically OK. ;-)

❝ Drawback: BUT what if the CV at interim is smaller than 0.3 ... :confused:

… or it is larger than 0.3 in stage 1 and in the pooled data set (n↑ = more precise estimate) you find one which is ≤0.3? If the inflation is real (still not sure) we have a problem – only with EMA’s method – in the CV-range 0.3–0.5. IMHO there are two options:

Iteratively adjust α.
Use a fixed α of ~0.030 for partial replicates and ~0.025 for full replicates if CV_WR ≤0.5 (see plots above). This should cover the entire range of designs and sample sizes of up to 96. The maximum adjustment (at 0.3) is almost independent from sample size (see plot below). Conservative for any CV >0.3…

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Complete thread:

‘alpha’ of scaled ABE? d_labes 2013-03-15 15:56 [RSABE / ABEL]
- ‘alpha’ of scaled ABE? Helmut 2013-03-15 17:27
  - ’alpha’ of scaled ABE: design d_labes 2013-03-16 20:10
    - N=24, 48 d_labes 2013-03-18 08:11
      - adaptive design without adjustment martin 2013-03-25 20:47
        
        α adjustment? Helmut 2013-03-26 15:21
        
        iteratively adjusted alpha martin 2013-03-26 16:19
        
        throw away our sample size tables? Helmut 2013-03-26 18:02
        
        if real martin 2013-03-26 19:44
        
        regulators don’t care? Helmut 2013-03-26 21:18
        
        adjusting α Helmut 2013-08-11 16:19
        
        target α in sim’s? Helmut 2013-03-27 15:38
        
        target α in sim’s? martin 2013-03-27 16:36
        
        If it is real: results Helmut 2013-03-28 23:20
        
        having alpha martin 2013-03-28 15:08
        
        fixed swr Helmut 2013-03-28 23:34
        
        fixed swr martin 2013-03-29 15:07
        
        Yes but no but yes but no but…Helmut 2013-03-29 16:10