Bioequivalence and Bioavailability Forum • Sequential Design = Inflation likely…

Sequential Design = Inflation likely… [RSABE / ABEL]

posted by Helmut – Vienna, Austria, 2014-09-30 17:03 (3878 d 21:10 ago) – Posting: # 13621
Views: 12,117

Hi ElMaestro

❝ It is an interesting quote but I do not understand much of its implications, to be honest. That might be just because I am rather inexperienced with rsABE etc.

See Fig.3 from Davit et al.*

[image]

Is this a sequential design or not? Forget the protocol review, just look at the left branch. Will the type I error be inflated? In some cases, yes. Remember that in conventional (unscaled) ABE the empiric α for some combinations of sample size and CV is substantially lower than the nominal α of 0.05. Similar here. If we don’t adjust α, the lower empiric than nominal level of TOST will protect us – maybe. But: We can expect to face inflation, especially close to CV_WR 30%.

❝ […] FDA have gone full tilt ahead with population BE for budesonide and other inhalation drugs at the in vitro level. I wonder how the pieces actually fit together.

Not my field of expertise. Go and have my next puff now.

Davit BM, Ling Chen M-L, Conner DP, Sam H. Haidar SH, Kim S, Lee CH, Lionberger RA, Makhlouf FT, Nwakama PE, Patel DT, Schuirmann DJ, Yu LX. Implementation of a Reference-Scaled Average Bioequivalence Approach for Highly Variable Generic Drug Products by the US Food and Drug Administration. AAPS J. 2012;14(4):915–24. doi:10.1208/s12248-012-9406-x.

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Science Quotes

Complete thread:

EMA: α-inflation – the suspicion begins to mount Helmut 2014-07-21 02:04
- EMA: α-inflation – the suspicion begins to mount ElMaestro 2014-07-21 09:24
  - Why simulate a simple AB|BA at all? Helmut 2014-07-21 16:14
    - Why simulate a simple AB|BA at all? ElMaestro 2014-07-21 20:50
      - Fancy smoothing? Helmut 2014-07-21 23:13
        
        Arbitrary smoothing? d_labes 2014-07-22 08:43
        
        Noise… Helmut 2014-07-22 13:31
        
        TSD Japonica… d_labes 2014-07-22 16:06
        
        TSD Japonica… Helmut 2014-07-22 17:50
        
        Noise debugged d_labes 2014-07-24 13:47
        
        Noise debugged Helmut 2014-07-24 15:07
        
        Shit happens d_labes 2014-07-24 16:09
      - Commentary d_labes 2014-07-22 08:18
        
        Commentary nobody 2014-09-15 08:24
        
        Commentary Helmut 2014-09-15 10:12
      - IBE/PBE = Two-Stage Helmut 2014-09-29 03:33
        
        IBE/PBE = Two-Stage ElMaestro 2014-09-29 15:16
        
        Sequential Design = Inflation likely…Helmut 2014-09-30 15:03