Bioequivalence and Bioavailability Forum • Add-on designs obsolete!

Add-on designs obsolete! [Two-Stage / GS Designs]

posted by Helmut – Vienna, Austria, 2014-06-17 15:36 (4024 d 03:03 ago) – Posting: # 13073
Views: 6,219

Hi Mahesh,

in Add-on designs one performs the study as a conventional fixed sample design and – if BE could not be demonstrated – add a second group of subjects and perform a new BE assessment of pooled data. This method was mentioned in Health Canada’s guidances from the early 1990s. It was shown in numerous publications that the patient’s risk will be inflated (i.e., >5%) by this method. Therefore, HC/HPFB/TGD abandoned it in 2012. Background:
- The entire α of 5% is already spent in the first analysis.
- Nothing is “left” for the second analysis. Therefore, due to multiple testing the type I error will be >5%. This is not acceptable.
The only regulation where Add-on designs are still acceptable is the Japanese.
In Two-Stage Sequential Designs you follow particular frameworks which will maintain the type I error at 5%. For details and references see my presentations, f.i. this one.

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Helmut Schütz

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Science Quotes

Add-on and Two-Stage Designs Mahesh M 2014-06-17 11:12
- Add-on designs obsolete!Helmut 2014-06-17 13:36
  - Add-on designs obsolete! Mahesh M 2014-06-18 06:38
  - Add-on designs obsolete! jag009 2014-06-18 16:04
    - Add-on designs obsolete! Helmut 2014-06-18 19:41