Bioequivalence and Bioavailability Forum

Life belt [Two-Stage / GS Designs]

posted by Helmut  – Vienna, Austria, 2012-09-05 17:20 (4630 d 01:22 ago) – Posting: # 9153
Views: 21,011

Dear Detlew!

❝ IMHO we should be glad that we have the option to widen the BE limits at all according to the EMA guidance in case of HVD's. This reduces the burden considerably for such formulations.

Cough. C_max only.
Pfizer’s world-record is 300+ subjects in a full replicate (no scaling)…

❝ Fetching also the advantages of a 2-stage design in this situation would be too much overkill.

That’s why I called GSD’s attempts in my first reply “courageous”.

❝ Moreover we have to be convinced that our API is HVD. That means that we must have a good reliable estimate of the intra-subject CV (of the reference) which has to be >30%. In that situation an additional life belt for missing or uncertain informations to plan the study aka "2-stage design" is superfluous.

Define “good reliable estimate of the intra-subject CV”.
Especially PPIs show CVs varying across studies from 30–90%. Some studies passed with 24 subjects whilst others failed with 120. Occasionally higher CVs were seen in larger studies; it’s more likely then to face outliers inflating the CV. That’s an example where a 2-stage design would not help because the CV estimated from the first stage would be too small anyway.

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


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Science Quotes

Complete thread:

• Potvin’s 2-stage adaptive design GSD 2012-08-17 20:56 [Two-Stage / GS Designs] 
  • Potvin’s 2-stage adaptive design + RSABE/ABEL Helmut 2012-08-18 00:39
    • Potvin’s 2-stage adaptive design + RSABE/ABEL GSD 2012-08-31 16:30
      • Tough job Helmut 2012-08-31 18:37
        • Tough job GSD 2012-08-31 19:23
          • C/D for EMA? Good luck! Helmut 2012-09-01 15:09
        • Surprise? d_labes 2012-09-05 12:57
          • Got it. Ages for sims to complete Helmut 2012-09-05 13:35
            • Life belt d_labes 2012-09-05 14:51
              • Life beltHelmut 2012-09-05 15:20
    • Power for Two stage Design K2K 2013-10-07 14:43
      • Power for Two stage Design Helmut 2013-10-07 14:59
        • Power for Two stage Design K2K 2013-10-08 14:35
          • “Interim power” Helmut 2013-10-08 14:58
            • “Interim power” K2K 2013-10-09 12:39
              • Validation of PowerTOST Helmut 2013-10-09 14:10
              • Phoenix/WinNonlin - power d_labes 2013-10-09 16:11
                • Phoenix/WinNonlin - power Helmut 2013-10-09 18:19
                  • power K2K 2013-10-10 08:36