Bioequivalence and Bioavailability Forum

C/D for EMA? Good luck! [Two-Stage / GS Designs]

posted by Helmut  – Vienna, Austria, 2012-09-01 17:09 (4677 d 21:47 ago) – Posting: # 9140
Views: 22,049

Hi GSD!

❝ […] I realized that 10^6 is a must when you go for Potvin’s 2-stage.

Yes – 1/√N hits.*

❝ ❝ Which one of Potvin’s methods are you aiming at?

❝

❝ Methods C/D.

Are you aware that the acceptability of C/D for EMA is limited (pun intended)? If you want to deal with ABEL, I reckon only Method B might be acceptable – though some member states even mistrust the validity of the power evaluation in the intermediate analysis at all. Right now C/D is only acceptable (without major discussions) in the US and Canada. Since HPFB does not allow scaling this leaves the FDA with an easier model (without the 50% cap – but the discontinuity at 30%).

❝ But if any of your sample CVs exceeds 30%, the acceptance limits are widened. They are no longer fixed at 0.8 and 1.25. When you enter your simulation with a starting CV of say 35%, most of your random samples will have an acceptance limit in the neighborhood of [0.7723, 1.2948]. In this case, when you still center it on ln(0.8), the simulated “type I error” will be huge.

Sounds like chicken-and-egg to me. The ratio and CV in the sims are independent – but the scaled acceptance range depends on the actual CV in every simulated study…

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• Takes a while to obtain a stable estimate (the red line on top is the critical limit of α>0.05):
  
  

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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 
  • 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 belt Helmut 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