Bioequivalence and Bioavailability Forum • Change to Method B?

Change to Method B? [Two-Stage / GS Designs]

posted by Helmut – Vienna, Austria, 2013-10-21 16:51 (4218 d 23:17 ago) – Posting: # 11719
Views: 25,507

Hi Kumar,

❝ We have back calculated the CV from the available literature it is ~21%. And the sample size is 28 for stage I.

OK, that’s not too bad (10⁶ simulations, exact power):

Method C
Overall power 92.0%, power in stage 1 90.6%.
Average total sample size 28 (n_5% 28, median 28, n_95% 28, n_max 66).
2.0% of studies proceed to the second stage.
Method B
Overall power 88.7%, power in stage 1 86.2%.
Average total sample size 28 (n_5% 28, median 28, n_95% 30, n_max 66).
5.5% of studies proceed to the second stage.
Conventional fixed sample design
Power 91.4%

Methods B and C have already a high chance to show BE in the first stage. If the sponsor is wary about EMA’s acceptance, consider changing to Method B. If you want to change to a conventional 2×2 cross-over – contrary to what I said before – there shouldn’t be ethical issues (power >90%). If the actual CV is 25%, power would still be 80.7%. Up to you. On the other hand, if the CV is higher than 25% or you have drop-outs the producer’s risk increases.

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Complete thread:

Acceptance by FDA/CDER Mahesh 2013-08-06 06:12 [Two-Stage / GS Designs]
- Two stage BE design ElMaestro 2013-08-06 10:05
- Two stage BE design Helmut 2013-08-06 15:31
  - Two stage BE design Mahesh 2013-08-07 06:51
    - Two stage BE design kumarnaidu 2013-10-17 15:08
      - Two stage BE design ElMaestro 2013-10-17 17:28
        
        Two stage BE design kumarnaidu 2013-10-18 05:59
        
        EMA vs. rest of the world Helmut 2013-10-18 14:42
        
        Two stage BE design — cold water thrown on our head Shuanghe 2013-10-18 10:05
        
        Open your mouth and forcefully spit the water out Helmut 2013-10-18 13:29
        
        Change in statistical design kumarnaidu 2013-10-19 07:52
        
        Bad idea Helmut 2013-10-19 15:04
        
        Bad idea kumarnaidu 2013-10-21 06:01
        
        Change to Method B?Helmut 2013-10-21 14:51
        
        Change to Method B? kumarnaidu 2013-10-22 06:15
        
        Simulations Helmut 2013-10-22 13:20
        
        Open your mouth and forcefully spit the water out Shuanghe 2013-10-22 09:03
        
        Reach for the stars Helmut 2013-10-22 13:05
        
        Alpha inflation in two stage design kumarnaidu 2013-12-04 13:43
        
        Deficiency letters Helmut 2013-12-04 14:50
        
        Deficiency letters kumarnaidu 2013-12-05 06:18
        
        Simulations Helmut 2013-12-05 15:51
        
        Simulations kumarnaidu 2013-12-05 16:07
        
        Simulations Helmut 2013-12-05 16:55
        
        Simulations kumarnaidu 2013-12-06 06:07
        
        Ejaculatio praecox Helmut 2013-12-06 14:30
        
        Ejaculatio praecox kumarnaidu 2013-12-06 15:13
        
        All effects fixed Helmut 2013-12-06 15:31
        
        All effects fixed kumarnaidu 2013-12-09 07:33
        
        EMA… Helmut 2013-12-09 12:45