Bioequivalence and Bioavailability Forum • Blind or not, Indecisions or Decisions

Blind or not, Indecisions or Decisions [Two-Stage / GS Designs]

posted by d_labes – Berlin, Germany, 2010-10-27 18:01 (5274 d 16:59 ago) – Posting: # 6090
Views: 15,527

Dear Jack,

❝ the reason I call this a one-stage design is that I would not formally test for equivalence at the time were one does the sample size re-estimation. Hence one would not need to spend any alpha at this time (as no testing is done and hence the EMA guide is not relevant) and hence no risk of the awkward situation that one could have to stop the trial early.

I wonder if the EMA will seeing this the same way. Especially claiming that the EMA guideline is not relevant :-D

❝ This is also the reason why doing the sample size re-estimation in a blinded fashion can make sense as using unblinded data will question the one-stage design.

The questions is why? Can you explain why an unblinded evaluation will have any influence?
All involved personal in an open study is unblinded. But the statistician should have a blindfold (this :pirate:

or better this one :cool:

❝ As for the question: "Can we expect to prove BE with a N_max of 120 subjects with some pre-specified power?"

❝

❝ I dont really see the problem there. You are not arriving at a test decision about BE if you decide to stop because you would need more resources than you have and hence it is not impacting your type-I-error.

Do you mean that the stopping the study due to exceeding N_max is not a decision about BE? I have thought up to now that this is equal to the decision: Given the data of the 'internal' pilot we can not expect to reject the Null: Bioinequivalence with reasonable resources. Thus we have to stay with the Null (aka accept H₀). In that direction I had understood hitting futility bounds in group sequential trials.
Or am I here totally wrong? :confused:

This is crucial in implementing a Monte Carlo simulation in which we would count 'BE' / 'not BE' to establish the type I and type II errors. As what shall I count hitting the futility criterion? 'Not BE' or a third answer? If you prefer a third, how to count them with respect to type I and type II errors (nominator/denominator)?

—
Regards,

Detlew

Complete thread:

2-stage design with interim sample size estimation d_labes 2010-10-05 15:09
- 2-stage design with interim sample size estimation Jack 2010-10-25 18:20
  - Null = bioINequivalence Helmut 2010-10-25 19:16
  - 2-stage design with interim sample size estimation d_labes 2010-10-26 13:28
    - 2-stage design with interim sample size estimation Jack 2010-10-26 18:26
      - Blind or not, Indecisions or Decisionsd_labes 2010-10-27 16:01
        
        Blind or not, Indecisions or Decisions Jack 2010-10-27 18:14
        
        Blind ? Ohlbe 2010-10-27 23:37
        
        Blind ? Jack 2010-10-28 10:24
        
        Blind 2Stage Astea 2019-05-30 10:37
        
        Blind 2Stage Helmut 2019-05-30 12:56
        
        Blind 2Stage and an elephant Astea 2019-05-31 14:36
        
        Which elephant? Helmut 2019-06-02 20:14
        
        Blind interim in parallel design? Astea 2019-06-03 01:47
        
        Blind men d_labes 2019-06-05 12:23
        
        The Blind Leading the Blind Astea 2019-06-06 00:55