Bioequivalence and Bioavailability Forum • Binding / Nonbinding futility rule

Binding / Nonbinding futility rule - alpha control [Two-Stage / GS Designs]

posted by Ben – 2019-03-30 10:52 (1993 d 19:42 ago) – Posting: # 20105
Views: 13,061

Dear Detlew,

Sorry, totally forgot about this post.

❝ Avoiding the conditional sample size re-estimation, i.e. using the conventional sample size re-estimation via

❝ interim.tsd.in(GMR1=0.89, CV1=0.2575165, n1=38, ssr.conditional = "no")

❝ gives n2=4. Ooops? Wow!

Ok, again: the recommendation here is to stop due to futility because the power of stage 1 is greater than the target power 80%. The result of n2 = 4 is correct in this situation. The reason is (i) we calculate n2 based on GMR which is 95% and (ii) we are not using conditional error rates, i.e. we ignore the magnitude of the p-values from stage 1.

❝ ❝ ❝ Binding, nonbinding - does it have an impact on the alpha control? I think not, but are not totally sure.

❝ ❝ Non-binding: Type 1 error is protected, even if the futility criterion is ignored.

❝

❝ Was also my thought because I didn't find any relationship to a futility rule in the proof of alpha control in the paper of Maurer et al. Or do I err here?

You are correct.

❝ ❝ Binding: Type 1 error is protected only if the futility criterion will be adhered to. ('Binding' is not common practice, authorities don't want this).

❝

❝ Are you sure for the binding case?

I believe so, yes.

❝ Of course the power may be compromized.

Agreed!

❝ I think that your statement for the binding case is only valid if you make a further adaption of the local alpha / critical values taking the futility rule into consideration.

No, I don't think that a further adaptation needs to be made. Should be mentioned in e.g. the book of Wassmer and Brannath. I will check this when I have more time.

❝ Do you have any experinces for your statement 'Binding' is not common practice, authorities don't want this'.

❝ If yes, what is/are the reason(s) given by authorities to abandon binding futility rule(s) or not to 'like' them?

Should also be mentioned in the book, but I haven't checked. I learned that in a workshop. I think the problem is that people may not believe you that you will always adhere to the stopping rule.

Best regards,
Ben.

Complete thread:

Finally: Exact TSD methods for 2×2 crossover designs Helmut 2018-04-21 17:17 [Two-Stage / GS Designs]
- Exact TSD methods: Example Helmut 2018-04-21 20:33
- Finally: Exact TSD methods for 2×2 crossover designs ElMaestro 2018-04-21 20:49
  - Flow chart (without details) Helmut 2018-04-21 21:41
    - naive questions regarding new functions in Power2Stage mittyri 2018-04-28 15:54
      - Some answers Helmut 2018-04-28 17:29
      - Some more "answers" d_labes 2018-04-29 21:11
        
        clarification regarding user Power2Stage guides mittyri 2018-04-30 13:41
- Technicality: Weigths for the inverse normal approach d_labes 2018-04-25 14:19
  - Selection of w and w* Helmut 2018-04-26 09:51
    - Selection of w and w* d_labes 2018-04-26 20:02
    - Now what? w & w* examples d_labes 2018-05-09 13:53
      - Now what? w & w* examples Ben 2018-06-10 20:12
        
        Now what? w & w* examples Helmut 2018-06-11 13:57
        
        Now what? w & w* examples Ben 2018-06-12 19:14
        
        a bug in interim.tsd.in()? mittyri 2018-06-11 23:27
        
        a bug in interim.tsd.in()? Ben 2018-06-12 19:32
        
        Nonbinding futility rule d_labes 2018-06-13 16:59
        
        Bad weather? Helmut 2018-06-13 19:23
        
        NLYW? d_labes 2018-06-14 10:18
        
        Nonbinding futility rule Ben 2018-06-13 20:26
        
        Nonbinding futility rule d_labes 2018-06-14 10:47
        
        Nonbinding futility rule Ben 2018-06-15 17:58
        
        Binding / Nonbinding futility rule - alpha control d_labes 2018-06-16 19:42
        
        Binding / Nonbinding futility rule - alpha controlBen 2019-03-30 09:52