Bioequivalence and Bioavailability Forum • Potvin method B subtleties

Potvin method B subtleties [Two-Stage / GS Designs]

posted by jdetlor – 2011-02-01 18:17 (5199 d 23:13 ago) – Posting: # 6531
Views: 26,325

Dear D Labes,

❝ Q1: Do you think I have inserted the right alpha values?

In terms of stage 1/2 location, they look correct to me.

❝ Q2: If yes in Q1: It may happen that in the sample size estimation step the resulting N may be lower then the sample size at stage 1, i.e. there is no stage 2 necessary. What to do then? Evaluate via stage 1 model but with alpha=alpha2=0.048 ?

Gould¹ discusses the allocation of alpha between stages and specifies the critical values (and hence the alpha values) should be the same for each stage to maintain rejection consistency. The determination of alpha relates to the allocation of subjects between stages.
What complicates the above with respect to Potvin et al. is the ratio of subjects is not known for the final analysis, and thus the impact on the choice of alpha would need to be evaluated through simulation.

❝ Q3: Do you think that the power calculation makes sense if executed with the point estimate from stage 1 instead of GMR=0.95?

Potvin et al. does mention this. I believe they reference Cui et al.² who determine that if this approach is applied naively, it can inflate the type I error rate up to 30%.

❝ Q4: Do you think Method B is nearer then Method C to the sentence "... The analysis of the first stage data should be treated as an interim analysis and both analyses conducted at adjusted significance levels (with the confidence intervals accordingly using an adjusted coverage probability which will be higher than 90%) ..." from the EMA guideline?

They both have interim analyses; method B evaluates BE initially, whereas method C evaluates the power, then BE. I don't know if you could say that one is closer than the other.

¹⁾Gould AL
Group sequential extensions of a standard bioequivalence testing procedure. Journal of Pharmacokinetics and Biopharmaceutics 1995; 23:57-86.
²⁾Cui L, Hung MJ, Wang S-J
Modification of sample size in group sequential clinical trials. Biometrics 1999; 55:853-857.

J. Detlor

Complete thread:

Potvin method B subtleties d_labes 2011-01-31 14:24 [Two-Stage / GS Designs]
- Potvin method B subtletiesjdetlor 2011-02-01 17:17
  - Potvin method B subtleties d_labes 2011-02-02 09:15
    - Potvin method B subtleties jdetlor 2011-02-02 16:08
      - Gould d_labes 2011-02-02 16:25
        
        Gould jdetlor 2011-02-02 17:02
- Another one ... d_labes 2011-02-07 14:32
  - Oops! Helmut 2011-02-07 15:24
    - Oops! d_labes 2011-02-07 16:29
      - Oops! Helmut 2011-02-07 16:47
        
        Oops! ElMaestro 2011-02-07 17:06
        
        Oops! Helmut 2011-02-07 17:17
        
        Oops! ElMaestro 2011-02-07 18:35
        
        Simul'ants in my pants d_labes 2011-02-08 09:07
        
        Need for speed... ElMaestro 2011-02-13 10:57
        
        Need for speed... d_labes 2011-02-15 14:06
        
        Need for speed... ElMaestro 2011-02-15 17:39
        
        Pocock alpha's d_labes 2011-02-16 09:18
        
        ElMaestro's brain ElMaestro 2011-02-16 09:32
        
        ElMaestro's brain d_labes 2011-02-16 10:05
        
        ElMaestro's brain ElMaestro 2011-02-16 12:07
        
        Numbers d_labes 2011-02-16 13:45
- Bonus counter-question ElMaestro 2011-02-07 23:44
  - Speed is the question d_labes 2011-02-08 08:36
- New paper (method D for PE 0.90) Helmut 2011-04-18 12:58
  - New paper (method D for PE 0.90) d_labes 2011-04-19 08:58
    - New paper (method D for PE 0.90) Helmut 2011-04-19 14:30
    - New paper (method D for PE 0.90) ElMaestro 2011-04-19 14:49
      - Stopping criterion # futility rule Helmut 2011-04-19 15:28