Bioequivalence and Bioavailability Forum • 2-stage design

2-stage design - power evaluation [Two-Stage / GS Designs]

posted by d_labes – Berlin, Germany, 2011-10-12 13:10 (4946 d 08:21 ago) – Posting: # 7474
Views: 20,443

Dear All!

In this thread I had already raised some questions concerning the decision scheme according to Potvin Method B if one is willing to use "unsymmetrical" nominal alpha values, f.i. according to O'Brian-Fleming alpha₁=0.005 and alpha₂=0.048.

Now sitting here and wondering again especially about the power check step.

What is the rationale behind that step?
What alpha value should therefore used? alpha₁ or alpha₂?
How should the decision scheme read in case of "unsymmetrical" nominal alpha values?

As you see from these questions I'm very unsure. But meanwhile had arrived at the following (O'Brian-Fleming alphas):

  Evaluate BE at stage 1 

  at alpha=alpha₁=0.005

      ↓              ↓

if BE met:       if BE not met:

stop: success    Evaluate power with alpha₂=0.048

                 at GMR=0.95

                     ↓                    ↓

                if power>80%           if power<80%

                Evaluate BE at stage1  Calculate sample size n_est with GMR=0.95

                with alpha₂=0.048      alpha₂=0.048 and variance from stage1

                     ↓                    ↓

                stop: success          continue to stage 2 with n₂=n_est-n₁ subjects

                      or fail          evaluate after stage 2 with alpha2=0.048

                                       using data from both stages

                                       success or fail

Any opinions about that?

Bonus question: Do you have an idea how decision scheme C should read?

More questions arise if the point estimator of stage 1 has to be taken into consideration. But that's another story.

—
Regards,

Detlew

Complete thread:

2-stage design - power evaluationd_labes 2011-10-12 11:10 [Two-Stage / GS Designs]
- No opinions out there? d_labes 2011-10-26 09:14
  - Opinion yes, answer no ElMaestro 2011-10-26 11:15
    - Decision scheme without (?) power check d_labes 2011-10-26 13:00
      - Decision scheme without (?) power check ElMaestro 2011-10-26 13:20
        
        Decision scheme 'without' power check d_labes 2011-10-26 14:51
        
        Decision scheme 'without' power check ElMaestro 2011-10-26 15:24
        
        Numerical example d_labes 2011-10-26 16:28
        
        Numerical example ElMaestro 2011-10-26 16:49
        
        Potvin C with unsymmetrical alphas d_labes 2011-10-27 14:54
        
        Potvin B, C, or D? Helmut 2011-10-27 22:52
        Two-stage (classical Pocock) and the FDA Helmut 2011-10-31 02:36
- Weirdo paper ElMaestro 2011-11-30 18:04
  - Weirdo paper Helmut 2011-11-30 23:45
    - Weirdo paper ElMaestro 2011-12-01 07:16