Bioequivalence and Bioavailability Forum • But what is the real problem?

But what is the real problem? [Two-Stage / GS Designs]

posted by Mikalai – Belarus, 2018-06-08 14:24 (2929 d 01:16 ago) – Posting: # 18871
Views: 8,573

Dear Helmut,
Thank you very much for your explanation. Could you, please, clarify a bit further?

❝ Nope. You calculate interim power after the first stage. If you want to use the GMR of the first stage as well (go fully adaptive) you might shoot yourself in the foot. Practically you need two futility criteria:

Stop if the GMR is outside [0.80, 1.25].
❝
Stop if the re-estimated sample size is above a pre-specified limit (U).

The methods of Karalis & Macheras might (!) have terrible power making their application ethically doubtful. Here it works with U 120 if n₁ 24 but not with n₁ 12 (power only ~73%). There are alternatives where you don’t stop if n₁+n₂>U but perform the the second stage in U–n₂ subjects. No problem with the Type I Error but might compromise power; I suggest simulations.

Are there any rules or recommendations for setting up the pre-specified limit (U) as a futility criterion?
Regards,
Mikalai

Complete thread:

Two-stage design and 'forced bioequivalence' Mikalai 2018-06-06 08:28
- Two-stage design and 'forced bioequivalence' ElMaestro 2018-06-06 10:53
  - Two-stage design and 'forced bioequivalence' Yura 2018-06-07 10:24
    - But what is the real problem? ElMaestro 2018-06-07 13:53
      - But what is the real problem? Yura 2018-06-07 14:59
        
        But what is the real problem? Mikalai 2018-06-07 15:47
        
        But what is the real problem? Helmut 2018-06-07 17:33
        
        But what is the real problem?Mikalai 2018-06-08 12:24
        
        U as a futility criterion Helmut 2018-06-08 14:00