Bioequivalence and Bioavailability Forum • two-stage design power 90% in sample size adaption

two-stage design power 90% in sample size adaption [Two-Stage / GS Designs]

posted by d_labes – Berlin, Germany, 2012-08-02 12:33 (4707 d 09:46 ago) – Posting: # 9020
Views: 15,216

Dear Yvonne,

❝ Can someone help me with the following question. We are currently planning for a two-stage design (potvin method C).

If you go for an EMA submission: Seems there is an Potvin C abhorrence. See Huanghe's and Helmut's discussion.

❝ My question is, if we go into the second stage and we have to do a sample size calculation, can we use a power of 90% (instead of 80%)? And of course more importantly :-D , would a sample size calculation based on 90% power be accepted by the authorities?

❝ In theory the power is the companies risk and not the consumers risk and thus no extra inflation of alpha would occur in a two stage design (because of a different use of power) or am I wrong here :confused: .

Using 90% power in the sample size adaption step leaves the validation range of the Potvin's methods. No one can guarantee that the patient's risk is bounded by 0.05 as long as he had not done extensive simulations.

Montague et.al. have shown that a deviation from the GMR=0.95 to GMR=0.90 lead to an alpha inflation if the Pocock nominal alpha's (0.0294, 0.0294 for stage 1,2) are used unchanged in methods B and C, respectively.

They argue that the same may take place if the target power is changed. Let me cite: "In particular, we have not considered cases where the desired power used in the method is anything other than 80%. Increasing the power used in the methods from 80 to 90% would be expected to have similar direction of effect as decreasing the GMR used in the methods from 0.95 to 0.90".

Montague TH, Potvin D, DiLiberti CE, Hauck WW, Parr AF, and DJ Schuirmann
Additional results for ‘Sequential design approaches for bioequivalence studies with crossover designs’
Pharmaceut Statist 11/1, 8–13 (2012), DOI: 10.1002/pst.483

—
Regards,

Detlew

Complete thread:

two-stage design power 90% second stage Yvonne 2012-08-02 09:50
- two-stage design power 90% second stage ElMaestro 2012-08-02 10:17
  - two-stage design power 90% second stage Yvonne 2012-08-02 11:47
    - two-stage design power 90% second stage ElMaestro 2012-08-02 11:54
- two-stage design power 90% in sample size adaptiond_labes 2012-08-02 10:33
  - two-stage design power 90% in sample size adaption ElMaestro 2012-08-02 11:29
    - two-stage design power 90% in sample size adaption Yvonne 2012-08-02 12:06
      - two-stage design power 90% in sample size adaption ElMaestro 2012-08-02 16:59
- Are simulations sufficient? …lenghty post! Helmut 2012-08-02 17:39
  - adjusted alpha = 0.045 d_labes 2012-08-03 11:33
    - adjusted alpha = 0.038 Helmut 2012-08-03 14:26
      - adjusted alpha by sims? d_labes 2012-08-03 15:48
        
        Yeah but, no but, yeah but, no but… Helmut 2012-08-03 16:39
        
        Yeah but, no but ... d_labes 2012-08-07 14:42
        
        Yeah but, no but ... Helmut 2012-08-07 15:14