Bioequivalence and Bioavailability Forum • Two Stage Design

Two Stage Design [Regulatives / Guidelines]

posted by Helmut – Vienna, Austria, 2008-08-28 13:50 (6081 d 19:45 ago) – Posting: # 2270
Views: 23,830

Dear JPL!

❝ I don't have access to the paper, but it is an interesting issue.

You should get it for about 30 USD - it’s worth it and really quite nice to read. The study which formed the basis of the publication was performed by the ‘The Product Quality Research Institute’ (PQRI) which is a non-profit organization founded in 1999. Members amongst others are FDA-CDER, Health Canada, USP, AAPS, PhRMA. A working group on sequential designs in BE was founded in 2003. They are really heavy weights (definitely not some obscure back-yard statisticians).
Each of the four methods was tested in 1 million (!) of simulated BE studies, with the exception of method A – which is even more strict than a simple add-on design (because it contained a stop criterion if in the first part power >80%). Method A was not considered further, because the alpha-risk was inflated.

❝ But what is meant by "evaluate the power at stage 1"?

This is just the validated decision procedure between the branches.

❝ Am I right that only sample size is adjusted, but intial assumptions on difference and variance are used otherwise?

Essentially the sample size is updated only based on the variance of part 1. Although in adaptive designs it’s possible to update the sample size both on a new estimate of CV and the size of the effect (in the BE setting the ratio T/R), only the former was studied and validated in the study; the latter is considered to be evaluated by the group.

—
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Helmut Schütz

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Complete thread:

Critical review of EU BE guideline (Rev.1) Helmut 2008-08-22 14:30 [Regulatives / Guidelines]
- Critical review of EU BE guideline (Rev.1) d_labes 2008-08-22 15:42
  - Critical review of EU BE guideline (Rev.1) Helmut 2008-08-23 02:02
    - Critical review of EU BE guideline (Rev.1) d_labes 2008-08-25 09:14
      - Variations Helmut 2008-08-25 11:06
- Critical review of EU BE guideline (Rev.1) Jaime_R 2008-08-23 16:47
  - Critical review of EU BE guideline (Rev.1) Ravi 2008-08-25 08:19
    - Two Stage Design Helmut 2008-08-25 11:43
      - Two Stage Design JPL 2008-08-28 09:44
        
        Two Stage DesignHelmut 2008-08-28 11:50
        
        Two Stage Design d_labes 2008-08-28 12:09
        Sequential Design Helmut 2008-11-05 13:22
  - Critical review of EU BE guideline (Rev.1) banusunman 2008-08-26 16:56
    - Washout Helmut 2008-10-15 16:02
- Critical review of EU BE guideline (Rev.1) d_labes 2008-08-25 09:49
  - Critical review of EU BE guideline (Rev.1) Helmut 2008-08-25 12:11
    - Critical review of EU BE guideline (Rev.1) d_labes 2008-08-25 13:03
    - Urban legend? Helmut 2008-11-21 16:06
      - Urban legend? d_labes 2008-11-24 15:06
- Critical review of EU BE guideline (Rev.1) d_labes 2008-08-25 11:16
- Critical review of EU BE guideline (Rev.1), tmax, MRT, LZ d_labes 2008-08-25 11:32
  - Critical review of EU BE guideline (Rev.1), tmax, MRT, LZ Helmut 2008-08-25 13:10
  - tmax, nonparametrics Helmut 2008-10-13 15:38
    - tmax, nonparametrics d_labes 2008-10-14 08:33
      - tmax, nonparametrics Helmut 2008-10-14 11:29
      - tmax, Canadian approach Helmut 2008-11-21 15:41
        
        tmax, Canadian approach d_labes 2008-11-24 13:53
        
        Early exposure, Canadian approach: GMR only! Helmut 2009-02-08 00:44
        
        Early exposure, Canadian approach: GMR only! d_labes 2009-02-09 08:50
        
        tmax; another example Helmut 2008-12-25 15:59
- Automatic integration janmacek 2008-08-27 12:21
  - Automatic integration Ohlbe 2008-08-27 14:49
    - Manual reintegration! H_Rotter 2008-08-28 11:28
      - Manual reintegration! ElMaestro 2008-08-28 12:44
- Subject accountability, Proc MIXED or equivalent d_labes 2008-09-02 11:13
  - Subject accountability, Proc MIXED or equivalent Ohlbe 2008-09-02 15:20
    - Subject accountability, Proc MIXED or equivalent d_labes 2008-09-02 16:30
- partial AUC, early exposure d_labes 2008-09-03 08:35
- HVDs? Helmut 2008-09-23 12:52
  - HVDs? d_labes 2008-09-23 14:20
  - HVDs? Helmut 2009-01-20 14:33
  - E.g., omeprazole Helmut 2009-03-06 17:21
- BCS-based Biowaiver Helmut 2008-09-25 15:48
  - Dissolution update Helmut 2008-10-13 12:43
- EUFEPS workshop Helmut 2008-12-23 17:03