Bioequivalence and Bioavailability Forum

Bootstrapping BE: Desultory thoughts [Study Assessment]

posted by Helmut – Vienna, Austria, 2021-07-09 16:50 (1249 d 11:06 ago) – Posting: # 22465
Views: 6,435

Hi ElMaestro,

❝ The term "robustness" lost its meaning to me some months ago following an opinion expressed by a regulator in relation to robustness and simulation.

Oh dear! Any details?

❝ […] in dissolution trials we can often do a simple f2 comparison and if it "fails" then bootstrapping of the same data is the final attempt and it may sometimes actually lead to approval.

Regrettably the other way ’round (see there). An ƒ₂ ≥50 does not guarantee acceptance any more. The lower bootstrapped CL ~~has to be~~ is preferred to be ≥50 as well.

❝ An area where I think bootstrapping is totally ok and very useful is when you want to derive a sample size and you have pilot trial data. If the residual is totally weirdly distributed in the pilot trial, then a sample size calc. in the classical fashion can be wasted time and effort even though the final study always has to be evaluated in the usual parametric fashion involving the assumption of a normal residual.

Agree – in principle.

❝ This is where a bootstrap sample size approach can be very justified and useful. But it, too, has some shortcomings. Such as the assumption of the GMR. You can't easily make provisions for assuming some other than what you have seen in the pilot. Nasty. :-D

Yep. Another issue are ‘outliers’ like in my example. Does it make sense to assume to face them in the pivotal as well? I hope not. Then what? Drop them from the pilot data and bootstrap that?

—
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Helmut Schütz

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Complete thread:

Results Analysis unique_one 2014-07-08 08:58 [Study Assessment]
- Results Analysis ElMaestro 2014-07-08 10:08
  - Results Analysis unique_one 2014-07-08 10:42
    - Don’t hurry; explore consequences Helmut 2014-07-08 12:00
      - Don’t hurry; explore consequences unique_one 2014-07-08 14:01
        
        The smaller a study, the more uncertain its results Helmut 2014-07-08 17:39
        
        The smaller a study, the more uncertain its results unique_one 2014-07-09 06:59
        
        The smaller a study, the more uncertain its results unique_one 2014-07-10 07:09
    - 156 ? d_labes 2014-07-08 12:03
      - 156 ? unique_one 2014-07-08 14:03
    - Results Analysis Shuanghe 2014-07-08 12:57
      - Results Analysis unique_one 2014-07-08 14:08
        
        Results Analysis Samaya B 2014-07-09 07:58
        
        bootstrap Shuanghe 2014-07-09 18:26
        
        bootstrap Weidson 2021-07-03 01:36
        
        Bootstrapping BE: An attempt in 🇷 Helmut 2021-07-08 13:50
        
        Bootstrapping BE: An attempt in 🇷 ElMaestro 2021-07-09 14:15
        
        Bootstrapping BE: Desultory thoughtsHelmut 2021-07-09 14:50
        
        Bootstrapping BE: Desultory thoughts ElMaestro 2021-07-09 16:29
        
        Bootstrapping BE: Desultory thoughts Helmut 2021-07-09 21:04
- Results Analysis Achievwin 2021-08-17 19:26

Bootstrapping BE: Desultory thoughts [Study As­sess­ment]

Complete thread:

Bootstrapping BE: Desultory thoughts [Study Assessment]