Bioequivalence and Bioavailability Forum • α and 1

α and 1–β [Power / Sample Size]

posted by Helmut – Vienna, Austria, 2017-12-27 15:31 (2301 d 16:37 ago) – Posting: # 18102
Views: 33,372

Hi Yura,

❝ ❝ If the protocol was approved by the IEC and the competent regulatory agency

❝

❝ yes, explanations are needed for estimating the sample size and design (that to reduce it)

Sure. But once explanations (better: assumptions) were accepted (i.e., the protocol approved) that’s the end of the story. That’s why I’m extremely wary of using the term “forced bioequivalence” in a regulatory context (see also this post and followings).
IMHO, post hoc power is crap. The chance to get one which is higher than planned is ~50%. Run my simulation code and at the end:

cat(nsims, "simulated studies with \u201Cpost hoc\u201D power of", "\n \u2265 target :", sprintf("%5.2f%%", 100*length(res[, 3][res[, 3] >= target])/nsims), "\n \u2265 achieved :", sprintf("%5.2f%%", 100*length(res[, 3][res[, 3] >= plan[["Achieved power"]]])/nsims), "\n \u2265 0.90 :", sprintf("%5.2f%%", 100*length(res[, 3][res[, 3] >= 0.9])/nsims), "\n [0.95, 0.99]:", sprintf("%5.2f%%", 100*length(res[, 3][res[, 3] >= 0.95 & res[, 3] <=0.99])/nsims), "\n \u2265 0.95 :", sprintf("%5.2f%%", 100*length(res[, 3][res[, 3] >= 0.95])/nsims), "\n")

With your example (CV 0.25, GMR 0.95, target power 80%, n 28, 10⁵ simulations):

1e+05 simulated studies with “post hoc” power of ≥ target : 49.92% ≥ achieved : 48.02% ≥ 0.90 : 22.93% [0.95, 0.99]: 8.40% ≥ 0.95 : 9.70%

Although the study was performed with 28 subjects for ~81% power, the chance to get a post hoc power of ≥ 90% is ~23% and ≥ 95% is ~10%. That’s clearly not “forced BE” and none of these studies should be questioned by regulators.*
I suggest to reserve this term to the context of study planning.

To quote ElMaestro: Being lucky is not a crime.
Let’s reverse the question. Would you mistrust a study which demonstrated BE despite its low post hoc power? I hope not. We endured this game for ages and it went where it belongs to: The statistical trash bin.

—
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Helmut Schütz

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Complete thread:

Power is getting high kms.srinivas 2017-12-26 07:39
- Power is getting high? d_labes 2017-12-26 12:08
- Stop estimating post hoc power! Helmut 2017-12-26 12:22
  - Stop estimating post hoc power! kms.srinivas 2017-12-26 13:00
    - Stop estimating post hoc power! ElMaestro 2017-12-26 14:11
    - Simulations Helmut 2017-12-26 15:51
      - Simulations BE-proff 2017-12-27 06:53
        
        Simulations ElMaestro 2017-12-27 07:25
        Simulations Yura 2017-12-27 08:23
        
        Simulations kms.srinivas 2017-12-27 09:11
        
        Simulations Yura 2017-12-27 10:07
        
        α and 1–β Helmut 2017-12-27 12:57
        
        α and 1–β Yura 2017-12-27 13:33
        
        α and 1–βHelmut 2017-12-27 14:31
        
        α and 1–β Yura 2017-12-28 06:50
        
        Educate the IEC and regulators Helmut 2017-12-28 11:30
        
        “Forced BE” 101 Helmut 2017-12-27 12:23
        
        “Forced BE” 101 kms.srinivas 2017-12-27 12:41
        
        Would you be so kind answering our questions? Helmut 2017-12-27 13:02
        
        Would you be so kind answering our questions? kms.srinivas 2017-12-28 05:53
        
        Yes, but why? Helmut 2017-12-28 11:47
        
        Yes, but why? DavidManteigas 2017-12-28 16:59
        
        Optimists and pessimists Helmut 2017-12-28 17:33
        
        "normal" GMR setting d_labes 2017-12-28 18:57
        
        Example for discussion mittyri 2017-12-28 22:06
        
        Example for discussion Helmut 2017-12-28 22:33
        
        I prefer to play it safe Helmut 2017-12-28 22:10
        
        Full ACK d_labes 2017-12-28 17:41
        About GMR 1.10 kms.srinivas 2017-12-29 13:20
        
        Better 0.95 or 0.90 Helmut 2017-12-29 16:18
        
        Yes, but why? Yura 2017-12-29 13:46
        Buffon's needle Astea 2018-01-20 23:55
        
        Buffon's needle Oleg777 2018-10-09 22:48
        
        0.95 or 1.05 Helmut 2018-10-10 13:41
        
        Buffon's needle Helmut 2018-10-10 12:46
        
        Buffon's needle Astea 2018-10-11 23:14
        
        School maths Helmut 2018-10-12 01:10
        
        School russian Astea 2018-10-12 12:41
        Offtop: Umschrift der westlichen Eigennamen auf Russisch mittyri 2018-10-12 23:25
        
        EEU? mittyri 2017-12-28 21:52
        
        EEU? Yura 2017-12-29 13:41
        
        EEU - pharmacokinetic equation??? mittyri 2017-12-29 14:11
        
        EEU? Beholder 2018-01-16 15:10
        
        Simulations xtianbadillo 2018-01-18 22:22
- Numbers don't lie ElMaestro 2017-12-28 20:13