Bioequivalence and Bioavailability Forum • “Overpowered” studies due to GLs

“Overpowered” studies due to GLs [Power / Sample Size]

posted by Helmut – Vienna, Austria, 2014-09-28 03:13 (4280 d 00:43 ago) – Posting: # 13603
Views: 20,122

Hi Khaoula,

❝ for minimum number of subject: it's not about possible significant treatment effect with low nuber of subject, low CV?

Likely. Let’s assume a 2×2 cross-over, T/R-ratio 0.95, n=12. For any CV ≤15.63% power will be >80%, for CV ≤13.39% >90%, for CV ≤9.85% >99%, etc. etc.
The lowest CVs I have seen so far were 5–7% (AUCs of valproic acid, methylphenidate). If you perform a study with a drug showing a CV of 6% in 12 subjects, power will be 99.99993%. In other words, a significant treatment effect is highly probable. See this presentation (slide 9): The red diamonds are sample sizes to reach at least 80% power. If you keep the sample size at 12 for low CVs, power will increase extremely (blue line).

BTW, the minimum sample size of 12 is arbitrary; some tables^1,2 go down to 4.

Diletti E, Hauschke D, Steinijans VW. Sample size determination for bioequivalence assessment by means of confidence intervals. Int J Clin Pharm Ther Toxicol. 1991;29(1):1–8. PMID 2004861.
Hauschke D, Steinijans VW, Diletti E, Burke M. Sample Size Determination for Bioequivalence Assessment Using a Multiplicative Model. J Pharmacokin Biopharm. 1992;20(5):557–61. PMID 1287202.

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Complete thread:

minimum number of subject in bioequivalence study khaoula 2014-09-27 11:14
- minimum number of subject in bioequivalence study ElMaestro 2014-09-27 11:26
  - minimum number of subject in bioequivalence study khaoula 2014-09-27 23:49
    - “Overpowered” studies due to GLsHelmut 2014-09-28 01:13
      - “Overpowered” studies due to GLs khaoula 2014-09-28 22:36
        
        “Overpowered” studies due to GLs Helmut 2014-09-29 03:51
      - Scientific Validation for the Sample Size Formula mreyes 2014-11-07 19:47
        
        Basic maths Helmut 2014-11-07 20:09
        
        Basic maths mreyes 2014-11-07 20:47
        
        Reference for CI ⇒ MSE Helmut 2014-12-14 01:51
        
        Reference for CI ⇒ MSE mreyes 2015-02-19 19:50
        
        Failed study: power <80%! Helmut 2015-02-20 19:09
        
        Failed study: power <80%! mreyes 2015-02-23 17:07
        
        Reported 99.98%, correct 1.4% Helmut 2015-02-23 17:38
        
        Reported 99.98%, correct 1.4% ElMaestro 2015-02-23 17:51
        
        GMR ∉ AR ⇒ power <5% Helmut 2015-02-24 01:33
        
        GMR ∉ AR ⇒ power <5% mreyes 2015-02-24 17:34