Bioequivalence and Bioavailability Forum

Geometric mean and CV [Power / Sample Size]

posted by Helmut  – Vienna, Austria, 2019-09-06 02:15 (1687 d 23:28 ago) – Posting: # 20546
Views: 6,391

Hi Rocco,

❝ […] is it even reasonable to use the geometric CV for the reference? Isn’t the CV you want to input into a sample calculation the CV corresponding to the difference of the Test and Reference? Since you do not have the Test group here, I am a bit confused as to what using the geometric CV of only the reference tells you. In your slides, you have a lone that says “if you have only mean and sd of the reference, a pilot study is unavoidable.”

❝

❝ What am I missing?

Oh dear, my slides always give only half of the picture (my is missing)…
Let’s start from a 2×2×2 crossover. We have the within-subject variabilities of T and R (CV_wT and CV_wR). Since this is not a replicate design, they are not accessible and pooled into the common CV_w.¹ One of the assumptions in ANOVA are identical variances. If they are not truly equal (say CV_wT < CV_wR) the CI is inflated: The “good” T is punished by the “bad” R.
Similar in a parallel design. You can assume that CV_wT = CV_wR and CV_bT = CV_bR and therefore, use the (pooled, total) CV_p of your FIM study. Here it is the other way ’round (you have the CV_p of R). If the CV of T is higher, bad luck, power compromised. If both are ~ equal, fine. If it is lower, you gain power. There is no free lunch.
If you are cautious: Pilot study or a Two-Stage-Design.² For the latter I recommend the function power.tsd.p() of package Power2Stage for . A reasonable stage 1 sample size is ~80% of what you estimate with sampleN.TOST(alpha=0.05...) of package PowerTOST and the CV_p of your FIM.

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1. Of course, the same holds for between-subject variabilities: CV_bT and CV_bR pooled to CV_b.
   
2. Fuglsang A. Sequential Bioequivalence Approaches for Parallel Design. AAPS J. 2014; 16(3):373–8. doi:10.1208/s1224801495711. Open access.

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Helmut Schütz


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Complete thread:

• Input for CV when small first-in-man has been run Rocco_M 2019-09-03 18:45 [Power / Sample Size] 
  • Geometric mean and CV Helmut 2019-09-05 14:05
    • Geometric mean and CV Rocco_M 2019-09-05 23:49
      • Geometric mean and CVHelmut 2019-09-06 00:15
        • Geometric mean and CV Rocco_M 2019-09-06 17:49
          • Geometric mean and CV Helmut 2019-09-06 18:15
            • Geometric mean and CV ElMaestro 2019-09-06 19:03
              • Geometric mean and CV Helmut 2019-09-07 09:57
                • Geometric mean and CV Rocco_M 2019-09-09 13:31
                  • Assumptions… Helmut 2019-09-09 14:09
                    • Assumptions… Rocco_M 2019-09-09 16:35
                      • Assumptions… Helmut 2019-09-09 17:19
                        • Assumptions… Rocco_M 2019-09-13 21:28
                          • t-test & Welch-test Helmut 2019-09-14 00:16
                            • sampleN.TOST and CI.BE Rocco_M 2019-09-17 22:02
                              • assumptions vs. realizations Helmut 2019-09-18 11:04