Bioequivalence and Bioavailability Forum

CVtotal ≠ CVintra + CVinter [Power / Sample Size]

posted by Helmut  – Vienna, Austria, 2015-05-15 15:05 (4050 d 18:27 ago) – Posting: # 14827
Views: 14,318

Hi John John,

❝ In a bioavailability study with six healthy volunteers:

I would never plan a pivotal study based on results of such a small pilot – especially if the variability is high. Let’s assume a CV of 30%. From six subjects we can calculate a confidence interval of the CV with 18–102%. Not meaningful.

❝ ...(Cmax; range 135–422 ng ml^-') and time to maximum (tmax; range 1.5–7.0 h) for the three tablet doses showed significant differences between subjects (P <0.009; between subject coefficients of variation (CVs) 34% and 27%, respectively). There were no within subject differences in C, (P = 0.32; mean within subject CV 11%

The quoted text leaves many questions open. I guess it was a crossover. Significant differences between subjects… Why report this at all? Since we know that results come from different sub­jects, this effect will  always  likely be significant.
Two values for CV_inter? How were those calculated? From the ANOVA you get only one. Some people use the (arithmetic!) SD/mean of treatments (like in the crappy paper above). Has nothing to do with the ANOVA on log-transfomed data.

❝ To calculate the sample size for a parallel study I use the total CV= 45?

No way! CVs are not additive (CV_pooled ≠ CV_intra + CV_inter). See the methylphenidate example from this post.

  MSe      MSs   CVintra CVinter CVpooled
0.004882 0.07675 7.00%   19.1%   20.4%

❝ or do I need the pooled variability?

Yes.

❝ Which is?

Not the slightest idea. Not accessible from what you posted. You need either the complete ANOVA or the raw data.

—
Dif-tor heh smusma 🖖🏼 Довге життя Україна! 
Helmut Schütz


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Complete thread:

• Extrapolation john john 2015-05-13 13:36 
  • CVinter (or CVtotal) from CVintra Helmut 2015-05-13 14:33
    • CVinter (or CVtotal) from CVintra nobody 2015-05-13 14:53
      • OT: Drug Res Helmut 2015-05-13 15:11
        • OT: Drug Res nobody 2015-05-13 15:18
          • completely OT Helmut 2015-05-13 15:29
            • completely OT nobody 2015-05-13 15:37
    • CVinter (or CVtotal) from CVintra john john 2015-05-14 12:16
      • CVtotal ≠ CVintra + CVinterHelmut 2015-05-15 13:05
        • CVtotal ≠ CVintra + CVinter john john 2015-05-15 13:13
          • CVtotal ≠ CVintra + CVinter Helmut 2015-05-15 13:14
            • CVtotal ≠ CVintra + CVinter john john 2015-05-15 13:50
              • CVtotal ≠ CVintra + CVinter Helmut 2015-05-15 14:07
                • CVtotal ≠ CVintra + CVinter john john 2015-05-15 15:07
                  • CVtotal ≠ CVintra + CVinter Helmut 2015-05-15 15:10