In bioavailability and bioequivalence studies, the pharmacokinetic parameters (AUC, Cmax) are often assumed to follow the log normal distribution. Further about log-normal distribution.
Saturday, July 05, 2008
Geometric Statistics, geometric CV, intra-subject variation
The common technique is to calculate the geometric statistics (geometric mean, geometric CV and geometric SD). Notice that the geometric CV is independent of the geometric mean (unlike the arithmetic CV which is dependent on the arithmetic mean) and the geometric CV is used in the sample size calculation. When calculating the geometric statistics, the data in original scale is log-transformed, then anti-log to transform back.
In crossover design, the geometric CV can be estimated from the mixed model and is used to gauge the intra-subject variation. Geometric CV = sqrt(exp(std^2)-1) or CV=sqrt(exp(variance)-1) where the std^2 is estimated by the MSE. Variance is from ODS ‘CovParms’ table of SAS PROC MIXEd. Another variation is inter-subject CV and the std^2 is estimated by the variance estimate for the random subject effect from the proc mixed procedure.
It should be cautioned that Geometric CV sometimes is just being called CV or intra-subject variability. I heard that some large pharmaceutical companies include 'intra-subject variability' in the standard data presentation for pharmacokinetic parameters.
The topic about the CV, geometric CV was discussed in Boomer.org (http://www.boomer.org/pkin/PK06/PK2006512.html), a discussion mailing list on bioavailability and bioequivalences. Boomer.org used to be a great resource for PK-related discussion. However, recently the discussion group was dominated by a lot of the junkies posted by Indian guys. I guess it is because of the booming generic drug development industry in India.