AngusMcLean ★★ USA, 20150516 17:11 (1989 d 04:45 ago) Posting: # 14840 Views: 5,706 

Phoenix WinNonlin 6.4 provides a routine for statistical comparison of Tmax from a 2 way crossover study (Latin Square, 2 periods, 2 sequences) as a nonparametric parameter and confidence intervals are provided. I do not see intrasubject and intersubject variances in the output and I have just made a post to the Pharsight site regarding this. For bioequivalence of Cmax and AUC pamameters intrasubject and intersubject variance is provided. So I am thinking how to obtain analogous information on Tmax parameter for a twoway crossover study. I wonder if anyone has done this. Angus Edit: Category changed. [Helmut] 
Helmut ★★★ Vienna, Austria, 20150516 18:50 (1989 d 03:07 ago) @ AngusMcLean Posting: # 14841 Views: 4,888 

Hi Angus, » Phoenix WinNonlin 6.4 […] I do not see intrasubject and intersubject variances… Parameters (like the mean & variance) define parametric statistics (hence, the name). Since this test is nonparametric, variance(s) don’t exist. Don’t get confused by PHX’s output, which gives also the median of test and reference. The PE of TR is not the difference of these medians. The test calculates all pairwise differences. Their median is called the HodgesLehmann estimator; the CI is calculated according to Moses^{1,2} (see also this thread). You will also notice that the CI is rarely symmetrical around the PE. If you want to dive deeper into the matter:
— Diftor heh smusma 🖖 Helmut Schütz The quality of responses received is directly proportional to the quality of the question asked. 🚮 Science Quotes 
AngusMcLean ★★ USA, 20150516 19:57 (1989 d 01:59 ago) @ Helmut Posting: # 14842 Views: 4,786 

Thanks Helmut: I will look at that paper. What we are seeking is a measure of the variability of the Tmax paramater in the test formulation and the variability of the Tmax parameter in the reference formulation. The data comes from a crossover design. In the absence of a distribution. One can do a frequency plot and a percentile analysis and simply compare to see if one is less variable than the other................ Angus 
Helmut ★★★ Vienna, Austria, 20150517 00:33 (1988 d 21:23 ago) @ AngusMcLean Posting: # 14843 Views: 4,836 

Hi Angus, » What we are seeking is a measure of the variability of the Tmax paramater in the test formulation and the variability of the Tmax parameter in the reference formulation. OK. » In the absence of a distribution. <nitpick> In the absence of a distribution defined by mean/variance. » One can do a frequency plot and a percentile analysis and simply compare to see if one is less variable than the other… Given the limited sample size in BE studies a histogram doesn’t tell too much. I would rather go with box plots categorized for treatments. Sometimes easier to interpret – especially if you have more than two treatments. — Diftor heh smusma 🖖 Helmut Schütz The quality of responses received is directly proportional to the quality of the question asked. 🚮 Science Quotes 