Factors influence in Anova [General Sta­tis­tics]

posted by Helmut Homepage – Vienna, Austria, 2015-11-05 20:33 (3386 d 07:40 ago) – Posting: # 15617
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Hi BE-proff,

❝ […] ANOVA assesses influence of different factors (subjects, treatment, period, sequence) on variation of PK-parameters.


OK; you are talking about a crossover.

❝ In my practice only subjects have always had significant impact on variation.


Anything else would be a big surprise. Subjects are different indeed.

❝ What can be reasons for signficant influence of treatment, period and sequence? ;-)


Treatment
Happens if the the CV is smaller + the T/R is more far away from 100% than assumed in study planning; the con­fi­dence interval does not include 100%. Reasons: The formulation and/or the study planning (over­powered?)Period
Doesn’t matter at all. Since both R and T are affected to the same degree, true differences will mean out. Try it: Take one of your datasets and multiply all results of the second period by 1,000. The PE and CI of T/R will be exactly the same like in the original dataset. Of course the period effect comes out highly sig­ni­fi­cant. Reasons: Generally unknown (subjects more relaxed in the 2nd period, lunar phase, thunderstorm, broken AC, whatsoever).

Sequence
Better called unequal carryover. It essentially means that subject’s PK response might be different if they receive formulations in the order RT as compared to the order TR. Tricky. If there would be a true sequence effect we cannot get an unbiased estimate of the treatment effect (technically these effects are “con­founded”). That’s bad.For references see this post. The EMA learned the lesson:

A test for carry-over is not considered relevant and no decisions regarding the ana­ly­sis (e.g. analysis of the first period only) should be made on the basis of such a test. The potential for carry-over can be directly addressed by examination of the pre-treatment plasma concentrations in period 2 (and beyond if applicable).


❝ Is it bad or not? :confused:


Define bad.

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