Group effects FDA/EMA [Two-Stage / GS Designs]

posted by Helmut Homepage – Vienna, Austria, 2013-04-19 14:34  – Posting: # 10438
Views: 33,350

Dear Detlew!

» But the most interesting part of my letter:
» "If all of the following criteria are met, it may not be necessary to test for group effects in the model:
»
» the clinical study takes place at one site;
» all study subjects have been recruited from the same enrollment pool;
» all of the subjects have similar demographics; and
» all enrolled subjects are randomly assigned to treatment groups at study outset
»
» In this latter case, the appropriate statistical model would include only the factors Sequence, Period, Treatment and Subject(nested within sequence."
»
» Can't imagine BE studies where this is not true, …

Interestingly FDA’s Stat Guidance (Section VII.A.) states

If a crossover study is carried out in two or more groups of subjects […], the statistical model should be modified to reflect the multigroup nature of the study. In particular, the model should reflect the fact that the periods for the first group are different from the periods for the second group. This applies to all of the approaches (average, population, and individual BE) described in this guidance.

(my emphases)

» … except multi-center studies, but these are rare for BE evaluation.

Yep.

» So what? Group effects are a Chimera?

Probably. What about EMA’s BE GL (Section 4.1.8)?

The statistical analysis should take into account sources of variation that can be reasonably [sic] assumed to have an effect on the response variable.

Group = not a reasonable effect?

» Too naïvely may be true :-D.

Alter schützt vor Torheit nicht. ;-)

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Cheers,
Helmut Schütz
[image]

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