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

Dear Detlew!

» But the most interesting part of my letter:

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» Can't imagine BE studies where this is not true, …

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

» … 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)?

» Too naïvely may be true .

» 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.

*not*a reasonable effect?» Too naïvely may be true .

*Alter schützt vor Torheit nicht.*—

Helmut Schütz

The quality of responses received is directly proportional to the quality of the question asked. 🚮

Science Quotes

*Dif-tor heh smusma*🖖Helmut Schütz

The quality of responses received is directly proportional to the quality of the question asked. 🚮

Science Quotes

### Complete thread:

- Potvin C in the EU Helmut 2013-04-16 17:40
- Potvin C in the EU ElMaestro 2013-04-17 02:31
- Potvin C in the EU Helmut 2013-04-17 12:23
- 2 Groups model FDA d_labes 2013-04-17 13:10
- 2 Groups model FDA Helmut 2013-04-17 16:37
- Group effects obsolete? d_labes 2013-04-18 09:55
- Group effects FDA/EMAHelmut 2013-04-19 14:34
- Group effects FDA/EMA mittyri 2014-08-21 15:34
- Group effects FDA/EMA ElMaestro 2014-08-21 17:31
- Group effects EMA mittyri 2014-10-01 11:25
- Group effects EMA ElMaestro 2014-10-01 11:31
- Group effects EMA Helmut 2014-10-01 13:24
- Group effects EMA VStus 2016-10-06 22:06
- Group effects EMA ElMaestro 2016-10-07 12:45
- Group effects EMA mittyri 2016-10-07 15:06
- Fixed effects model with Group term mittyri 2016-10-09 13:27
- Fixed effects model: changing the F, p values mittyri 2016-10-10 18:33
- Fixed effects model: changing the F, p values ElMaestro 2016-10-10 20:10
- Fixed effects model: changing the F, p values Helmut 2016-10-11 00:17
- Holy War of type III d_labes 2016-10-11 13:17
- Significance of Group effect in Russia: why the type III is so 'important' mittyri 2016-10-11 15:07

- Fixed effects model: changing the F, p values zizou 2016-10-11 01:06
- FDA group model in R mittyri 2016-10-11 13:43
- FDA group model in R ElMaestro 2016-10-12 01:07
- FDA group model in R VStus 2016-10-17 15:32
- FDA group model in R ElMaestro 2016-10-17 18:58
- FDA group model in R VStus 2016-10-20 13:57

- FDA group model in R ElMaestro 2016-10-17 18:58

- FDA group model in R mittyri 2016-10-11 13:43

- Fixed effects model: changing the F, p values ElMaestro 2016-10-10 20:10
- Fixed effects model with Group term VStus 2016-10-20 13:54

- Fixed effects model: changing the F, p values mittyri 2016-10-10 18:33

- Fixed effects model with Group term mittyri 2016-10-09 13:27

- Group effects EMA mittyri 2016-10-07 15:06

- Group effects EMA ElMaestro 2016-10-07 12:45

- Group effects EMA VStus 2016-10-06 22:06

- Group effects FDA/EMA zizou 2016-12-31 02:54
- Group effects FDA/EMA Helmut 2017-06-03 14:57

- Group effects EMA mittyri 2014-10-01 11:25

- Group effects FDA/EMA ElMaestro 2014-08-21 17:31

- Group effects FDA/EMA mittyri 2014-08-21 15:34

- Group effects FDA/EMAHelmut 2013-04-19 14:34
- 2 Groups model FDA hiren379 2013-08-22 14:32
- Homework Helmut 2013-08-23 11:53

- Group effects obsolete? d_labes 2013-04-18 09:55

- 2 Groups model FDA Helmut 2013-04-17 16:37

- 2 Groups model FDA d_labes 2013-04-17 13:10

- Potvin C in the EU Helmut 2013-04-17 12:23

- Potvin C in the EU ElMaestro 2013-04-17 02:31