Let’s forget the Group-by-Treatment interaction, please! [Regulatives / Guidelines]
❝ Your opinion is very important for Russian BEBAC amateurs, so I'm expecting your approach will be 'carved in Russian stone'
If they are following the forum (are they?) I want to make one point clear:
I do not advocate routinely using the group procedures of the FDA!
On the contrary, all criteria for not using them are usually fulfilled (i.e., the simple model of pooled data can be used).

I would say that the EMA accepts without reservation that the group effect “cannot be reasonably assumed to have an effect on the response variable.”
❝ ❝ The nasty thing is that the Group-by-Treatment interaction test has low power (therefore, testing at the 0.1 level). You should expect a false positive rate at the level of the test …
❝
❝ Could you please clarify this point? I saw many times the problem of power for Sequence term for simple model …
Senn1 (who always strongly argued against testing the sequence – or better unequal carryover – effect!) writes:
Because the power of the test is low, being based on between-patient difference, a high nominal level of significance (usually 10%) is used.
An interesting statement by the EMA2 concerning the treatment by covariate interaction:The primary analysis should include only the covariates pre-specified in the protocol and no treatment by covariate interaction terms. […] Tests for interactions often lack statistical power and the absence of statistical evidence of an interaction is not evidence that there is no clinically relevant interaction. Conversely, an interaction cannot be considered as relevant on the sole basis of a significant test for interaction. Assessment of interaction terms based on statistical significance tests is therefore of little value [sic].
(my emphases)❝ … and Group-by-Treatment interaction for FDA model I. Is it possible to prove that with sims? Or somebody did this work analytically?
Don’t know. I’m in contact with a Canadian CRO to collect empiric evidence (like D’Angelo et al.3 did for carryover). We will include only studies where groups were separated by just a couple of days and all of the FDA’s criteria for pooling were fulfilled. A great deal of work but seemingly ~⅒ of studies show a significant group-by-treatment interaction.

❝ I suspect a lot of fun with replicate designs. Your model specification with group […] works well even there, but it doesn't mean that this model is applicable for replicate designs (as we discussed elsewhere).
Yep.
- Senn S. Crossover Trials in Clinical Research. Chichester: Wiley; 2nd ed. 2002. p. 58.
- EMA. Guideline on adjustment for baseline covariates in clinical trials. London: 26 February 2015. EMA/CHMP/295050/2013.
- D’Angelo G, Potvin D, Turgeon J. Carryover effects in bioequivalence studies. J Biopharm Stat. 2001; 11(1–2): 35–43. doi:10.1081/BIP-100104196.
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
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Helmut Schütz
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The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes
Complete thread:
- Russian «Экспертами» and their hobby Helmut 2017-04-29 00:46 [Regulatives / Guidelines]
- Low power of Group-by-Treatment interaction mittyri 2017-04-29 22:57
- Let’s forget the Group-by-Treatment interaction, please!Helmut 2017-04-30 13:54
- Let’s forget the Group-by-Treatment interaction, please! ElMaestro 2017-05-01 16:19
- Some answers Helmut 2017-05-02 01:10
- Some answers ElMaestro 2017-05-02 09:04
- Example Helmut 2017-05-02 12:35
- Sensitivity of term? mittyri 2017-05-02 18:29
- Simulations Helmut 2017-05-05 14:38
- loosing specificity due to low sensitivity mittyri 2017-05-08 23:28
- loosing specificity due to low sensitivity Helmut 2017-05-09 00:55
- loosing specificity due to low sensitivity mittyri 2017-05-08 23:28
- Loss in power Helmut 2017-05-06 17:31
- Interval between groups Helmut 2017-05-08 19:02
- IMP handling mittyri 2017-05-08 23:40
- IMP handling Helmut 2017-05-09 01:08
- IMP handling mittyri 2017-05-08 23:40
- Loss in power Helmut 2017-05-14 17:22
- Simulations Helmut 2017-05-05 14:38
- Some answers ElMaestro 2017-05-02 09:04
- No convergence in JMP and Phoenix WinNonlin Helmut 2017-05-25 15:26
- Ouch?!??? ElMaestro 2017-05-25 16:24
- Some answers Helmut 2017-05-02 01:10
- Let’s forget the Group-by-Treatment interaction, please! ElMaestro 2017-05-01 16:19
- Let’s forget the Group-by-Treatment interaction, please!Helmut 2017-04-30 13:54
- Russian «Экспертами» and their hobby Artem Gusev 2017-05-02 16:13
- be careful with mixed models mittyri 2017-05-02 17:53
- be careful with mixed models Artem Gusev 2017-05-03 11:02
- p-value(s) in model 2 Helmut 2017-05-05 14:48
- be careful with mixed models mittyri 2017-05-02 17:53
- Russian «Экспертами» following the EEU GLs Helmut 2017-05-24 20:17
- Russian «Экспертами» following the EEU GLs Beholder 2017-05-24 22:37
- Penalty for carelessness mittyri 2017-05-25 08:52
- Russian «Экспертами» following the EEU GLs Beholder 2017-05-25 10:43
- Russian «Экспертами» following the EEU GLs Mikalai 2018-01-04 10:43
- Belarus = member of the EEU Helmut 2018-01-04 13:08
- Belarus = member of the EEU Mikalai 2018-01-04 19:49
- Trying your model for EEU mittyri 2018-01-04 22:04
- Trying your model for EEU Helmut 2018-01-05 00:06
- help us to stop it, please... Astea 2018-01-10 12:09
- help us to stop it, please... Beholder 2018-01-10 12:49
- regulators convinced by science? d_labes 2018-01-10 15:15
- regulators convinced by science? Beholder 2018-01-10 17:14
- Чёрт побери! d_labes 2018-01-10 18:53
- regulators convinced by science? Astea 2018-01-10 19:10
- regulators convinced by science? Beholder 2018-01-10 17:14
- help us to stop it, please... Astea 2018-01-10 12:09
- Trying your model for EEU Helmut 2018-01-05 00:06
- Belarus = member of the EEU Helmut 2018-01-04 13:08
- Russian «Экспертами» following the EEU GLs Beholder 2017-05-24 22:37
- Low power of Group-by-Treatment interaction mittyri 2017-04-29 22:57