Study conduct in groups [Design Issues]
Hi Felipe,
Probably a misunderstanding. The biostatistician was prolly thinking loud: The need for dosing in groups arise when you cannot dose all subjects in the same time/day.
Those are not considered big deals either, but it also comes down to who's judging your dossier.
In (average) BE you test the null hypothesis:
Test differs from Ref.
In contrast, when you look at an ANOVA with all its impressive P-values they are test of other null hypotheses:
Test equals Ref.
Sequence TR equal Sequence RT.
Period 1 equals Period 2.
Subjects 1 equals Subject 2 equals .... subject N.
Group 1 equals Group 2.
All these tests are interesting and look like advanced science. They don't deal so much with the important issue at hand.
The real BE null hypothesis just requires the two treatment effects as the residual variance. All these three come from the model fit, not from the anova, although you'll often see it explained wrongly in certain books or guidelines. Simply stated you do (well, should) not really need an ANOVA to judge bioequivalence.
Note an important pitfall related to the above: When you look at an ANOVA with a significant treatment effect, then you are rejecting the null hypothesis Test equals Ref, but this doesn't say anything definitive about your acceptance or rejection of the null hypothesis: Test differs from Ref.
The reason is the equivalence margin.
Finally, group is a between-factor. It does not affect the residual variance if the model is specified correctly.
I hope this helps.
❝ Once I have questioned the same inclusion of group effect analysis and the biostat said that this effect could appear when you cannot give the treatments to whole sample size at the same time/day. (statement 1)
Probably a misunderstanding. The biostatistician was prolly thinking loud: The need for dosing in groups arise when you cannot dose all subjects in the same time/day.
❝ However group effect is not a big deal such as sequence, treatment or period effect. (statement 2)
Those are not considered big deals either, but it also comes down to who's judging your dossier.
In (average) BE you test the null hypothesis:
Test differs from Ref.
In contrast, when you look at an ANOVA with all its impressive P-values they are test of other null hypotheses:
Test equals Ref.
Sequence TR equal Sequence RT.
Period 1 equals Period 2.
Subjects 1 equals Subject 2 equals .... subject N.
Group 1 equals Group 2.
All these tests are interesting and look like advanced science. They don't deal so much with the important issue at hand.
The real BE null hypothesis just requires the two treatment effects as the residual variance. All these three come from the model fit, not from the anova, although you'll often see it explained wrongly in certain books or guidelines. Simply stated you do (well, should) not really need an ANOVA to judge bioequivalence.
Note an important pitfall related to the above: When you look at an ANOVA with a significant treatment effect, then you are rejecting the null hypothesis Test equals Ref, but this doesn't say anything definitive about your acceptance or rejection of the null hypothesis: Test differs from Ref.
The reason is the equivalence margin.
Finally, group is a between-factor. It does not affect the residual variance if the model is specified correctly.
I hope this helps.
—
Pass or fail!
ElMaestro
Pass or fail!
ElMaestro
Complete thread:
- Study conduct in groups Smitha 2015-02-02 04:21 [Design Issues]
- Study conduct in groups ElMaestro 2015-02-02 08:21
- Study conduct in groups Helmut 2015-02-02 13:08
- Study conduct in groups Smitha 2015-02-04 04:30
- Study conduct in groups Helmut 2015-02-04 12:57
- Study conduct in groups felipeberlinski 2015-02-04 22:36
- Study conduct in groupsElMaestro 2015-02-04 23:58
- Significant ≠ relevant Helmut 2015-02-05 00:49
- Significant ≠ relevant Astea 2016-03-24 20:10
- Significant ≠ relevant ElMaestro 2016-03-24 23:12
- Significant ≠ relevant zizou 2016-03-25 21:41
- Loss of power etc. Helmut 2016-03-26 14:46
- Loss of power etc. Astea 2016-03-27 21:18
- Loss of power etc. zizou 2016-03-27 23:44
- Combined power? Helmut 2016-03-28 14:29
- Loss of power etc. Astea 2016-03-28 23:57
- Loss of power etc. ElMaestro 2016-03-29 00:16
- Mystery Helmut 2016-03-29 17:28
- Back to the Future Astea 2016-03-29 21:57
- Back to the Future ElMaestro 2016-03-29 23:11
- Using lectures != Reading them mittyri 2016-03-30 00:17
- Back to the Future ElMaestro 2016-03-29 23:11
- Back to the Future Astea 2016-03-29 21:57
- Loss of power etc. Helmut 2016-03-26 14:46
- Significant ≠ relevant Astea 2016-03-24 20:10
- Study conduct in groups felipeberlinski 2015-02-04 22:36
- Study conduct in groups Helmut 2015-02-04 12:57
- Study conduct in groups Smitha 2015-02-04 04:30