Moloko
☆

Russia,
2020-12-22 10:41
(26 d 20:35 ago)

Posting: # 22153
Views: 363

## Significant effects [General Sta­tis­tics]

Hi all,

Could somebody help me with my doubts about significant sequence/treatment/period
effects in BE study? I got the following anova results in 2x2x4 design:

                 DF Sum Sq Mean Sq      F   P-val sequence          1  0.558   0.558 10.269   0.002 period            3  0.566   0.189  3.472   0.021 treatment         1  0.075   0.075  1.384   0.244 sequence:subject 23  7.632   0.332  6.102  <0.001 residual         69  3.752   0.054

My СI-s are within the range of 80.000% - 125.000%, so formally BE acceptance criterion is met. But these p-values scare me...

I don't have much experience in BE and I think it is not good then period or sequence factor influences PK-parameter.

thanks!

Helmut
★★★

Vienna, Austria,
2020-12-22 15:27
(26 d 15:49 ago)

@ Moloko
Posting: # 22154
Views: 307

## Significant effects: Don’t worry, be happy!

Hi Moloko,

» Could somebody help me with my doubts about significant sequence/treatment/period
» effects in BE study?

Search the forum for sequence effect, treatment effect, and period effect. Lots of posts, references, etc.

» My СI-s are within the range of 80.000% - 125.000%, so formally BE acceptance criterion is met.

Excellent. Open a bottle of champagne.

» But these p-values scare me...
»
» I don't have much experience in BE and I think it is not good then period or sequence factor influences PK-parameter.
• Unless the the study was extremely imbalanced (say, almost all subjects in one sequence and the rest in the other), period effects mean out, since both T and R are affected to the same extent. Nothing to worry about.
• Sequence effects (actually unequal carry-over) can not be “corrected” by a statistical method – only avoided by design (sufficiently long washout). It was shown in a large meta-analysis that in properly designed studies a significant effect is seen in ~ the level of the test and hence, likely is a statistical artifact (false positive). Forget it.
• Even a significant treatment effect is not important. Only the CI-inclusion counts.
• The fact that subjects differ is trivial. Only if you don’t see a significant effect you should start to worry (monozygotic twins or triplets in the study?) because it would violate the assumption of independence.

Dif-tor heh smusma 🖖
Helmut Schütz

The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes
Moloko
☆

Russia,
2020-12-23 12:24
(25 d 18:52 ago)

@ Helmut
Posting: # 22158
Views: 265

## Significant effects: Don’t worry, be happy!

Helmut, thank you very much for response!

It seems like I couldn't find the correct keywords when searching for posts earlier..
So now I can immerse myself in reading