## Phoenix WinNonlin Crossover object for Tmax test [Nonparametrics]

Dear 0521,

» Dear Helmut Schütz,

Not interested in other opinions?

» I read the "The Use Of Non-Parametric Methods In The Statistical Analysis" document（PMID: 4556704）

Good start!

» 1. Determine if the P value of the sequence is greater than 0.05,

It depends on the significance level you've chosen (p). WNL cannot do that for you.

» 2. If the P value of the sequence is less than 0.05, the test of "Treatment" cannot be performed.

I would follow the text of the article you referred:

Corresponding sequence test (unequal carry-over) in ANOVA couldn't be a reason for analysis interruption. Likely unequal carryover doesn’t exist in a properly designed study (sufficiently long washout), hence false positives could happen.

» 3. If the P value of the sequence is greater than 0.05, it is judged whether the P value of the treatment is greater than 0.05.

» 4. If the P value of the Treatment is greater than the equivalent, otherwise it is not equivalent.

Significant != not Equivalent and vice versa! That's why we are using confidence intervals, not p-values in our BE decisions.

» 5. If the P value of the sequence and the P value of the Period are both greater than 0.05, a sign test can be used instead of the rank sum test used in the above steps.

You omit

Yes, it could, but WNL does the trick with 3.4:

Using the p-values from the Effects sheet is the same as using p-values from ANOVA: good exploratory analysis without any credible conclusions regarding bioequivalence.

It is better to compare CIs to some reference limits as Helmut noted here.

» Dear Helmut Schütz,

Not interested in other opinions?

» I read the "The Use Of Non-Parametric Methods In The Statistical Analysis" document（PMID: 4556704）

Good start!

» 1. Determine if the P value of the sequence is greater than 0.05,

It depends on the significance level you've chosen (p). WNL cannot do that for you.

`no sequence effect (or drug residual effect) `

in WNL terminology.» 2. If the P value of the sequence is less than 0.05, the test of "Treatment" cannot be performed.

`No treatment effect given no sequence effect`

in WNL terminology.I would follow the text of the article you referred:

`Finally, it is appropriate to note here that if the residual effects cannot be deleted from the model, then the test procedures described in section 3.2 and 3.3 are no longer valid`

Corresponding sequence test (unequal carry-over) in ANOVA couldn't be a reason for analysis interruption. Likely unequal carryover doesn’t exist in a properly designed study (sufficiently long washout), hence false positives could happen.

» 3. If the P value of the sequence is greater than 0.05, it is judged whether the P value of the treatment is greater than 0.05.

» 4. If the P value of the Treatment is greater than the equivalent, otherwise it is not equivalent.

Significant != not Equivalent and vice versa! That's why we are using confidence intervals, not p-values in our BE decisions.

» 5. If the P value of the sequence and the P value of the Period are both greater than 0.05, a sign test can be used instead of the rank sum test used in the above steps.

You omit

`3.3 Testing the equality of period effects when residual effects are absent`

3.4 Testing the equality of direct effects and residual effects simultaneous

(`[no period effect given no sequence effect] and [no treatment and no sequence effect]`

in WNL terminology)Yes, it could, but WNL does the trick with 3.4:

`Since the bivariate Wilcoxon test requires only an ordinal scale for ranking across subjects, it should be used instead of the sign test for general situations in which residual and/or period effects are unequal and within subject linear functions are invalid.`

Using the p-values from the Effects sheet is the same as using p-values from ANOVA: good exploratory analysis without any credible conclusions regarding bioequivalence.

It is better to compare CIs to some reference limits as Helmut noted here.

—

Kind regards,

Mittyri

Kind regards,

Mittyri

### Complete thread:

- Question：Using Phoenix WinNonlin Crossover object for Tmax test - 0521, 2018-11-09 07:02 [Nonparametrics]
- Phoenix WinNonlin Crossover object for Tmax test - mittyri, 2018-11-11 00:21
- Phoenix WinNonlin Crossover object for Tmax test - 0521, 2018-11-11 10:56
- Tmax Hypothesis testing - mittyri, 2018-11-11 23:21
- Tmax Hypothesis testing - 0521, 2018-11-12 07:15
- neglecting periods for Tmax - mittyri, 2018-11-16 22:52

- Tmax Hypothesis testing - 0521, 2018-11-12 07:15

- Tmax Hypothesis testing - mittyri, 2018-11-11 23:21

- Phoenix WinNonlin Crossover object for Tmax test - 0521, 2018-11-11 10:56

- Phoenix WinNonlin Crossover object for Tmax test - mittyri, 2018-11-11 00:21