Bioequivalence and Bioavailability Forum

❝ Not interested in other opinions?

Thank you very much for your reply, I welcome anyone to reply to this post.

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

❝ Good start!

This paper is a reference to the Crossover object in the WinNonlin User Guide.

So I think I should follow the paper to interpret the results of the WinNonlin Crossover object.

❝ ❝ 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.

I assume that the significance level is 0.05.

❝ no sequence effect (or drug residual effect) in WNL terminology.

Does the first row of the effects sheet not indicate a test for sequence effects?

❝ ❝ 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.

Does the second row of the effects sheet not indicate a test for treatment effects?

❝ 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if the residual effects cannot be deleted from the model, then the test procedures described in section 3.2 and 3.3 are no longer valid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.

Although I also think that the residual effect can not be used as a reason for the interruption test,
However, for this paper, 3.2 and 3.3 depend on 3.1, and only after the 3.1 test is passed, the tests of 3.2 and 3.3 can be performed.

❝ ❝ 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.

I agree.

Do you want to tell me this:
1. In the effect sheet, the P value judgment of the Treatment is independent of the sequence and the period.
2. All P values in the effect sheet are only statistically significant. The P value has no substantial clinical significance and should not be overly concerned. We should pay more attention to the results in the Confidence Intervals sheet.
3. For the effect sheet, we should pay attention to whether the median of Treatment_Diff_( T - R ) has clinical significance.

Other questions:
1. For the nonparametric test of Tmax, is the only way to calculate the P value using "Mann–Whitney U test"?
2. For the non-parametric test of Tmax, can we use the "Wilcoxon signed rank test" to calculate the P value?
3. For the effect sheet, is the "Conclusion_Diff_(T - R)" confidence interval "0" necessary?

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Edit: Full quote removed. Please delete everything from the text of the original poster which is not necessary in understanding your answer; see also this post #5! [Mittyri]