# Bioequivalence and Bioavailability Forum

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sudy
Junior

India,
2018-04-07 11:22

Posting: # 18651
Views: 508

## Tmax Analysis [Nonparametrics]

Dear All,

I have a discussion point for Tmax analysis using NP test.

I have calculated the significant p-value for Tmax on replicate data (T R T R) by splitting in T1 R1 and T2 R2. Diffecrence1= T1-R1 and Diffecrence2= T2-R2. I have used NP test on these differences.

First is it a correct approach logically?

As i assume, tmax is nothing but a one of the protocol time point, not a derived data. So i did not calculated the average of T1&T2 and R1&R2 = T-R.

Second, i am getting p-value significant. How to interpret the data then?
I have used total 80 subjects; out of these 60 subjects have tmax value same for both Test and reference (i.e. T1 R1 and T2 R2). As a result, differences are zero for 60 subjects.

NP test was performed by using wilcoxon signed rank test, so no rank will be assigned to these 60 subjects as their diff are zero. Only 20 subjects have non-zero value and are very much vary from each other, due to this i am getting p-value significant.

From data, my 60 out of 80 subject have Tmax value of test product similar to reference. This is good actually. But from NP test, p-value is significant. How to handle this case?
Is there any guideline recommendation?

Regards,
Sudy

mittyri
Senior

Russia,
2018-04-09 19:44

@ sudy
Posting: # 18657
Views: 341

## Tmax Analysis

Hi Sudy,

» I have calculated the significant p-value for Tmax on replicate data (T R T R) by splitting in T1 R1 and T2 R2. Diffecrence1= T1-R1 and Diffecrence2= T2-R2. I have used NP test on these differences.
»
» First is it a correct approach logically?

I didn't get the reason of splitting by replicate.
I would follow one of the methods explained here by Detlew. Note that exact tests are preferred due to ties.

Kind regards,
Mittyri
sudy
Junior

India,
2018-04-20 14:15

@ mittyri
Posting: # 18708
Views: 124

## Tmax Analysis

» I didn't get the reason of splitting by replicate.
» I would follow one of the methods explained here by Detlew. Note that exact tests are preferred due to ties.

Hi Mittyri,

I have splitted in two parts, as i already explained, Tmax of test and tmax of reference is not a generated data, it ia one of the protocol defined time points, So logically we have to compare tmax of test to reference. If i take the average of T&T and R&R, the resulted value will not give a clearity about Tmax of formulations.

Second i case of ties, logically we can prove the similarity in terms of Tmax for test and Referecne. But statistically, it will give significant p-value, which means there is a difference. This diffecenre is due to non-ties values. So how to justify. Actually, we can not say there is a significant difference in tmax.

Thanks

mittyri
Senior

Russia,
2018-04-21 13:58

@ sudy
Posting: # 18713
Views: 80

## Tmax Analysis

Hi Sudy,

» If i take the average of T&T and R&R, the resulted value will not give a clearity about Tmax of formulations.

OK, do you think splitting to T1 and T2 and comparing to R1 and R2 is more reasonable method?
Why are you comparing T1 to R1 and not to R2? Or would you compare all 4 combinations? What if some will say 'no difference' and one will say 'there's a difference'?
If you do not want to go with average since that kinda 'parametric' then switch to method 2 described in the link above

» Second i case of ties, logically we can prove the similarity in terms of Tmax for test and Referecne. But statistically, it will give significant p-value, which means there is a difference. This diffecenre is due to non-ties values. So how to justify. Actually, we can not say there is a significant difference in tmax.

For me logically means statistically proven. If you cannot justify the abscence of difference scientifically then it's just 'a feeling', not logic.
So please explain why don't you want to check the difference with one of the methods described in peer-reviewed papers from the link?

Kind regards,
Mittyri
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