## Non-parametric N [Power / Sample Size]

Hi Alex,

That’s black magick. Why 15%?

No idea. In the EMA’s bracketing approach you perform a Non-Superiority test with an upper margin of 1.25. All of this stuff (including BE) is not related to the therapeutic range at all.

Even then it’s not an easy job.

Yes.

Likely. But as I wrote before: Under the premise of no saturable pre-systemic metabolism.

No idea. Once you have the result of a pilot, consider a scientific advice. Sweden?

❝ So we would calculate our N based on a non-parametric test for T-max differences (I have heard some epidemologists saying its ok to calculate with T-Test and increase like 15%)

That’s black magick. Why 15%?

- If (if!) the distribution is normal, the Wilcoxon signed-rank test (for paired differences) and the Mann–Whitney
*U*test (for independent samples) have an asymptotical power of \(\small{3/\pi\approx95.5\%}\).

- If the distribution is
*not*normal (*e.g.*,*t*_{max}), power of nonparametric tests are*higher*than the ones of the corresponding*t*-tests.

❝ Kind of related, I guess no concern exists about the almost sure increase in Cmax if it doesnt go beyond the therapeutic range inst it?

No idea. In the EMA’s bracketing approach you perform a Non-Superiority test with an upper margin of 1.25. All of this stuff (including BE) is not related to the therapeutic range at all.

❝ Not possible to calculate N for Tmax but to perform certain simulations with some parameters.

Even then it’s not an easy job.

❝ So better to run a pilot without and seein what comes?

Yes.

❝ if you are right Tmax will come sooner (with a higher Cmax).

Likely. But as I wrote before: Under the premise of no saturable pre-systemic metabolism.

❝ Would it support a SmPC change?

No idea. Once you have the result of a pilot, consider a scientific advice. Sweden?

—

Helmut Schütz

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*Dif-tor heh smusma*🖖🏼 Довге життя Україна!_{}Helmut Schütz

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### Complete thread:

- N calculation for trial about PK superiority alejandro_jo1990 2022-09-01 14:40 [Power / Sample Size]
- Bracketing approach Helmut 2022-09-01 15:02
- SmPC change is the whole thing alejandro_jo1990 2022-09-01 16:18

- N calculation for trial about PK superiority dshah 2022-09-02 11:52
- The efocus is faster absorption alejandro_jo1990 2022-09-02 18:57
- The efocus is faster absorption Helmut 2022-09-03 00:46
- Non-parametric N alejandro_jo1990 2022-09-06 00:26
- Non-parametric NHelmut 2022-09-06 17:02
- Non-parametric N alejandro_jo1990 2022-09-15 14:56

- Non-parametric NHelmut 2022-09-06 17:02

- Non-parametric N alejandro_jo1990 2022-09-06 00:26

- The efocus is faster absorption Helmut 2022-09-03 00:46

- The efocus is faster absorption alejandro_jo1990 2022-09-02 18:57

- Bracketing approach Helmut 2022-09-01 15:02