## Confuse a Cat Inc. [BE/BA News]

Hi Ohlbe,

» My gut feeling is that all they expect to get are descriptive statistics: report median Tmax for Test, median Tmax for Reference, …

So far so good. Standard for ages.

» … calculate a % difference (however inappropriate this may be), …

It is indeed.

» … pass if it is not more than 20%, otherwise fail.

That’s my understanding as well.

» Consequence: if you have more than 20% difference between sampling times around the expected Tmax, you're screwed if median Tmax values are different even by just one sampling time, …

Correct. IMHO, you need

» … even if this has strictly no clinical relevance (this could be brought up in the comments to the draft guideline: come on guys, are you sure a Tmax of 10' for one formulation and 15' for the other is really something totally unacceptable ?

Exactly. Recall what the almighty oracle stated in the BE-GL:

» I mean, even for tadalafil you should be able to keep yourself busy until it works).

Tadalafil shows an effect

Not by chance. It’s common that the time point of

» Range: no expectation described. No idea.

The range is completely useless. Like the mean it has a breakdown point of zero. Imagine with \(\small{n\rightarrow \infty}\): $$\small{\left\{R_1=1,\ldots, R_n=1\phantom{.25}\right\} \rightarrow \textrm{Range}(R)=0\phantom{.25}}\\\small{\left\{T_1=1,\ldots, T_n=1.25\right\} \rightarrow \textrm{Range}(T)=0.25}$$ Good luck in calculating a ratio.

» Of course I may be totally wrong.

So am I.

» My gut feeling is that all they expect to get are descriptive statistics: report median Tmax for Test, median Tmax for Reference, …

So far so good. Standard for ages.

» … calculate a % difference (however inappropriate this may be), …

It is indeed.

» … pass if it is not more than 20%, otherwise fail.

That’s my understanding as well.

» Consequence: if you have more than 20% difference between sampling times around the expected Tmax, you're screwed if median Tmax values are different even by just one sampling time, …

Correct. IMHO, you need

*equally*spaced intervals until absorption is essentially complete (in a one compartment model at least two times the expected*t*_{max}in all subjects) and

- likely narrower intervals than usual.

*t*_{max}will drive the sample size. How much larger will it have to be? Not the slightest idea. Likely*much*larger.» … even if this has strictly no clinical relevance (this could be brought up in the comments to the draft guideline: come on guys, are you sure a Tmax of 10' for one formulation and 15' for the other is really something totally unacceptable ?

Exactly. Recall what the almighty oracle stated in the BE-GL:

[…] if rapid release is claimed to be clinically relevant and of importance for onset of action or is related to adverse events, there should be no apparent difference in median t_{max} and its variability between test and reference product.

» I mean, even for tadalafil you should be able to keep yourself busy until it works).

Tadalafil shows an effect

*before**t*_{max}. So what?Not by chance. It’s common that the time point of

*E*_{max}is <*t*_{max}.» Range: no expectation described. No idea.

The range is completely useless. Like the mean it has a breakdown point of zero. Imagine with \(\small{n\rightarrow \infty}\): $$\small{\left\{R_1=1,\ldots, R_n=1\phantom{.25}\right\} \rightarrow \textrm{Range}(R)=0\phantom{.25}}\\\small{\left\{T_1=1,\ldots, T_n=1.25\right\} \rightarrow \textrm{Range}(T)=0.25}$$ Good luck in calculating a ratio.

» Of course I may be totally wrong.

So am I.

—

Helmut Schütz

The quality of responses received is directly proportional to the quality of the question asked. 🚮

Science Quotes

*Dif-tor heh smusma*🖖_{}Helmut Schütz

The quality of responses received is directly proportional to the quality of the question asked. 🚮

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### Complete thread:

- EMA: New product-specific guidances Helmut 2022-04-08 15:17 [BE/BA News]
- How would you implement it? ElMaestro 2022-04-09 11:45
- Confuse a Cat Inc. Helmut 2022-04-09 18:40
- Confuse a Cat Inc. ElMaestro 2022-04-09 21:47
- Confuse a Cat Inc. Ohlbe 2022-04-11 11:29
- So many questions, so few answers Helmut 2022-04-11 13:03
- Preliminary simulations Helmut 2022-04-30 14:59
- Preliminary simulations ElMaestro 2022-04-30 19:10
- Preliminary simulations Helmut 2022-05-01 15:56

- Preliminary simulations ElMaestro 2022-04-30 19:10
- Simulated distributions Helmut 2022-05-02 13:43

- Confuse a Cat Inc. ElMaestro 2022-04-09 21:47

- Confuse a Cat Inc. Helmut 2022-04-09 18:40

- How would you implement it? ElMaestro 2022-04-09 11:45