Helmut
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Vienna, Austria,
2013-06-22 20:40
(4043 d 06:25 ago)

Posting: # 10865
Views: 6,636
 

 tmax in EEA applications [Surveys]

Dear all,

with the IR GL operational for almost three years now and the MR GL approaching (see also this post) I’m curious what is your practice. I’m talking only about formulations where tmax is clinical relevant (mostly rapid onset, rarely AE related).
We all know that “A statistical evaluation of tmax is not required.” Does that mean that it is not accept­able as well? I read that “A non-parametric analysis is not acceptable”, but

<nitpicking>
this paragraph is related to ANOVA and log-transformation.
</nitpicking>

“[…] there should be no apparent* difference in median tmax and its X between test and reference product.”
where X = “variability” (IR GL) and “range” (MR draft).

My practice (as it was since the mid 1980s):
  • Descriptive statistics of tmax of the formulations, i.e.,
    x̃, 25/75 percentiles, minimum, maximum; box plots.
  • Ignore the “not acceptable” statement and perform a nonparametric test (generally I state an acceptance range of ±something in the protocol).
    Calculate PE and ~90% CI.
  • Report no relevant difference in tmax, CI including zero, and similar :blahblah:
Experience so far: no problems.

Questions:
1. What do you do now? _____________
2. Do you consider changing your practice in the near future? [ ] yes [ ] no
3. If yes, what are you planning to do? _____________


  • Would somebody be so nice and explain to me what “apparent” in this context possibly might mean? Any non-zero number is apparent to me. I guess it should read “relevant”.

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d_labes
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Berlin, Germany,
2013-06-24 10:11
(4041 d 16:53 ago)

@ Helmut
Posting: # 10868
Views: 5,335
 

 tmax in EEA applications

Dear Helmut,

❝ 1. What do you do now?

Act like you described for your practice.

❝ 2. Do you consider changing your practice in the near future? [ ] yes [ ] no

No.

❝ 3. If yes, what are you planning to do?

Not applicable.

❝ * Would somebody be so nice and explain to me what “apparent” in this context possibly might mean? Any non-zero number is apparent to me. I guess it should read “relevant”.

Sorry but I have not the slightest idea why they use that wording here.

BTW: What means EEA?

Regards,

Detlew
Helmut
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Vienna, Austria,
2013-06-24 14:35
(4041 d 12:29 ago)

@ d_labes
Posting: # 10870
Views: 5,228
 

 EEA unveiled

Dear Detlew,

encouraging answers. ;-)

❝ ❝ 2. Do you consider changing your practice in the near future? [ ] yes [ ] no

❝ No.


Never considered Sauter’s confusing plot?* I used it only once (and will not in the future). R-code upon request.

[image]

❝ BTW: What means EEA?


European Economic Area = EU + Iceland, Liechtenstein, and Norway.


  • Sauter R, Steinijans VW, Diletti E, Böhm E, Schulz H-U. Presentation of results from bioequivalence studies. Int J Clin Pharm Ther Toxicol. 1992:30/Suppl.1;S7–30.

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d_labes
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Berlin, Germany,
2013-06-24 18:20
(4041 d 08:44 ago)

@ Helmut
Posting: # 10872
Views: 5,117
 

 Sauter's tmax plot

Dear Helmut,

❝ Never considered Sauter’s confusing plot?


No. I personally couldn't find any convincing argument or any benefit why I should. You said it: confusing.

Regards,

Detlew
Helmut
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Vienna, Austria,
2013-06-24 18:38
(4041 d 08:26 ago)

@ d_labes
Posting: # 10873
Views: 5,254
 

 Sauter's tmax plot

Dear Detlew,

❝ I personally couldn't find any convincing argument or any benefit why I should. You said it: confusing.


Yes. Though the plot looks like a histogram the width of the bars depends on the sampling schedule; only the heights are important. Most – if not all – viewers would associate the frequency with the areas, which is completely false. Should stay in the waste bin.

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