MGR
★    

India,
2007-12-13 08:27
(5950 d 11:47 ago)

Posting: # 1367
Views: 7,114
 

 Confidence interval [General Sta­tis­tics]

Dear all,

I have a doubt regarding the 90% Confidence Interval, as if the confidence interval limit of Cmax (Fed study) is increased when compared to the fasting study. From this can we say that the absorption of Cmax is high when compared to Reference drug.

But according to the label and literature "In fed conditions the rate and absorption of Cmax will be increased when compared to fasting conditions" but in our study the mean Cmax is decreased when compared to the fasting study, as the mean Cmax of reference is also decreased and less than Test mean Cmax. From this point can we consider that the rate and absorption of Test is better than Reference drug? Please anyone clarify this. Thanks in advance.

--
Edit: Category changed. [HS]

Regards,
MGR
Helmut
★★★
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Vienna, Austria,
2007-12-13 16:54
(5950 d 03:20 ago)

@ MGR
Posting: # 1372
Views: 5,751
 

 Confidence interval

Dear MGR!

❝ ... if the confidence interval limit of Cmax (Fed study) is increased when compared to the fasting study.

What do you mean by 'the confidence limit is increased'? :confused:
Do you mean, the upper CL of Cmax in the fed study is higher than the upper CL of Cmax in the fasting study - while the PE/GMR (point estimate / geometric mean ratio) is essentially the same?
If yes, the CVintra obviously is higher, which can be caused by numerous reasons:
  • smaller sample size,
  • pure chance, or
  • 'true' higher variability in the fed state.

❝ From this can we say that the absorption of Cmax is high when compared to Reference drug.


Just have a look at the point estimate.

❝ But according to the label and literature "In fed conditions the rate and absorption of Cmax will be increased when compared to fasting conditions" but in our study the mean Cmax is decreased when compared to the fasting study, as the mean Cmax of reference is also decreased and less than Test mean Cmax.


Attention: the innovator has done a food interaction study (i.e, a 2x2 cross-over study of his procuct in fed vs fasting conditions), whereas you are comparing results from two studies; results may differ just by chance!

❝ From this point can we consider that the rate and absorption of Test is better than Reference drug?


Now I'm even more confused. Would you please come up with some data from both studies (PE and 90% CIs).

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MGR
★    

India,
2007-12-21 06:54
(5942 d 13:19 ago)

@ Helmut
Posting: # 1409
Views: 5,608
 

 Confidence interval

Dear HS,

❝ Do you mean, the upper CL of Cmax in the fed study is higher than the upper CL of Cmax in the fasting study -


Yes. the upper CL of Cmax fed is higher than the Upper CL of Cmax fasting study.


And the data of fasting and fed is mentioned below:

Fasting study:

90% CI of AUC0-t, AUC0-inf and Cmax are 99.88 to 117.06, 98.50 to 113.52 and 96.51 to 121.54 respectively.
GMRatio: AUC0-t, AUC0-inf and Cmax are 108.13, 105.74 and 108.31 respectively.

Fed study:

90% CI of AUC0-t, AUC0-inf and Cmax are 98.92 to 141.62, 105.20 to 140.79 and 98.34 to 154.01 respectively.
GMRatio: AUC0-t, AUC0-inf and Cmax are 118.36, 121.70 and 123.06 respectively.

here the CVintra of fasting and fed conditions are 24.65 and 50.04 respectively for Cmax.

But according to the label the innovator had done the study in fasting conditions only. But according to the statement of the innovator that the Cmax of the drug will increase in fed condition is it implies that the sample size is small when compared to fasting condition. but we had take same sample size for both the studies (28).

Thank you very much for your explanation.

Regards,
MGR
vydanark
●    

2007-12-26 12:24
(5937 d 07:50 ago)

@ MGR
Posting: # 1424
Views: 5,593
 

 Confidence interval

Dear MGR,

Fasting study:

❝ 90% CI of AUC0-t, AUC0-inf and Cmax are

❝ 99.88 to 117.06, 98.50 to 113.52 and 96.51 to 121.54 respectively.

❝ GMRatio: AUC0-t, AUC0-inf and Cmax are

❝ 108.13, 105.74 and 108.31 respectively.

Fed study:

❝ 90% CI of AUC0-t, AUC0-inf and Cmax are

❝ 98.92 to 141.62, 105.20 to 140.79 and 98.34 to 154.01 respectively.

❝ GMRatio: AUC0-t, AUC0-inf and Cmax are

❝ 118.36, 121.70 and 123.06 respectively.


It appears that the rate and extent of release of your test formulation is highly significant when compared with reference formulation under fed conditions.

❝ here the CVintra of fasting and fed conditions are 24.65 and

❝ 50.04 respectively for Cmax.


Probably the high intra CV in fed state could be due to lack of enough sample size.

❝ But according to the label the innovator had done the study in fasting

❝ conditions only. But according to the statement of the innovator that the

❝ Cmax of the drug will increase in fed condition is it implies that the

❝ sample size is small when compared to fasting condition. but we had take

❝ same sample size for both the studies (28).


What is the rationale behind selecting the same sample size for both fasting and fed studies? As label suggests there will be increase in rate and extent of release of formulation you could have opted more sample size under fed conditions.
MGR
★    

India,
2008-01-05 13:23
(5927 d 06:51 ago)

@ vydanark
Posting: # 1472
Views: 5,509
 

 Confidence interval

Dear HS,

Kindly please give me some more suggestions regarding this. I would be a greatful and helpful for me.

Thank you.

Regards,
MGR
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