Bioequivalence and Bioavailability Forum • MHRA query on Cmax BE study

Jasmin
●

2007-08-04 10:02
(6492 d 13:14 ago)

(edited on 2007-08-04 12:51)
Posting: # 961
Views: 7,182

MHRA query on Cmax BE study [Outliers]

Dear All,

one of BE study already submitted in MHRA on 18 volunter in 2005.now we got query.

The query is,our study Cmax range is 78.14 to 125.58 but as per guidline 80 - 125.other peremeter is in limit.
the Cmax range is out of limit.

we have performed BE study of lower strength.

my question is...

how can we solve this query?

Can we recalculate using picked one volunteer data and resubmit?

using parameter confidential interval 90%, CV of intra subject veriability Cmax 17.70 , ratio (%) of least squares means(Cmax) 99.06 and p-value of ANOVA Cmax is 0.9453.

can any one help me solve this query otherwise we perform new BE study.

with best regards

Jasmin

--
Category changed [Jaime]

Helmut
★★★

Vienna, Austria,
2007-08-04 15:18
(6492 d 07:59 ago)

@ Jasmin
Posting: # 962
Views: 6,873

MHRA query on Cmax BE study

Post reply

Dear Jasmin!

❝ … 18 volunter … Cmax range is 78.14 to 125.58

So your point estimate of the full data set (n=18) is 99.06%, CV 42.5%, right?

❝ Can we recalculate using picked one volunteer data and resubmit?

See #3 of the Q&A Document to the Note for Guidance on BA/BE.

❝ using parameter confidential interval 90%, CV of intra subject veriability

❝ Cmax 17.70 , ratio (%) of least squares means(Cmax) 99.06 and p-value of

❝ ANOVA Cmax is 0.9453.

I don’t understand the results you are giving for the reduced data set (n=17): If excluding the one subject who is supposed to be responsible for the high variability (CV 42.5% → 17.7%), how is it possible that the point estimate stays the same?!

❝ can any one help me solve this query otherwise we perform new BE study.

If you opt for a new study (because the re-submission was not accepted), you should:

try to find an explanation for the conditions resulting in the outlier in the first study,
try to optimize your inclusion/exclusion criteria and monitoring during the study,
remember that statistical criteria alone are not accepted, and
define conditions for exclusion in the protocol according to Section 5.3 of ICH-E9.

—
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Helmut Schütz

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Jasmin ● 2007-08-04 17:31 (6492 d 05:45 ago) @ Helmut Posting: # 963 Views: 5,761	MHRA query on Cmax BE study Post reply
	Dear HS, thanks for reply. I am not able to explain my full problem due to less experience in this field. all result and perameter only for 18 volunteer. as per guidline we should submit new study and I will remember all point which you suggest. thanks again with best regeards Jasmin