Bioequivalence and Bioavailability Forum • Population BE for in-vitro data

Ankita
☆

India,
2011-06-24 17:32
(5479 d 04:33 ago)

Posting: # 7170
Views: 7,311

Population BE for in-vitro data [Regulatives / Guidelines]

Hi All,

Can anybody help me in to calculate 95% upper bound with population BE for in-vitro data. I have used the SAS code given in the link http://www.pqri.org/commworking/minutes/pdfs/dptc/psdpcwg/Addl/DC01-526048-v1-PBE_Description_for_PQRI_Prof_Comp.pdf and based on the reference http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm070118.pdf

Please help me to clarify the calculation of a2, a3, a4, a5 and V which is used to calculate H₀ in the below SAS code.

a2 = 0.0313 - (13.624/f_T) - (10.182/f_R) - (29.155/(f_T*f_R)) + (25.121/(f_T*f_R)) - (5.623/(f_R*f_R));

a3 = -0.0306 + (10.236/f_T) + (13.495/f_R) - ( 9.822/(f_T*f_R)) - (12.207/(f_T*f_R)) + (32.396/(f_R*f_R));

a4 = 0.0243 - ( 8.113/f_T) - ( 4.703/f_R) - (12.564/(f_T*f_R)) + (14.810/(f_T*f_R)) + (3.528/(f_R*f_R));

a5 = ((a1 + a2 + a3)/t) - 1 - a4;

V = (a1 + (a2*C) + (a3*C*C))/(1 + (a4*C) + (a5*C*C));

UCL = del + (V*sqrt(M));

LCL = del - (V*sqrt(M));

E0 = del*del;

H0 = max(LCL*LCL, UCL*UCL);

Regards

Ankita

d_labes
★★★

Berlin, Germany,
2011-06-29 11:07
(5474 d 10:58 ago)

@ Ankita
Posting: # 7182
Views: 6,437

Critical value

Post reply

Dear Ankita,

the answer to your question can be found in the references you gave (especially http://www.fda.gov/downloads/DrugsGuidanceComplianceRegulatoryInformation/Guidances/ucm070118.pdf page 7).
An example of the sentence "People able to read are clearly in advantage in reading" :cool:

.

What the SAS code excerpt you cite does is the calculation of the critical value (V as a function of the two group variances and their degrees of freedom) and with that the confidence interval for the difference
(µ_T-µ_R)
the very first term in the population BE criterion.

The test used for that end is a variant of a test for comparing two means without the assumption of equal variances.
This is commonly termed Behrens-Fisher problem.

The more commonly known (approximate) solution to the Behrens-Fisher problem is the Welch t-test.
Search the forum for that.

The guidance suggest to use the Lee-Gurland^1,2,3 variant instead of the Welch test because this is said to have better performance with small sample sizes.

¹Lee A.F.S., J. Gurland
"Size and power of test for equality of means of two normal populations with unequal variances"
J Amer Statist Assoc, 70, 933-941 (1975)

²Lee A.F.S., N.S. Fineberg
"A fitted test for the Behrens-Fisher problem"
Comm Statist- Theory Meth, 20, 653-666 (1991)

³Lee A.F.S.
"Coefficients of lee-gurland two-sample test on normal means"
Comm Statist- Theory Meth, 24, 1743-1768 (1995)

Astonishing enough I havn't found any software which delivers the Lee-Gurland test out of the box, even not in R. :ponder:

—
Regards,

Detlew

Ankita ☆ India, 2011-06-30 21:06 (5473 d 00:59 ago) @ d_labes Posting: # 7196 Views: 6,166	Critical value Post reply
	Dear d_labes, Thanks for the response. Regards, ankita

krishna
☆

India,
2013-06-18 16:01
(4754 d 06:04 ago)

@ Ankita
Posting: # 10807
Views: 5,308

Population BE for in-vitro data

Post reply

❝ http://www.pqri.org/commworking/minutes/pdfs/dptc/psdpcwg/Addl/DC01-526048-v1-PBE_Description_for_PQRI_Prof_Comp.pdf[/link] and based on the reference http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm070118.pdf

Hi all,

As per the above FDA guidline for in-vitro PBE, it was mentioned (page no. 4) that point estiamate should fall in (90 - 111). But from the recent Budesonide suspension OGD guidance http://www.fda.gov/downloads/Drugs/.../Guidances/UCM319977.pdf, there is no such criteria except the 95% Upper bound < =0. What is the rationale behind this, can any body calrify me? As per my understanding, point estiamte criteria drive the results in a good way like scaled average bioequivalence. Correct me if I am wrong.

Thanks in advance,

Krishna.

krishna
☆

India,
2013-06-19 14:03
(4753 d 08:02 ago)

(edited on 2013-06-20 08:46)
@ krishna
Posting: # 10815
Views: 5,203

Population BE for in-vitro data

Post reply

❝ As per the above FDA guidline for in-vitro PBE, it was mentioned (page no. 4) that point estiamate should fall in (90 - 111). But from the recent Budesonide suspension OGD guidance http://www.fda.gov/downloads/Drugs/.../Guidances/UCM319977.pdf, there is no such criteria except the 95% Upper bound < =0. What is the rationale behind this, can any body clarify me? As per my understanding, point estimate criteria drive the results in a good way like scaled average bio equivalence. Correct me if I am wrong.

Hi all,

As per my knowledge, point estimate criteria prevents not to shift the mean ratio too far from 1.

Thanks,

Krishna.

Helmut
★★★

Vienna, Austria,
2013-06-19 20:24
(4753 d 01:41 ago)

@ krishna
Posting: # 10825
Views: 5,025

Population BE for in-vitro data

Post reply

Hi Krishna!

❝ Hi Helmut,

❝

❝ Any thoughts on this?

No (aka no time & currently no interest in the topic). Why are you addressing me personally? I don’t like pushy questions. Please read the Forum’s Policy, in particular: Don’t fork! BTW, you can your post within 24 hours. If you want to add something, go ahead. Don’t reply to yourself.

—
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz

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