Bioequivalence and Bioavailability Forum

Main page Policy/Terms of Use Abbreviations Latest Posts

 Log in |  Register |  Search

Back to the forum  2018-07-23 00:40 CEST (UTC+2h)
GM
Junior

India,
2018-03-07 06:25

Posting: # 18502
Views: 870
 

 95% Upper bound calculation [RSABE / ABEL]

Hello All :waving:,

Hope all are doing well...!!!

Do anybody suggest manual calculation of 95% upper bound in RSABE approach....

Actually I am trying to do this for IVPT study analysis using guidance Acyclovir 5% cream. But here the reference treatment was replicated more than 2 times.

Is it possible to follow the RSABE approach as per the Progesterone Guidance..?

Kindly suggest me something relavent to this.

Thankyou in Advance :-).

Regards,
GM
Katrin_Ti
Junior

Austria,
2018-03-09 14:05

@ GM
Posting: # 18509
Views: 606
 

 95% Upper bound calculation

» Do anybody suggest manual calculation of 95% upper bound in RSABE approach....
» Actually I am trying to do this for IVPT study analysis using guidance Acyclovir 5% cream. But here the reference treatment was replicated more than 2 times.
» Is it possible to follow the RSABE approach as per the Progesterone Guidance..?

Hello,

actually the FDA draft guidance on acyclovir cream recommends the use of the RSABE approach as stated in the Progesterone Guidance.
See acyclovir cream guidance on page 18:
26. One possible way to perform the analysis in order to derive the upper bound of this CI is to use an approach similar to that described in the FDA Draft Guidance on Progesterone (recommended Apr 2010; revised Feb 2011), with appropriate modifications for this replicate experimental design.


Greetings
Katrin


Edit: Full quote removed. Please delete everything from the text of the original poster which is not necessary in understanding your answer; see also this post #5! Guidance linked. [Helmut]
GM
Junior

India,
2018-03-13 05:09

@ Katrin_Ti
Posting: # 18525
Views: 522
 

 95% Upper bound calculation

Hi Katrin,

» actually the FDA draft guidance on acyclovir cream recommends the use of the RSABE approach as stated in the Progesterone Guidance.

» See acyclovir cream guidance on page 18:
» 26. One possible way to perform the analysis in order to derive the upper bound of this CI is to use an approach similar to that described in the FDA Draft Guidance on Progesterone (recommended Apr 2010; revised Feb 2011), with appropriate modifications for this replicate experimental design.


Thanks for the reply. I understand this in the same way.

But my question is, as per progesterone guideance the RSABE calculation is rightway to do for IVPT..?
Because, we are not using Test and Reference formulations on the same cell (like healthy volunteers in PK) :confused:.

If YES, what are that necessary changes you suggest?

Kindly help me in this regards.

Thank you in advance.

Regards,
GM
Katrin_Ti
Junior

Austria,
2018-03-13 09:31

@ GM
Posting: # 18526
Views: 515
 

 95% Upper bound calculation

Hi,

as the guidence for acyclovir creams defines:

The replicate skin sections from donor 1 dosed with the test product may be denoted as T11,
T21, ..., Tr1, and likewise from donor 2, T12, T22, ..., Tr2, and so forth up to n donors; T1n,
T2n, ..., Trn. Similarly, the replicate skin sections dosed with the RLD product may be denoted as R1n, R2n, ..., Rrn.



That means that you need the same number of replicates from each donor (for R and T) for further calculations.

Calculate the point estimate, inter-donor variability and within reference variability using the log-transformed data (as defined in the acyclovir cream guidance).
If SWR >= 0.294 use the RSABE approach and calculate the upper bound of the CI as described in the Progesterone guidance.
I think the SAS code described in the progesterone guidance has to be modified but I can not help you with this task.

Greetings
Back to the forum Activity
 Thread view
Bioequivalence and Bioavailability Forum |  Admin contact
18,547 posts in 3,941 threads, 1,190 registered users;
online 14 (0 registered, 14 guests [including 14 identified bots]).

[The] impatience with ambiguity can be criticized in the phrase:
absence of evidence is not evidence of absence.    Carl Sagan

The BIOEQUIVALENCE / BIOAVAILABILITY FORUM is hosted by
BEBAC Ing. Helmut Schütz
HTML5 RSS Feed