Emax and Ed50

Phoenix Certara Forums Phoenix WNL basics
1

Dear simon pls refer link: Bioequivalence and Bioavailability Forum • SAS: Emax and ED50 we are having phoenix winnonlin version 6.3 software its possible to calculate emax and ed50 by (Fitting based on the assumption of nonlinear mixed effect model (population model) or Fitting based on nonlinear least square regression pooling individual observation (naive pooled data method) Winnonlin v 6.3 ? pls guide to do in Winnonlin i tried in winnonlin but the values are not matching. pls guide me how to calculate emax and ed5o using population or naive pool method in Winnonlin. some one suggest in Winnonmix only able to calculate emax and ed50 using population or naive pool method .

2

Karthik, Please can you post your project, what sort of data do you have; from how many dose levels? Do you have PK Data? Naive pool is possible with either WNL classic PD models (101 to 108) will give you Emax and EC50, the equivalent models can also be built in Phoenix engine. If you have NLME then you can also build more sophisticated Pop models Simon

emax.jpg
emax.jpg634×456 110 KB

3

Dear sir thanks for your reply. we are planning to do Skin blanching study (Vasoconstrictor Response) for pilot study as per the FDA guideline. we want to calculate Emax and Ed50 by using any one of the method. Pls finds the below link for FDA guidance. Topical Dermatologic Corticosteroids: in Vivo Bioequivalence | FDA i took the data from this and then i calculated the Emax and Ed50 but the values are not matching so only i planned to perform in the SAS. so pls guide if its possible to calculate from Winnonlin.

4

Karthik, if you would like assistance please post the Phoenix project you created where “the values are not matching”. Simon

5

Dear sir

pls find the data for Skin blanching i took from the guideline i arranged according to the data in a sequential order like subject, time and AUEC(pls refer the page no. 28 in FDA guideline) from that i tried Winnonlin classical model. its showing error and I m new to this kind of study.

Thanks and regards
Karthik [file name=Skin_Blanching_Study.phxproj size=156325]Certara | Drug Development Solutions (153 KB)

6

Dear Karthrik Can you write the mathematical model you want to use. Thanks in advance; Serge

7

Dear Sir this is the mathematical formula given in that guideline. E=E0 + Emax*D/(ED50 + D). thanks and regards Karthik

8

Dear Kartrik
I made some corrections in your model and ran it with both the Population naïve pool and individual fitting too. Of course you cannot really trust too much the individual fits because not all indiviudals have enough information when using only their own values. The population fit worked very well and I got

tvEC50 1.23924
tvE0 -0.976706
tvEmax -39.2535
stdev0 20.2865

when using the model you recommended.
The project is attached. I hope it helps.
best
Serge [file name=Skin_Blanching_Study_serge_add_official.phxproj size=1295277]Certara | Drug Development Solutions (1.24 MB)

9

Dear Serge

thanks for your valuable help. its very useful for me to understand.

As per before Program the mathematical formula is

E = E0 + Emax * C / (EC50 + C)

whether we can able assign the formula like this

E = E0 + (Emax * C) / (EC50 + C)

Pls find the attachment of FDA Guideline for Skin blanching Page 4 and for results Page No.28. [file name=Topical_dermatologic_corticosteroids___1995.pdf size=2719376]Certara | Drug Development Solutions (2.59 MB)

10

Hi Karthik! [quote]As per before Program the mathematical formula is E = E0 + Emax * C / (EC50 + C) whether we can able assign the formula like this E = E0 + (Emax * C) / (EC50 + C)[/quote] Are you kidding; what’s your problem? There are even some acronyms to remember the order of operations. UK: BODMAS (Brackets, raise to the power Of, Division, Multiplication, Addition, Subtraction) US: PEMDAS (Parentheses, Exponentation, Multiplication/Division, Addition/Subtraction) or if you prefer “Please Excuse My Dear Aunt Sally”.