ED50 Calculations

[CraigWW]

I need to calculate the ED50 for a vasoconstriction pilot bioequivalence for corticosteroids as specified in the FDA Guidance "Guidance Topical Dermatologic Corticosteroids: In Vivo Bioequivalence" 2 June 1995. Please help me learn to do this in SAS.
Thanks

[Cynthia_sas]

Hi:
Example 71.1 in the PROC PROBIT documentation specifically mentions dosages and ED50:
http://support.sas.com/documentation/cdl/en/statug/63033/HTML/default/statug_probit_sect034.htm#

cynthia

[CraigWW]

Since the response for vasoconstriction pilot studies is AUC, not the number of subjects responding to a particular dose Proc Probit can not be used.

[Doc_Duke]

This article may help, it used something called an Emax model.

Clinical Pharmacology & Therapeutics 66, 346–357 (1 October 1999) | doi:10.1053/cp.1999.v66.a101209

Try a google search for
ed50 bioequivalence dermatologic

[CraigWW]

Thanks Doc,

An Emax model is what I am looking for.

Craig

[k2k]

dear craigWW.

i need the same for vasoconstriction study. if u have the sas code can u share me or guide me in this.

[ssinojia]

Hi All,

I want to calculate the ED50 and EMax using population model in SAS? Is there any built in procedure available in SAS to do this? I have read on some paper about SAS MIXLIN Macro, anyone have idea about this Macro?

[Irla]

Hi! 

Have you found any code in SAS to calculate Emax with vasoconstriction data? I'm currently with the same issue. Thank you in advance

[ssinojia]

Hi Irla,

I didn’t find exact code as such however I was able to calculate ED50 using PROC NLMIXED by fitting the model. I don’t have that handy but you can try searching ED50 or Emax modeling with PROC NLMIXED. I am sure you will get some good results with Google.

[Irla]

Hey, thank you for answering me. I'll try to find it right now!

[Irla]

Hey! Since you told me you got to calculate it, can I ask you something? I've found a NLIN code, probably I'll be able to reproduce it in SAS. 

But there some parameters to put on the code where I'm stuck. We use DOSE DURATION X AUEC, right? In the formula we have to type the inicial values, right? How do I find them? What about the slope, how to obtain this data?

that is the code: 

proc nlin data = dr;
  parms top = 68.875 bottom = 20.575 EC50 = 1 hill = 1;
  model response = top + (bottom - top) / 
  (1 + (concentration / EC50)**hill);
run;

[ssinojia]

Hi,

I don’t remember them now, but I used to get that from my statistician. Then used to see model fitting. Again I used NLMIXED.

[SteveDenham]

First off, you may want to check the parameterization of the model that you are using. The example at the link below uses a more "interpretable" parameterization that you might find also has better properties for your goal.

If you don't have a good idea from prior knowledge as to what the best starting value(s) might be, you might try a grid search over a range of reasonable values. You don't need the exact starting values this way, and if several combinations of starting values lead to the same optimum solution, you get what you are looking for without knowing a precise set of values.  This also can help you avoid converging to a saddle point rather than an extremum.  See the documentation for the PARAMETER statement in NLIN  https://documentation.sas.com/doc/en/pgmsascdc/9.4_3.4/statug/statug_nlin_syntax12.htm and this example which goes into various parameterizations for an ED50 model  https://documentation.sas.com/doc/en/pgmsascdc/9.4_3.4/statug/statug_nlin_examples04.htm 

Good luck. 

SteveDenham

[ssinojia]

Hi Steve, thanks for your inputs. It’s helpful.