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Add+Mult Error model feature


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#1 Lance Wollenberg

Lance Wollenberg

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Posted 05 August 2015 - 04:00 PM

Can anyone explain to me how to correctly parameterize the additive + multiplicative (combined error model).  I understand how to integrate the additive portion of the error model in PML, however I am getting confused by the following "sqrt(1 + C^2 * (CMultStdev/sigma())^2))".  

 

Just as an example, if my proportional error is 30% what is the value of CmultStdev? 0.30? sqrt(0.30). 

 

I am asking because I have a model already fit in NONMEM and I would like to transfer this over and use NLME to run some simulations?

 

Thanks!



#2 smouksassi1

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Posted 05 August 2015 - 05:30 PM

Can anyone explain to me how to correctly parameterize the additive + multiplicative (combined error model).  I understand how to integrate the additive portion of the error model in PML, however I am getting confused by the following "sqrt(1 + C^2 * (CMultStdev/sigma())^2))".  

 

Just as an example, if my proportional error is 30% what is the value of CmultStdev? 0.30? sqrt(0.30). 

 

I am asking because I have a model already fit in NONMEM and I would like to transfer this over and use NLME to run some simulations?

 

Thanks!

 

Hi Lance,

When you use this you get model code:

error(CEps = 1)
observe(CObs = C + CEps * sqrt(1 + C^2 * (CMultStdev/sigma())^2))

 

in model results outputs you will get:

Stdev0: (square root of CEps variance) additive error on concentration scale  say you got : 2 mg/L
CMultStdev: proportional error on percent scale say you got: 0.20 ( 20%)

if you are coming from nonmem model with

Y=F +EPS(1) + F*EPS(2)
then 
$SIGMA
4 ; variance of additive var 
0.04; variance of proportional part
VAR(Y) = VAR (EPS(1))  + F^2*VAR(EPS(2))

var of eps(1) is sigma and so on


now if you want to deouble check here is the derivation:

Variance of CObs= Variance of (CEps * sqrt(1 + C^2 * (CMultStdev/sigma())^2))); we remove C since not a random variable            

                             = Variance of (CEPS) *(1 + C^2 * (CMultStdev/sigma())^2))
                                                               ( we square the second term variance rules, then sqrt is removed)

                              = Variance of (CEPS) +  Variance of (CEPS)* C^2*(CMultStdev/sigma())^2

                               =Variance of (CEPS) +  Variance of (CEPS)* C^2*(CMultStdev)^2/Variance of (CEPS)

                               =Variance of (CEPS)+   C^2*(CMultStdev)^2

 

so additive part variance is CEPS and porportional part variance is C^2*(CMultStdev)^2

we typically report square root of CEPS ( stdev0) and the proportional part in percent Cmultstdev


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