Re: Random effect on ALAG between dose events
No, there is no other solution except IOV.
One option to lessen the impart of the discrepancy is to have inflated residual error in the some interval post-dose
;TAD: time after dose
SD=THETA()
IF(TAD.LE.XX) SD=SD*THETA()
$ERROR
Y=TY*(1+SD*EPS(1))
$SIGMA
1 FIX
Then observations close to the dose (with uncertain dose time) will have less influence on PK parameters.
Regards,
Leonid
Quoted reply history
On 8/12/2020 4:51 AM, Tingjie Guo wrote:
> Dear NMusers,
>
> I'm modeling a PK data set with a discrepancy between the documented dosing time and the actual dosing time. According to our clinical practice, actual dosing time is always >= documented time. I added a ALAG with IIV to address this issue using the following formulation.
>
> ALAG1 = THETA(5) * EXP(ETA(5))
>
> This indeed improved the model fitting quite a lot. However, this parameterization does not reflect the reality as I expect the ETAs should vary between each dosing event rather than only between patients. So I expect a "inter dose event variability" would better make sense to this end. Since there are too many dosing events per patients, a IOV-like approach is doable but not preferred. And it may not accurately reflect "inter dose event variability" either. I was wondering if there is any good solution to this problem? Any comments are very much appreciated!
>
> Warm regards,
> Tingjie Guo