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Steady state with additional multiple dosing


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#1 veenu.bala

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Posted 16 June 2020 - 03:35 PM

Hello,
 
I was trying to model some data in which the patients continuously take their drug daily before the time of enrollment in study and once a day is taking throughout the study period. and at the time of study start they were assumed to be on steady state. On the first visit pre dose sample was taken and then dosed and 2 hr and 6 hr. time point was recorded. Additional blood samples were taken on their subsequent visit ever 4 weeks upto 28 weeks (one blood sample after dose in clinic). I used your recent webinar to map steady state and additional dose altogether. Here is the link.
 
https://www.youtube....h?v=4PpZHGAHlsQ
   
My model is running only with one compartment additive error model with return code 1. when i am trying any other model it is showing for certain id's steady state not reached unable to execute. Some time it is showing for certain Id's Error (Model.C): non-finite_ypred. One more thing I observed with one compartment additive model is the omega table showing very high values like ncl = 46.30, nKa = 61 and NV = 6.2. I am using initial estimates from literature. 

When I am looking doses output then it is showing three doses at 24 hours. I am also not getting this. 
We want to predict interoccassion variability in this project. so, before adding this as a covariate wanna make sure about base model. Theta table for one compartment additive is also fine with displaying all %CV values within 20%. I can't attach full project and excel sheet but I am attaching a part of excel and mapping details for SS and addl.
 
 
Thanks 
 
 
Veenu

Attached Thumbnails

  • SS_mapping.png
  • data set.png
  • Addl mapping.png
  • dose_output.png

Edited by veenu.bala, 16 June 2020 - 04:19 PM.


#2 Ana Henry

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Posted 16 June 2020 - 07:52 PM

Hello Veenu,
It would be best to see your project but by looking at your output it appears that you are indicating that steady state starts at 24 hours, this is probably because your steady state variable (we cannot see from the screenshots how that looks like) might have a flag for steady state at 24 hours when it should probably be at 0 hrs. This is just a guess based on your screenshots.

Best,

Ana Henry

Edited by Simon Davis, 25 June 2020 - 08:10 AM.

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#3 veenu.bala

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Posted 22 June 2020 - 02:10 PM

Thanks Ana,

I tried to run my project with different initial estimate from literature and it is running for now and also BSV decreased with 2-compartment multiplicative error model. but when I am doing SS at 0 time, model is not running.

Veenu

Edited by Simon Davis, 25 June 2020 - 08:10 AM.


#4 veenu.bala

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Posted 26 June 2020 - 05:22 PM

Hello Veenu,
It would be best to see your project but by looking at your output it appears that you are indicating that steady state starts at 24 hours, this is probably because your steady state variable (we cannot see from the screenshots how that looks like) might have a flag for steady state at 24 hours when it should probably be at 0 hrs. This is just a guess based on your screenshots.

Best,

Ana Henry

Hello,

 

Here I am uploading my project. I tried with SS at 24 hours and SS 0 hrs. My models are not running with SS 0 hrs and each time it is saying SS not reached for a particular ID's. However some odels are running with SS=24 hrs but giving a very high volume, clearance and Ka values. Could you please see my project and help me to tell where I am doing mistake. 

One more thing my data contains some BLQ and missing observations so I censored those points and BLQ output used as model input.

 

I really appreciate your help to get me out of this. 

 

thanks

 

Veenu

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