NONMEM Users Network Archive

Hosted by Cognigen

Re: [NMusers] RE: Large errors in the estimation of volume of distribution (Vd) for sparse data

From: Kajsa Harling <kajsa.harling_at_farmbio.uu.se>
Date: Mon, 16 Nov 2015 14:41:17 +0100
Regarding the error message from PsN vpc: I can see from the message that you are using a *very* old version of PsN. I suggest that you install the latest version and try again.

Best regards,
Kajsa Harling

On 11/10/2015 05:12 AM, HUI, Ka Ho wrote:

Thanks for your responses!

 

Nitin, I encountered an error when generating VPC by PsN. It says “No DV values found after filtering original data. At lib/tool/npc.subs.pm line 2215.” What does it mean?

 

Felix, Past published data suggested similar parameter estimates and models compared to my final model. This is PO and I fixed Ka at a pre-estimated value (So no estimation of fixed or random effect).

 

Ahmad, Yes. The CV is even larger.

 

Matthew

 

 

 

From: Abu Helwa, Ahmad Yousef Mohammad - abuay010 [mailto:ahmad.abuhelwa_at_mymail.unisa.edu.au]
Sent: Tuesday, November 10, 2015 5:34 AM
To: HUI, Ka Ho <matthew.hui_at_link.cuhk.edu.hk>; nmusers_at_globomaxnm.com
Subject: RE: Large errors in the estimation of volume of distribution (Vd) for sparse data

 

Hi Mathew,

 

Have you tried using an exponential model for vd ? like this:  Vd = TEHTA(1)*EXP(ETA(1))

 

Ahmad.

 

 

From: felix boakye-agyeman [mailto:boakyefe_at_gmail.com]
Sent: Tuesday, November 10, 2015 12:41 AM
To: HUI, Ka Ho <matthew.hui_at_link.cuhk.edu.hk>
Subject: Re: [NMusers] Large errors in the estimation of volume of distribution (Vd) for sparse data

 

Hello,

   Do you have historical data to compare you data to? (Do you know if you are hitting a local minimum)

Is this iv or po,  if its po how is your Ka?

You may also be over-parameterized due to your data

 

From: Kaila, Nitin [mailto:Nitin.Kaila_at_pfizer.com]
Sent: Tuesday, November 10, 2015 12:14 AM
To: HUI, Ka Ho <matthew.hui_at_link.cuhk.edu.hk>
Subject: RE: Large errors in the estimation of volume of distribution (Vd) for sparse data

 

Matthew.

 

Construct visual predictive check (VPC) plots, using all the estimates of the bootstrap runs, as that will be a more true estimate of overall variability in the Cp predictions.

 

Use the –rawres option in PsN to perform the VPC, and then compare your original final model VPC plot with the VPC plot with all estimates of the bootstrap.    

 

Nitin

 

From: owner-nmusers_at_globomaxnm.com [mailto:owner-nmusers_at_globomaxnm.com] On Behalf Of HUI, Ka Ho
Sent: Monday, November 9, 2015 9:43 AM
To: nmusers_at_globomaxnm.com
Subject: [NMusers] Large errors in the estimation of volume of distribution (Vd) for sparse data

 

 

Dear all,

 

I have some population PK data which are in general very sparse (95% have only 1 blood sample between 2 successive doses). I developed a population PK model with the one-compartment model with 1st order absorption. The progress is generally okay except that whenever a random effect, i.e. *(1+ETA(1)), is used to describe distribution of Vd, OMEGA would be estimated to be very large (around 45% in terms of CV, with 80% Shrinkage), despite statistical significance (dOF approx. -5.5). So I dropped the random effect and expressed Vd in terms of a single fixed effect. When the final model has come out, I performed bootstrap and found that most estimates are accurate except Vd, which has a very large standard error and bias (mean 232, bias 49, SE 156), while the estimates for CL and other parameters look normal. I then constructed the predictive plots for the developed model using both the original estimates (i.e. estimates using my original dataset) (#1) and estimates from one of the bootstrap runs which has an extreme estimate of Vd (9xx) (#2), and found out that the two plots of plasma profiles are quite different in terms of the shape (#1 is “taller”, #2 is much flatter) but have similar average Cp.

 

These seem to be suggesting that given my sparse data, it is impossible to require accurate estimations of both CL and Vd. Apart from fixing Vd to a fixed value, is there any other possible solutions? Or is there anything that I might have overlooked?

 

Thanks and regards,

Matthew



  

Received on Mon Nov 16 2015 - 08:41:17 EST

The NONMEM Users Network is maintained by ICON plc. Requests to subscribe to the network should be sent to: nmusers-request_at_iconplc.com. Once subscribed, you may contribute to the discussion by emailing: nmusers@globomaxnm.com.