Re: simulation with uncertainty of THETA
Ying,
I think its a reasonable starting point to add 30-40% BSV to PKPD parameters but for simulation you should also think carefully about adding an off-diagonal covariance to reflect the very common correlation between random BSV.
The subject of your email suggests you are using CV% to refer to the uncertainty of THETA. If you a really interested in simulating uncertainty as well as variability (BSV) then you should be thinking about all the parameters (THETA, OMEGA, SIGMA). Once again if you add uncertainty you should be thinking about the correlation between the parameters.
Can you explain more clearly what the objective of your simulation might be?
Best wishes,
Nick
Quoted reply history
On 8/07/2013 10:18 p.m., Ying Zhang wrote:
> Dear all,
>
> When do the simulation, if I have all of the parameter information from literature and internal data, I will fix the PKPD parameter and add about 30% for PK and 40% for PD as IIV. But my question is do we need to think about the CV% of THETA, since we fixed it, we could not add it in one run. if it is necessary, for instance, we will add 20% of CV to one mean THETA, how to do it, or does PsN can implement this issue?
>
> Best
> Ying
--
Nick Holford, Professor Clinical Pharmacology
Dept Pharmacology & Clinical Pharmacology, Bldg 503 Room 302A
University of Auckland,85 Park Rd,Private Bag 92019,Auckland,New Zealand
office:+64(9)923-6730 mobile:NZ +64(21)46 23 53 FR +33(7)85 36 84 99
email: [email protected]
http://holford.fmhs.auckland.ac.nz/
Holford NHG. Disease progression and neuroscience. Journal of Pharmacokinetics
and Pharmacodynamics. 2013;40:369-76
http://link.springer.com/article/10.1007/s10928-013-9316-2
Holford N, Heo Y-A, Anderson B. A pharmacokinetic standard for babies and
adults. J Pharm Sci. 2013:
http://onlinelibrary.wiley.com/doi/10.1002/jps.23574/abstract
Holford N. A time to event tutorial for pharmacometricians. CPT:PSP. 2013;2:
http://www.nature.com/psp/journal/v2/n5/full/psp201318a.html
Holford NHG. Clinical pharmacology = disease progression + drug action. British
Journal of Clinical Pharmacology. 2013:
http://onlinelibrary.wiley.com/doi/10.1111/bcp.12170/abstract