2 replies to this topic

[cxzhang]

Dear all,

 

For a popPK model I am working on, I estimated interoccasion variability (IOV) for CL for 4 different occasions, assuming the IOV estimates to be the same for all 4 occasions due to limited data availability. Therefore, I obtained 4 identical omega estimates and 4 identical standard error estimates for the four occasions (i.e. IOV on CL for occasion 1 =  IOV on CL for occasion 2 = IOV on CL for occasion 3 = IOV on CL for occasion 4). My understanding is that I only need to report one estimate and its standard error for IOV on CL as my model output, instead of reporting the same set of values 4 times defined by the occasions. However, I do not know what to report for the shrinkage associated with IOV on CL. In the Omega sheet, 4 different shrinkage values were shown associated with the 4 occasions, ranging from 0.3 to 0.9. From looking at published studies, people report only one shrinkage value for each IOV tested. How can I obtain an overall shrinkage value to report for the IOV on CL? The number of data points for each occasion are different (e.g. intense sampling on occasion 1 and 4, sparse sampling on occasion 2 and 3), in case this matters.

 

Thank you for your help!

Edited by cxzhang, 13 October 2023 - 05:48 PM.

[smouksassi1]

while IOV  OCC 1, 2 , 3.. have a common variance

the posthocs will be different i.e the individual occasion specific etaclocc1 , will be different and hence you will get 

and occasion specific shrinkage

 

not sure it makes sense to compute an overall shrinkage over all occasions 

[cxzhang]

while IOV  OCC 1, 2 , 3.. have a common variance

the posthocs will be different i.e the individual occasion specific etaclocc1 , will be different and hence you will get 

and occasion specific shrinkage

 

not sure it makes sense to compute an overall shrinkage over all occasions 

 

Thank you smoukasassi1 for your reply! Yes, I do agree with you. I understand why there are separate shrinkage values for each occasion. Therefore, I am very confused by what I've seen in popPK literature because when IOV shrinkage is reported, only 1 value is usually presented, such as in the example below (Chan et al., Pharm Res. 2020 Jan 6;37(2):25. 

doi: 10.1007/s11095-019-2752-y.).

 

For IOV to make sense, there have to be multiple occasions defined. Therefore, several shrinkage values should have been estimated for each occasion. I should probably rephrase my question:

1. Why do people report only one shrinkage value for each IOV? What is this single shrinkage value telling us and is this standard practice? 

2. Is there a way to obtain a single shrinkage value?

3. Or is this due to some algorithm differences in how IOV is calculated between NONMEM and Phoenix NLME? 

 

Thank you!

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Edited by cxzhang, 13 October 2023 - 05:13 PM.