criteria for implementing BSV-V2 and BSV-Q

3 messages 3 people Latest: Mar 19, 2014

criteria for implementing BSV-V2 and BSV-Q

From: Carolien Hazendonk Date: March 19, 2014 technical
Dear all, In the present project a two compartmental structural model adequately describes our data. Estimated parameters are Cl, V1, Q and V2, between-subject varibility is estimated for CL and V1 - estimates are precise. In the further development of the structural model introduction of BSV on either V2 and Q produced a significant drop in objective function of -17 points. Estimates were however large (>100%) with moderate precision (40-50%) and large shrinkage (40-50%). We are aware that interpreting the goodness of fit plots with these shrinkage values is not reliable (Savic & Karlsson 2009). We are wondering what criteria to use for implementing BSV-V2 and BSV-Q in the structural model. Kind regards, Carolien Hazendonk Drs. H.C.A.M. Hazendonk, M.D. PhD-student Department of (Pediatric)Hematology, Erasmus University Medical Center Rotterdam E-mail address: [email protected]

RE: criteria for implementing BSV-V2 and BSV-Q

From: Devin Pastoor Date: March 19, 2014 technical
Dear Carolien, What type of sampling/how many subjects do you have data for? I think there are three main ways of handling your issue - first you can remove the the BSV on V2 and or Q (you may only try it on one). The second is to use the resulting model but to keep in mind that you are dealing with certain baised diagnostic plots and to interpret carefully. Lastly, if you have prior data on the compound from other studies you can fix those values to published or prior results. I think each approach has its place, and would just keep in mind what you are trying to use your model for and be careful to document the assumptions you are making as you make inferences/decisions based on the results from the model. Best of luck, Devin Pastoor Clinical Research Scientist Center for Translational Medicine University of Maryland, School of Pharmacy
Quoted reply history
From: [email protected] [mailto:[email protected]] On Behalf Of H.C.A.M. Hazendonk Sent: Wednesday, March 19, 2014 12:54 PM To: [email protected] Cc: H.C.A.M. Hazendonk Subject: [NMusers] criteria for implementing BSV-V2 and BSV-Q Dear all, In the present project a two compartmental structural model adequately describes our data. Estimated parameters are Cl, V1, Q and V2, between-subject varibility is estimated for CL and V1 - estimates are precise. In the further development of the structural model introduction of BSV on either V2 and Q produced a significant drop in objective function of -17 points. Estimates were however large (>100%) with moderate precision (40-50%) and large shrinkage (40-50%). We are aware that interpreting the goodness of fit plots with these shrinkage values is not reliable (Savic & Karlsson 2009). We are wondering what criteria to use for implementing BSV-V2 and BSV-Q in the structural model. Kind regards, Carolien Hazendonk Drs. H.C.A.M. Hazendonk, M.D. PhD-student Department of (Pediatric)Hematology, Erasmus University Medical Center Rotterdam E-mail address: [email protected]<mailto:[email protected]>

Re: criteria for implementing BSV-V2 and BSV-Q

From: Ekaterina Gibiansky Date: March 19, 2014 technical
Dear Carolien, Compare predictions (PRED and IPRED) between the models without and with BSV on the parameters of the second compartment. It could be that extra ETA accomodates few outlying points. 17 points of OF is not much (unless your data set is small). You may be better off with a stable model with fewer random effects unless you see a real improvement of the model in diagnostic plots (including VPC). Regards, Katya Ekaterina Gibiansky, Ph.D. CEO&CSO, QuantPharm LLC Web: www.quantpharm.com Email: EGibiansky at quantpharm.com
Quoted reply history
On 3/19/2014 12:53 PM, H.C.A.M. Hazendonk wrote: > Dear all, > > In the present project a two compartmental structural model adequately describes our data. Estimated parameters are Cl, V1, Q and V2, between-subject varibility is estimated for CL and V1 - estimates are precise. In the further development of the structural model introduction of BSV on either V2 and Q produced a significant drop in objective function of -17 points. Estimates were however large (>100%) with moderate precision (40-50%) and large shrinkage (40-50%). We are aware that interpreting the goodness of fit plots with these shrinkage values is not reliable (Savic & Karlsson 2009). We are wondering what criteria to use for implementing BSV-V2 and BSV-Q in the structural model. > > Kind regards, > > Carolien Hazendonk > > Drs. H.C.A.M. Hazendonk, M.D. PhD-student > Department of (Pediatric)Hematology, > > Erasmus University Medical Center Rotterdam > > E-mail address: [email protected]