I would use a population approach but would not pool the sparse data. I think it would be appropriate to start with a 2 compartment model and get the objective function. You can then try more compartment and see if it improves the obj statistically. I have doubts about being able to fit the 4 compartment model under that sampling design. I would also perform a bootstrapping approach to assess quantitatively the precision of all the model parameters. Serge Guzy
_____ From: [EMAIL PROTECTED] [mailto:[EMAIL PROTECTED] On Behalf Of Mulla Hussain - Senior Pharmacist Sent: Wednesday, February 28, 2007 8:57 AM To: [email protected] Subject: [NMusers] Best approach with limited data Hi I have sparse data from n=69 individuals from 3 dose levels, and rich data from 1 individual at 1 dose level, following the deployment of a drug eluting device. In the 69 individuals I have a single plasma sample, and a single tissue sample (both collected at the same time point). The sample time points range from 0.25 to 120 days (post deployment), 2 individuals contributing at each time point. In the 1 individual I have greater than 8 sample points in each biophase. The rich data from the 1 individual suggests 2 compartment disposition in both plasma and tissue (a 4 compartment model described the data quite well in WinNonLin). Pooling the sparse data at each dose level, suggests 2 compartment disposition in both blood and plasma. My questions are:- 1) Would you take a population approach to this data? - can mean population parameters and their variability be robustly estimated? 2) Would you expect the parameters of a 4 cmpt model (8 thetas and at least 4 omegas) to be reliably estimated with this data? Any thoughts much appreciated. Thanks Hussain Mulla Department of Pharmacy University Hospitals of Leicester NHS Trust Glenfield Hospital Leicester England This e-mail, including any attached files, may contain confidential and / or privileged information and is intended for the exclusive use of the addressee(s) printed above. If you are not the addressee(s), any unauthorised review, disclosure, reproduction, other dissemination or use of this e-mail, or taking of any action in reliance upon the information contained herein, is strictly prohibited. If this e-mail has been sent to you in error, please return to the sender. No guarantee can be given that the contents of this email are virus free - The University Hospitals of Leicester NHS Trust cannot be held responsible for any failure by the recipient(s) to test for viruses before opening any attachments. The information contained in this e-mail may be the subject of public disclosure under the Freedom of Information Act 2000 - unless legally exempt from disclosure, the confidentiality of this e-mail and your reply cannot be guaranteed. Copyright in this email and any attachments created by us remains vested in the University Hospitals of Leicester NHS Trust. -- The information contained in this email message may contain confidential or legally privileged information and is intended solely for the use of the named recipient(s). No confidentiality or privilege is waived or lost by any transmission error. If the reader of this message is not the intended recipient, please immediately delete the e-mail and all copies of it from your system, destroy any hard copies of it and notify the sender either by telephone or return e-mail. Any direct or indirect use, disclosure, distribution, printing, or copying of any part of this message is prohibited. Any views expressed in this message are those of the individual sender, except where the message states otherwise and the sender is authorized to state them to be the views of XOMA.
