Re: rounding issues with PK data

From: Bill Denney Date: June 10, 2013 technical Source: mail-archive.com
Hi Nele, For the first point, if you have values that are rounded like that and you will be mixing rounded and non-rounded values, then the simplest way to handle it would be to have a different additive error term for measurements that were or were not subject to the rounding. A more complex method would be to implement something akin to the M2 method but using both a lower and upper limit for the range of values that would be mapped to each value in the file. The higher complexity is unlikely to be worth it. With the sampling times only being documented as dates, to give the full answer, we'd need more information: is there a non-terminal phase to the half-life that extends beyond the first day? Is the terminal half-life > ~5 days? What is there a need for more precision than 1 day resolution to the half-life and is it possible (i.e. even if you had data down to the second, would your SE be <1 day for half-life)? Generally, if the half-life is more than about 5 days, there should be no major issue with only having dates of collection. Thanks, Bill
Quoted reply history
On Jun 10, 2013, at 2:57, "Kaessner, Nele" <[email protected]<mailto:[email protected]>> wrote: Dear nmusers, I have PK data from a compound with a very long half-life (weeks). I have two issues with this data and would very much like to hear your opinion on this: · Concentrations were rounded to integers, with LLOQ of 1. This means a concentration value of 2 could span values from 1.5-2.49, and unfortunately there is no way to find out what was originally measured, and I have quite a few measurements around LLOQ. How would you handle this in the coding (also later when mixing with additional data that was not rounded), and how will this rounding influence my parameter estimates? · The sampling times were only documented as dates (except for the day of dosing). With a long half-life compound, do you consider this to be critical? Your opinions would be very welcome. Best regards Nele ______________________________________________________________ Dr. Nele Käßner Principal Scientist Modeling and Simulation Global Pharmacometrics Experimental Medicine Takeda Pharmaceuticals International GmbH Thurgauerstrasse 130 8152 Glattpark-Opfikon (Zürich) Switzerland Visitor address: Alpenstrasse 3 8152 Glattpark-Opfikon (Zürich) Switzerland Phone: (+41) 44 / 55 51 404 Mobile: (+41) 79 / 654 33 99 mailto: [email protected]<mailto:[email protected]> http://www.takeda.com -------------------------------------------------------------------- The content of this email and of any files transmitted may contain confidential, proprietary or legally privileged information and is intended solely for the use of the person/s or entity/ies to whom it is addressed. If you have received this email in error you have no permission whatsoever to use, copy, disclose or forward all or any of its contents. Please immediately notify the sender and thereafter delete this email and any attachments.
Jun 10, 2013 Nele Kaessner rounding issues with PK data
Jun 10, 2013 Bill Denney Re: rounding issues with PK data
Jun 10, 2013 Jeroen Elassaiss-Schaap RE: rounding issues with PK data