How to calculate confidence interval (CI) and prediction interval (PI) of individual prediction (IPRED) in NONMEM

2 messages 2 people Latest: Feb 14, 2020
Hi, I have a question on ADVAN5 and ADVAN7 related to dose event record. This is a general linear model. Can these two models allow multiple doses in compartment 1 and 3, simultaneously? Best regards, Sam Liao Pharmax Research, Inc.
Quoted reply history
On 7/19/2018 11:50 AM, Bauer, Robert wrote: > NONMEM 7.4 provides a straight-forward means of evaluating the standard error of IPRED and other table outputted parameters, by use of the option $TABLE … VARCALC=1. Please see nm743.pdf for more information on this, located at > > https://nonmem.iconplc.com/nonmem743 > > Robert J. Bauer, Ph.D. > > Senior Director > > Pharmacometrics R&D > > ICON Early Phase > > 820 W. Diamond Avenue > > Suite 100 > > Gaithersburg, MD 20878 > > Office: (215) 616-6428 > > Mobile: (925) 286-0769 > > [email protected] <mailto:[email protected]> > > www.iconplc.com http://www.iconplc.com/ > > *From:* [email protected] [ mailto: [email protected] ] *On Behalf Of *Kyun-Seop Bae > > *Sent:* Wednesday, July 18, 2018 8:56 PM > *To:* [email protected] > > *Subject:* [NMusers] How to calculate confidence interval (CI) and prediction interval (PI) of individual prediction (IPRED) in NONMEM > > Dear NMusers, > > Someone (several months ago via email) asked me how to calculate a confidence interval and prediction interval for individual prediction using R (might be with my “wnl" package”). > > At that time, I suggested the delta method for a confidence interval and simulation for prediction interval like visual predictive check (VPC). > > He/She then asked me how about using NONMEM script in p220 (for the prediction interval) and p221 (for the confidence interval) of Ette and William's ‘Pharmacometrics: The Science of Quantitative Pharmacology’(2007), when I could not answer about that and still recommended to use simulation technique. > > Now I can answer a little more about how to calculate those (although somewhat naïve way) in NONMEM (maybe in older versions only). > > NONMEM code in p220 should be corrected like the following; > > “VARCP = 2*G(1,1)*G(2,1)*OMEGAF(1,2) + VARCP > > “VARCP = 2*G(1,1)*G(3,1)*OMEGAF(1,3) + VARCP > > “VARCP = 2*G(2,1)*G(3,1)*OMEGAF(2,3) + VARCP > > “VARCP = VARCP + IPRED**2*SIGMAF(1,1) + VARCP*SIGMAF(1,1) + SIGMAF(2,2) > > And, NONMEM code in p221 should be corrected like the following; > > “VARCP = 2*G(1,1)*G(2,1)*OMEGAF(1,2) + VARCP > > “VARCP = 2*G(1,1)*G(3,1)*OMEGAF(1,3) + VARCP > > “VARCP = 2*G(1,1)*G(4,1)*OMEGAF(1,4) + VARCP > > “VARCP = 2*G(2,1)*G(3,1)*OMEGAF(2,3) + VARCP > > “VARCP = 2*G(2,1)*G(4,1)*OMEGAF(2,4) + VARCP > > “VARCP = 2*G(3,1)*G(4,1)*OMEGAF(3,4) + VARCP > > One of the references for the biggest different line is p180 of <Mood AM, Graybill F, Boes DC. Introduction to the theory of statistics. 3e. 1974>. > > Sincerely, > > Kyun-Seop Bae MD PhD > > Professor > > Department of Clinical Pharmacology and Therapeutics > > Asan Medical Center, University of Ulsan, Republic of Korea > >
Hi Sam, As far as I know, the simple answer is yes. You just have to specify a CMT data item for each dose to match the $MODEL record numbering of the compartments and the rate constants used by ADVAN5 and ADVAN7. In principle you can have as many doses as you want administered to any compartment at the same time and to multiple compartments at the same time. You have to specify a dosing record for each dose and each compartment. There may be an internal NONMEM limit but I am not aware of one. Best wishes, Nick -- 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(6)62 32 46 72 email: [email protected] http://holford.fmhs.auckland.ac.nz/ http://orcid.org/0000-0002-4031-2514 Read the question, answer the question, attempt all questions
Quoted reply history
From: [email protected] <[email protected]> On Behalf Of Sam Liao Sent: Saturday, 15 February 2020 10:36 AM To: [email protected] Cc: Bauer, Robert <[email protected]>; Lisa <[email protected]> Subject: Re: [NMusers] How to calculate confidence interval (CI) and prediction interval (PI) of individual prediction (IPRED) in NONMEM Hi, I have a question on ADVAN5 and ADVAN7 related to dose event record. This is a general linear model. Can these two models allow multiple doses in compartment 1 and 3, simultaneously? Best regards, Sam Liao Pharmax Research, Inc. -- Sam Liao