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 <br /><br /> ICON plc made the following annotations. ------------------------------------------------------------------------------ This e-mail transmission may contain confidential or legally privileged information that is intended only for the individual or entity named in the e-mail address. If you are not the intended recipient, you are hereby notified that any disclosure, copying, distribution, or reliance upon the contents of this e-mail is strictly prohibited. If you have received this e-mail transmission in error, please reply to the sender, so that ICON plc can arrange for proper delivery, and then please delete the message. Thank You, ICON plc South County Business Park Leopardstown Dublin 18 Ireland Registered number: 145835
