Re: %RSE for IIV when expressed as %CV instead of variance

On Sat, May 11, 2024 at 12:09 PM Nick Holford <[email protected]> wrote: > > > Thanks to Karam who retrieved the quote I mentioned from Stuart Beal. > > > > > > -- > > Nick Holford, Professor Emeritus Clinical Pharmacology, MBChB, FRACP > > mobile: NZ+64(21) 46 23 53 ; FR+33(6) 62 32 46 72 > > email: [email protected] > > web: http://holford.fmhs.auckland.ac.nz/ > > > > *From:* karam alali <[email protected]> > *Sent:* Saturday, May 11, 2024 7:31 PM > *To:* Nick Holford <[email protected]> > *Subject:* Re: [NMusers] %RSE for IIV when expressed as %CV instead of > variance > > > > Hi Prof. Nick, > > > > I got a capture of the original quote from web archive: > > > > > https://web.archive.org/web/20050117183801/ http://gaps.cpb.ouhsc.edu/nm/91sep2697.html > https://web.archive.org/web/20050117183801/http:/gaps.cpb.ouhsc.edu/nm/91sep2697.html > > > > Best Regards, > > > > Karam Alali > > Ph.D. Candidate > > Universiti Sains Malaysia > > > > On Sun, 12 May 2024, 2:10 am Nick Holford, <[email protected]> > wrote: > > Hi Anita, > > > > Some history on expressing the variance estimate of the random effects of > a parameter can be found here: > > > https://web.archive.org/web/20050117183801/ http://gaps.cpb.ouhsc.edu/nm/91sep2697.html > https://web.archive.org/web/20050117183801/http:/gaps.cpb.ouhsc.edu/nm/91sep2697.html > > Stuart Beal wrote about this issue in 1997 and cautioned that > the interpretation is in the eye of the user because NONMEM does > not require ETAs to be normally distributed: "Many discussions state that > ETA is assumed to be normal, but these are often misleading. While there > are sometimes good reasons for making this assumption, the NONMEM > methodology largely avoids the assumption." He proposed the term "apparent > coefficient of variation" as a way of implying a normal distribution of > ETA. "Since we do not need to make the normality assumption, it does > not follow that the "extra accuracy" given by the lognormal formula > really represents extra accuracy; it can just as well be garbage. Suppose > we want to really do the right thing, and CV is large (perhaps as > a pragmatic matter, we will judge the CV to be large when the results from > the two formulas differ substantially). Then we should probably avoid > reporting the CV as a "CV", but report it as an "apparent CV"." > > > > Unfortunately, the original quote that I cited from Stuart Beal (the > originator of NONMEM) no longer seems to be available. > > http://gaps.cpb.ouhsc.edu/nm/91sep2697.html > > In the example you provide you mention ETA so presumably you are referring > to random parameter variability not residual error. I encourage you not to > use the acronym “IIV” because without other information is not clear if > this means “inter individual variability” (e.g. PPV, population parameter > variability of a parameter) or “intra individual variability” describing > residual unexplained variability, RUV (“residual error”). > > The relative standard error can be estimated using a non-parametric > bootstrap by dividing the standard deviation of the bootstrap distribution > by the average of the bootstrap distribution of the parameters. The > non-parametric BS does not make the assumption that the uncertainty of the > parameters is normal and therefore symmetrical. > > Best wishes, > > > > Nick > > > > NOTE: The address for Anita Moein [email protected] was bounced by the > University of Auckland email server. This may be linked to the red warning > shown below. > > > > -- > > Nick Holford, Professor Emeritus Clinical Pharmacology, MBChB, FRACP > > mobile: NZ+64(21) 46 23 53 ; FR+33(6) 62 32 46 72 > > email: [email protected] > > web: http://holford.fmhs.auckland.ac.nz/ > > > > *From:* [email protected] <[email protected]> *On > Behalf Of *Anita Moein > *Sent:* Saturday, May 11, 2024 3:09 PM > *To:* [email protected] > *Subject:* [NMusers] %RSE for IIV when expressed as %CV instead of > variance > > > > Caution - Forged External Domain! > This e-mail cannot be validated and may not have been sent by the sender > shown in the 'From' field. > If you were not expecting to receive this e-mail we recommend you contact > the sender to confirm that they sent it. > If you believe this email was legitimately sent, we suggest the sender > notify their e-mail administrator that it has been received as a forged > (fake) e-mail by the University of Auckland. > Please contact the Staff Service Centre on extension 86000 if you require > further assistance. > > Dear All: > > > > I have a question regarding reporting ETAs as %CV instead of variance. > > > > In NONMEM the IIV estimate is reported as variance with associated RSE%. > > > > How can I convert the IIV Estimate and RSE% to report it as CV%? > > > > Thank you! > > > > Best, > > Anita > > > > > > > > > *Anita Moein* > > Senior Scientist > > Modeling and Simulation | Clinical Pharmacology | Genentech > > Phone: (650) 866 7701 | Cell: (415) 254 7972 > > > > > >