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

Hi Anita, Some history on expressing the variance estimate of the random effects of a parameter can be found here: https://www.mail-archive.com/[email protected]/msg02542.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 -- 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]<mailto:[email protected]> web: http://holford.fmhs.auckland.ac.nz/