Re: CrcL or Cr in pediatric model

Hi Jakob, I am sorry, I made an error in that model, it should be CL=THETA(1)*(WT/70)^(3/4) * [1+THETA(2)*(RF-RF0)] For subjects with the normal RF (RF=RF0) the second term is one. As always, all covariate expressions should be centered at "normal" values. Leonid -------------------------------------- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web: www.quantpharm.com e-mail: LGibiansky at quantpharm.com tel: (301) 767 5566 Ribbing, Jakob wrote: > Leonid, > > As I understand the linear model you suggested it can be simplified* to > this structure: > THETA(1)*((WT/70)^(3/4)+THETA(2)*CRCL) > > I call this additive, because the two covariates affect TVCL in an > absolute sense, without interaction. My main message was that I find > this model appealing, because it has the properties: > a)There is a linear increase of CL with CRCL > b)An increase in CRCL increases CL with an absolute number which is the > same for two subjects with different WT > > The same can not be said about this model: > TVCL=THETA(1)*(WT/70)^(3/4) * RF^GAMMA > The latter model carries a built-in interaction which may provide a > better description of the data in situations where e.g. non-renal > elimination decreases with CRCL or where the secretory component of > renal elimination is more important for creatinine than for the drug. > However, in the opposite situations the interaction would be working in > the wrong direction (assuming GAMMA<1). Maybe we can leave what > basic-model assumption we want to use as a matter of personal or > drug-specific preference? > > Best > > Jakob > > PS > Nonmem users is like an octopus: Just when you think you are free one of > its threads pulls you back in again :>) > Much of this discussion is around additivity. If I have understood the > definition of additivity wrong, then I apologies on beforehand, so that > this can still be my final "contribution" to this thread. Likewise if I > misunderstood what model Leonid was actually suggesting... > DS > > *This is how I have simplified the suggested linear model: > TVCL=THETA(1)*(WT/70)^(3/4) * (1+THETA(2)*RF)= > =THETA(1)*(WT/70)^(3/4) * (1+THETA(2)*CRCL/(WT/70)^(3/4)) = > =THETA(1)*(WT/70)^(3/4)+THETA(1)*(WT/70)^(3/4)*THETA(2)*CRCL/(WT/70)^(3/ > 4)= > =THETA(1)*((WT/70)^(3/4)+THETA(2)*CRCL) > > Or =THETA(1)* (WT/70)^(3/4)+THETA(1)*THETA(2)*CRCL > Similar: THETA(1)* (WT/70)^(3/4)+THETA(2)*CRCL (where the interpretation > of THETA(2) changed from the line before) >