Re: Rational of using IOV

On 2/11/2010 2:34 a.m., Buclin Thierry wrote: > Dear James, > > I always thought that intra-individual variability (IIV) classically represented the immovable limit on the gains to be expected from TDM -- IOV being indeed used only in a minority of population PK analyses. Both intra- and inter-occasion variability actually represent nuisance. We agree on the point that specifying an IOV term in a model will decrease the residual IIV. But wouldn't this precisely give a falsely favorable impression about potential gains from a TDM program? Am I wrong to think so? > > Kind regards > > Thierry > > *De :*James G Wright [mailto:[email protected]] > *Envoyé :* lundi, 1 novembre 2010 14:04 > *À :* Buclin Thierry > *Objet :* Re: [NMusers] Rational of using IOV > > Dear Thierry, > > I hope you are well. I think you are right to highlight the importance of IOV for TDM, but I would argue it is very important to include it in the model. This is because IOV places an immovable limit on the gains from TDM. The classic error is to develop a TDM strategy mistakenly lumping IOV with IIV, and drastically over-estimating the utility of TDM. > > Best regards, James > > On 01/11/2010 11:55, Buclin Thierry wrote: > > Hi Nicolas > > My short answer would be another question: "what is the aim of your analysis ?" > > IOV is fine to split variability into inter-individual, intra-individual-inter-occasion and intra-individual-intra-occasion random components. This is excellent for data description, and can bring interesting insight into the mechanisms explaining variability. But if you want to use your results for prediction, e.g. to devise a TDM program, you won't be able to draw relevant information from IOV: a blood sample obtained in a patient on a certain occasion won't inform you on your patient's behavior on another occasion; in this situation, a model merely distinguishing inter-individual and intra-individual variability components is easier to exploit. Thus, there may be good reasons not to use IOV even when it would be possible. > > Kind regards > > Thierry > > Thierry Buclin, MD, PD, > > Division of Clinical Pharmacology and Toxicology > > University Hospital of Lausanne (CHUV) > > Lausanne - SWITZERLAND > > tel +41 21 314 42 61 > > fax +41 21 314 42 66 > > On 1/11/2010 10:53 a.m., Nicolas SIMON wrote: > > Dear colleagues, > > could someone give me an advice about the rational of using IOV in a particular circumstance? > > We have data from a clin trial with 3 occasions for each patient. It was a chemotherapy and the patients have received up to 7 cures. The issue is that the 3 occasions differ from one patient to another. > > Patient X may have be seen on cure 3, 5 and 7 while patient X+1 was seen on cure 2, 5 and 6 or whatever... > > It seems to me that combining the 1st occ of all patients is meaningless (as for 2nd and 3rd). Shall we use as many occasions as cures (7 in our dataset)? In that case, how many patients by occ is relevant as a minimum? For certain occ we may have few patients. Combining cures is hazardous and has no clinical justification. > > Best regards > Nicolas > > Pr Nicolas SIMON > Universite de la Mediterranee (Aix-Marseille II) > > -- > James G Wright PhD, > Scientist, Wright Dose Ltd > Tel: UK (0)772 5636914 -- Nick Holford, Professor Clinical Pharmacology Dept Pharmacology& Clinical Pharmacology University of Auckland,85 Park Rd,Private Bag 92019,Auckland,New Zealand tel:+64(9)923-6730 fax:+64(9)373-7090 mobile:+64(21)46 23 53 email: [email protected] http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford