Re: [NMusers] Rational of using IOV

Nicolas,

Within subject variability in a parameter (e.g. clearance) can be
predictable ('fixed effect') e.g. associated with maturation of renal
function in young children, or can be unpredictable ('random effect')
i.e. apparently varying randomly from occasion to occasion.

IOV is usually used to describe the random between occasion
variability. Because this is by assumption a random source of
variability it makes no difference which occasion (or treatment) you
associate it with. In your case you have 3 occasions for each patient.
Just number the occasion 1,2 and 3 for every patient and estimate IOV in
the usual way as a random effect with variance described by OMEGA.

I assume you use the word 'cure' to mean treatment rather than complete
remission of the disease. If you think there may be non-random
differences between occasions e.g. due to different treatments on each
occasion, then you can model these with a predictable ('fixed effect')
treatment covariate model with each treatment type representing a
different value of the treatment covariate. If you only have a few
patients for a particular treatment type then of course you are unlikely
to detect a treatment type effect and should be very cautious about
accepting any effect you find as being real (Ribbing & Johnson 2004).

Best wishes,

Nick

Ribbing J, Jonsson EN. Power, Selection Bias and Predictive Performance
of the Population Pharmacokinetic Covariate Model. Journal of
Pharmacokinetics and Pharmacodynamics. 2004;31(2):109-34.

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)
>
>

--
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: n.holford_at_auckland.ac.nz
http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford


Received on Sun Oct 31 2010 - 18:51:43 EDT