RE: [NMusers] Minimum patients number and reference to Laputa in Gullivers Travels

Mark,

The best guess of an expert may well be what is most cost-efficient for
designing a study. However, it needs to be tailored to the particular study
which requires more information that we have been provided with and more
effort than we are likely to put in. Therefore, my advice to Ahmed is to get
someone who is experienced onboard. Don't rely on general advice on a
listserv for designing your trial if you don't have the expertise yourself.

BTW As you mention it, I think that the rule about etas can be particularly
misleading and I can't really see what basis it has. With dense data, the
number of subjects will influence the number of etas for which an estimate
can be obtained in manner that is far from linear (which the rule implies).
It will of course be related to the precision with which a variance will be
estimated, but that's not the question.

Mats




Mats Karlsson, PhD
Professor of Pharmacometrics
Div. of Pharmacokinetics and Drug Therapy
Dept. of Pharmaceutical Biosciences
Faculty of Pharmacy
Uppsala University
Box 591
SE-751 24 Uppsala
Sweden
phone +46 18 471 4105
fax +46 18 471 4003
mats.karlsson_at_farmbio.uu.se


        
        

        



-----Original Message-----
From: owner-nmusers_at_globomaxnm.com [mailto:owner-nmusers_at_globomaxnm.com] On
Behalf Of Mark Sale - Next Level Solutions
Sent: Sunday, January 28, 2007 22:27
Cc: nmusers_at_globomaxnm.com
Subject: [NMusers] Minimum patients number and reference to Laputa in
Gullivers Travels

Mats,
 These "rules of thumb" are exactly as you suspect, a well intentioned
best guess. But, lacking other answers, (and for all this discussion,
I don't recall another answer to the question, with the exception of
Serge, who suggests a simulation based method). It isn't clear to me
that an answer based in experience, admitted incomplete, is more likely
to lead in the wrong direction than no answer at all. I have found the
academic discussion from people smarter than I am very interesting,
just haven't seen an answer to the question (again, except perhaps from
Serge who I agree with, that simulation is the best way to answer the
question or how many. Optimal design is probably a very good, and as
Steve points out a very fast, way to answer when).
  Experience also suggests that practical matters drive sample size as
much as theoretical
> > Minimum 10 patients per eta would mean 50-60 patients.
> > I'm sure this number would give optimal results but as
> > a matter of fact I don't think I would be able to
> > reach it.

At which point, we need the academics to try to rescue an underpowered
study.




Mark Sale MD
Next Level Solutions, LLC
www.NextLevelSolns.com


> -------- Original Message --------
> Subject: RE: [NMusers] Minimum patients number...
> From: "Mats Karlsson" <mats.karlsson_at_farmbio.uu.se>
> Date: Sun, January 28, 2007 3:49 pm
> To: "'Mark Sale - Next Level Solutions'" <mark_at_nextlevelsolns.com>
> Cc: <nmusers_at_globomaxnm.com>
>
> Mark,
>
> Although I realize that the rules of thumb are well-intended ways to help
> less experienced along, the data requirements are so situation-dependent
> that any such general rule is likely to guide in the wrong direction more
> often than not.
>
> If indeed the "empiric observations" you refer to is from a database
> collected and analyzed for the purpose of coming up with these rules, it
> would be interesting to learn more about it. Otherwise, I guess it is like
> most rules of thumb that we try to formulate - just a best guess by an
> experienced analyst.
>
> Best regards,
> Mats
>
>
> Mats Karlsson, PhD
> Professor of Pharmacometrics
> Div. of Pharmacokinetics and Drug Therapy
> Dept. of Pharmaceutical Biosciences
> Faculty of Pharmacy
> Uppsala University
> Box 591
> SE-751 24 Uppsala
> Sweden
> phone +46 18 471 4105
> fax +46 18 471 4003
> mats.karlsson_at_farmbio.uu.se
>
>
>
>
>
>
>
>
>
> -----Original Message-----
> From: owner-nmusers_at_globomaxnm.com [mailto:owner-nmusers_at_globomaxnm.com]
On
> Behalf Of Mark Sale - Next Level Solutions
> Sent: Saturday, January 27, 2007 20:50
> Cc: nmusers_at_globomaxnm.com
> Subject: RE: [NMusers] Minimum patients number...
>
> Mats,
> The "rules of thumb" are indeed empiric observations from one
> variable. But, if you have two dependent variables, you have twice the
> data (one time point, two DVs), and twice the parameters. So, I think
> the rule may be consistent, but I don't know how valuable it is in the
> first place.
>
>
>
> Mark Sale MD
> Next Level Solutions, LLC
> www.NextLevelSolns.com
>
>
> > -------- Original Message --------
> > Subject: RE: [NMusers] Minimum patients number...
> > From: "Mats Karlsson" <mats.karlsson_at_farmbio.uu.se>
> > Date: Sat, January 27, 2007 11:41 am
> > To: "'Ahmed Hawwa'" <ahawwa1_at_yahoo.com>, <nmusers_at_globomaxnm.com>
> >
> > Hi,
> >
> > I think that all the rules of thumb that have been mentioned are based
on
> > the assumption that you have a single observed variable. If you observe
> > several, you certainly can expect to estimate more parameterers.
> >
> > Mvh,
> > Mats
> >
> >
> > Mats Karlsson, PhD
> > Professor of Pharmacometrics
> > Div. of Pharmacokinetics and Drug Therapy
> > Dept. of Pharmaceutical Biosciences
> > Faculty of Pharmacy
> > Uppsala University
> > Box 591
> > SE-751 24 Uppsala
> > Sweden
> > phone +46 18 471 4105
> > fax +46 18 471 4003
> > mats.karlsson_at_farmbio.uu.se
> >
> >
> >
> >
> >
> >
> >
> >
> >
> > -----Original Message-----
> > From: owner-nmusers_at_globomaxnm.com [mailto:owner-nmusers_at_globomaxnm.com]
> On
> > Behalf Of Ahmed Hawwa
> > Sent: Saturday, January 27, 2007 02:10
> > To: nmusers_at_globomaxnm.com
> > Subject: RE: [NMusers] Minimum patients number...
> >
> > Hi all,
> >
> > Thank you all indeed for the valuable commenets. I
> > have actually 19 patients only and I need to look into
> > the PK parameters of two metabolites.
> >
> > Minimum 10 patients per eta would mean 50-60 patients.
> > I'm sure this number would give optimal results but as
> > a matter of fact I don't think I would be able to
> > reach it.
> >
> > > I would suggest that you assess each case on its
> > > merits and determine the
> > > effectiveness of any proposed design using either
> > > simulation linked with
> > > estimation (which is tedious, slow, not optimal but
> > > often effective)
> >
> > Regarding using simultation do you mean to put certain
> > values of thetas and then run a simulation and compare
> > results with the actual concentrations or did I miss
> > the point?
> >
> > > or an
> > > information theoretic technique (such as optimal
> > > design).
> > > The optimal design software WinPOPT
> > > (www.winpopt.com), which is freely
> > > available, allows you to rapidly assess the
> > > effectiveness of various designs
> > > as well as optimize a design within your specific
> > > study constraints (e.g.
> > > clinic visit times etc).
> >
> > I think one of my study constrains is clinic visit
> > times since patients taking our drug are actually
> > outpatients and we are able to collect one sample only
> > at each clinic visit. would this software be of any
> > help??
> >
> > Looking to hear from you soon.
> >
> > Regards,
> > ahawwa
> >
> >
> >
> >
> >
>
____________________________________________________________________________
> > ________
> > Cheap talk?
> > Check out Yahoo! Messenger's low PC-to-Phone call rates.
> > http://voice.yahoo.com


Received on Sun Jan 28 2007 - 17:47:29 EST