RE: ETABAR p-value

-----Original Message----- From: [EMAIL PROTECTED] [mailto:[EMAIL PROTECTED] On Behalf Of Mats Karlsson Sent: Wednesday, February 21, 2007 12:32 AM To: [EMAIL PROTECTED] Cc: [email protected] Subject: RE: [NMusers] ETABAR p-value Dear Leonid, In your case there is no reason to expect the mean of the etabar to be zero, so a test of it does actually not make sense. You have pronounced shrinkage in your posthoc etas and then you don't know what the distribution should be (apart from expected median of zero). We have noted mean posthoc eta significantly different from zero even when the model is correct (see reference below for some more discussion on the "uselessness" of posthoc etas). http://www.aapspharmaceutica.com/search/abstract_view.asp?id=941&ct=06Ab stra cts 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 [EMAIL PROTECTED] -----Original Message----- From: [EMAIL PROTECTED] [mailto:[EMAIL PROTECTED] On Behalf Of Leonid Gibiansky Sent: Tuesday, February 20, 2007 20:49 To: Mats Karlsson Cc: [email protected] Subject: Re: [NMusers] ETABAR p-value Mats, Thanks for your reply. I think I found where the problem was: to estimate the probability of observed ETAbar, I used the distribution with the variance estimated by the nonmem (0.97) while t-test uses variance estimated from the data (0.11784 in this case). In this particular case, variance estimated from the data is much lower than OMEGA(3,3) because the POSTHOC ETA3 distribution is rather non-normal, resulting in a small p-value. Thanks Leonid Mats Karlsson wrote: > Dear Leonid, > > The etabar test is a t-test of the mean of the posthoc etas. I would > not discard a model just because of this not being the case as there > may be other reasons than misspecification for a no-zero mean of posthoc etas. Only > when data are very rich and there is no shrinkage (or when eta > shrinkage is > identically large for both positive and negative etas) would we expect > the mean of posthoc etas to be zero. > > 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 > [EMAIL PROTECTED] > > > > > > > > > > -----Original Message----- > From: [EMAIL PROTECTED] > [mailto:[EMAIL PROTECTED] On > Behalf Of Leonid Gibiansky > Sent: Tuesday, February 20, 2007 18:25 > To: [email protected] > Subject: [NMusers] ETABAR p-value > > Dear All, > Could anyone help me to interpret ETAbar p value? I have: > > TOT. NO. OF OBS RECS: 1486 > TOT. NO. OF INDIVIDUALS: 213 > > ETABAR: -0.52E-02 -0.27E-01 -0.93E-01 > P VAL.: 0.90E+00 0.24E+00 0.81E-04 > > ETA1 ETA2 ETA3 > ETA1 4.08E-01 > ETA2 2.26E-01 2.31E-01 > ETA3 0.00E+00 0.00E+00 9.70E-01 > > which looks too low for me for eta3. I checked that p of > abs(mean(eta)) > > 0.093 is about 0.17 for > normally distributed variable with SD=sqrt(0.97) and about 200 patients. > >> sum1 <- 0 >> for(i in 1:1000000) if(abs(mean(rnorm(213,0,sqrt(0.97))))> 0.093) >> sum1 <- > sum1+1 >> print(sum1/1000000) > [1] 0.168624 > > > How exactly this p-value is computed (NONMEM V) ? > > Thanks > Leonid > > > > > > -- The information contained in this email message may contain confidential or legally privileged information and is intended solely for the use of the named recipient(s). No confidentiality or privilege is waived or lost by any transmission error. If the reader of this message is not the intended recipient, please immediately delete the e-mail and all copies of it from your system, destroy any hard copies of it and notify the sender either by telephone or return e-mail. Any direct or indirect use, disclosure, distribution, printing, or copying of any part of this message is prohibited. Any views expressed in this message are those of the individual sender, except where the message states otherwise and the sender is authorized to state them to be the views of XOMA.