Re: OFV by endpoint of joint models?

On Mon, Oct 10, 2022 at 10:45 PM Mats Karlsson <[email protected]> wrote: > Hi Matts, > > > > One opportunity to learn about the expected fit of a model to data in > relation to the actual fit is to use the PsN functionality “simeval”. In > this functionality multiple data sets are simulated from the final model > and the realized design. The OFV per subject (and the overall OFV) can be > assessed after evaluation (i.e., MAXEVAL=0) or estimation of each of the > simulated data sets. This will provide reference OFV distributions with > which the real data OFV (subject or total study population) can be compared > in a PPC like manner. This is developed from Largajolli et al. ( > https://www.page-meeting.org/default.asp?abstract=3208). > > > > In your case, you are interested in learning about the relative > contribution of the different variables of a joint model. While not having > tried it, I imagine that you can, based on your final joint model(s), > obtain the expected OFV distribution one variable at a time as well as them > jointly. From this it ought to be possible to learn some about the quality > of the model with respect to variable A, variable B and their joint > distribution in describing the real data. > > > > Best regards, > > Mats > > *From:* [email protected] <[email protected]> *On > Behalf Of *Stephen Duffull > *Sent:* den 10 oktober 2022 21:56 > *To:* Jeroen Elassaiss-Schaap (PD-value) <[email protected]> > *Cc:* Matts Kågedal <[email protected]>; [email protected] > *Subject:* RE: [NMusers] OFV by endpoint of joint models? > > > > HI Jeroen > > > > I tested this with additive error (i.e. interaction has no influence) and > combined. Rank order was not preserved. > > > > To be clearer, this was a PK only example and I compared sum(CIWRES^2) for > each individual vs PHI(). I was trying to see if I could get the PHI() per > analyte for a multiple response model and thought that a quick way of doing > this was to grab the relative contribution from CIWRES. > > > > Cheers > > > > Steve > > > > *From:* Jeroen Elassaiss-Schaap (PD-value) <[email protected]> > *Sent:* Tuesday, 11 October 2022 8:36 am > *To:* Stephen Duffull <[email protected]> > *Cc:* Matts Kågedal <[email protected]>; [email protected] > *Subject:* Re: [NMusers] OFV by endpoint of joint models? > > > > Hi Steven, > > > > Thanks for sharing! CWRES is “polluted” by the ETA gradients more directly > compared to OFV. One would however hope for rank order consistency. Did you > also test this without interaction? Might also be interesting to test the > other residuals that nonmem offers in that respect. > > > > Cheers > > Jeroen > > http://pd-value.com > https://apc01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fpd-value.com%2F&data=05%7C01%7Cstephen.duffull%40otago.ac.nz%7C1017274f1209442cc1b408daaaf6aab3%7C0225efc578fe4928b1579ef24809e9ba%7C0%7C0%7C638010273680373817%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=VG6Wo1oVz8Ti2jcYV0hY%2BdqZTETwRUgxbARS4eRhoY4%3D&reserved=0 > [email protected] > @PD_value > +31 6 23118438 <+31%206%2023118438> > -- More value out of your data! > > > > Op 10 okt. 2022 om 18:51 heeft Stephen Duffull < > [email protected]> het volgende geschreven: > > Hi Jeroen > > I note your thought about CWRES and OFV. In some exploratory work, we did > not find that the rank order of abs(CIWRES) or CIWRES^2 and PHI() was > preserved (with FOCEI) for continuous data. I had anticipated some rank > similarity. > > Cheers > > Steve > ________________________________________ > Stephen Duffull | Professor > Otago Pharmacometrics Group > School of Pharmacy | He Rau Kawakawa > University of Otago | Te Whare Wānanga o Otāgo > Dunedin | Ōtepoti > Aotearoa New Zealand > Ph: 64 3 479 5099 > > > > > > -----Original Message----- > From: [email protected] <[email protected]> On > Behalf Of Jeroen Elassaiss-Schaap (PD-value B.V.) > Sent: Tuesday, 11 October 2022 4:07 am > To: Matts Kågedal <[email protected]>; [email protected] > Subject: Re: [NMusers] OFV by endpoint of joint models? > > Hi Matts, > > The easiest way to assess is when one of two endpoints is modeled directly > (TTE, logistic regression) as often is the case, than look at the Y value > for those endpoints, as reported in the PRED variable. The sum of those > values is the ofv, or proportional to it, for that particular endpoint - > the other endpoint is than affected in the inverse way. > > If you have multiple continuous endpoints it becomes more complicated. > You could either look at the sum of absolute CWRES to get an idea, but not > exact in terms of ofv comparison. Another approximate comparison would be > to run the model without evaluation (e.g. MAXEVAL=0) with the original > msfofile as $MSFI for the separate endpoints (by e.g. > IGN(DVID.NE.x) where x is your endpoint). It is not exact, again, as it > ignores the correlation between endpoints but should get you in the > neighborhood. As an improvement to this method you could force evaluation > at the original posthocs by reading them in in your datafile > - this would still ignore correlation but the effect would be largely > diminished because the posthocs are fixed to those estimated with > correlation. > > Hope this helps, > > Jeroen > > > https://apc01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fpd-value.com%2F&data=05%7C01%7Cstephen.duffull%40otago.ac.nz%7C1ebbd4a5cbce449913f108daaad22217%7C0225efc578fe4928b1579ef24809e9ba%7C0%7C0%7C638010116756566698%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=PEGSjbNvoRzu%2B6AbaXCXTHlNGkGc28Eb7QgKu1tE9sM%3D&reserved=0 > [email protected] > @PD_value > +31 6 23118438 > -- More value out of your data! > > On 10-10-2022 16:03, Matts Kågedal wrote: > > Hi all, > > I have a question related to the objective function value when > > multiple endpoints are modelled jointly. Specifically I would like to > > know if a change in in OFV between models is driven primarily by one > > of the endpoints or if both contributes to the change, or maybe they > > are even driving the OFV in oposite directions. > > > > Is there a way to get some form of partial OFV by endpoint? > > Best regards, > > Matts > > > > > > > > > > > > När du har kontakt med oss på Uppsala universitet med e-post så innebär > det att vi behandlar dina personuppgifter. För att läsa mer om hur vi gör > det kan du läsa här: http://www.uu.se/om-uu/dataskydd-personuppgifter/ > > E-mailing Uppsala University means that we will process your personal > data. For more information on how this is performed, please read here: > http://www.uu.se/en/about-uu/data-protection-policy >