[NMusers] Extreme values of CWRESI in NONMEM 7.4.1?

From: Paolo Denti <paolo.denti_at_uct.ac.za>
Date: Thu, 16 Nov 2017 11:34:26 +0200

Dear all,
I am reporting about a suspicious behaviour I am observing with CWRESI in N=
ONMEM 7.4.1.

I have a patent/metabolite model which fits the data decently in terms of V=
PCs and other diagnostics, but the CWRESI have some EXTREME values (e.g. so=
me are less than -15 and more than +40). After checking for outliers or mis=
takes in the dataset and finding no obvious reason for this, I realised som=
ething funny was happening.

For all those patients with extreme CWRESI values, all the CWRESI were exac=
tly the same as WRES. I noticed that this happened for other subjects as we=
ll, without extreme values. In fact it was observed in a number of consecut=
ive patients in the dataset, then the CWRESI and WRES were different once a=
gain for a number of IDs, then different again.
I pasted below the beginning of my output table (I hope it won't get horrib=
ly mangled in the email). You can see for ID 1002 things are fine, but for =
the next subject, all CWRESI and WRES are 100% the same, which I find very =
odd. Going on in the table, one then encounters the crazy values (e.g. +40)=
 in those patients where CWRESI=WRES.

After thinking that I had messed up something in the code (although I have =
a fairly standard $ERR chunk), I reran the same models with NM 7.3 and no e=
xtreme CWRESI were to be seen and in no patient CWRESI=WRES. I tried ifor=
tran and gfortran, same results.

Not sure if this is a bug or something has changed in the implementation of=
 CWRESI in the new version? Anything that needs to be added into the code? =
Did anyone else experience something similar?

Thanks for sharing your experience,
Paolo


 ID TIME Y DV PRED =
     WRES IPRED IWRES CWRESI
1002 0 1.11E-07 0 1.11E-07 0 1.11E-07 =
     -3.9E-06 0
1002 24 0.003244 0 0.000414 0 0.003244 =
     -0.11491 0
1002 47.17 0.004529 0.0234 0.000633 0.80448 0.004529 =
     0.66837 0.7499
1002 47.17 0.001072 0.00782 8.13E-05 0.57553 0.001072 =
     0.8618 0.76168
1002 47.27 0.004351 0 0.000601 0 0.004351 =
     -0.15409 0
1002 47.27 0.004351 0 0.000601 0 0.004351 =
     -0.15409 0
1002 48.27 0.94518 0.967 4.5118 -0.95261 0.94518 0.10129 -1.=
1938
1002 48.27 0.077732 0.0657 0.33279 0.53181 0.077732 -0.=
40398 0.55325
1002 49.27 2.7804 2.58 6.0306 -0.4145 2.7804 -0.3187 -0.798
1002 49.27 0.35996 0.339 0.65388 0.57726 0.35996 -0.15724 0.8=
6232
1002 51.25 3.1544 3.09 3.9118 0.63922 3.1544 -0.09023 -0.=
068
1002 51.25 0.67321 0.814 0.64312 1.0183 0.67321 0.56538 1.0395
1002 53.25 2.2343 2.48 2.0147 1.1994 2.2343 0.48601 0.69346
1002 53.25 0.61916 0.821 0.37813 1.2318 0.61916 0.88123 0.60795
1002 55.23 1.3392 1.56 0.91675 1.0769 1.3392 0.72666 0.70831
1002 55.23 0.41051 0.485 0.16968 1.1534 0.41051 0.49014 -0.11759
1003 0 1.17E-07 0 1.17E-07 0 1.17E-07 =
     -4.1E-06 0
1003 23.92 2.19E-05 0 0.000106 0 2.19E-05 =
     -0.00078 0
1003 46.58 4.65E-05 0.0234 0.000208 0.82167 4.65E-05 =
     0.82766 0.82167
1003 46.58 8.66E-06 0.00782 2.55E-05 0.56411 8.66E-06 =
     0.99888 0.56411
1003 46.63 4.52E-05 0 0.000202 0 4.52E-05 =
     -0.0016 0
1003 46.63 4.52E-05 0 0.000202 0 4.52E-05 =
     -0.0016 0
1003 47.68 1.1432 1.09 5.096 -0.99314 1.1432 -0.20478 =
     -0.99314
1003 47.68 0.065831 0.053 0.39584 0.43182 0.065831 -0.=
50191 0.43182
1003 48.67 5.38 6.44 6.427 0.93526 5.38 0.87171 0.93526
1003 48.67 0.57361 0.907 0.7257 0.60985 0.57361 1.571 0.60985
1003 50.65 3.6587 3.71 4.0526 -0.30631 3.6587 0.061999 =
     -0.30631
1003 50.65 0.65408 0.662 0.68469 -0.03219 0.65408 0.032746 =
     -0.03219
1003 52.65 1.5856 1.82 2.0167 -0.16771 1.5856 0.65208 -0.=
16771
1003 52.65 0.33653 0.402 0.38292 0.080183 0.33653 0.5252 0.0=
80183
1003 54.65 0.58013 0.594 0.86702 -0.41124 0.58013 0.10342 -0.=
41124
1003 54.65 0.12566 0.12 0.16026 -0.07836 0.12566 -0.12016 =
     -0.07836
1004 0 1.69E-07 0 1.69E-07 0 1.69E-07 =
     -6E-06 0
1004 23.83 0.000114 0 0.000285 0 0.000114 =
     -0.00404 0
1004 46.33 0.000242 0.0234 0.000576 0.8068 0.000242 =
     0.82074 0.8068
1004 46.33 3.76E-05 0.00782 7.31E-05 0.57412 3.76E-05 =
     0.99518 0.57412
1004 46.4 0.000233 0 0.000555 0 0.000233 =
     -0.00824 0
1004 46.4 0.000233 0 0.000555 0 0.000233 =
     -0.00824 0
1004 47.38 4.3404 4.59 3.1408 0.54238 4.3404 0.25445 0.54238
1004 47.38 0.34788 0.295 0.20459 -0.38164 0.34788 -0.41035 =
     -0.38164
1004 48.38 5.5978 5.57 4.1733 0.22522 5.5978 -0.02199 0.2=
2522
1004 48.38 0.69068 0.669 0.4033 0.58087 0.69068 -0.08485 0.5=
8087
1004 50.38 3.1389 3.62 2.4749 0.42327 3.1389 0.67784 0.42327
1004 50.38 0.59966 0.721 0.3565 0.7287 0.59966 0.54698 0.7287
1004 52.38 1.4082 1.55 1.1339 -0.29857 1.4082 0.44389 -0.=
29857
1004 52.38 0.30079 0.434 0.18172 1.7245 0.30079 1.1949 1.7245
1004 54.37 0.54719 0.555 0.45719 -0.3361 0.54719 0.061603 -0.=
3361
1004 54.37 0.11383 0.114 0.071932 0.039771 0.11383 0.0=
03873 0.039771







--
------------------------------------------------
Paolo Denti, PhD
Pharmacometrics Group
Division of Clinical Pharmacology
Department of Medicine
University of Cape Town

K45 Old Main Building
Groote Schuur Hospital
Observatory, Cape Town
7925 South Africa
phone: +27 21 404 7719
fax: +27 21 448 1989
email: paolo.denti_at_uct.ac.za<mailto:paolo.denti_at_uct.ac.za>
------------------------------------------------

Disclaimer - University of Cape Town This e-mail is subject to UCT policies=
 and e-mail disclaimer published on our website at http://www.uct.ac.za/abo=
ut/policies/emaildisclaimer/ or obtainable from +27 21 650 9111. If this e-=
mail is not related to the business of UCT, it is sent by the sender in an =
individual capacity. Please report security incidents or abuse via csirt_at_uc=
t.ac.za



Received on Thu Nov 16 2017 - 04:34:26 EST

This archive was generated by hypermail 2.3.0 : Fri Sep 27 2019 - 16:56:57 EDT