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tensfeldt / openNCA

openNCA computation engine is an R package that provides for generation of pharmacokinetic parameter estimates using non-compartmental (NCA) pharmacokinetic analysis methods.
MIT License
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2019-11-23 tc016 M3SS is not reporting estimated interpolated concentration points associated with Partial Aucs requested #57

Closed tensfeldt closed 4 years ago

tensfeldt commented 4 years ago

No partial AUCs are reported in parameter results Estimated concentration dataset is missing entries for 240 and 460 as indicated by the partial aucs specified below.

  AUC.1.T1 AUC.1.T2 AUC.2.T1 AUC.2.T2 AUC.3.T1 AUC.3.T2
1        0       24       48      240       24      460
> table(d$PKPTMS, d$TREATXT)

      100 mg PF-05231023 IV 140 mg PF-05231023 IV 25 mg PF-05231023 IV 5 mg PF-05231023 IV
  0                      20                    18                   20                  18
  0.5                    20                    18                   20                  18
  1                      20                    18                   20                  18
  1.5                    20                    18                   20                  18
  2                      20                    18                   20                  18
  3                      20                    18                   20                  18
  5                      20                    18                   20                  18
  9                      20                    18                   20                  18
  13                     20                    18                   20                  18
  24                     20                    18                   20                  18
  48                     10                     9                   10                   9
  72                     10                     9                   10                   9
  96                     10                     9                   10                   9
  168                    10                     8                   10                   9
  408                    10                     9                   10                   9
> r
       SDEID CENDINF1 CMAX1 FLGACCEPTPREDOSE TMAX1 TLAST KEL KELTMLO KELTMHI KELNOPT KELRSQ FLGACCEPTKEL THALF THALFF   AUCLAST1
1   12596809     1090  1090                0   1.0    72  NA      NA      NA       0     NA            0    NA     NA   39414.86
2   34123765       NA 68200                0   1.0   408  NA      NA      NA       0     NA            0    NA     NA 1233130.16
3   46932787     6540  7910                0  13.0   408  NA      NA      NA       0     NA            0    NA     NA  166341.57
4   48481731       NA  1880                0   1.5    72  NA      NA      NA       0     NA            0    NA     NA   71502.45
5   54146338    27000 31300                0   1.5   408  NA      NA      NA       0     NA            0    NA     NA  553899.66
6   56316208     7670  8690                0   1.5   408  NA      NA      NA       0     NA            0    NA     NA  123475.40
7   65585724    27900 30200                0   1.5    72  NA      NA      NA       0     NA            0    NA     NA 1454700.15
8   70843384    41100 47600                0  24.0   408  NA      NA      NA       0     NA            0    NA     NA  826075.00
9   86918796     6590  8780                0   1.5   408  NA      NA      NA       0     NA            0    NA     NA  147794.44
10  87055773       NA 10900                0   1.5   408  NA      NA      NA       0     NA            0    NA     NA  140794.35
11  93495406    29100 29800                0   1.5    72  NA      NA      NA       0     NA            0    NA     NA 1523101.44
12 104901531     1800  1800                0   1.0    72  NA      NA      NA       0     NA            0    NA     NA   69963.81
13 115532321       NA 30800                0   2.0   408  NA      NA      NA       0     NA            0    NA     NA  544310.74
14 139290479    66700 78700                0   2.0   408  NA      NA      NA       0     NA            0    NA     NA 1151283.85
15 161254335    58800 61900                0   1.5   408  NA      NA      NA       0     NA            0    NA     NA 1019871.21
16 176001863       NA 32100                0   1.5    72  NA      NA      NA       0     NA            0    NA     NA  937101.80
      AUCTAU1   MRTLAST  MRTIVIFP1 AUCXPCTP       CAV1       CLTAU1       VSSP1 TIMEU AMOUNTU DOSEU VOLUMEU CONCU KELU  CLU     AUCU
1    39414.86  29.33725         NA       NA   547.4286 1.268557e-04          NA    HR      NA    MG       L NG/ML 1/HR L/HR NG.HR/ML
2  1233130.16  81.44387 1291281382       NA 17126.8077 1.135322e-04 146602.0374    HR      NA    MG       L NG/ML 1/HR L/HR NG.HR/ML
3   166341.57  98.03909         NA       NA  2310.2996 1.502932e-04          NA    HR      NA    MG       L NG/ML 1/HR L/HR NG.HR/ML
4    71502.45  30.42027         NA       NA   993.0896 6.992767e-05          NA    HR      NA    MG       L NG/ML 1/HR L/HR NG.HR/ML
5   553899.66 105.03661         NA       NA  7693.0508 1.805381e-04          NA    HR      NA    MG       L NG/ML 1/HR L/HR NG.HR/ML
6   123475.40 105.15631    4647518       NA  1714.9362 2.024695e-04    940.9806    HR      NA    MG       L NG/ML 1/HR L/HR NG.HR/ML
7  1454700.15  31.56342         NA       NA 20204.1687 6.874269e-05          NA    HR      NA    MG       L NG/ML 1/HR L/HR NG.HR/ML
8   826075.00  94.89329         NA       NA 11473.2639 1.210544e-04          NA    HR      NA    MG       L NG/ML 1/HR L/HR NG.HR/ML
9   147794.44 104.42602         NA       NA  2052.7006 1.691539e-04          NA    HR      NA    MG       L NG/ML 1/HR L/HR NG.HR/ML
10  140794.35 104.05874   19387473       NA  1955.4771 1.775639e-04   3442.5161    HR      NA    MG       L NG/ML 1/HR L/HR NG.HR/ML
11 1523101.44  32.15881         NA       NA 21154.1867 6.565551e-05          NA    HR      NA    MG       L NG/ML 1/HR L/HR NG.HR/ML
12   69963.81  31.20123         NA       NA   971.7196 7.146552e-05          NA    HR      NA    MG       L NG/ML 1/HR L/HR NG.HR/ML
13  544310.74 102.56267         NA       NA  7559.8713 1.837186e-04          NA    HR      NA    MG       L NG/ML 1/HR L/HR NG.HR/ML
14 1151283.85  75.37810 1012222007       NA 15990.0535 1.216034e-04 123089.6106    HR      NA    MG       L NG/ML 1/HR L/HR NG.HR/ML
15 1019871.21  83.65606  233925934       NA 14164.8779 1.372722e-04  32111.5359    HR      NA    MG       L NG/ML 1/HR L/HR NG.HR/ML
16  937101.80  25.73535         NA       NA 13015.3028 1.493968e-04          NA    HR      NA    MG       L NG/ML 1/HR L/HR NG.HR/ML
   AUMCU AUCNORMU AURCU CONCNORMU RATEU VOLUMEWU CLWU    STUDY SITEID   SUBJID RAND               TREATXT TRTCD PKCOLL PKBDFLD
1     NA       NA    NA        NA    NA       NA   NA B2901002   1001 10011009    9   5 mg PF-05231023 IV     B  POINT  PLASMA
2     NA       NA    NA        NA    NA       NA   NA B2901002   1004 10041088   47 140 mg PF-05231023 IV     E  POINT  PLASMA
3     NA       NA    NA        NA    NA       NA   NA B2901002   1004 10041015   22  25 mg PF-05231023 IV     C  POINT  PLASMA
4     NA       NA    NA        NA    NA       NA   NA B2901002   1005 10051006    1   5 mg PF-05231023 IV     B  POINT  PLASMA
5     NA       NA    NA        NA    NA       NA   NA B2901002   1004 10041043   34 100 mg PF-05231023 IV     D  POINT  PLASMA
6     NA       NA    NA        NA    NA       NA   NA B2901002   1005 10051043   17  25 mg PF-05231023 IV     C  POINT  PLASMA
7     NA       NA    NA        NA    NA       NA   NA B2901002   1004 10041039   33 100 mg PF-05231023 IV     D  POINT  PLASMA
8     NA       NA    NA        NA    NA       NA   NA B2901002   1002 10021007   27 100 mg PF-05231023 IV     D  POINT  PLASMA
9     NA       NA    NA        NA    NA       NA   NA B2901002   1004 10041011   21  25 mg PF-05231023 IV     C  POINT  PLASMA
10    NA       NA    NA        NA    NA       NA   NA B2901002   1004 10041005   19  25 mg PF-05231023 IV     C  POINT  PLASMA
11    NA       NA    NA        NA    NA       NA   NA B2901002   1002 10021009   28 100 mg PF-05231023 IV     D  POINT  PLASMA
12    NA       NA    NA        NA    NA       NA   NA B2901002   1001 10011002   11   5 mg PF-05231023 IV     B  POINT  PLASMA
13    NA       NA    NA        NA    NA       NA   NA B2901002   1004 10041033   32 100 mg PF-05231023 IV     D  POINT  PLASMA
14    NA       NA    NA        NA    NA       NA   NA B2901002   1003 10031028   41 140 mg PF-05231023 IV     E  POINT  PLASMA
15    NA       NA    NA        NA    NA       NA   NA B2901002   1003 10031014   37 140 mg PF-05231023 IV     E  POINT  PLASMA
16    NA       NA    NA        NA    NA       NA   NA B2901002   1003 10031027   39 140 mg PF-05231023 IV     E  POINT  PLASMA
                   PKTERM VISITU VISIT     HT     WT AGEDERU AGEDER WTUNI WTRAW HTUNI HTRAW RACES SEX              ETHNIC
1  PF-05231023 N-TERMINAL    DAY    15 198.12 105.33      YR     53    LB 232.2    IN  78.0     B   M NOT HISPANIC/LATINO
2  PF-05231023 N-TERMINAL    DAY    25 152.40  71.08      YR     60    LB 156.7    IN  60.0     W   F     HISPANIC/LATINO
3  PF-05231023 N-TERMINAL    DAY    25 162.56  77.16      YR     51    LB 170.1    IN  64.0     W   F     HISPANIC/LATINO
4  PF-05231023 N-TERMINAL    DAY    15 172.72  84.82      YR     49    LB 187.0    IN  68.0     W   M     HISPANIC/LATINO
5  PF-05231023 N-TERMINAL    DAY    25 162.56  85.91      YR     61    LB 189.4    IN  64.0     W   F     HISPANIC/LATINO
6  PF-05231023 N-TERMINAL    DAY    25 165.10  69.36      YR     59    LB 152.9    IN  65.0     W   M     HISPANIC/LATINO
7  PF-05231023 N-TERMINAL    DAY    15 172.72  75.93      YR     58    LB 167.4    IN  68.0     W   M     HISPANIC/LATINO
8  PF-05231023 N-TERMINAL    DAY    25 166.88  80.74      YR     66    LB 178.0    IN  65.7     W   M     HISPANIC/LATINO
9  PF-05231023 N-TERMINAL    DAY    25 170.18  80.74      YR     65    LB 178.0    IN  67.0     W   M     HISPANIC/LATINO
10 PF-05231023 N-TERMINAL    DAY    25 177.80  81.65      YR     55    LB 180.0    IN  70.0     B   M NOT HISPANIC/LATINO
11 PF-05231023 N-TERMINAL    DAY    15 172.97  88.00      YR     64    LB 194.0    IN  68.1     W   M     HISPANIC/LATINO
12 PF-05231023 N-TERMINAL    DAY    15 165.86  81.01      YR     46    LB 178.6    IN  65.3     W   M     HISPANIC/LATINO
13 PF-05231023 N-TERMINAL    DAY    25 157.48  77.34      YR     56    LB 170.5    IN  62.0     W   F     HISPANIC/LATINO
14 PF-05231023 N-TERMINAL    DAY    25 173.74  78.47      YR     68    LB 173.0    IN  68.4     W   F NOT HISPANIC/LATINO
15 PF-05231023 N-TERMINAL    DAY    25 167.64  97.52      YR     47    LB 215.0    IN  66.0     W   M NOT HISPANIC/LATINO
16 PF-05231023 N-TERMINAL    DAY    15 175.26  92.44      YR     42    LB 203.8    IN  69.0     W   M NOT HISPANIC/LATINO
                  ACTTRT ACTTRTS
1    5 mg PF-05231023 IV       B
2  140 mg PF-05231023 IV       E
3   25 mg PF-05231023 IV       C
4    5 mg PF-05231023 IV       B
5  100 mg PF-05231023 IV       D
6   25 mg PF-05231023 IV       C
7  100 mg PF-05231023 IV       D
8  100 mg PF-05231023 IV       D
9   25 mg PF-05231023 IV       C
10  25 mg PF-05231023 IV       C
11 100 mg PF-05231023 IV       D
12   5 mg PF-05231023 IV       B
13 100 mg PF-05231023 IV       D
14 140 mg PF-05231023 IV       E
15 140 mg PF-05231023 IV       E
16 140 mg PF-05231023 IV       E
 [ reached 'max' / getOption("max.print") -- omitted 60 rows ]
> e
[1] PKDATAROWID SDEID       TIME        CEST_KEL    CEST_INT    CEST_EXT    CEST_C0     CEST_TLAST 
<0 rows> (or 0-length row.names)
jhhughes256 commented 4 years ago

Update

I can partly replicate this as of by loading tc016 and making the following changes:

mct$OPTIMIZEKEL <- 1
mct$AUC.1.T1 <- 0
mct$AUC.1.T2 <- 24
mct$AUC.2.T1 <- 48
mct$AUC.2.T2 <- 240
mct$AUC.3.T1 <- 24
mct$AUC.3.T2 <- 460

I have activated OPTIMIZEKEL for this test case as tc016 has no FLGEXKEL == 0 values provided by a user.

The time points for this testcase are:

> table(d$PKPTMS, useNA = "always")

   0  0.5    1  1.5    2    3    5    9   13   24   48   72   96  168  408 <NA> 
  76   76   76   76   76   76   76   76   76   76   38   38   38   37   38    0

The output was:

    PKDATAROWID     SDEID  TIME   CEST_KEL CEST_INT     CEST_EXT CEST_C0 CEST_TLAST
1      34680748  12596809   1.5   922.4714       NA           NA      NA         NA
2      34680749  12596809   2.0   914.6196       NA           NA      NA         NA
3      34680750  12596809   3.0   899.1159       NA           NA      NA         NA
4      34680751  12596809   5.0   868.8925       NA           NA      NA         NA
5      34680752  12596809   9.0   811.4594       NA           NA      NA         NA
6      34680753  12596809  13.0   757.8225       NA           NA      NA         NA
7     -34680754  12596809  24.0   627.9059       NA           NA      NA         NA
8     -34680755  12596809  48.0   416.5805       NA           NA      NA         NA
9     -34680756  12596809  72.0   276.3779       NA           NA      NA   276.3779
10           NA  12596809 240.0         NA       NA   15.6363100      NA         NA
11           NA  12596809 460.0         NA       NA    0.3636426      NA         NA
12     34682241  34123765   1.5 63575.0642       NA           NA      NA         NA
13     34682242  34123765   2.0 63070.1172       NA           NA      NA         NA
14     34682243  34123765   3.0 62072.2230       NA           NA      NA         NA
15     34682244  34123765   5.0 60123.5507       NA           NA      NA         NA
16     34682245  34123765   9.0 56407.8134       NA           NA      NA         NA
17     34682246  34123765  13.0 52921.7149       NA           NA      NA         NA
18    -34682247  34123765  24.0 44406.2581       NA           NA      NA         NA
19    -34682248  34123765  96.0 14084.7055       NA           NA      NA         NA
20    -34682249  34123765 168.0  4467.3642       NA           NA      NA         NA
21           NA  34123765 460.0         NA       NA   42.4189938      NA         NA
22    -34681288  46932787  96.0  1655.1580       NA           NA      NA         NA
23    -34681289  46932787 168.0  1074.4041       NA           NA      NA         NA
24    -34681290  46932787 408.0   254.4456       NA           NA      NA   254.4456
25           NA  46932787 460.0         NA       NA  186.2319624      NA         NA

The output for est_data shows that the extrapolated point 460 is always provided in est_data, however 240 is only provided when it is considered to be an extrapolated value. It does not appear when it is interpolated. This may be related to #54.

jhhughes256 commented 4 years ago

I've also noticed that the est_data output for SDEID == 34123765 (included in the comment above) has no value for CEST_TLAST. Is this working as intended @tensfeldt? Should every individual have a value for CEST_TLAST in est_data or is it only when it is included in the KEL regression that it appears in est_data?

jhhughes256 commented 4 years ago

Update

As of commit 18821dca00 this issue appears to be fixed. Please note that to test this issue OPTIMIZEKEL must equal 1, as tc016 has flags$FLGEXKEL == 1 for all records.

The updated results are shown below. Time point 48 is a mixed existing/interpolated point, point 240 is a mixed interpolated/extrapolated point, point 460 is an extrapolated point.

est_data

    PKDATAROWID     SDEID  TIME   CEST_KEL  CEST_INT     CEST_EXT CEST_C0 CEST_TLAST
1      34680748  12596809   1.5   922.4714        NA           NA      NA         NA
2      34680749  12596809   2.0   914.6196        NA           NA      NA         NA
3      34680750  12596809   3.0   899.1159        NA           NA      NA         NA
4      34680751  12596809   5.0   868.8925        NA           NA      NA         NA
5      34680752  12596809   9.0   811.4594        NA           NA      NA         NA
6      34680753  12596809  13.0   757.8225        NA           NA      NA         NA
7     -34680754  12596809  24.0   627.9059        NA           NA      NA         NA
8     -34680755  12596809  48.0   416.5805        NA           NA      NA         NA
9     -34680756  12596809  72.0   276.3779        NA           NA      NA   276.3779
10           NA  12596809 240.0         NA        NA   15.6363100      NA         NA
11           NA  12596809 460.0         NA        NA    0.3636426      NA         NA
13     34682241  34123765   1.5 63575.0642        NA           NA      NA         NA
21     34682242  34123765   2.0 63070.1172        NA           NA      NA         NA
31     34682243  34123765   3.0 62072.2230        NA           NA      NA         NA
41     34682244  34123765   5.0 60123.5507        NA           NA      NA         NA
51     34682245  34123765   9.0 56407.8134        NA           NA      NA         NA
61     34682246  34123765  13.0 52921.7149        NA           NA      NA         NA
71    -34682247  34123765  24.0 44406.2581        NA           NA      NA         NA
101          NA  34123765  48.0         NA 32500.000           NA      NA         NA
81    -34682248  34123765  96.0 14084.7055        NA           NA      NA         NA
91    -34682249  34123765 168.0  4467.3642        NA           NA      NA         NA
111          NA  34123765 240.0         NA  3424.000           NA      NA         NA
12           NA  34123765 460.0         NA        NA   42.4189938      NA         NA
14           NA  46932787  48.0         NA  5053.333           NA      NA         NA
22    -34681288  46932787  96.0  1655.1580        NA           NA      NA         NA
32    -34681289  46932787 168.0  1074.4041        NA           NA      NA         NA
52           NA  46932787 240.0         NA   900.700           NA      NA         NA
42    -34681290  46932787 408.0   254.4456        NA           NA      NA   254.4456
62           NA  46932787 460.0         NA        NA  186.2319624      NA         NA

data_out

       SDEID    AUC0_24  AUC48_240  AUC24_460
1  104901531   30033.67   60537.05   87766.05
2  115532321  544310.74 1168268.77 1873863.52
3   12596809   17924.53   23187.94   37267.84
4  139290479 1151283.85 1454957.40 2366346.68
5  161254335 1019871.21 1602976.56 2473776.81
6  176001863  503841.29  328706.96  609406.58
7  181090944  147000.51  237615.12  390816.09
8  192572639   26087.56   76068.43  114867.27
9  249494359  939855.48 1181130.30 1850076.35
10 252389071  116467.22  122213.99  199314.83
11 290825038  491075.67  596478.19  972069.22
12 303601078  125541.11  293577.00  458445.91
13 322018548   27010.89   64460.65   95720.12
14 323495986   30863.47   45565.34   72344.07
15 324958357  156936.77  301446.58  456191.70