```
library(dplyr)
library(qpNCA)
library(knitr)
```

```
mutate_cond <- function (.data, condition, ..., envir = parent.frame()){
condition <- eval(substitute(condition), .data, envir)
if(!any(condition))return(.data) # do nothing if nothing to do
.data[condition, ] <- .data[condition, ] %>% mutate(...)
.data
}
locf <- function(x){
good <- !is.na(x)
positions <- seq(length(x))
good.positions <- good * positions
last.good.position <- cummax(good.positions)
last.good.position[last.good.position == 0] <- NA
x[last.good.position]
}
```

We use the internal Theoph dataset as input file, modify the data and add necessary columns

Furthermore, we introduce some missing values, LOQ values and time deviations

```
head(Theoph) %>% kable()
```

Subject | Wt | Dose | Time | conc |
---|---|---|---|---|

1 | 79.6 | 4.02 | 0.00 | 0.74 |

1 | 79.6 | 4.02 | 0.25 | 2.84 |

1 | 79.6 | 4.02 | 0.57 | 6.57 |

1 | 79.6 | 4.02 | 1.12 | 10.50 |

1 | 79.6 | 4.02 | 2.02 | 9.66 |

1 | 79.6 | 4.02 | 3.82 | 8.58 |

```
input.data <- Theoph
#we need nominal time variable for some tasks.
ntad <- data.frame(rn=c(1:11),ntad=c(0,0.25,0.5,1,2,4,5,7,9,12,24))
input.data %<>%
group_by(Subject) %>%
mutate(subject=as.numeric(Subject),
rn=row_number(),
dose=Dose*Wt,
bloq=ifelse(conc==0,1,0),
loq=0.1,
excl_th=0
) %>%
left_join(ntad) %>%
ungroup %>%
arrange(subject,ntad) %>%
select(subject,ntad,tad=Time,conc,dose,bloq,loq,excl_th)
```

```
## Joining, by = "rn"
```

```
input.data %<>%
mutate_cond(condition=subject==2&ntad%in%c(24),conc=NA) %>%
mutate_cond(condition=subject==4&ntad%in%c(9),conc=NA) %>%
mutate_cond(condition=subject==3&ntad==9,excl_th=1) %>%
mutate_cond(condition=subject==6&ntad==24,conc=0,bloq=1) %>%
filter(!(subject==5&ntad==12))
```

```
loqed.data = input.data %>%
correct.loq(
by = "subject",
nomtimevar = "ntad",
timevar = "tad",
depvar = "conc",
bloqvar = "bloq",
loqvar = "loq",
loqrule = 1
)
# Result:
loqed.data %>% filter(loqrule.nr!="") %>% select(subject,ntad,conc,loqrule.nr,loqrule.txt) %>% kable()
```

subject | ntad | conc | loqrule.nr | loqrule.txt |
---|---|---|---|---|

1 | 0 | 0 | LOQ1 | BLOQ values before first measurable concentration set to 0 |

3 | 0 | 0 | LOQ1 | BLOQ values before first measurable concentration set to 0 |

4 | 0 | 0 | LOQ1 | BLOQ values before first measurable concentration set to 0 |

5 | 0 | 0 | LOQ1 | BLOQ values before first measurable concentration set to 0 |

6 | 0 | 0 | LOQ1 | BLOQ values before first measurable concentration set to 0 |

6 | 24 | NA | LOQ1 | BLOQ values after first measurable concentration set to missing |

7 | 0 | 0 | LOQ1 | BLOQ values before first measurable concentration set to 0 |

8 | 0 | 0 | LOQ1 | BLOQ values before first measurable concentration set to 0 |

9 | 0 | 0 | LOQ1 | BLOQ values before first measurable concentration set to 0 |

12 | 0 | 0 | LOQ1 | BLOQ values before first measurable concentration set to 0 |

```
th = loqed.data %>%
est.thalf(
by = "subject",
timevar = "tad",
depvar = "conc",
includeCmax = "Y",
exclvar = "excl_th"
)
# Result:
head(th) %>% kable()
```

subject | no.points | intercept | lambda_z | r.squared | adj.r.squared | start_th | end_th | thalf | includeCmax | points_excluded |
---|---|---|---|---|---|---|---|---|---|---|

1 | 3 | 8.212078 | 0.0915758 | 0.9989638 | 0.9979276 | 9.22 | 23.85 | 7.569107 | Y | N |

2 | 3 | 8.959057 | 0.0777431 | 0.9964163 | 0.9928325 | 6.98 | 12.05 | 8.915865 | Y | N |

3 | 6 | 8.688001 | 0.0818231 | 0.9962482 | 0.9953103 | 2.02 | 24.12 | 8.471285 | Y | Y |

4 | 3 | 8.703249 | 0.0962171 | 0.9999286 | 0.9998572 | 7.03 | 24.08 | 7.203989 | Y | N |

5 | 5 | 10.568234 | 0.0948933 | 0.9957650 | 0.9943534 | 3.62 | 24.17 | 7.304489 | Y | N |

6 | 3 | 12.790536 | 0.1192526 | 0.9867217 | 0.9734435 | 7.03 | 12.00 | 5.812428 | Y | N |

```
plot_reg(
loqed.data,
by = "subject",
th = th,
bloqvar = "bloq",
timevar = "tad",
depvar = "conc",
timelab = "Time (h)",
deplab = "Conc (ng/mL)",
exclvar = "excl_th",
plotdir = NA
)
```

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```
ctmax = input.data %>% calc.ctmax(
by = "subject",
timevar="tad",
depvar="conc"
)
# Result:
head(ctmax) %>% kable()
```

subject | cmax | tmax |
---|---|---|

1 | 6.44 | 1.15 |

2 | 7.09 | 3.48 |

3 | 7.56 | 2.02 |

4 | 8.00 | 0.98 |

5 | 8.20 | 1.02 |

6 | 8.33 | 1.92 |

```
ct.data= loqed.data %>%
correct.time(
by="subject",
nomtimevar="ntad",
timevar="tad",
depvar="conc",
th=th,
tau=24,
tstart=4,
tend=9,
teval=12,
reg="sd",
method=1
)
```

```
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```

```
# Result:
ct.data %>% filter(subject<=5&(trule.nr!=""|create.nr!="")) %>% select(subject,ntad,conc,applies.to.time,trule.nr,trule.txt,create.txt) %>% kable()
```

subject | ntad | conc | applies.to.time | trule.nr | trule.txt | create.txt |
---|---|---|---|---|---|---|

1 | 4 | 5.53 | TSTART | SDT-2 | Concentration ( 5.53 ) at deviating time ( t=3.57 instead of 4 ) corrected to 5.353 by interpolation (sample taken too early) | |

1 | 9 | 3.46 | TEND | SDT-2 | Concentration ( 3.46 ) at deviating time ( t=9.22 instead of 9 ) corrected to 3.515 by interpolation (sample taken too late) | |

1 | 12 | 2.78 | TEVAL | SDT-2 | Concentration ( 2.78 ) at deviating time ( t=12.1 instead of 12 ) corrected to 2.804 by interpolation (sample taken too late) | |

1 | 24 | 0.92 | TAU | SDT-3 | Concentration ( 0.92 ) at deviating time ( t=23.85 instead of 24 ) corrected to 0.907 by extrapolation (sample taken too early) | |

2 | 4 | 7.09 | TSTART | SDT-2 | Concentration ( 7.09 ) at deviating time ( t=3.48 instead of 4 ) corrected to 6.943 by interpolation (sample taken too early) | |

2 | 12 | 3.53 | TEVAL | SDT-2 | Concentration ( 3.53 ) at deviating time ( t=12.05 instead of 12 ) corrected to 3.544 by interpolation (sample taken too late) | |

2 | 24 | NA | TAU | SDT-2 | Concentration ( NA ) at deviating time ( t=24.22 instead of 24 ) corrected to NA by interpolation (sample taken too late) | |

3 | 4 | 6.59 | TSTART | SDT-2 | Concentration ( 6.59 ) at deviating time ( t=3.53 instead of 4 ) corrected to 6.37 by interpolation (sample taken too early) | |

3 | 9 | 4.57 | TEND | SDT-2 | Concentration ( 4.57 ) at deviating time ( t=9.07 instead of 9 ) corrected to 4.576 by interpolation (sample taken too late) | |

3 | 12 | 3.00 | TEVAL | SDT-2 | Concentration ( 3 ) at deviating time ( t=12.1 instead of 12 ) corrected to 3.052 by interpolation (sample taken too late) | |

3 | 24 | 1.25 | TAU | SDT-2 | Concentration ( 1.25 ) at deviating time ( t=24.12 instead of 24 ) corrected to 1.267 by interpolation (sample taken too late) | |

4 | 4 | 5.87 | TSTART | SDT-2 | Concentration ( 5.87 ) at deviating time ( t=3.6 instead of 4 ) corrected to 5.687 by interpolation (sample taken too early) | |

4 | 9 | NA | TEND | SDT-2 | Concentration ( NA ) at deviating time ( t=9.03 instead of 9 ) corrected to NA by interpolation (sample taken too late) | |

4 | 12 | 2.69 | TEVAL | SDT-2 | Concentration ( 2.69 ) at deviating time ( t=12.12 instead of 12 ) corrected to 2.731 by interpolation (sample taken too late) | |

4 | 24 | 0.86 | TAU | SDT-2 | Concentration ( 0.86 ) at deviating time ( t=24.08 instead of 24 ) corrected to 0.872 by interpolation (sample taken too late) | |

5 | 4 | 7.50 | TSTART | SDT-2 | Concentration ( 7.5 ) at deviating time ( t=3.62 instead of 4 ) corrected to 7.162 by interpolation (sample taken too early) | |

5 | 12 | NA | Missing record at t=12 added | |||

5 | 24 | 1.05 | TAU | SDT-2 | Concentration ( 1.05 ) at deviating time ( t=24.17 instead of 24 ) corrected to 1.093 by interpolation (sample taken too late) |

```
cc.ct.data = ct.data %>%
correct.conc(
by ="subject",
nomtimevar="ntad",
tau=24,
tstart=4,
tend=9,
teval=12,
th=th,
reg="sd",
ss="n",
route="EV",
method=1
)
```

```
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```

```
# Result:
cc.ct.data %>% filter(crule.nr!="") %>% select(subject,ntad,conc,applies.to.conc,crule.nr,crule.txt) %>% kable()
```

subject | ntad | conc | applies.to.conc | crule.nr | crule.txt |
---|---|---|---|---|---|

2 | 0 | 0.15 | PREDOSE | SDC-1 | Missing or measurable concentration at (SD) PREDOSE set to 0 |

2 | 24 | NA | TAU | SDC-3 | Missing concentration at t=24 corrected to 1.394 by extrapolation |

4 | 9 | NA | TEND | SDC-2 | Missing concentration at t=9 corrected to 3.769 by interpolation |

5 | 12 | NA | TEVAL | SDC-2 | Missing concentration at t=12 corrected to 4.139 by interpolation |

6 | 24 | NA | TAU | SDC-3 | Missing concentration at t=24 corrected to 0.72 by extrapolation |

10 | 0 | 0.24 | PREDOSE | SDC-1 | Missing or measurable concentration at (SD) PREDOSE set to 0 |

11 | 0 | 0.74 | PREDOSE | SDC-1 | Missing or measurable concentration at (SD) PREDOSE set to 0 |

```
tab_corr = cc.ct.data %>%
tab.corr(
by="subject",
nomtimevar="ntad"
)
# Result:
tab_corr %>% kable()
```

subject | ntad | applies.to | rule.nr | rule.txt |
---|---|---|---|---|

1 | 0 | NA | LOQ1 | BLOQ values before first measurable concentration set to 0 |

1 | 4 | TSTART | SDT-2 | Concentration ( 5.53 ) at deviating time ( t=3.57 instead of 4 ) corrected to 5.353 by interpolation (sample taken too early) |

1 | 9 | TEND | SDT-2 | Concentration ( 3.46 ) at deviating time ( t=9.22 instead of 9 ) corrected to 3.515 by interpolation (sample taken too late) |

1 | 12 | TEVAL | SDT-2 | Concentration ( 2.78 ) at deviating time ( t=12.1 instead of 12 ) corrected to 2.804 by interpolation (sample taken too late) |

1 | 24 | TAU | SDT-3 | Concentration ( 0.92 ) at deviating time ( t=23.85 instead of 24 ) corrected to 0.907 by extrapolation (sample taken too early) |

2 | 0 | PREDOSE | SDC-1 | Missing or measurable concentration at (SD) PREDOSE set to 0 |

2 | 4 | TSTART | SDT-2 | Concentration ( 7.09 ) at deviating time ( t=3.48 instead of 4 ) corrected to 6.943 by interpolation (sample taken too early) |

2 | 12 | TEVAL | SDT-2 | Concentration ( 3.53 ) at deviating time ( t=12.05 instead of 12 ) corrected to 3.544 by interpolation (sample taken too late) |

2 | 24 | TAU | SDT-2 | Concentration ( NA ) at deviating time ( t=24.22 instead of 24 ) corrected to NA by interpolation (sample taken too late) |

2 | 24 | TAU | SDC-3 | Missing concentration at t=24 corrected to 1.394 by extrapolation |

3 | 0 | NA | LOQ1 | BLOQ values before first measurable concentration set to 0 |

3 | 4 | TSTART | SDT-2 | Concentration ( 6.59 ) at deviating time ( t=3.53 instead of 4 ) corrected to 6.37 by interpolation (sample taken too early) |

3 | 9 | TEND | SDT-2 | Concentration ( 4.57 ) at deviating time ( t=9.07 instead of 9 ) corrected to 4.576 by interpolation (sample taken too late) |

3 | 12 | TEVAL | SDT-2 | Concentration ( 3 ) at deviating time ( t=12.1 instead of 12 ) corrected to 3.052 by interpolation (sample taken too late) |

3 | 24 | TAU | SDT-2 | Concentration ( 1.25 ) at deviating time ( t=24.12 instead of 24 ) corrected to 1.267 by interpolation (sample taken too late) |

4 | 0 | NA | LOQ1 | BLOQ values before first measurable concentration set to 0 |

4 | 4 | TSTART | SDT-2 | Concentration ( 5.87 ) at deviating time ( t=3.6 instead of 4 ) corrected to 5.687 by interpolation (sample taken too early) |

4 | 9 | TEND | SDT-2 | Concentration ( NA ) at deviating time ( t=9.03 instead of 9 ) corrected to NA by interpolation (sample taken too late) |

4 | 9 | TEND | SDC-2 | Missing concentration at t=9 corrected to 3.769 by interpolation |

4 | 12 | TEVAL | SDT-2 | Concentration ( 2.69 ) at deviating time ( t=12.12 instead of 12 ) corrected to 2.731 by interpolation (sample taken too late) |

4 | 24 | TAU | SDT-2 | Concentration ( 0.86 ) at deviating time ( t=24.08 instead of 24 ) corrected to 0.872 by interpolation (sample taken too late) |

5 | 0 | NA | LOQ1 | BLOQ values before first measurable concentration set to 0 |

5 | 4 | TSTART | SDT-2 | Concentration ( 7.5 ) at deviating time ( t=3.62 instead of 4 ) corrected to 7.162 by interpolation (sample taken too early) |

5 | 12 | NA | - | Missing record at t=12 added |

5 | 12 | TEVAL | SDC-2 | Missing concentration at t=12 corrected to 4.139 by interpolation |

5 | 24 | TAU | SDT-2 | Concentration ( 1.05 ) at deviating time ( t=24.17 instead of 24 ) corrected to 1.093 by interpolation (sample taken too late) |

6 | 0 | NA | LOQ1 | BLOQ values before first measurable concentration set to 0 |

6 | 4 | TSTART | SDT-2 | Concentration ( 6.85 ) at deviating time ( t=3.5 instead of 4 ) corrected to 6.597 by interpolation (sample taken too early) |

6 | 24 | NA | LOQ1 | BLOQ values after first measurable concentration set to missing |

6 | 24 | TAU | SDT-2 | Concentration ( NA ) at deviating time ( t=24.3 instead of 24 ) corrected to NA by interpolation (sample taken too late) |

6 | 24 | TAU | SDC-3 | Missing concentration at t=24 corrected to 0.72 by extrapolation |

7 | 0 | NA | LOQ1 | BLOQ values before first measurable concentration set to 0 |

7 | 4 | TSTART | SDT-2 | Concentration ( 7.54 ) at deviating time ( t=3.5 instead of 4 ) corrected to 7.323 by interpolation (sample taken too early) |

7 | 9 | TEND | SDT-2 | Concentration ( 5.33 ) at deviating time ( t=9.02 instead of 9 ) corrected to 5.335 by interpolation (sample taken too late) |

7 | 12 | TEVAL | SDT-2 | Concentration ( 4.19 ) at deviating time ( t=11.98 instead of 12 ) corrected to 4.185 by interpolation (sample taken too early) |

7 | 24 | TAU | SDT-2 | Concentration ( 1.15 ) at deviating time ( t=24.65 instead of 24 ) corrected to 1.306 by interpolation (sample taken too late) |

8 | 0 | NA | LOQ1 | BLOQ values before first measurable concentration set to 0 |

8 | 4 | TSTART | SDT-2 | Concentration ( 5.66 ) at deviating time ( t=3.53 instead of 4 ) corrected to 5.663 by interpolation (sample taken too early) |

8 | 9 | TEND | SDT-2 | Concentration ( 4.11 ) at deviating time ( t=8.8 instead of 9 ) corrected to 4.042 by interpolation (sample taken too early) |

8 | 12 | TEVAL | SDT-2 | Concentration ( 3.16 ) at deviating time ( t=11.6 instead of 12 ) corrected to 3.096 by interpolation (sample taken too early) |

8 | 24 | TAU | SDT-2 | Concentration ( 1.12 ) at deviating time ( t=24.43 instead of 24 ) corrected to 1.188 by interpolation (sample taken too late) |

9 | 0 | NA | LOQ1 | BLOQ values before first measurable concentration set to 0 |

9 | 4 | TSTART | SDT-2 | Concentration ( 9.75 ) at deviating time ( t=3.52 instead of 4 ) corrected to 9.385 by interpolation (sample taken too early) |

9 | 9 | TEND | SDT-2 | Concentration ( 6.11 ) at deviating time ( t=9.03 instead of 9 ) corrected to 6.117 by interpolation (sample taken too late) |

9 | 12 | TEVAL | SDT-2 | Concentration ( 4.57 ) at deviating time ( t=12.05 instead of 12 ) corrected to 4.595 by interpolation (sample taken too late) |

9 | 24 | TAU | SDT-2 | Concentration ( 1.17 ) at deviating time ( t=24.15 instead of 24 ) corrected to 1.212 by interpolation (sample taken too late) |

10 | 0 | PREDOSE | SDC-1 | Missing or measurable concentration at (SD) PREDOSE set to 0 |

10 | 4 | TSTART | SDT-2 | Concentration ( 10.21 ) at deviating time ( t=3.55 instead of 4 ) corrected to 9.901 by interpolation (sample taken too early) |

10 | 9 | TEND | SDT-2 | Concentration ( 7.14 ) at deviating time ( t=9.38 instead of 9 ) corrected to 7.285 by interpolation (sample taken too late) |

10 | 12 | TEVAL | SDT-2 | Concentration ( 5.68 ) at deviating time ( t=12.1 instead of 12 ) corrected to 5.734 by interpolation (sample taken too late) |

10 | 24 | TAU | SDT-3 | Concentration ( 2.42 ) at deviating time ( t=23.7 instead of 24 ) corrected to 2.366 by extrapolation (sample taken too early) |

11 | 0 | PREDOSE | SDC-1 | Missing or measurable concentration at (SD) PREDOSE set to 0 |

11 | 4 | TSTART | SDT-2 | Concentration ( 8.58 ) at deviating time ( t=3.82 instead of 4 ) corrected to 8.549 by interpolation (sample taken too early) |

11 | 9 | TEND | SDT-2 | Concentration ( 6.89 ) at deviating time ( t=9.05 instead of 9 ) corrected to 6.904 by interpolation (sample taken too late) |

11 | 12 | TEVAL | SDT-2 | Concentration ( 5.94 ) at deviating time ( t=12.12 instead of 12 ) corrected to 5.977 by interpolation (sample taken too late) |

11 | 24 | TAU | SDT-2 | Concentration ( 3.28 ) at deviating time ( t=24.37 instead of 24 ) corrected to 3.36 by interpolation (sample taken too late) |

12 | 0 | NA | LOQ1 | BLOQ values before first measurable concentration set to 0 |

12 | 4 | TSTART | SDT-2 | Concentration ( 8.74 ) at deviating time ( t=3.5 instead of 4 ) corrected to 8.352 by interpolation (sample taken too early) |

12 | 9 | TEND | SDT-2 | Concentration ( 5.9 ) at deviating time ( t=9.1 instead of 9 ) corrected to 5.957 by interpolation (sample taken too late) |

12 | 24 | TAU | SDT-2 | Concentration ( 1.57 ) at deviating time ( t=24.35 instead of 24 ) corrected to 1.649 by interpolation (sample taken too late) |

```
par = cc.ct.data %>%
calc.par(by = 'subject',
tau=24,
teval=12,
tstart=4,
tend=9,
route="EV",
method=1)
# Result:
head(par) %>% kable()
```

subject | route | method | tlast | clast.obs | tlast.ok | t0.ok | aucall | auclast | aumcall | aumclast | mrtall | mrtlast | calc.tau | auctau | aumctau | tau | calc.teval | auc12 | teval | calc.part | auc4_9 | tstart | tend | c0 | area.back.extr |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|

1 | EV | 1 | 23.85 | 0.92 | 1 | 1 | 73.77555 | 73.77555 | 609.1524 | 609.1524 | 8.256833 | 8.256833 | 1 | 73.97837 | 612.3497 | 24 | 1 | 51.75887 | 12 | 1 | 21.64179 | 4 | 9 | NA | NA |

2 | EV | 1 | 12.05 | 3.53 | 1 | 1 | 62.25685 | 62.25685 | 354.0998 | 354.0998 | 5.687724 | 5.687724 | 1 | 91.67850 | 808.1730 | 24 | 1 | 62.08000 | 12 | 1 | 28.32875 | 4 | 9 | NA | NA |

3 | EV | 1 | 24.12 | 1.25 | 1 | 1 | 88.55995 | 88.55995 | 739.5346 | 739.5346 | 8.350666 | 8.350666 | 1 | 88.40890 | 737.1499 | 24 | 1 | 62.71486 | 12 | 1 | 26.17989 | 4 | 9 | NA | NA |

4 | EV | 1 | 24.08 | 0.86 | 1 | 1 | 80.44595 | 80.44595 | 614.9855 | 614.9855 | 7.644705 | 7.644705 | 1 | 80.37666 | 614.1894 | 24 | 1 | 58.89166 | 12 | 1 | 23.37641 | 4 | 9 | NA | NA |

5 | EV | 1 | 24.17 | 1.05 | 1 | 1 | 102.32475 | 102.32475 | 767.2143 | 767.2143 | 7.497837 | 7.497837 | 1 | 102.14258 | 767.7359 | 24 | 1 | 70.75194 | 12 | 1 | 28.50079 | 4 | 9 | NA | NA |

6 | EV | 1 | 12.00 | 3.01 | 1 | 1 | 67.48030 | 67.48030 | 349.9481 | 349.9481 | 5.185929 | 5.185929 | 1 | 89.85776 | 670.2872 | 24 | 1 | 67.48030 | 12 | 1 | 27.80327 | 4 | 9 | NA | NA |

```
# Create a covariates file, containing at least the dose given
cov = input.data %>%
distinct(subject,dose)
par <- par %>%
calc.par.th(
by="subject",
th=th ,
covariates=cov,
dose="dose",
factor=1,
reg="sd",
ss="n"
)
# Result:
head(par) %>% kable()
```

subject | method | tlast | clast.obs | tlast.ok | t0.ok | aucall | auclast | aumcall | aumclast | mrtall | mrtlast | calc.tau | auctau | aumctau | tau | calc.teval | auc12 | teval | calc.part | auc4_9 | tstart | tend | c0 | area.back.extr | no.points | intercept | lambda_z | r.squared | adj.r.squared | start_th | end_th | thalf | includeCmax | points_excluded | dose | factor | reg | ss | route | clast.pred | aucinf.obs | aucinf.pred | aumcinf.obs | aumcinf.pred | cl.f.obs | cl.f.pred | mrtinf.obs | mrtinf.pred | vz.f.obs | vz.f.pred | vss.obs | vss.pred | pctextr.obs | pctextr.pred | pctback.obs | pctback.pred | cl.obs | cl.pred | vz.obs | vz.pred | cl.f.ss | cl.ss |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|

1 | 1 | 23.85 | 0.92 | 1 | 1 | 73.77555 | 73.77555 | 609.1524 | 609.1524 | 8.256833 | 8.256833 | 1 | 73.97837 | 612.3497 | 24 | 1 | 51.75887 | 12 | 1 | 21.64179 | 4 | 9 | NA | NA | 3 | 8.212078 | 0.0915758 | 0.9989638 | 0.9979276 | 9.22 | 23.85 | 7.569107 | Y | N | 320.000 | 1 | sd | n | ev | 0.9245229 | 83.82187 | 83.87126 | 958.4620 | 960.1793 | 3.817620 | 3.815371 | 11.434510 | 11.448252 | 41.68807 | 41.66352 | NA | NA | 11.985320 | 12.037150 | NA | NA | NA | NA | NA | NA | NA | NA |

2 | 1 | 12.05 | 3.53 | 1 | 1 | 62.25685 | 62.25685 | 354.0998 | 354.0998 | 5.687724 | 5.687724 | 1 | 91.67850 | 808.1730 | 24 | 1 | 62.08000 | 12 | 1 | 28.32875 | 4 | 9 | NA | NA | 3 | 8.959057 | 0.0777431 | 0.9964163 | 0.9928325 | 6.98 | 12.05 | 8.915865 | Y | N | 319.770 | 1 | sd | n | ev | 3.5108576 | 107.66280 | 107.41657 | 1485.2925 | 1479.1583 | 2.970107 | 2.976915 | 13.795782 | 13.770299 | 38.20411 | 38.29168 | NA | NA | 42.174223 | 42.041671 | NA | NA | NA | NA | NA | NA | NA | NA |

3 | 1 | 24.12 | 1.25 | 1 | 1 | 88.55995 | 88.55995 | 739.5346 | 739.5346 | 8.350666 | 8.350666 | 1 | 88.40890 | 737.1499 | 24 | 1 | 62.71486 | 12 | 1 | 26.17989 | 4 | 9 | NA | NA | 6 | 8.688001 | 0.0818231 | 0.9962482 | 0.9953103 | 2.02 | 24.12 | 8.471285 | Y | Y | 319.365 | 1 | sd | n | ev | 1.2072785 | 103.83680 | 103.31468 | 1294.7180 | 1275.7434 | 3.075644 | 3.091187 | 12.468778 | 12.348132 | 37.58892 | 37.77888 | NA | NA | 14.712367 | 14.281349 | NA | NA | NA | NA | NA | NA | NA | NA |

4 | 1 | 24.08 | 0.86 | 1 | 1 | 80.44595 | 80.44595 | 614.9855 | 614.9855 | 7.644705 | 7.644705 | 1 | 80.37666 | 614.1894 | 24 | 1 | 58.89166 | 12 | 1 | 23.37641 | 4 | 9 | NA | NA | 3 | 8.703249 | 0.0962171 | 0.9999286 | 0.9998572 | 7.03 | 24.08 | 7.203989 | Y | N | 319.800 | 1 | sd | n | ev | 0.8579476 | 89.38407 | 89.36274 | 923.1107 | 922.3753 | 3.577819 | 3.578673 | 10.327463 | 10.321700 | 37.18484 | 37.19372 | NA | NA | 9.999676 | 9.978193 | NA | NA | NA | NA | NA | NA | NA | NA |

5 | 1 | 24.17 | 1.05 | 1 | 1 | 102.32475 | 102.32475 | 767.2143 | 767.2143 | 7.497837 | 7.497837 | 1 | 102.14258 | 767.7359 | 24 | 1 | 70.75194 | 12 | 1 | 28.50079 | 4 | 9 | NA | NA | 5 | 10.568234 | 0.0948933 | 0.9957650 | 0.9943534 | 3.62 | 24.17 | 7.304489 | Y | N | 319.365 | 1 | sd | n | ev | 1.0663923 | 113.38981 | 113.56255 | 1151.2620 | 1157.2576 | 2.816523 | 2.812239 | 10.153135 | 10.190486 | 29.68094 | 29.63579 | NA | NA | 9.758423 | 9.895693 | NA | NA | NA | NA | NA | NA | NA | NA |

6 | 1 | 12.00 | 3.01 | 1 | 1 | 67.48030 | 67.48030 | 349.9481 | 349.9481 | 5.185929 | 5.185929 | 1 | 89.85776 | 670.2872 | 24 | 1 | 67.48030 | 12 | 1 | 27.80327 | 4 | 9 | NA | NA | 3 | 12.790536 | 0.1192526 | 0.9867217 | 0.9734435 | 7.03 | 12.00 | 5.812428 | Y | N | 318.560 | 1 | sd | n | ev | 3.0577347 | 92.72084 | 93.12112 | 864.4906 | 872.6506 | 3.435689 | 3.420921 | 9.323585 | 9.371135 | 28.81018 | 28.68634 | NA | NA | 27.222078 | 27.534915 | NA | NA | NA | NA | NA | NA | NA | NA |

```
par_all = left_join(par, ctmax)
```

```
## Joining, by = "subject"
```

```
# Result:
head(par_all) %>% kable()
```

subject | method | tlast | clast.obs | tlast.ok | t0.ok | aucall | auclast | aumcall | aumclast | mrtall | mrtlast | calc.tau | auctau | aumctau | tau | calc.teval | auc12 | teval | calc.part | auc4_9 | tstart | tend | c0 | area.back.extr | no.points | intercept | lambda_z | r.squared | adj.r.squared | start_th | end_th | thalf | includeCmax | points_excluded | dose | factor | reg | ss | route | clast.pred | aucinf.obs | aucinf.pred | aumcinf.obs | aumcinf.pred | cl.f.obs | cl.f.pred | mrtinf.obs | mrtinf.pred | vz.f.obs | vz.f.pred | vss.obs | vss.pred | pctextr.obs | pctextr.pred | pctback.obs | pctback.pred | cl.obs | cl.pred | vz.obs | vz.pred | cl.f.ss | cl.ss | cmax | tmax |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|

1 | 1 | 23.85 | 0.92 | 1 | 1 | 73.77555 | 73.77555 | 609.1524 | 609.1524 | 8.256833 | 8.256833 | 1 | 73.97837 | 612.3497 | 24 | 1 | 51.75887 | 12 | 1 | 21.64179 | 4 | 9 | NA | NA | 3 | 8.212078 | 0.0915758 | 0.9989638 | 0.9979276 | 9.22 | 23.85 | 7.569107 | Y | N | 320.000 | 1 | sd | n | ev | 0.9245229 | 83.82187 | 83.87126 | 958.4620 | 960.1793 | 3.817620 | 3.815371 | 11.434510 | 11.448252 | 41.68807 | 41.66352 | NA | NA | 11.985320 | 12.037150 | NA | NA | NA | NA | NA | NA | NA | NA | 6.44 | 1.15 |

2 | 1 | 12.05 | 3.53 | 1 | 1 | 62.25685 | 62.25685 | 354.0998 | 354.0998 | 5.687724 | 5.687724 | 1 | 91.67850 | 808.1730 | 24 | 1 | 62.08000 | 12 | 1 | 28.32875 | 4 | 9 | NA | NA | 3 | 8.959057 | 0.0777431 | 0.9964163 | 0.9928325 | 6.98 | 12.05 | 8.915865 | Y | N | 319.770 | 1 | sd | n | ev | 3.5108576 | 107.66280 | 107.41657 | 1485.2925 | 1479.1583 | 2.970107 | 2.976915 | 13.795782 | 13.770299 | 38.20411 | 38.29168 | NA | NA | 42.174223 | 42.041671 | NA | NA | NA | NA | NA | NA | NA | NA | 7.09 | 3.48 |

3 | 1 | 24.12 | 1.25 | 1 | 1 | 88.55995 | 88.55995 | 739.5346 | 739.5346 | 8.350666 | 8.350666 | 1 | 88.40890 | 737.1499 | 24 | 1 | 62.71486 | 12 | 1 | 26.17989 | 4 | 9 | NA | NA | 6 | 8.688001 | 0.0818231 | 0.9962482 | 0.9953103 | 2.02 | 24.12 | 8.471285 | Y | Y | 319.365 | 1 | sd | n | ev | 1.2072785 | 103.83680 | 103.31468 | 1294.7180 | 1275.7434 | 3.075644 | 3.091187 | 12.468778 | 12.348132 | 37.58892 | 37.77888 | NA | NA | 14.712367 | 14.281349 | NA | NA | NA | NA | NA | NA | NA | NA | 7.56 | 2.02 |

4 | 1 | 24.08 | 0.86 | 1 | 1 | 80.44595 | 80.44595 | 614.9855 | 614.9855 | 7.644705 | 7.644705 | 1 | 80.37666 | 614.1894 | 24 | 1 | 58.89166 | 12 | 1 | 23.37641 | 4 | 9 | NA | NA | 3 | 8.703249 | 0.0962171 | 0.9999286 | 0.9998572 | 7.03 | 24.08 | 7.203989 | Y | N | 319.800 | 1 | sd | n | ev | 0.8579476 | 89.38407 | 89.36274 | 923.1107 | 922.3753 | 3.577819 | 3.578673 | 10.327463 | 10.321700 | 37.18484 | 37.19372 | NA | NA | 9.999676 | 9.978193 | NA | NA | NA | NA | NA | NA | NA | NA | 8.00 | 0.98 |

5 | 1 | 24.17 | 1.05 | 1 | 1 | 102.32475 | 102.32475 | 767.2143 | 767.2143 | 7.497837 | 7.497837 | 1 | 102.14258 | 767.7359 | 24 | 1 | 70.75194 | 12 | 1 | 28.50079 | 4 | 9 | NA | NA | 5 | 10.568234 | 0.0948933 | 0.9957650 | 0.9943534 | 3.62 | 24.17 | 7.304489 | Y | N | 319.365 | 1 | sd | n | ev | 1.0663923 | 113.38981 | 113.56255 | 1151.2620 | 1157.2576 | 2.816523 | 2.812239 | 10.153135 | 10.190486 | 29.68094 | 29.63579 | NA | NA | 9.758423 | 9.895693 | NA | NA | NA | NA | NA | NA | NA | NA | 8.20 | 1.02 |

6 | 1 | 12.00 | 3.01 | 1 | 1 | 67.48030 | 67.48030 | 349.9481 | 349.9481 | 5.185929 | 5.185929 | 1 | 89.85776 | 670.2872 | 24 | 1 | 67.48030 | 12 | 1 | 27.80327 | 4 | 9 | NA | NA | 3 | 12.790536 | 0.1192526 | 0.9867217 | 0.9734435 | 7.03 | 12.00 | 5.812428 | Y | N | 318.560 | 1 | sd | n | ev | 3.0577347 | 92.72084 | 93.12112 | 864.4906 | 872.6506 | 3.435689 | 3.420921 | 9.323585 | 9.371135 | 28.81018 | 28.68634 | NA | NA | 27.222078 | 27.534915 | NA | NA | NA | NA | NA | NA | NA | NA | 8.33 | 1.92 |