AUClast is not estimated
suramanitha opened this issue · 4 comments
suramanitha commented
I am testing a data set in PKNCA for NCA parameters, however I am unable to get AUClast. I am not sure what is missing, my conc vs time plots look good as well
Below is the code I used:
myconc <- PKNCAconc(data=myrawconcdata,
formula=Concentration~Time|Subject)
mydata <- PKNCAdata(myconc,
intervals=data.frame(start=c(0,0), end=c(29, Inf),
tmax=TRUE,
cmax=TRUE,
tlast=TRUE,
auclast =c(TRUE,TRUE)
))
knitr::kable(PKNCA.options("single.dose.aucs"))
myresults <- pk.nca(mydata)
kable(as.data.frame(myresults))
summary(myresults)
start end N auclast cmax tmax tlast
0 29 4 NC 15400 18.5 [11.0, 29.0] 29.0 [29.0, 29.0]
0 Inf 4 NC 15400 18.5 [11.0, 29.0] 75.0 [60.0, 90.0]
suramanitha commented
billdenney commented
I'm not certain how you generated myrawconcdata from the source data. I think that the underlying issue is that you likely ran as.numeric() on the concentration data without handling the "Not Detected" values (or equivalently filtered out the "Not Detected" rows). Setting those to zero and converting to numeric appears to fix the issue.
Can you confirm that this is what you were expecting?
library(rio)
library(PKNCA)
myrawconcdata <- import("https://github.com/billdenney/pknca/files/6689350/NCA_df.xls")
myconc <- PKNCAconc(data=myrawconcdata,
formula=Concentration~Time|Subject)
mydata <- PKNCAdata(myconc,
intervals=data.frame(start=c(0,0), end=c(29, Inf),
tmax=TRUE,
cmax=TRUE,
tlast=TRUE,
auclast =c(TRUE,TRUE)
))
# Issue, concentrations are not numeric
myresults <- pk.nca(mydata)
#> No dose information provided, calculations requiring dose will return NA.
#> Error in check.conc.time(conc, time): Error with interval Subject=31002, start=0, end=29: Concentration data must be numeric and not a factor
# Make concentrations numeric (replicate what I think was the previous issue,
# note the warning, "NAs introduced by coercion")
numeric_conc_with_na <- myrawconcdata
numeric_conc_with_na$Concentration <- as.numeric(numeric_conc_with_na$Concentration)
#> Warning: NAs introduced by coercion
myconc <- PKNCAconc(data=numeric_conc_with_na,
formula=Concentration~Time|Subject)
mydata <- PKNCAdata(myconc,
intervals=data.frame(start=c(0,0), end=c(29, Inf),
tmax=TRUE,
cmax=TRUE,
tlast=TRUE,
auclast =c(TRUE,TRUE)
))
# warnings indicating the issue is that the AUC will not be calculated when the
# starting time is before the first measurement time
myresults <- pk.nca(mydata)
#> No dose information provided, calculations requiring dose will return NA.
#> Warning in pk.calc.auxc(conc = conc, time = time, ..., options = options, :
#> Requesting an AUC range starting (0) before the first measurement (8) is not
#> allowed
#> Warning in pk.calc.auxc(conc = conc, time = time, ..., options = options, :
#> Requesting an AUC range starting (0) before the first measurement (8) is not
#> allowed
#> Warning in pk.calc.auxc(conc = conc, time = time, ..., options = options, :
#> Requesting an AUC range starting (0) before the first measurement (8) is not
#> allowed
#> Warning in pk.calc.auxc(conc = conc, time = time, ..., options = options, :
#> Requesting an AUC range starting (0) before the first measurement (8) is not
#> allowed
#> Warning in pk.calc.auxc(conc = conc, time = time, ..., options = options, :
#> Requesting an AUC range starting (0) before the first measurement (4) is not
#> allowed
#> Warning in pk.calc.auxc(conc = conc, time = time, ..., options = options, :
#> Requesting an AUC range starting (0) before the first measurement (4) is not
#> allowed
#> Warning in pk.calc.auxc(conc = conc, time = time, ..., options = options, :
#> Requesting an AUC range starting (0) before the first measurement (8) is not
#> allowed
#> Warning in pk.calc.auxc(conc = conc, time = time, ..., options = options, :
#> Requesting an AUC range starting (0) before the first measurement (8) is not
#> allowed
#> Warning in pk.calc.auxc(conc = conc, time = time, ..., options = options, :
#> Requesting an AUC range starting (0) before the first measurement (8) is not
#> allowed
#> Warning in pk.calc.auxc(conc = conc, time = time, ..., options = options, :
#> Requesting an AUC range starting (0) before the first measurement (8) is not
#> allowed
as.data.frame(myresults)
#> start end Subject PPTESTCD PPORRES exclude
#> 1 0 29 31002 auclast NA <NA>
#> 2 0 29 31002 cmax 513291.60 <NA>
#> 3 0 29 31002 tmax 22.00 <NA>
#> 4 0 29 31002 tlast 29.00 <NA>
#> 5 0 Inf 31002 auclast NA <NA>
#> 6 0 Inf 31002 cmax 513291.60 <NA>
#> 7 0 Inf 31002 tmax 22.00 <NA>
#> 8 0 Inf 31002 tlast 90.00 <NA>
#> 9 0 29 31003 auclast NA <NA>
#> 10 0 29 31003 cmax 145025.68 <NA>
#> 11 0 29 31003 tmax 29.00 <NA>
#> 12 0 29 31003 tlast 29.00 <NA>
#> 13 0 Inf 31003 auclast NA <NA>
#> 14 0 Inf 31003 cmax 145025.68 <NA>
#> 15 0 Inf 31003 tmax 29.00 <NA>
#> 16 0 Inf 31003 tlast 29.00 <NA>
#> 17 0 29 91001 auclast NA <NA>
#> 18 0 29 91001 cmax 2688.58 <NA>
#> 19 0 29 91001 tmax 29.00 <NA>
#> 20 0 29 91001 tlast 29.00 <NA>
#> 21 0 Inf 91001 auclast NA <NA>
#> 22 0 Inf 91001 cmax 2688.58 <NA>
#> 23 0 Inf 91001 tmax 29.00 <NA>
#> 24 0 Inf 91001 tlast 60.00 <NA>
#> 25 0 29 91002 auclast NA <NA>
#> 26 0 29 91002 cmax 4065.34 <NA>
#> 27 0 29 91002 tmax 15.00 <NA>
#> 28 0 29 91002 tlast 29.00 <NA>
#> 29 0 Inf 91002 auclast NA <NA>
#> 30 0 Inf 91002 cmax 4065.34 <NA>
#> 31 0 Inf 91002 tmax 15.00 <NA>
#> 32 0 Inf 91002 tlast 90.00 <NA>
#> 33 0 29 111001 auclast NA <NA>
#> 34 0 29 111001 cmax 10033.27 <NA>
#> 35 0 29 111001 tmax 11.00 <NA>
#> 36 0 29 111001 tlast 29.00 <NA>
#> 37 0 Inf 111001 auclast NA <NA>
#> 38 0 Inf 111001 cmax 10033.27 <NA>
#> 39 0 Inf 111001 tmax 11.00 <NA>
#> 40 0 Inf 111001 tlast 60.00 <NA>
summary(myresults)
#> start end N auclast cmax tmax tlast
#> 0 29 5 NC 24100 [1430] 22.0 [11.0, 29.0] 29.0 [29.0, 29.0]
#> 0 Inf 5 NC 24100 [1430] 22.0 [11.0, 29.0] 60.0 [29.0, 90.0]
#>
#> Caption: auclast, cmax: geometric mean and geometric coefficient of variation; tmax, tlast: median and range
# Make concentrations numeric (replicate what I think was the previous issue,
# note the warning, "NAs introduced by coercion")
numeric_conc_without_na <- myrawconcdata
numeric_conc_without_na$Concentration[numeric_conc_without_na$Concentration == "Not Detected"] <- 0
# It is still a character vector
numeric_conc_without_na$Concentration
#> [1] "0" "0" "0"
#> [4] "8152.5900000000001" "131055.08" "485765.44"
#> [7] "513291.59999999998" "510105.15000000002" "411936.07000000001"
#> [10] "351694.02000000002" "215456.22" "0"
#> [13] "0" "0" "252.22"
#> [16] "244.31999999999999" "312.63" "27438.02"
#> [19] "145025.67999999999" "0" "0"
#> [22] "233.28" "1354.6099999999999" "1991.0599999999999"
#> [25] "1927.4000000000001" "2056.96" "2688.5799999999999"
#> [28] "1974.8" "439.37" "0"
#> [31] "0" "1078.6700000000001" "3066.52"
#> [34] "4065.3400000000001" "2310.21" "963.85000000000002"
#> [37] "157.50999999999999" "61.549999999999997" "71.909999999999997"
#> [40] "0" "0" "0"
#> [43] "2862.2399999999998" "10033.27" "435.98000000000002"
#> [46] "256.27999999999997" "275.48000000000002" "0"
# Make it numeric (note that there are no warnings this time)
numeric_conc_without_na$Concentration <- as.numeric(numeric_conc_without_na$Concentration)
numeric_conc_without_na$Concentration
#> [1] 0.00 0.00 0.00 8152.59 131055.08 485765.44 513291.60
#> [8] 510105.15 411936.07 351694.02 215456.22 0.00 0.00 0.00
#> [15] 252.22 244.32 312.63 27438.02 145025.68 0.00 0.00
#> [22] 233.28 1354.61 1991.06 1927.40 2056.96 2688.58 1974.80
#> [29] 439.37 0.00 0.00 1078.67 3066.52 4065.34 2310.21
#> [36] 963.85 157.51 61.55 71.91 0.00 0.00 0.00
#> [43] 2862.24 10033.27 435.98 256.28 275.48 0.00
myconc <- PKNCAconc(data=numeric_conc_without_na,
formula=Concentration~Time|Subject)
mydata <- PKNCAdata(myconc,
intervals=data.frame(start=c(0,0), end=c(29, Inf),
tmax=TRUE,
cmax=TRUE,
tlast=TRUE,
auclast =c(TRUE,TRUE)
))
# No warnings given about AUC calculations
myresults <- pk.nca(mydata)
#> No dose information provided, calculations requiring dose will return NA.
as.data.frame(myresults)
#> start end Subject PPTESTCD PPORRES exclude
#> 1 0 29 31002 auclast 8537334.42 <NA>
#> 2 0 29 31002 cmax 513291.60 <NA>
#> 3 0 29 31002 tmax 22.00 <NA>
#> 4 0 29 31002 tlast 29.00 <NA>
#> 5 0 Inf 31002 auclast 29550799.00 <NA>
#> 6 0 Inf 31002 cmax 513291.60 <NA>
#> 7 0 Inf 31002 tmax 22.00 <NA>
#> 8 0 Inf 31002 tlast 90.00 <NA>
#> 9 0 29 31003 auclast 703113.31 <NA>
#> 10 0 29 31003 cmax 145025.68 <NA>
#> 11 0 29 31003 tmax 29.00 <NA>
#> 12 0 29 31003 tlast 29.00 <NA>
#> 13 0 Inf 31003 auclast 703113.31 <NA>
#> 14 0 Inf 31003 cmax 145025.68 <NA>
#> 15 0 Inf 31003 tmax 29.00 <NA>
#> 16 0 Inf 31003 tlast 29.00 <NA>
#> 17 0 29 91001 auclast 46935.09 <NA>
#> 18 0 29 91001 cmax 2688.58 <NA>
#> 19 0 29 91001 tmax 29.00 <NA>
#> 20 0 29 91001 tlast 29.00 <NA>
#> 21 0 Inf 91001 auclast 92815.28 <NA>
#> 22 0 Inf 91001 cmax 2688.58 <NA>
#> 23 0 Inf 91001 tmax 29.00 <NA>
#> 24 0 Inf 91001 tlast 60.00 <NA>
#> 25 0 29 91002 auclast 55158.96 <NA>
#> 26 0 29 91002 cmax 4065.34 <NA>
#> 27 0 29 91002 tmax 15.00 <NA>
#> 28 0 29 91002 tlast 29.00 <NA>
#> 29 0 Inf 91002 auclast 64099.84 <NA>
#> 30 0 Inf 91002 cmax 4065.34 <NA>
#> 31 0 Inf 91002 tmax 15.00 <NA>
#> 32 0 Inf 91002 tlast 90.00 <NA>
#> 33 0 29 111001 auclast 61098.48 <NA>
#> 34 0 29 111001 cmax 10033.27 <NA>
#> 35 0 29 111001 tmax 11.00 <NA>
#> 36 0 29 111001 tlast 29.00 <NA>
#> 37 0 Inf 111001 auclast 69340.76 <NA>
#> 38 0 Inf 111001 cmax 10033.27 <NA>
#> 39 0 Inf 111001 tmax 11.00 <NA>
#> 40 0 Inf 111001 tlast 60.00 <NA>
summary(myresults)
#> start end N auclast cmax tmax tlast
#> 0 29 5 249000 [1310] 24100 [1430] 22.0 [11.0, 29.0] 29.0 [29.0, 29.0]
#> 0 Inf 5 386000 [3060] 24100 [1430] 22.0 [11.0, 29.0] 60.0 [29.0, 90.0]
#>
#> Caption: auclast, cmax: geometric mean and geometric coefficient of variation; tmax, tlast: median and rangeCreated on 2021-06-21 by the reprex package (v2.0.0)
suramanitha commented
Thank you for looking at this. Now i can see the issue. I had converted the "Not detected" as missing in my testing and this resulted in not outputting the AUClast. Then i converted the "Not detected" at Time =0 to 0 , then i was able to see the AUClast. Now the problem is solved.
billdenney commented
Great!