Once a calculation is complete, the steps to extract the desired results from the results object are described below.
To extract results, first results must be available. The example below comes from the Introduction and Usage vignette and is reproduced here simply to have results available. See that vignette for more details about running PKNCA.
library(PKNCA)
suppressPackageStartupMessages(library(dplyr))
d_conc <-
as.data.frame(datasets::Theoph) %>%
mutate(Subject=as.numeric(as.character(Subject)))
## Generate the dosing data
d_dose <- d_conc[d_conc$Time == 0,]
d_dose$Time <- 0
conc_obj <-
PKNCAconc(
d_conc,
conc~Time|Subject
)
dose_obj <-
PKNCAdose(
d_dose,
Dose~Time|Subject
)
data_obj <- PKNCAdata(conc_obj, dose_obj)
results_obj <- pk.nca(data_obj)In many scenarios, individual results may need to be excluded from
summaries. To exclude results, use the exclude()
function.
Several exclusion functions are built into PKNCA. The built-in functions will exclude all results that either apply to the current value or are dependencies of the current value. For example, \(AUC_\infty\) depends on \(\lambda_z\), and excluding based on span ratio will exclude all parameters that depend on \(\lambda_z\), including \(AUC_\infty\).
To see the built-in functions, type ?exclude_nca at the
R command line and review that help page. To use them, provide the
function to the FUN argument of exclude() as
illustrated below.
results_excl_span <- exclude(results_obj, FUN=exclude_nca_span.ratio())
# Without any exclusions applied, the 'exclude' column is all NA.
as.data.frame(results_obj) %>%
filter(Subject == 1)## # A tibble: 14 × 6
## Subject start end PPTESTCD PPORRES exclude
## <dbl> <dbl> <dbl> <chr> <dbl> <chr>
## 1 1 0 24 auclast 92.4 <NA>
## 2 1 0 Inf cmax 10.5 <NA>
## 3 1 0 Inf tmax 1.12 <NA>
## 4 1 0 Inf tlast 24.4 <NA>
## 5 1 0 Inf clast.obs 3.28 <NA>
## 6 1 0 Inf lambda.z 0.0485 <NA>
## 7 1 0 Inf r.squared 1.00 <NA>
## 8 1 0 Inf adj.r.squared 1.00 <NA>
## 9 1 0 Inf lambda.z.time.first 9.05 <NA>
## 10 1 0 Inf lambda.z.n.points 3 <NA>
## 11 1 0 Inf clast.pred 3.28 <NA>
## 12 1 0 Inf half.life 14.3 <NA>
## 13 1 0 Inf span.ratio 1.07 <NA>
## 14 1 0 Inf aucinf.obs 215. <NA># With exclusions applied, the 'exclude' column has the reason for exclusion.
as.data.frame(results_excl_span) %>%
filter(Subject == 1)## # A tibble: 14 × 6
## Subject start end PPTESTCD PPORRES exclude
## <dbl> <dbl> <dbl> <chr> <dbl> <chr>
## 1 1 0 24 auclast 92.4 <NA>
## 2 1 0 Inf cmax 10.5 <NA>
## 3 1 0 Inf tmax 1.12 <NA>
## 4 1 0 Inf tlast 24.4 <NA>
## 5 1 0 Inf clast.obs 3.28 <NA>
## 6 1 0 Inf lambda.z 0.0485 Span ratio < 2
## 7 1 0 Inf r.squared 1.00 Span ratio < 2
## 8 1 0 Inf adj.r.squared 1.00 Span ratio < 2
## 9 1 0 Inf lambda.z.time.first 9.05 Span ratio < 2
## 10 1 0 Inf lambda.z.n.points 3 Span ratio < 2
## 11 1 0 Inf clast.pred 3.28 Span ratio < 2
## 12 1 0 Inf half.life 14.3 Span ratio < 2
## 13 1 0 Inf span.ratio 1.07 Span ratio < 2
## 14 1 0 Inf aucinf.obs 215. Span ratio < 2You may also write your own exclusion function. The exclusion
functions built-into PKNCA are a bit more complex than required because
they handle options and manage general functionality that may not apply
to a user-specific need. To write your own exclusion function, it should
follow the description of how to write your own exclusion function as
described in the details section of ?exclude.
Excluding specific results has the benefit that full control is provided. But, excluding specific points allows for errors to also enter the analysis because parameters that depend on the excluded parameter will not be excluded.
mask_exclude_cmax <-
results_obj %>%
as.data.frame() %>%
dplyr::mutate(
mask_exclude=Subject == 1 & PPTESTCD == "cmax"
) %>%
"[["("mask_exclude")
results_excl_specific <-
exclude(
results_obj,
mask=mask_exclude_cmax,
reason="Cmax was actually above the ULOQ"
)
# Without any exclusions applied, the 'exclude' column is all NA.
results_obj %>%
as.data.frame() %>%
filter(Subject == 1)## # A tibble: 14 × 6
## Subject start end PPTESTCD PPORRES exclude
## <dbl> <dbl> <dbl> <chr> <dbl> <chr>
## 1 1 0 24 auclast 92.4 <NA>
## 2 1 0 Inf cmax 10.5 <NA>
## 3 1 0 Inf tmax 1.12 <NA>
## 4 1 0 Inf tlast 24.4 <NA>
## 5 1 0 Inf clast.obs 3.28 <NA>
## 6 1 0 Inf lambda.z 0.0485 <NA>
## 7 1 0 Inf r.squared 1.00 <NA>
## 8 1 0 Inf adj.r.squared 1.00 <NA>
## 9 1 0 Inf lambda.z.time.first 9.05 <NA>
## 10 1 0 Inf lambda.z.n.points 3 <NA>
## 11 1 0 Inf clast.pred 3.28 <NA>
## 12 1 0 Inf half.life 14.3 <NA>
## 13 1 0 Inf span.ratio 1.07 <NA>
## 14 1 0 Inf aucinf.obs 215. <NA># With exclusions applied, the 'exclude' column has the reason for exclusion.
results_excl_specific %>%
as.data.frame() %>%
filter(Subject == 1)## # A tibble: 14 × 6
## Subject start end PPTESTCD PPORRES exclude
## <dbl> <dbl> <dbl> <chr> <dbl> <chr>
## 1 1 0 24 auclast 92.4 <NA>
## 2 1 0 Inf cmax 10.5 Cmax was actually above the…
## 3 1 0 Inf tmax 1.12 <NA>
## 4 1 0 Inf tlast 24.4 <NA>
## 5 1 0 Inf clast.obs 3.28 <NA>
## 6 1 0 Inf lambda.z 0.0485 <NA>
## 7 1 0 Inf r.squared 1.00 <NA>
## 8 1 0 Inf adj.r.squared 1.00 <NA>
## 9 1 0 Inf lambda.z.time.first 9.05 <NA>
## 10 1 0 Inf lambda.z.n.points 3 <NA>
## 11 1 0 Inf clast.pred 3.28 <NA>
## 12 1 0 Inf half.life 14.3 <NA>
## 13 1 0 Inf span.ratio 1.07 <NA>
## 14 1 0 Inf aucinf.obs 215. <NA>More than one exclusion can be applied sequentially to results as in the example below.
mask_exclude_lz <-
results_obj %>%
as.data.frame() %>%
dplyr::mutate(
mask_exclude=Subject == 1 & PPTESTCD == "lambda.z"
) %>%
"[["("mask_exclude")
# Starting from the exclusion example above where short span ratios were
# excluded, exclude Cmax for Subject 1, too.
results_excl_multi <-
exclude(
results_excl_span,
mask=mask_exclude_cmax,
reason="Cmax was actually above the ULOQ"
)
results_excl_multi <-
exclude(
results_excl_multi,
mask=mask_exclude_lz,
reason="Issue with lambda.z fit"
)
# With exclusions applied, the 'exclude' column has the reason for exclusion.
# More than one reason may appear if more than one exclusion is applied.
results_excl_multi %>%
as.data.frame() %>%
filter(Subject == 1)## # A tibble: 14 × 6
## Subject start end PPTESTCD PPORRES exclude
## <dbl> <dbl> <dbl> <chr> <dbl> <chr>
## 1 1 0 24 auclast 92.4 <NA>
## 2 1 0 Inf cmax 10.5 Cmax was actually above the…
## 3 1 0 Inf tmax 1.12 <NA>
## 4 1 0 Inf tlast 24.4 <NA>
## 5 1 0 Inf clast.obs 3.28 <NA>
## 6 1 0 Inf lambda.z 0.0485 Span ratio < 2; Issue with …
## 7 1 0 Inf r.squared 1.00 Span ratio < 2
## 8 1 0 Inf adj.r.squared 1.00 Span ratio < 2
## 9 1 0 Inf lambda.z.time.first 9.05 Span ratio < 2
## 10 1 0 Inf lambda.z.n.points 3 Span ratio < 2
## 11 1 0 Inf clast.pred 3.28 Span ratio < 2
## 12 1 0 Inf half.life 14.3 Span ratio < 2
## 13 1 0 Inf span.ratio 1.07 Span ratio < 2
## 14 1 0 Inf aucinf.obs 215. Span ratio < 2Summary results are obtained using the aptly named
summary() function. It will output a
summary_PKNCAresults object that is simply a data.frame
with an attribute of caption. The summary is generated by
evaluating summary statistics on each requested parameter. Which summary
statistics are calculated for each parameter are set with
PKNCA.set.summary(), and they are described in the caption.
When a parameter is not requested for a given interval, it is
illustrated with a period (.), by default (customizable
with the not.requested.string argument to
summary()). When a parameter is required to calculate
another parameter, but it is not specifically requested, it will not be
shown in the summary.
The summary will have one column for each grouping variable other than the subject grouping variable; one column each for the start and end time; and one column per parameter calculated.
summary(results_obj)## start end N auclast cmax tmax half.life aucinf.obs
## 0 24 12 74.6 [24.3] . . . .
## 0 Inf 12 . 8.65 [17.0] 1.14 [0.630, 3.55] 8.18 [2.12] 115 [28.4]
##
## Caption: auclast, cmax, aucinf.obs: geometric mean and geometric coefficient of variation; tmax: median and range; half.life: arithmetic mean and standard deviationWhen values are excluded as described above, the excluded values are not included in the summary (note that half.life and aucinf.obs differ).
summary(results_excl_span)## start end N auclast cmax tmax half.life
## 0 24 12 74.6 [24.3] . . .
## 0 Inf 12 . 8.65 [17.0] 1.14 [0.630, 3.55] 7.36 [0.742]
## aucinf.obs
## .
## 105 [16.4]
##
## Caption: auclast, cmax, aucinf.obs: geometric mean and geometric coefficient of variation; tmax: median and range; half.life: arithmetic mean and standard deviationA listing of all calculated values is available using
as.data.frame().
as.data.frame(results_obj) %>%
head(20)## # A tibble: 20 × 6
## Subject start end PPTESTCD PPORRES exclude
## <dbl> <dbl> <dbl> <chr> <dbl> <chr>
## 1 1 0 24 auclast 92.4 <NA>
## 2 1 0 Inf cmax 10.5 <NA>
## 3 1 0 Inf tmax 1.12 <NA>
## 4 1 0 Inf tlast 24.4 <NA>
## 5 1 0 Inf clast.obs 3.28 <NA>
## 6 1 0 Inf lambda.z 0.0485 <NA>
## 7 1 0 Inf r.squared 1.00 <NA>
## 8 1 0 Inf adj.r.squared 1.00 <NA>
## 9 1 0 Inf lambda.z.time.first 9.05 <NA>
## 10 1 0 Inf lambda.z.n.points 3 <NA>
## 11 1 0 Inf clast.pred 3.28 <NA>
## 12 1 0 Inf half.life 14.3 <NA>
## 13 1 0 Inf span.ratio 1.07 <NA>
## 14 1 0 Inf aucinf.obs 215. <NA>
## 15 2 0 24 auclast 67.2 <NA>
## 16 2 0 Inf cmax 8.33 <NA>
## 17 2 0 Inf tmax 1.92 <NA>
## 18 2 0 Inf tlast 24.3 <NA>
## 19 2 0 Inf clast.obs 0.9 <NA>
## 20 2 0 Inf lambda.z 0.104 <NA>Excluded values remain in the listing.
as.data.frame(results_excl_span) %>%
head(20)## # A tibble: 20 × 6
## Subject start end PPTESTCD PPORRES exclude
## <dbl> <dbl> <dbl> <chr> <dbl> <chr>
## 1 1 0 24 auclast 92.4 <NA>
## 2 1 0 Inf cmax 10.5 <NA>
## 3 1 0 Inf tmax 1.12 <NA>
## 4 1 0 Inf tlast 24.4 <NA>
## 5 1 0 Inf clast.obs 3.28 <NA>
## 6 1 0 Inf lambda.z 0.0485 Span ratio < 2
## 7 1 0 Inf r.squared 1.00 Span ratio < 2
## 8 1 0 Inf adj.r.squared 1.00 Span ratio < 2
## 9 1 0 Inf lambda.z.time.first 9.05 Span ratio < 2
## 10 1 0 Inf lambda.z.n.points 3 Span ratio < 2
## 11 1 0 Inf clast.pred 3.28 Span ratio < 2
## 12 1 0 Inf half.life 14.3 Span ratio < 2
## 13 1 0 Inf span.ratio 1.07 Span ratio < 2
## 14 1 0 Inf aucinf.obs 215. Span ratio < 2
## 15 2 0 24 auclast 67.2 <NA>
## 16 2 0 Inf cmax 8.33 <NA>
## 17 2 0 Inf tmax 1.92 <NA>
## 18 2 0 Inf tlast 24.3 <NA>
## 19 2 0 Inf clast.obs 0.9 <NA>
## 20 2 0 Inf lambda.z 0.104 <NA>