Function for creating sampling designs.
create_sampling_design.Rd
Sampling times can usually be pre-specified if the dosing schedule is fixed.
In that case a scheme can be specified with static timepoints e.g.
time = c(1, 7.5, 25, 31.5)
for taking peak-trough samples at dose
1 and 4 for an 8-hour regimen.
However, when the dosing interval is adaptive, the peak and trough sampling
times cannot stay static and have to be adapted on-the-fly during
simulations. In that case, it is possible to use when
to specify
sampling at peak
, trough
or dose
concentrations. In that case, the
time
is not allowed. If not exact peak and trough concentrations should be
sample, use the offset
parameter to sample e.g. an hour post-peak, or
shortly before true troughs.
Usage
create_sampling_design(
time = NULL,
when = NULL,
offset = NULL,
scatter = NULL,
at = NULL,
lloq = 0,
anchor = c("dose", "day")
)
Arguments
- time
a vector of numeric values. If no
at
values are specified, these will be used as the fixed sampling times in the simulated trial. Ifat
values are supplied, the sampling times will be calculated adaptively during the trial. Theat
determine which dose or day is used as reference, andtime
will be relative to the specifiedat
anchor.- when
character vector of same length as
time
(or single value) determining how to interpret the provided samplingtime
. IfNULL
will use the dose time as offset (default). Other options are:cmax
orpeak
, which will use the end of infusion as the base for thetime
, orcmin
ortrough
, which will use the time of next dose as the offset, ormiddle
orcmid
which will use the middle between the anchored dose and the next, orrandom
which takes a random time point between the anchored dose and the next.- offset
offset from standardized PK moments specified in
when
, e.g.c(1, -1)
withwhen = c("peak", "trough")
to sample 1 hour after peak and 1 hour before trough.- scatter
optional random variation in time, specified as the standard deviation, e.g.
scatter = 0.1
to allow for variation in sampling time with an SD of 0.1 hours. Only implemented for sampling times (not for regimen_update designs), not applicable for or target designs. Random variation does not protect for peaks or troughs becoming sampled during infusion or in previous / next dose. So value forscatter
should be chosen appropriately and probably used in conjunction with appropriateoffset
values.- at
numeric vector of the dose or day number to "anchor" the sampling times to. Vector needs to be of same length as
time
. Ifanchor
is set today
, then the first dose in that day is used. If later doses in the day are preferred, the anchor can also be specified fractionally, e.g.1.5
will use the time of the first dose in the second half of the 1st day.- lloq
lower limit of quantification for TDMs
- anchor
either
day
ordose
. Single value required, i.e. anchor types cannot be mixed.
Examples
# to sample at 1.5/8.5/23.5 hours
create_sampling_design(time = c(1.5, 11.5, 23.5))
#> $lloq
#> [1] 0
#>
#> $scheme
#> base offset at anchor
#> 1 dose 1.5 1 dose
#> 2 dose 11.5 1 dose
#> 3 dose 23.5 1 dose
#>
# to sample at the peak (end of infusion) and trough (start of
# next dose) of each dose
create_sampling_design(
when = c("peak", "trough")
)
#> $lloq
#> [1] 0
#>
#> $scheme
#> base offset at anchor scatter
#> 1 peak 0 1 dose 0
#> 2 trough 0 1 dose 0
#>
# to sample 30 min post-peak and 30-min pre-trough for the first dose
create_sampling_design(
when = c("peak", "trough"),
offset = c(0.5, -0.5),
at = c(1, 1)
)
#> $lloq
#> [1] 0
#>
#> $scheme
#> base offset at anchor scatter
#> 1 peak 0.5 1 dose 0
#> 2 trough -0.5 1 dose 0
#>
# The same as above, but now for the first and third dose
create_sampling_design(
when = c("peak", "trough", "peak", "trough"),
offset = c(0.5, -0.5, 0.5, -0.5),
at = c(1, 1, 3, 3),
anchor = "dose"
)
#> $lloq
#> [1] 0
#>
#> $scheme
#> base offset at anchor scatter
#> 1 peak 0.5 1 dose 0
#> 2 trough -0.5 1 dose 0
#> 3 peak 0.5 3 dose 0
#> 4 trough -0.5 3 dose 0
#>