Link a secondary parameter to the interval it is calculated against

A secondary parameter needs a result from a second profile: renal clearance divides an amount excreted in urine by a plasma AUC, an accumulation ratio compares one dosing interval with another, and a metabolite ratio compares two analytes. This adds the request and the linkage columns (interval_id on the reference interval and <param>_ref on the intervals calculating the parameter) that pk.nca() reads.

Usage

interval_add_secondary(
  data,
  param,
  reference = NULL,
  target_groups = NULL,
  ref_id = NULL,
  ref_vary = NULL,
  ...
)

Arguments

data

A PKNCAdata object or a data.frame of intervals.

param

The name of one secondary NCA parameter (see pknca_parameter_table() for which parameters are secondary).

reference

A data.frame describing the reference interval: its columns are start, end, and/or group columns of the intervals, every column must match (and) for at least one of its rows (or). A named list is accepted and coerced. When no interval matches, one is created and the creation is reported with a pknca_message_secondary_created_interval message. NULL (the default) takes the group_ref given to PKNCAdata() (resolved for param when it is parameter-specific), or derives the reference from the data (see Details).

target_groups

A data.frame of group values restricting the parameter request to matching intervals, with the same matching rules as reference. NULL (the default) requests it on every interval that is not a reference interval.

ref_id

The interval_id to give the reference interval. The default of NULL keeps an identifier the reference rows already have and otherwise generates one matching the class of the interval_id column. A ref_id that differs from the identifier the reference rows already have renames that interval, which is an error when another interval points at the old identifier or already has ref_id. Reference rows that already carry more than one interval_id are an error (pknca_error_secondary_ref_ambiguous_spec) when ref_id is given, as it cannot name more than one interval.

ref_vary

The group columns in which the reference may differ from the interval calculating param, such as "period" in a crossover (see "Group columns that may differ"). They are written into the <param>_ref_vary column of the linked intervals, so the names may not contain spaces or commas (per-link declarations need group column names without spaces or commas; give such a column to PKNCAdata() instead). The default of NULL writes nothing, so the ref_vary given to PKNCAdata() applies, and character(0) declares that no column may differ (overriding that default).

...

Ignored.

Value

The input with the parameter requested and the linkage columns set, after check.interval.specification().

Details

The reference interval gains whatever the linked calculation reads from it (the plasma AUC for a renal clearance, for example) without being announced, as calculating any dependency is.

An interval that already names a different reference for param is left alone with a pknca_warning_secondary_ref_exists warning, so that the helper never silently re-points an analysis.

With reference = NULL the reference is derived from the data, which needs a PKNCAdata object (a bare intervals data.frame carries no concentrations to derive it from). The group_ref given to PKNCAdata() is used when it is set. Otherwise the derivation applies where the parameter is measured on an interval collection while everything it references is a spot sample (renal clearance) and the concentration data declare a collection volume: each interval takes the profile with no collection volume that differs from its own in the fewest group columns. This is the same derivation pk.nca() makes on its own, written out into the returned intervals instead of being ephemeral. Anything the derivation cannot resolve is an error here (pknca_error_secondary_needs_ref) rather than the NA result the automatic path gives, so narrow the request with target_groups when some intervals are not meant to calculate param.

When the parameter pairs an interval collection with spot-sample references (renal clearance: an amount excreted against a plasma AUC) and the reference interval is created by the PKNCAdata method, the created interval spans the collections whole: a collection that begins inside the interval contributes its full amount (see pk.nca()), so a collection running past the interval's end extends the created reference's end to time + duration of the latest collection. An explicit end in reference overrides the extension, and the data.frame method (which has no concentration data) copies the test interval's times unchanged.

Group columns that may differ

A reference is matched on the requesting group's own values in every group column except the ones the reference interval names: with groups treatment+subject and reference = data.frame(treatment = "iv"), each subject's oral profile uses that subject's IV profile. When the concentration data are also grouped by a column that the reference treatment does not share, such as the period of a crossover, the IV profile is in a different period than the oral one and is not found (pknca_error_secondary_ref_value_missing).

ref_vary names such columns. The reference is then matched on every other group column and on the reference interval's own columns, and takes whichever value of the varying columns has the reference interval's results. Exactly one may: more than one (a replicate design giving the reference twice) is an error (pknca_error_secondary_ref_vary_ambiguous) naming the requesting group and the candidates. A candidate counts when the reference interval has a result row for it, even an NA one, so a replicate design with one administration that could not be fitted is still ambiguous rather than silently using the other. It is resolved by adding a group column that tells them apart to the intervals and naming it in reference. A varying column that the reference interval names is pinned by it. The subject column cannot vary, as a reference is always the subject's own profile.

The declaration is stored per link as column names separated by commas in the <param>_ref_vary column of the intervals, so it can also be written by hand. NA there takes the ref_vary of PKNCAdata() (which declares the varying columns once for every link of the data), and "" declares that no column varies. The result names the reference's group in its <group column>_ref columns and in PPANMETH ("Reference interval: treatment=iv, period=1, 0-Inf").

See also

interval_add_param(), pknca_ref(), pk.nca()

Other Interval specifications: add.interval.col(), check.interval.specification(), choose.auc.intervals(), get.interval.cols(), get.parameter.deps(), interval_add_impute(), interval_add_param(), pknca_cdisc_codes(), pknca_check_parameter_classification(), pknca_concepts(), pknca_interval_table(), pknca_match_route(), pknca_parameter_table(), pknca_presets(), pknca_ref()

Examples

intervals <-
  data.frame(
    PCSPEC = c("plasma", "urine"),
    start = 0, end = 24,
    auclast = c(TRUE, FALSE),
    ae = c(FALSE, TRUE)
  )
interval_add_secondary(
  intervals,
  param = "clr.last",
  reference = data.frame(PCSPEC = "plasma")
)
#>   start end auclast auclast_se auclast_df aucall aucall_se aucall_df aumclast
#> 1     0  24    TRUE      FALSE      FALSE  FALSE     FALSE     FALSE    FALSE
#> 2     0  24   FALSE      FALSE      FALSE  FALSE     FALSE     FALSE    FALSE
#>   aumclast_se aumclast_df aumcall aumcall_se aumcall_df aucint.last aucint.all
#> 1       FALSE       FALSE   FALSE      FALSE      FALSE       FALSE      FALSE
#> 2       FALSE       FALSE   FALSE      FALSE      FALSE       FALSE      FALSE
#>   aumcint.last aumcint.all    c0  cmax  cmin  tmax  tmin tlast tfirst clast.obs
#> 1        FALSE       FALSE FALSE FALSE FALSE FALSE FALSE FALSE  FALSE     FALSE
#> 2        FALSE       FALSE FALSE FALSE FALSE FALSE FALSE FALSE  FALSE     FALSE
#>   cl.last cl.all cl.int.all cl.int.last mrt.last mrt.all mrt.int.all
#> 1   FALSE  FALSE      FALSE       FALSE    FALSE   FALSE       FALSE
#> 2   FALSE  FALSE      FALSE       FALSE    FALSE   FALSE       FALSE
#>   mrt.int.last mrt.iv.last vss.last vss.iv.last vss.all vss.int.all
#> 1        FALSE       FALSE    FALSE       FALSE   FALSE       FALSE
#> 2        FALSE       FALSE    FALSE       FALSE   FALSE       FALSE
#>   vss.int.last   cav cav.int.last cav.int.all ctrough cstart   ptr  tlag
#> 1        FALSE FALSE        FALSE       FALSE   FALSE  FALSE FALSE FALSE
#> 2        FALSE FALSE        FALSE       FALSE   FALSE  FALSE FALSE FALSE
#>   deg.fluc swing  ceoi aucabove.predose.all aucabove.trough.all count_conc
#> 1    FALSE FALSE FALSE                FALSE               FALSE      FALSE
#> 2    FALSE FALSE FALSE                FALSE               FALSE      FALSE
#>   count_conc_measured totdose volpk    ae clr.last clr.obs clr.pred    fe
#> 1               FALSE   FALSE FALSE FALSE    FALSE   FALSE    FALSE FALSE
#> 2               FALSE   FALSE FALSE  TRUE     TRUE   FALSE    FALSE FALSE
#>   ertlst ermax ertmax erint erlst ratio.cmax ratio.auclast ratio.aucint.last
#> 1  FALSE FALSE  FALSE FALSE FALSE      FALSE         FALSE             FALSE
#> 2  FALSE FALSE  FALSE FALSE FALSE      FALSE         FALSE             FALSE
#>   ratio.aucint.all sparse_auclast sparse_auc_se sparse_auc_df sparse_aumclast
#> 1            FALSE          FALSE         FALSE         FALSE           FALSE
#> 2            FALSE          FALSE         FALSE         FALSE           FALSE
#>   sparse_aumc_se sparse_aumc_df time_above aucivlast aucivlast_se aucivlast_df
#> 1          FALSE          FALSE      FALSE     FALSE        FALSE        FALSE
#> 2          FALSE          FALSE      FALSE     FALSE        FALSE        FALSE
#>   aucivall aucivall_se aucivall_df aucivint.last aucivint.all aucivpbextlast
#> 1    FALSE       FALSE       FALSE         FALSE        FALSE          FALSE
#> 2    FALSE       FALSE       FALSE         FALSE        FALSE          FALSE
#>   aucivpbextall aucivpbextint.last aucivpbextint.all aumcivlast aumcivlast_se
#> 1         FALSE              FALSE             FALSE      FALSE         FALSE
#> 2         FALSE              FALSE             FALSE      FALSE         FALSE
#>   aumcivlast_df aumcivall aumcivall_se aumcivall_df aumcivint.last
#> 1         FALSE     FALSE        FALSE        FALSE          FALSE
#> 2         FALSE     FALSE        FALSE        FALSE          FALSE
#>   aumcivint.all half.life r.squared adj.r.squared lambda.z.corrxy lambda.z
#> 1         FALSE     FALSE     FALSE         FALSE           FALSE    FALSE
#> 2         FALSE     FALSE     FALSE         FALSE           FALSE    FALSE
#>   lambda.z.time.first lambda.z.time.last lambda.z.n.points clast.pred
#> 1               FALSE              FALSE             FALSE      FALSE
#> 2               FALSE              FALSE             FALSE      FALSE
#>   span.ratio tobit_residual adj_tobit_residual lambda.z.n.points_blq
#> 1      FALSE          FALSE              FALSE                 FALSE
#> 2      FALSE          FALSE              FALSE                 FALSE
#>   thalf.eff.last thalf.eff.iv.last kel.last kel.iv.last kel.all kel.int.all
#> 1          FALSE             FALSE    FALSE       FALSE   FALSE       FALSE
#> 2          FALSE             FALSE    FALSE       FALSE   FALSE       FALSE
#>   kel.int.last cl.iv.all cl.iv.last cl.ivint.all cl.ivint.last cl.sparse.last
#> 1        FALSE     FALSE      FALSE        FALSE         FALSE          FALSE
#> 2        FALSE     FALSE      FALSE        FALSE         FALSE          FALSE
#>   f.last f.int.last f.int.all mrt.sparse.last mrt.iv.all mrt.ivint.all
#> 1  FALSE      FALSE     FALSE           FALSE      FALSE         FALSE
#> 2  FALSE      FALSE     FALSE           FALSE      FALSE         FALSE
#>   mrt.ivint.last vz.all vz.int.all vz.int.last vz.iv.all vz.iv.last
#> 1          FALSE  FALSE      FALSE       FALSE     FALSE      FALSE
#> 2          FALSE  FALSE      FALSE       FALSE     FALSE      FALSE
#>   vz.ivint.all vz.ivint.last vz.last vss.iv.all vss.ivint.all vss.ivint.last
#> 1        FALSE         FALSE   FALSE      FALSE         FALSE          FALSE
#> 2        FALSE         FALSE   FALSE      FALSE         FALSE          FALSE
#>   vss.sparse.last aucinf.obs aucinf.obs_se aucinf.obs_df aucinf.pred
#> 1           FALSE      FALSE         FALSE         FALSE       FALSE
#> 2           FALSE      FALSE         FALSE         FALSE       FALSE
#>   aumcinf.obs aumcinf.obs_se aumcinf.obs_df aumcinf.pred aucint.inf.obs
#> 1       FALSE          FALSE          FALSE        FALSE          FALSE
#> 2       FALSE          FALSE          FALSE        FALSE          FALSE
#>   aucint.inf.pred aumcint.inf.obs aumcint.inf.pred aucivinf.obs aucivinf.obs_se
#> 1           FALSE           FALSE            FALSE        FALSE           FALSE
#> 2           FALSE           FALSE            FALSE        FALSE           FALSE
#>   aucivinf.obs_df aucivinf.pred aucivpbextinf.obs aucivpbextinf.pred
#> 1           FALSE         FALSE             FALSE              FALSE
#> 2           FALSE         FALSE             FALSE              FALSE
#>   aumcivinf.obs aumcivinf.obs_se aumcivinf.obs_df aumcivinf.pred aucpext.obs
#> 1         FALSE            FALSE            FALSE          FALSE       FALSE
#> 2         FALSE            FALSE            FALSE          FALSE       FALSE
#>   aucpext.pred kel.iv.all kel.ivint.all kel.ivint.last kel.sparse.last cl.obs
#> 1        FALSE      FALSE         FALSE          FALSE           FALSE  FALSE
#> 2        FALSE      FALSE         FALSE          FALSE           FALSE  FALSE
#>   cl.pred cl.int.inf.obs cl.int.inf.pred cl.iv.obs cl.iv.pred f.obs f.pred
#> 1   FALSE          FALSE           FALSE     FALSE      FALSE FALSE  FALSE
#> 2   FALSE          FALSE           FALSE     FALSE      FALSE FALSE  FALSE
#>   f.int.obs f.int.pred mrt.obs mrt.pred mrt.int.inf.obs mrt.int.inf.pred
#> 1     FALSE      FALSE   FALSE    FALSE           FALSE            FALSE
#> 2     FALSE      FALSE   FALSE    FALSE           FALSE            FALSE
#>   mrt.iv.obs mrt.iv.pred mrt.md.obs mrt.md.pred mrt.ivmd.obs mrt.ivmd.pred
#> 1      FALSE       FALSE      FALSE       FALSE        FALSE         FALSE
#> 2      FALSE       FALSE      FALSE       FALSE        FALSE         FALSE
#>   vz.obs vz.pred vz.int.inf.obs vz.int.inf.pred vz.iv.obs vz.iv.pred
#> 1  FALSE   FALSE          FALSE           FALSE     FALSE      FALSE
#> 2  FALSE   FALSE          FALSE           FALSE     FALSE      FALSE
#>   vz.sparse.last vss.obs vss.pred vss.iv.obs vss.iv.pred vss.md.obs vss.md.pred
#> 1          FALSE   FALSE    FALSE      FALSE       FALSE      FALSE       FALSE
#> 2          FALSE   FALSE    FALSE      FALSE       FALSE      FALSE       FALSE
#>   vss.ivmd.obs vss.ivmd.pred vss.int.inf.obs vss.int.inf.pred cav.int.inf.obs
#> 1        FALSE         FALSE           FALSE            FALSE           FALSE
#> 2        FALSE         FALSE           FALSE            FALSE           FALSE
#>   cav.int.inf.pred ratio.aucinf.obs ratio.aucinf.pred thalf.eff.obs
#> 1            FALSE            FALSE             FALSE         FALSE
#> 2            FALSE            FALSE             FALSE         FALSE
#>   thalf.eff.pred thalf.eff.iv.obs thalf.eff.iv.pred kel.obs kel.pred kel.iv.obs
#> 1          FALSE            FALSE             FALSE   FALSE    FALSE      FALSE
#> 2          FALSE            FALSE             FALSE   FALSE    FALSE      FALSE
#>   kel.iv.pred kel.int.inf.obs kel.int.inf.pred auclast.dn aucall.dn
#> 1       FALSE           FALSE            FALSE      FALSE     FALSE
#> 2       FALSE           FALSE            FALSE      FALSE     FALSE
#>   aucinf.obs.dn aucinf.pred.dn aumclast.dn aumcall.dn aumcinf.obs.dn
#> 1         FALSE          FALSE       FALSE      FALSE          FALSE
#> 2         FALSE          FALSE       FALSE      FALSE          FALSE
#>   aumcinf.pred.dn cmax.dn cmin.dn clast.obs.dn clast.pred.dn cav.dn ctrough.dn
#> 1           FALSE   FALSE   FALSE        FALSE         FALSE  FALSE      FALSE
#> 2           FALSE   FALSE   FALSE        FALSE         FALSE  FALSE      FALSE
#>   clr.last.dn clr.obs.dn clr.pred.dn PCSPEC interval_id clr.last_ref
#> 1       FALSE      FALSE       FALSE plasma        ref1         <NA>
#> 2       FALSE      FALSE       FALSE  urine        <NA>         ref1

# A crossover where each subject received the IV reference in a different
# period than the oral treatment
intervals_crossover <-
  data.frame(treatment = c("iv", "oral"), start = 0, end = Inf, aucinf.obs = TRUE)
interval_add_secondary(
  intervals_crossover,
  param = "f.obs",
  reference = data.frame(treatment = "iv"),
  ref_vary = "period"
)
#>   start end auclast auclast_se auclast_df aucall aucall_se aucall_df aumclast
#> 1     0 Inf   FALSE      FALSE      FALSE  FALSE     FALSE     FALSE    FALSE
#> 2     0 Inf   FALSE      FALSE      FALSE  FALSE     FALSE     FALSE    FALSE
#>   aumclast_se aumclast_df aumcall aumcall_se aumcall_df aucint.last aucint.all
#> 1       FALSE       FALSE   FALSE      FALSE      FALSE       FALSE      FALSE
#> 2       FALSE       FALSE   FALSE      FALSE      FALSE       FALSE      FALSE
#>   aumcint.last aumcint.all    c0  cmax  cmin  tmax  tmin tlast tfirst clast.obs
#> 1        FALSE       FALSE FALSE FALSE FALSE FALSE FALSE FALSE  FALSE     FALSE
#> 2        FALSE       FALSE FALSE FALSE FALSE FALSE FALSE FALSE  FALSE     FALSE
#>   cl.last cl.all cl.int.all cl.int.last mrt.last mrt.all mrt.int.all
#> 1   FALSE  FALSE      FALSE       FALSE    FALSE   FALSE       FALSE
#> 2   FALSE  FALSE      FALSE       FALSE    FALSE   FALSE       FALSE
#>   mrt.int.last mrt.iv.last vss.last vss.iv.last vss.all vss.int.all
#> 1        FALSE       FALSE    FALSE       FALSE   FALSE       FALSE
#> 2        FALSE       FALSE    FALSE       FALSE   FALSE       FALSE
#>   vss.int.last   cav cav.int.last cav.int.all ctrough cstart   ptr  tlag
#> 1        FALSE FALSE        FALSE       FALSE   FALSE  FALSE FALSE FALSE
#> 2        FALSE FALSE        FALSE       FALSE   FALSE  FALSE FALSE FALSE
#>   deg.fluc swing  ceoi aucabove.predose.all aucabove.trough.all count_conc
#> 1    FALSE FALSE FALSE                FALSE               FALSE      FALSE
#> 2    FALSE FALSE FALSE                FALSE               FALSE      FALSE
#>   count_conc_measured totdose volpk    ae clr.last clr.obs clr.pred    fe
#> 1               FALSE    TRUE FALSE FALSE    FALSE   FALSE    FALSE FALSE
#> 2               FALSE   FALSE FALSE FALSE    FALSE   FALSE    FALSE FALSE
#>   ertlst ermax ertmax erint erlst ratio.cmax ratio.auclast ratio.aucint.last
#> 1  FALSE FALSE  FALSE FALSE FALSE      FALSE         FALSE             FALSE
#> 2  FALSE FALSE  FALSE FALSE FALSE      FALSE         FALSE             FALSE
#>   ratio.aucint.all sparse_auclast sparse_auc_se sparse_auc_df sparse_aumclast
#> 1            FALSE          FALSE         FALSE         FALSE           FALSE
#> 2            FALSE          FALSE         FALSE         FALSE           FALSE
#>   sparse_aumc_se sparse_aumc_df time_above aucivlast aucivlast_se aucivlast_df
#> 1          FALSE          FALSE      FALSE     FALSE        FALSE        FALSE
#> 2          FALSE          FALSE      FALSE     FALSE        FALSE        FALSE
#>   aucivall aucivall_se aucivall_df aucivint.last aucivint.all aucivpbextlast
#> 1    FALSE       FALSE       FALSE         FALSE        FALSE          FALSE
#> 2    FALSE       FALSE       FALSE         FALSE        FALSE          FALSE
#>   aucivpbextall aucivpbextint.last aucivpbextint.all aumcivlast aumcivlast_se
#> 1         FALSE              FALSE             FALSE      FALSE         FALSE
#> 2         FALSE              FALSE             FALSE      FALSE         FALSE
#>   aumcivlast_df aumcivall aumcivall_se aumcivall_df aumcivint.last
#> 1         FALSE     FALSE        FALSE        FALSE          FALSE
#> 2         FALSE     FALSE        FALSE        FALSE          FALSE
#>   aumcivint.all half.life r.squared adj.r.squared lambda.z.corrxy lambda.z
#> 1         FALSE     FALSE     FALSE         FALSE           FALSE    FALSE
#> 2         FALSE     FALSE     FALSE         FALSE           FALSE    FALSE
#>   lambda.z.time.first lambda.z.time.last lambda.z.n.points clast.pred
#> 1               FALSE              FALSE             FALSE      FALSE
#> 2               FALSE              FALSE             FALSE      FALSE
#>   span.ratio tobit_residual adj_tobit_residual lambda.z.n.points_blq
#> 1      FALSE          FALSE              FALSE                 FALSE
#> 2      FALSE          FALSE              FALSE                 FALSE
#>   thalf.eff.last thalf.eff.iv.last kel.last kel.iv.last kel.all kel.int.all
#> 1          FALSE             FALSE    FALSE       FALSE   FALSE       FALSE
#> 2          FALSE             FALSE    FALSE       FALSE   FALSE       FALSE
#>   kel.int.last cl.iv.all cl.iv.last cl.ivint.all cl.ivint.last cl.sparse.last
#> 1        FALSE     FALSE      FALSE        FALSE         FALSE          FALSE
#> 2        FALSE     FALSE      FALSE        FALSE         FALSE          FALSE
#>   f.last f.int.last f.int.all mrt.sparse.last mrt.iv.all mrt.ivint.all
#> 1  FALSE      FALSE     FALSE           FALSE      FALSE         FALSE
#> 2  FALSE      FALSE     FALSE           FALSE      FALSE         FALSE
#>   mrt.ivint.last vz.all vz.int.all vz.int.last vz.iv.all vz.iv.last
#> 1          FALSE  FALSE      FALSE       FALSE     FALSE      FALSE
#> 2          FALSE  FALSE      FALSE       FALSE     FALSE      FALSE
#>   vz.ivint.all vz.ivint.last vz.last vss.iv.all vss.ivint.all vss.ivint.last
#> 1        FALSE         FALSE   FALSE      FALSE         FALSE          FALSE
#> 2        FALSE         FALSE   FALSE      FALSE         FALSE          FALSE
#>   vss.sparse.last aucinf.obs aucinf.obs_se aucinf.obs_df aucinf.pred
#> 1           FALSE       TRUE         FALSE         FALSE       FALSE
#> 2           FALSE       TRUE         FALSE         FALSE       FALSE
#>   aumcinf.obs aumcinf.obs_se aumcinf.obs_df aumcinf.pred aucint.inf.obs
#> 1       FALSE          FALSE          FALSE        FALSE          FALSE
#> 2       FALSE          FALSE          FALSE        FALSE          FALSE
#>   aucint.inf.pred aumcint.inf.obs aumcint.inf.pred aucivinf.obs aucivinf.obs_se
#> 1           FALSE           FALSE            FALSE        FALSE           FALSE
#> 2           FALSE           FALSE            FALSE        FALSE           FALSE
#>   aucivinf.obs_df aucivinf.pred aucivpbextinf.obs aucivpbextinf.pred
#> 1           FALSE         FALSE             FALSE              FALSE
#> 2           FALSE         FALSE             FALSE              FALSE
#>   aumcivinf.obs aumcivinf.obs_se aumcivinf.obs_df aumcivinf.pred aucpext.obs
#> 1         FALSE            FALSE            FALSE          FALSE       FALSE
#> 2         FALSE            FALSE            FALSE          FALSE       FALSE
#>   aucpext.pred kel.iv.all kel.ivint.all kel.ivint.last kel.sparse.last cl.obs
#> 1        FALSE      FALSE         FALSE          FALSE           FALSE  FALSE
#> 2        FALSE      FALSE         FALSE          FALSE           FALSE  FALSE
#>   cl.pred cl.int.inf.obs cl.int.inf.pred cl.iv.obs cl.iv.pred f.obs f.pred
#> 1   FALSE          FALSE           FALSE     FALSE      FALSE FALSE  FALSE
#> 2   FALSE          FALSE           FALSE     FALSE      FALSE  TRUE  FALSE
#>   f.int.obs f.int.pred mrt.obs mrt.pred mrt.int.inf.obs mrt.int.inf.pred
#> 1     FALSE      FALSE   FALSE    FALSE           FALSE            FALSE
#> 2     FALSE      FALSE   FALSE    FALSE           FALSE            FALSE
#>   mrt.iv.obs mrt.iv.pred mrt.md.obs mrt.md.pred mrt.ivmd.obs mrt.ivmd.pred
#> 1      FALSE       FALSE      FALSE       FALSE        FALSE         FALSE
#> 2      FALSE       FALSE      FALSE       FALSE        FALSE         FALSE
#>   vz.obs vz.pred vz.int.inf.obs vz.int.inf.pred vz.iv.obs vz.iv.pred
#> 1  FALSE   FALSE          FALSE           FALSE     FALSE      FALSE
#> 2  FALSE   FALSE          FALSE           FALSE     FALSE      FALSE
#>   vz.sparse.last vss.obs vss.pred vss.iv.obs vss.iv.pred vss.md.obs vss.md.pred
#> 1          FALSE   FALSE    FALSE      FALSE       FALSE      FALSE       FALSE
#> 2          FALSE   FALSE    FALSE      FALSE       FALSE      FALSE       FALSE
#>   vss.ivmd.obs vss.ivmd.pred vss.int.inf.obs vss.int.inf.pred cav.int.inf.obs
#> 1        FALSE         FALSE           FALSE            FALSE           FALSE
#> 2        FALSE         FALSE           FALSE            FALSE           FALSE
#>   cav.int.inf.pred ratio.aucinf.obs ratio.aucinf.pred thalf.eff.obs
#> 1            FALSE            FALSE             FALSE         FALSE
#> 2            FALSE            FALSE             FALSE         FALSE
#>   thalf.eff.pred thalf.eff.iv.obs thalf.eff.iv.pred kel.obs kel.pred kel.iv.obs
#> 1          FALSE            FALSE             FALSE   FALSE    FALSE      FALSE
#> 2          FALSE            FALSE             FALSE   FALSE    FALSE      FALSE
#>   kel.iv.pred kel.int.inf.obs kel.int.inf.pred auclast.dn aucall.dn
#> 1       FALSE           FALSE            FALSE      FALSE     FALSE
#> 2       FALSE           FALSE            FALSE      FALSE     FALSE
#>   aucinf.obs.dn aucinf.pred.dn aumclast.dn aumcall.dn aumcinf.obs.dn
#> 1         FALSE          FALSE       FALSE      FALSE          FALSE
#> 2         FALSE          FALSE       FALSE      FALSE          FALSE
#>   aumcinf.pred.dn cmax.dn cmin.dn clast.obs.dn clast.pred.dn cav.dn ctrough.dn
#> 1           FALSE   FALSE   FALSE        FALSE         FALSE  FALSE      FALSE
#> 2           FALSE   FALSE   FALSE        FALSE         FALSE  FALSE      FALSE
#>   clr.last.dn clr.obs.dn clr.pred.dn treatment interval_id f.obs_ref
#> 1       FALSE      FALSE       FALSE        iv        ref1      <NA>
#> 2       FALSE      FALSE       FALSE      oral        <NA>      ref1
#>   f.obs_ref_vary
#> 1           <NA>
#> 2         period