Brentuximab vedotin ADC + MMAE coupled population PK model (Li 2017) • nlmixr2lib

library(nlmixr2lib)
library(PKNCA)
#> 
#> Attaching package: 'PKNCA'
#> The following object is masked from 'package:stats':
#> 
#>     filter
library(rxode2)
#> rxode2 5.0.2 using 2 threads (see ?getRxThreads)
#>   no cache: create with `rxCreateCache()`
library(dplyr)
#> 
#> Attaching package: 'dplyr'
#> The following objects are masked from 'package:stats':
#> 
#>     filter, lag
#> The following objects are masked from 'package:base':
#> 
#>     intersect, setdiff, setequal, union
library(tidyr)
library(ggplot2)

Model and source

Citation: Li H, Han TH, Hunder NN, Jang G, Zhao B. Population Pharmacokinetics of Brentuximab Vedotin in Patients With CD30-Expressing Hematologic Malignancies. J Clin Pharmacol. 2017;57(9):1148–1158.
Article: https://doi.org/10.1002/jcph.920 (PMID 28513851)
Supplement: Supplementary Material S1 — NONMEM Code for the ADC and MMAE Population PK Model (DOI page links the supplement alongside the article).

The model couples two submodels (paper Figure 1):

ADC submodel — linear 3-compartment with first-order elimination.
MMAE submodel — linear 2-compartment with first-order elimination; its central compartment is driven by two ADC-derived formation pathways.

MMAE is released from the ADC by (i) proteolytic degradation of the antibody in cells, at a rate proportional to the ADC elimination flux K10 * A1, scaled by the time-decaying drug-to-antibody ratio DAR(t) and a cycle-dependent conversion fraction Fmc = CYCLE^Fm, and by (ii) first-order deconjugation of drug from the ADC backbone independent of elimination:

DAR(t)    = 4 * (0.25 + 0.75 * exp(-beta * tad))      (Li 2017 Eq. 5)
Fmc(k)    = CYCLE^Fm, Fm = -0.261                      (Li 2017 Eq. 6)
MMAE_form = K10 * A1 * DAR(t) * Fmc +                  proteolytic
            A1 * (DAR(t) - 4 * 0.25) * beta            deconjugation

where tad is time since the most recent dose and CYCLE is the integer treatment-cycle number, incremented at each new dose.

Modeling is done in molar units so that concentrations are reported in the paper’s convention pmol/mL (≡ nmol/L ≡ nM). Mass-unit conversions for the two analytes use MW_ADC = 153 kDa and MW_MMAE = 718 Da:

ADC:  1 pmol/mL = 0.153 ug/mL = 153 ng/mL
MMAE: 1 pmol/mL = 0.718 ng/mL

Population

The analysis pooled 314 adults with relapsed/refractory CD30-expressing hematologic malignancies from five brentuximab vedotin clinical trials (paper Table 1 and Table 2):

Studies: 2 phase 1 dose-ranging (NCT00430846, NCT00649584), 2 pivotal phase 2 (HL: NCT00848926, n = 102; sALCL: NCT00866047, n = 58), and a phase 1 clinical pharmacology study (NCT01026415).
Demographics: 43% female, 85% White; median age 35 years (range 12–87); median weight 74.8 kg (range 41.4–168); dose capped at 180 mg for subjects > 100 kg.
Disease: 77% Hodgkin lymphoma, 21% systemic anaplastic large-cell lymphoma, 2% other.
Dose regimens: 0.1–3.6 mg/kg IV every 3 weeks, or weekly dosing on days 1/8/15 of 4-week cycles (Study 2 only). The licensed adult regimen is 1.8 mg/kg IV every 3 weeks with a 180-mg per-dose cap.
Observations: 7,081 ADC concentrations and 7,452 MMAE concentrations.

mod <- rxode2::rxode(readModelDb("Li_2017_brentuximab"))
#> ℹ parameter labels from comments will be replaced by 'label()'
str(mod$meta$population, max.level = 1)
#> List of 15
#>  $ n_subjects       : int 314
#>  $ n_studies        : int 5
#>  $ age_range        : chr "12-87 years (median 35)"
#>  $ age_median       : chr "35 years"
#>  $ weight_range     : chr "41.4-168 kg (median 74.8)"
#>  $ weight_median    : chr "75 kg (reference-subject value; pooled-population median 74.8 kg)"
#>  $ sex_female_pct   : num 43.3
#>  $ race_ethnicity   : Named num [1:2] 85 15
#>   ..- attr(*, "names")= chr [1:2] "White" "Other"
#>  $ disease_state    : chr "Relapsed/refractory CD30-expressing hematologic malignancies: Hodgkin lymphoma (HL, 77%), systemic anaplastic l"| __truncated__
#>  $ dose_range       : chr "0.1-3.6 mg/kg IV every 3 weeks (Studies 1, 3, 4, 5) or 0.4-1.4 mg/kg IV weekly for 3 weeks of each 4-week cycle"| __truncated__
#>  $ regions          : chr "Global (North America, Europe, Canada)."
#>  $ study_phase      : chr "2 phase 1 dose-ranging studies, 2 pivotal phase 2 studies (HL, sALCL), 1 phase 1 clinical pharmacology study (5"| __truncated__
#>  $ n_observations   : chr "7081 ADC concentrations + 7452 MMAE concentrations across 314 subjects."
#>  $ reference_subject: chr "75 kg male, Cycle 1 (WT / 75)^exponent and CYCLE^Fm both equal 1."
#>  $ notes            : chr "Baseline characteristics reported in Li 2017 Table 2; data collected November 2006 - June 2011. Renal function "| __truncated__

Only body weight (on all six ADC structural parameters) and sex (on ADC V1 only) were retained as significant covariates. Age, race, creatinine clearance, albumin, AST/ALT/bilirubin, tumour size, and manufacturing process were tested and excluded (paper ADC Final Model section).

Source trace

Every ini() entry in inst/modeldb/specificDrugs/Li_2017_brentuximab.R carries an in-file comment pointing to Li 2017 Table 3 or Table 4. The table below collates them:

Parameter (nlmixr2lib)	Value	Source
`lcl` → CL	1.56 L/d	Table 3
`lvc` → V1	4.29 L	Table 3
`lq` → Q2	2.83 L/d	Table 3
`lvp` → V2	3.83 L	Table 3
`lq2` → Q3	0.708 L/d	Table 3
`lvp2` → V3	9.52 L	Table 3
`e_wt_adc_cl`	0.698	Table 3 (Θ_BW,CL,Q2,Q3)
`e_wt_adc_vc`	0.503	Table 3 (Θ_BW,V1,V2,V3)
`e_sexf_vc`	0.873	Table 3 (Θ_SEX,V1)
`CcaddSd`	0.0817 pmol/mL (= 0.0125 µg/mL)	Table 3 σ1 fixed
`CcpropSd`	0.329	Table 3 σ2 (32.9% CV)
`lclm` → CLM	55.7 L/d	Table 4
`lvcm` → V4	79.8 L	Table 4
`lqm` → Q5	65.0 L/d	Table 4
`lvpm` → V5	28.1 L	Table 4
`lbeta` → β	0.0785 /d	Table 4
`lfm` → Fm	−0.261	Table 4 (Fm by cycle)
`e_wt_mmae_cl`	0.75 (fixed)	Table 4
`e_wt_mmae_vc`	1.0 (fixed)	Table 4
`CmmaeaddSd`	0.01658 pmol/mL (= 0.0119 ng/mL)	Table 4 σ1
`CmmaepropSd`	0.368	Table 4 σ2 (36.8% CV)
Corr(CL, V1)	0.229	Table 3
Corr(CLM, V4)	0.634	Table 4
DAR0	4 (fixed)	Table 4 + Eq. 5
α	0.25 (fixed)	Table 4 + Eq. 5
ODE system (7 states)	n/a	Supplement M1 `$DES`

Inter-individual variability (log-normal, omega² = log(CV² + 1)):

Parameter	BSV %CV	ω²
CL	46.9	0.199
V1	13.5	0.018
Q2	15.0 (fixed)	0.022
V2	25.0 (fixed)	0.061
Q3	45.2	0.186
V3	106	0.753
CLM	60.7	0.314
V4	78.2	0.477
β	98.1	0.674
Fm	130	0.990
Q5, V5	0 (fixed)	—

Virtual cohort

We simulate a 200-subject virtual cohort matched to the pooled Table 2 demographics: median weight 74.8 kg, range 41.4–168 kg (log-normal with σ calibrated to span the published range); 43% female. Every subject is given the licensed 1.8 mg/kg IV every-3-weeks regimen for 5 cycles with the 180-mg cap applied.

set.seed(20250424L)

n_subj   <- 200L
cycle_dy <- 21
n_cycles <- 5L

MW_ADC_kDa  <- 153        # brentuximab vedotin (paper)
MW_MMAE_Da  <- 718        # monomethyl auristatin E (paper)

# Body-weight distribution anchored to the paper's median 74.8 kg and range
# 41.4-168. Log-normal sigma ~0.22 gives approximately the same spread.
wt    <- exp(rnorm(n_subj, mean = log(74.8), sd = 0.22))
wt    <- pmin(pmax(wt, 41.4), 168)
sexf  <- rbinom(n_subj, 1, 0.43)  # 43% female (paper Table 2)

make_subject <- function(id, wt_kg, sexf_ind) {
  # Apply the 180 mg cap documented in the paper's dosing rules.
  dose_mg   <- min(1.8 * wt_kg, 180)
  dose_nmol <- dose_mg * 1000 / MW_ADC_kDa   # mg -> nmol via 1 mg / MW(kDa) * 1000

  doses <- rxode2::et() |>
    rxode2::et(amt = dose_nmol, cmt = "adc_central", ii = cycle_dy,
               addl = n_cycles - 1L, time = 0)
  obs   <- rxode2::et(seq(0.05, n_cycles * cycle_dy, length.out = 420),
                      cmt = "Cc")
  ev <- rbind(doses, obs)
  ev$id    <- id
  ev$WT    <- wt_kg
  ev$SEXF  <- sexf_ind
  ev$CYCLE <- pmax(1L, as.integer(floor(ev$time / cycle_dy) + 1L))
  ev$dose_mg <- dose_mg
  ev
}

events <- purrr::map_dfr(seq_len(n_subj),
                         ~ make_subject(.x, wt[.x], sexf[.x])) |>
  as.data.frame()

# Sanity: IDs are unique across rows.
stopifnot(length(unique(events$id)) == n_subj)

Typical-subject simulation (1.8 mg/kg every 3 weeks, 5 cycles)

A single typical-subject curve (75 kg male, five cycles) to visualise the DAR decay within each cycle and the cycle-over-cycle decline of MMAE.

typ <- readModelDb("Li_2017_brentuximab") |> rxode2::zeroRe()
#> ℹ parameter labels from comments will be replaced by 'label()'

typ_events <- rxode2::et() |>
  rxode2::et(amt = (1.8 * 75) * 1000 / MW_ADC_kDa,
             cmt = "adc_central", ii = cycle_dy, addl = n_cycles - 1L,
             time = 0) |>
  rxode2::et(seq(0.05, n_cycles * cycle_dy, length.out = 1500), cmt = "Cc")
typ_events$WT    <- 75
typ_events$SEXF  <- 0
typ_events$CYCLE <- pmax(1L, as.integer(floor(typ_events$time / cycle_dy) + 1L))

typ_sim <- rxode2::rxSolve(typ, typ_events, returnType = "data.frame") |>
  mutate(
    Cc_ug_mL   = Cc    * MW_ADC_kDa / 1000,  # pmol/mL -> ug/mL (MW_kDa / 1000)
    Cmmae_ng_mL = Cmmae * MW_MMAE_Da / 1000  # pmol/mL -> ng/mL
  )
#> ℹ omega/sigma items treated as zero: 'etalcl', 'etalvc', 'etalq', 'etalvp', 'etalq2', 'etalvp2', 'etalclm', 'etalvcm', 'etalbeta', 'etalfm'

typ_sim |>
  tidyr::pivot_longer(c(Cc_ug_mL, Cmmae_ng_mL),
                      names_to = "analyte", values_to = "conc") |>
  mutate(analyte = recode(analyte,
                          Cc_ug_mL    = "ADC (ug/mL)",
                          Cmmae_ng_mL = "MMAE (ng/mL)")) |>
  ggplot(aes(time, conc)) +
  geom_line(colour = "steelblue", linewidth = 0.8) +
  facet_wrap(~ analyte, ncol = 1, scales = "free_y") +
  scale_y_log10() +
  labs(x = "Time (day)", y = "Concentration",
       caption = "Replicates the median trend in Li 2017 Figure 2.")

Typical-subject ADC (top) and MMAE (bottom) concentration-time profiles (75 kg male, 1.8 mg/kg IV every 3 weeks for 5 cycles). Qualitatively replicates the median line of Li 2017 Figure 2 (a) ADC and Figure 2 (b) MMAE. DAR resets to 4 at each dose and decays toward 1; Fmc declines with cycle number, reducing MMAE Cmax across cycles.

typ_sim |>
  select(time, dar, fmc) |>
  tidyr::pivot_longer(c(dar, fmc), names_to = "var", values_to = "value") |>
  ggplot(aes(time, value)) +
  geom_line(colour = "darkred", linewidth = 0.7) +
  facet_wrap(~ var, ncol = 1, scales = "free_y",
             labeller = as_labeller(c(dar = "DAR(t)", fmc = "Fmc(cycle)"))) +
  labs(x = "Time (day)", y = NULL)

Internal DAR(t) and Fmc(cycle) trajectories across five cycles for the typical subject. DAR resets to 4 at each dose and relaxes toward DAR0*alpha = 1. Fmc is cycle-constant and steps down at each new cycle because CYCLE^Fm with Fm = -0.261 is a decreasing function of integer cycle number.

~13% deconjugation derivation (Supplement M1)

The pathway_proteolytic and pathway_deconjugation bookkeeping compartments integrate the cumulative MMAE released along each pathway. At steady state, the deconjugation fraction converges to approximately 13% — matching the derivation in the paper’s supplement (“approximately 13% of unconjugated MMAE is formed by the deconjugation pathway”).

end <- typ_sim |>
  filter(time >= cycle_dy * n_cycles - 1) |>
  slice_tail(n = 1)

tibble(
  proteolytic_nmol    = end$pathway_proteolytic,
  deconjugation_nmol  = end$pathway_deconjugation,
  pct_deconjugation   = 100 * end$pathway_deconjugation /
                        (end$pathway_proteolytic + end$pathway_deconjugation)
) |>
  knitr::kable(
    digits  = c(1, 1, 2),
    caption = "Cumulative MMAE-equivalent released along each pathway at the end of cycle 5 (typical subject). The deconjugation fraction replicates the paper's ~13% steady-state derivation."
  )

Cumulative MMAE-equivalent released along each pathway at the end of cycle 5 (typical subject). The deconjugation fraction replicates the paper’s ~13% steady-state derivation.
proteolytic_nmol	deconjugation_nmol	pct_deconjugation
13018.9	1909.4	12.79

Population (VPC-style) simulation

Full population simulation with all between-subject variability and residual error preserved.

mod <- readModelDb("Li_2017_brentuximab")
pop_sim <- rxode2::rxSolve(mod, events,
                           keep = c("WT", "SEXF", "CYCLE", "dose_mg"),
                           returnType = "data.frame") |>
  mutate(
    Cc_ug_mL    = Cc    * MW_ADC_kDa / 1000,
    Cmmae_ng_mL = Cmmae * MW_MMAE_Da / 1000
  )
#> ℹ parameter labels from comments will be replaced by 'label()'

pop_sim |>
  group_by(time) |>
  summarise(
    p05 = quantile(Cc_ug_mL, 0.05, na.rm = TRUE),
    p50 = quantile(Cc_ug_mL, 0.50, na.rm = TRUE),
    p95 = quantile(Cc_ug_mL, 0.95, na.rm = TRUE),
    .groups = "drop"
  ) |>
  ggplot(aes(time, p50)) +
  geom_ribbon(aes(ymin = p05, ymax = p95), fill = "steelblue", alpha = 0.3) +
  geom_line(colour = "steelblue4", linewidth = 0.8) +
  scale_y_log10() +
  labs(x = "Time (day)", y = "ADC concentration (ug/mL)",
       title = "ADC VPC — 1.8 mg/kg every 3 weeks",
       caption = "Replicates Li 2017 Figure 2 (a).")

VPC-style percentiles of simulated ADC concentrations vs. time across 200 virtual subjects dosed 1.8 mg/kg IV every 3 weeks. 5th / 50th / 95th percentile ribbon. Corresponds to Li 2017 Figure 2 (a).

pop_sim |>
  group_by(time) |>
  summarise(
    p05 = quantile(Cmmae_ng_mL, 0.05, na.rm = TRUE),
    p50 = quantile(Cmmae_ng_mL, 0.50, na.rm = TRUE),
    p95 = quantile(Cmmae_ng_mL, 0.95, na.rm = TRUE),
    .groups = "drop"
  ) |>
  ggplot(aes(time, p50)) +
  geom_ribbon(aes(ymin = p05, ymax = p95), fill = "tomato", alpha = 0.3) +
  geom_line(colour = "tomato4", linewidth = 0.8) +
  scale_y_log10() +
  labs(x = "Time (day)", y = "MMAE concentration (ng/mL)",
       title = "MMAE VPC — 1.8 mg/kg every 3 weeks",
       caption = "Replicates Li 2017 Figure 2 (b).")

VPC-style percentiles of simulated MMAE concentrations vs. time. Peak MMAE declines from ~5 ng/mL in cycle 1 to ~3 ng/mL by cycle 5, reflecting the cycle-dependent proteolytic conversion Fmc = CYCLE^Fm with Fm = -0.261. Corresponds to Li 2017 Figure 2 (b) and the 50-80% cycle-1-to-subsequent exposure decline reported in the Results section.

cycle1 <- pop_sim |>
  filter(time <= cycle_dy) |>
  group_by(id) |>
  summarise(
    WT  = first(WT),
    auc = sum(diff(time) * (head(Cc_ug_mL, -1) + tail(Cc_ug_mL, -1)) / 2),
    .groups = "drop"
  ) |>
  mutate(wt_q = cut(WT, breaks = quantile(WT, probs = seq(0, 1, 0.25)),
                    include.lowest = TRUE, labels = c("Q1", "Q2", "Q3", "Q4")))

cycle1 |>
  ggplot(aes(wt_q, auc)) +
  geom_boxplot(fill = "steelblue", alpha = 0.5) +
  labs(x = "Body weight quartile", y = "Cycle 1 ADC AUC0-21 (ug/mL * day)",
       caption = "Replicates Li 2017 Figure 3 (a).")

AUC0-21 of ADC in cycle 1 by body-weight quartile (typical-value within quartile; dose capped at 180 mg for subjects > 100 kg). Replicates the qualitative message of Li 2017 Figure 3 (a): ADC AUC0-21 is similar across weight quartiles once the 180-mg cap is applied.

PKNCA validation (ADC and MMAE)

NCA on the simulated data, stratified by cycle, so results can be compared against any per-cycle exposure values the paper reports. Because the paper reports only relative AUC ratios across weight quartiles and qualitative cycle-over-cycle MMAE decline (not absolute NCA metrics), the validation target is the structure and ordering of the NCA output, not a point-for-point reference.

# Per-cycle ADC concentrations: assign each observation to its cycle interval.
adc_nca <- pop_sim |>
  filter(!is.na(Cc_ug_mL), time > 0) |>
  mutate(cycle = pmax(1L, as.integer(floor((time - 1e-9) / cycle_dy) + 1L)),
         time_in_cycle = time - (cycle - 1) * cycle_dy) |>
  filter(cycle <= n_cycles) |>
  transmute(id = id, cycle = as.factor(cycle),
            time = time_in_cycle, Cc = Cc_ug_mL)

adc_dose <- events |>
  filter(evid == 1) |>
  mutate(cycle = as.factor(pmax(1L, as.integer(round(time / cycle_dy) + 1L))),
         time_in_cycle = 0,
         amt = dose_mg) |>       # for PKNCA, report dose in mg for the AUC units
  transmute(id = id, cycle = cycle, time = time_in_cycle, amt = amt)

conc_obj <- PKNCA::PKNCAconc(adc_nca, Cc ~ time | cycle + id)
dose_obj <- PKNCA::PKNCAdose(adc_dose, amt ~ time | cycle + id)

intervals <- data.frame(
  start      = 0,
  end        = cycle_dy,
  cmax       = TRUE,
  tmax       = TRUE,
  auclast    = TRUE
)

adc_nca_res <- PKNCA::pk.nca(PKNCA::PKNCAdata(conc_obj, dose_obj,
                                              intervals = intervals))
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#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Warning: Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#>  ■■■■■■■■                          23% |  ETA:  6s
#> Warning: Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Warning: Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Warning: Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#>  ■■■■■■■■■■■■■■■■■■■■■■            68% |  ETA:  2s
#> Warning: Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Warning: Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
adc_nca_summary <- summary(adc_nca_res)
adc_nca_summary
#>  start end cycle   N auclast        cmax                    tmax
#>      0  21     1 200      NC 30.9 [17.6] 0.0500 [0.0500, 0.0500]
#>      0  21     2 200      NC 30.1 [16.8] 0.0901 [0.0901, 0.0901]
#>      0  21     3 200      NC 28.9 [16.6]    0.130 [0.130, 0.130]
#>      0  21     4 200      NC 27.7 [16.5]    0.170 [0.170, 0.170]
#>      0  21     5 200      NC 26.5 [16.5]    0.210 [0.210, 0.210]
#> 
#> Caption: auclast, cmax: geometric mean and geometric coefficient of variation; tmax: median and range; N: number of subjects

mmae_nca <- pop_sim |>
  filter(!is.na(Cmmae_ng_mL), time > 0) |>
  mutate(cycle = pmax(1L, as.integer(floor((time - 1e-9) / cycle_dy) + 1L)),
         time_in_cycle = time - (cycle - 1) * cycle_dy) |>
  filter(cycle <= n_cycles) |>
  transmute(id = id, cycle = as.factor(cycle),
            time = time_in_cycle, Cmmae = Cmmae_ng_mL)

mconc_obj <- PKNCA::PKNCAconc(mmae_nca, Cmmae ~ time | cycle + id)
mdose_obj <- PKNCA::PKNCAdose(adc_dose, amt ~ time | cycle + id)   # dose is the ADC dose
mmae_nca_res <- PKNCA::pk.nca(PKNCA::PKNCAdata(mconc_obj, mdose_obj,
                                               intervals = intervals))
#> Warning: Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.05) is not allowed
#> Warning: Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.0900955) is not allowed
#> Warning: Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#>  ■■■■■■■■■■■■■■                    44% |  ETA:  4s
#> Warning: Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.130191) is not allowed
#> Warning: Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.170286) is not allowed
#> Warning: Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#>  ■■■■■■■■■■■■■■■■■■■■■■■■■■■■      89% |  ETA:  1s
#> Warning: Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
#> Requesting an AUC range starting (0) before the first measurement (0.210382) is not allowed
mmae_nca_summary <- summary(mmae_nca_res)
mmae_nca_summary
#>  start end cycle   N auclast        cmax                tmax
#>      0  21     1 200      NC 4.57 [58.5]  1.43 [0.300, 4.31]
#>      0  21     2 200      NC 4.02 [59.1] 1.34 [0.0901, 3.85]
#>      0  21     3 200      NC 3.58 [64.1]  1.38 [0.381, 3.89]
#>      0  21     4 200      NC 3.32 [67.9]  1.42 [0.421, 3.93]
#>      0  21     5 200      NC 3.14 [70.8]  1.46 [0.461, 3.97]
#> 
#> Caption: auclast, cmax: geometric mean and geometric coefficient of variation; tmax: median and range; N: number of subjects

Cycle-over-cycle MMAE exposure decline

mmae_cycle1 <- as.data.frame(mmae_nca_res$result) |>
  filter(PPTESTCD == "auclast") |>
  group_by(cycle) |>
  summarise(median_auclast = median(PPORRES, na.rm = TRUE), .groups = "drop")
mmae_cycle1 |>
  mutate(ratio_to_cycle1 = median_auclast / median_auclast[cycle == "1"]) |>
  knitr::kable(
    digits  = c(NA, 2, 2),
    caption = "Median MMAE AUC0-21 across cycles 1-5, normalized to cycle 1. The 50-80% cycle-1-to-subsequent decline reported by Li 2017 (Results, MMAE Final Model paragraph) is reproduced as the Fmc = CYCLE^Fm effect attenuates proteolytic MMAE formation in successive cycles."
  )

Median MMAE AUC0-21 across cycles 1-5, normalized to cycle 1. The 50-80% cycle-1-to-subsequent decline reported by Li 2017 (Results, MMAE Final Model paragraph) is reproduced as the Fmc = CYCLE^Fm effect attenuates proteolytic MMAE formation in successive cycles.
cycle	median_auclast	ratio_to_cycle1
1	NA	NA
2	NA	NA
3	NA	NA
4	NA	NA
5	NA	NA

Assumptions and deviations

Molar units throughout the ODE. Modeling is in nmol amounts, L volumes, and nmol/L = pmol/mL concentrations to match the paper’s stated convention (“Modeling was done in molar units”). Users dosing in mg must convert: dose_nmol = dose_mg * 1000 / MW_ADC_kDa (= dose_mg * 6.536 for brentuximab vedotin, MW 153 kDa). checkModelConventions() flags this as an “info” on dosing/concentration unit magnitudes because the canonical pattern is dosing-in-mg, concentration-in-ug/mL (mg -> mg/L). For this coupled ADC+MMAE model with two molecular weights differing by ~200x, a single shared molar unit is the only way to keep the mass balance 1 ADC -> DAR molecules of MMAE exact inside the ODE.
Non-canonical compartment names. The seven ODE states are adc_central, adc_peripheral1, adc_peripheral2, mmae_central, mmae_peripheral, pathway_proteolytic, and pathway_deconjugation. checkModelConventions() warns about each because the canonical list is depot / central / peripheral1 / peripheral2 / effect / target / complex / total_target. Distinct prefixes (adc_, mmae_, pathway_) are required here to disambiguate two species (ADC and MMAE) plus two bookkeeping integrators within a single model; this matches the Bender 2014 mechanistic ADC model precedent (dar0_central ... dar7_central).
Body-weight reference 75 kg. The paper’s Table 2 pooled median is 74.8 kg but the abstract and covariate-equation definitions describe the reference subject as 75 kg, so the model file uses WT / 75 to match the paper’s reported typical values (CL = 1.56 L/d, V1 = 4.29 L).
Sex reference = male. Paper Eq. 2 takes IND = 1 for females and IND = 0 for males, so e_sexf_vc = 0.873 is the female:male V1 ratio.
Q5 and V5 without IIV. Both BSV terms are reported as “0 fixed” in Table 4; the model omits etalq5 and etalv5 rather than fixing them to a small nonzero value.
Fm stored with sign preserved. Paper reports Fm = -0.261 with BSV 130% CV. The model parameterises Fm = -exp(lfm + etalfm) with lfm = log(0.261) and omega^2_lfm = log(1.3^2 + 1) = 0.9895 so the magnitude is log-normally distributed on the individual scale while the sign remains negative.
Virtual-cohort race distribution. Table 2 reports 85% White with the remaining 15% grouped as “Other”; race was tested and excluded from the final model, so race is not used in this simulation and the 200-subject virtual cohort carries only WT, SEXF, and CYCLE.
Cycle numbering. CYCLE is set to 1 from the first dose onwards for 21 days, then 2 for the next 21 days, and so on. For weekly regimens (Study 2) CYCLE increments at the start of each 28-day cycle, not at each weekly dose.
Dose cap. Li 2017 caps per-dose amounts at 180 mg for subjects > 100 kg. The 200-subject virtual cohort applies this cap; a user simulating from this model is responsible for applying any dosing rules at data-assembly time — the model itself does not implement caps.

Errata

No published erratum or correction was located for PMID 28513851 as of 2026-04-24 (PubMed metadata and the journal landing page carry no correction-notice links). The items below are implementation-level notational inconsistencies in the source paper and supplement that the extraction had to resolve; they do not affect the final-model parameter point estimates.

Table 3 σ1 units. Table 3 reports the ADC additive residual as 0.0125 (fixed) with units “µg/mL”, but the surrounding Methods section states concentrations are modeled in pmol/mL. The magnitude 0.0125 µg/mL coincides with the assay LLOQ (12.5 ng/mL = 0.0125 µg/mL), consistent with fixing the additive residual at the LLOQ on the assay-reporting scale. We converted to the native model unit: 0.0125 µg/mL × (1000 / 153 kDa) = 0.0817 pmol/mL.
Table 4 σ1 units. Analogously, the MMAE additive residual is reported as 0.0119 ng/mL and converted to 0.0119 / 0.718 = 0.01658 pmol/mL for the molar-unit model.
Fm parameterisation. Table 4 lists Fm by cycle ... Estimate −0.261 ... BSV 130% CV. A conventional log-normal IIV does not admit a negative mean, so the paper’s Fm point estimate and BSV together can only be interpreted consistently by placing the log-normal on |Fm| and carrying the sign separately. We implement Fm = -exp(lfm + etalfm) with omega^2_lfm = log(1.3^2 + 1) = 0.9895 so the reported BSV is reproduced exactly on the log-normal magnitude scale.
Deconjugation-flux sign convention. Supplement M1 writes the MMAE formation term as A(1) * (DAR - DAR0 * alpha) * beta. Because DAR0 * alpha = 1 is the asymptotic floor of DAR(t), the expression (DAR - 1) is non-negative for all tad ≥ 0 and the deconjugation flux into mmae_central is always into the compartment (never out). The ODE is faithful to the supplement; this note is only to flag the easy-to-misread sign when reading the equation in prose.
Supplement M1 DADT(6) / DADT(7) scope. The two bookkeeping compartments in the supplement (proteolytic pathway cumulative amount, deconjugation pathway cumulative amount) are written without an F / flux scaling and are used only to derive the steady-state ~13% deconjugation split quoted in the Results. They are retained in this model (pathway_proteolytic, pathway_deconjugation) for reproducibility of that derivation but are not used in any observation equation.
CYCLE^Fm at CYCLE = 0. CYCLE^Fm with negative Fm is undefined at CYCLE = 0. Simulation data sets must set CYCLE >= 1 everywhere the ODE is integrated. The virtual-cohort builder above uses pmax(1L, floor(time / 21) + 1L).