Compare a bioequivalence dataset across regulatory frameworks

be_compare() runs be_assess() under several regulatory frameworks and stacks the results, so the same study can be judged side by side under the different reference-scaling rules. Frameworks that the design does not support (for example NTID on a partial replicate) are skipped with a warning.

Usage

be_compare(
  object,
  reference_col,
  reference_value,
  endpoints = c("cmax", "aucinf.obs", "aucinf.pred", "auclast"),
  regulators = c("ABE", "EMA", "HC", "GCC", "FDA"),
  model_type = NULL,
  alpha = 0.1,
  subject = NULL,
  sequence = NULL,
  period = NULL,
  design = NULL
)

Arguments

object

A PKNCAresults object or a tidy long data.frame with a PPTESTCD column of parameter names, a PPORRES/PPSTRES column of values, and subject/sequence/period/treatment columns.

reference_col

The column identifying the formulation/treatment.

reference_value

The value of reference_col that is the reference formulation.

endpoints

Character vector of NCA parameters (matched against PPTESTCD) to assess.

regulators

A character vector of regulatory frameworks to compare (see be_regulator()).

model_type

The model for the average-BE point estimate, one of "lmer" (mixed model, for crossover/replicate designs), "anova" (fixed-effects, for parallel designs), "isc" (intra-subject contrasts, the FDA reference-scaled path), or "nlme" (treatment-specific mixed model). When NULL (default) it is chosen from the design and regulator.

alpha

The significance level; the confidence interval has level 1 - alpha (default 0.10 gives the 90% interval).

subject, sequence, period

Column names for the subject, randomization sequence, and period. When NULL they are taken from the PKNCAresults object or detected from common column names. sequence may be absent.

design

An optional be_design() object; computed from the data when NULL.

Value

An object of class be_compare (a data.frame) with the be_assess() columns for every endpoint, test formulation, and regulator.

See also

be_assess()

Other Bioequivalence: be_assess(), be_dataset(), be_design(), be_expand_limits(), be_extract_param(), be_fit_model_single(), be_fit_models(), be_regulator(), be_table(), be_within_var()

Examples

set.seed(1)
nsub <- 24
seqs <- rep(c("TRTR", "RTRT"), length.out = nsub)
b <- stats::rnorm(nsub, sd = 0.4)
d <- do.call(rbind, lapply(seq_len(nsub), function(i) {
  trt <- strsplit(seqs[i], "")[[1]]
  data.frame(
    subject = i, sequence = seqs[i], period = seq_along(trt), treatment = trt,
    PPTESTCD = "auclast",
    PPORRES = exp(log(100) + ifelse(trt == "T", 0.04, 0) + b[i] +
                    stats::rnorm(length(trt), sd = 0.45)),
    stringsAsFactors = FALSE
  )
}))
be_compare(d, reference_col = "treatment", reference_value = "R",
           endpoints = "auclast", regulators = c("EMA", "HC", "GCC", "FDA"))
#> Warning: Units were not found in the data; omitting the `units` column. Supply units via a PKNCAresults object or `PPSTRESU`/`PPORRESU` columns.
#> Bioequivalence comparison across EMA, HC, GCC, FDA (90% CI)
#> 
#>  regulator endpoint test gmr_percent ci_lower ci_upper cvwr_percent limit_lower
#>        EMA  auclast    T          98    85.72   112.04        34.11       77.71
#>         HC  auclast    T          98    85.72   112.04        34.11       77.71
#>        GCC  auclast    T          98    85.72   112.04        34.11       75.00
#>        FDA  auclast    T          98    85.75   112.00        34.11          NA
#>  limit_upper criterion pass
#>       128.68        NA TRUE
#>       128.68        NA TRUE
#>       133.33        NA TRUE
#>           NA  -0.05081 TRUE