nca.report¶

The tables and the methods sentence of a regulatory report.

ICH M13A (2024, section 2.2.2.2) names what the pharmacokinetic section of a bioequivalence report carries: the summary statistics of every parameter ("n, geometric mean, geometric coefficient of variation, median, arithmetic mean, standard deviation, minimum and maximum"), the ratio \(\mathrm{AUC}_{0\text{-}t}/\mathrm{AUC}_{0\text{-}\infty}\) of every subject with the acceptance rule that the study is questioned when the ratio is below 80 % "in more than 20% of the observations", and a description of the methods, verbatim "the non-compartmental methods used to derive the PK parameters from the raw data should be reported, e.g., linear trapezoidal method for AUC and the number of data points of the terminal log-linear phase used to estimate kel". The FDA ANDA bioequivalence guidance repeats the list.

M13A_STATISTICS is the first, acceptability_table the second and methods_line the third; every number they report comes from an NCAResult, so the report is assembled from the analysis rather than typed.

acceptability_table ¶

acceptability_table(
    result,
    dim,
    *,
    threshold=0.8,
    share=0.2,
    include_excluded=False,
    **indexers,
)

The acceptability of the extrapolation of every subject, and the verdict.

One row per sample with \(\mathrm{AUC}_{0\text{-}t_\mathrm{last}}\), \(\mathrm{AUC}_{0\text{-}\infty}\), their ratio

\[q = \frac{\mathrm{AUC}_{0\text{-}t_\mathrm{last}}} {\mathrm{AUC}_{0\text{-}\infty}}\]

and whether it is below threshold. ICH M13A (2024, 2.2.2.2) questions a study in which \(q\) is below 80 % "in more than 20% of the observations", which is the verdict: True while the share of the samples below the threshold is at most share. Only the samples with a finite ratio are counted, a sample without a terminal phase being no observation of the rule.

Parameters:

Name	Type	Description	Default
`result`	`NCAResult`	the result of the individual samples	required
`dim`	`str`	the sample dimension of the subjects	required

Other Parameters:

Name	Type	Description
`threshold`	`float`	the smallest acceptable ratio, 0.8 of ICH M13A
`share`	`float`	the share of the samples which may fall below it, 0.2 of ICH M13A
`include_excluded`	`bool`	count the excluded samples as well
`**indexers`	`Any`	coordinate label per remaining sample dimension

Returns:

Type	Description
`DataFrame`	The table with the columns of the sample dimensions, `auc_last`,
`bool`	`auc_inf_obs`, `ratio` and `below`, and the verdict of the rule.

Raises:

Type	Description
`ValueError`	if `dim` is not a sample dimension of the result, or if the result carries no `auc_last` or `auc_inf_obs`.

methods_line ¶

methods_line(options, result)

The sentence of the methods section which names how the analysis ran.

The trapezoid rule of the areas, the rule which selected the terminal log-linear phase and the number of points it used, which is what ICH M13A (2024, 2.2.2.2) and the FDA ANDA bioequivalence guidance ask a report to state.

Parameters:

Name	Type	Description	Default
`options`	`NCAOptions`	the options of the analysis	required
`result`	`NCAResult`	its result, for the number of terminal points	required

Returns:

Type	Description
`str`	The sentence, without a leading or trailing space.