feat: add bioequivalence inferential statistics functions#547
Open
billdenney wants to merge 6 commits into
Open
feat: add bioequivalence inferential statistics functions#547billdenney wants to merge 6 commits into
billdenney wants to merge 6 commits into
Conversation
Add fitbe_models(), fitbe_table(), and fitbe_calculate() to compute average bioequivalence statistics from NCA results: per-endpoint linear mixed-effects models on log-transformed values, geometric mean ratios with 90 percent confidence intervals, Satterthwaite degrees of freedom, and intra-subject CV. The functions consume the long-format output of a PKNCAresults object directly. The statistical engine packages (lme4, lmerTest, emmeans) are Suggests and guarded with requireNamespace(); tests skip when they are absent. Adds the v50-bioequivalence vignette, tests, and documentation. Formalizes the prototype workflow from PR 490. Co-Authored-By: Claude Opus 4.7 (1M context) <noreply@anthropic.com>
Member
Author
|
Based on the functions @Sang-j111 build in #490 |
Starting-point design for extending the bioequivalence functions on this branch (PR #547) into the full reference-scaled / regulatory assessment space of replicateBE (EMA/HC/GCC ABEL) and PowerTOST (FDA RSABE/NTID), plus a regulatory-comparison assessor and the nlmixr2mbbe integration contract. Build-ignored under design/. Co-Authored-By: Claude Fable 5 <noreply@anthropic.com>
# Conflicts: # NEWS.md
… layer Add a regulatory bioequivalence decision and reference-scaling layer on top of the average-BE (fitbe_*) foundation, covering all major frameworks: * be_assess() - full pass/fail assessment for ABE, EMA/HC/GCC expanding limits (ABEL), and the FDA reference-scaled RSABE/NTID/HVNTID frameworks. Accepts a PKNCAresults object or a tidy long data.frame. * be_compare() - assess one dataset under several frameworks side by side. * be_regulator() / be_expand_limits() - internalized regulatory constants and scaled acceptance limits (single source of truth). * be_design() - crossover design classification and framework feasibility. * be_within_var() - within-subject variability (swR/swT, CVwR/CVwT, swT:swR ratio CI) by ANOVA (default) or a mixed model. * print/format/summary/as.data.frame methods for the new classes. All regulatory constants and criteria are internalized, so PKNCA does not depend on PowerTOST or replicateBE; the implementation was validated against those packages during development and the tests pin the resulting expected values (within-subject variances match replicateBE's estimator and the ABEL limits match its scaled-limit output exactly). The FDA RSABE/NTID/HVNTID criteria implement the linearized Howe/Hyslop bound from the guidances. Extends the v50-bioequivalence vignette with a reference-scaling section. Co-Authored-By: Claude Opus 4.8 <noreply@anthropic.com>
Unify all nine bioequivalence functions (fitbe_* and be_*) under the capitalized @family Bioequivalence tag so they group under a single "Bioequivalence" heading. Co-Authored-By: Claude Opus 4.8 <noreply@anthropic.com>
billdenney
commented
Jun 10, 2026
| group_cols <- NULL | ||
| if (inherits(object, "PKNCAresults")) { | ||
| assert_PKNCAresults(object) | ||
| data <- as.data.frame(as.data.frame(object, filter_excluded = TRUE)) |
Member
Author
There was a problem hiding this comment.
Please only use as.data.frame() once.
Replace every function defined inside another bioequivalence function with a top-level helper or a base-R primitive, so no closures are created per call and the helpers are independently testable: * be_within_var(): arm_var_anova() -> .be_arm_var() / .be_arm_var_na() * be_design(): the per-subject pattern lambda -> .be_subject_pattern(); the replication-count lambdas vectorized (tapply over a logical); the first-value lambda -> `[`; drop the unused per_order line * .be_isc(): the per-subject contrast lambda -> .be_subject_ilat() * be_compare(): tryCatch() with an inline error handler -> try() + inherits() * summary.be_compare(): the cell-selection lambda -> `[` No behavior change; all bioequivalence tests pass. Co-Authored-By: Claude Opus 4.8 <noreply@anthropic.com>
This file contains hidden or bidirectional Unicode text that may be interpreted or compiled differently than what appears below. To review, open the file in an editor that reveals hidden Unicode characters.
Learn more about bidirectional Unicode characters
Sign up for free
to join this conversation on GitHub.
Already have an account?
Sign in to comment
1 participant
Add this suggestion to a batch that can be applied as a single commit.This suggestion is invalid because no changes were made to the code.Suggestions cannot be applied while the pull request is closed.Suggestions cannot be applied while viewing a subset of changes.Only one suggestion per line can be applied in a batch.Add this suggestion to a batch that can be applied as a single commit.Applying suggestions on deleted lines is not supported.You must change the existing code in this line in order to create a valid suggestion.Outdated suggestions cannot be applied.This suggestion has been applied or marked resolved.Suggestions cannot be applied from pending reviews.Suggestions cannot be applied on multi-line comments.Suggestions cannot be applied while the pull request is queued to merge.Suggestion cannot be applied right now. Please check back later.
Add fitbe_models(), fitbe_table(), and fitbe_calculate() to compute average bioequivalence statistics from NCA results: per-endpoint linear mixed-effects models on log-transformed values, geometric mean ratios with 90 percent confidence intervals, Satterthwaite degrees of freedom, and intra-subject CV. The functions consume the long-format output of a PKNCAresults object directly.
The statistical engine packages (lme4, lmerTest, emmeans) are Suggests and guarded with requireNamespace(); tests skip when they are absent. Adds the v50-bioequivalence vignette, tests, and documentation. Formalizes the prototype workflow from PR 490.