Changes in version 0.1.0                        

First release. Decisions are local and are stated as such in every
result.

Model definition

  - pkpd_model() reads ODE models written for rxode2 (code, compiled
    models or model functions) and records outputs, doses (bolus_dose(),
    infusion_dose()), known input signals, known constants and initial
    conditions.
  - reference_models() and reference_model() provide ten acceptance
    models with expected results fixed from primary literature or
    analytical derivation.

Structural identifiability

  - structural_identifiability() decides local structural
    identifiability with Lie derivatives evaluated at the known initial
    state, checked by the rank and null space of output sensitivities
    solved with rxode2. A decision is made only if all random points and
    both methods agree; otherwise the result is unresolved. Identifiable
    monomial combinations (for example V/F) are reported.

Practical identifiability and design

  - practical_identifiability() computes the expected Fisher information
    for a sampling design with additive, proportional, combined or
    exponential residual error (residual_error()), with doses from the
    model or from an event table.
  - compare_designs() and experiment() compare user-supplied candidate
    designs: added outputs, sampling times or dose levels.
  - classify_profiles() classifies likelihood profiles of nlmixr2 fits
    (bounded, one-sided, flat, shallow; Raue et al. 2009) using
    nlmixr2extra::profileFixed() with warm-started re-estimation, and
    sets them against the structural result.

Validation

  - All ten acceptance models (and a variant) agree with their expected
    results at four seeds, and the two structural methods agree at every
    point.
  - Expected RSEs agree with the spread of 1,000 repeated estimates
    within 0.96–1.08 in four scenarios; limitations at RSEs of 30–40%
    are documented.
  - Profile classification is correct for all ten parameters of three
    synthetic nlmixr2 fits.
  - Vignettes: reference models, nimotuzumab TMDD (public nimoData), PSA
    decline and regrowth.