Coverage and Validation Map

This page is the consolidated source of truth for three related questions:

What analysis, estimation, PK, simulation, and workflow surfaces exist?
What kinds of tests back each surface?
Where are the concrete tests that enforce those claims?

Use this page when you want the test-backed inventory of the project. Use the other pages around it for narrower purposes:

testing.md: how to run the suite and how the pytest tiers are organized
validation_matrix.md: what validation level the project claims for each surface
external_validation_benchmarks.md: the external datasets and third-party tools used as anchors
analysis_validation_gaps.md: what is still weak and what should be added next

How to read this page

Test types:

Unit: local deterministic checks, formulas, invariants, and boundary behavior
Integration: short end-to-end workflows composed from multiple components
Regression: checked-in numerical baselines used to detect drift
External validation: agreement against independent software, literature values, SciPy, or exact closed forms

Validation character:

Analytic/reference-heavy: the strongest footing; relies on closed forms, exact identities, SciPy, literature tables, or cross-tool references
Behavioral/integration-heavy: useful coverage, but more about consistent behavior than independent truth

Estimation methods

Surface	Main implementation	Main tests	Test types present	Validation character
FO	`estimation/fo.py`	`tests/unit/estimation/test_fo.py`, `tests/external_validation/test_estimation_reference.py`, `tests/external_validation/test_vs_nlmixr2.py`, `tests/regression/test_cross_method_validation.py`	Unit, regression, external	Analytic/reference-heavy
FOCE / FOCEI	`estimation/foce.py`	`tests/unit/estimation/test_foce.py`, `tests/external_validation/test_estimation_reference.py`, `tests/external_validation/test_vs_nlmixr2.py`, `tests/external_validation/test_vs_nonmem.py`, `tests/regression/test_cross_method_validation.py`	Unit, regression, external	Analytic/reference-heavy
Laplacian	`estimation/laplacian.py`	`tests/unit/estimation/test_laplacian.py`, `tests/external_validation/test_estimation_reference.py`, `tests/regression/test_cross_method_validation.py`	Unit, regression, external	Analytic/reference-heavy
SAEM	`estimation/saem.py`	`tests/unit/estimation/test_saem.py`, `tests/external_validation/test_saem_reference.py`, `tests/external_validation/test_vs_monolix.py`, `tests/regression/test_regression.py`	Unit, regression, external	Mixed; credible but thinner than FO/FOCEI
IMP / IMPMAP	`estimation/imp.py`	`tests/unit/estimation/test_imp.py`, `tests/external_validation/test_estimation_reference.py`, `tests/external_validation/test_imp_empirical_reference.py`, `tests/regression/test_regression.py`	Unit, regression, external	Mixed; strong analytic core, narrower empirical breadth
BAYES(Laplace)	`estimation/bayes.py`	`tests/unit/estimation/test_bayes.py`, `tests/external_validation/test_bayes_empirical_reference.py`, `tests/regression/test_regression.py`	Unit, regression, external	Mixed; strong on local Gaussian path, narrower global parity claims
BAYES(NUTS)	`estimation/nuts.py`	`tests/unit/estimation/test_nuts.py`, `tests/external_validation/test_bayes_empirical_reference.py`, `tests/regression/test_regression.py`	Unit, regression, limited external	Behavioral plus some exact-target checks; still second-tier
Nonparametric (NPML / NPEM)	`estimation/nonparametric.py`	`tests/unit/estimation/test_nonparametric.py`, `tests/external_validation/test_vs_pharmpy.py`, `tests/regression/test_cross_method_validation.py`, `tests/regression/test_regression.py`	Unit, regression, external	Mixed; solid weight/support checks, still narrower empirical breadth
Estimation diagnostics / result summaries	`estimation/base.py`, result helpers	`tests/unit/estimation/test_estimation_base.py`, `tests/unit/estimation/test_shrinkage.py`, `tests/external_validation/test_covariance_reference.py`	Unit, external	Good structural coverage

PK subroutines and solver surfaces

Surface	Main implementation	Main tests	Test types present	Validation character
ADVAN1	`pk/analytical/advan1.py`	`tests/unit/pk/test_advan.py`, `tests/unit/model/test_individual_validation.py`, `tests/external_validation/test_pk_subroutines_reference.py`, `tests/integration/test_pk_integration.py`	Unit, integration, external	Analytic/reference-heavy
ADVAN2	`pk/analytical/advan2.py`	`tests/unit/pk/test_advan.py`, `tests/unit/model/test_symbolic_gradient_advan2.py`, `tests/external_validation/test_pk_subroutines_reference.py`, `tests/integration/test_theophylline.py`, `tests/integration/test_pk_integration.py`	Unit, integration, external	Analytic/reference-heavy
ADVAN3	`pk/analytical/advan3.py`	`tests/unit/pk/test_advan3.py`, `tests/unit/validation/test_numerical_accuracy.py`, `tests/external_validation/test_pk_subroutines_reference.py`, `tests/integration/test_two_compartment.py`	Unit, integration, external	Analytic/reference-heavy
ADVAN4	`pk/analytical/advan4.py`	`tests/unit/pk/test_advan4.py`, `tests/integration/test_pk_integration.py`	Unit, integration	Good, but less externally anchored than ADVAN1-3
ADVAN5	`pk/analytical/advan5.py`	`tests/unit/pk/test_advan5.py`, `tests/integration/test_examples.py`	Unit, integration	Strong within its model family
ADVAN7	`pk/analytical/advan7.py`	`tests/unit/pk/test_advan7.py`, `tests/unit/api/test_model_builder_validation.py`	Unit	Functional expm-backed validation now exists; empirical breadth still minimal
ADVAN11	`pk/analytical/advan11.py`	`tests/unit/pk/test_advan11.py`	Unit	Strong formula-level checks
ADVAN12	`pk/analytical/advan12.py`	`tests/unit/pk/test_advan12.py`	Unit	Strong formula-level checks
ADVAN6 general ODE	`pk/ode/advan6.py`	`tests/unit/pk/test_ode_advan6.py`, `tests/unit/test_native_cvodes.py`, `tests/unit/rust/test_rust_python_parity.py`	Unit, dedicated native lane	Strong on mechanics; empirical breadth depends on estimator path
ADVAN8 stiff ODE	`pk/ode/advan8.py`	`tests/unit/pk/test_ode_advan6.py`, `tests/unit/pk/test_advan13_sensitivity.py`	Unit	Good numerical/mechanical coverage
ADVAN10 Michaelis-Menten	`pk/ode/advan10.py`	`tests/unit/pk/test_ode_advan6.py`, `tests/external_validation/test_extended_models_reference.py`	Unit, external	Good reference footing
ADVAN13 sensitivities	`pk/ode/advan13.py`	`tests/unit/pk/test_advan13_sensitivity.py`, `tests/unit/test_native_cvodes.py`	Unit, dedicated native lane	Good mechanics/sensitivity coverage; narrower workflow breadth
ADVAN16-style DDE	`pk/ode/dde.py`	`tests/unit/pk/test_dde.py`, `tests/integration/test_examples.py`	Unit, integration	Good functional coverage
Transit / parallel / EHC absorption	`pk/absorption/`	`tests/unit/pk/test_absorption.py`	Unit	Good within implemented subset
PBPK	`pk/pbpk/`	`tests/unit/pk/test_pbpk.py`, `tests/integration/test_examples.py`	Unit, integration	Functional, but still narrower than core compartmental PK
TRANS parameterizations	parser + PK routing	`tests/unit/pk/test_transforms.py`, `tests/unit/api/test_model_builder_validation.py`	Unit	Good selector/parameterization coverage

Diagnostics, simulation, and NCA

Surface	Main implementation	Main tests	Test types present	Validation character
Simulation engine	`simulation/engine.py`	`tests/unit/simulation/test_engine.py`	Unit	Strong behavioral/core mechanics
VPC / pcVPC	`simulation/vpc.py`	`tests/unit/simulation/test_pcvpc.py`, `tests/integration/test_vpc_pipeline.py`, `tests/regression/test_diagnostics_regression.py`, `tests/external_validation/test_diagnostics_reference.py`	Unit, integration, regression, external	One of the strongest surfaces
NPDE	`simulation/npde.py`	`tests/unit/simulation/test_npde.py`, `tests/regression/test_diagnostics_regression.py`, `tests/external_validation/test_diagnostics_reference.py`	Unit, regression, external	One of the strongest surfaces
NPC	`simulation/npc.py`	`tests/unit/simulation/test_npc.py`, `tests/external_validation/test_diagnostics_reference.py`	Unit, external	Good formula-level footing
SSE	`simulation/sse.py`	`tests/unit/simulation/test_sse.py`, `tests/regression/test_diagnostics_regression.py`	Unit, regression	More behavioral than externally anchored
Diagnostic tables / GOF helpers	`plots/diagnostics.py`, plotting modules	`tests/unit/plots/test_diagnostics.py`, `tests/unit/plots/test_plots.py`, `tests/unit/plots/test_simulation_plots.py`	Unit	Mixed; many deterministic checks, fewer independent references
Core dense-profile NCA	`nca/nca.py`	`tests/unit/nca/test_nca.py`, `tests/regression/test_diagnostics_regression.py`, `tests/external_validation/test_vs_pknca.py`, `tests/external_validation/test_vs_winnonlin_indometh.py`	Unit, regression, external	One of the strongest surfaces
Multidose NCA	`nca/nca.py` multidose helpers	`tests/unit/nca/test_multidose_nca.py`	Unit	Good local numerical coverage
Sparse NCA	`nca/sparse.py`	`tests/unit/nca/test_sparse_nca.py`	Unit	Good analytical checks within its scope
Urine NCA	`nca/urine.py`	`tests/unit/nca/test_urine_nca.py`	Unit	Good analytical checks
Crossover BE / power / sample size	`nca/crossover.py`	`tests/unit/nca/test_crossover.py`, `tests/external_validation/test_bioequivalence_reference.py`, `tests/external_validation/test_nca_reference.py`	Unit, external	Good formula/reference coverage
CDISC PP export	`nca/cdisc_pp.py`	`tests/unit/nca/test_cdisc_pp.py`	Unit	Structural/export coverage

Analysis and model families

Surface	Main implementation	Main tests	Test types present	Validation character
Direct and mechanistic PD / PK-PD	`models/pkpd.py`	`tests/unit/models/test_pkpd.py`, `tests/unit/models/test_sequential.py`, `tests/integration/test_emax_pd.py`, `tests/regression/test_pd_models_regression.py`, `tests/regression/test_pkpd_models_regression.py`	Unit, integration, regression	Broad functional coverage
Population PD	`models/population_pd.py`	`tests/unit/models/test_population_pd.py`, `tests/regression/test_pd_models_regression.py`	Unit, regression	Good recovery-focused coverage
TTE / survival	`models/tte.py`	`tests/unit/models/test_tte.py`, `tests/external_validation/test_extended_models_reference.py`	Unit, external	Strong reference footing
Count models	`models/count.py`	`tests/unit/models/test_count.py`, `tests/external_validation/test_extended_models_reference.py`	Unit, external	Strong reference footing
Ordered categorical / proportional odds	`models/categorical.py`	`tests/unit/models/test_categorical.py`, `tests/external_validation/test_extended_models_reference.py`	Unit, external	Strong reference footing
CTMC / Markov / HMM	`models/categorical.py`, `models/markov.py`	`tests/unit/models/test_categorical.py`, `tests/unit/models/test_markov.py`, `tests/external_validation/test_extended_models_reference.py`	Unit, external	Strong reference footing
TMDD	`models/tmdd.py`	`tests/unit/models/test_tmdd.py`, `tests/external_validation/test_extended_models_reference.py`	Unit, external	Strong limit-case/reference checks
Static DDI analysis	`models/ddi.py`	`tests/unit/models/test_ddi.py`	Unit	Strong formula-level checks
Covariate effect functions	covariate/effect helpers	`tests/unit/covariate/test_effects.py`, `tests/external_validation/test_covariate_effects_reference.py`	Unit, external	Good formula/reference coverage
Model comparison and information criteria	result/model-comparison helpers	`tests/unit/inference/test_model_comparison.py`, `tests/external_validation/test_inference_reference.py`	Unit, external	Strong formula/reference coverage
Bootstrap / SCM	`simulation/bootstrap.py`, `simulation/scm.py`	`tests/unit/inference/test_bootstrap.py`, `tests/unit/inference/test_bootstrap_bca.py`, `tests/unit/scm/test_scm_base_convergence.py`, `tests/unit/covariate/test_scm.py`	Unit	Good workflow mechanics, lighter independent references

Workflow, parsing, outputs, and GUI

Surface	Main implementation	Main tests	Test types present	Validation character
Control-stream parsing/runtime	parser + runtime layers	`tests/unit/parser/`, `tests/integration/test_control_stream_mixture.py`, `tests/integration/test_control_stream_prior.py`, `tests/integration/test_control_stream_simulation.py`	Unit, integration	Broad supported-subset coverage
NONMEM-style writers/readers	`io/nonmem_output.py`, result readers	`tests/unit/output/test_output_writers.py`, `tests/unit/output/test_nonmem_reader.py`	Unit	Good structural/export coverage
Data preprocessing / BLQ / covariate imputation	`data/`, `preprocessing/`	`tests/unit/data/test_preprocessor.py`, `tests/unit/data/test_impute.py`, `tests/unit/data/test_blq.py`, `tests/integration/test_blq_pipeline.py`	Unit, integration	Good workflow coverage
GUI workflows and review shell	`src/openpkpd_gui/`	`tests/unit/gui/`, `tests/unit/gui/test_shell_smoke.py`, `tests/unit/gui/test_results_workflow.py`	Unit	Strong workflow-shell coverage, lighter empirical references

Dedicated release lanes

These are explicit coverage lanes for routes that should not be inferred only from the broad suite:

Lane	Command	Main surfaces covered
Symbolic route	`just run-tests-symbolic`	SymPy-backed analytical kernels, symbolic ETA gradients, symbolic guards
Native CVODES route	`just run-tests-native-cvodes`	Rust/native extension, CVODES wiring, native/sensitivity parity, serial native performance gate
Strict release suite	`just run-tests-release`	Release-gated unit/integration/regression/external-validation path with strict fixture enforcement

External anchors and citations

This page intentionally keeps citation detail light and defers bibliographic authority to the dedicated reference pages:

external_validation_benchmarks.md lists the concrete external tools, datasets, and benchmark assets used by the tests
citations.md contains the full bibliographic references for the literature and public benchmark sources mentioned across the validation docs

The main external anchors referenced by the coverage map are:

nlmixr2, NONMEM, Monolix, and Pharmpy for cross-tool estimation checks
scipy.stats, scipy.linalg, and scipy.integrate for exact numerical references
public PKNCA and WinNonlin-backed Indometh tables for NCA benchmarks

Current strongest areas

NCA, especially dense-profile NCA with public PKNCA and WinNonlin-backed anchors
VPC / pcVPC / NPDE / NPC
FO / FOCE / FOCEI / Laplacian estimation formulas and core workflows
TTE, count, categorical, CTMC/HMM, and TMDD limit-case checks
ADVAN1/2/3 analytical PK

Current thinner areas

ODE-heavy advanced estimators beyond the strongest FO/FOCEI paths
PBPK and DDE compared with the depth available for core PK subroutines
Bootstrap / SCM / SSE external anchoring relative to the strongest diagnostic and NCA areas
BAYES(NUTS) and some mixed-endpoint empirical paths, which remain intentionally second-tier

Recommended maintenance rule

When a method or workflow changes, update this page together with:

the concrete tests
validation_matrix.md
external_validation_benchmarks.md if the external anchor set changed

That keeps support claims, test inventory, and external evidence synchronized.