pystatsbio 4.0.0

Biotech and pharmaceutical statistical computing for Python

PyStatsBio

Biotech and pharmaceutical statistical computing for Python.

Built on PyStatistics for the general statistical computing layer. PyStatsBio provides domain-specific methods for the drug development pipeline: dose-response modeling, sample size/power, diagnostic accuracy, non-compartmental pharmacokinetics, epidemiological measures, meta-analysis, and generalized estimating equations for clustered data.

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Design Philosophy

PyStatsBio follows the same principles as PyStatistics:

1. Fail fast, fail loud — no silent fallbacks or "helpful" defaults
2. Explicit over implicit — require parameters, don't assume intent
3. R-level validation — every function is validated against a named R reference

Each function states exactly which R function it replicates and to what tolerance.

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What's New in 4.0

Version 4.0 is a correctness release from a full validation sweep of every module against its R reference (drc, PKNCA/NonCompart, pROC/epiR, pwr/PowerTOST, metafor, geepack). It fixes several results that were silently wrong and now agree with the R references to tight tolerances:

• doseresponse.ec50() returns the true EC50/ED50 for the asymmetric models (LL.5, W1.4, W2.4, BC.5), by solving the fitted curve for the half-maximal dose rather than returning the raw location parameter (which was off by up to ~27%).
• doseresponse.fit_drm(model="W2.4") no longer converges to an inferior local optimum on decreasing data.
• epi.epi_2by2 population attributable fraction now uses the exposure prevalence in Levin's formula.
• meta.rma reports estimator-specific I²/H² (the default REML/PM previously reported the DerSimonian-Laird value).
• pk.nca terminal-slope selection uses the WinNonlin/NonCompart "best-fit" rule, matching the reference tools.

Breaking change: epi.rate_standardize(method="indirect") now requires a standard_weights argument (the standard population's age distribution) to compute the standardized rate — previously it was silently wrong. The SIR is unaffected.

What's New in 3.0

Version 3.0 tracks the PyStatistics 5.0 API. It requires pystatistics>=5.0 and will not run on 4.x. PyStatsBio's own statistical results are unchanged; the breaking change is the raised dependency floor plus one relayed value:

• GLM/GEE family names are lowercase. Following PyStatistics 5.0's naming cleanup, the Gamma family now reports result.family_name == "gamma" (was "Gamma"), consistent with "gaussian", "binomial", and "poisson". Code that compared against the capitalized "Gamma" must switch to "gamma".

Everything introduced in 2.0 — the …Solution result objects, the descriptive power-analysis parameters, the hyphenated option values, and the ValidationError / ConvergenceError / NumericalError taxonomy — is unchanged.

What's New in 2.0

Version 2.0 is a consistency release that aligns the whole library with the PyStatistics 4.0 API conventions. It contains breaking changes; the statistical results themselves are unchanged. Requires pystatistics>=4.0.

• Every function returns a …Solution object with uniform .backend_name, .timing, .warnings, and .info accessors plus a Jupyter HTML view. All the previous result fields still work (e.g. result.n, result.auc).
• Power-analysis parameters are now descriptive: effect_size (was d/f/h), n_groups (was k), hazard_ratio (was hr), coef_variation (was cv), std (was sd), prop1/prop2 (was p1/p2), and test_type (was type).
• Option values use hyphens, not dots: alternative="two-sided" / "one-sided", test_type="two-sample" / "one-sample". mantel_haenszel's measure takes "odds-ratio" / "risk-ratio".
• GPU precision lives in the backend string: backend="gpu" (float32) or backend="gpu_fp64" (CUDA float64); the separate use_fp64 flag is removed.
• Errors are ValidationError / ConvergenceError / NumericalError — the first subclasses the builtin ValueError, so existing except ValueError code keeps working.

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Quick Start

# --- Clinical trial power / sample size ---
import numpy as np
from pystatsbio import power

# Solve for sample size (two-sample t-test); effect_size is Cohen's d
result = power.power_t_test(effect_size=0.5, power=0.80, alpha=0.05, test_type="two-sample")
print(result.n)          # per-group sample size
print(result.summary())

# Solve for power given n
result = power.power_t_test(n=64, effect_size=0.5, alpha=0.05, test_type="two-sample")
print(result.power)

# Paired t-test
result = power.power_paired_t_test(effect_size=0.3, power=0.80, alpha=0.05)
print(result.n)

# Two proportions (effect_size is Cohen's h)
h = 2 * (np.arcsin(np.sqrt(0.50)) - np.arcsin(np.sqrt(0.30)))
result = power.power_prop_test(effect_size=h, power=0.80, alpha=0.05)
print(result.n)

# Survival (log-rank); the effect is the hazard ratio
result = power.power_logrank(hazard_ratio=0.6, power=0.80, alpha=0.05)
print(result.n)

# Non-inferiority for means
result = power.power_noninf_mean(
    delta=0.0, std=1.0, margin=0.5, power=0.80, alpha=0.05
)
print(result.n)

# Crossover bioequivalence (PowerTOST method)
result = power.power_crossover_be(coef_variation=0.20, power=0.80, alpha=0.05)
print(result.n)          # subjects per sequence

# Cluster-randomized trial
result = power.power_cluster(
    effect_size=0.5, icc=0.05, cluster_size=20, power=0.80, alpha=0.05
)
print(result.n)          # clusters per arm


# --- Dose-response modeling ---
from pystatsbio import doseresponse

dose = np.array([0.001, 0.01, 0.1, 1.0, 10.0, 100.0])
response = np.array([2.1, 3.5, 12.0, 48.0, 87.5, 97.8])

# Fit 4PL (LL.4) model
result = doseresponse.fit_drm(dose, response, model="LL.4")
print(result.params)        # CurveParams(bottom, top, ec50, hill)
print(result.params.ec50)   # the fitted EC50
print(result.summary())

# Fit 5PL (asymmetric)
result = doseresponse.fit_drm(dose, response, model="LL.5")
print(result.params)

# Extract EC50 with confidence interval
ec50_result = doseresponse.ec50(result)
print(ec50_result.estimate, ec50_result.ci_lower, ec50_result.ci_upper)

# Relative potency (reference vs. test compound)
ref_result = doseresponse.fit_drm(dose, response, model="LL.4")
test_result = doseresponse.fit_drm(dose * 3, response, model="LL.4")
rp = doseresponse.relative_potency(ref_result, test_result)
print(rp.ratio, rp.ci_lower, rp.ci_upper)

# Benchmark dose (BMD/BMDL)
bmd_result = doseresponse.bmd(result, bmr=0.10)
print(bmd_result.bmd, bmd_result.bmdl)

# Batch fitting (GPU-accelerated for HTS)
# dose_matrix / response_matrix: (n_curves, n_doses) arrays
responses = np.random.rand(500, 6) * 100
doses = np.tile(dose, (500, 1))
batch = doseresponse.fit_drm_batch(doses, responses, model="LL.4", backend="auto")
print(batch.ec50)        # shape (500,) — one EC50 per curve


# --- Diagnostic accuracy ---  (binary labels come first, then the scores)
from pystatsbio import diagnostic

labels = np.array([0, 0, 0, 1, 1, 0, 1, 1, 0, 1])
scores = np.array([0.1, 0.4, 0.35, 0.8, 0.9, 0.15, 0.6, 0.75, 0.55, 0.95])

# ROC curve + AUC (with DeLong CI)
roc_result = diagnostic.roc(labels, scores)
print(roc_result.auc, roc_result.auc_ci_lower, roc_result.auc_ci_upper)

# Compare two correlated ROC curves (DeLong test)
scores2 = np.random.rand(10)
roc2 = diagnostic.roc(labels, scores2)
test_result = diagnostic.roc_test(
    roc_result, roc2, predictor1=scores, predictor2=scores2, response=labels
)
print(test_result.p_value)

# Full diagnostic accuracy at a cutoff
da = diagnostic.diagnostic_accuracy(labels, scores, cutoff=0.5)
print(da.sensitivity, da.specificity, da.ppv, da.npv)

# Optimal cutoff selection
cutoff = diagnostic.optimal_cutoff(roc_result, method="youden")
print(cutoff.cutoff, cutoff.sensitivity, cutoff.specificity)

# Batch AUC for biomarker panel screening
# 200 candidate biomarkers on 100 subjects -> (n_subjects, n_markers)
panel = np.random.rand(100, 200)
batch_auc = diagnostic.batch_auc(np.random.randint(0, 2, 100), panel, backend="auto")
print(batch_auc.auc)     # shape (200,) — one AUC per biomarker


# --- Pharmacokinetics (NCA) ---
from pystatsbio import pk

time = np.array([0, 0.5, 1, 2, 4, 6, 8, 12, 24])
conc = np.array([0, 8.5, 12.1, 10.4, 7.2, 4.9, 3.1, 1.4, 0.3])

result = pk.nca(time, conc, route="ev", dose=100.0)
print(result.cmax, result.tmax)
print(result.auc_last, result.auc_inf)
print(result.half_life)
print(result.clearance, result.vz)
print(result.summary())


# --- Epidemiological measures ---
from pystatsbio import epi

# 2x2 table: exposed/unexposed x case/control
table = np.array([[30, 70], [10, 90]])
result = epi.epi_2by2(table)
# risk_ratio / odds_ratio are EpiMeasure value objects (estimate + CI)
print(result.risk_ratio.estimate, result.odds_ratio.estimate)
print(result.summary())

# Mantel-Haenszel stratified analysis
tables = np.array([[[30, 70], [10, 90]], [[20, 80], [15, 85]]])
result = epi.mantel_haenszel(tables, measure="odds-ratio")
print(result.pooled_estimate.estimate, result.cmh_p_value)


# --- Meta-analysis ---
from pystatsbio import meta

effects = np.array([0.5, 0.3, 0.8, 0.6, 0.4])
variances = np.array([0.1, 0.15, 0.2, 0.12, 0.18]) ** 2   # sampling variances

# Random-effects meta-analysis (method: 'DL', 'REML', or 'PM')
result = meta.rma(effects, variances, method="DL")
print(result.estimate, result.ci_lower, result.ci_upper)
print(result.tau2, result.I2)
print(result.summary())


# --- GEE (clustered data) ---
from pystatsbio import gee

y = np.random.randn(200)
X = np.random.randn(200, 3)
cluster_id = np.repeat(np.arange(40), 5)
result = gee.gee(y, X, cluster_id, family="gaussian", corr_structure="exchangeable")
print(result.coefficients, result.robust_se)
print(result.summary())

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Modules

Module	Status	Description
power/	Complete	Sample size and power for clinical trial designs
doseresponse/	Complete	4PL/5PL curve fitting, EC50, relative potency, BMD, batch HTS
diagnostic/	Complete	ROC, AUC, sensitivity/specificity, optimal cutoff, batch biomarker
pk/	Complete	Non-compartmental PK analysis (NCA): AUC, Cmax, CL, Vd, MRT
epi/	Complete	Epidemiological measures: 2x2 tables, rate standardization, Mantel-Haenszel
meta/	Complete	Meta-analysis: fixed/random effects, DerSimonian-Laird, REML
gee/	Complete	Generalized estimating equations for clustered/longitudinal data

power — Sample Size and Power

Function	R equivalent
power_t_test()	pwr::pwr.t.test()
power_paired_t_test()	pwr::pwr.t.test(type="paired")
power_prop_test()	pwr::pwr.2p.test()
power_fisher_test()	pwr::pwr.2p.test() (via Cohen's h)
power_logrank()	gsDesign::nSurv()
power_anova_oneway()	pwr::pwr.anova.test()
power_anova_factorial()	pwr::pwr.f2.test()
power_noninf_mean()	TrialSize::TwoSampleMean.NIS()
power_noninf_prop()	TrialSize::TwoSampleProportion.NIS()
power_equiv_mean()	TrialSize::TwoSampleMean.Equivalence()
power_superiority_mean()	TrialSize::TwoSampleMean.NIS()
power_crossover_be()	PowerTOST::sampleN.TOST(), power.TOST(method="nct")
power_cluster()	clusterPower, CRTSize (ICC-adjusted)

doseresponse — Dose-Response Modeling

Function	R equivalent
fit_drm()	drc::drm()
fit_drm_batch()	vectorized drc::drm()
ec50()	drc::ED()
relative_potency()	drc::EDcomp() with parallelism test
bmd()	drc::bmd() / BMDS

Models: LL.4 (4PL), LL.5 (5PL), W1.4 (Weibull-1), W2.4 (Weibull-2), BC.5 (Brain-Cousens hormesis).

diagnostic — Diagnostic Accuracy

Function	R equivalent
roc()	pROC::roc() with DeLong CI
roc_test()	pROC::roc.test() (DeLong)
diagnostic_accuracy()	epiR::epi.tests()
optimal_cutoff()	OptimalCutpoints::optimal.cutpoints()
batch_auc()	vectorized pROC::auc()

pk — Non-Compartmental Analysis

Function	R equivalent
nca()	PKNCA::pk.nca() / NonCompart::sNCA()

AUC methods: linear, log, linear-up/log-down (FDA default). Routes: iv (intravenous), ev (extravascular).

epi — Epidemiological Measures

Function	R equivalent
epi_2by2()	epiR::epi.2by2()
rate_standardize()	epitools::ageadjust.direct() / ageadjust.indirect()
mantel_haenszel()	stats::mantelhaen.test()

meta — Meta-Analysis

Function	R equivalent
rma(method="DL")	meta::metagen(method="DL") / metafor::rma()
rma(method="REML")	metafor::rma(method="REML")
rma(method="PM")	metafor::rma(method="PM")
cochran_q() / i_squared() / h_squared()	metafor::rma()$QE / $I2 / $H2

gee — Generalized Estimating Equations

Function	R equivalent
gee()	geepack::geeglm()

Families: gaussian, binomial, poisson. Correlation structures: independence, exchangeable, ar1, unstructured.

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Installation

pip install pystatsbio

# With GPU support (requires PyTorch)
pip install pystatsbio[gpu]

# Development
pip install pystatsbio[dev]

Requires Python 3.11+. Core dependencies: pystatistics, numpy, scipy.

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License

MIT

Author

Hai-Shuo ([e-mail])