Refua Clinical
PK/PD-driven virtual patient and clinical trial simulation toolkit. Generate copula-based virtual patients, run adaptive multi-arm trials, and produce tailored protocols ready for stakeholder review.
What Is Refua Clinical?
Refua Clinical is a simulation package for PK/PD-driven clinical trial design. It generates copula-based virtual patients, runs adaptive multi-arm trial simulations with Bayesian response-adaptive allocation, and produces a tailored protocol that can be re-simulated with modified inputs.
The package directly integrates with the core Refua toolkit, accepting ADMET profiles and affinity predictions as inputs to inform simulation parameters automatically.
Key Capabilities
- Population PK/PD simulation with inter-individual variability
- Virtual patient generation using Gaussian copulas
- Estimand-aware analysis (treatment policy, hypothetical, composite, while-on-treatment)
- Bayesian response-adaptive allocation with early stopping
- Dynamic external-control borrowing with discounting
- Multi-objective design optimization with Pareto front outputs
Complete Trial Design Toolkit
Virtual Patients
Generate realistic virtual patient populations using Gaussian copulas with configurable marginals and covariate effects for each trial arm.
Protocol Recommendation
Score candidate designs on simulated operating characteristics and expected cost to recommend optimal sample sizes and interim cadences.
Multi-Objective Optimization
Explore the trade-off frontier between power, cost, and timeline with Pareto-front outputs for informed decision-making.
Value-of-Information
Run VOI scenarios to determine whether additional enrollment is worth the investment before committing to expansion decisions.
Transportability
Assess covariate shift, overlap scores, and risk levels for extrapolating results from reference to target populations.
Explainable Advice
Generate narratives, interim decision-card summaries, and prioritized actionable recommendations for stakeholder review.
End-to-End Workflow
Configure
Initialize a trial config with init-config or accept ADMET inputs from Refua.
Simulate
Run the PK/PD simulation with virtual patients, adaptive allocation, and early stopping rules.
Protocol
Generate a tailored protocol recommendation with optimal sample size and interim schedule.
Optimize
Run multi-objective optimization and VOI analysis to refine the design.
Advise
Generate explainable advice with narratives and prioritized recommendations.
Biologics & Small Molecules
Refua Clinical supports both small molecule and biologics modalities. Biologics mode adds IV/SC route support, interval dosing, and optional TMDD-like clearance scaling for antibody and protein therapeutics.
The ADMET-aware simulation path automatically adjusts PK parameters based on Refua ADMET profiles, creating a seamless bridge from molecular design to clinical trial planning.
Supported Modalities
- Small molecules with oral PK models
- Biologics with IV/SC administration routes
- Interval dosing (q14d, q28d, etc.)
- TMDD-like clearance scaling
- ADMET-informed PK parameter adjustment
Get Started
Installation
pip install refua-clinicalWith ADMET integration:
pip install "refua-clinical[admet]"One-Shot Workup
refua-clinical workup \
--config config.yaml \
--output-dir artifacts/full_workup \
--include-sensitivityPython API
from refua_clinical import ClinicalStudy
study = (
ClinicalStudy.default()
.trial(
trial_id="oncology-demo",
indication="Oncology",
phase="Phase II",
replicates=96,
)
.set("enrollment.total_n", 220)
)
run = study.simulate()
protocol = run.recommend_protocol(replicates_per_candidate=30)
print(run.summary["power"], protocol.protocol["protocol_id"])Design Better Trials
Refua Clinical brings modern simulation methods and regulatory-informed defaults to clinical trial design, helping teams make better decisions before the first patient is enrolled.