GUIP1

GUIP1 implements model-guided adaptive dose-escalation methods to identify the maximum tolerated dose (MTD) in phase I cancer clinical trials.

Key Features:

• Model-guided adaptive designs: Incorporates Continual Reassessment Method (CRM), Escalation with Overdose Control (EWOC), Time-to-Event Continual Reassessment Method (TITE-CRM), and Time-to-Event Escalation with Overdose Control (TITE-EWOC) for dose-toxicity modeling.
• MTD definition: Targets estimation of the maximum tolerated dose (MTD), defined as the highest dose resulting in an acceptable level of severe toxicity during the first cycle of treatment.
• CRM implementation: Implements CRM using Bayesian or maximum likelihood estimation and interfaces with R packages dfcrm and bcrm.
• TITE-EWOC implementation: Includes a TITE-EWOC method developed within GUIP1 to address late-onset toxicity scenarios.
• Simulation capability: Enables simulation of phase I clinical trials to assess model behavior and trial outcomes under specified scenarios.

Scientific Applications:

• Phase I oncology dose escalation: Estimating the MTD for investigational therapies in phase I cancer clinical trials using adaptive model-based designs.
• Toxicity management: Modeling and controlling immediate, cumulative, and late-onset toxicities during dose-escalation decisions.
• Design evaluation: Simulating trial scenarios to compare performance of CRM, EWOC, TITE-CRM, and TITE-EWOC designs.

Methodology:

Implements CRM (Bayesian or maximum likelihood), EWOC, TITE-CRM, and a GUIP1-developed TITE-EWOC; CRM implementations leverage R packages dfcrm and bcrm and the package provides trial simulation functionality.