Phase II Two-Stage Single-Arm Clinical Trials for Testing Toxicity Levels.

Area of Science:

• Clinical Trials Methodology
• Pharmaceutical Safety Evaluation
• Biostatistics

Background:

• Simon's two-stage designs are standard for phase II efficacy trials.
• Assessing patient safety and adverse events is critical in clinical trials.
• Existing designs may not optimally address safety concerns in early-phase trials.

Purpose of the Study:

• To adapt Simon's two-stage designs for phase II safety studies.
• To develop a procedure for terminating or continuing safety trials based on adverse event rates.
• To provide a practical tool for designing two-stage safety trials.

Main Methods:

• Modification of design parameters from efficacy-focused Simon's designs.
• Prescribed procedure based on type I/II error rates and first-stage adverse event proportions.
• Simulation studies to evaluate design properties and relationships with efficacy endpoints.

Main Results:

• Demonstrated adaptability of Simon's designs for safety endpoints.
• Established a clear decision-making process for trial continuation or termination.
• Investigated the interplay between safety and efficacy endpoints in two-stage designs.

Conclusions:

• Simon's two-stage designs can be effectively repurposed for phase II safety studies.
• The proposed methodology provides a structured approach to managing adverse events.
• A free R package (gen2stage) is available to facilitate the implementation of these safety designs.