A simple and flexible graphical approach for adaptive group-sequential clinical trials.

Area of Science:

• Biostatistics
• Clinical Trial Design
• Pharmaceutical Research

Background:

• Group-sequential designs are common in clinical trials for early stopping.
• Adaptive designs allow for modifications based on interim results, increasing efficiency.
• Existing graphical methods for group-sequential designs need extension for adaptive features.

Purpose of the Study:

• To introduce a novel graphical approach for testing multiple hypotheses in group-sequential clinical trials.
• To extend existing graphical group-sequential designs to accommodate midterm design modifications in adaptive trials.
• To provide a visual and iterative framework for complex adaptive clinical trial strategies.

Main Methods:

• Development of a graphical methodology for adaptive group-sequential trial designs.
• Extension of the Maurer and Bretz graphical framework to incorporate adaptive elements.
• Application of the method to two distinct clinical trial scenarios.

Main Results:

• The proposed graphical approach allows for iterative testing strategies and visualization of complex designs.
• Demonstrated feasibility through a three-armed gold-standard trial with patient reallocation.
• Illustrated effectiveness in a confirmatory two-stage adaptive design with treatment selection.

Conclusions:

• The graphical approach provides a flexible and visual tool for adaptive clinical trial design.
• This methodology facilitates structured study objectives and efficient decision-making in adaptive trials.
• The approach is practical for real-world clinical trial applications, enhancing statistical rigor.