An adaptive group sequential phase II design to compare treatments for survival endpoints in rare patient entities

Area of Science:

• Biostatistics
• Clinical Trial Design
• Rare Diseases

Background:

• Standard clinical trial designs face challenges in rare disease research due to limited data and unavailable treatments.
• Essential study parameters are often difficult or impossible to obtain for rare conditions, hindering trial planning.

Purpose of the Study:

• To present a novel two-stage adaptive design for clinical trials involving right-censored time-to-event data.
• To address the challenges of conducting clinical trials for rare diseases, using a rare subtype of renal-cell carcinoma as motivation.

Main Methods:

• The proposed design is a two-stage adaptive approach for time-to-event data analysis.
• It incorporates a two-sided statistical test.
• The design allows for interim decisions, including stopping for futility or continuing with a re-estimated sample size.

Main Results:

• Simulation studies were conducted to analyze the properties of the proposed adaptive design.
• The design facilitates the initiation of trials with limited information and allows for data-driven adjustments.

Conclusions:

• Adaptive designs offer a flexible framework for rare disease clinical trials, enabling studies to commence and adapt as data emerge.
• This two-stage design provides a structured method for decision-making during the trial, optimizing resource allocation and information gain.