Combining factorial and multi-arm multi-stage platform designs to evaluate multiple interventions efficiently.

Area of Science:

• Clinical Trial Design
• Biostatistics
• Pharmaceutical Research

Background:

• Factorial and multi-arm multi-stage (MAMS) platform designs present distinct advantages in clinical research.
• The practical implications of integrating these two powerful methodologies remain underexplored.

Purpose of the Study:

• To propose and describe practical methods for a combined factorial-MAMS platform design.
• To explore the advantages and disadvantages of this hybrid approach in clinical trials.

Main Methods:

• Developing a combined design within the platform trial framework for interventions without expected interactions.
• Illustrating the design with diagrams and detailing its properties, including considerations for interactions and power.
• Specifying procedures for interim and final analyses, eligibility criteria, and sequential stratified randomization.

Main Results:

• The combined design shares properties with standard factorial and MAMS designs, such as managing intervention interactions and defining stopping rules.
• Specific features include calendar time or event-driven analyses, broad eligibility, sequential randomization, and the use of concurrent controls.
• The design requires careful analysis to ensure the use of only concurrent controls.

Conclusions:

• A combined factorial-MAMS design synergizes the efficiencies of both factorial and MAMS platform trials.
• This integrated design facilitates addressing multiple research questions and evaluating numerous new treatments within a single protocol.
• It is particularly valuable for rapidly responding to public health crises, such as the COVID-19 pandemic.