Switching Design for Assessment of Interchangeability in Biosimilar Studies

Area of Science:

• Biostatistics
• Clinical Trial Design
• Pharmacoeconomics

Background:

• Assessing biosimilar switchability and interchangeability is crucial for reliable clinical evaluation.
• Optimal trial designs are needed to enhance statistical efficiency in biosimilar switching studies.
• Carryover effects present a challenge in crossover trial design.

Purpose of the Study:

• To explore optimal trial design strategies for biosimilar switching studies.
• To enhance statistical efficiency in treatment effect estimation under carryover settings.
• To evaluate the impact of balanced and uniform structures on trial efficiency.

Main Methods:

• Theoretical variance-based evaluation of two-treatment switching designs in three- and four-period crossover trials.
• Analysis using a linear mixed-effect model for log-transformed responses.
• Enumeration and classification of 247 three-period and 65,519 four-period designs, including those with a non-switching arm (NSA).

Main Results:

• Strongly Balanced Uniform-within-Period designs with a Non-Switching Arm (SBUwP-NSA) consistently achieved minimum variance.
• Uniform-within-Period designs with a Non-Switching Arm (UwP-NSA) showed equivalent efficiency in the absence of carryover.
• Commonly used dedicated switching designs were 50-55% less efficient than optimal designs.

Conclusions:

• Incorporating strong balance and uniformity properties yields substantial efficiency gains in biosimilar switching studies.
• Optimal designs provide quantitative guidance for improved estimation precision in interchangeability assessments.
• The findings support the selection of efficient crossover designs for biosimilar research.