Implementation of the Anchor-Based Indirect Comparison Method for Equivalence Margin Derivation in Biosimilar...

Area of Science:

• Pharmacometrics
• Clinical Trial Design
• Biostatistics

Background:

• Traditional meta-analysis for equivalence margin (EQM) derivation relies on direct comparisons.
• Complex treatment regimens often lack direct comparative data.
• Indirect comparisons are needed for situations with available comparator-to-reference and comparator-to-placebo data.

Purpose of the Study:

• To propose and validate an anchor-based indirect comparison method for EQM derivation.
• To address the challenge of deriving EQM when direct comparative data is absent.
• To present a case study in the biosimilar setting.

Main Methods:

• Utilized an anchor-based indirect comparison to estimate the treatment effect of Reference vs. Placebo.
• Calculated the difference in treatment effects and summed variances for the new variance estimate.
• Performed multiple sensitivity analyses to assess transitivity and consistency assumptions.

Main Results:

• Demonstrated EQM derivation using the anchor-based indirect comparison method.
• Included sensitivity analyses such as direct comparisons to similar reference drugs and impact of varying treatment effects.
• Applied the method to a planned efficacy trial in the biosimilar context.

Conclusions:

• Anchor-based indirect comparison is a viable approach for EQM derivation.
• Health authorities may accept this method if supported by thorough sensitivity analyses.
• This method offers a solution for complex treatment scenarios lacking direct comparative data.