A Critical Appraisal of Matching-Adjusted Indirect Comparisons in Spinal Muscular Atrophy

Area of Science:

• Pharmacoeconomics
• Biostatistics
• Clinical Trial Analysis

Background:

• Indirect treatment comparisons (ITCs) are vital for therapy evaluation without direct trials.
• Matching-adjusted indirect comparison (MAIC) is a specific ITC method used when individual patient data from one study contrasts with aggregate data from another.

Purpose of the Study:

• To critically assess the conduct and reporting quality of Matching-adjusted indirect comparisons (MAICs) for spinal muscular atrophy (SMA) treatments.
• To identify potential biases and areas for improvement in MAIC methodology within the context of SMA.

Main Methods:

• A literature search identified three MAICs comparing approved SMA therapies: nusinersen, risdiplam, and onasemnogene abeparvovec.
• MAIC quality was evaluated against established best practice principles, including justification, trial comparability, confounder control, outcome consistency, baseline characteristic reporting, and reporting completeness.

Main Results:

• Significant variability in the quality of analysis and reporting was observed across the three MAICs.
• Identified biases included inadequate control for confounders/effect modifiers, inconsistent outcome definitions, post-adjustment baseline imbalances, and incomplete reporting of key methodological elements.

Conclusions:

• The quality of MAICs for SMA treatments is inconsistent, necessitating rigorous evaluation against best practices.
• Improvements in the conduct and reporting of MAICs are crucial for reliable comparative efficacy assessments in rare diseases like SMA.