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

Abstract

In the absence of head-to-head trials, indirect treatment comparisons (ITCs) are often used to compare the efficacy of different therapies to support decision-making. Matching-adjusted indirect comparison (MAIC), a type of ITC, is increasingly used to compare treatment efficacy when individual patient data are available from one trial and only aggregate data are available from the other trial. This paper examines the conduct and reporting of MAICs to compare treatments for spinal muscular atrophy (SMA), a rare neuromuscular disease. A literature search identified three studies comparing approved treatments for SMA including nusinersen, risdiplam, and onasemnogene abeparvovec. The quality of the MAICs was assessed on the basis of the following principles consolidated from published MAIC best practices: (1) justification for the use of MAIC is clearly stated, (2) the included trials with respect to study population and design are comparable, (3) all known confounders and effect modifiers are identified a priori and accounted for in the analysis, (4) outcomes should be similar in definition and assessment, (5) baseline characteristics are reported before and after adjustment, along with weights, and (6) key details of a MAIC are reported. In the three MAIC publications in SMA to date, the quality of analysis and reporting varied greatly. Various sources of bias in the MAICs were identified, including lack of control for key confounders and effect modifiers, inconsistency in outcome definitions across trials, imbalances in important baseline characteristics after weighting, and lack of reporting key elements. These findings highlight the importance of evaluating MAICs according to best practices when assessing the conduct and reporting of MAICs.

Keywords: Best practices; Comparative effectiveness; Critical appraisal; Indirect treatment comparison; Matching-adjusted indirect comparison; Neuromuscular disease; Nusinersen; Onasemnogene abeparvovec; Risdiplam; Spinal muscular atrophy.

Fig. 1

Example of reporting weighted and unweighted analyses [20]. Weighted analysis considered the factors highlighted in Table 3. Unweighted analysis was conducted in a subpopulation of ENDEAR/SHINE created on the basis of an age restriction to match the inclusion criteria used in STR1VE. ^aHR < 1.00 indicates a lower risk of an event in the STR1VE US cohort than in the ENDEAR/SHINE cohort. HR > 1.00 indicates a higher risk of an event in the STR1VE US cohort than in the ENDEAR/SHINE cohort. Shading denotes 95% CIs