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. 2024 Jun 24:15:1368525.
doi: 10.3389/fneur.2024.1368525. eCollection 2024.

Clinical meaningfulness and psychometric robustness of the MG Symptoms PRO scales in clinical trials in adults with myasthenia gravis

Antoine Regnault  1 , Ali A Habib  2 , Kristin Creel  1 , Henry J Kaminski  3 , Thomas Morel  4
Affiliations

Clinical meaningfulness and psychometric robustness of the MG Symptoms PRO scales in clinical trials in adults with myasthenia gravis

Antoine Regnault et al. Front Neurol. .

Abstract

Objectives: The objective of this research was to generate psychometric evidence supporting the myasthenia gravis (MG) symptoms patient-reported outcome (PRO) scales as a fit-for-purpose measure of severity of core symptoms of MG and provide information allowing their meaningful interpretation using data from a phase 3 study in MG.

Methods: Data from the MycarinG study, a phase 3 study of rozanolixizumab in patients with generalized MG who experience moderate to severe symptoms (ClinicalTrials.gov Identifier: NCT03971422) were analyzed with both classical test theory (CTT) and Rasch measurement theory (RMT). Meaningful within-individual change and group-level meaningful change were estimated for three MG Symptoms PRO scales using anchor- and distribution-based methods. Anchor-based methods used patient global impression of severity (PGIS) and change (PGIC) in MG symptoms as anchors.

Results: Good measurement properties of the MG Symptoms PRO scales were shown in the sample of 200 participants: good to excellent reliability (test-retest and internal consistency reliability) and validity (associations between items and scores within the MG Symptoms PRO scales and between the MG Symptoms PRO scores and other clinical outcomes-MG ADL, QMG score, MGC score, and MGFA classes-were as expected); and the items showed good coverage of the continuum and fit to the Rasch model. Triangulation of the anchor- and distribution-based method results led to the definition of clinically meaningful within-patient improvement in scores for Muscle Weakness Fatigability (-16.67), Physical Fatigue (-20.00), and Bulbar Muscle Weakness (-20.00), with associated ranges. Benchmarks are also proposed for the interpretation of group-level results.

Conclusion: The strong psychometric performance of the MG Symptoms PRO scales and the information generated to guide its interpretation supports its use in clinical trials for demonstrating the clinical benefits of new treatments targeting core symptoms of MG (muscle weakness fatigability, physical fatigue, bulbar muscle weakness, respiratory muscle weakness, and ocular muscle weakness).

Keywords: clinically meaningful change; fatigue; muscle weakness; myasthenia gravis (MG); patient reported outcomes (PRO); psychometric analysis.

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Conflict of interest statement

AR and KC were employees of Modus Outcomes, a patient-centered outcome research consultancy that received payment from UCB to conduct this research. TM was an employee and a shareholder of UCB Pharma. The authors declare that this research and the MycarinG clinical study mentioned herein were funded by UCB Pharma. The funder was involved in the study design, data collection and analysis, decision to publish and preparation of the manuscript.

Figures

Figure 1
Figure 1
Visualization of estimates from anchor-based and distribution-based analyses used to determine meaningful within-patient change for improvement for the MG Symptoms PRO Muscle Weakness Fatigability score in the MycarinG study.
Figure 2
Figure 2
Visualization of estimates from anchor-based and distribution-based analyses used to determine meaningful within-patient change for improvement for the MG Symptoms PRO Physical Fatigue score in the MycarinG study.
Figure 3
Figure 3
Visualization of estimates from anchor-based and distribution-based analyses used to determine meaningful within-patient change for improvement for the MG Symptoms PRO Bulbar Muscle Weakness score in the MycarinG study.
See this image and copyright information in PMC

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