Development and Validation of a New Measure of Impairment in Myasthenia Gravis: The Myasthenia Gravis Impairment Index

Objectives: The aim of this dissertation was to develop a measure of the impairments in patients with Myasthenia Gravis (MG), that would quantify disease severity and detect change in clinical trials and practice. The specific objectives were to determine: 1) content validity through the development of a conceptual framework of disease severity at the impairment level and subsequent item generation and reduction; 2) inter-rater and test-retest reliability; 3) construct validity; 4) responsiveness and the minimal important dierence of the measure. Methods: These included a qualitative study of patients experiences to develop a conceptual framework of disease severity in MG. Additionally, items were obtained from the literature or developed de novo and input from clinicians and MG experts was obtained for a final draft of the measure. The measure was field-tested in a broad population of MG patients to determine feasibility, reliability, construct validity and responsiveness. Results: A conceptual framework of MG-related impairments was developed where both the severity of the impairments and fatigability defined overall disease severity. A first draft was assessed by 18 patients through cognitive debriefing and by 78 international specialists through a survey. The second draft had 7 examination and 22 patient-reported items. Field-testing included 200 MG patients with 54 of these included in reliability evaluation and 50 in the responsiveness studies. All items hadPh.D