Addressing Outcome Measure Variability in Myasthenia Gravis Clinical Trials

Jeffrey T. Guptill, From the Duke University School of Medicine (J.T.G.), Durham, NC; argenx US (J.T.G.), Boston, MA; University of Miami School of Medicine (M.B., V.G.), FL; Biohaven Pharmaceuticals (V.G.), New Haven, CT; University of California, Irvine (A.A.H.); The University of North Carolina School of Medicine (J.F.H.), Chapel Hill; Division of Neurology (C.B.-T.), Department of Medicine, University of Toronto, Ontario, Canada; Yale University School of Medicine (R.J.N.), New Haven, CT; Columbia University (I.L.), New York, NY; Medical University of South Carolina (K.R.), Charleston; Kansas University Medical Center (M.M.D.), Kansas City; School of Public Health (G.R.C.), University of Alabama at Birmingham; and George Washington University School of Medicine & Health Sciences (H.J.K.), DC. jeffrey.guptill@duke.edu mbenatar@med.miami.edu.
Michael Benatar, From the Duke University School of Medicine (J.T.G.), Durham, NC; argenx US (J.T.G.), Boston, MA; University of Miami School of Medicine (M.B., V.G.), FL; Biohaven Pharmaceuticals (V.G.), New Haven, CT; University of California, Irvine (A.A.H.); The University of North Carolina School of Medicine (J.F.H.), Chapel Hill; Division of Neurology (C.B.-T.), Department of Medicine, University of Toronto, Ontario, Canada; Yale University School of Medicine (R.J.N.), New Haven, CT; Columbia University (I.L.), New York, NY; Medical University of South Carolina (K.R.), Charleston; Kansas University Medical Center (M.M.D.), Kansas City; School of Public Health (G.R.C.), University of Alabama at Birmingham; and George Washington University School of Medicine & Health Sciences (H.J.K.), DC.
Volkan Granit, From the Duke University School of Medicine (J.T.G.), Durham, NC; argenx US (J.T.G.), Boston, MA; University of Miami School of Medicine (M.B., V.G.), FL; Biohaven Pharmaceuticals (V.G.), New Haven, CT; University of California, Irvine (A.A.H.); The University of North Carolina School of Medicine (J.F.H.), Chapel Hill; Division of Neurology (C.B.-T.), Department of Medicine, University of Toronto, Ontario, Canada; Yale University School of Medicine (R.J.N.), New Haven, CT; Columbia University (I.L.), New York, NY; Medical University of South Carolina (K.R.), Charleston; Kansas University Medical Center (M.M.D.), Kansas City; School of Public Health (G.R.C.), University of Alabama at Birmingham; and George Washington University School of Medicine & Health Sciences (H.J.K.), DC.
Ali A. Habib, From the Duke University School of Medicine (J.T.G.), Durham, NC; argenx US (J.T.G.), Boston, MA; University of Miami School of Medicine (M.B., V.G.), FL; Biohaven Pharmaceuticals (V.G.), New Haven, CT; University of California, Irvine (A.A.H.); The University of North Carolina School of Medicine (J.F.H.), Chapel Hill; Division of Neurology (C.B.-T.), Department of Medicine, University of Toronto, Ontario, Canada; Yale University School of Medicine (R.J.N.), New Haven, CT; Columbia University (I.L.), New York, NY; Medical University of South Carolina (K.R.), Charleston; Kansas University Medical Center (M.M.D.), Kansas City; School of Public Health (G.R.C.), University of Alabama at Birmingham; and George Washington University School of Medicine & Health Sciences (H.J.K.), DC.
James F. Howard, From the Duke University School of Medicine (J.T.G.), Durham, NC; argenx US (J.T.G.), Boston, MA; University of Miami School of Medicine (M.B., V.G.), FL; Biohaven Pharmaceuticals (V.G.), New Haven, CT; University of California, Irvine (A.A.H.); The University of North Carolina School of Medicine (J.F.H.), Chapel Hill; Division of Neurology (C.B.-T.), Department of Medicine, University of Toronto, Ontario, Canada; Yale University School of Medicine (R.J.N.), New Haven, CT; Columbia University (I.L.), New York, NY; Medical University of South Carolina (K.R.), Charleston; Kansas University Medical Center (M.M.D.), Kansas City; School of Public Health (G.R.C.), University of Alabama at Birmingham; and George Washington University School of Medicine & Health Sciences (H.J.K.), DC.
Carolina Barnett-Tapia, From the Duke University School of Medicine (J.T.G.), Durham, NC; argenx US (J.T.G.), Boston, MA; University of Miami School of Medicine (M.B., V.G.), FL; Biohaven Pharmaceuticals (V.G.), New Haven, CT; University of California, Irvine (A.A.H.); The University of North Carolina School of Medicine (J.F.H.), Chapel Hill; Division of Neurology (C.B.-T.), Department of Medicine, University of Toronto, Ontario, Canada; Yale University School of Medicine (R.J.N.), New Haven, CT; Columbia University (I.L.), New York, NY; Medical University of South Carolina (K.R.), Charleston; Kansas University Medical Center (M.M.D.), Kansas City; School of Public Health (G.R.C.), University of Alabama at Birmingham; and George Washington University School of Medicine & Health Sciences (H.J.K.), DC.
Richard J. Nowak, From the Duke University School of Medicine (J.T.G.), Durham, NC; argenx US (J.T.G.), Boston, MA; University of Miami School of Medicine (M.B., V.G.), FL; Biohaven Pharmaceuticals (V.G.), New Haven, CT; University of California, Irvine (A.A.H.); The University of North Carolina School of Medicine (J.F.H.), Chapel Hill; Division of Neurology (C.B.-T.), Department of Medicine, University of Toronto, Ontario, Canada; Yale University School of Medicine (R.J.N.), New Haven, CT; Columbia University (I.L.), New York, NY; Medical University of South Carolina (K.R.), Charleston; Kansas University Medical Center (M.M.D.), Kansas City; School of Public Health (G.R.C.), University of Alabama at Birmingham; and George Washington University School of Medicine & Health Sciences (H.J.K.), DC.
Ikjae Lee, From the Duke University School of Medicine (J.T.G.), Durham, NC; argenx US (J.T.G.), Boston, MA; University of Miami School of Medicine (M.B., V.G.), FL; Biohaven Pharmaceuticals (V.G.), New Haven, CT; University of California, Irvine (A.A.H.); The University of North Carolina School of Medicine (J.F.H.), Chapel Hill; Division of Neurology (C.B.-T.), Department of Medicine, University of Toronto, Ontario, Canada; Yale University School of Medicine (R.J.N.), New Haven, CT; Columbia University (I.L.), New York, NY; Medical University of South Carolina (K.R.), Charleston; Kansas University Medical Center (M.M.D.), Kansas City; School of Public Health (G.R.C.), University of Alabama at Birmingham; and George Washington University School of Medicine & Health Sciences (H.J.K.), DC.
Katherine Ruzhansky, From the Duke University School of Medicine (J.T.G.), Durham, NC; argenx US (J.T.G.), Boston, MA; University of Miami School of Medicine (M.B., V.G.), FL; Biohaven Pharmaceuticals (V.G.), New Haven, CT; University of California, Irvine (A.A.H.); The University of North Carolina School of Medicine (J.F.H.), Chapel Hill; Division of Neurology (C.B.-T.), Department of Medicine, University of Toronto, Ontario, Canada; Yale University School of Medicine (R.J.N.), New Haven, CT; Columbia University (I.L.), New York, NY; Medical University of South Carolina (K.R.), Charleston; Kansas University Medical Center (M.M.D.), Kansas City; School of Public Health (G.R.C.), University of Alabama at Birmingham; and George Washington University School of Medicine & Health Sciences (H.J.K.), DC.
Mazen M. Dimachkie, From the Duke University School of Medicine (J.T.G.), Durham, NC; argenx US (J.T.G.), Boston, MA; University of Miami School of Medicine (M.B., V.G.), FL; Biohaven Pharmaceuticals (V.G.), New Haven, CT; University of California, Irvine (A.A.H.); The University of North Carolina School of Medicine (J.F.H.), Chapel Hill; Division of Neurology (C.B.-T.), Department of Medicine, University of Toronto, Ontario, Canada; Yale University School of Medicine (R.J.N.), New Haven, CT; Columbia University (I.L.), New York, NY; Medical University of South Carolina (K.R.), Charleston; Kansas University Medical Center (M.M.D.), Kansas City; School of Public Health (G.R.C.), University of Alabama at Birmingham; and George Washington University School of Medicine & Health Sciences (H.J.K.), DC.
Gary R. Cutter, From the Duke University School of Medicine (J.T.G.), Durham, NC; argenx US (J.T.G.), Boston, MA; University of Miami School of Medicine (M.B., V.G.), FL; Biohaven Pharmaceuticals (V.G.), New Haven, CT; University of California, Irvine (A.A.H.); The University of North Carolina School of Medicine (J.F.H.), Chapel Hill; Division of Neurology (C.B.-T.), Department of Medicine, University of Toronto, Ontario, Canada; Yale University School of Medicine (R.J.N.), New Haven, CT; Columbia University (I.L.), New York, NY; Medical University of South Carolina (K.R.), Charleston; Kansas University Medical Center (M.M.D.), Kansas City; School of Public Health (G.R.C.), University of Alabama at Birmingham; and George Washington University School of Medicine & Health Sciences (H.J.K.), DC.
Henry J. Kaminski, From the Duke University School of Medicine (J.T.G.), Durham, NC; argenx US (J.T.G.), Boston, MA; University of Miami School of Medicine (M.B., V.G.), FL; Biohaven Pharmaceuticals (V.G.), New Haven, CT; University of California, Irvine (A.A.H.); The University of North Carolina School of Medicine (J.F.H.), Chapel Hill; Division of Neurology (C.B.-T.), Department of Medicine, University of Toronto, Ontario, Canada; Yale University School of Medicine (R.J.N.), New Haven, CT; Columbia University (I.L.), New York, NY; Medical University of South Carolina (K.R.), Charleston; Kansas University Medical Center (M.M.D.), Kansas City; School of Public Health (G.R.C.), University of Alabama at Birmingham; and George Washington University School of Medicine & Health Sciences (H.J.K.), DC.

Document Type

Journal Article

Publication Date

9-5-2023

Journal

Neurology

Volume

101

Issue

10

DOI

10.1212/WNL.0000000000207278

Abstract

An increasing number of clinical trials are enrolling patients with myasthenia gravis (MG). A lack of standardization in the performance of outcome measures leads to confusion among site research teams and is a source of variability in clinical trial data. MGNet, the NIH-supported Rare Disease Clinical Research Network for MG, views standardization of MG outcome measures as a critical need. To address this issue, a group of experts summarized key outcome measures used in MG clinical trials and a symposium was convened to address issues contributing to outcome measure variability. Consensus recommendations resulted in changes to outcome measure instructions and, in some cases, modifications to specific instruments. Recommended changes were posted for public commentary before finalization. Changes to the MG-Activities of Daily Living, MG-Quality of Life-15r, and MG-Impairment Index were limited to adding details to the administration instructions. Recommendations for proper positioning of participants and how to score items that could not be performed because of non-MG reasons were provided for the MG Composite. The Quantitative MG (QMG) score required the most attention, and changes were made both to the instructions and the performance of certain items resulting in the QMG-Revised. The Postintervention Status was believed to have a limited role in clinical trials, except for the concept of minimal manifestation status. As a next step, training materials and revised source documents, which will be freely available to study teams, will be created and posted on the MGNet website. Further studies are needed to validate changes made to the QMG-Revised.

Department

Neurology

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