SPECIAL REPORT Myasthenia Gravis: Recommendations for Clinical Research Standards Alfred Jaretzki III, MD, Richard J. Barohn, MD, Raina M. Ernstoff, MD, Henry J. Kaminski, MD, John C. Keesey, MD, Audrey S. Penn, MD, and Donald B. Sanders, MD, Task Force of the Medical Scientific Advisory Board of the Myasthenia Gravis Foundation of America Department of Surgery, Columbia Presbyterian Medical Center, New York, New York; the Department of Neurology, University of Texas Southwestern Medical Center, Dallas, Texas; the Neurology Service, William Beaumont Hospital, Royal Oak, Michigan; the Departments of Neurology and Neurosciences, Case Western Reserve University, Department of Veterans Affairs Medical Center, University Hospitals of Cleveland, Cleveland, Ohio; Department of Neurology, University of California at Los Angeles, Los Angeles, California; the National Institute for Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland; and the Department of Medicine, Duke University Medical Center, Durham, North Carolina The need for universally accepted classifications, grading systems, and methods of analysis for patients undergoing therapy for MG is widely recognized and is particularly needed for therapeutic research trials. The Medical Sci- entific Advisory Board (MSAB) of the Myasthenia Gravis Foundation of America (MGFA) formed a Task Force in May 1997 to address these issues. Initially, the Task Force planned to develop classifications and outcome measures pertaining only to standardizing thymectomy trials. How- ever, it quickly became apparent that their efforts should apply to all therapeutic trials for MG, and thus the scope of the mission was expanded. During the development of these recommendations, the Task Force faced numerous dilemmas for which no universally satisfactory solution was available. Dilemmas were defined as “situations that require one to choose between two equally balanced alternatives or predica- ments that seemingly defy satisfactory solutions.” The Task Force members agreed at the outset, however, that their primary goal was to develop a uniform set of classifications to be used in the comparative analysis of the various therapeutic interventions for MG. With this as the primary goal, a consensus was gradually devel- oped. In developing a consensus, at least two meetings were held each year during a 3-year period. Between meetings there was exchange of all proposals by elec- tronic and surface mail, consultation with national and international experts in the field, critical analysis of all proposals, and many revisions. All conflicts (both minor and major) were resolved by vote. Virtually all issues were eventually approved unanimously; a few received a plurality of six. This report presents the work of the Task Force and proposes classification systems and definitions of re- sponse to therapy designed to achieve more uniformity in recording and reporting clinical trials and outcomes research. Although designed primarily for research pur- poses, we think physicians may find some of the recom- mendations useful in the clinical management of patients with MG. MGFA Clinical Classification This classification (Table 1) is designed to identify sub- groups of patients with MG who share distinct clinical features or severity of disease that may indicate different prognoses or responses to therapy. It should not be used to measure outcome. It defers quantitative assessment of muscle weakness to the more precise Quantitative MG Score for Disease Severity, defers response to therapy to the MGFA Postintervention Status and the Quantitative MG Score, and defers the status of medication to the Therapy Status classification. The fluctuating extent and severity of MG, and the variable predominance of the muscle groups involved, makes it extremely difficult to classify these patients. Most existing classifications are modifications of Osser- man’s [1], separating patients with purely ocular involve- ment from those with generalized weakness, and further separating those with mild, moderate, or severe general- ized weakness. Osserman classifications have included categories based on the course of the disease, such as “acute fulminating” and “late severe,” and at times also included categories for muscle atrophy and childhood onset. Experienced clinicians have devised other classifi- cations to monitor response to treatment, some based on the degree of disability or age at onset, and others that include quantitative measurements of specific muscle function, such as arm abduction time and vital capacity. In general, these classifications use subjective assess- ments and lack quantification. What one physician may regard as “mild,” another might regard as “moderate” or “severe.” Furthermore, some experienced clinicians be- lieve that oropharyngeal involvement is more dangerous, and perhaps different than limb weakness, and thus should be identified by the classification system. Some Reprinted with permission from Neurology 2000;55:16 –23 (© AAN Enter- prises, Inc.). Additional material related to this article can be found on the Neurology Web site at www.neurology.org. Consult the Table of Contents for the July 12 issue to find the title link for this article. See also Neurology 2000;55:3– 4, 7–15. Address reprint requests to The Myasthenia Gravis Foundation of Amer- ica, Inc, 123 West Madison, Suite 800, Chicago, IL 60602; e-mail: myastheniagravis@msn.com. Ann Thorac Surg 2000;70:327–34 • 0003-4975/00/$20.00 Published by Elsevier Science Inc PII S0003-4975(00)01595-2