PROBLEMS OF EXPERIMENTAL TRIALS OF THERAPY IN MULTIPLE SCLEROSIS: REPORT BY THE PANEL ON THE EVALUATION OF EXPERIMENTAL TRIALS OF THERAPY IN MULTIPLE SCLEROSIS

Multiple sclerosis has become a focus of growing interest to neurologists, general physicians, and the public. The disorder has an uneven but worldwide distribution and is present in approximately 30 to 60 people per 100,000 in the temperate zones of the world. Though some of these individuals remain unaffected by serious disability, in the majority the disease leads to crippling and ultimately premature death. To the public a special appeal lies in the frequent occurrence of multiple sclerosis in the young adult, often with disruption of early family life. To date no satisfactory treatment for the amelioration or cure of the disease has been discovered. Since its etiology and pathogenesis have eluded detection, it is not surprising that therapeutic attempts have been empiric and often unscientific. Reports of benefit from various types of therapy based on uncontrolled observations have led to unwarranted and occasionally widespread application of methods whose value remained unsubstantiated. In recent years criticisms have been made of the lack of adequate controls in trials of therapy. The difficulties inherent in judging the effects of therapy have been stressed.', * These are: (1) Lack of precision in diagnosis. (2) The erratic and unpredictable course of the disease with periods of spontaneous remission of symptoms. (3) Lack of a direct method for investigating activity of the disease. (4) The existence of only crude parameters for quantitating and recording the clinical course of the disease. (5) The irreversibility of gliosis and its masking effect on disease activity elsewhere in the nervous system. (6) Psychological disturbances, including hysterical tendencies, in some patients. (7) Problems of keeping large groups of patients under standard conditions of therapy or control for long periods (necessary because of the chronicity and erratic nature of the disease). Attempts to apply some degree of scientific control to therapeutic investigations in multiple sclerosis, however, have been made r e ~ e n t l y . ~ ~ Because of the prevalence of poorly controlled therapy reports, the National Institute of Neurological Diseases and Blindness provided financial support for a Symposium on the Evaluation of Drug Therapy in Neurologic and Sensory Diseases* which was held at the University of Wisconsin in May, 1960. Ten panels composed of investigators, clinicians, and statisticians met to consider the problem of experimental trials of therapy in various areas of nervous system disease. The results of the discussions were subsequently published.6 The conclusions reached by the Panel on Multiple Sclerosis comprised essentially a statement of the problems that needed study and solution to permit the design of a protocol for sound experimental trials of therapy. Thus, they formed merely a point of departure for future study. As an outgrowth of the initial considerations of the Panel on Multiple Sclerosis, a continuing panel was formed which held a series of workshops on the problem.