Measuring the impact of therapeutic intervention

Abstract

DMT= : disease-modifying therapy; EDSS= : Expanded Disability Status Scale; HRQoL= : health-related quality of life; MS= : multiple sclerosis; MSFC= : Multiple Sclerosis Functional Composite. In 1981, 113 years after Jean Martin Charcot's initial description of multiple sclerosis (MS), an international workshop considered the challenges facing investigators in developing effective therapies for MS.1 Many of the neurologists at the workshop felt that the hurdles were too great and that efforts to develop effective therapies would require a fundamental understanding of the etiology of the disease. Prominent among the hurdles were the variability of the disease—both between and within patients—and difficulties measuring the disease. In hindsight, the 1981 workshop was a watershed event. Since then, in only 29 years, there has been remarkable progress in measuring and treating MS. Patients are now diagnosed earlier and with greater accuracy with the advent of MRI and its inclusion in diagnostic criteria.2 In addition, there has been a lively debate on the best approach to measuring the disease. Are traditional measures optimal? Does a treatment effect on relapses translate into a meaningful long-term therapeutic response for the patient? Does the Kurtzke Expanded Disability Status Scale (EDSS) optimally measure MS-related disability? Does a therapeutic effect on the EDSS during the relapsing-remitting stage of MS mean there will be a reduction in irreversible disability? Is the EDSS optimal for developing therapies for the progressive stages of MS? Are there more precise and responsive measures of disability that could supplant the EDSS, such as the Multiple Sclerosis Functional Composite (MSFC)? What about patient-reported outcomes that more meaningfully reflect the impact of the disease on the patient? Answers will emerge as nontraditional measures are included in clinical studies. What about measures of neuropsychological function, fatigue, and measures of bowel, bladder, and sexual function? What is the economic effect of treatment? …