You get what you measure

Abstract

Since the emergence of the modern therapeutic era in multiple sclerosis (MS), the field has focused on identifying agents to prevent long-term disability progression. In lieu of measuring the true endpoint of interest, long-term disability progression, clinical trials typically measure surrogate endpoints, such as short-term disability progression or changes in lesion burden on MRI.1 Because these surrogates can be measured earlier and more easily than long-term disability progression, clinical trials can be shorter and smaller. The critical issue, however, is whether changes induced by a therapy on a surrogate endpoint reliably predict the clinical benefit on the true endpoint. Surrogate endpoints are measures which correlate with clinically important (true) endpoints of interest; however, this criterion alone is not sufficient to define a surrogate endpoint.2 Ideally, surrogates are in the only causal pathway for disease progression. That is, for short-term disability progression to be a good surrogate for long-term disability progression, long-term progression should be solely mediated by short-term progression. Also, the treatment under study must affect the true …