ABSTRACT
Even today, regulatory bodies worldwide continue to focus on the tried-and-true paradigm of randomized, controlled clinical trials for new therapies (often requiring placebo-controlled data), and the general experimental paradigm used to develop evidence of safety and efficacy of agents for MS has changed little since the early 1980s. While new outcome measures have been developed and become more sophisticated (such as magnetic resonance imaging and the pursuit of biological markers of disease activity), and while new scales for disability have evolved, MS clinical trials still follow a pattern that begins with exploratory mechanistic (including preclinical) studies, continues into toxicity and safety studies (phase I), through preliminary exploratory studies (phase II) and then into registration studies (phase III), in which, in sequence,
biological mechanism is explored, dosing studies are performed and proof of therapeutic principle is developed prior to well-controlled studies to establish safety and efficacy.
