The challenge of long-term studies in multiple sclerosis: use of pooled data, historical controls, and observational studies to determine efficacy

There have been considerable advances in our understanding of the impact of a number of new approaches to the treatment of multiple sclerosis (MS) in the past decade.[1] We owe much of this progress to the use of modern clinical trial methodology, especially the classic randomized controlled clinical trial design.[2,3] The final quarter of the last century witnessed the transition to this more rigorous approach from what had been applied earlier, including personal observations, small case-controlled studies and retrospective series, and studies using historical controls.[4] With the ascendancy of randomized trials we have seen increasingly careful scrutiny of the details of trial design and conduct. This has been critical to the efforts to identify promising trends and ultimately progress to better therapies for MS patients.