Designing an Endovascular Trial – What Elements are Essential and Why CCSVI Trials Might Differ from Disease Modifying Trials?
Kottil W. Rammohan, M.D. Background: “Liberation” of CCSVI has been associated with reports of variable efficacy both in the short as well as in the long term. Most claims of efficacy has however not withstood the scientific rigors of double-blind trials. Many of these trials have suffered from ill-defined criteria of venous insufficiency, inadequate sample sizes, soft subjective endpoints, and most of all poorly defined criteria of response.
Design: Endovascular trial design to show short-term symptomatic efficacy is different from long-term studies that show effects on the ability of intervention to modify the natural history of MS. All trials should define the populations studied with rigorous criteria for CCSVI, and define change using validated instruments. Analysis of efficacy in short-term trials should not utilize standard group comparisons of sham vs. real intervention although this may be appropriate for long-term studies. Instead, analysis of both groups for responders would be the preferred mode of analysis.
Conclusion: Short-term trial design and responder analysis as a novel approach to defining effects of CCSVI will be discussed.
I understand this part: the CCSVI trials thus far have had "ill-defined criteria of venous insufficiency, inadequate sample sizes, soft subjective endpoints, and most of all poorly defined criteria of response."
I understand the difference between a short-term trial looking for symptomatic efficiency as opposed to a long-term trial looking for effects of the intervention on the MS disease course. I value both sides there: symptomatic relief is wonderful, and an impact on the course of MS would also be wonderful if that is what comes to pass.
I do not understand the part about that the analysis of efficacy in short-term trials as it relates to standard group comparisons of sham vs real intervention. What is the difference between that and the analysis of both groups for responders?