A lengthy interview of Dr. Michael E. Shannon, chair of the CCSVI Coalition’s Scientific Advisory Board, regarding the Canadian clinical trials. He suggests that what is needed is an adaptive phase II/phase III trial.
More specifically, I am talking about what is known as an adaptive Phase II/III trial which would permit a very rapid and seamless transition from the Phase II trial, subject of course to interim assessments of safety and efficacy, to a full Phase III trial. This would still address all the regulatory requirements, answering all the key safety and efficacy questions, but save significant time and cost.
Some thoughts on protocols:
So let’s talk about that framework or protocol for a moment. Putting together the protocol is probably the most critical process for any trial and requires highly experienced, well informed subject matter experts working collaboratively with clinical trial design specialists, statisticians and regulatory experts. Together they produce a document that defines in great detail every aspect of the trial, from patient selection to data analysis. Issues such as the number and type of patients are central to success. Determining what will be measured as an outcome must be carefully thought out with full agreement from all stakeholders. The determination of primary, secondary and tertiary outcome measures is essential if the real benefits of a treatment are to be fully appreciated. Finally, the actual therapeutic intervention must be made clear and in many cases, investigators need to be trained on the experimental procedure to ensure standardization. The intervention for CCSVI can be no exception.
Do you see this particular clinical trial as posing more than the usual challenges?
Yes I do. There are controversies regarding the most appropriate diagnostic approach. There is also a problem with the level of experience among Canadian investigators, which can only be resolved through proper training. But if we have no depth in this country, who will provide the training? It is noteworthy in this regard that many members of the CCSVI Coalition’s Scientific Advisory Board have had a great deal of experience with both the diagnosis and treatment of CCSVI. Most are very familiar with the treatment procedure and many routinely train other professionals.
Studies involving CCSVI intervention have proven very complex to interpret and the treatment presents some interesting challenges from a “blinding” perspective. Ideally, clinical trials should be double blinded, that is to say, neither the patient nor the investigator knows whether the actual treatment was received. Although both of these can be addressed using the concept of primary and secondary investigators, it will be a challenge to control.
Finally, I am somewhat concerned that the controversies regarding the role CCSVI may play in the pathogenesis of MS and the therapeutic merit of CCSVI treatment may have extended beyond the boundaries of healthy scientific debate. I think that everyone needs to humble themselves a little in the interest of good science and ultimately to realize the best possible outcome for our MS patients.
There's a lot worth quoting in this interview. Dr. Shannon comes across well.