North52 wrote:Dr. Sclafani,
Do you think it is really possible to do a truly blinded study of balloon angioplasty in MS patients? I see a number of obstacles that may be difficult to overcome. Ballooned patients seem to feel the ballooning procedure which would decrease the effectiveness of blinding. Deep consious sedation could potentially alleviate this problem, but I suspect this is probably not ethical as it may increase the procedural risk. Another way around it would be to balloon a normal portion of the vein in controls so they feel the procedure, but again I suspect this is not ethical.
Another problem I forsee is that sham patients would want to know if they were sham. They could always get a doppler done on their own to see if they still have any decreased flow. I suspect you will gradually lose your control group over time. One answer to this problem would be to to do a short term study, eg 3 months and look at variables that respond immediately to angio such as fatigue, cognition and perhaps immediate improvement in strength, vision etc. By doing a short term study, you can offer the sham group balloon angio after the 3 months and use them as your treatment arm. This way anyone entering the study would be offered ballooning within a 3 month period. If results are convicing and are shown to be safe, for eg in reduction of fatigue, that may provide sufficient evidence for the medical community to condone this procedure.
Curious to hear your thoughts on this.
When i was first considering performing liberation back in September 2009 , i had a meeting with dr aaron miller and fred lublin from mt sinai medical center in manhattan. Not being very well versed in MS, i sought them out to get their take on the subject of ccsvi. They were very skeptical and most concerned about a treatment that had not gone through the type of evaluation and study that they were used to. They did not buy into much of Paolo's work. But they were extraordinarily bright men, passionate about their patients and very knowledgable about MS
i remember dr milller asking me " putting aside our objections and doubts, how would you design a trial?" We spoke about this for a long time. The idea of sham operations seemed, as you say, to be a necessary component. But how to ethically and humanely, operate on people without treating them? While I can do the procedure under local anesthesia, i would need to put patients under deep sedation at the least so that none would know whether the balloon had been inflated. Another component of a trial that would not likely pass IRB approval.
then came the most important component. Who will pay? Many $millions would be necessary to fund a large multicenter trial. Who has the deep pockets? and Who would fund it without more information than a case series without real control of 65 patients, less than half of whom had durable results. is unlikely to happen until AFTER there is more cohort studies, and the many wrinkles are worked out.