NZer1 wrote:Thanks all,
I do understand the outcomes, my point has always been the same, WHY design a trial the way they have?
The trial design is very typical for evaluating a medical intervention, as far as I can tell. You might check out a few other published medical trial results, and I think you'll see that
the most robust studies tend to have similar designs (small unblinded Phase 1 for safety, then somewhat larger Phase 2 that is randomized, double-blinded and placebo controlled).
NZer1 wrote:I wonder why in Phase 2 there was a constraint on the treatment that it was only to achieve a maximum of 50% improvement, no more?
I'm pretty sure the 50% VHISS improvement in Phase 2 was
not intentional. I'd imagine there was a fair bit of head-scratching when the researchers were finally allowed to analyze the data.
NZer1 wrote:The safety research concept as a stand alone Phase 1 and not inclusive part of the entire trial appears to be an expensive waste of money available and potential for finding a deeper understanding, when the task is performed anyway.
If 75% gives one outcome, why was 75% chosen and not any other figure to experiment with the safety concept?
Again, I think they do the surgery, and then measure the VHISS improvement, hoping to achieve the 75% threshold.
Regarding the Phase 1 portion of the trial, this safety trial was almost certainly required (by the University, or by the FDA, I'm not sure). You cannot ethically do a trial to see how effective a procedure is until you have demonstrated that the procedure is safe. BNAC doesn't make these rules, but they do have to play by them. Now, back in the good old days (ahem!) before these rules were in place, you could just round up some prisoners or patients from the free clinic, and go right into a big effectiveness trial. That saved money, but had some horrendous outcomes. Be thankful that's forbidden now, even if sometimes the new rules seem wasteful.
NZer1 wrote:And in Phase 2 50% tops is used with differently selected patients from Phase 1, it gives a purposeful impression OR it gives an impression that separate theories were being tested.
Were the researchers united in both the trial stages or was there complete separation of Phase 1 and Phase 2 projects?
Again, Phase 1 and Phase 2 trials have different goals. To make the Phase 2 results (where you compare outcomes between groups), you want the people in the two groups to be as similar as possible at the start. So you use very restrictive enrollment criteria. But those strict criteria make it hard to get enough patients, so for Phase 1 you use more relaxed criteria. I beleive this is also very typical.
NZer1 wrote:Could the trial have been planned differently and achieved more CCSVI understandings if there had been more progression of treatment stages with the same criteria for patient selection and then the safety finding would have been based on boarder knowledge of degrees of risk with percentage of resizing, blinded or not.
I don't entirely follow what you're suggesting, but keep in mind that there is a standard, well established way to organize trials. If you deviate from that design, it makes it more likely that your results will not be trusted by other scientists (getting these things right is hard), and that in turn likely makes it harder to get funding. So researchers have good reasons to stick to tried and true study designs.
In fact, I believe the reason people were so excited about this study is precisely because it was the first to use the "gold standard" of study designs: the randomized, double-blind, placebo controlled study.
NZer1 wrote:The safety understanding would have evolved with trial and outcome in Phase 2 rather than selecting a set figure Phase 1 with no other criteria and saying one percentage was safe on 10 subjects that were picked by 'xyz' screening?
No, you can't do that. You want as many people as possible in Phase 2, but it's not ethical to submit a large group of people to a treatment whose safety hasn't been demonstrated (according to some specific requirements).
NZer1 wrote:What percentage and criteria will be chosen for Phase 3, will it match Phase 2 in some regard and what is the purpose of the patient picking criteria with a disease with an unknown disease progression?
You should read up on clinical trials. There will be no Phase 3. Those terms, e.g. "Phase 1" and "Phase 2", have specific meanings specified by the FDA for medical trials. See
http://en.wikipedia.org/wiki/Phase_1_clinical_trial
NZer1 wrote:My favourite question,
WHY? WHY? WHY?
My favorite answer: Google it!
/Scut