Doc, while it's true what you're saying about the cross over design making the trial tougher to interpret, I believe that if new trials were started today, all patients would be treated with the vaccine from the beginning. Trial results would be compared with historical data. The question in my mind is whether the regulators will accept the historical data at the time a trial, which may take a decade or longer to run, is what's available at the time the trial begins, or wait to gather the historical data essentially when the trial is concluding. I would suspect that while some goals might be established at the beginning, at the end the regulators would consider how treatment had evolved during the trial and the final goals could be adjusted to reflect it.
I've always been a believer in giving the Drs. as many tools as possible, so if a product is doing good for some percentage of the patient population, and not causing harm, it ought to gain approval. The regulators often don't see it this way. You really never know how great a new product may be until it's approved, until that time a specific protocol has been used, and it can only be judged by how it did in that protocol. After approval Drs. can use it as they choose and may find much more effective ways of using it. Certainly in our case UCLA has found the addition of Poly-ICLC and/or Keytruda make a huge difference, but what if those trials had never been run. I suspect that DCVax-L would still have been approved, but the benefit of the addition of other products would take much longer, but in time it would have happened. It may take years, but in time it may be found that other products do even better than those we know of today, but the key is they need the vaccine to be effective.
Gary
Bullish
