There was nothing in the 10K that surprised me.
Did we not already know about pseudo progression? Numerous academic papers, unrelated to DCVax, have discussed this issue. Dr. Liau has discussed this for years. No unblinding was necessary.
Did we not already know that cross over arms make clinical trial statistics more challenging? This is a general problem with cross over arm trials but are necessary to achieve patient compliance and follow up. No unblinding was necessary.
I believe that the FDA and other health regulators operate with the overarching goal of improving the lives of patients. While there is a long history that led to the art of interpreting trial data, there are no hard and fast rules. Many arguments (including a few from today’s twitter feed) are too simplistic to be convincing. I believe the health regulators consider the entire context.
The use of external controls is an innovative way to address the specific challenges of some clinical trials, including the DCVax pivotal trial. External controls are not a panacea but they are becoming an accepted tool to allow better interpretation of clinical data. One cannot just slap a set of external control data on a single arm trial and be done with it. There are subtleties in how an external control can be used to provide a better interpretation compared to one without an external control. I think these subtleties will be apparent once an academic paper on DCVax is published and I believe the health regulators will consider the entire context. Isn’t that what any caring person would do?
There are clues in the DCVax blinded data (e.g. look at the subgroups) that suggest whether it is producing a survival response.
There are clues in the external controls data (e.g. look at the variance) shown by Liau that suggest whether exclusion criteria (or some of the other reasons single arm trials fail) lead to the strong survival result.
There are also clues in how those with best information are acting. You all know what they are so decide for yourself if those who knew their trial failed would be so eagerly acquire warrants that will all expire worthless.
Lastly, there are subtleties in how external controls can be properly used to better interpret clinical trial results. I think these will be apparent once an academic paper on DCVax is published.
Fortunately for all of us, bulls and bears, we will soon see the data that we have been debating about for years and we can then shift to the next set of never-ending arguments.
