There hasn't been much talk regarding the protocol approval changes. They got Health Canada approval to get more data on the CR at 450 day patients. I'm guessing that if the protocol covers 450 days then you need approval before you chase down more confidential patient data.
As well, recall that they announced:
"Optional Maintenance Study II Treatment -Patients currently receive a mandatory maintenance Study II Treatment at 180 days; however, this has been optimized to allow optional maintenance Study II Treatments, at the discretion of the Principal Investigator ("PI") based on the patient's response. For patients who have achieved a CR or IR at any point in time and have demonstrated a duration of that CR or IR, no further maintenance Study II Treatments would be administered; however, if the patient recurs at any scheduled assessment visit (i.e.: 90, 180, 270, 360 or 450 days), then that patient would be eligible to receive up to 2 maintenance Study II Treatments at the discretion of the PI to assist the patient in achieving a CR."
This is an interesting modification. I feel like there is some nuances in why they have requested this modificaton.
Recall that as it stands, people get treated at time 0 and 180 days. But there is a good chance that those who are non-responders at day 90 drop out to move on to the next trial or to have bladder resection. They are allowed to do that and then they are considered NR for the entire duration of the trial. So the study has always suffered, in my opinion, from losing patients after only one treatment.
If you look at the 90 day time-point, the non-responders are about 36%. That is 36% that you likely cannot get a second crack at because they have exited by the 180 day time-point.
Recall that the protocol is as follows
- day 0 get treated
- month 1, urine for cytology
- month 2, urine for cytology
- month 3 urine for cytology THEN you go to cystoscopy (why go to scope without that information. It has to be that way)
The timing of results means that the urologist knows the urine cytology before you go to the procedure room. Likely days or a week or two before.
If urine positive for cancer cells then you are either an IR or an NR. As such, they can say to the patient, "if you want, given that you are going to procedure room, we can do one more treatment". Most would say "why not". That means that your 3 month IR and NR's are going to get a 2nd treatment at 90 days quite often. Versus now when you may just opt out of study and not bother with waiting till 6m scope and maintenance treatment. So they are now keeping a lot of the 90 day dropouts in the study. And converting some of them to CR or IR by doing two treatments back to back.
So in many ways, the change in protocol is really a way to try two treatments at the early part of the study. One at day 0 and one at day 90. Then you get maintenance at day 180 so some will get 3 treatments. All the better. Some cancer treatments are more likely to work if you have a chance to repeat a few times to chase down the last cancer cells.
This is the big reason for the change in my opinion.
There are not really that many that flip CR to NR later in study. The big drop off is from day 0 to 90 (the ones that didn't go CR at all). The new study protocol variation does allow you to offer a second maint treatment to the 270 day and 360 day people if they want. Again, you will usually know the cytology in the urine BEFORE you go to the procedure room.
The ones that are NR early on are getting one more "why-not" treatment at 90 days.
I realize I'm stating the obvious but it was not obvious to me until I thought about it sequentially.