There are some post stating that "Tobi never performed more than 1%" in the Cayston Tobi trial. This is misleading.
Cayston and Tobi trial results were compared to PREDICTED results from a prior Tobi PIII trial. This statement above should say "Tobi never performed more than 1% better than prior Tobi PIII results." Based on TOBI prior PIII trial, the results were predicted for each cycle (day 28, 56, etc) and trial results are measured against these predicted results.
This is very different than saying that Tobi never performed more than 1%, implying relative or % change in FEV1.
In the Cayston Tobi trial it is no coincident that Tobi falls within +- 1-2% of the predicted result throughout the trial; Tobi results are expected to be consistent with prior PIII trial results. Trial integrity would be challenged if Tobi results had been significantly different than its historical results.
Also, non-inferiority trials agree on a margin or delta for which the test drug (Arikace) results can be less than the control drug (Tobi) and still be non-inferior. Given that, there are four possible outcomes from the Arikace Tobi non-inferiority trial:
1. Inferior. Arikcase results are less than the Tobi results MINUS the margin
2. Non-inferior. Arikace results are greater than the Tobi results MINUS the margin
3. Superior. Arikace results are greater than Tobi results PLUS the margin
4. Inconclusive. Results have too much variability.
The larger the margin, the wider the range for a non-inferior result, and higher hurdles for superior and inferior Conversely the smaller the margin the narrower the range for a non-inferior, and a lower hurdle for superior and inferior. Driving down a 6 lane highway - a large margin - is pretty easy. Driving down a narrow one lane road - small margin - ditch on the left is inferior and ditch on the right is superior.
In the Cayston Tobi trial margin was 4% relative change of FEV1 %predicted at Day 28.
Read the thread to see why windy is wrong, this particular post is just some additional information with respect to Cayston.
Cayston's performance in their comparator trial vs TOBI was 8% at end of 1st 28 on-days, and it then went below 0% at the end of the 3rd 28-off days. Do google images TOBI vs Cayston. The mean performance was 2%. The 8% and 2% were used to support approval.
TOBI's historical use in patient population was over 80%. We may see similar rates in the Arikace trial, which would support the expectation that TOBI's performance in the Arikace trial will never exceed 2%, with an average close to 0%.
Past Arikace trials support a FEV1 improvement at the end of the 3rd 28-off days over 4.5%, at least. That is magnitudes better than Cayston. Further, the open label study shows consistent efficacy over 6, not 3, full 28-56 cycles.
Not an assumption. Based on fact. FDA has very specific guidelines regarding non-inferior trials (comparator trials). In adition the industry is littered with presentations and opinions on non-inferior trial
Google "Guidance for Industry Non-Inferiority Clinical Trials" for the FDA guidelines. Google FDA non-inferior trials for literature that explains in common terms.
In addition, think about it. Tobi is the standard and proven drug, albeit with a resistance issues. It defies critical thinking to believe that Tobi showed only a 1% FEV1 % improvement at day 28.
BTW...I am long with a bunch of shares. IMO, the best way to protect investment is with lots of digging and research, a contrarian hypothesis, and due diligence. I have too many shares to leave it to guess, hope, intuition or a message board.