Logic, Math & Statistics

[huntingonthebluffs]

I have been around math and statistics most of my academic and adult life, including many years building computer models to estimate computer resource requirements based on large corporate businesses, subsidiaries, major projects, etc. These tools, of course, will only take you so far in arriving at the likely outcome. I know there are differences in regards to application to the process of developing and bringing a drug through the maze to the market and usually the deeper and wider analysis provides quality of the estimate of actual results. Of course, as can be expected, these efforts take time and can be costly depending on the level of accuracy desired. Don’t get me wrong, logic, math, statistical and numerical analysis, modeling etc. are indispensable in the world we live in today.

What I have seen is a very large percentage of the time just using a few pieces of data with logic or statistics to shortcut getting to an answer generally is error prone and can even result in catastrophic outcomes if used by itself. I observed shortcuts being taken much more often with highly intelligent people, where there was a strong tendency to use deductive logic and limited statistics with few basic variables versus doing or being able to do the hard work to understand more significant and encompassing variables / aspects of the work in hand. And of course there are many who will use inductive logic to develop a big picture of what will happen. Depending on cost, time and importance, the efforts likely include testing against simple, typical and detailed models as well as looking at the historical guide posts along the way and how well deductive and / or inductive logic has proven out in similar situations. And especially, the track record of those in the trenches providing inputs will often provide the guiding lights and a truer sense of the windage one should apply to his/her estimates. And of course, frequently those in management above those in the trenches will often try to manipulate the modeler by increasing or decreasing general variables, especially tweaking odds based on incentives.

So for my analysis, which I no longer try, am interested in or even able to indulge in the heavy math, I would look at the human inputs, and in the case of Imetelstat, that includes, Drs. Tefferi, Lane, Raza, Steensma and those on the boards helping us understand the power of the science, maybe especially those on the front line like Irish Trader’s John and others who have actually tried the drug in battling their hemo cancers and the many “recent” efforts (e.g. last 5 years or so) in lab research around the world. While I have been hardcore retired for 10 years, I still recognize how this can be expected to proceed from here simply, typically or with complexity. Given what we have heard from doctors, labs, patients, corporate executives, etc versus the manipulation coming out of the minds of the naysayers, I honestly can’t see any room for failure; only degrees of major success. Yes, only how massive will the results be in the battle against cancer and how effectively will the principals be able to deliver, improve and expand the use of imetelstat.

Yes, we know the FDA, Janssen/JNJ and Geron are applying all the logic, math, statistics, models and the like, but they also have “all the useful data / inputs” and know the likely windage gained from the CR/PR/CI’s, patients, labs, business minds, competitors, etc. and the areas where Imetelstat is strongest, where it will be most effective by itself or with other drugs, when and where mutations occur and where the line is that mutations can prevent Imetelstat from “doing it’s thing”, where the competition is and will likely move towards, what frontiers Imetelstat will likely achieve or not. Their chess game is thought out many moves beyond what we have and can do.

I believe the question in the minds of most patients though, many no longer with us, is what are the powers to be waiting for, hiding behind or motivated by for not acting? For the most part, everyone knows and expects some mistakes will be made, adjustments will be needed but for the sake of those in dire need, can they begin now making this drug generally available? That is what patients want! And how does continuing to drag this out, weigh against all those that have passed on that could have benefited? I’m glad that is not on my conscience. But I truly wonder, are they so risk adverse, unable / unwilling to act or think outside the box, maybe… Let’s hope and pray, not! It is way past time.

So then, once Imetelstat is approved for R/R MF and MDS, let them strive every day to improve the safety, efficacy and scope / coverage of Imetelstat, etc. Just take the first steps now! For me, the CD was never a question, it was always what efforts and speed will be applied after the CD to deliver Imetelstat to the many patients in need and then quickly proceed on to its many possibilities. So far I'm very disappointed and sad really at what should have been. I'm hopeful that will all change very soon.

I for one, am not holding my breath on how 3Q2018 unfolds. And honestly, I’m not trying to over simplify, but given the endless trail of progress and success, it comes down to: can the FDA/EMA, Janssen/JNN and Geron, screw up a two piece puzzle? In my opinion, impossible!

[tutt]

Thank you for your eloquence. May Imetelstat help millions sooner rather than later.

[huntingonthebluffs]

Thank you tutt for such a kind comment. Yes, definitely sooner rather than later! The "tick tock" of the clock drawing us closer to the CD and beyond is not the same "tick tock" the patients with terminal cancer are hearing.

While I must admit, it is certainly difficult at best to see how over the top confirmation bias such as mine could move the science or help here in any way. Yet it could possibly impact sentiment and in doing so might challenge others to prove it right or wrong. Either way that will only happen with new real data versus our manipulation of what has already been provided to us. Can it not be clearly said, that to date, putting the pluses and minuses on opposite ends of the scale can only justify the strikingly impressive views of those of us with confirmation bias.

In my view, looking at the scales today, I don’t see any situation under which JNJ would not continue and ramp up the CTs or the FDA/EUA to find the ways open to hurry this drug and science along while maintaining some semblance of regulator oversite?

While there is so much we don’t know, and what we do know opens the doors to many interpretations. Yet, in my view, most have a positive slant and even forexample in the fluid discussions re: a MF control arm versus ethical aversion, seems that however this turns out, the 4.7 arm has provided much meaningful information to both Janssen and the government agencies watching from their condescending perches. While the 9.4 arm provided much better results for most, maybe all, the 4.7 arm seems to me to have been much more ethical than a placebo and as soon as the results began to diverge the decision was made rather quickly to offer the option of the 4.7 patients switching to 9.4 was finalized and acted on. And so like this question on ethics, the answers coming from every page yet to be turned on the CT, we will be provided astounding highlights of findings that will change the direction of where we go with hemo cancer treatment regimens and show the way to the next segment of discovery for this amazing science. I wish blessings on all who are involved and have a role to play in making and bringing such potential to reality.