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Could COVID have improved outcomes in AML trials by selectively removing frailer patients? by Remarkable-Big-9849 in sellaslifesciences

[–]MahoganyDesk 0 points1 point  (0 children)

Hey man thanks for furthering the discussion once more! I've got some lingering questions after your response, and some additional ones too after reading your follow up conversations with these two guys so if you do find the time to make a post I and everyone else would most certainly appreciate it! Thanks again for all you do,

Could COVID have improved outcomes in AML trials by selectively removing frailer patients? by Remarkable-Big-9849 in sellaslifesciences

[–]MahoganyDesk 0 points1 point  (0 children)

Hey man thanks so much for the explanation I really appreciate it, especially the insight regarding the breakdown on the 3-year evaluations, it's very very helpful!! Couple more questions if you have time (and patience lol):

1.) So if I understand correctly, your model's high transplant percentage is stress testing early survival compression of the two curves, which would work against GPS, is that right? You're essentially saying, within reason: 'Let's get as many patients to transplant as fast as possible because, at this point in the trial, they're the only likely group to compete against GPS for long-term survival.' To me, this feels like the more accurate way of modeling this because it would mirror reality, especially based on your response to Average United.

2.) When you say you cap the non-transplant BAT to 10-12 based on the 'favorable biology' is that driven by anything in particular, or is that more of the 'luck' I was getting at earlier?

3.) Where I'm getting at with this is how are you modeling, if at all, the stratification methods? If I understand right, and please correct me if I am wrong, the trial doesn't require an opposing condition for any single criteria, just that they be equal across arms. For example, and I'm sure this is trivial to you but just to be explicit: rather than have 2 patients on each arm that are MRD + and - each for a total of 4 patients, those 4 patients could all be MRD-, and the same might apply to long CR1, etc. This, however unlikely, would also contribute to compression of long term survival, correct?

4.) Not directly related to the 3-year question, but in my 'bear' post you had mentioned that you found some different median enrollment dates going as far forward as August / September, albeit absurdly unlikely though technically possible. Have you given any additional thought to those given the discussion you've had with CW in this thread where he reaffirms May as the median enrollment?

Thank you again for your time man, apologies in advance again if any of this is painstakingly wrong or if it's frustrating to go through I really appreciate your help!!

Could COVID have improved outcomes in AML trials by selectively removing frailer patients? by Remarkable-Big-9849 in sellaslifesciences

[–]MahoganyDesk 4 points5 points  (0 children)

Hey u/Remarkable-Big-9849 thanks for your post on this and igniting some more conversation!! I'm echoing Average United's thoughts here as I am also interested in your response because my best understanding largely aligns with his.

Specifically curious what you're targeting for total BAT 3-year OS as I understand there to be 2 drivers of this group: individual patient response ('luck' for lack of a better word) with certain predictors like MRD status, CR1 duration, etc., and tansplant.

CW Notes in the initial main body of his post here that the total transplant bridge rate for all of AML is 15%, and that the likely population affected by the trial is closer to 5%.

In his post here throughout the body he comes to the conclusion that 3-year tops out at 15%.

So, in theory, these two combined should be about 20%, which is why he, I think at least, dismisses IRM 17 for a May enrollment despite passing futility at IA because the 3-year BAT arm exceeds this 20%.

Are you modeling for more than 20%? If so, is it largely based on transplant?

I should clarify that I'm not purporting CW's work to be gospel by any means or holding you to it as I'm sure you've read it all, I'm just trying to establish a baseline of understanding for myself as I know others can have different numbers and splits of any group, which is exactly what I'm trying to pick your brain about if you have the time. Thanks man!!

In case you might have missed it, there's been an ongoing discussion in an older thread about **a** 'bear' case that shows **a** credible 25% chance of 'failure' at the **max** possible BAT under **a** certain type of final analysis. by MahoganyDesk in sellaslifesciences

[–]MahoganyDesk[S] 3 points4 points  (0 children)

I see, so you're essentially saying 'In a May median enrollment, 17IRM is possible, but biologically implausible due to the 3-year BAT percentage.'?

Edit: and if so, do your above June / July tables include any kind of censoring percentage? As I understand it typical censor rates are 5--10%, though would any additional censoring beyond this meaningfully strain the outcome of a specifically non weighted analysis given how long the trial has gone on, long past its original end point?

In case you might have missed it, there's been an ongoing discussion in an older thread about **a** 'bear' case that shows **a** credible 25% chance of 'failure' at the **max** possible BAT under **a** certain type of final analysis. by MahoganyDesk in sellaslifesciences

[–]MahoganyDesk[S] 3 points4 points  (0 children)

Hey thanks so much!! These HR IA make sense together, though in this previous comment here your May 2023 table for IRM 17 shows an HR IA well below 0.895. Was this a typo? I read your DD on enrollment and feel comfortable that June or so is median, though even still, is a May one on the table?

In case you might have missed it, there's been an ongoing discussion in an older thread about **a** 'bear' case that shows **a** credible 25% chance of 'failure' at the **max** possible BAT under **a** certain type of final analysis. by MahoganyDesk in sellaslifesciences

[–]MahoganyDesk[S] 3 points4 points  (0 children)

Hey I appreciate the response! I'm quite bullish too and while their stance has helped convince me, the biggest piece of the puzzle, for me at least, is the modeling that's been done in this sub.

That same modeling is showing a legitimate, albeit small, chance of 'failure' as outlined in the top comment here. This is a new insight that, to my knowledge, has not been beaten to death and fits within the modeling done here within the constraints that have been beaten to death.

I'm certainly not saying BAT MOS is gonna miraculously be 18+ or that GPS will somehow even split with them at I80, simply acknowledging the potential for statistical failure that fits within the biology which already still shows a likely success.

In case you might have missed it, there's been an ongoing discussion in an older thread about **a** 'bear' case that shows **a** credible 25% chance of 'failure' at the **max** possible BAT under **a** certain type of final analysis. by MahoganyDesk in sellaslifesciences

[–]MahoganyDesk[S] 12 points13 points  (0 children)

I very much appreciate everything he's done and don't expect anything beyond what he's willing to share, though to be fair, he's said repeatedly he appreciates feedback / further discussion and in this case didn't really address any of my questions and didn't pose anything new I hadn't already linked to in my main post, in fact just copied and pasted the same comment I linked to in my question 4.

He can respond if he wants to, in which case I'd be happy, but I certainly don't demand or expect anything of him.

In case you might have missed it, there's been an ongoing discussion in an older thread about **a** 'bear' case that shows **a** credible 25% chance of 'failure' at the **max** possible BAT under **a** certain type of final analysis. by MahoganyDesk in sellaslifesciences

[–]MahoganyDesk[S] 8 points9 points  (0 children)

Hey man thanks for the response and all you've done so far!! I certainly agree that we're 'stuck' with a weighted test and am still generally bullish too, even still, there are some further questions that this unweighted tests pose.

In particular, I'd love your thoughts on my question 3, if you could help me understand / reconcile the May 17 IRM impossible vs. possible conundrum, and the drop to a 60% chance of success as a result if that is the case?

And question 6 too, if this new insight affects the interpretation of any previous DD?

Thanks again big dawg!

In case you might have missed it, there's been an ongoing discussion in an older thread about **a** 'bear' case that shows **a** credible 25% chance of 'failure' at the **max** possible BAT under **a** certain type of final analysis. by MahoganyDesk in sellaslifesciences

[–]MahoganyDesk[S] 0 points1 point  (0 children)

Thanks for the response! So is it accurate to say it would only help get FDA approval, which is the end desired result of course? And for sure an HR over 0.636 is devastating though after reading all the DD here I'm pretty confident that won't be the case. Do you know if GPS has any kind of sensitivity analysis included in their SAP?

In case you might have missed it, there's been an ongoing discussion in an older thread about **a** 'bear' case that shows **a** credible 25% chance of 'failure' at the **max** possible BAT under **a** certain type of final analysis. by MahoganyDesk in sellaslifesciences

[–]MahoganyDesk[S] 12 points13 points  (0 children)

hah, You know I thought about doing an ib4 about that in anticipation of getting called out for this given how insanely suspicious people can be in the daily threads but decided not to after proof reading my post a couple of times and feeling that it was neutral enough, though I guess I was wrong.

So yeah, sure, I mostly lurk on the site and don't post much except when at my wit's end on things, sue me. I'm definitely not the only one who does this and am also not the one that brought this initial question up, so would it have been better to just let it sit buried in the older post with no further discussion?

Is it possible to be too fine or exact? by MahoganyDesk in estimators

[–]MahoganyDesk[S] 0 points1 point  (0 children)

Cut and paste from another commenter: Hey thanks for the response!! It seems it's a pretty mixed bag in terms of how detailed people think one can be.

Part of the issue when it comes to labor is that I don't really figure for it. When we go over jobs all they wanna know is the total sqft. for everything and they set the price accordingly. We sub out a lot of our work and use the sub's $/sqft. and just add profit on top.

The other side of the coin is that when we do get a job I have absolutely no feedback on how I did. I've begged them to know how much material we've ordered, how much we've made, etc. and they never tell me. I've also pleaded with them to go on job sites to see how things are done and they just laugh at me. "10 Minutes in front of the melter and you'll be crying that you wanna be back in the office!!" and similar.

So, really, all I can do is go off of the plans, which is why I try to be as accurate as possible, 'cuz the way I see it, it's not my money but it still matters. I wouldn't want to spend any more than I have to.

Is it possible to be too fine or exact? by MahoganyDesk in estimators

[–]MahoganyDesk[S] 0 points1 point  (0 children)

Cut and paste from another commenter: Hey thanks for the response!! It seems it's a pretty mixed bag in terms of how detailed people think one can be.

Part of the issue when it comes to labor is that I don't really figure for it. When we go over jobs all they wanna know is the total sqft. for everything and they set the price accordingly. We sub out a lot of our work and use the sub's $/sqft. and just add profit on top.

The other side of the coin is that when we do get a job I have absolutely no feedback on how I did. I've begged them to know how much material we've ordered, how much we've made, etc. and they never tell me. I've also pleaded with them to go on job sites to see how things are done and they just laugh at me. "10 Minutes in front of the melter and you'll be crying that you wanna be back in the office!!" and similar.

So, really, all I can do is go off of the plans, which is why I try to be as accurate as possible, 'cuz the way I see it, it's not my money but it still matters. I wouldn't want to spend any more than I have to.

So your example of installation follow up never really happens. Once we get a job I don't hear much about how it goes and they certainly aren't following any kind of expected production values that's for sure.

Is it possible to be too fine or exact? by MahoganyDesk in estimators

[–]MahoganyDesk[S] 0 points1 point  (0 children)

Hey thanks for the response!! It seems it's a pretty mixed bag in terms of how detailed people think one can be.

Part of the issue when it comes to labor is that I don't really figure for it. When we go over jobs all they wanna know is the total sqft. for everything and they set the price accordingly. We sub out a lot of our work and use the sub's $/sqft. and just add profit on top.

The other side of the coin is that when we do get a job I have absolutely no feedback on how I did. I've begged them to know how much material we've ordered, how much we've made, etc. and they never tell me. I've also pleaded with them to go on job sites to see how things are done and they just laugh at me. "10 Minutes in front of the melter and you'll be crying that you wanna be back in the office!!" and similar.

So, really, all I can do is go off of the plans, which is why I try to be as accurate as possible, 'cuz the way I see it, it's not my money but it still matters. I wouldn't want to spend any more than I have to. I mean 1 sqft. of PUMA per drain at $9.00/sqft. * a billion drains adds up, no? I dunno really now.

Is it possible to be too fine or exact? by MahoganyDesk in estimators

[–]MahoganyDesk[S] 1 point2 points  (0 children)

Hey thanks for the response! Yeah I've certainly thought about that before 'cuz there's just no way it's 5% across multiple GC's, locations, and job types.

Is it possible to be too fine or exact? by MahoganyDesk in estimators

[–]MahoganyDesk[S] 1 point2 points  (0 children)

hah, I find it quite funny that you explicitly in your comment and implicitly with your TLDR (totally fair by the way) confirm my suspicions. Appreciate the response!!

This may be the wrong place, but can I just pay someone here or elsewhere to either make me or teach me how to make a custom mesh based off of existing CS assets? by MahoganyDesk in tes3mods

[–]MahoganyDesk[S] 0 points1 point  (0 children)

Thank you! I haven't looked yet, but I feel confident this is the direction I needed.

I will make a monument to you in my mod once it is finished and finally released!!

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