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***OFFICIAL CYDY/Leronlimab Thread*** (7 Viewers)
- Thread starter This_Guy
- Start date
Last academic posting (I promise). Here is a nice review of significant AEs seen with placebo arms in a variety of immunotherapy trials in cancer. In no way do they link these to the active therapy being more effective than placebo.
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2717560
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2717560
BassNBrew
Footballguy
adonis
Footballguy
I’mthe efficacy data is also good, just not basing it off of AE data!!
- not trying to give you a hard time, just truly curious how to look at it another way.I'm trying to understand a perspective that doesn't make it look like Nader is misrepresenting the results.
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I don't think it is a good thing, but even with a vaccine there will still be needs for treatment. People will still get COVID, especially in the short term.
Love the analysis. That is what is great about this board. So many people with so much knowledge in so many areas.
Thank you for sharing. Don't stop.
Polish Hammer
made of glass
One topic that's been discussed a lot lately is SAE and the relation to potentially considering that a measure for efficacy. The bottom line is you can't really know exactly how they are going to interplay. However, there could be commonality if you look at the things that the FDA considers to be an SAE and cross reference that with the list of items that were being scored for the primary outcome of the study. There's probably going to be some crossover between those lists, but there's no way to know for sure until they release the data whether or not that overlap is actually occurring.
caustic
Footballguy
So I know pretty much nothing about medicine — but from a pure statistical standpoint, I think your two-proportion test is as good as it gets for us laymen. Potentially making adjustments based on certain patients getting multiple SAEs would require medical expertise and more data, and I have neither.
Capella
Footballguy
adonis
Footballguy
Always enjoy the input. Serious question.
It was suggested earlier that SAE's would only be recorded if they could be tied to the drug.
If that's the case, how can SAE's be recorded for the placebo group? This is a double-blinded study. How can anyone involved who is scoring what constitutes an SAE has no idea who got the drug or not. This whole thing is complicated. So I have two questions:
1) If SAE's are only adverse events that can be attributed to the drug, how can anyone in the placebo group have an SAE since they're given only saline?
2) If the trial is double-blinded, how can folks assess whether an adverse event is related to the drug or not? Is this only done after unblinding?
⚡DEADHEAD⚡
Footballguy
I'll ask again. He's not the only dude in the room. Are they all buffoons? I don't think so. I think Kelly is a pretty sharp guy. Is he in constant damage control?
If I'm in management there, I observe that whenever NP does his shill-show, the stock price goes down. If I get fired, fine, then accelerate my options and I'll cash out and adi-effing-os.
This dude single-handedly has cost us millions and millions of dollars in market cap.
SENSATIZE
Charlie Harper
Footballguy
I hope the Stock Thread stays on the 2nd page. 2 threads is dumb.
drunken slob
Footballguy
Depends, are you in it for the Covid, or, the Cancer/HIV? I'm here for the latter. Covid success is just a small part of the overall LL picture, IMO
#notselling
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Charlie Harper
Footballguy
FDA Significant Adverse Events
Kudos to Polish Hammer for the link. I think this helps us infer if we could get anything from the significance of the SAE. I think in this case it can.
djmich
Footballguy
I'm settled on all we can deduce from the SAE data is that leronlimab doesnt cause SAE. If you notice, in the PR it specifically calls out that the SAE's were not caused by LL. It didnt say well because we observed less SAE than the placebo that therefore we can conclude it is safe. Similarly, if the LL cohort DID have more SAE's that on its own wouldn't mean it caused more SAE's.
In this case the whole reference to SAE%'s is not worth a conclusion and potentially misleading (although not necessarily intentionally misleading...data is data).
I am optimistic that there was some correlation, but assuming that is a leap. Fortunately not one needed to take once the efficacy data comes out (at least until we encounter the data saga sure to come with that)
Confusing, yes.
In this case the whole reference to SAE%'s is not worth a conclusion and potentially misleading (although not necessarily intentionally misleading...data is data).
I am optimistic that there was some correlation, but assuming that is a leap. Fortunately not one needed to take once the efficacy data comes out (at least until we encounter the data saga sure to come with that)
Confusing, yes.
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Good question:
1) That’s the difficult part, but the article linked explains how placebo arms can have AEs. It is was one way to tell if an AE is related to a drug though. Let’s say we saw significant hypertension with Len, but saw the same rated in the placebo group. That AE would likely be attributed to factors besides Len (such as disease process).
2) That is usually why investigators usually attribute to a drug, unless clearly not related, and why they are saying not drug related is a big deal. What you are looking for are differences between the two arms. Let’s say Len caused neutropenia in 50% of patients and placebo caused neutropenia in 15% of patients. In each case we would attribute to drug or not when still blinded, at unblinding we would note the difference and say Len caused neutropenia in patients.
Chaz McNulty
Footballguy
Great posting. So if we assume that the event is not being hit by a bus, and the event is something like having to go on breathing support, then the SAE's could technically spill over into other outcomes of the study. A patient needing breathing support will probably remain hospitalized longer than one that doesn't.
I think there is definitely a relationship with SAE's and some of the endpoints.
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djmich
Footballguy
I think the only thing worth calling out is that this implies an SAE occurs only if it is associated with the medical product. I think there are SAE's and then SAE's that can be associated with the product.
There were a bunch of SAE's from the placebo...no way the placebo caused them.
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Don't Noonan
Footballguy
What is an SAE?
djmich
Footballguy
Penguin
Footballguy
adonis
Footballguy
Thanks for the response. Helpful to talk this through, and by all means i'm not saying i'm right, just trying to think through stuff.
My central point is that what seems to be happening is during the course of the trial, patients are self-reporting SAE's or they're being recorded by the doctors. At the time, they're double-blinded so they're just recorded as a patient having a bad adverse affect that seems related or noteworthy. To me, the fact that this self-reporting, or reports by doctors for patients in the leronlimab wing is 'significantly' (my word) less than in the placebo group, indicates to me that individuals receiving leronlimab experienced as a whole fewer adverse effects to report.
Once the trial is unblinded, or people authorized take a peek and categorize the SAE's, they looked at the ones attributed to patients in the leronlimab wing and decided that NONE of the reported SAE's were truly related to leronlimab.
So you have a ton of SAE's reported in the placebo group, where no drug was given but saline. These are bad effects people have. Then in the leronlimab group, LESS folks have bad side effects, and of those that do, none are related to leronlimab.
To me, that not only shows the safety of leronlimab, but the difference in SAE's seems relevant. If 2 populations are given different shots, and one group that's double the size of the other ends up having fewer reports of people feeling ####ty, that seems important.
Again, i'm not shutting you down...i'm presenting this view to see where the weakness is and to get further feedback.
Zegras11
Footballguy
All true, trials are just not statistically designed that way! AEs are drug related not necessary disease related - though I agree there is some common sense correlation.
AEs being looked at are if the drug causes harm to a patient. It doesn’t mean if a COVID disease related symptom gets worse (decreases O2 sats or something like that) compared to placebo.
BassNBrew
Footballguy
adonis
Footballguy
This makes sense. That's likely why no p value was released, because there's no level of significance for this evaluation.
However, I think if you were to see 90% SAE's for say, shortness of breath in a placebo group, and 10% shortness of breath in a population twice that size given a drug, you could form some conclusions about whether the drug helps prevent that symptom. And I would think there would be some level at which those differences are statistically significant, based on the specifics of the SAE's being compared between the groups.
But simply comparing generic SAE's from one group to another doesn't provide sufficient information to get any level of confidence (literal), however it can be highly suggestive if the total number of SAE's appears to be 'significantly' less in the drug group than the placebo group.
fred_1_15301
Footballguy
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Capella
Footballguy
Capella
Footballguy
Those guys are all scientists I thought. I figure they’re being sciency and figure they don’t know more about PR than them the CEO.
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Insoxicated
@pmedina @Polish Hammer @Whyatt
1) is it normal for safety data to come out in advance of efficacy data like this?
2) if YES: how long typically until efficacy follows?
3) If NO, what are plausible reasons why they would crunch/release data in this order in this case?
Thanks!
1) is it normal for safety data to come out in advance of efficacy data like this?
2) if YES: how long typically until efficacy follows?
3) If NO, what are plausible reasons why they would crunch/release data in this order in this case?
Thanks!
FreeBaGeL
Footballguy
Right, I think we're all in agreement here. Even if the SAE study is meant to only be used for measuring safety, just by logical deduction it can give us some clue to potential efficacy.
If 2000 terminal brain cancer patients are split in half for a test of a drug vs. a placebo and all 1000 of the patients getting the placebo have an SAE (ie death) and 0 of the patients getting the drug have an SAE we can pretty logically deduce that the drug is majorly effective, even though technically that is not what that study was designed to tell us.
Obviously those are hyperbolic numbers compared to what we're talking about here but the underlying point remains the same, it is at least worth looking at the numbers we have to determine if there is a statistically significant difference of 5/56 vs. 8/29 or whatever the numbers are as a way to potentially make a guess on efficacy results prior to the real ones being released.
If 2000 terminal brain cancer patients are split in half for a test of a drug vs. a placebo and all 1000 of the patients getting the placebo have an SAE (ie death) and 0 of the patients getting the drug have an SAE we can pretty logically deduce that the drug is majorly effective, even though technically that is not what that study was designed to tell us.
Obviously those are hyperbolic numbers compared to what we're talking about here but the underlying point remains the same, it is at least worth looking at the numbers we have to determine if there is a statistically significant difference of 5/56 vs. 8/29 or whatever the numbers are as a way to potentially make a guess on efficacy results prior to the real ones being released.
adonis
Footballguy
I wasn't asked, but anyone with basic math skills and access to the SAE data could've released these results within a day. That's almost certainly why they were released first. I can't comment on what's normal, but in this case they likely wanted something out and this was easy to compile.
FreeBaGeL
Footballguy
Yeah I mean it seems pretty obvious we are talking about one of two scenarios here.
1) "Oh crap NP said we'd have something out on Tuesday and it's not ready yet, but the safety data is easy to do so let's just do that real quick to give them something to chew on".
Or
2) "Oh crap the efficacy data is horrible this is going to suck. But the safety data is good so let's release that first to ease people in".
Let's go #1.
1) "Oh crap NP said we'd have something out on Tuesday and it's not ready yet, but the safety data is easy to do so let's just do that real quick to give them something to chew on".
Or
2) "Oh crap the efficacy data is horrible this is going to suck. But the safety data is good so let's release that first to ease people in".
Let's go #1.
The primary objective of a phase II trial is efficacy. You typically wouldn’t release secondary objectives first because the trial was designed to answer the primary objective (efficacy)
As for the time, not sure with an ID treatment, in cancer efficacy can take months to evaluate. Based on what I know, in a disease like COVID this should be MUCH quicker since the efficacy endpoint (better from COVID or not) occurs much quicker.
sorry, ID = infectious disease
Chaz McNulty
Footballguy
So how does the placebo cause harm? And it seems that Cytodyn is saying that none of their SAE's are drug related.
I think that SAE's are negative events period.
Don Hutson
Footballguy
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dkp993
Footballguy
adonis
Footballguy
The fact that NP went on a paid spot today basically whining shows that at least he is feeling pressure.
I think the problem is that the skills that got him and the company this far, are not the skills required to take it to the next level. Either he has to adjust and find another speed that's less reactive to daily sentiment and step up his PR game, or he'll be golden parachuted out to make way for someone who can. No ill will go NP...seems like a great guy. I've been in jobs where what got me to one level wasn't necessarily working for me once I got there and in some cases it didn't work out, and in others I found a new speed that worked better for me and the position. NP needs to adjust if he's able.
PennState-JD
Footballguy
So it looks like several will get their wish— uplist to Nasdaq before getting significant news. My take is that a skip or Phase 3 was a Hail Mary, so here we are with a likely move to Phase 3 with expanded samples that provides more confidence that the results do not occur by chance. Increases the risk of another company beating them to the punch, but those same companies are going to have to jump through the same hoops. Thinking this goes on a couple more months but the science seems sound. Still multiple indications in play.
Read the JAMA article. Placebos have a long history of causing adverse effects.
Agree on the second point. SAEs are typically negative! Though I could link to some super nerdy stuff with immunotherapy treatments that suggest higher AEs actually suggest the drug is working in diseases such as melanoma.
adonis
Footballguy
They are...but they're negative events baselined by the prevalence of negative events in the placebo category. The discussion above made that dawn on me.
The example was that if placebo had 10% high blood pressure SAE, and the drug group also had 10%, it's unlikely the drug caused it. If it was 10% placebo, 50% drug group, drug group likely increased likelihood of the high blood pressure SAE. And if the drug was 0% and placebo 10%, seems reasonable to question whether the drug lowered it or not, but that part of the trial isn't set up to make a judgment on that. That part comes in the efficacy portion.
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Chaz McNulty
Footballguy
