ryanc97
Senior Member (Voting Rights)
Oh I agree. I just find it relieving that he tried Dara on 5 patients and says 4 has improvements. How exactly, we wont know, but still.
Teclistamab for ME/CFS
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Utsikt
Senior Member (Voting Rights)
I don’t think you understand what I’ve been saying, but I won’t bang on about it more than this: we can’t know if there was an improvement, and we can’t know if dara caused it. The data is very unreliable and any effect might be purely bias and confounders. It might even maks a negative effect of the drug for all we know.
someUsername
Established Member
A few Points,
0) is there evidence that he wants to enrich himself? He has an onkological clinic, He could Just do His everyday Work and be fine.
I think what he does is a good way to get a sued and lose money or worse.
Also from His Twitter it seems Like He tries to prescribes things via insurance and then hassels with the insurance company.
He Just seems Like a crazy, overconfident guy, who is willing to take risks, and does not Care about spelling. And I mean this positive. I think the enrichment is more emotional and Not monitary.
i)Teclistamab has evidence to Work for (other?) autoimundiseases.
E.g.
sonntagsvorlesung.charite.de
pmc.ncbi.nlm.nih.gov
It is further similar to Dara as in that It also Targets LLPC.
And is usually given in cancer patients after a CD38 mab has been tried.
So there is some reasoning behind it, and its Not some crazy baseles Experiment.
ii) concerning consent: As I mentioned before, different people have different "Personal cost functions". Data for Tecil risk is available, and currently It seems that people go to Habets especially because they want these kind of treatments, and we can not just assume that their consent is "not real".
People do all kind of dangerous things to have mundane and fleeting benefits: to get some short Adrenalin kick, to have some fun, to impress someone etc.;
it is plausible that there are people willing to take a risk to get even a small chance to get rid of something that literally sucks life dry for years and years.
iii) concerning the data:
Above all, I do not think that he gives Tecil to people with the goal to collect data, this would be (inspired but) unethical.
You should only give Treatment to a Patient If you think that the expected outcome for that Patient will be positive.
Collecting Data is an add on.
The Claim that the Data is unusable and the Arguments given for that Claim are unconvincing for me.
The cyclo trial begun by annecdotal evidence. Some people did Chemo, felt better, and reportet: I feel better.
This is def Not great Data - but It was enough to indicate further investigation.
Of course you can argue here that there was less reason for Placebo in the Cyclo case because people were Not expecting to get better, but there are other ways in which this Data is "muddy".
I think we Just really need to have a good Prior with which we Interpret this Data -- because we simply are not in a position to do science from the Ivory Tower.
0) is there evidence that he wants to enrich himself? He has an onkological clinic, He could Just do His everyday Work and be fine.
I think what he does is a good way to get a sued and lose money or worse.
Also from His Twitter it seems Like He tries to prescribes things via insurance and then hassels with the insurance company.
He Just seems Like a crazy, overconfident guy, who is willing to take risks, and does not Care about spelling. And I mean this positive. I think the enrichment is more emotional and Not monitary.
i)Teclistamab has evidence to Work for (other?) autoimundiseases.
E.g.
Press: Charité – Universitätsmedizin Berlin
Information on the range of services at Charité – Universtätsmedizin Berlin for patients, physicians, students and scientists
sonntagsvorlesung.charite.de
Teclistamab‐Induced Remission of Chronic Immune Thrombocytopenia in a Patient With Multiple Myeloma - PMC
We report the case of a 76‐year‐old woman with refractory immune thrombocytopenia (ITP) and multiple myeloma (MM) who achieved remission of both conditions following teclistamab treatment. After failing multiple ITP therapies, her platelet count ...
pmc.ncbi.nlm.nih.gov
It is further similar to Dara as in that It also Targets LLPC.
And is usually given in cancer patients after a CD38 mab has been tried.
So there is some reasoning behind it, and its Not some crazy baseles Experiment.
ii) concerning consent: As I mentioned before, different people have different "Personal cost functions". Data for Tecil risk is available, and currently It seems that people go to Habets especially because they want these kind of treatments, and we can not just assume that their consent is "not real".
People do all kind of dangerous things to have mundane and fleeting benefits: to get some short Adrenalin kick, to have some fun, to impress someone etc.;
it is plausible that there are people willing to take a risk to get even a small chance to get rid of something that literally sucks life dry for years and years.
iii) concerning the data:
Above all, I do not think that he gives Tecil to people with the goal to collect data, this would be (inspired but) unethical.
You should only give Treatment to a Patient If you think that the expected outcome for that Patient will be positive.
Collecting Data is an add on.
The Claim that the Data is unusable and the Arguments given for that Claim are unconvincing for me.
The cyclo trial begun by annecdotal evidence. Some people did Chemo, felt better, and reportet: I feel better.
This is def Not great Data - but It was enough to indicate further investigation.
Of course you can argue here that there was less reason for Placebo in the Cyclo case because people were Not expecting to get better, but there are other ways in which this Data is "muddy".
I think we Just really need to have a good Prior with which we Interpret this Data -- because we simply are not in a position to do science from the Ivory Tower.
someUsername
Established Member
He is the opposite of a good data source. Even to a layman it becomes instantly apparent that he has absolutely no idea what he is doing, that includes no idea about any drugs he uses and even dosages. I don't know those things either, but I certainly would want my doctor to. He is a collection of all the nonsense that trends on Twitter and that's pretty apparent because we only posts whatever nonsense is currently trending on Twitter. If you have a doctor that is risk friendly the lowest standard you'd want is that he still at least knows what he's doing.
ryanc97
Senior Member (Voting Rights)
Do you have the X tweet where he says the effect is not long lasting for Dara? Also, I find it interesting he first tweeted about Dara in Oct 2023. This might have even before Fluge did it.
Regarding the whole data debate, it is like a beggar refusing a free meal because it is not a michelin starred restaurant. but everyone has diff views. Haha
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Utsikt
Senior Member (Voting Rights)
Intent is irrelevant, because his actions positions himself as a go to doc for anyone that wan’t to experiment. That will generate both material and immaterial value for him, off the backs of vulnerable and often desperate patient groups.
Which is why doctors have to hold back! They have taken an oath to first do no harm. A skydiving instructor has not. Big difference.
The Fluge and Mella Dara pilot study was public announced in 2022 and also started at around that time point. On S4ME there are mentions of anti-CD38 discussion going back to ~2000. He just seems to pick up whatever is popular in the internet, here are some of his tweets:
I think by this point it’s clear that he’s already said enough. Nothing is left to discuss.
Jonathan Edwards
Senior Member (Voting Rights)
It's more like a beggar refusing a tupperware box filled with what looks like sawdust laced with deadly nightshade. Most beggars get wise enough to pick and choose a bit.
I have been in this guys shoes with the first use of rituximab in rheumatic disease and no way would I have ever offered treatments like this. The priority was, indeed, that I had confidence that the treatment might be beneficial, but I had got peer review from four international immunology experts first, and had published my reasons.
someUsername
Established Member
I think there is an irreconcilable ideological difference.
I guess we both agree that given all Data we have we can give an possiblitly distribution of what the outcome of a Treatment might be - and this is in some sense a quite straight forward objective debate we can have.
But you do not seem to believe in the second distribution, the idividual cost function.
[
I am Not Sure If everyone is clear what I mean so I will explain a bit:
The expected value of a betting 1€ on 1000 coin Flips, or betting 1000€ on 1 coinflip is the same (0) and in that case I think It is easy to know the underlying possiblitly distribution. Since the expected value of both bets are the Same,
Which one you should prefere is entirly dependend on your cost function.
E.g. when someone holds you at gunpoint and demamds 1000€ from you, you should defenetly take the bet where you gambel 1 time for the 1000€, because than you will have a 50/50 Chance of surviving.
When on the other Hand your wife and Kids are going to leave you when they hear you lost 1000€ and nothing much in your life will improve if you win 1000€, then defenetly take the bet where you gambel 1€ a thousand times.
]
To make a sensible Decision about a Treatment (or anything in Life), you need more than Just the possiblitly distribution of outcomes, but you need a cost function that gives meaning to these outcomes.
So I dont know whats your prob distribution for dara or Tecil looks like, but I find it very difficult to make a judgement if Something makes sense or not, without considering what the cost of each Outcome (including No Treatment) for each person is.
What I mean to say, lets Just pretend to agree on some random (simplified) probability distribution and say: medication X has a 20% Chance of working, and a 5% Chance of Killing me, the alterntive beeing ~6yrs Till Treatment.
How can anyone except myself know If this is a bet I want to take ?
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Jonathan Edwards
Senior Member (Voting Rights)
Believe you me, I believe in that absolutely. I have had to handle the adverse effects of both disease and drugs in individual people over spans of twenty to thirty years. Many of them were the most important people in my life, whom I saw most often and knew best. Some died. Some survived in misery for a decade.
I have seen idiot colleagues trying out things with no good rationale for fifty years and I have seen a few colleagues (like Oystein Fluge) do things properly. The problem with getting things wrong is not just that it can be as bad as the disease but it also brings in guilt, regret, animosity, and all sorts of other causes of misery.
The reality is that 99% of these things do great harm and no good. Once in a lifetime I thought I had identified something that had better odds. I was lucky enough to be right but looking back, if I had known the effects it would have on just two of two hundred people I treated I might have pulled out.
The argument that people can hurt themselves if they want to doesn't wash for me. We are all together in this in mutual support, or should be. (Maybe some cultures don't even do that any more.) When things go wrong they go wrong for everybody.
My wife and I had five children. Four of them died. I do not need lectures about cost to the individual.
someUsername
Established Member
This was really Not meant this way, but rather Just trying to "formalize" Decision making informed by statistical physics/information theory.
It was Not meant as in you dont get suffering, and I surly dont want to Take it there, or believe this.
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Jonathan Edwards
Senior Member (Voting Rights)
Why not try real life instead?
Utsikt
Senior Member (Voting Rights)
@someUsername
It’s the easiest thing in the world to fool oneself. I suspect you’re vastly underestimating the risks and overestimating the benefits for a whole host of reasons. Your cost function is no good if it’s running on faulty data.
It’s the easiest thing in the world to fool oneself. I suspect you’re vastly underestimating the risks and overestimating the benefits for a whole host of reasons. Your cost function is no good if it’s running on faulty data.
Utsikt
Senior Member (Voting Rights)
(Edited to remove a reference to a now removed comment.)
Nobody are under any obligation to entertain anyones wishes with regards to unproven treatments.
Freedom of choice is always limited by other’s freedom. I understand the desire to try something, but I really hope anyone takes some time to at least consider the ethical and moral implications of asking someone that has sworn an oath to first do no harm, to enable someone to put themselves at a not insignificant risk of physical and mental harm.
JE has shared his personal experiences of testing what turned out to be a successful treatment, and the cost it had and still has for him. The expected cost of letting someone try any of these drugs is higher because they have a non-zero chance of not working and are just as dangerous.
Nobody are under any obligation to entertain anyones wishes with regards to unproven treatments.
Freedom of choice is always limited by other’s freedom. I understand the desire to try something, but I really hope anyone takes some time to at least consider the ethical and moral implications of asking someone that has sworn an oath to first do no harm, to enable someone to put themselves at a not insignificant risk of physical and mental harm.
JE has shared his personal experiences of testing what turned out to be a successful treatment, and the cost it had and still has for him. The expected cost of letting someone try any of these drugs is higher because they have a non-zero chance of not working and are just as dangerous.
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ryanc97
Senior Member (Voting Rights)
Anyway, we all have different utility functions, we weigh our costs and benefits differently. As such we all make decisions we think are +EV but under different perspectives.
But the main thing is, for me at least, if I see some positive evidence coming out of Habet's crazy Teclistamab trials, ethics aside, I will interpret it as more evidence that supports the underlying theory of Daratumumab, as BCMAs are another receptor on the surface of LLPCs and target it.
If it fails, then it would make the underlying theory less valid. So just need to wait for him to do this thing.
There is time value of money in finance, such as the rate you get from borrowing from a bank. There is time value here too, do you want to wait years before knowing the result of the phase II trial or do you want to experiment yourself right now with unclear data, knowing that the longer you wait you might risk worsening of your condition.
But the main thing is, for me at least, if I see some positive evidence coming out of Habet's crazy Teclistamab trials, ethics aside, I will interpret it as more evidence that supports the underlying theory of Daratumumab, as BCMAs are another receptor on the surface of LLPCs and target it.
If it fails, then it would make the underlying theory less valid. So just need to wait for him to do this thing.
There is time value of money in finance, such as the rate you get from borrowing from a bank. There is time value here too, do you want to wait years before knowing the result of the phase II trial or do you want to experiment yourself right now with unclear data, knowing that the longer you wait you might risk worsening of your condition.
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It’s not only that. Frequently trial results are not cut and dry clear. Suppose a trial shows a “medium risky” drug demonstrated 30% improvement for 40% of the patients. This level of improvement would likely be enough to get approved by regulators, but you still wouldn’t know whether it works for YOU. There is still a risk of taking it and getting no improvement.
Utsikt
Senior Member (Voting Rights)
You propose doing that with -mabs?
ryanc97
Senior Member (Voting Rights)
My plan would be yes, that for Ritux and Dara. I would have to do alot of research and putting papers into ChatGPT and then putting together a plan of action/protocol, pre treatment and during treatment. But I acknowledge it is very very risky. I have a suspicion Rituximab is more dangerous, just from the 20% adverse reactions in the P3 trial alone. But from my knowledge, depleting ABs is more risky than depleting B cells as in the latter, you still have some ABs around to fight infections.
I also understand that the more severe you are the riskier it is as you have a higher risk of a stronger side reaction to any drug. Why this is the case, I am not sure.
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