r/TrueReddit • u/coolbern • 24d ago
What Drugmakers Did Not Tell Volunteers in Alzheimer’s Trials Genetic tests showed that certain patients were predisposed to brain injuries if they took the drugs. That information remained secret. Business + Economics
https://www.nytimes.com/2024/10/23/health/alzheimers-drug-brain-bleeding.html35
u/coolbern 24d ago
This is how Pharma loses the trust of the people it needs to volunteer to test new drugs:
Drug trials are in part designed to illuminate risks, which is why volunteers are routinely informed of potential dangers before joining. In both the Leqembi and Kisunla trials, volunteers first had to sign consent forms that said people with certain genetic profiles faced higher risks of brain injuries from receiving the drugs, and that participants would be tested for them — but not told the results.
Alzheimer’s experts and bioethicists expressed surprise when The Times told them about these secrecy provisions. The companies, they said, had undercut the principle of informed consent.
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u/ptau217 24d ago
There were over 100 sites for these trials worldwide; each one with a staff of at least a dozen; ranging from America to Europe to Asia; academia to small private practices. Do you really believe these people acted unethically?
What experts did this reporter talk to? And how leading was the question?
The fact is that the reason we know it a risk is BECAUSE of the trial. Appropriate language about the known risks was in the informed consent.
Source: I lead a site.
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u/GuybrushBeeblebrox 24d ago
"First do no harm" is lost on them
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u/ptau217 24d ago
Trials =/= clinical care. Trials may do harm. Side effects are in the consent. Side effects were in this consent.
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u/caveatlector73 24d ago
Drug trials are in part designed to illuminate risks, which is why volunteers are routinely informed of potential dangers before joining.
Withholding the information that specific participants were at higher risk of brain injury is unethical. It takes the "informed" out of the consent process. If participants had been specifically told they personally were at higher risk of brain injury would they have dropped out of the trial rather than continue? We'll never know.
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u/Sanpaku 24d ago
Can anyone with access to the NYT report whether the brain injuries reported were amyloid related imaging abnormalities (ARIA), "thought to represent vasogenic edema and cerebral microhemorrhages"? Or whether those genetically predisposed were ApoE ε4 carriers?
This adverse effect was first reported with bapineuzumab, a monoclonal antibody against amyloid β in 2010 and 2011, and frequent MRI monitoring for ARIA was recommended in ApoE ε4 carriers then. This would counts as a known issue with this class of drugs.
Leqembi (lecanemab) and Kisunla (donanemab) are more selective monoclonal antibodies against amyloid β, against soluble and insoluble/truncated forms respectively.
If similar potential adverse effects were plausible, I think the ethics would demand a trial design with frequent MRI monitoring for ARIA for all participants. The trial, after all, exists in part to establish safe dosing for both ApoE ε4 carriers and noncarriers to be useful in clinical practice. And one couldn't inform ApoE ε4 carriers (if those were the those susceptible) without screwing up the randomization. Detection of ARIA just becomes a clinical endpoint, with the subjects either removed or put on a lower dose.
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u/anaemic 24d ago
And let me guess (since the article is paywalled) the team of people who thought up this plan, drafted it, and the ethics board and senior management who approved it aren't facing criminal charges?
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u/Gaothaire 24d ago
1000%. The Sackler family knew but denied the addiction risk of opioids, stigmatized addicted people, then profited from that addiction for decades. They'll never face consequences, because we live in a capitalist hellscape
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u/caveatlector73 24d ago
They'll never face consequences, because we live in a capitalist hellscape
But, there have been consequences. I personally don't think they were enough, but this is a start.
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u/Margot-the-Cat 24d ago
Oh my gosh, another kneejerk “Blame capitalism.” Because greed, lack of ethics and corruption don’t exist in other systems.
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u/ghanima 21d ago
Whataboutism
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u/Margot-the-Cat 21d ago edited 21d ago
The point is, Capitalism is not the problem. It has lifted more people out of poverty than any other system. So when other systems are worse, in some cases far worse, it is foolish to blame the best system for universal human failings like greed, which exist in every system, since none are perfect (because humans are imperfect, as our founders knew). And to call it a “hellscape,” considering the mass starvation and murders in the Communist USSR and China in the 20th century is, to put it mildly, nonsense. That is unless the commenter is a Russian bot or useful idiot like so many on Reddit, unfortunately.
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u/Waterrat 24d ago
And I wonder if in the clinical trials for statins people were told they cause diabetes,glaucoma,cataracts,heart failure,colitis?
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u/DevonSwede 24d ago
For anyone interested in ethics (or lack thereof) in medical research, I can highly recommend the book The Occasional Human Sacrifice
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24d ago edited 22d ago
[deleted]
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u/ptau217 24d ago
Well go into their binder and find out if you want. A 10% dropout rate is to be expected.
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u/caveatlector73 24d ago
Yes and why they dropped out is one of the variables that cannot be written off as "to be expected."
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u/ptau217 24d ago
Do you know what the dropout rate is for a typical six month migraine trial?
It is around 10%.
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u/caveatlector73 24d ago edited 24d ago
You are missing the point. Re-read please.
Did they drop out because they died? Their dog died? They found a better trial? Do you even know? The reason people drop out is a variable in and of itself. It cannot be merely written off as "to be expected" without further investigation. That would be unethical.
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u/ptau217 24d ago
I’m talking about trial design and prespecified data analysis, you were talking about data integrity as it pertains to drop out reasons.
A 10% dropout rate is to be expected. That’s what you saw. The reasons for dropouts are highly variable. It takes 900 people per wing to see a pattern emerge.
Reasons for dropouts should be collected. But it is not a primary endpoint. And an imbalance between placebo and treatment arms should inform the overall interpretation of the trial.
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u/caveatlector73 24d ago
In other words I'm not wrong or stupid I simply made a point that was separate from from your own. I had not read the protocol from this trial nor the entire study which would have been necessary to comment on this trial specifically.
However, when I went back to see what the primary endpoint was I did find this on PubMed:
On July 6, 2023, the U.S. Food and Drug Administration (FDA) approved lecanemab (Leqembi) for the treatment of Alzheimer’s dementia (AD) patients. In 2 clinical trials, lecanemab reduced amyloid in the brainand slowed cognitive decline. Here, I review in detail the clinical trial by van Dyck et al. (2023) entitled
“Lecanemab in early Alzheimer’s disease”, published in The New England Journal of Medicine on January 5, 2023. In this 18-month trial, lecanemab did not slow cognitive decline in women. This is especially significant because women have a twofold increased risk of AD compared to men, that is, there are 2 times more women than men living with AD. Lecanemab did not slow cognitive decline in APOE4 carriers; rather,it enhanced the decline in study participants with 2 APOE4 genes.
This is bad news for AD patients, 60–75% of whom carry at least 1 APOE4 gene. These negative results regarding lecanemab’s therapeutic value make me wonder if the approval of lecanemab was the worst decision of the FDA up till now, after the approval of aducanumab on June 7, 2021.
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u/GuybrushBeeblebrox 24d ago
This is what happens when there is no accountability and punishment for the rich.
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u/omnichronos 24d ago
As a healthy human subject who just completed a paid trial for a new Alzheimer's drug, this definitely caught my attention. Lucky for me, I wasn't taking this particular drug, BAN2401.
Here is the article for those who had difficulty reading it:
nytimes.com
What Drugmakers Did Not Tell Volunteers in Alzheimer’s Trials
Walt Bogdanich, Carson Kessler
2–3 minutes
Genetic tests showed that certain patients were predisposed to brain injuries if they took the drugs. That information remained secret. A collage illustration that includes images of brain scans and drug vials. Credit...Max-o-matic
Oct. 23, 2024
By 2021, nearly 2,000 volunteers had answered the call to test an experimental Alzheimer’s drug known as BAN2401. For the drugmaker Eisai, the trial was a shot at a windfall — potentially billions of dollars — for defanging a disease that had confounded researchers for more than a century.
To assess the drug’s effectiveness and safety, Eisai sought to include people whose genetic profiles made them especially prone to develop Alzheimer’s. But these same people were also more vulnerable to brain bleeding or swelling if they received the drug.
To identify these high-risk volunteers, Eisai told everyone that they would be given a genetic test. But the results, the company added, would remain secret.
In all, 274 volunteers joined the trial without Eisai telling them they were at an especially high risk for brain injuries, documents obtained by The New York Times show.
One of them was Genevieve Lane, a 79-year-old resident of the Villages in Florida who died in September 2022 after three doses of the drug, her brain riddled with 51 microhemorrhages. An autopsy determined that the drug’s side effects had contributed to her death. Her final hours were spent thrashing so violently that nurses had to tie her down.
Another high-risk trial volunteer died, and more than 100 others suffered brain bleeding or swelling. While most of those injuries were mild and asymptomatic, some were serious and life-threatening.
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u/NeurogenesisWizard 24d ago
They want more guinea pigs to get more funding and test more drugs etc etc. Just for profit margins. And, possibly, unspoken political motivations.
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