Three FDA Advisers Resign over Agency’s Approval of Alzheimer’s Drug(nytimes.com)
nytimes.com
Three FDA Advisers Resign over Agency’s Approval of Alzheimer’s Drug
https://www.nytimes.com/2021/06/10/health/aduhelm-fda-resign-alzheimers.html
6 comments
Unfortunately, this sort of experimentation will simply lead to much quackery. As it stands, there is no cure for dementia. Allowing every company to market their own "treatment" does not make the situation better. It only allows the companies with the slickest marketing to exploit the elderly (and their families who desperately want to feel they did "all they could"). All the while, real dementia research (controlled, scientific research) may actually slow down as people leave clinical trials because they already bought some medicine.
Dementia is a symptom of multiple different conditions, not a disease per se. Sometimes the symptom can be cured by treating the root cause.
For example, an elderly woman I know was experiencing dementia. Her physicians ran a series of tests and diagnosed a bone marrow disorder. The dementia was caused by lack of oxygen to the brain from insufficient red blood cell production. So they cured the dementia by administering periodic blood transfusions.
For example, an elderly woman I know was experiencing dementia. Her physicians ran a series of tests and diagnosed a bone marrow disorder. The dementia was caused by lack of oxygen to the brain from insufficient red blood cell production. So they cured the dementia by administering periodic blood transfusions.
So we make it free until verified. Problem solved, filters for frauds, prolongs a few lives, ends pointless suffering in others, and creates a huge block of efficacy data. Win/win
Right now it's worse than you state. Any completely unprovem acupuncture, herbal, chiropractic, homeopathic, etc treatment can get sold with basically no restrictions. Only medicine requires science. It's the worst of all worlds right now.
You also have to really struggle to convince me that there is an ethical case of banning someone from doing what they want with their own body.
I mean, you would probably say someone it is good to donate to medical research. You would also probably say it is good to volunteer for a medical study. But it's somehow wrong to give money to get the treatment? Makes no sense to me.
You also have to really struggle to convince me that there is an ethical case of banning someone from doing what they want with their own body.
I mean, you would probably say someone it is good to donate to medical research. You would also probably say it is good to volunteer for a medical study. But it's somehow wrong to give money to get the treatment? Makes no sense to me.
While it might be a struggle to convince you what you can or cannot do to your body, nobody but you should be compelled to pay for the materials. Given social or insurance based medical systems in most countries, the rights of the many win out.
Medical claims have a regulatory regime around them though, and alternative therapies are generally not allowed to make medical claims. This is not enforced as carefully as it should be in my opinion, but it definitely exists.
Sherwin Nuland wrote in his book "How We Die" that he really regretted getting experimental treatment for his brother who was dying of cancer. The side effects of the drugs were quite painful and his brother ended up dying anyways. He argued that people who are going to die should be allowed to die in the most peaceful and least painful way possible rather than gamble on some unproven treatment. That said, Alzheimer's is such a horrific disease that it's hard to imagine a peaceful or pain free death. People literally starve to death from "forgetting" the ability swallow. Sorry to hear about your loss. Nuland talked about euthanasia in his book as well. He gave an example of a professor who had Alzheimer's and decided to take his own life rather than wait for the disease to progress. Rather than forcing people like that to do that, Nuland believes palliative care and euthanasia has a role to play in such cases.
This drug has already failed to be effective, it's extremely expensive, and it has bad side effects that require periodic MRIs to check for brain inflammation.
If the amyloid plaque hypothesis is wrong (which it almost certainly is based on the failure of other drugs) the destruction if amyloid plaques is likely to be harmful to the brain with no benefit.
Looking this as a 1% chance of a cure is not really accurate because if this drug was really capable of completely curing Alzheimer's there is no way the existing trials wouldn't have found that.
The article also describes additional reasons why it is generally bad to approve drugs that most likely don't actually work.
If the amyloid plaque hypothesis is wrong (which it almost certainly is based on the failure of other drugs) the destruction if amyloid plaques is likely to be harmful to the brain with no benefit.
Looking this as a 1% chance of a cure is not really accurate because if this drug was really capable of completely curing Alzheimer's there is no way the existing trials wouldn't have found that.
The article also describes additional reasons why it is generally bad to approve drugs that most likely don't actually work.
There's a lot of great arguments presented in the article for why we shouldn't go "balls to the wall on experimentation". The drug costs $56k a year, can cause some severe brain bleeding and swelling, and requires regular MRIs which can put quite a strain (and cost) on the system. These are some significant negatives for a drug that hasn't been proven to be effective at all.
I think that makes the case for balls to the wall experimentation. Let whoever is interested and can afford it try this drug. If they have good results, lets cover it with medicaid. If not, try something else.
If we cut out regulations and trials and requirements and so on for what medical treatments people can try, then a bunch of stuff will be tried. Most of it will be bad, but some may show effect and we can iterate on that and get better medicines.
I don't advocate this style for every possible treatment. If we already have good treatments or if the illness isn't too bad, then we definitely should not risk things on trials. However, in this case, it is a disease that kills old people and we don't have any good treatments for it. Why not let people who want to experiment aggressively.
If we cut out regulations and trials and requirements and so on for what medical treatments people can try, then a bunch of stuff will be tried. Most of it will be bad, but some may show effect and we can iterate on that and get better medicines.
I don't advocate this style for every possible treatment. If we already have good treatments or if the illness isn't too bad, then we definitely should not risk things on trials. However, in this case, it is a disease that kills old people and we don't have any good treatments for it. Why not let people who want to experiment aggressively.
One problem is that it’s actually extremely difficult to derive meaningful information from data collected outside of the context of a clinical trial.
So you’d be giving greenlight to tons of fraudsters, exposing people to potentially way more suffering than their baseline disease causes, AND not learning anything from doing so.
So you’d be giving greenlight to tons of fraudsters, exposing people to potentially way more suffering than their baseline disease causes, AND not learning anything from doing so.
On top of that, we currently have a grossly overburdened healthcare system that in no way could support this. This presents so many clear problems that I wonder if the people are thinking critically about the long term effects of an unregulated drug market.
1. Knowledge -> How will doctors possibly keep track of the knowledge of all of these new drugs? If they don't need to be verified beyond a claim, they could be getting thousands of options. How do they pick between one drug with no proof, and another drug with no proof -- especially if they all have negative side effects?
2. Data -> All of the data for these drugs will be extremely if not impossible to derive. This will probably result in it taking even longer for evidence of the drug's efficacy to be built.
3. Resources -> Hospitals across North America are understaffed and overworked. How could they possibly find time to not only learn the entire treatment path for new drugs and all the necessary information, but to do this countless times across all their patients? MRI machines are already backlogged quite a bit, do we really think they could weather the storm of an unregulated drug market?
4. Liability -> Whether we like it or not, this adds quite a bit of liability to a hospital. Insurance will absolutely be against this, and would likely greatly increase the number of people trying to sue the hospital.
5. Fallout/Complications -> Can you imagine the strain of the additional complications that arise out of allowing free use of untested drugs? Imagine how much more expensive a patient would be if they got a brain bleed from a medication that they would never have had previously. This isn't just like "I tried a drug and it did nothing", it's more like "I tried a drug that had the potential to kill me. I had severe complications that required me to be in the hospital for 2 months but the drug still did nothing to help my problem."
Effectively, we'd be breaking our own healthcare system by breaking down our regulations. Regulations are written in blood. They're there for a reason.
1. Knowledge -> How will doctors possibly keep track of the knowledge of all of these new drugs? If they don't need to be verified beyond a claim, they could be getting thousands of options. How do they pick between one drug with no proof, and another drug with no proof -- especially if they all have negative side effects?
2. Data -> All of the data for these drugs will be extremely if not impossible to derive. This will probably result in it taking even longer for evidence of the drug's efficacy to be built.
3. Resources -> Hospitals across North America are understaffed and overworked. How could they possibly find time to not only learn the entire treatment path for new drugs and all the necessary information, but to do this countless times across all their patients? MRI machines are already backlogged quite a bit, do we really think they could weather the storm of an unregulated drug market?
4. Liability -> Whether we like it or not, this adds quite a bit of liability to a hospital. Insurance will absolutely be against this, and would likely greatly increase the number of people trying to sue the hospital.
5. Fallout/Complications -> Can you imagine the strain of the additional complications that arise out of allowing free use of untested drugs? Imagine how much more expensive a patient would be if they got a brain bleed from a medication that they would never have had previously. This isn't just like "I tried a drug and it did nothing", it's more like "I tried a drug that had the potential to kill me. I had severe complications that required me to be in the hospital for 2 months but the drug still did nothing to help my problem."
Effectively, we'd be breaking our own healthcare system by breaking down our regulations. Regulations are written in blood. They're there for a reason.
Yeah, the level of thought behind proposals like this leaves something to be desired. Benefit of living a life downstream of a mostly functional drug safety regime...
The drug only costs $56k because medicare can't negotiate. The parent was saying the bar for medicare paying for it should be decoupled from the bar for banning it. I agree.
Parent is saying very clearly that you should not need FDA approval to sell a drug that claims to treat some specific diseases.
That would remove all incentives to actually seek regulatory approval for drugs. We'd end up with an unlimited number of treatments trying to convince desperate laypeople of their benefits.
Another angle: yes, you would be willing to try any experimental drug you're reading about these days. So would I. But that's because the current regulatory system ensures that "experimental drugs" are usually at least good-faith efforts to produce a working, beneficial drug.
Another angle: yes, you would be willing to try any experimental drug you're reading about these days. So would I. But that's because the current regulatory system ensures that "experimental drugs" are usually at least good-faith efforts to produce a working, beneficial drug.
It seems like it would useful to have some kind of probationary approval for situations like this. If the data isn't convincing and the only alternative patients have is death, approve the drug under the condition that the manufacturer must greatly subsidize the cost until they have data that is convicing or the manufacturer loses confidence and withdraws from the market.
This might be a terrible idea given how complex and delicate the incentive structures are in healthcare.
This might be a terrible idea given how complex and delicate the incentive structures are in healthcare.
That's what large scale Stage 3 clinical trials are supposed to be.
This is basically how the law currently works.
If you are terminally ill you can apply for compassionate use from the FDA. And/or join a study. I think I read a while back that some large percentage of people dying of cancer were members of studies for drugs in process.
You can also get permission directly from a doctor under the "right to try" bill that was passed a few years ago.
I think all options must be after phase I is passed if I remember
If you are terminally ill you can apply for compassionate use from the FDA. And/or join a study. I think I read a while back that some large percentage of people dying of cancer were members of studies for drugs in process.
You can also get permission directly from a doctor under the "right to try" bill that was passed a few years ago.
I think all options must be after phase I is passed if I remember
This would be an ok mindset if the cost for treatment was zero or close to zero.
Currently, the cost of medication is very high (>$50k) and the vast majority is paid for by insurance, specifically Medicare.
So it’s a small chance for cure (maybe 1%) vs the cost that’s the equation.
I think this would incentivize lots of other drugs that are very expensive but known to not cure, or could potentially cure and the “science facade” would actually crowd out other potential cures.
Look at the supplement industry where there really isn’t any regulation, it’s mostly homeopathy taking advantage of people who want a fix. It’s like lotto in that it’s a waste of money but gives hope.
I frequently hear “just try it, what’s the harm” but the harm is the cost of trying lots of things. And a system where trying it incentivizes marketing and not cures isn’t very helpful.
Currently, the cost of medication is very high (>$50k) and the vast majority is paid for by insurance, specifically Medicare.
So it’s a small chance for cure (maybe 1%) vs the cost that’s the equation.
I think this would incentivize lots of other drugs that are very expensive but known to not cure, or could potentially cure and the “science facade” would actually crowd out other potential cures.
Look at the supplement industry where there really isn’t any regulation, it’s mostly homeopathy taking advantage of people who want a fix. It’s like lotto in that it’s a waste of money but gives hope.
I frequently hear “just try it, what’s the harm” but the harm is the cost of trying lots of things. And a system where trying it incentivizes marketing and not cures isn’t very helpful.
I don't think we should be wildly experimenting with cures for terminal illness in the elderly. I don't think we should be putting much effort into them at all, in fact. The elderly are going to die soon no matter what you do. We should be focusing our efforts on things that are terminal at a young age.
Yikes, read through to the end to understand why the FDA approved this drug despite no support (ten against, one uncertain) from their advisory panel:
> Dr. Stein also defended the agency’s decision to approve the drug for such a broad group of patients, saying it could be relevant beyond the early stages of Alzheimer’s. "Because amyloid is a hallmark of the disease through its entire course, the expectation is that this drug will provide benefit across that spectrum," Dr. Stein said.
That expectation was not borne out as clinically significant in the trials, yet the beta-amyloid hypothesis lives on.
> Dr. Stein also defended the agency’s decision to approve the drug for such a broad group of patients, saying it could be relevant beyond the early stages of Alzheimer’s. "Because amyloid is a hallmark of the disease through its entire course, the expectation is that this drug will provide benefit across that spectrum," Dr. Stein said.
That expectation was not borne out as clinically significant in the trials, yet the beta-amyloid hypothesis lives on.
What the FDA is doing is in effect allowing Biogen to run a large scale clinical trial while charging full price for the drug. This would normally be a terrible idea, but Alzheimer's is such a devastating and long lasting disease that patients as well as insurance companies might well be willing to subsidize Biogen just to find out if this thing really works or not. Such is the gloomy reality of an incurable, progressive, and fatal disease.
This is a potentially dangerous direction to be taking the approval process in, though. It’s not meant to be for experimental treatments with at best inconclusive efficacy. Being an approved treatment is supposed to mean that an agent is efficacious against a disease.
“Efficacious”, though shouldn't be viewed as a binary, but as a sliding scale where the cutoff for any particular application depends on the balance of risks, available alternative treatments, etc.
Why shouldn’t it be viewed as a binary? They couldn’t find any evidence it was effective! You can’t get much more of a zero than that. Out of eleven, ten members of the advisory board were against approval and one was uncertain. I’ve got no idea why this drug was approved, unless it was an emotional appeal to the plight of Alzheimer’s patients, which should not guide which treatments we use.
The problem here is that by “approving” the drug, the FDA implies that it truly works. People will take it expecting improvement, but their time will be wasted and their hopes dashed. The approval process itself will lose credibility, and that will hurt everyone.
By being devastating and long lasting, Alzheimer’s is not exceptional, compared to say cancer or even CVD.
This decision really changes the perception of what the FDA is there for, if not to ensure efficacy and safety, then what?
By being devastating and long lasting, Alzheimer’s is not exceptional, compared to say cancer or even CVD.
This decision really changes the perception of what the FDA is there for, if not to ensure efficacy and safety, then what?
Can someone who has access tell us why the price is so high? It seems cruel to make a medical treatment so expensive. You know some people will do anything to help loved ones overcome Alzheimer's, no matter the cost. If the high cost is avoidable, then it's predatory exploitation of inelastic demand.
Go read up on the history of ACTH (Acthar Gel) if you want to see how far this sort of stuff goes. Short summary is its a medication that cost approx $20 a vial for 50+ years and then got hiked to $40,000 a vial in the United States. It was the best known (gold standard) treatment for things like infantile spasms in newborns.
If it worked, $56K per year for a brand new drug for Alzheimer's isn't really that bad.
The problem is that is doesn't work. However, people will feel compelled to get it for their suffering relative as it is the only "approved" treatment.
The problem is that is doesn't work. However, people will feel compelled to get it for their suffering relative as it is the only "approved" treatment.
Likely years ago somebody at Biogen used a spreadsheet to calculate NPV under a range of scenarios, and from that decided to license this drug from Neurimmune. So it’s this or nothing, unfortunately.
It's a monoclonal antibody. Biologics are expensive to produce.
What's stopping revocation of approval? Or is that fixed in stone now?
The manufacturer, Biogen, is ordered to continue studying the efficacy of the drug as a condition of approval. The results of this continued investigation are due in - seriously - nine years. Meanwhile, anyone with any stage the disease will receive treatment; fortunately (?), Medicare is expected to bear the burden of this expense.
Stock prices mostly
The FDA approved the use of OxyContin, including banning the original formulation when the patent was about to expire so the Sacklers could change a small detail and continue to profit from the massacre it created. Why was this the straw that broke the camels back?
The FDA serves Big Pharma, not citizens.
The FDA serves Big Pharma, not citizens.
I imagine companies pitching (and discounting) any idea they can come up with and patients signing up for the best deals. As soon as someone starts to show something promising they get tax payer money and become locked in as the cure.
I just don't see any reason not to go balls to the wall on experimentation when you are treating the dying elderly. My grandfather died with some type of dementia. If I were in charge of his care I would have taken any experimental treatment over just letting him die with medical care that didn't have a chance of saving him. Better to take 1% chance of cure and 99% death than 100% chance of death.