Experts Have Resigned from an FDA Committee over Alzheimer's Drug Approval
npr.org
npr.org
He makes an interesting point that when the FDA approves a drug, it means that Medicare is automatically on the hook to pay for it, and that a more sensible system might decouple approval and mandated reimbursement by having multiple levels of approval (e.g. 1 star = this is probably safe, 2 stars = it's definitely safe, 3 = there's weak/controversial evidence for efficacy, 4 stars = it is safe and it works, etc.).
But it's interesting to me that we hear about FDA scientists resigning when a panel is too permissive, but not when it's too restrictive. Can we chalk this up to something about the kind of people the FDA recruits? I can recall just one instance of an FDA official pushing the institution to go faster, and that was when the doctor's wife died of cancer [1].
[0] https://astralcodexten.substack.com/p/adumbrations-of-aducan...
[1] https://www.nytimes.com/2016/01/03/us/politics/fda-regulator...
Maybe that means building randomized trials into treatment in a much more regular way (like with the Covid RECOVERY trials, where any doctor could enroll patients with a web form, and source the candidate treatment from the local pharmacy), which vastly reduces cost for treatments already on the market with other indications. And perhaps altering the balance of risk for patients with life-threatening or terminal diseases.
Now, imagine that after safety is verified to a 1 or 2-star level, we don't make the drug approved for general use, but doctors can freely enroll in randomized trials as you proposed? That way we're getting the efficacy data quickly but safely.
Maybe a minor point, but we do have to unbundle safety from efficacy in some sense to get off the ground here. The question is, what exactly is allowed to happen after safety is established but efficacy is not yet established?
I think the key would be having clear centralized standards for how the trials are conducted, or you could have doctors skirting the system and just using it as de-facto prescription, and patients being put at risk for ineffective treatment without producing any valid evidence.
If the system were set up so that doctors would have a lot to lose if they didn't follow the system, trust could work here. We already trust doctors as professionals on many other things...
But this already happens for certain treatments. The FDA already regulates a separate category with loose efficacy requirements for dietary supplements and herbal remedies. These medically irrelevant treatments are immensely popular, they're just forbidden from marketing specific medical claims and being actually toxic. People still end up taking FDA approved treatments like Ivermectin for non-FDA-approved purposes based on Facebook recommendations.
Why do we always have to make people's choices for them? They're grown adults capable of making their own decisions and their own mistakes. If they want to ignore the science and the credibility of the FDA process, they should be free to do so.
Because I am not a scientist and need an authoritative body that I can have some semblance of trust in to decide what medicine I can put in my body and a Dr can prescribe to me. And we have tried the unregulated route before and we had people taking cough syrup with heroine in it and other snake oils.
I mean, even with the FDA, we have people using animal dosage de-wormer to treat Covid with no evidence that it works and a lot of evidence that it will fuck up your guts...so as much as you want to play the "we're adults capable of making decisions" card, that statement really doesn't mean much in reality.
That'll only serve to increase distrust in the FDA. Yeah, it's safe, but also, it's no good for anything. You wonder if that's the purpose of such initiatives, destroying trust in the public authorities to better be able to sell snake oil.
The benefits of separating them are relevant to this exact Alzheimer treatment; It has controversial efficacy, but now the FDA had to decide between "all doctors, insurance, and Medicare must cover/prescribe it" or "no one is allowed to do anything with it".
It will also serve to speed up the notoriously slow and expensive process to make something available and make grey-area treatments available. This completely fucked the FDA's early response to the initial need for COVID-19 testing kits. The FDA made a mistake as all organizations do, but its approval system is so inflexible it prevented many safe and realistically effective testing kits from being made available.
Most people -- including myself -- are unequipped to evaluate the science behind most drugs. That supposed to be why the FDA exists. I do not want to make my own mistakes here, since they can very easily be fatal, or at least have long-term consequences. I want a trusted body of experts to give me a recommendation that's as well-informed and unbiased as possible. The FDA may or may not be as good as they should be at being that body, but it is absolutely needed.
No one is arguing to get rid of safety requirements or the FDA. The FDA will still be empowered to give a recommendation based on efficacy, but the lack of an efficacy recommendation should not prevent people from getting a treatment. The FDA is necessarily conservative, slow, and sometimes makes mistakes. That has a real cost if it acts as the sole gatekeeper for efficacy, a prime example being early COVID-19 test kits.
imagine someone is in need of an effective treatment, but they don't like it or heard some rumors on tv or youtube, then instead they take an ineffective drug and think they aren't contagious, yet now they are potential spreaders of a disease... that doesn't sound safe at all to me.
Because "ineffective" in your question actually means "not proven by the FDA to be effective" and the FDA, like all organizations, isn't perfect or perfectly responsive. For example, early COVID testing kits by third party labs that were safe and realistically effective but not yet approved. For example, this Alzheimer treatment that has controversial efficacy but the FDA could only choose between banning it completely or forcing insurance & Medicare to cover it.
We can make exceptions in scenarios where ineffective treatments have unusually high external risks such as the COVID-19 pandemic before effective vaccines were available. Now, someone who pays attention to the FDA can use an FDA approved vaccine to immunize themselves to the disease spread by people who make decisions based on YouTube rumors. Sounds safe enough to me. We each make our own choices.
> We each make our own choices.
I don't think the lack of credible evidence of efficacy in the supplement market is for lack of trying. If an alternative medicine is actually effective, it just becomes medicine that the majority of people can trust and use.
In the US, supplements must be vitamins or minerals, botanical products, amino acids or enzyme products.
Drug companies can't develop a new compound and then try to sell it as a supplement unless it meets those requirements, which it probably won't, because drug companies rarely develop new compounds that are also found in nature or in your body already.
OP is saying we could change the laws that configure the distinction you draw.
Because desperate sick people and their loved ones make excellent marks. Without standards, some doctor or medical company will milk every last penny from someone with the false promise of some sort of hope.
Not to mention second order effects. The more common it is for medicine to be seen not working, the more people will distrust the medical system.
People are already "milked" on supplements and herbal remedies (which is at least still regulated to be safe, not necessarily true for a lot of informal quackery out there): people buy a lot of them without FDA approval or a medical prescription in the hopes that it somehow helps them. It's just fine. Rigorous FDA approval has & will always be available for people to use. They're grown adults, let them make that decision.
If people distrust the medical system because products outside the medical system have failed them, well, people are allowed to be stupid.
> They're grown adults capable of making their own decisions and their own mistakes.
we dont live in isolated bubbles, so there is a limit to how far we can go with putting everything on the shelf and let everyone do what they want with it
On the other hand for a drug that’s safe but maybe not effective, there’s a lot of money to be made off of people willing to do anything to prolong their time with their loved ones who have been diagnosed with Alzheimer’s. Aside from that, the FDA can hurt it’s reputation by approving drugs that just don’t work too frequently and be accused of being in the pockets of the pharma companies. There’s a stronger possibility of corruption affecting the decision, and whether that corruption is real or perceived doesn’t matter much for public trust.
MHRA: approval for marketing and sale within the UK
NICE: analyse cost/benefit ratio and safety profile for use within NHS (which is then approved by the NHS CCGs)
https://www.cms.gov/newsroom/press-releases/cms-opens-nation...
"Today, the Centers for Medicare & Medicaid Services (CMS) is opening a National Coverage Determination (NCD) analysis, a process that will allow the agency to carefully review and determine whether Medicare will establish a national Medicare coverage policy for monoclonal antibodies targeting amyloid for the treatment of Alzheimer’s disease."
Our current research/science publishing system is not well suited to evaluating very small effects. Not that there may any system well suited to that.
Whenever a trade deal comes up between the US and Australia, they always want to kill our PBS system that negotiates lower drug prices with pharmaceutical companies.
Although in practice I guess this would probably not be very different from 'not approved', in which case it seems right for the FDA to reject ineffective drugs.
In any case, one thing we definitely do not want is to incentivize the creation of ineffective drugs, especially expensive ones.
It could also be pretty awesome if there was a labeling requirement on all FDA approved drugs for effect size, from a red "not very effective" to a yellow "moderately effective" to green "highly effective".
I think you miss the point of the parent post. The point would be to allow drug companies to sell drugs that are reasonably safe, but efficacy is unknown. This would allow drugs and products to come to patients quicker, in a way that is decoupled from reimbursement.
>It could also be pretty awesome if there was a labeling requirement on all FDA approved drugs for effect size, from a red "not very effective" to a yellow "moderately effective" to green "highly effective".
You are in luck! The FDA has what are literally called "Labeling Requirements" for all approved drugs, which includes a description effect sizes and side effects. You can find the effect sizes by searching "Prescribing information [Drug Name]". It doesn't include a color code, but does have "X% of patients had Y effect, Z% of patients had N effect, ect"
1) Timing: There are people who suffer and die while products are held up in lengthy phase 3 approvals. 2) Human Impact: There are drugs& devices which are safe, but have weak efficacy data. For some like aducanumab, if they work, they could help millions of people today. This puts the FDA in a tough spot weighing a big potential benefit to society against things medicare costs for a low/no efficacy drug.
Im personally not advocating for throwing open the gates to any snake oil. I think a reasonable proposal would be to require robust data on safety, a strong argument for why it should work, and require monitoring of efficacy after approval.
If time tells that your magic pills dont work, they get pulled from the market. If time tells that they do work, you get your gold star
The first link in this post explains it better than I can.
It's just a sign that the FDA is so horribly broken, it probably can't be recovered.
One note that I think would be important is that we should stop using the term "approved" or "not approved" and instead used "banned" or "not banned", as this is a more clear way to describe the situation. For example, in Sep 2020, it was completely obvious that taking a covid vaccine if you were elderly was dramatically better than waiting for COVID. But you could not, because the government said no. It didn't matter how informed you were, how much your doctor would agree, the answer was no. You go to jail if you try to take it. That should be called "banned".
As I recall, the claim (by the dissenters) in the article was that big names in research had staked their reputation on the plaque theory. Those big names were claimed to use their weight to suppress any research into alternative theories. The article then stated that the little bit of research into alternative explanation seemed promising, and that there were trials on removing plaque that did not seem to cure Alzheimer.
This news about a controversion FDA approval feels like it is related to this controversy. And to my mind, it strengths the case for 'plaque does not cause Alzheimer'.
A narrative of this-one-theory-being-kept-down-by-the-man is attractive, but a bit thin in practice. The amount we do not know about anything in biology (especially the brain) is staggering. Few researchers are willing to make definitive statements owing to our ignorance in the space. Biological research is the closest one can come to direct manifestation of Murphy's Law.
Many are invested in the amyloid hypothesis, but only because it is the most compelling target to date. Everyone knows the emperor has no clothes. If/when better evidence comes to light, the field would move accordingly. Until that time, pharma companies will keep throwing billions of dollars at abeta hoping that their compound will have an effect where others have failed.
Edit: corrected typo pointed out from below
When speaking of biology, assume we know less than we think.
I think should have been "we do not know"
However a series of high profile articles and editorials have said that we have. For the latest example, read https://www.scientificamerican.com/article/alzheimers-inc-wh....
Given that, I will continue to believe that this area of science absolutely have acted in a non-scientific way.
This is a bit of an idealistic view.
It's entirely possible for large players within a given system to pick and choose winners, specifically in where they direct funding. This isn't the same thing as actively platforming against a particular path, just funding the one that they see as most promising.
I think the argument here revolves not around the "gerontologists hate this one trick that big pharma doesn't want you to know" but rather than there's some small number of people making decisions based on their own biases with regard to research directions and there's a dissenting group that would like to see broader research done before committing the finite available resources to just that one path.
In short, there are good reasons at this point to believe that amyloid-β's primary function is as antimicrobial peptide, and thus various infections may cause the seeding of amyloid-β deposits. These deposits may then persist for years beyond any useful benefit, especially if the brain's clearance mechanisms are impaired.
Note that, per [2]:
Importantly, in the antimicrobial protection model, neurodegeneration is not mediated by pathogen activities that directly kill neurons. Rather, Aβ innate immune pathways targeting pathogens mediate the AD [Alzheimer's Disease] neuropathogenesis that leads to widespread neurodegeneration. Thus, our model is consistent with the amyloid cascade hypothesis and overwhelming data showing the primacy of Aβ in AD pathology.
[1]. Dominy et al (2019). Porphyromonas gingivalis in Alzheimer’s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors. https://doi.org/10.1126/sciadv.aau3333
[2]. Eimer et al (2018). Alzheimer’s Disease-Associated β-Amyloid Is Rapidly Seeded by Herpesviridae to Protect against Brain Infection. https://doi.org/10.1016/j.neuron.2018.06.030
While it may be considered andectoal, this fits with what i've seen in my family. In my mind and from what i've read it seems to be more of a combination of factors - diabetes, an APOE gene, toss in a little depression/loss of purpose/retirement/isolation, etc
I find the studies with gamma interesting: https://www.alzheimers.gov/clinical-trials/gamma-induction-a...
I think it would be good to bring more attention to noticing when things start to slip, because as things progress there can be less openess to trying new things/focus on maintaining state.
To me that indicates that this isn't a controversy between scientists, but an example of corruption / regulatory capture. Biogen spent a bunch of money researching a drug based on an unproven theory. When their results were very poor, the FDA allowed them to switch to accelerated approval, then ignored their unanimous panel of experts to grant that approval. This allows Biogen to sell an extremely expensive drug and recoup some of their loses before the ongoing studies required under accelerated approval further undermine the drug's claims of effectiveness.
For what it is worth, there seems to be a lot of internal debate around the causes, symptoms, and treatments of CTE. In fact, there are debates as to whether CTE is a distinct tauopathy or even exists at all (at least in the form the public understands it).
"As NPR's Jon Hamilton has reported:
"This drug has generated all kinds of excitement because it is the first approved drug that does more than just relieve the symptoms of Alzheimer's. This drug actually affects an underlying disease process by reducing the amount of sticky amyloid plaque that builds up in the brain. The catch is that removing this plaque may not actually help patients avoid memory loss and thinking problems. One big study showed that it did. Another showed that it didn't.""
In other words, the drug works against what may be a symptom of the disease, but hasn't reliably been shown to do anything for the actual problem.
Science is hard.
Oh, and by the way,
"The drug will be administered through infusions every four weeks, resulting in a yearly cost of about $56,000, the companies said. That's the list price, which doesn't necessarily reflect the out-of-pocket costs for someone who has insurance and/or Medicare. Preliminary estimates suggest patients' copayments for the drug could cost around $11,500 annually."
---
It is natural to ask: "sure, we see amyloid-β plaques with Alzheimer's Disease, but could there be a confounder, rather than amyloid-β being the cause?" However, we have strong evidence that it's the cause.
In fact, in a subset of cases, we have smoking gun evidence that amyloid is the cause: certain mutations or duplications of the APP (amyloid precursor protein), PS1 & PS2 (presenilin 1 & presenilin 2, parts of the enzyme γ-secretase involved in cleaving APP to make amyloid-β) genes guarantee that one gets Alzheimer's, and typically quite early (between the age of 30 and 60 for the onset of clinical symptoms). We have mapped out the structure and function of the corresponding proteins extremely well, and we know how, functionally, those specific mutations affect the behavior of those proteins: either to increase total amyloid-β production, or to increase production of the specific peptide (amyloid-β 42) implicated in Alzheimer's Disease. [1] I am not aware of another plausible effect of those mutations besides this one, and the mutations guarantee you get Alzheimer's Disease.
Now, this represents approximately 1% of Alzheimer's cases, the so-called autosomal dominant variety, so it's a priori conceivable that the other cases have a different cause. In the remaining cases, we have evidence consistent with an impairment of amyloid clearance mechanisms, however that evidence is more circumstantial and in some cases compatible with other hypotheses. But the disease looks like exactly the same disease as the 1% of cases in which we have smoking gun evidence of amyloid being the cause: we still see the same progression of amyloid-β, followed by a progression of hyperphosphorylated tau, followed by neurodegeneration and cognitive decline, and with the same sequence of brain regions and cognitive symptoms.
Suppose there are two bank robberies. In the first, we have smoking gun evidence of the culprit: a video camera showing a guy getting out of his car, with a clear image of his face and the license plate, and then of him walking into the bank, pointing a gun at the teller, the teller handing over a bag of cash, and him walking out with that bag of cash. In the second: we also have footage of the same guy and the same license plate at the scene of the crime, but an occlusion prevents clear footage of the exact moment of the robbery. However, the robbery occurred in the same town and on the same day, and eyewitness reports are that the robbery was conducted in basically the same manner. In that case, is there much question as to the identity of the robber?
**
As for the track record of amyloid-targeting therapy for Alzheimer's, I think it's fair to say that it's been less successful than hoped for but that also:
1) There has been a mixture of benefit and no effect; rather than the mixture of benefit, no effect, and harm which you'd expect to see if the drugs really were useless. For example:
A) The recent phase 2 trial of the similar drug donanemab showed success in its primary endpoint of reducing cognitive decline, by 32% (p = 0.04). [2]
B) The recent phase 2b trial of another similar drug lecanemab had promising results, although it didn't pass its primary endpoint, arguably due to a needlessly convoluted Bayesian statistical analysis. It showed reductions in cognitive decline of 26%, 30%, or 47% (p = 0.125, 0,034, or 0.017), depending on endpoint. [3]
C) With respect to aducanumab [4], the first phase 3 trial, EMERGE, passed its primary endpoint and all pre-designated secondary cognitive endpoints, with p-values for the high dose arm between 0.0006 and 0.0493 (0.0120 on the primary endpoint), and effect sizes ranging from an 18% slowdown to a 40% slowdown in cognitive decline (22% on the primary endpoint).
The second phase 3 trial, ENGAGE, did not show statistically significant benefits on any pre-designated endpoints, but the effect sizes still ranged from -3% to 18% (-2% on the primary endpoint). So given only pre-designated endpoints, we have two trials, one of which showed a clear benefit, and the other of which showed no effect, or very slight benefit if we give some weight to pre-designated secondary endpoints. From a Bayesian perspective, this has to be seen as weak evidence of benefit.
Lastly, both trials showed a substantial and significant (p < 0.001 in EMERGE, p < 0.01 in ENGAGE) reduction in phosphorylated tau, a neuropathology both regionally and chronologically highly correlated with volume loss and cognitive decline in Alzheimer's Disease.
2) The amyloid cascade hypothesis offers explanations for past failures of amyloid-targeting therapy, for example poor target specificity (some therapies such as semagacestat were not proven to engage amyloid in the first place, and were also known to produce other toxic effects unrelated to reduction in amyloid), deficient screening of participants (in some cases, patients were selected only for cognitive symptoms and not for the presence of amyloid, thereby reducing statistical power), and not intervening early enough (no one believes amyloid is the main proximate cause of neurodegeneration, so if you intervene late, it might be too late to prevent the cascade of problems it's believed to cause).
By contrast, I'm not aware of alternative hypotheses which even offer a story which can account for the known facts, such as the aforementioned evidence in the APP and PS1/PS2 genes.
**
For those interested in learning more, a good starting point for the current state of the science is [5]. A more up-to-date and comprehensive review paper is [6].
[1] Haass et al (2012). Trafficking and proteolytic processing of APP. https://doi.org/10.1101/cshperspect.a006270
[2] Mintun et al (2021). Donanemab in Early Alzheimer’s Disease. https://doi.org/10.1056/nejmoa2100708
[3] Swanson et al (2021). A randomized, double-blind, phase 2b proof-of-concept clinical trial in early Alzheimer's disease with lecanemab, an anti-Aβ protofibril antibody. https://doi.org/10.1186/s13195-021-00813-8
[4] Petersen et al (2019). EMERGE and ENGAGE Topline Results: Two Phase 3 Studies to Evaluate Aducanumab in Patients With Early Alzheimer’s Disease. https://investors.biogen.com/static-files/ddd45672-9c7e-4c99...
[5] Selkoe and Hardy (2016) The amyloid hypothesis of Alzheimer's disease at 25 years. https://doi.org/10.15252/emmm.201606210
[6] Long and Holtzman (2019) Alzheimer Disease: An Update on Pathobiology and Treatment Strategies. https://doi.org/10.1016/j.cell.2019.09.001
If amyloid plaques are just a symptom, then it's much less obvious that treating them will have positive effects on the symptoms you actually care about.
I could see this treatment being something like exercise and diet for type-2 diabetes. Exercise and diet may help prevent diabetes, but neither will "cure" the condition once the point-of-no-return has been crossed. In other words, you can turn a cucumber into a pickle, but you can't turn a pickle back into a cucumber.
Such an odd contrast as they passed a drug which had a number of failed studies and only one marginally successful one.
It probably makes more sense if we view the FDA not as a monolith but a collection of lots of individuals, some of which don't communicate or work together directly.
As a result all of our laws, relationships, products, theories, judgement, pedagogy, spirituality and platforms are composed and interpreted by a dizzying array of perspectives and values. Our brains can't handle the combinatorics, so we just personify them and anyone we associate with them is just a fragment of the whole.
A quorum is the minimum number of members that must be present in some body or group for them to be allowed to make decisions. The number is given in the group's articles of association; there's nothing messy about it.
A "consensus" occurs when enough members of a group or body agree with a proposal, that the remainder "consent" to that proposal, even if they don't fully agree with it. Consensus is messy, partly because the meaning of the word is open to dispute; and partly because "consensus" doesn't address the case where the group or body is irreconcilably split on the issue at hand.
I don't care to address the word "democracy"; that word has as many meanings as there are people on the planet.
You don't expect it in the FDA because the trade-offs between safety, efficacy, urgency, clinical/statistical significance, and other dimensions are going to be rather specific to each silo of expertise/each product, and rather difficult to fully prescribe and encode a priori. So out of necessity, some amount of discretion and autonomy are going to be provided to each group of specialists, and you are bound to get inconsistency.
Consider the review process for paper submissions to scientific journals. You can't prescribe an exhaustive checklist to Nature reviewers and ask them to mechanically follow it. You need to give the reviewers some autonomy. And with that autonomy will come inconsistency.
What do you think I am asking for?
Which is all probably already the case. The standard is probably rather loosely defined out of necessity, due to the reasons I suggested previously, and it follows that "inconsistency" will necessarily come from the part of the policy that allows for discretion. It doesn't follow that this inconsistency is bad, it could mean that in one domain or one product, certain considerations should get more weight. That's the point of the discretion, to allow the specialists to upweight and downweight those considerations that matter more or less for a given product.
So my point is that some inconsistency is to be expected, a subset of it is good, and no inconsistency would actually be a cause for concern.
What are we disagreeing about?
Remember - my comments about policy were a response to this:
> It probably makes more sense if we view the FDA not as a monolith but a collection of lots of individuals, some of which don't communicate or work together directly.
The comment I was replying to implied that the discrepancy was simply due to disparate groups of people not in communication.
Your view now seems to be the opposite - it is that they are in communication, and have a policy but that subject matter is complex and will legitimately generate the range of responses we see.
But in terms of analyzing these organizations it's an excellent point that we can't assume consistency. They are complex and contradictory.
As a comparison, look at how nearly all of the big social media platforms all struggle with policy interpretation and enforcement around topics such as misinformation or hate speech.
Sure, so we should be able to see what guidance was followed.
> Discretion from the regulators is needed to accommodate for cases that don't fit neatly into existing policies.
Discretion doesn’t mean policy can be ignored. Discretion would be part of the policy, and we should be able to see what discretion was used to come to these decisions.
Nothing about one drug being denied approval despite having more successful trials than another drug alone demonstrates that policy was ignored or that it wasn't considered.
No, it doesn’t ‘demonstrate’ it, but it certainly makes it into a candidate explanation that can’t be dismissed.
For example, why are they even involved in a discussion of booster doses of the Pfizer vaccine when they've given it full approval? Shouldn't that be at the discretion of physicians or other prescribers?
Why isn't acyclovir available over the counter?
Why has cannabis been treated as a mortally dangerous substance?
Why have miracle berries inexplicably classified as an illegal undeclared sweetener (https://www.theatlantic.com/health/archive/2014/05/can-mirac..., https://en.wikipedia.org/wiki/Miraculin#cite_note-Atlantic-2...)?
I think the role of the FDA has expanded much too far.
Also related: https://news.ycombinator.com/item?id=27734268, https://news.ycombinator.com/item?id=27671127
Here are a few review papers I could dig up in a couple of minutes:
2019: https://juniperpublishers.com/pmcij/PMCIJ.MS.ID.555601.php
2017: https://sciendo.com/article/10.1515/cpp-2017-0003
2011: https://pubmed.ncbi.nlm.nih.gov/21764150/
2009: https://pubmed.ncbi.nlm.nih.gov/20010032/ (with focus on dementia)
Scientific American blog post: https://blogs.scientificamerican.com/bering-in-mind/one-last...
However, she did have a moment a few months before where her symptoms seemed to completely vanished for a couple hours after a doctor flushed out her Alzheimer's meds. Unfortunately I was not there, but my mom said she was suddenly completely attentive and remembered everything like her old self during that time. I don't know if it was coincidence, related to the meds, or if the flushing process did something (I'm told it was intense). I wouldn't be surprised if other patients have experienced similar things, but I don't think it's related to death.
It was bizarre interacting with him during this lucidity. He was able to do most physical things without assistance (he still had a bad hip) and you could engage with him in conversation. He knew who I was without prompting, something he hadn’t been able to do for about 4 years. He knew all his children and grandchildren. He also shared stories from his middle years, something he had stopped doing during the early stages.
It wore off though, in about a week or so he began to have the brain fog set in. His doctor was also not too happy to hear about the withdrawal.
The only person who seemed disturbed and worried about this moment of lucidity was his caretaker, who had worked with dozens of elderly folks with memory issues prior. She said it almost always happened before a sudden decline. She was right, about 3 weeks later he became very ill and then died within a few months.
For instance the sister for a famous (for the state) news reporter would seem to come out of it a bit to talk about her sister, but mostly she just walked along the walls, tracking the trim with her fingers and mumbling to herself.
It is a nice myth to pull at your heart strings
https://www.cnbc.com/2021/08/31/two-senior-fda-vaccine-regul...
For drugs like this the drug company pays the patients' total out of pocket (co-payment) in full on the first infusion. The patient never has anything to pay in this case...if they have insurance.
If instead they even required patients to still cover out of pocket portion, prices would need to be way lower.
You see this overseas. People pay out of pocket. I was in a fair number of developing countries, it's actually a bit nuts for westerners. The process to get for example things like basic antibiotics is near over the counter. Other items are INSANELY cheap. And accessibility (if you have USD) is good.
https://en.wikipedia.org/wiki/Regulatory_capture
This kind of story is all too common. These are NOT scientific or medical organizations anymore because of how corrupt they are.
> The latest exit comes from Dr. Aaron Kesselheim, a professor at Harvard Medical School who is also director of the Program On Regulation, Therapeutics, And Law at Brigham and Women's Hospital. He said the FDA is greenlighting Aduhelm despite not having enough proof that the drug will help Alzheimer's patients.
Running another trial makes sense if “test subjects” are needed but giving the drug general availability when the previous trial failed and was actually stopped because of failure doesn’t make much sense to me.
In my mind, there are two main issues. The first is what other alternatives would be overlooked because of an approved treatment, including further research.
The other issue is money. These medicines cost a lot of money, and it there's no improvement it's a waste of resources not only for the patient, but also for the insurance pool they're in. If it's something that's not expensive, go nuts, but thousands of dollars to move the metric but not the symptoms doesn't make sense to me.
Everything in life is a gamble. How you interpret the results is you own undoing.
Also this drug is crazy expensive for something which doesn't even work.
The biggest problem is this is a gamble with other people's money because medicare and the taxpayers are on the hook for the bill.
Now--I wish the FDA would revisit approval data on every anti-depressant since Prozac, and including Prozac.
Irving Kirch was the first to look at all the drug trials, and not just cherry pick. His study is in Lancet.
https://www.psychologytoday.com/us/blog/psych-unseen/201802/...
You could argue that society-wide COVID lockdowns and forced vaccinations, in reaction to a virus which is really only driving excess deaths in that generation, would never have been supported if that cohort was smaller or less influential.
And in fact it may have had a massive impact.
> Between 205,000 and 300,000 coronavirus cases across the U.S. can be traced back to the Boston conference, say the scientists, whose findings were published in the journal Science on Thursday.
https://www.cbsnews.com/news/boston-biogen-medical-conferenc...