>One big problem is the FDA's slowness regarding treatments for otherwise fatal diseases like GBM.
What do you mean by slowness? They can't skip all the safety stuff!
What do you mean by slowness? They can't skip all the safety stuff!
The FDA (and EMA in Europe) are the only thing that protects desperate patients from fraudsters, charlatans and pharma-companies just looking for a return on their investment.
While Aduhelm reduces Aβ it has no clinically significant effect. Still, the FDA approved it. Mercifully it'll be discontinued in November.
The covid vaccine represented a huge policy failure by the FDA. While people in nursing homes died in droves we got small clinical trials. When you've got 90 year olds in a congregate setting facing a 50% chance of death, maybe it's time to stop pretending thalidomide may be lurking around every corner. The pediatric trials were just as bad. Due to their sizing it was statistically impossible to detect rare adverse effects. Yet, vaccination was delayed for children while these fruitless trials ran.
In my own experience I had a low cost, high throughput covid testing protocol ready to go in early April 2020. It took the FDA until August 2020 to provide templates and another month to grant emergency use authorization. We could've drastically ramped up testing when it was needed most of the FDA has treated an emergency like an emergency.
Throughout 2020, more than 9% of all people in nursing homes died of covid. Depending on age case fatality rates were upwards of 50%. The vaccine should've been offered to these people on a compassionate use basis. Even at the time it was obvious that actual harm posed by the virus vastly outweighed any hypothetical risk of adverse vaccine reaction. Drastically expanding the vaccinated population through compassionate use would have rapidly provided efficacy and safety data.
That's just about most difficult population to determine primary cause of death for. Most people in nursing homes have multiple comorbidities and a long list of medications. Its easy enough to know when someone died with Covid, its much more difficult (if not impossible) to know after the fact whether that's what caused their death or if the infection began after an existing condition worsened and weakened their immune system further.
> Drastically expanding the vaccinated population through compassionate use would have rapidly provided efficacy and safety data.
That wouldn't have helped get efficacy or safety data for the general public though. Vaccinating that population could absolutely have helped determine efficacy for that population and I agree it feels like a reasonable action given the potential risks for that population, but the data wouldn't be useful for the general public that are younger and/or in better health prior to infection.
Nursing home quality, COVID-19 deaths, and excess mortality https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8776351/
At the peak, excess nursing home mortality was nearly 6000 per week. Quibbling about "died with covid" versus "died of covid" isn't a useful exercise. Dead is dead and the excess mortality came from somewhere.
It isn't quibbling when the specific topic is whether or not to treat a population with an untested vaccine (assuming the trials were skipped for at risk populations as proposed above).
In a general sense, I totally agree the "with" versus "of" debate isn't useful. But when considering giving an at risk population an untested vaccine, how is that not important? Any intervention could have downsides, and more importantly an preventative intervention for a secondary infection may not be worth the risk depending on the risk profiles.
One tricky question that would have to be answered is whether the excess deaths were related to changes in nursing home treatment and general conditions. Nursing homes were effectively locked down in many areas, reducing human contact and potentially negatively impacting care. Vaccines would have no impact there, and if the untested vaccine has negative side effects we would have only made things worse.
Strokes, heart attacks, circulatory issues, etc are likely pretty common in that population and any increase there after treatment may go unnoticed as a change. If you do recognize it they'd have to stop treatments entirely as you wouldn't know whether its a risk to everyone or specific to some combination of age, comorbidities, and/or other medications.
In the UK, nursing homes were discovered to be sedating patients and not administering water and nutrition. I wouldn't be surprised to learn the same happened in the US.
The refusal rates were already too high with anti-vax people making up lies/distorting data. If they actually had real data things would've been much worse.
Anti-vaxxers simply don't care about truth vs. falsehoods. They don't care about the actual 3-phase clinical trial with tens of thousands of participants.
You could let the public make an actual decision based on actual information, rather than telling them little, projecting false certainty, and then trying to force them to do what you think is the best course. I mean, look, not everyone can be treated like adults. But I think the majority of people can. Tell them the truth, and let them decide.
That event will then be used in a way that is wildly out of context as fodder by all the anti-vaxxers out there to scare people into not getting vaccinated later when the vaccine is safer.
For the next 50 years anti-vaxxers and scammers will be using that event to scare people about vaccines.
It is not worth the risk because of the potential outcomes.
If a vaccine is rolled out and kills thousands, the example you gave, why shouldn't some people take notice of that and be concerned? Is there no level of risk that would also make you consider not taking a new and untested, or under tested, vaccine?
At the end of the day, in my opinion, there is no magic number for vaccine acceptance that is a metric to define beforehand. Refusal rates are a backward looking metric only and simply reflect the willingness to participate and trust in the general public.
Far more covid vaccines were given out to more people then almost all prescription medications have been. They were FDA approved officially in 2021, and at the end of the day all of the covid vaccines given an EUA were much safer than even mundane things like driving a car.
High vaccine uptake rates save lives. Pretending otherwise requires you to misrepresent the data.
The pharma industry has been consistently producing what would easily be called life saving miracles in any other context. Anyone unable to see that is the biased one.
But lets be real, you almost certainly already know that. So you very likely fall into the category of people who intentionally misrepresent the data so you can pretend that vaccines are a bad thing.
Of course it is possible that the highly political, near-religious atmosphere during the Covid-Circus biased the reporting for the mRNA vaccines in the other direction. But this has to be objectively studied. That never happened. One of the many things that make me deeply distrust the mRNA vaccines.
Your very general statement "so you can pretend that vaccines are a bad thing" shows your propaganda. I am vaccinated against several pathogens. But the topic "immune system" is really complicated, the knowledge up to date is not sufficient to force people. Especially vaccination of children has to be thoroughly justified. Search on Google Scholar for "Peter Aabye".
You mean before vaccines became extremely politicized? I think we can safely assume those numbers aren't useful anymore now that the well has been poisoned.
>But this has to be objectively studied.
There were plenty of double blind studies on the covid vaccines. Those are the gold standard. I'm not even sure what you are asking for here.
I asked for studies on the reliability of VAERS data about the Covid vaccines.
RCTs are just one brick of the science building. And of the plenty you think exist, I have encountered only a few good ones, yet. The Cleveland Clincs study is one of them, but they justctested for infection and didn't include the outcome all-cause mortality or hospitalization for some unknown reasons. The US veterans study seems to prove a lower mortality for vaccinated, but the cohort is for sure not representative. Btw, those two showed a clearly monotonic increasing probability of acquiring a Covid19 infection with number of vaccinations.
RCT fanatism is not helpful.
> Imagine if an early covid vaccine had killed thousands. That would have had a massive chilling effect on vaccine uptake. You're making it sound like the chilling effect would be a bad thing, when it would actually be the correct response. There are plenty of examples in the history of medicine of the cure being worse than the disease.
We had safer vaccines available though so switching to them is even better, which we did.
> You're making it sound like the chilling effect would be a bad thing, when it would actually be the correct response.
That chilling effect would still exist when the vaccine was safe, making it the incorrect response. Conversations like this make it very clear why we need to be very careful about vaccine safety and we should never release a vaccine that will kill thousands EVEN if that vaccine would save lives overall.
The FDA approved it via accelerated approval. The intent being "allow access to promising medicine while additional data is collected".
There's also the part where distribution was done in a way that deliberately killed people so that racial equality goals could be met. Perhaps the worst example of this kind of thinking were teachers in SF getting vaccinated but school not starting again.
EMA has some people that were recruited from Big Pharma.
The issue is that with some illnesses/stages, we do not have a good treatment, and a lot of people would like the calculus to be different. We do have compassionate drug rules, but they're a pain for many people.
I'm not in that situation, and not sure how I'd react; but I can see how, having an incurable illness, with tons of suffering or a few months left to live, I might want to try everything. Hydroxychloroquine, Chinese acupuncture, herbal remedies, and experimental treatments.
Do they not already?
In effect we regulated doing stuff so much in the name of safety that we ended up in an infinite "analysis paralysis" mode where the you have to absolutely prove zero harm from new products/services while completely ignoring the harm the current status quo does.
See current debates over AI, self-driving cars, and of course, meds.
You should have a probability distribution over possibilities, based on your experience with similar drugs, expert hunches and animal trials. You then use that to estimate risks and benefits. Then compare this risk-reward profile with the risks of doing nothing -- in this case, near certain death from brain cancer.
This "can't presume to know" framework is just sophistry. And I think deep down you know that, if you had a death sentence from brain cancer you'd be begging them to let you in the trial even if they "couldn't presume to know".
It’s extremely challenging if not impossible to obtain informed consent in this situation.
We’ve been through this before where a fancy new treatment with promising early/lab results usurped conventional therapy only to later be found inferior.
Earlier TKIs and NSCLC are a recent example that comes to mind.
This is decision making under uncertainty. It's bad practice to say that uncertainty always means "don't do it".
In huge oversimplification some crazy or fraudulent people will claim it cures blindness or cold sores, some other people will believe them and will have to deal with the real danger-to-lethal consequences, with the rest of society paying for their medical care afterwards.
Pretty effective.
In Australia throwing a few diseased lungs on the packs and increasing public awareness has seen usage drop from 35% of the population in 1980 to 11% today.
Not all the drop is purely related to advertising, price increases and restricting sale to out of sight locked access in shops have also helped.
https://www.tobaccoinaustralia.org.au/chapter-1-prevalence/1...
That's exactly correct bart, it reduced smoking by over two thirds and kept it that way.
> still doesn't stop 11% of people from doing so.
Like seatbelts, vaccines, and all other health and safety procedures that also don't have a 100% total absolute success rate .. nor never claimed to.
Who wants to wrap people in bubble wrap and lock them away from the world? Are you advocating for that?
On the books, totally worth it.
Australia is a democracy with many small parties and several quasi independant larger party (three main large parties) members, there's been scope for almost anyone to campaign to repeal anti-smoking policy by either running directly or by lobbying their local of federal rep.
People have campaigned for hunting, for cannabis, for many things .. so far no one, to my knowledge, has campaigned to repeal the anti smoking policies.
Are they not addictive? Then it seems a stretch to compare them to cigarettes.
It's a cure for lyme disease, impotence, ALS, chronic fatigue, cancer and aging. Trials are pending but what are you waiting for, do you want to die for lack of trying? 10k/dose.
Nice name choice for your example; I was thinking of paracetamoxyfrusebendroneomycin myself, yours is better.
My mum bought into a lot of homeopathy and Bach flower remedies. Thought she was doing me and dad a favour by getting both, and even "secretly" gave dad doses of the latter (and I was a kid so didn't have much say), so I was fortunate both categories were basically nothing.
But her and dad?
One of the Bach flower remedies was "for memory"… she got Alzheimer's about 20 years younger than her mother.
When my dad was dying of cancer, there was some mineral he thought he was short of (magnesium?), and he didn't realise the homeopathic pills labelled "magnesium" didn't actually contain any magnesium.
IMO, prevent use of addictive ingredients, but beyond that inform, don't forbid.
That said, I think we would get most of the benefit of regulation if we just required an advisory consultation with your GP before you could buy a product whose safety wasn't established. A lot of the danger of overregulation rests on trivial inconvenience vs outlawing experimentation, and I think something like that could split both groups. "Yes, I want to enable experimental mode on my body."
https://www.ema.europa.eu/en/human-regulatory-overview/resea...
The issue, as comes up incessantly in all manner of situations, is the way we regulate drugs as a whole. A lack of safety testing should mean a higher standard of informed consent should be used, not that it should be illegal for someone to get ahold of it
I see lots of benefit to regulatory agencies controlling what claims can be made about medications and holding people selling them to account for quality control failures. Agencies preventing consenting adults from making their own risk-reward calculations does badly on both principle and outcomes
Any system / regulator still needs to force companies to prove their treatment has the claimed effect, and block any that simply don't. On safety, I think there's more wiggle room, however. Treatment here can be based on likely ill effects vs the known effects of the illness of the patient.
An RCT, the gold standard by which medicines are often tested, can easily show a negligible effect size because of the vast confound space of individual differences. A medicine that works perfectly for many of a study's participants will be considered "ineffective" routinely
And hey, in cases like that I think the regulators should absolutely have the power to say "selling this without explaining these caveats is criminal fraud", but not that people can't try the drug anyway if informed of the risks and low likelihood of success as determined by the agency's analysis
In an effort to standardize process and appease large incumbent industry players (often, as here, by erecting enormous entry barriers in front of lucrative markets), we frequently create metrics that are too blunt and remedies that favor governments flexing disproportionate power over the lives and choices of individuals
Weak regulation that allows non-medical products to masquerade as medicine is not the same as “nothing can be done.” Things absolutely can be done.
This situation is made even worse by the Controlled Substances Act and the Analogue Act, which not only artificially restrict both supply and access to a ton of effective medications, but also create this onerous donuthole where a substance can be shown to be effective enough to warrant criminalization, but not pass the rigorous standards to be approved as medicine. It would be a lot better for everyone but enormous pharmaceutical monopolies and police states if we kept regulatory bodies' role to quality control, an official standard by which medical claims could be judged as a guide for laypeople, and fraud prevention.
This is a regulation failure because a good regulatory framework shouldn’t allow this at all. It’s not about whether “the FDA’s hands are clean,” it’s about what system should be in place that gets us to the outcome we want. In my mind, this would be a place where ineffective treatments aren’t allowed (because why should they be?), but safety/efficacy is then traded off against what the patient needs.
Coming from outside the USA, it sounds to me like the regulatory system isn’t achieving any of that? I think I agree with the broad thrust of what you’re putting forward, my issue only comes with the “guide” part. Medical experts need to be the ones leading the treatment because… well… they’re the experts.
Don’t get me wrong, I can see how Americans distrust government after having a president suggest drinking bleach during Covid might work live on TV.
One can be fast and safe, it's just that requires spending a lot of money.
It's analogous to cache prefetching and branch prediction in CPUs, except the cost of bad predictions is measured in millions of dollars rather than tens of CPU cycles, and also that the predictions are much harder.