"...i find the FDAs policies and procedures eminently sensible..."
Damn shame the FDA was asleep at the wheel during the opioid epidemic! (It's a shame you've not bothered to justify that statement in the light of overwhelming evidence to the contrary.)
The FDA did SFA to stop Purdue Pharma selling—sorry—pushing boxes of OxyContin to all and sundry as if they were kids lollipops despite the fact that it would have been aware of over a hundred or more years of solid medical evidence of the dangers of narcotics and narcotic addiction. The fact that any opioid narcotic that's capable of killing pain is addictive—and if not very carefully managed—very addictive is 101 medical/pharmacy knowledge. Even kids know the fact!
Armed with this knowledge the FDA knew what Purdue was doing was completely unacceptable, so why didn't it act?
The FDA still has a lot to answer for its negligence over the Purdue/Opioid crisis. Its ethics are nothing like they were in Frances Kelsey's day.
—
Later edit: Let me add Frances Kelsey was a true hero, she saved many kids from developing terrible deformities! Despite current criticism of the FDA by many including myself, we should never forget her contribution to medicine.
> If a doctor subscribes to stereotypes of what an addict looks like — nonwhite, from a low-income community — the physician may assume their white, middle-class patients are immune to addiction, he says.
Yeah, I'm not a bit surprised, but in my view there's an even deer systemic reason and we need to fix it.
The overriding issue is that medicos, pharmacists and opioid drug manufacturers should know the dangers of opioids like the back of their hand. I'd even argue that such knowledge is almost a priori in the sense that the vast majority of medical professionals would have already known the essential details before they'd even entered training from the fact that it's common knowledge that opioids are very addictive and dangerous if not managed with considerable care.
As I see it, just about everyone knows the multiple reasons behind the decades-old war on drugs by just about every government anywhere on the planet. Even if the way this war was and is still being conducted is ineffective and counterproductive (which, incidentally, is my view), one would have had to have been Sleeping Beauty and have slept though the past 100 years not to know that narcotic opioids, heroin, morphine, etc. along with stimulants, cocaine, methamphetamine, etc. are at the center of this war. (When I was a kid, drugs were never an issue as fortunately we kids never came across any—not even pot! That's to say, with respect to knowledge about drugs, we kids were about as naïve as it gets, nevertheless, even as a nine or ten year old, I'd heard of heroin and morphine and was very well aware of their dangers!)
What I am saying is that the relationship between opioids and addiction is so well known—and that these facts are so central to medical and pharmacy training—that it's impossible for professionals not to know about such matters. Thus, the fact that everyone wasn't immediately up in arms and pointing to the problem and demanding that something be done about the problem is very strange indeed. I'd go so far as to say that it's a sociological phenomenon worthy of research. It's not just a matter of penalizing and disciplining the perpetrators but getting to the core of why it actually happened given that basic training, existing laws, dispensing protocols, FDA rules, FDA experience etc. any one of which should have been able to prevent the crisis but didn't.)
(In my opinion, the opioid crisis has a similar ring it to what happened at Boeing with the 737 Max where once the notion critical systems engineering and attention to safety details was paramount and inculcated deep within every level of the organization and its work culture but which in recent times vanished. Clearly, we have to get to the heart of the problem and understand it before we can rectify it.)
As a European who had to deal with getting a medical devices approved both in the EU and in the US: mad respect for the FDA.
There is lots of paperwork required on both sides, but the difference is who accompanies the project. In the EU it's bureaucracts with zero domain knowledge, in the US it's domain experts who asked the right questions and were strict, but also genuinely helpful.
From a "well what did you expect" perspective - delaying drugs and asking for more safety data is occasionally going to result in scary drugs getting caught and kept off the market.
The problem is the flip side - when wonder drugs are delayed causing unnecessary pain and suffering - generates no human interest stories. The damage of increasing cost of drugs and delaying the rate of improvement because of delays in the approval process is also an unknown.
The FDA is a process - every time something goes wrong, bureaucrats take heat and then tighten the standards. This process is going to be more conservative about approving drugs than is rational.
These are problems that would have been solved without the preemptive FDA ban on unapproved drugs.
Society, as usual, over-reacted, and created a set of highly restrictive rules that have cost probably millions of lives over the subsequent decades.
A much more sensible law in the aftermath of the drug scandals of the 1930s and 40s, that would have run a much much lower risk of having a myriad negative consequences, would have been a requirement to include on any drug, a disclosure of whether it is approved by the FDA. Non-approved drugs could have been required to include a warning that the FDA recommends a person not take the drug as it has not been verified to be effective or safe.
This provides most of the benefits of the FDA's role as gatekeeper, without most of the harm done by heavily restricting a market and making it totally dependent on a single central authority. Providing consumers with the ability to ignore the warnings of the FDA would have acted as a lifeline/failsafe in cases where the FDA erred.
As someone who works in the healthcare industry I agree. I think the FDA does a very good job all things considered. They have approved drugs that were desperately needed (Avastin for breast cancer) based on little evidence, only to later pull them when the data didn’t support approval. They appropriately balance risk versus benefit.
And there is more at stake than most people realize. Approve a vaccine that isn’t safe and people will lose trust in general and will refuse any vaccine. Then what?
Lots of Monday morning armchair drug regulators in this thread.
That's sort of a different situation. Thalidomide did what it was supposed to, but ended up having horrible unknown (at the time) side effects. The FDA correctly didn't approve it based on the lack of safety data.
Opiates also do what they're supposed to, but the fact that they're addictive wasn't a mystery. They're safe if taken and prescribed as instructed. The failure is more on the DEA and other enforcement bodies for not dealing with the obvious prescription abuse. The FDA doesn't make controlled substance decisions.
There's lots of controversy about opiates being excessively addictive even when used 'on label'. I didn't find it with a bit of searching, but I remember an article about the 'extended release' aspect of Oxycontin tending to encourage addictive use patterns (because it didn't really work for 6 hours).
Figuring that out wouldn't necessarily be an up front trial kind of thing though.
A while ago I posed a similar question and the answers/downvotes made it clear to me why; Americans have a broken model of pain management. Americans think that opiates are necessary to manage the pain from most surgeries, back pain, headaches etc., so, they get opiates to do that, with the obvious and foreseeable catastrophic consequences.
A friend of mine was very briefly hooked. He had pretty serious leg surgery after an accident at an air force base, and the Veterans Affairs doctor basically wrote him out a prescription for a massive quantity of pills with the instructions to take as needed.
So, naturally, he sat around with nothing to do during recovery but to play video games, drink beer and pop pills.
Pain management is definitely not taken seriously enough by some doctors, and too many people are too trusting that their overworked doctors and nurses know better.
Both myself and my wife also have chronic pain from past injuries (back pain mostly, plus some arthritis for me) but we manage with stretching, liberal amounts of tiger balm, and the occasional ibuprofin.
I had relatively routine surgery last year that affected my kidneys. It took a few days to recover, and after a few days I wasn't getting any better so they sent me to the ER. I had Percocet that they prescribed me after the surgery, but the ER doctor wrote me a prescription for straight oxycodone because he was concerned that the acetaminophen in Percocet is sufficiently damaging to the kidneys that I really shouldn't be taking them.
I have to be honest, I was really hesitant to fill that prescription. I did after a few hours when the pain got unbearable (at 1 in the morning, they filled it in 5 minutes which also makes me worried that pharmacy would be an easy robbery target...), and damn they did work quite well. I only needed them for 2 days, and I didn't get the sense of being high that I expected, and had no issues stopping them. I can't say I didn't wonder what would have happened if I needed them for a week or more, or if I had previously been addicted to opiates.
It just seems hard to believe in modern times there's nothing in between NSAIDs/Tylenol and full on opioids for managing pain, especially for this sort of post-op temporary use case.
No kidding. Years ago I had a collapsed lung and surgery to repair it, and they sent me home with some kind of opioid. I took one and felt great for about a half an hour. Then the room started spinning and I spent about 4 hours trying not to puke, which would have been really painful with a bunch of stitches in the side of my abdomen. Once that passed, I threw the rest of those things away and just took some tylenol and tried to just move carefully to avoid pain.
This highlights something I think more people should do: be as careful as possible while healing, and accept the fact of enduring some amount of pain. Sure, there are people with chronic pain problems, and extreme acute pain that probably calls for the big guns, but the fact that you were able to deal with it using tylenol and some self-care is IMO a good thing.
A bunch of years ago I broke two ribs, and decided not to go see a doctor, after a doctor friend told me they wouldn't be able to do anything about it, aside from prescribing pain medication and telling me to try not to move much (with the caveat that if at any point I started to have trouble breathing, I must call 911 and get myself to the ER). It wasn't a particularly fun 6-8 weeks of healing, and I took the max recommended dose of OTC ibuprofen many of the days, but I got through it. Would it have been nicer to have zero pain? Sure. But I don't think the addiction risks of something like an opiate would have been worth it, and the healing process serves as a reminder to me to take better care of my body.
(Just to be clear, because I'm sure someone will put words in my mouth otherwise: no, I don't think this "grin and bear it" method works for all situations! When it's possible and reasonable to get by with minimal pain medication, I think people are better off. But I think many people -- aided and abetted by overzealous prescription-writing by some doctors -- go too far in trying to remove all pain, to their detriment.)
This is my same reaction to opiates. After telling my doctors I didn't want anything opiate-related for anything. I had a year and a half of really bad colds and strep that was probably at-that-point undiagnosed asthma, and the docs kept giving me codeine syrup. After getting ignored for so long, I switched to telling them I'm allergic to opiates. Now it's in my records and now it doesn't come up anymore.
Ibuprofen was already a huge step up from Paracematol, which is another step up from Aspirin. The fact that ibuprofen is also much better tolerated, has fewer side effects, and has to be dosed less often means you're taking the best non-opioid painkiller we know of as your first-line option.
Well, lucky for you, both (in fact, all three) are still available. But, as a statistical matter, Ibuprofen is safer. Not only because the liver is such a contentious point for drug elimination, including alcohol, but due to the ability to fix overdoses. Even with minor overdoses (such as mixing with alcohol), paracematol causes permanent liver damage, whereas stomach ulcers can be repaired. More than 100,000 people die annually from Paracematol overdoses. Ibuprofen is sold more, and has fewer than 16,000 deaths.
Kidneys cannot be repaired. You'll need hemodialysis if you overdose on ibuprofen. I don't know the state of the research on the topic, but I expect locations offering OTC NSAIDs to have issues with acute and chronic kidney injury that goes pretty much unnoticed. Especially in populations with high diabetes prevalence. One of the reasons for higher paracetamol mortality is because people commit suicide using it (especially common among teenagers).
"More than 100,000 people die annually from Paracetamol overdoses."
The fact is we seem to be damned if we do or damned if we don't. We desperately need a reasonably effective and safe painkiller. If 100,000 actually die from paracetamol per year then there's a reasonable excuse for banning it. But what do we replace it with given that many cannot take NSAIDs for various reasons?
- Pharmacists and doctors repeatedly say paracetamol/acetaminophen is very safe if taken according to directions, the trouble is, that in excess, it shuts the liver down and it cannot recover/clear the drug in time before real trouble sets in. Moreover, it's not very effective as a painkiller.
- NSAIDs, ibuprofen and aspirin, cause bleeding of the stomach and other major issues, even hearing loss in high doses.
- The newer COX-2 selective NSAID Rofecoxib, aka Vioxx, was very effective at certain forms of pain relief but was banned by the FDA after it was found to cause cardiac effects in susceptible people including heard attacks. (Another criticism I have of the FDA is the inordinate length of time it took for the FDA to remove Vioxx from the market after its cardiac effects became known—this was around three years. (I recall reading a paper in the AAAS journal Science that outlined Vioxx's cardiac effects and thinking to myself that the drug would have to be banned. That was some three years before the FDA actually banned it).
- Celecoxib, also a newer COX-2 selective NSAID that is in the same class as Vioxx, hasn’t yet been banned but it still has the potential to cause cardiac effects. Moreover, it is not as effective a painkiller as Vioxx was.
- Then there's the dangerously addictive opioids.
- Once we had another rather effective painkiller but it too has been long banned. APC was a mixture of aspirin, phenacetin and caffeine and it was rather effective except for the fact that it rotted one's kidneys, many instances of kidney disease were attributed to its use
Alas, there's precious little else, especially anything that's safe.
Unfortunately, my wife has very unpleasant reactions to acetaminophen / paracetamol, and I notice roughly zero reduction on pain from it. Fortunately, neither of us has stomach issues, so we stick to ibuprofen.
TBF, they should stop selling most things OTC. In the current US system that would mean massive additional costs to the consumer, but that is really a policy problem and not a medical one.
Where would you draw the line? Being unable to buy something simple like ibuprofen OTC would (as you point out) mean massive costs for people, and to what benefit? Is there really a huge problem with people overdosing on ibuprofen and suffering permanent damage or death?
And even if there is, would we really expect requiring a prescription to fix that problem? That doesn't seemed to have kept opiates from ruining people's lives.
Codeine is metabolized to morphine, so it's not really 'in-between'. Plus it's a bad painkiller due to variability in pharmacokinetics. Good practice would be to not use it anymore.
Now, there also is stuff such as tramadol (WHO ladder step 2). But it also can be abused, and is indeed sold on the streets.
"Codeine is metabolized to morphine, so it's not really 'in-between'. Plus it's a bad painkiller due to variability in pharmacokinetics."
Right, and as you say it'd be a good practice to stop using it, especially if it's OTC, which, as mentioned above, it still is in some countries.
It used to be OTC where I am but it's now only available by script. I recall decades ago taking combination codeine/paracetamol (aka acetaminophen) for headaches and the codeine definitely exacerbated them, moreover it was not very effective as a painkiller.
It turned out that whilst paracetamol wasn't very effective by itself the headaches didn't rebound as they did with the codeine mixture. All up, NSAIDs—aspirin, ibuprofen—were better even though they caused minor stomach upset.
Yup. Tried gummies and hemp cigarettes both. I thought the hemp cigs helped the back pain a bit, but not so much the joint pain. The effect was small enough that it wasn't worth the money to keep doing it. We get much more mileage out of stretching and tiger balm- especially the back patches and arthritis lotion formulations.
6 months at most, I think. CBD products are becoming trendy out here, but actual flower is much harder to come by, hence attempting the hemp cigarettes (hempettes?).
Maybe I'll try again this spring or summer when I get back into doing some light forestry, but I almost prefer to not mask the pain so I know I'm not making things worse.
There is a great Freakonomics podcast on the opiate crisis. If you want to get some food for thought about the American approach to pain management, how it is done elsewhere, and some background on the opiate crisis.
(Looks like episodes 402 and 403, from a quick search.)
Many American regulatory institutions have crumbled in the past few decades, the FAA being a particularly jarring example.
In some cases it seems like peoples' trust in those regulators may be fueled by nostalgia, but the FDA does seem like one of the few agencies that has retained some measure of independence.
Looking at what has happened in this nation's other industries and institutions, only one crippling decades-long medical crisis doesn't seem all that bad.
That's not an explanation for why the FDA has failed to address the regulatory aspects of the opioid crisis, but an argument for why we should discount or ignore that failure. At the very least – this is a non sequitur.
I disagree. Regulatory capture is a clear and present danger to the United States, and it is contributing to a breakdown in accountability across all sectors of the nation's economy and society.
So I offered it as an explanation for why the FDA could be well-respected and reasonably functional, while the United States fails to address some acute public health issues.
Things could be much worse; at least they don't turn a blind eye when huge sums of money are not involved. It's still very rare for a drug's approval to be pushed through via fraud, and there are a lot of diseases that need treating. They have a solid track record, even now.
The FAA are the ones responsible for stopping shit like the 737Max fiasco. Yes, Boeing did it, and many people there deserve to go to prison, but the FAA is supposed to be the guardrail ensuring they can't get away with it in the first place. It was an objective failure, and it has eroded the trust in them - point in case, most other aviation regulators did their own checks on the 737 Max before allowing it back to service, which usually doesn't happen ( EASA trusts FAA's ratings and vice versa).
The US opiate crisis has its roots deep in US healthcare culture and the blame lies on both sides of the doctor-patient fence. US docs used to prescribe opiates like candies, but US patients expect to feel no pain at all and are extremely aggressive legally speaking. Those two aspects go hand in hand.
Exactly, the FDA was not only completely incompetent but indirectly responsible for the deaths of thousands. It should have pounced on Purdue at the very outset.
Unlike much medical/drug research, knowledge about opioids and opioid addiction is well known.
The FDA irresponsibly failed to act on a no-brainer.
It's also very easy, especially at the moment and with the benefit of hindsight, for people to be going that the FDA last March should have said "F it. Go out with whatever vaccines you think will work and see how it goes." Which is what a fair number of people believe (at least other than those who still feel testing was rushed).
My thinking on this was the exact opposite. Emergencies like this are precisely when you need these types of agencies the most, because you're talking about treatments that will be taken by a huge amount of people in a short timespan. Negative effects from treatment could end up as a catastrophe on their own. It's more important than ever to get it right.
Also when I tried seeing what people that actually develop vaccines had to say. It sounded like crash programs to produce a vaccine would take a year before there was enough capacity to mass vaccinate people. And then six months to vaccinate everyone. The required trials didn't slow anything down because they were done in parallel.
Also, some of the vaccines they developed for covid didn't work. A year ago people were somewhat dubious about mRNA vaccines because they'd never been tried before. And then previous vaccines attempts have also resulted in vaccines that make the infection worse. Or caused dangerous side effects.
I don't think with vaccines there is this 'one neat trick' that professionals have overlooked somehow.
And even six months into parallel speculative manufacturing and multiple vaccines approved or on track to be approved for emergency use, the US--in spite of vaccinating at one of the highest rates in the world--still needs to up its rate considerably to hit 50% of the population over the summer sometime. The idea that if the FDA had only washed its hands of the whole approval procedure thing in March, things would be fine now is just a complete fantasy.
I guess it depends on the danger of the virus. If the virus is as congagious as covid for example, but it kills 40% of people even among the young, there would be far less concerns about giving experimental vaccines to healthy people. I hope the vaccine production lines we are building now will stay well oiled until the inevitable hit of the next pandemic.
Sure. Given a very different set of facts, a rational government administration should have/would have pushed through highly risky treatments as not being worse than the alternatives. Would be an awful situation if millions were killed or had permanent side-effects but couldn't be worse than the alternatives.
On the other hand, it's likely that thousands of people will die due to the delay in approving the AstraZeneca vaccine. There are always tradeoffs, and it's not at all clear that the FDA is operating at the optimal level of caution.
In total, Thalidomide caused around 2,000 deaths and 10,000 birth defects. Compare that to the 100,000 people that the FDA killed by not approving a single beta blocker sooner. The FDA waited until 1981 to let doctors prescribe Timolol to prevent heart attacks. Stunningly, the FDA bragged that approving Timolol would save up to 17,000 lives a year.[1] That same drug had been in use in Europe since the mid-70s, meaning that the FDA tacitly admitted to killing 100,000 people by forbidding its use in the US. Even the original beta blocker (propranolol) wasn't allowed to be used for angina or hypertension until 1978, 13 years after it had been approved in Europe. That delay likely killed more than 100,000 people.
The FDA is also the reason why epi-pens are so expensive[2], why Martin Shkreli was able to jack up the price of Daraprim[3], why many drugs suffer from shortages[4], and why home testing for covid was delayed for so long[5]. And don't forget that covid community spread was discovered in February of 2020 only because researchers risked jail time by violating the FDA's prohibition on testing.[6]
Yes, the FDA lets leaders avoid an occasional political snafu. But the organization kills far more people than it saves.
So, defensive language aside, I think that the FDA has a point in its white paper. The reason we don’t have cures for a lot of diseases is not so much that pesky regulations keep great drugs from getting to the market. It’s that we don’t know enough – yep, even in 2015 – to make so many great drugs.
Now, when I mentioned that we’d surely have killed off more people by doing drug research by the more direct routes, the reply is that we’ve been killing people off by moving too slowly as well. That’s a valid argument. But under the current system, we choose to have people die passively, through mechanisms of disease that are already operating, while under the full-speed-ahead approaches, we might lower that number by instead killing off some others in a more active manner. It’s typically human of us to choose the former strategy. The big questions are how many people would die in each category as we moved up and down the range between the two extremes, and what level of each casualty count we’d find “acceptable”.
So while it’s not crazy to say that we should be less risk-averse, I think it is silly to say that the FDA is the only (or even main) thing holding us back. I think that this has a tendency to bring on both unnecessary anger directed at the agency, and raise unfulfillable hopes in regards to what the industry can do in the near term. Neither of those seem useful to me.
The replies to my comment here nicely delimit the cleft stick the FDA is in. You are on the "oh, god, just let them try it already! the FDA are stick in the mud beancounters just holding everyone back" side.
A few others are on the "But this one time, they didn't pull Vioxx fast enough, and look at what it got us!!" side.
For myself, I'm glad that 1. i don't have to walk that tightrope and 2. there are enough people to make an institution old enough to have memory that _do_ walk that tightrope.
But i'm pretty sure that sanity is somewhere in the middle, case by case, agonizingly slow clinical trial by agonizingly slow clinical trial.
"So while it’s not crazy to say that we should be less risk-averse"
Surely the way around that is to expand temporary/experimental approvals. This would require the patient to be properly and adequately informed of the risks of taking any new drug after which he/she would sign consent which would indemnify pharma, researchers, FDA etc.
That said, any such approach should be very tightly controlled to ensure unethical cowboys in the pharma industry don't take advantage of it.
"You hereby acknowledge that neither the safety nor efficacy of this....procedure/substance has not been established. As a result of taking it, literally anything could happen to you and/or your future unborn children."
It is already really hard to assess costs and benefits of medical treatments; expecting an ordinary person--dealing with a scary diagnosis--to do so with even less information seems ethically...fraught.
Given your quoted text was written by hprotagonist, perhaps you should be addressing him in the first instance rather than me. But then you've also addressed me by asking 'What would that consent form look like?' and that impinges on or is inferred from what I said in reply to hprotagonist.
That said, as I've addressed the matter of the wonderful Frances Kelsey and her rigorous approach to the approval of thalidomide, I will address issue of experimental treatments more in general as well as emphasizing same issues with respect to COVID-19 and the ongoing shemozzle that surrounds them.
As with the Frances Kelsey/thalidomide matter where the outcome could have been truly disastrous for thousands of unborn kids if Kelsey had not dealt with it as a matter of urgency and that she had done so with rigor and tenacity, a similar situation exists with the various therapies for COVID-19, especially those that are truly experimental and or have not yet demonstrated their medical effectiveness. As you rightly acknowledge when you quote hprotagonist where he says "that neither the safety nor efficacy of this....procedure/substance has not been established. As a result of taking it, literally anything could happen to you and/or your future unborn children."
As with just about any vexing matter, I'd assert that the key issues always involve both its magnitude and our perceived urgency to rectify it, thus it's the product of both that will determine how soon and how proactively we will act. As COVID-19 is an out-of-control pandemic that continues to kill people on mass, we are forced to act urgently in order to stem its spread. This call to urgent action alters everything, as it has now forces us to undertake risks that are not normally associated with responsible prudent behaviour.
As I mentioned in an earlier post on a different issue, 'desperate times call for desperate measures'—and with desperate measures come very considerable risks. Moreover, with COVID-19, when it comes to weighing up options, the luxury of time is not on our side. And as we've seen everywhere, that has had a considerable and often very detrimental bearing on the ways we've responded to the pandemic not to mention the many decisions we've already made in our attempts to combat it.
Such experiences are not new to human beings, as we've faced many similar situations in the past. The problem here however is that we've not learned much from the fact. For instance, we could have drawn valuable knowledge from well-established protocols that have evolved from battlefield triage experience. Here, ambulance personnel, stretcher-bearers and medicos charged with aiding the wounded and dying face terrible extremes that they would never experience in normal life. As an experience, it's as bad as it ever gets, and that's why it's such a worthwhile and relevant example in our ongoing battle with COVID-19. Moreover, tragically, such experience is all too commonplace (thus it's a realistic one): as the history of warfare shows, battlefield triage situations have occurred many hundreds and hundreds—if not thousands—of times in the past, and no doubt, they will continue to occur repeatedly into the future. Not learning from the experience of history is a form collective madness.
There is any number of instances where with enormous courage and often without previous experience, rescuers have had to make decisive life-changing decisions in an instant—an instant that encompasses anything and everything that's truly relevant at this point, from triage decisions and concomitant actions thereof, to considerations of one's own safety and the safety of others around one, to one's own ethical behaviour and related humanitarian considerations. Moreover, rescuers not only have to remain self-composed to adequately manage the enormous stress they are under but also they must remain capable of performing their appalling and arduous task without fail, and for that, they call heavily on their training.
As a medico in a war triage situation, you will be surrounded with dozens of wounded and dying soldiers and you'll only have split seconds to decide between those who may likely live and thus be rescued and those who you will have to leave out on the battlefield to die—and you'll have to do all that almost automatically as you'll have precious little time to think through your actions. Right, you will find yourself in an ethically fraught situation—one that's as ghastly and truly horrible as it's ever possible to be in.
This is where training is crucial—vitally important. You will have been trained to be decisive, objective and as unemotional as it's possible to be in these circumstances in order that you will not only save as many lives as is humanly possible but also later to stop you going mad from PTSD—or at least ameliorating its effect (as you can comfort yourself from knowing that you've performed your duty to the extent of doing everything humanly possible in extremely difficult circumstances).
The logistics of introducing new and untested procures into the treatment of COVID-19 are similar to the triage scenario mentioned above. As a professional involved in the decision-making process, one would have to quickly weigh up the potential benefits that any new procedure would likely bring for the patient against possible unforeseen and potentially life threatening risks—and then be honest and as forthright as is possible with the patient by explaining everything.
One's decisions will involve risks and sometimes they will be wrong and will result in disastrous consequences, at other times one's decisions will be correct but force majeure—an act of God will intervene and things will go horribly wrong. One may even make correct decisions based on the best advice available but ultimately in the light of further experience, this advice may also prove to be wrong.
What one cannot do is to procrastinate or vacillate around making hard decisions, or failing to make them at all, or by watering them down because of nonsensical political reasons. For as we have all too often seen in the recent past, these dubious and hesitant actions have cost many, many lives. As all us know by now, this deadly virus waits for no one.
With COVID-19, we are in new territory. Only later after the results of our present decisions and actions have been properly assessed, and after the statisticians have analyzed the data contained within their integrands, that a new best practice will be established for this current COVID-19 scenario.
In the interim, we have to act as professionally as is possible by not only taking the best advice available but also by making informed decisions based actual evidence gathered from procedures and things that have already been demonstrated to work.
By acting in as truly professional manner as is humanly possible, it is unlikely that your worst dreamt scenario that 'literally anything could happen' will, in fact, actually happen.
Taking the median of public opinion does not result in an accurate understanding of reality. The FDA optimizes for minimizing scandals, not for helping people. That’s why they kill 100x more people by not approving good things than they do by approving bad things.
"Even the original beta blocker (propranolol) wasn't allowed to be used for angina or hypertension until 1978, 13 years after it had been approved in Europe. That delay likely killed more than 100,000 people."
I was unaware that propranolol was approved as late as that in the US. This seems very strange as Sir James Black's work on propranolol was widely known and he was widely respected before he was knighted and awarded the Nobel Prize for his work with both propranolol and cimetidine.
Why on earth did the FDA take so long to approve it given that there was no other beta blocker available at the time? (Thus, the hypertension issue could easily have been perceived as a crisis even allowing propranolol to be, say, approved on a temporary basis much earlier on.)
Looking at the FDA's record of approvals, it's hard to see any consistent granularity in its approach. I'm curious as to why this may be the case.
The article you reference mentions a major Norwegian study showing that it prevents death had just concluded. So the FDA was acting on fresh data.
In addition, timolol is one of many molecules in the beta-blocker class and propranolol, another beta-blocker, was already approved in the US since 1973. And from a quick cursory google search, it appears there is no difference between the two when it comes to reducing hypertension and future risk of heart attacks.
The FDA approved propranolol in 1973, but not for treatment of hypertension or angina. It wasn't until 1978 that they allowed beta blockers to treat those diseases (which are the bulk of lives saved by beta blockers).
The WaPo article does talk about a study that had just concluded, but Timolol had been studied for over a decade previously, and had been used in Europe for years. I didn't have to look hard to find a US study done in 1976 that praised Timolol's effectiveness in protecting cardiac muscle after a heart attack.[1]
If you doubt that Timolol is far more effective at preventing heart attacks than propranolol, then why believe the rest of the WaPo article? It references a study that you can't find on the Internet because it was published over 40 years ago.
The bottom line is this: Despite the drug being considered safe by the relevant European authorities, the FDA forbade US doctors from prescribing it. Had the FDA simply allowed doctors to prescribe compounds approved by their European counterparts, they would have avoided tens of thousands of deaths.
But the FDA does not dictate how drugs can be used, only whether they can be marketed and sold. There is nothing stopping a physician in the US from using propranolol for preventing heart attacks before the FDA gives its blessing for that use.
If you look at cancer treatments today most uses (not drugs, uses) are not formally approved by the FDA. It all based on research, publications and guidelines.
Sure, but that kind of makes sense for why the FDA acts like they do, if you want more risky off-label treatments without the large studies the FDA requires, your doctor (and you) can take the risk at your (and their) option.
I think your position, and that of the FDA is based on emotion, and not any logical reasoning.
The Thalidomide crisis cased a few thousand issues.
The risk-benefit analysis clearly favored lifting the ban on COVID vaccines after successful phase 1 trials, in June 2020 or so. They decided they should be banned until further study, during a pandemic.
The FDA was empowered explicitly by congress to take more aggressive action during such a time. They opted instead to ignore that mandate, and instead run things like normal, albeit with taking reasonable time to respond to a crisis. The deaths of 100,000 to 400,000 could be directly blamed on the simple fact that for most of this crisis, we had not 1 but approximately 8 vaccines that were all expected to be safe and work, and all turned out to be safe and to work. Vaccines candidates are not like Thalidomide, period.
It's important for citizens to publically shame the FDA for their actions, and demand change from our elected officials.
Thalidomide babies were my age and not unknown where I grew up. Limb deformities differed: sometimes they had flipper-like appendages, sometimes shortened limbs. (FWIW while cruelty was extremely common back then I never saw a single case of anyone handicapped being made fun of. Nor did I ever witness any racist behavior in my racially integrated neighborhood.)
There was a locally famous dude at the public pool who was kind of the coolest guy around. His legs stopped at knee length and he would pull himself up the high dive ladder, walk on his hands to the end of the diving board, and casually launch himself off the end perfectly every time. It was spectacular.
I love stories of people thoughtfully doing their jobs and having huge life saving impact like this.
I was saying to my wife on a recent drive, that there's some civil engineer somewhere who figured out you can embed those little light reflectors into highway lane markets, and some other engineer who figured out those perpendicular cuts in the asphalt that vibrate your car before you run off the road.
Both of these probably naturally arose in the context of their work, and both of these things passively save hundreds of lives daily.
I recently listened to an interesting episode about those reflectors on the 99 Percent Invisible podcast. This [1] is an associated article on their site that seems to have similar content to the episode I listened to.
While this is great and all, the comments indicate that tons of doses circulated the USA as samples. There are two people in the comments claiming to be survivors from these samples.
If this is true, then the article is incorrect. It appears that Americans were just denied compensation because the drug wasn't approved.
I'm sure the harm would have been much greater had the FDA approved the medication. But it seems unfair to say they were no victims in the USA.
And now Thalidomide is used in treating cancer and sold for over $200 a pill.
Quite a nice markup for telling the patients not to get pregnant while on treatment.
Only one enantiomer caused birth defects - and a defect in the original manufacturing process created L- as well as D- chiral species. Pretty sure it no longer contains the problem enantiomer.
>At the time of the drug's development, scientists did not believe any drug taken by a pregnant woman could pass across the placental barrier and harm the developing fetus
It's not an entirely crazy concept. There are several barriers in the body that isolate systems from one another that can be challenging to cross, and the blood-brain barrier is probably the most difficult of all of them. The existence of the blood-brain barrier has been known since the early 20th century (despite the difficulty of actually finding it!), and it wouldn't be entirely crazy to a priori believe that the placental barrier would be similarly strong. As it turns out though, the placental barrier is probably the weakest such barrier.
> the placental barrier is probably the weakest such barrier
At least, in humans (and other primates and rodents, but not most mammals). Human embryos/fetuses receive more nourishment and achieve more growth during prenatal development in part because the placenta invades the uterine wall much more—for lack of a better word—parasitically than in other mammalian species. That's great for a lot of developmental stuff for the fetus, but it does make transfer of (say) drugs considerably easier. (It also is the source of a lot of the common maternal complications in human pregnancy and is the reason one should at least be in contact with medical doctors while pregnant, even if a low-intervention or home birth plan is intended....)
I mean, people think all kinds of things that seem plausible at the time and look crazy in hindsight to future generations. This is what progress looks like.
Medicine used to be, and in substantial part still is, a disordered heap of hypotheses relying on practical experience and relayed by the stars of the field. There are plenty of strange examples throughout history. For example, we used to believe until not so long ago that infants couldn't feel pain (with all the 'interesting' consequences on practice you can imagine).
I'm less than convinced that anyone sincerely believed that. It seems more plausible that it's a lie they told themselves to paper over other cultural, profit, or institutional pressure.
Of course people believed strange things! As I said, the field is far from being hard science even today (am MD myself). What do you think "expert opinion" actually means? Well, just that... and the literature is full of such opinions driving many important guidelines for practice in the real world.
As recently as 1999, it was commonly stated that babies could not feel pain until they were a year old.[0]
Also reminds me how people were blaming for FDA for vaccine delays including President Trump.
It’s not a vaccine, until it’s proven safe. While FDA isn’t perfect they have stringent procedures to prove something is safe.
The way FAA let Boeing ship planes that killed people, and lost their trust, same applies to FDA. If people die and have irreversible damage, it’s on their hands.
On the other hand, there are costs with delaying approval. This is pretty obvious with the Covid vaccines, probably at least 200,000 on the dead side of the ledger.
Another cost that's harder to quantify is the cost in lives and misery of drugs never developed because it's for an uncommon and there's no way to make back the money needed to pay for FDA approval.
There are like 50+ COVID vaccines in development. Which one do you administer? Forget about side effects, half of them are probably duds! Can we afford to administer billions of vaccines that don’t even work?
>Can we afford to administer billions of vaccines that don’t even work?
the seen and the unseen strikes again
We have already sacrificed trillions of dollars in shutting down or greatly restricting the global economy for a year, so any questions of "can we afford" are totally moot by now
I don't just mean dollars. Getting everyone vaccinated is a huge national effort, nine to twelve months long, that we need almost everyone to participate in. Everyone has to trust the institution. So what happens if the first two vaccines were benign but also ineffective? How do you convince 300 million people that this time we've got it right?
It's worth noting the fastest ever vaccine development before this was 4 years; the early COVID vaccines were developed & authorized in 9 months and a large risk production ramp was started before authorization was granted.
Yes? 10 billion vaccine doses that cost $100 each would be a trillion dollars. Which is somewhere between 7% and 25% of the total cost of COVID-19 to the US.
The real question is whether we can afford to use our non-emergency drug approval process in a time of crisis. This time the answer is probably "yes, and it probably only cost a few tens of thousands of lives and a few trillion dollars" but if the disease in question had been Ebola instead of COVID I worry that we would have seen the same ineffective response that optimizes for minimizing liability instead of maximizing effectiveness.
The problem is not administering one vaccine. If you were pretty sure which one to use you could take a gamble- which is exactly what we have done with early auth of the Moderna and Pfizer! But If you don’t yet know which ones actually work yet, do you give everyone ten different experimental vaccines in one shot?
With the agonizingly slow rollout of the current vaccine, we wouldn't be administering billions of vaccines without soon finding out if it is efficacious or not.
> Can we afford
Evidently we can afford to spend several trillion dollars and hundreds of thousands of deaths waiting 6 months for the vaccine trials.
That's because the FDA basically told them it would be rejected unless they spent months collecting more data. Similar situation with the Novavax vaccine, which seems to have even better results than the AstraZeneca one.
No. It's just that there's no penalty for being anonymous and wrong on the internet, even here, and people get a thrill and a small sense of boost in their self-esteem putting down experts in a field. They don't know more than the experts, but they suffer no consequences from saying this. That's all. The FDA is one of the crown jewels of the United States and maybe the world. It breaks hearts in the development of pharmaceuticals and medical devices that barely miss efficacy thresholds and that earns it enemies. It also prevents dishonest scam artists and psychopaths from selling fake or harmful cures as medicine, and those people, as we've clearly seen recently, have no sense of decency and attack anything that prevents them from personal benefit.
Thank god for the FDA. Thank god for Frances Kelsey.
Consider that the other commenter likely does not know who you are or whether you are trustworthy, even on the off chance that they would be interested in taking such a bet with a trustworthy person.
Your bet is nonsense, and nobody is making the argument you're framing the bet against. There's not the slightest similarity in the massive teratogenicity of thalidomide vs waiting a few months for safety data on a vaccine. Not getting an EUA is not at all equivalent to a black label. You completely ignore we have two vaccines that work better already, that have research behind them from post-SARS1 and MERS research with the mRNA approaches. Astra will get approved after it proves its safety.
Where did I miss anyone mentioning sars-covid-2 besides you? You are the one that brought it up, and I still have no idea why you did. The FDA is right to make sure vaccines are safe. We know AZD1222 is less effective already, so it better be at least equivalently safe and that requires data.
> Not getting an EUA is not at all equivalent to a black label.
It is equivalent though, because without an EUA it's illegal to give that vaccine. Right now, we are supply constrained on vaccines - the choice for the people on the margin is not "AstraZeneca now or Moderna now", it's "AstraZeneca now or Moderna in a few months, during which time there's an uncontrolled pandemic raging". Or rather, that would be the choice, except that the AstraZeneca vaccine is illegal to distribute so the only choice is "take your chances with no protection at all".
> There's not the slightest similarity in the massive teratogenicity of thalidomide vs waiting a few months for safety data on a vaccine.
You're right. They're not comparable. Spuriously waiting for Covid data is way worse than thalidomide. The latter resulted in two thousand deaths, whereas the former will result in two million deaths.
The UK, where the main difference is the approval of the AZ vaccine, is forecast to reach herd immunity four months before the United States.[1] America is currently averaging 3500 deaths per day.[2] That's an unecessary 127 deaths per 100,000 persons.
Since we're comparing total worldwide deaths from Thalidomide, that would result in 6 million unnecessary deaths if FDA policies were adopted globally.
So if the AZ vaccine was the only vaccine available to save Americans’ lives (which it’s not) and it was 100% effective (which it’s not) and the FDA delayed its rollout by a month, by your argument the FDA’s delay would have caused 105,000 (3500 x 30) unnecessary deaths.
1. Those numbers don’t work. There are other vaccines in play which can have a disproportionate impact on the death rate if they’re properly targeted at people at highest risk of severe infection. You don’t need herd immunity to prevent most deaths.
2. I’m still not seeing the ‘two million’ deaths you mentioned?
The context is that there's a pandemic going on and the FDA is being a bit slow at approving vaccines. Historical failures of the drug industry like thalidomide explain why the FDA is currently extremely cautious about approving drugs. So you can imagine why some people might get a little worked up when they see a story about thalidomide at this moment in history.
The FDA approved emergency use authorizations for both Pfizer and Moderna within 3 weeks of receiving the applications.
Johnson & Johnson just submitted their application, with emergency use approval expected by the end of the month if there is nothing wrong with J&J's data.
I don't see how this is "a bit slow". It's rather fast, considering that the FDA does their own analysis of the submitted raw data and has a committee of outside experts and representatives of consumers, industry, and sometimes patients also weigh in.
It’s not actually being slow once submissions are made . As said, other vaccines were approved more quickly. And if you want a comparison, it’s acting much more quickly than the EMA seems to be.
Now, the interesting part is why they (apparently) delayed the submission of the AS vaccine by requesting more data...?
Vaccine manufacturers certainly aren’t willing to take that bet. They are exempt from any liability of harm. [1] At least before COVID you could litigate in secret vaccine courts. Now even that is off the table.
Allowing a problematic vaccine at this point will likely have further reaching consequences than the people who experience side effects. Public doubt over vaccines is high and a bad one getting through will give people legitimate cause for concern going forward. The current anti-vaxxer movement is nothing compared to what will happen if a bad Covid vaccine gets approved.
Make sure you count the number of people who will die from preventable disease due to fear of vaccines over the coming decades. Plus add in the likelihood of another pandemic and the deaths caused by both the additional scrutiny over vaccines for it and the public's reluctance to trust them.
Astra Zeneca could not ensure that it dosed people correctly in their trials. This is clown school stuff. The head of the Oxford team described textbook p-hacking at a press conference and admitted they were doing it, saying essentially that it didn't matter if some datasets showed that the vaccine didn't work so long as some subsets of data did. Given this, ANY papers from this group are highly suspect. This isn't quite as extreme as what Didier Raoult stuff, but it's basically the same thing, just less extreme and slightly more sophisticated.
This same team has claimed to have vaccines for multiple viral diseases in the past including for example Chikungunya. None of their studies could be replicated. It's not in the popular psyche in the US because these are not diseases that affect people in the West, but finding supposed cures for them are great for getting grants. Nothing they have done has actually been found to work in the fullness of time. It's not like it sort of worked but not well enough to be statistically significant or that it had some low incidence side-effect. The stuff they came up with was mostly indistinguishable from placebo in trials run by third parties.
They have made crazy claims about their Covid research since March 2020 while serious scientists who have produced stuff that actually works were more focused on stuff in the lab. They continue to make outlandish claims, for example claiming they had developed the first ever monoclonal antibody drug for Covid. This was in the weeks after Trump and ex NJ Gov Christie were successfully treated with Regeneron's and Eli Lilly's monoclonal antibody drugs respectively, and of course the British press and Oxford boosters spread it around in the media.
The "studies" that were published that show "efficacy" had vanishingly few over 65s in the treated population but had over 65s in the control. If you look at it carefully, it's not clear the claimed efficacy is much more than a difference in population characteristics. Their apologists claim they performed worse than Pfizer/Moderna because it's possible the treated took more risks because they had symptoms from the vaccine and so knew they were immune. The only problem with this claim is that the Moderna and Pfizer vaccines caused more flu-like symptoms.
This is pure conjecture, but I suspect the UK and EU approvals have more to do with Brexit politics than actual science. It also has to do with the fact that the head of the Oxford team is from the "right" family background. Unlike the US, this sort of thing matters a lot in the EU, even the UK. The UK government is looking good but the reduction in UK deaths is only partially real. More than half the decrease in Covid deaths in the UK is fake because excess deaths went up simultaneously with a decrease Covid deaths. Of course the EU doesn't want to look bad post Brexit so they had to approve and show they were vaccinating their population just as quickly as the UK was. Despite the EU approval, Poland, Germany and France are taking steps to limit the usage of this vaccine in their countries. I wouldn't be surprised if more European countries do so as well.
I for one sincerely hope the Astra Zeneca vaccine is NOT approved by the FDA. Would you rather have a real vaccine or pretend to have been vaccinated and get infected later? Even if the Astra Zeneca vaccine has the claimed 70% efficacy (it doesn't against the new strains), and if R0 is >5 as it is for the new South African and UK variants, it will only slow, not stop the epidemic.
Meanwhile, the US is doubling the number of people vaccinated per day every two weeks, and this is with vaccines that incontrovertibly work about as well a any vaccine in history. Exponential growth is bad when it's an epidemic but it's very, very good when it's a startup or the scaling up of a treatment. Resources are always limited. I'd much rather spend them on getting more Pfizer and Moderna vaccines into people's arms than waste time, energy and resources on something that isn't a solution even in the best possible scenario.
The JNJ and Novavax vaccines are looking just as good and are much easier to manufacture and distribute. The top line numbers are a bit worse only because their treated population was different and more challenging to get an immune response out of and infected with the strain the Moderna and Pfizer vaccines were tested on plus many people who had the new strains. The Astra Zeneca vaccine looks like a candidate for countries where a cold logistics chain is hard but it really isn't. It adds the spike protein to an adenovirus. Adenovirus infections generally don't cause many symptoms but after one or two infections you are immune. If you are immune to adenoviruses, your immune system is likely to take out the vaccine before it has the chance to train your immune system to go after the spike protein. The problem here is that adenovirus infections are far more common in areas where cold logistics chains are difficult.
I can't say this will cause Thalidomide like side effects but I would happily take a bet at 10-1 odds that within 5 years, data will come to light that shows serious problems with either the safety of efficacy of the Astra Zeneca vaccine. That implies that I think the chances there are problems are >10%, which is much too high for approval given the IFR of Covid.
Efficacy is irrelevant. Rolling out AZ vaccines will not slow down Pfizer/Moderna vaccination rates, because the bottleneck is supply. Even assuming J&J + Novavax there's still a drastic supply bottleneck.
At worse, we'll just give a bunch of people a placebo. I don't believe there's lack of efficacy, but with millions of subjects, the answer will be apparent in a matter of weeks. If so we'll simply re-innoculate those people with Pfizer/Moderna. There's literally zero cost to this scenario, besides monetary spending that's a rounding error in the federal budget.
The only consideration should be safety. I'm so confident in safety that I'm willing to give you 10-1 odds, up to $500/$5000 that there will be no more than 35,000 deaths attributed to the AZ vaccine globally within five years.
What about increased deaths due to people taking more risks because they think they are safe? Most deaths are in over 65s. AZ has released absolutely no data on over 65s, nada. There is independent data from Germany that shows the AZ vaccine is essentially indistinguishable from placebo in over 65s.
What you are suggesting may be the right thing to do somewhere other than the US, so long as its accompanied by an effective warning that the vaccination may or may not work so you still have to be careful. The important operative word regarding the warnings being effective. My comments are entirely in response to an earlier commenter stating that the FDA should approve AZ, which means it's US specific. The single biggest bottleneck right now is vials, not vaccine production. AZ vaccine production will compete for this.
Besides, do you really think AZ is going to be able to magically scale up from 0 in the US with the UK and EU already fighting over production and do this faster than an absolute lazer focus on increasing Pfizer/Moderna production and distribution? The US is currently doubling the number of people vaccinated per day every 2 weeks. We did this despite a massive snowstorm on the East Coast. It might seem bad but the rate of vaccinations is growing exponentially. It's mostly a solved problem. You just don't see it yet. Exponential growth! It's the same thing that makes high R0 epidemics so bad, only in reverse.
There is data from germany? There was a media blitz about low covid infection prevention in ages over 65, but the confidence interval was between something like -130% to 90%, so it's more of a case of missing data
Most deaths are in over 65s. If the confidence interval on the vaccine working on over 65s is -130% to 90%, how can you possibly claim this vaccine will do anything. Their conclusions were based on data submitted by Astra Zeneca and data Astra Zeneca did not initially submit.
Breaking news this AM: South Africa just halted the use of the Astra Zeneca vaccine. It's being spun as being done because of evidence it doesn't work on the new strain. I strongly suspect once all the data is in, this vaccine will be found to be indistinguishable from placebo.
There is no data from Germany. The German commission on vaccination concluded, based on the data provided by AZ, that a) there is no reason to believe that AZ is unsafe and b) there is currently insufficient data on efficacy in ages over 65 to recommend vaccination.
> What about increased deaths due to people taking more risks because they think they are safe? Most deaths are in over 65s. AZ has released absolutely no data on over 65s, nada. There is independent data from Germany that shows the AZ vaccine is essentially indistinguishable from placebo in over 65s.
Then why not allocate AZ to the population it is most effective? The whole argument with efficacy across different brackets appears like a (simple) maxflow problem.
A friend of mine was part of the AZ trials, the control wasn't a placebo because lack of side effects would let the person know which group they were in. Instead it was some other common vaccine that would produce similar side effects as the real one.
This was the case with all the trials, not just the AZ one. However, there was a difference in side effects between the vaccinated and controls in all three. The difference was larger for the Moderna/Pfizer vaccines.
Also, there wasn't one AZ trial. There were 8 or 9 in different countries. But for reasons only known to AZ/Oxford, their studies are based on data only from 2 and part of the data from a third.
You make some interesting claims, do you have any sources? Would be interested to read more.
> They have made crazy claims about their Covid research since March 2020 while serious scientists who have produced stuff that actually works were more focused on stuff in the lab. They continue to make outlandish claims, for example claiming they had developed the first ever monoclonal antibody drug for Covid. This was in the weeks after Trump and ex NJ Gov Christie were successfully treated with Regeneron's and Eli Lilly's monoclonal antibody drugs respectively, and of course the British press and Oxford boosters spread it around in the media.
From what I can tell, it looks like Oxford started their trial in September [1] and all other reference I can find for the other drug you are mentioning, "bamlanivimab", seems to come after that date. Not sure why this is such an issue? The trials for example started in October [2]. The second reference there also seems quite critical of the drug you are mentioning:
* Bamlanivimab showed no benefit in the ACTIV-3 trial involving hospitalized patients with COVID-19.
* Bamlanivimab failed to achieve the primary endpoint of viral load reduction in a trial involving outpatients with COVID-19 (BLAZE-1). It may have caused some debatable improvements in secondary endpoints.
* Eli Lilly is now testing a cocktail of bamlanivimab plus another antibody. The company seems to realize that bamlanivimab might have some efficacy, but it’s far from a wonder drug.
* The IDSA and NIH guidelines recommend against generally using bamlanivimab.
* Somehow, bamlanivimab has nonetheless achieved an Emergency Use Authorization via the FDA and is being used at some centers.
> The "studies" that were published that show "efficacy" had vanishingly few over 65s in the treated population but had over 65s in the control. If you look at it carefully, it's not clear the claimed efficacy is much more than a difference in population characteristics. Their apologists claim they performed worse than Pfizer/Moderna because it's possible the treated took more risks because they had symptoms from the vaccine and so knew they were immune. The only problem with this claim is that the Moderna and Pfizer vaccines caused more flu-like symptoms.
A few things here:
1. It doesn't seem any of the Pfizer/BioNTech, Moderna or Oxford trials have enough data for over 65s. You can see MHRA public assessments here saying the same thing. Pfizer vaccine In this document on page 48 [3]. Oxford/AZ vaccine on page 53 [4]. Moderna (not the full public assessment report) page 9 [5].
For example, even the FDA says the same about the Moderna vaccine trial:
> The small number participants and cases in some subgroups, such as participants >75 years of age and participants in certain racial subgroups, limits the interpretability of the individual VE results, but are displayed for completeness. [6]
2. Oxford seem to be the only ones who have published their studies on the vaccines, unless I have missed anything? So it's hard to scrutinise the other vaccine studies.
3. Your last comment seems unsubstantiated.
> This is pure conjecture, but I suspect the UK and EU approvals have more to do with Brexit politics than actual science. It also has to do with the fact that the head of the Oxford team is from the "right" family background. Unlike the US, this sort of thing matters a lot in the EU, even the UK. The UK government is looking good but the reduction in UK deaths is only partially real. More than half the decrease in Covid deaths in the UK is fake because excess deaths went up simultaneously with a decrease Covid deaths. Of course the EU doesn't want to look bad post Brexit so they had to approve and show they were vaccinating their population just as quickly as the UK was. Despite the EU approval, Poland, Germany and France are taking steps to limit the usage of this vaccine in their countries. I wouldn't be surprised if more European countries do so as well.
That is pure conjecture, do you have anything to try and justify this? Especially for your last sentence there, it does seem odd countries are not allowing for over 65s considering there isn't enough data from the other vaccines (unless I have misunderstood this, happy to be corrected). They have more data, but it is still not enough data?
> I for one sincerely hope the Astra Zeneca vaccine is NOT approved by the FDA. Would you rather have a real vaccine or pretend to have been vaccinated and get infected later? Even if the Astra Zeneca vaccine has the claimed 70% efficacy (it doesn't against the new strains), and if R0 is >5 as it is for the new South African and UK variants, it will only slow, not stop the epidemic.
I think calling the vaccine not real is a bit inflammatory. Why is it not real? The new study pre-print seems to support that is a very good "real" vaccine [7]. It also does appear that all the vaccines are less efficacious against other variants such as the one in SA, but seems to be similarly effective to the UK one [8]:
> Oxford researchers say their analysis found similar levels of efficacy against the old variant (84%) and the "Kent" B117 one (74.6%), which was spotted in the South East in September and caused a sharp rise in cases before Christmas.
> Dr June Raine, chief executive of the UK's regulator, the MHRA, said the findings were "very reassuring". Dr Peter English, consultant in communicable disease control, said: "This is excellent news, as it indicates that the vaccine works effectively at preventing illness, even with the variant virus."
---
> I can't say this will cause Thalidomide like side effects but I would happily take a bet at 10-1 odds that within 5 years, data will come to light that shows serious problems with either the safety of efficacy of the Astra Zeneca vaccine. That implies that I think the chances there are problems are >10%, which is much too high for approval given the IFR of Covid.
The results from the UK rolling out the Oxford vaccine should be released next week I believe. I dare say you will be proved wrong. Mass issues with the vaccine would surely be out in the wild right now and be reported on.
All-in-all, this seems like quite a different understand of the information out there, and I think much of what you say isn't justified. You definitely seem to have a strong dislike for the Oxford team and the vaccine, nor do you seem to be fond of the UK and/or EU institutions from my understanding of your comment. I'd rather place my trusts in the MHRA, EMA and JCVI and similar agencies who have access to all the data and are happy with the information provided to them.
The UK is showing decreasing deaths from Coronavirus while excess deaths (deaths over the baseline level of expected deaths not attributable to Covid, which are usually very steady) have gone up by more than half the supposed Covid decrease. Simultaneous with the rollout of the Astra Zeneca vaccine, the UK has had a new very stringent lockdown. The actual decrease, net of excess deaths does not seem any more than one would have expected from the new lockdown.
25% of the participants in the Pfizer and Moderna trials were over 65, 40% over 55, according your citations. 0 over 65 in the Astra Zeneca. There weren't enough over 65s and certainly not enough over 75s to come up with confidence intervals as tight as one would like in those subgroups for Pfizer/Moderna. Remember it's hard to recruit older participants because they often have co-morbidities that can cause all kinds of problems when you analyze the data. That's very different from Astra Zeneca. In particular, it's bad because the Astra Zeneca did actually recruit over 65s for the treatment groups. They just chose not to release that data while retaining some over 65s in the control.
This AM South Africa suspended use of the Astra Zeneca vaccine because data collected by South African authorities found it wasn't effective. It's being spun as it's not effective enough against the new strain. I suspect given a few months, we will find the vaccine doesn't work against any strain.
The UK is showing decreasing deaths from Coronavirus while excess deaths (deaths over the baseline level of expected deaths not attributable to Covid, which are usually very steady) have gone up by more than half the supposed Covid decrease. Simultaneous with the rollout of the Astra Zeneca vaccine, the UK has had a new very stringent lockdown. The actual decrease, net of excess deaths does not seem any more than one would have expected from the new lockdown.
25% of the participants in the Pfizer and Moderna trials were over 65, 40% over 55, according your citations. 0 over 65 in the Astra Zeneca. There weren't enough over 65s and certainly not enough over 75s to come up with confidence intervals as tight as one would like in those subgroups for Pfizer/Moderna. Remember it's hard to recruit older participants because they often have co-morbidities that can cause all kinds of problems when you analyze the data. That's very different from Astra Zeneca. In particular, it's bad because the Astra Zeneca did actually recruit over 65s for the treatment groups. They just chose not to release most of that data while retaining some over 65s in the control.
This AM South Africa suspended use of the Astra Zeneca vaccine because data collected by South African authorities found it wasn't effective. It's being spun as it's not effective enough against the new strain, you still get the mild Covid etc by Oxford apologists. I suspect given a few months, we will find the vaccine doesn't work against any strain.
Already upvoted but also: thanks for the in-depth comment. I haven't been following vaccines beyond Moderna and Pfizer over the past few months.. woah.
I had no idea that the posting of this article was in any way related to current vaccine approval efforts, but I can assure you that holding a rhetorical gun to my head immediately after reading the article has done nothing but make me extremely skeptical of whatever product AZ is peddling.
As a biomedical person, i find the FDAs policies and procedures eminently sensible, perhaps especially when they chafe, and this is why.
I do not envy them their jobs even the littlest bit, but I’m glad they’re around.