Covid vaccine makers commit to not seek approval until complete Phase III trials | Hacker News Reader

Covid vaccine makers commit to not seek approval until complete Phase III trials

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The New York Times has a chart, updated daily, of all the vaccines in development.[1] This is worldwide, not US.

Phase I: 24

Phase 2: 14

Phase 3: 9

Limited approval: 3 (CanSinoBio, Gamaleya Research Institute (Russia), Sinovac)

Full approval: 0

That's not even including the hundred or so still in lab or animal testing. It's encouraging; something is likely to work.

The real question is, how effective are the ones that make through the safety tests? Nobody really knows yet. The FDA (pre-Trump push) announced that their minimal effectiveness for approval was 50%, which is low for a vaccine. Moderna is aiming for 60%. Effectiveness times fraction of population getting it has to be > 70% or so to stop the epidemic with a vaccine alone. That's the "herd immunity" fraction for a disease with a growth rate of 3.

Useful questions:

- If a vaccine is only partially effective, will an antibody test tell if it worked?

- Will taking one vaccine limit the effectiveness of another vaccine taken later? That's happened for a few vaccines.[2] It's usually more of a timing thing; some vaccines should not be given within a few weeks of other vaccines.[3]

- Could widespread use of a moderately effective vaccine cause people to abandon mask-type precautions and cause an epidemic spike in the unprotected part of the population?

Is someone working those issues effectively?

[1] https://www.nytimes.com/interactive/2020/science/coronavirus...

[2] https://www.tandfonline.com/doi/pdf/10.1080/21645515.2015.10...

[3] https://www.ok.gov/health2/documents/IMM_PRG_5-20_Intervals_...

> That's the "herd immunity" fraction for a disease with a growth rate of 3.

Only if you assume (1) perfectly homogeneous mixing and (2) nobody is naturally immune (either due to cross-reactivity with immune responses to other coronaviruses or for any other reason).

To add to this, the effective reproduction number (what I think the GP is referring to?) varies not just with the prevalence of immunity, but also with the contact network of the population in question.

Currently the effective reproduction number is not 3, in most places, because we're avoiding large gatherings and, depending on the region, wearing masks and avoiding indoor gatherings.

If many more people were immune, even if we hadn't reached herd immunity, we could safely relax restrictions on gatherings without causing another wave. Concerts would still be out of the question, but dinner parties and hair salons would no longer be so concerning.

> Despite this marked difference in virus replication in the lungs, reduction in viral shedding from the nose was not observed.

So vaccinated people will not get too sick, not self-isolate, but will still shed the virus? That sounds concerning for the non-vaccinated.

[] ChAdOx1 nCoV-19 vaccination prevents SARS-CoV-2 pneumonia in rhesus macaques

It seems to me that right now, it is easier to identify people who are at high risk of serious infection than it is to identify people who are spreaders.

If multiple vaccines are ready at the same time, who will decide which vaccine is distributed to which people? Would it be regional? Random?

I imagine it would be constrained on shipping logistics, initially. Vaccines require temp. controlled shipping.

Effectively random.

Some are easier to make, some are more stable, some require special handling, some are more effective... it may mean different one are used according to fit.

Of all the different vaccine "types" mentioned in the article (proteins, whole virus, mRNA, etc), which of those general types of vaccines are the most traditional, the most widely used, the most experimental, the most novel, etc?

I'm genuinely curious if "tried and true old vaccine tech" will come out on top in this case, or if "fancy new vaccine tech" will lead the way.

Proteins and whole virus are the most common. mRna is new and I think at least some companies are taking advantage of the epidemic to push the technology forward.

I hope that the benchmark for approval is "for a given group, the risk of the vaccine is lower than the risk of COVID".

This has some good commentary: https://marginalrevolution.com/marginalrevolution/2020/09/on... some thoughtful commentary.

I believe that for at risk populations it is very likely that taking a phase III vaccine candidate is the safer option right now, let alone after another month of data.

I think let anyone who wants to volunteer to take it make their own risk assessment but be required to send data back. The only real arguments I have seen against this are political or paternalistic. But I also think people should be allowed to run human challenge studies on volunteers, which is also an ethical no brainier. But that doesn't seem to be happening either.

It basically feel like the world in 2020 decided the answer to the "trolley car problem" https://en.wikipedia.org/wiki/Trolley_problem. 2020 society's action seems to be: "inaction causing 5 deaths is better than action causing 1 death".

If the vaccine confers only limited immunity - but the users run off and act like they are immune for life - we could pretty quickly end up in a situation where giving a vaccine could result in 5 deaths where 1 only would have happened without it because people would have been more careful.

This is why it is important to understand not only that it doesn't kill people, but how much immunity it provides.

That's what they said about masks, and that turned out to be wrong too. Assuming that people are idiots never helps

But you have some broad idea if a mask is having some effect (e.g. if your mouth and nose are tightly covered). With a vaccine, the protection or lack thereof is invisible to you and others.

Anyone who's been getting flu vaccines surely has a pretty good idea how ineffective they can be.

Flu vaccines are effective — but the government has to try to predict which specific strains of flu will be active that season. If they mispredict, you might get the flu despite having the vaccine since you got a different strain.

For COVID-19, there is a known set of strains that hopefully won't change. So a vaccine targeted towards that set should work, at least temporarily.

The following is just me speculating: from what I have heard, coronaviruses are called such because of distinctive proteins on the outside of the cell that are hard for the virus to change. If a vaccine elicited an immune response to target such a protein, then it should be effective for all the strains.

My point was not that Covid vaccines will be ineffective, just that people have relatively little faith in flu vaccines right now (although I still get one every year, because better than nothing).

And I think people will see a covid vaccine as more like a flu vaccine than an MMR vaccine.

It's invisible to you until you actually realize it's (partly or fully) ineffective by getting sick. With a mask, you have some general idea well before you'd actually get sick. You can see if someone's wearing a mask properly, but you can't analyze their immune cells and the specific pathogen strains they might be exposed to.

Assuming that people will behave responsibly doesn't have a great track record either.

In UI design, I've found that "idiot" is not that useful a concept. I think its more useful to think through particular thought processes.

A mask is

1. A constant reminder of the presence of the pandemic.

2. Fallible in ways that humans can easily visualise.

Vaccines on the other hand are indistinguishable from magic.

Err, what do you mean? Mask usage in the US is extremely dependent on what municipality you live in, both legally and culturally. I'd say assuming people are idiots would have been very welcome at the start of this. It's a major reason why we are the worst-hit country in the world.

"they" (who?) said that ppe was in short supply and should be reserved for medical personnel.

Well obviously this depends on what you mean by "they". But a leading narrative during the early part of the pandemic was that masks were not good, for various reasons, one of which was that they didn't actually offer protection, but people think that they do, so people will be less careful.

This was so much part of the narrative that there were later pieces about how bad this narrative ended up being, e.g. in the NYTimes.

So for sure, it was a real thing.

Sure, and if we wait for too long the worldwide economy will collapse and then we'll have a gazillion deaths from side effects. We can't go down the path of wild assumptions because it won't lead us anywhere.

If the vaccine confers limited immunity we can at least do a better work at protecting the elderly who are extremely vulnerable. And then, as research progresses we'll have better knowledge on how to fight this thing.

The phase 3 trial is where the safety and efficacy of a vaccine is determined for various groups. The risk/benefit decision you suggest can’t be made until it has been done.

It’s like the trolley problem but you don’t know whether more people will be killed if you throw the switch or not.

Also, if people are encouraged to take a vaccine that later turns out to have significant, previously unknown negative side effects, they will be less likely to take vaccines in the future. Squandered trust is very, very costly to regain so needs to be accounted for in a risk analysis.

The data we have gives some information about the risks, although it not a completely clear picture. There is uncertainty, but any sort of risk/benefit analysis has to deal with uncertainty.

I don't think OP is arguing that people be encouraged to take the vaccine, just that the option be made available to them if they want it. I don't think it would squander trust if it is explicitly repeated that the vaccine is not known to be effective yet and that there are still potential side effects, and the recipient acknowledges they understand.

Absolutely this.

I'm in an at-risk population, as are the two others in my household, and this pattern of perpetually delaying is driving me insane.

I'll gladly take a 0.1% chance of an unspecified SAE over a 50% chance of death. I'm about to the point where I'd consider outright bribing someone at a research lab to slip me a dose of any of them, even if I had to administer it myself.

The Moderna trial is enrolling, I know someone who is in it. You only have a 50% chance of getting the vaccine, but given your preferences, why not sign up for the trial?

Because I've left home exactly once since the second week of April, and I'm not leaving again until I have a 100.0% chance of getting the vaccine, full stop.

Meanwhile, Russia just today announced it is starting the release of the first batch of its own vaccine to the public.

https://www.aljazeera.com/news/2020/08/sputnik-russia-corona...

Correct, and this announcement is, among other things, a response to that.

Not sure why this got downvoted, it's not like the person is endorsing Russia's decision. I'm highly skeptical a country that refused to go on lockdown and underreported cases would make a safe vaccine faster than the rest of the world.

> country that refused to go on lockdown

What? Moscow lockdowns were some of the harshest outside East Asia.

I think grandparent meant "refused to go on lockdown on time". I have contacts in khazan ( not sure if orthographied correctly), the harsh lockdowns were due to a miscomprehension of the word "exponential growth" and overused hospitals.

>refused to go on lockdown on time Not sure if there was a definitive understanding when it was on time. As far as I remember, lockdown in Moscow started on March 23.

Well. As of now the Russian vaccine doesn't look like a trustworthy solution. Recently Russians published article in The lancet [1], but scientists who read this have a lot of questions. Especially on data consistency. They even published open letter to head of vaccine research Denis Logunov with open questions [2].

According to first reaction by Denis Logunov (don't have a link on this) the open letter doesn't worth to answer. Unless The lancet asks to react.

imho: It actually shouldn't be a surprise that if the government is corrupted, the other governmental institutions most likely do not function well either. This research center is a governmental institution. And might be interested and involved in some political games as well.

[1]: https://www.thelancet.com/journals/lancet/article/PIIS0140-6...

[2]: https://cattiviscienziati.com/2020/09/07/note-of-concern/

upd: formatting

This is nonsense -- I'm at high risk, and I'd take a flight to Russia right now to get a dose of Sputnik V if I knew I wouldn't catch COVID-19 on the trip.

Those grandstanding against these vaccines in the name of safety should know that they're directly responsible for deaths, and what's about to happen is we will just end up with a candidate from the least scrupulous manufacturer, because data are easy to manipulate and there's a lot of money on the line. I'd almost guarantee that this announcement means we've just traded a stable delivery platform for one of the mRNA candidates with risks that may be unknowable potentially for decades.

I'm a progressive and I get it that everything Trump does is necessarily frustrating, but whoever politicized this in response to his November 1st deadline should be ashamed, including whoever started the pledge that some of these companies signed today.

[Speaking as non-high-risk person,] I'd trust scientists to define when a vaccine is safe. The pledge is a politic action, but is explicitly against politic influence.

And what will happen if you get the vaccine and it doesn't work, but you live your life assuming that it did. You'll stop being as cautious as you are today, and if by any chance you get infected you'll die. How on earth is that a better solution?

I assume nothing.

I've left home exactly once since the second week of April, the next time I leave will be to get vaccinated (whether next week or years from now), and the very next time I leave after that will be to get my antibody levels checked. If the level is satisfactory, I'll resume leaving with an N95 or KN95 mask at all times until more is known.

I've recently heard an argument that the probability of being injured/killed by a vaccine (e.g. due to complications, allergies, etc.) is on average greater than the probability of covid causing damage/fatality to an individual, therefore if people are administered these vaccines then we'll actually see an increase in mortality/illness.

Can anyone speak to this? I'm not sure how legitimate this is, but it sounds somewhat convincing enough to be concerning.

EDIT: Downvoting someone for asking questions, even if based on a false premise, is completely shameful, especially when there's no claim to fact and it's clearly not made to be inflammatory. This community should encourage asking questions. Think carefully before throwing around a downvote as a marker of disagreement.

I think ruling that out is the point of a phase 3 trial.

Exactly. Realistically vaccines are very safe, very occasionally they aren't. So you start small and increase the sample size gradually to manage that risk until you have enough data to show both efficacy and safety.

To be fair: it's also a global pandemic, and one very poorly controlled in the US. So there is real and quantifiable risk to being "too slow", also. Balancing between the two extremes isn't well-served by a static protocol, you'd do something different for a vaccine against ebola (where you want to take your time because there are very few cases) than you would for covid (more urgent, low thousands of people dying every day) than you would have in the 50's for polio (an ongoing global catastrophe).

So... sure. It's not at all unreasonable that an "emergency" vaccine approval might happen. Which is why it's such a disaster that the FDA has given the appearance of being politicized (c.f. the plasma nonsense announcement, the right wing journalist hired as a press manager by the white house and then fired from within the bureaucracy). There is real concern that this administration really would "cheat" with a vaccine announcement in a way unsupported by the science.

So now worry about blowback is forcing the pharma companies to, perhaps, err in the opposite direction by ruling out an emergency approval. I'm not sure that's right either.

(Or maybe they all know there's no way they'll have valid data before November and are just trying to shut the debate down early.)

> Realistically vaccines are very safe, very occasionally they aren't

Tell that to all the people bill gates fucked up with his third world vaccine program

What are your sources?

This is simply not the case except when talking about a totally untested vaccine. The whole point of phase III trials is to confirm "safety and efficacy" in a wide population. Moderna, for instance, aims to enroll 30k people in it's (currently ongoing) phase III trial. After that, it's just a matter of data analysis. The FDA would certainly not approve a vaccine that had comorbidity higher than the disease it is trying to treat.

Somewhere around 0.5-1% of people who are infected with COVID die and a larger share experience very serious symptoms, some of which can be long lasting/permanent. The risks for the elderly are even higher, something like 15% death rate for people older than 80.

In comparison the risks of a vaccine are much much much smaller, as long as the risks are similar to existing approved vaccines. The testing process is explicitly designed to make sure that no vaccine gets released that causes more harm than good.

For comparison here is the symptom sheet for the flu vaccine https://www.who.int/vaccine_safety/initiative/tools/vaccinfo... Or an easier to read summary https://immunizebc.ca/side-effects The risks of serious complications for flu vaccine are closer to 1 in 100,000 or 1 in 1 million, and even then the effects are usually much less serious than death.

EDIT: Downvoting someone for asking questions, even if based on a false premise, is completely shameful, especially when there's no claim to fact and it's clearly not made to be inflammatory.

A lot of inflammatory topics are raised by asking questions based on false premises.

If you assert that a vaccine is more likely to kill/injury you than the disease it prevents, it is more than reasonable for others to assume you that are trolling rather than satisfying your curiosity, especially since you could have asked it in a different manner: what is the risk of being injured/killed by the vaccine compared to the risk of being injured/killed by the disease itself?

And nobody knows the answer to that question, yet. That's why they're doing the Phase III trials right now.

Try finding out how many people have died from vaccines that have passed phase 1 & 2 in the past few decades.

The number seems to be closer to zero than anything else.

Even one of the worst vaccine disasters, the Cutter incident in 1955, seems to have resulted in only some 10 deaths, of which 5 were indirectly caused.

What’s the timeline for Phase III trials? The article doesn’t seem to say. I don’t feel reassured that those won’t be rushed.

It's a moving target, so it's hard to say. Phase 3 trials depend entirely on the number of infected in the control group. Current estimates seem to indicate we may start seeing preliminary results in early Q4 with vaccines on target for an early 2021 date for implementation. These are the most aggressive schedules of course. Few are giving conservatives estimates right now, but I've seen June floated for more reasonable timelines.

My impression is that this was done to specifically counter Donald Trump rushing a vaccine prior to the election. I don't think it was really made to give any security beyond that

Any increase in testing time will give some, albeit hard to measure, improvement in safety of the vaccine. Or am I missing something?

Trump has made some very worrisome statements intended on either rushing a vaccine or placing the blame for the lack of it into whoever refuses to rush it.

Then the FDA answered with a non-statement that said basically "there's no conspiracy, we are fully invested into doing our job". And, of course, that gave a clear signal that the FDA felt pressured and was reported worldwide with that bias.

So, I read the GP saying that the manufacturers are telling the FDA "we know better than you" in an attempt to conserve their own credibility. Notice that this is a very bad message to pass into their own regulator, and worrisome for different reasons. But as long as it's only PR, it's not a real problem.

How about "rushing" the vaccine to you know... end the pandemic? Or would you rather more people die "from covid" to hurt Trumps chances of winning?

I'd rather more people die to Covid than find out 20 million people have failing livers and 5 million were born with birth defects because they rushed a vaccine without enough testing.

COVID has already caused at least that many people to have measurable levels of internal organ damage.

Source?

Vaccines shouldn't be rushed because that's how you kill people with vaccines. Phase 3 vaccine trials take 18-24 months for very good reasons.

The bigger issue is if they rush a drug that does long term harm to people, it could destroy the company. This is a drug that they will be giving out to 300+ million people in the US along. Screwing it up would result in a massive amounts of lawsuits that they may not recover from. They don't want to risk that just for some political capital with a person who may not be in power in a few months.

The fix for that is easy: have the FDA authorization grant them immunity from vaccine safety or efficacy liability.

Man that is a good solution. That way we get a vaccine immediately! Who cares if it’s saline. Or arsenic.

The way these things are worded only protect from unintentional damage.

Reputational damage would be a greater risk; this could quite easily turn into the greatest pharmaceutical scandal in history.

I feel like ending the pandemic is not a motivation that is likely to make a researcher (an expert) rush things and end up hurting more people. Greed or glory is much more likely to be a motivator for that kind of mistake.

Let me clarify what I think the parent meant.

This announcement was made very shortly after Trump started making claims that a vaccine could be ready "late October/early November". Trump is a known fool, and even were he not, his losing prospects at re-election, combined with the criticism of his administration's response to the pandemic make it seem like he could be pushing vaccine makers to rush a treatment to pump up voter support.

I believe vaccine makers are diplomatically responding to the Trump headline by saying "We aren't going to rush this for the wrong reasons."

Thanks for clarifying! This is exactly what I meant

I wouldn't have thought the companies involved are primarily thinking of that. The risk to the companies is that Trump going on about skipping trials will hurt public confidence in any vaccine that is finally released, even if such skipping never happens. This announcement may serve to reassure some people that the manufacturers are going to behave themselves even if the government is negligent.

Also, probably, reassure some shareholders. The reputational risks involved in this trial-skipping stuff are horrific.

The virus is pretty bad, right? Ought we be making a cost-benefit analysis where we compare the risks of side effects from the vaccine to the risks of the spread of the virus? In comparison to a vaccine like Gardisil, which surely prevents far fewer deaths than a covid-19 vaccine will, wouldn’t such an analysis actually indicate that the trials be rushed to some extent?

I’m feeling anxious that the current political milieu has a few factors pushing against deployment of a vaccine:

1. Republicans have been downplaying the virus the whole time, so they don’t take the need for a vaccine seriously.

2. Democrats are justifiably afraid of Trump pushing out a vaccine to get a pre-election “win”.

What I’m worried about:

1. Huge numbers of people dying every day from covid-19, with so many people out of work and struggling, with no end in sight other than a vaccine.

What’s the worst-case scenario for undiscovered side-effects on a treatment that has already been tested on thousands of people for months, and how probable is that risk?

No point shipping a vaccine early if it doesn't actually work. That could do more damage, people thinking it's safe to be around others maskless, when in fact the world population instead received an ineffective vaccine.

We already know that some of the vaccine candidates work (ie. immune response). I’m not arguing we should ship untested vaccines, but challenging how many months we need to wait after testing.

We know that they trigger an immune response, but that alone doesn't necessarily mean much.

For example, an early SARS vaccine candidate triggered an immune response in tests, but that immune response in practice actually made SARS infections worse.[1]

[1]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3335060/

Yeah, certainly we ought to see how animals and people with the vaccine react when exposed to the virus, but have we not already done that in the months these vaccine candidates have been tested? The current trials did things like give the vaccine to thousands of Brazilian health-care workers, which should have uncovered any issues like that (in the article you linked, the issue was uncovered by testing in a small sample of animals).

We have a process with three stages of trials. No vaccine candidate has yet gone through all three stages, no.

What I’m arguing is that we don’t need complete phase 3 trials to establish efficacy - we can establish that based on early data from those (and earlier) trials, while accepting larger error bars on the risk of side effects.

I think you're misunderstanding the problem space here. We don't expect a coronavirus vaccine to prevent close to 100% of infections, so it's not a binary question of working vs. not working. The question is, how strong of an effect at what level of confidence is required to conclude that it's working well enough?

The effect needs to be strong, because in ordinary times, many social circles cross paths and a much higher level of human contact occurs. The average person won't read into the nuance of 'the vaccine is X% effective, depending on risk factors Y and Z'. They'll rush to their ordinary behavior. While there isn't a vaccine, it's easier to obligate folks into social distancing. That strategy won't exist anymore once we have a vaccine, regardless of its efficacy.

I agree, but that's what the challenge is. We have to solve for the values of X, Y, and Z where we're comfortable with people's inevitable rush back to their ordinary behavior, and it's extraordinarily hard to figure out what those values should be.

> We don't expect a coronavirus vaccine to prevent close to 100% of infections

Why not? I would have thought we do. Most vaccines do (flu notwithstanding).

I don't know the biological reasons behind it (I don't even know if the reasons are known, or if it's just based on early results), but Dr. Fauci's said that scientists are hoping for 75% effectiveness and 50-60% effectiveness would be acceptable. (https://www.cnbc.com/2020/08/07/coronavirus-vaccine-dr-fauci...)

And not working that's actually the better outcome of a bad vaccine. It could also have side effects that are worse than COVID-19.

Covid isn't that bad when compared to the potential harm that a dangerous vaccine could cause when injected into billions of people. Particularly because deploying the vaccine would not immediately stop all the covid19 damage. Further, deploying a dangerous or innefective vaccine would also cause significant long term damage to public health by fueling doubt in healthcare; particuarly since antivaccers are already a growing public health concern.

If we want to rush the process safely, the way forward is a challenge trial; where we deliberatly expose vaccinated people to the virus to see if they get infected. If you cannot get that experiment passed an ethics review board, you should not be able to get widespread deployment of an untested vaccine passed.

Given the way this story is going, I’m somewhat expecting a future where right-wingers refuse to wear masks but happily take the vaccine, while the left goes antivax and refuses to take it (because it was “rushed by Trump”) but continues to wear masks. Perhaps by our powers combined, we’ll defeat the virus!

That's why they want to absolutely make sure it won't cause a damage. The vaccine in 1976 was rushed for political reasons and that didn't end up well besides hurting many people it is also still used as an argument why you should not vaccinate.

I feel we are overweighting the importance of the political meta-game here and underweighting the real ongoing suffering caused by the virus (in terms of health, but also in economic deprivation).

But if we’re going to talk about the meta-game, I think a swift return to normalcy after the vaccine is distributed could do a lot for the public’s opinion of the importance of vaccination. It could marginalize the antivax movement for decades to come.

Vaccine won't restore normalcy at least not immediately.

> I think a swift return to normalcy after the vaccine is distributed could do a lot for the public’s opinion of the importance of vaccination. It could marginalize the antivax movement for decades to come.

A bad vaccine could absolutely cause havoc. And do the exact opposite, that's why they are being careful. If our president wouldn't politicize it, they wouldn't even have to say it.

Why would the people who refuse to wear masks take a vaccine? They think the virus is a hoax.

Not OP, and don’t feel strongly, but I’ll give my opinion on what might make that happen:

Mask is visible - sign of compliance. You can get a flu shot and not tell your ultra-right-wing friends. Even on the right there is a spectrum of course, and folks march to the beat with certain signals, masks seem to be one of them thanks to behavioral modeling from leadership.

Right wingers who don't wear a mask are not motivated by their friends seeing them without a mask. They are individualists. They do it because they see it as resisting being controlled by anyone or subjugated. They are also heavily anti-vax for the same reason. The amount of pressure there is in public to wear a mask is enough that it selects for individualists as the people not wearing masks.

I think if Trump were to triumphantly and controversially announce approval of a vaccine, it would become a badge of honor among his fans.

They think whatever Trump tells them to think. So if Trump tells them to take a shot, they will take the shot (FOR FREEDOM!).

This is quite simply false based on a worst case scenario of a 1976 Swine Flue vaccine level fallout, which had <10ppm cases for those given the vaccine (of which ~50% had severe effects or died).

https://en.wikipedia.org/wiki/Guillain%E2%80%93Barr%C3%A9_sy...

Your chance of getting COVID over the next year is certainly greater than 1% even if you live in a fairly unaffected area of the US (and are likely closer to 10% without extreme measures), while your chance of dying is almost 1% and severe effects (hospitalization) are in the 3-5% range.

https://covid19-scenarios.org/

About 20 million people are expected to get COVID over the next year and over 500 people per day are expected to die every day in the US until there is a vaccine. That is with current economic closure, before schools reopen, and with some fraction of people wearing masks.

Even if you think your chances of becoming very sick from COVID are <1/1000 (no pre-existing conditions <30yrs old), and you think you are so very careful that your chances of illness are 1% , and you don't care about spreading to anyone else... you are better off taking the worst case vaccine we know of.

The worst case vaccine to ever hit the market which is a significantly different thing than the worst case vaccine we’ve ever developed.

Do you know how many failed drugs go into a successful one? The success rate is absolutely abysmal.

Do you read Derek Lowe?

https://blogs.sciencemag.org/pipeline/archives/2020/09/03/co...

If you don't, you should... and yes, I do. The swine flu vaccine was accelerated. Many drugs for cancer will literally kill you (slower than the cancer), so the safety of a drug needs to be measured against placebo and demonstrate significant improvement. First, do no harm.

For what it's worth, The infection fatality rate 20-29 I have seen is about 7/100,000. I have seen many drugs with higher death rates form side-effects.

Deaths are not the only metric. We still don't know the potential long-term side effects of COVID, even for "low-risk" people.

https://www.theatlantic.com/health/archive/2020/08/long-haul...

The death rate for GBS from the swine flu vaccine was considered horrific at ~5ppm. I don't wish that on anyone, but I'd note that its still 10x better than the COVID death rate for the cohort you've found (average 25), and I certainly hope they don't asymptomatically spread that disease to parents (50) or grandparents (75), which are orders of magnitude worse off.

Who considers it horrific and in what context?

Here are some common causes of death for ages 20-29 in the USA[1]:

Poisoning kills 460 ppm

suicide kills 336 ppm

Motor vehicles kill 331 ppm

Homicide kills 245 ppm

Heart disease kills 80 ppm

[1] https://webappa.cdc.gov/sasweb/ncipc/leadcause.html

Are you arguing that the 1976 Swine Flue vaccine incident is the worst possible case or the worst possible case on record? If the former, then what is your evidence or reasoning for that? If the latter, how do we know that this is the worst case we can expect?

Well, the worst case is that the vaccine is actually a highly contagious world ending bioweapon that causes the extinction of humanity, so the latter.

How do you know that the current death rate for COVID19 won't eventually be much higher for those who have "recovered"? Maybe all those asymptomatic youngsters are actually going to develop horrible debilitating lung and blood disorders? We work with the data we have, and nothing suggests the vaccines are worse than the virus or even 1000x less bad.

Of course we should test them and find the best one(s), and an extra month or three are worth the potential risk trade-off... waiting 3 years "to be sure" is just going to needlessly kill millions.

It sounds like in judgment of which is worse: over or underestimating the risks of the virus versus taking additional time for more testing.

How many other nations are doing this besides Russia? Why not? If you’re asking me to make a bet, I’m going to side with the vast majority of nation-states. not a guarantee by any means, but the best choice unless I decide to go back to school to study viral infections.

If the virus was 10x more deadly (if it was 10x more contagious we'd almost all have it by now), I'd probably advocate for even more accelerated testing and deployment (we're close to the edge for full deployment over the next 9 months even in developed countries as it is). It's a trade-off between deaths from the virus and from a vaccine... once the vaccine is 100x lower risk than the virus you start rolling out to high risk profiles (front line medical and essential workers along with 60+ / pre-existing) since they have disproportionate >10x risk of transmission & death... then as production and deployment catch up roll out to medium (30s-50s especially with kids) after another 3-6 months and eventually low risk profiles (those 20s and under without kids or pre-existing conditions). That extra 6 month delay balances some of the risk between virus and vaccine. Since we'll have several different vaccines to choose from we can also pick the most effective ones that have the lowest side effects for later inoculation, while higher risk groups just need some protection today.

>How do you know that the current death rate for COVID19 won't eventually be much higher for those who have "recovered"? Maybe all those asymptomatic youngsters are actually going to develop horrible debilitating lung and blood disorders?

The same could be said about the vaccine since we will have no long term studies.

The 1976 swine flu outbreak is one example of what can go wrong if you rush a vaccine: https://en.wikipedia.org/wiki/1976_swine_flu_outbreak

It was rushed by the Ford administration for political reasons and got a lot of people very sick.

Is this the worst-case scenario? It doesn’t sound nearly as bad as covid-19.

My concern is that there’s an agency whose job is to minimize the risk of harm from a covid-19 vaccine, but not an agency whose job is to balance the risk of harm from a vaccine with the ongoing harm from not having a vaccine.

It's not the worst case, just the worst one that's happened in a vaccine deployed at scale. The dengue vaccine is a famous example of why careful research and approval processes are required; it's effective and not too inherently dangerous, but was found to actually make the disease worse for people who haven't been infected in the past.

"Is this the worst-case scenario? It doesn’t sound nearly as bad as covid-19."

This is a case where the media hysteria surrounding the risks of Covid isn't helping anyone. If polling is to be believed, the general public significantly overestimates their personal risk of mortality from the virus:

https://us.beyondbullsandbears.com/2020/07/28/on-my-mind-the...

As noted by the link above, the vast majority of that risk is concentrated in the oldest/sickest people. If everyone in the population is given a vaccine with even a fraction of a percent mortality, it could vastly exceed the risk posed by the virus to younger people.

It would be tragic, for example, to see any serious side-effects from a vaccine in people under the age of 20, who have essentially no risk from infection.

Maybe we should first distribute the vaccine to the elderly, then? It sounds like the trade-off benefits and risk would be different there.

Maybe. You still have to be careful, though: your prior assumption is that older/sicker people are more likely to have side-effects from anything. It's also hard to find big enough groups of old/sick people to do sensitive statistical experiments.

Vaccine development is hard.

On top of that, there are cases of many vaccines which are much less effective in the elderly.

While secondary causes are likely causing much of the higher mortality in the elderly, sometimes the immune system is just... not as strong. And yes, that does mean something other than COVID-19 could come along an 'get that person', but... here's my point:

https://www.cda-adc.ca/jcda/vol-66/issue-10/551.html

Hepatitis B surface antigen (HBsAg) induces neutralizing antibodies (anti-HBs) that protect against HBV infection. ... Response to vaccine following a 3-dose series is typically greater than 95% in young, healthy people, although it decreases with age (< 90% response at age 40 and only 75% response at age 60). Other factors such as smoking, obesity and chronic disease decrease vaccine efficacy and may be used to predict risk of nonresponse.6 Adverse events are minimal, although mild injection-site reactions may occur in 20% of recipients.

Quite a few vaccines are like this. Less effective on the elderly. So we could end up with an even larger horror show, with some COVID-19 vaccines.

Such as, it has some bad side effects, AND, doesn't really help the most-at-risk group as much as desired!

What really bugs me is, there are what? Greater than 70 vaccines in development?

Some governments have pre-picked supposed winners. On top of all the other political bull going on, are they going to stick with those winners, regardless of outcome? Or have preferentiality to those specific vaccines?

Because I can imagine some being highly effective and safe, and others being the reverse.

Absolutely. Prioritize those at highest risk of Covid complications (elderly, comorbidities) or those at high risk of exposure (front line healthcare workers).

It will be interesting once vaccines become available. Vaccinating several billion people will have a lot of operational challenges and will likely take upwards of a year to complete.

Not necessarily. Yes, the risk from Covid-19 is larger. But you do not know how well the vaccine works for elderly people. If the protection of the vaccine is relatively low, just vacinating elderly people does not make a huge difference in the outcome, if the general population has a lot of infected people. Vaccination is only partly about protecting the individual and a lot about preventing the spread of disease.

Take Rubella. If you are not pregnat, which means every male, you are at no risk by the disease. But Rubella gets vaccinated against these days as a standard vaccination, as the best way to preent pregnant women to get infected is, to prevent the spread in the population. And it is really nastily infective. When I was in the last year of high school, we had a breakout and to my knowledge, every single pupil in that year got infected.

> It would be tragic, for example, to see any serious side-effects from a vaccine in people under the age of 20, who have essentially no risk from infection.

They have little risk of death if they have no comorbidities, but even for a 20 year old, just getting COVID-19 is likely gonna be worse than the side effects from almost any vaccine imaginable. I've had vaccine side effects and I've had COVID and I'd take ten more vaccine side effects over one COVID, please.

There's also the fact that vaccines are never 100% effective and that herd immunity is important, so the 20 year old still needs the vaccine to protect the older people they may run across. So even if the 20 year old is personally somehow guaranteed an asymptomatic, no-damage infection from COVID, they still need the vaccine. Vaccines don't just protect you, they protect everyone else, and a large part of their efficacy in reducing total population mortality is through these herd immunity effects, not just from protecting the individual people who've been vaccinated.

> just getting COVID-19 is likely gonna be worse than the side effects from almost any vaccine imaginable

Do you have any non-anecdotal articles that quantify this?

Do you just want to do more research, or are you contending that you think the harm from COVID-19 is actually less than the harm from the most severe side effects of a vaccine we've ever seen?

In what age group? The 1976 vaccine actually killed people and gave Guillain Barré to many more, so that's your worst-case outcome. So far, under 20 years of age, the fatality rate for Covid is measured in low-single-digit thousandths of a percent (i.e. under a thousand in the US).

https://www.medrxiv.org/content/10.1101/2020.08.24.20180851v...

Yeah, the worst vaccine mortality rate ever was still not remotely as bad as that, and you're not considering that a vaccine given to a 20 year old is helping to protect all the other people said 20 year old comes into contact with, who will have substantially higher mortality rates from COVID.

"Yeah, the worst vaccine mortality rate ever was still not remotely as bad as that"

Citation required.

40 million people got it, only 25 died: https://www.latimes.com/archives/la-xpm-2009-apr-27-sci-swin...

I'll leave the math as an exercise for the reader, but that's a really low mortality rate, orders of magnitude less than even young healthy people who've gotten COVID-19.

25 people that we know about for sure. There were hundreds of cases of Guillain Barré, and many more that weren't definitively linked to the virus. Now scale that to billions of people.

And despite your comment on other subthreads, we don't make these decisions by directly comparing naïve mortality counts. It's not like it's acceptable to hurt N-1 people, just because the virus hurt N people. If a vaccine kills / cripples hundreds of young people, nobody is going to take the vaccine. It's pointless to debate this.

https://www.thelancet.com/journals/eclinm/article/PIIS2589-5...

Even with experimental concerns like the small sample size, 55% incidence of long-term neurological effects is pretty alarming

"I've had vaccine side effects and I've had COVID and I'd take ten more vaccine side effects over one COVID, please."

I don't know what side-effects you've had from vaccines, but when I talk about risks, I'm not talking about headaches...people actually died from from the 1976 H1N1 vaccine.

... yeah, and way more people are dying from COVID than have ever died from all vaccines put together.

Let's quantify "a lot of people".

Out of 45 million vaccinated, 450 got Guillain-Barré Syndrome. I couldn't find info on if any of them died.

That would have been acceptable if it had stopped a disaster, but as it turned out the 1976 Swine Flu epidemic never really materialized as expected.

With Covid killing 1000 Americans per day, I think we should happily accept those odds of side effects or worse.

Yeah, um, the point of trials is to find out what those odds are.

They can easily be much, much, much worse.

Also, what the reduction is risk of catching the disease in question is.

There’s no hard line where we need to test for t months, and then we will find out if the vaccine is safe. There is no magic threshold where suddenly we know the answer for sure. It’s more like: the size of the error bars on our estimate of the harm y in quality-adjusted-life-years (QALY) is constrained by some function on the time t, where there is diminishing returns as t increases. It’s always going to be possible that there’s some side-effect that doesn’t show up until t+1 months.

Further, we could build an expression of our estimate z of the total harm caused by the virus (including downstream harms like “deaths of despair” from economic damage). By minimizing y-z over t, we can find out the best time to release the vaccine (maybe to the most at-risk populations first).

I don’t think anyone at the FDA is doing this calculation. I think they are just trying to get y below some threshold, which is probably quite low compared to z. My goal in this conversation is to advocate for the people who will suffer and die because of that gap - and hope there is someone better qualified than me that fills that role in the government helping decide what to do. My fear is that the FDA is a highly conservative institution using processes that aren’t well-adapted to the current epidemic.

To add more color, I think if the vaccine comes out with unexpected side-effects, heads will roll at the FDA. But no heads will roll at the FDA over the many thousands who could have been saved by releasing a vaccine sooner.

I don’t think your fear is well founded. The fact that these vaccines are already in phase 3 trials, despite being developed earlier this year, is a testament to how much the FDA understands the current situation. Look up how long it usually takes a vaccine to get from development to phase three trials, I can guarantee you it’s not six months. People in this thread are quite alarmist. Vaccine trials usually take a long time, because whatever is trying to be cured isn’t a pandemic. In a pandemic you can run trials and get results quickly in a large area. Any side effects of these vaccines are going to show up quickly, it runs through your bloodstream and then your immune system takes care of it. We’re running large phase three trials and we’ll have a sense of effectiveness and general safety in a few months.

Fauci spoke on this matter recently. He said that phase 3 completion is not dependent on time, but rather dependent on the number of events (infections) in the control group.

This to me suggests the main blocker for approval now is proving efficacy, and that we already have enough data to conduct the time-based safety analysis you described with reasonable confidence.

There is another potential safety concern that the vaccine could exacerbate COVID infections. I don't know how critical this concern is, but it would also be constrained by number of infection events, not time.

I completely agree.

They can’t easily be “much, much, much” worse for a vaccine that has already been through orders of magnitude more screening than the Swine Flu vaccine.

The Precautionary Principle cuts both ways, and I think this breaks peoples’ brains.

The death rate for the syndrome is 7.5% according to wiki, so maybe 40 deaths?

https://en.wikipedia.org/wiki/Guillain%E2%80%93Barr%C3%A9_sy...

If a few hundred people get a brutal side-effect, that's enough ammo for anti-vaxers to severely cripple the general public's trust in our public health systems.

Somewhat frustratingly, this vaccine needs to be held to the same standards of safety & efficacy as any other vaccine, but I do wish they'd let immunocompromised people get access to the thing a notch earlier than they would otherwise.

Well, I don’t know what to do about that, but it seems to me that not releasing a vaccine which:

- Lowers the public’s chance of contracting COVID by 50%

- Causes 0.001% of the public to get seriously ill.

...then withholding that vaccine from everyone because some people who don’t understand probability may have a temper-tantrum would be deeply immoral.

None of this contradicts your point per se, but I don’t know what to do about it.

AFAIK immunocompromised people are legitimately excluded from vaccination and have to rely on herd immunity.

I think a lot of ammo for anti-vaxers comes from the government and media not being completely honest about vaccine side-effects. That's because it is difficult for an individualist or a socialist to separate public health from individual health. The CDC is not your personal physician. The CDC worries when newspapers publish facts about vaccines, such that some vaccines can cause severe and traumatic side effects, while being 52% effective, because they worry about obtaining herd immunity and need people to accept the vaccine for that. They want you to go through weird little side-effects, like not enjoying alcohol for months, so you don't infect a senior they count in the flu statistics. It's when "do no harm" means sacrificing the lives of a few to save the many.

Then there are political and funding concerns. If your own government funds your research to investigate if Agent Orange is harmful to the point of culpability costing billions, you are very careful and delicate with your conclusions. If your vaccination tests show that black Africans show more severe adverse effects, or that, maybe yes, the connection between vaccination and (worsening of) autism is both plausible and understudied, what do you do? For them its a single kid, maybe 2-3 in 100.000 which will start to suffer from autism years earlier, and a disease eradicated. For anti-vaxers, it is their kid.

Essential workers and at-risk people are first in line to receive the vaccine. The hope was availability in September, and public rollout in the beginning of 2021.

The anti-vax conspiracy mud has completely destroyed online information about this subject. There are more such subjects, where it is very difficult to find what the anti-activists are freaking out about. For instance, my gut tells me that physical and mental torture can be effective to obtain useful information. That that's why the mob, military, and police mainly use it for. But, online, nothing: torture is completely ineffective for the first 10 pages of Google. The Holocaust is another obvious one. 5G rollout ("completely safe, maybe, we don't know for sure. Improved Youtube streaming is important tho!"). Or try to find information on how the riots created a spike in infections. All news sites report on the same non-peer reviewed non-scientific institute paper, saying the riots caused spikes is a lie, yet the paper clearly postulates that riots increased infection for black participants and their families, but taken on the whole, they likely caused non-protestors to stay at home more for fear of violence and this reduced virus spread.

You don’t need to go so far back. The 2009 swine flu pandemic vaccine caused Narcolepsy in about 10 / 100 000 vaccinated, all of which were children aged 12-16 (which is not a group included in trials, by the way).

https://en.wikipedia.org/wiki/Pandemrix

slight aside, but from that link, was surpised to see "jet injectors" were used in 1970s.... i just toally assumed this stuff was sci-fi...

https://en.wikipedia.org/wiki/File:8365_loresOLDSCHOOL.jpg

I think this used at least at late 80's in developing world, I'm 30 and have a scar (almost impossible to notice). My parents have very deep scars.

Yep, I think everyone from my parents generation in morocco have a very distinguishable, large round scar that resembles a burn scar. Not only does it look painful, but it also looks like an absolutely perfect way to spread diseases. They were lucky AIDs wasn't really around at the time!

with so many people out of work and struggling

This concern can be addressed other ways. I run two subreddits aimed at helping people establish an online income (as part of the goal).

In a post-covid world, I think we will do more good if we focus more on adapting to a new reality where increased germ control is a permanent expectation rather than expecting a vaccine to fix everything and allow us to return to "business as usual."

I do think there will be a permanent adjustment in society to deal with the risks created by this type of virus in the future. Tell everyone to start wearing masks as soon as the outbreak starts, instead of telling them that masks are only for idiots and healthcare workers. Isolate travelers from affected areas before it has a chance to spread, and so on. But I also expect that just about every occupation from industries that are shut down will continue to exist in this new world.

Well, I didn't say anything about eliminating jobs. Just that I, personally, see no reason to tie the idea of going back to work to a vaccine.

I think we would do better to look for germ control solutions that are already proven and available currently. As one example, ordering online or calling ahead and picking up is a way to support local eateries while minimizing the spread of germs. I'm a big fan of Little Caesar's pizza portal as a contactless pick-up option and I don't see any reason we can't actively promote such existing practices right here, right now, instead of seemingly hanging all hopes on "there will be a vaccine and after it comes out, we can just keep doing the same things the same way."

That seems like needless suffering to me. We don't know how long that will take and, in the mean time, people need to survive right now. Not having any money/resources at all coming in for X months is not survivable for most people who don't have savings and the like to live off of.

I agree that we should try to adjust to the world we find ourselves in, but there’s only so much problem-solving effort to go around, and I think most people are already trying to do what they can. It’s tough to reshape society on a dime.

I, personally, think there is insufficient focus on doing what is doable in the here and now. Society is reshaped all the time, every day, by every choice ever person makes. If we aren't even trying to push it in X direction because we are spending our energy justifying not bothering to try that -- "because it's too tough" -- then that strikes me as self-fulfilling prophecy.

I get really tired of self-fulfilling prophecy. Given what is at stake, I think we can and should do better than simply justifying our failures to adequately rise to the occasion.

I think this comment is correct and is something that is being missed in the present conversation. For those who disagree -- isn't it better to take realistic steps to help people instead of just crossing our fingers and waiting for a vaccine?

It just seems terribly dismissive of all the people who want and demand a return to business as usual. A plan for handling the coronavirus that doesn't include "here's when we'll open the bars" is missing a huge piece of the problem.

I honestly fail to see a connection between your statement and mine.

I don't generally drink alcohol and I have a permanently compromised immune system, so hanging out at bars isn't some normal part of my life. So I don't understand what you feel is so essential to "here's when we'll open the bars."

Also, a bar up the street from me has already re-opened and (when they were just doing take-out beer) I posted a photo of their take-out beer sign to the local subreddit I run at some point, even though I don't personally drink. So please don't take this as me being a tea-totaller who is dismissing alcohol when I say "I don't get it. I honestly don't get it. Can you please clarify?"

I guess I'm not sure how to respond. It's not about bars specifically; it's about returning to an environment where people are free to crowd about if they'd like. As long as there are top-down rules to micromanage where I can go and how many others I can go with, the problem isn't solved. "Maybe we should just get used to those rules" isn't a solution - in all but the hardest-hit areas, the rules are most of the problem!

top-down rules to micromanage

I don't operate that way. Generally speaking, that's antithetical to how I operate in life.

I think if we have more support for remote work for people who want/need it and more support for options like Little Caesar's pizza portal which allows for contactless take-out, that helps make life possible for the most vulnerable people. Given how long people are living and our success in keeping alive a lot of people with incurable conditions who need permanent accommodation, this doesn't impinge on the people who want to do a group activity.

If anything, it frees up space for them to have their group thing without so much exposure to random people so their group thing is safer to attend.

I had someone on HN say something to me once about wanting to "hug their mom" and how my comment on HN was somehow antithetical to that. I live with my two adult sons and I have a permanently compromised immune system. I feel strongly that being exposed to "your group" is generally less problematic than being exposed constantly to random stranger with god-knows-what other strains.

I'm not at all arguing for denying people the ability to go out. I've, in fact, been given hell for making statements about not liking mask mandates and not liking the lock down.

My Walmart is closed at night right now and before it closed I and my sons were managing germ control in part by doing a lot of our shopping at 2am when the Walmart was dead. And that's not possible now and going to Walmart is currently one of the most hazardous things we have to do.

So I'm not all interested in doing what you are seemingly arguing against. And I don't see how it has anything at all to do with what I am advocating for and stated above.

Edit:

I feel like you added this after I began typing and I didn't initially see it: "Maybe we should just get used to those rules" isn't a solution - in all but the hardest-hit areas, the rules are most of the problem!

I don't disagree with that. Reading into my statement that I am advocating for "just get used to the rules" is wildly misinterpreting my comment. I said nothing about accepting our current lock down rules at all.

Maybe I misunderstood, because I'm on board with everything you're describing here. Most people I've seen who say they don't want to return to "business as usual" mean that we should just have restrictions in place forever, but if we're just talking about additive changes to let people avoid diseases if they'd like, I'm all in favor.

Back in March, I had extra money for some reason and the pandemic was hitting my small town in terms of things closing and hours being limited, etc. I made a point of going every single day to get pizza from the Little Caesar's.

When I began going, the staff was standing around with nothing to do and they were scared the location was going to permanently close. They didn't have enough business to survive.

I walk everywhere, so when I get pizza, it's very visible. People see me carrying a pizza box down the street and at least once someone asked me "Oh, is the Little Caesar's open?" and I was able to say "Yes! It is!" without violating social distancing.

I began using the pizza portal, which had been there for some time but never got used. One of the early times I used it, someone stared at me the entire time and now mine is not the only order in it.

The Little Caesar's removed the two chairs from their lobby and added hand sanitizer and made some other changes, but the big change is that -- at least in part because of me modeling it -- locals began calling ahead or ordering online instead of walking in and ordering. Even when they walk in, they frequently go sit in their car to wait for their order instead of standing in the Little Caesar's to wait.

They are busier than I have ever seen them in the three years I have lived here and they were hiring new employees during the pandemic. I always have to wait for my order now because they are always busy, yet it is safer than it has ever been for me to get food from there -- which is a constant concern for me because of my incurable medical condition.

Meanwhile, in recent months I have seen multiple local eateries advertised as for sale, presumably because the pandemic is negatively impacting the restaurant business generally.

Ordering online or by phone and getting takeout is a best practice for germ control and it's available right now and we can improve on that model with relatively small tweaks, like making hand sanitizer standard at all businesses, and larger tweaks, like making pizza portal style pick up options available at other eateries. And it in no way requires any government rules trying to micromanage your behavior.

It's about opening up options that actually work and promoting things that are already proven to work and are already available so the economy doesn't have to be strangled by this pandemic. It's an approach that doesn't require us to choose between economic health and physical health. It's an approach that works because it respects the need for both and does so without asking anyone to jump through giant hoops now in hopes of some potential, but not guaranteed, payoff somewhere down the road after x, y or z happens.

Thank you for engaging me.

Idk. I think framing the problem in this way is missing a huge piece of the problem. Just because people want or demand a thing doesn’t mean that we as a society are going to be able to deliver it.

I think we need to think seriously about the fact that, even if COVID goes away, lockdowns like this could become part of the “new normal” (?) anyways. And by the time that happens a lot of affected businesses will already be gone or have to change.

You're not entirely wrong, but the flip side of the coin is that people won't comply with a rule just because we as a society would like them to. People will lock down for immediate severe outbreaks, as they used to for polio, but the longer lockdowns continue the more people will just say "no" and ignore them.

I can definitely envision fascist-lite elected officials using lockdowns in the future willy nilly, because the people precisely have gone along with it.

To be clear, I'm actually arguing for finding solutions so that we can put a stop to such things.

I have zero interest in giving government officials any excuse to do such things. Finding actual solutions that actually work is the strongest possible means to combat such an outcome.

Everyone wants to return to normal, but there’s still a pandemic. “We’ll open the bars when it’s safe” isn’t a satisfying answer but what good would lying about a timeline be?

It establishes a standard for when we need to start looking at alternate plans. The virus isn't going to completely disappear, so there's a very serious risk that "we'll open bars when it's safe" will end up meaning "we'll never open bars". Just look at Australia, where Victoria has been under strict curfew for something like 5 months this year because the only standard they set for leaving is "safe". If our plan is going to end up meaning bars stay closed for a decade, we need to throw it out and come up with an alternate plan, or we're just going to end up with no plan as people and politicians lose their tolerance for further restrictions.

I'm glad someone else realizes that individuals (outside unusually-nerdy HN readers... myself included) do not have infinite patience for enjoyable things being shut down. The DGAF attitude will hit a tipping point whether we want it to or not and jailing 40% of the population isn't possible, even in America with it's love of outsized incarceration [0].

[0] http://news.bbc.co.uk/2/shared/spl/hi/uk/06/prisons/html/nn2...

A bad vaccine is pretty bad, and can easily be much worse than the virus. That's why we test them.

>>I don’t feel reassured that those won’t be rushed.

actually I am. Vaccine makers don't gain much by doing something risky (considering the negatives) so they'll check the ones seeking election at all costs.

especially right now, a failure when so many are paying attention (and large part of population is now anti-vaxers) could actually ruin the company.

should have added that that the vaccine has very limited $$ potential (can't charge a gazillion for it due to bad PR and competition) and most makers have hundred billion brands that can be ruined by this. So they aren't going to risk their company for this. Lastly, suppose Acme Pharma released it against all common sense, all over the media scientists would talk against it, so lose-lose.

This! I have some experience with the big pharma companies and they are risk adverse, even when it comes to PR. They often have billions of dollars coming in from approved products, and they are often more worried about that existing revenue than any potential future revenue.

However, these companies got a lot of money to ramp up production ahead of approval ("at-risk manufacturing") often by governments. If the vaccine is a fluke, they might be in trouble.

They probably could get some countries to indemnify them, they'd probably survive the damage to their reputation.

Countries including the USA, under the VICP. Vaccine makers are at very limited liability.

I would imagine a COVID vaccine would be put under the homeland security act like the smallpox vaccine was. Means you have to try and sue the government.

Well, this is a case of high risks and high rewards. I don't know a lot about business, but I don't find it hard to imagine that there's some companies out there that are willing to take the risk, especially if they have some kind of government agreement that can alleviate their liability.

They are hundreds of vaccines in work. Not really. The rich are hunkering down and no one is rushing to use the Russian or Chinese one

Under normal times I would agree.

There is already employer liability protection in the Senate stimulus bill, I wouldn't be surprised to see some sort limited liability clause added for vaccine makers as well.

Also with only 38.9 approval rating of Trumps covid response, and him trailing in the polls I wouldn't be shocked to see him trying to pressure some sort of deliverable around the end of Oct, which is when some of the 3rd phase ends.

EDIT:

From Trump

> "We’re gonna have a vaccine very soon. Maybe even before a special date. You know what date I’m talking about."

I heard somewhere that we should be prepared for middle of next year. They don't want politics to influence the safety of it. Releasing a vaccine that would cause damage would be devastating for the company.

I'm wondering how do they test it, do they inject volunteers with the vacine, and they tell them to go infect themselves with a virus that 1 time out of 100 will kill them and an unknown percentage disable them?

Not to mention people's health...

> I'm wondering how do they test it, do they inject volunteers with the vacine, and they tell them to go infect themselves with a virus that 1 time out of 100 will kill them and an unknown percentage disable them?

Obviously no

They get a large set of people (tens of thousands), half placebo, and then check rates afterwards.

The larger the set the faster the results, but a large set is expensive. "Afterwards" is sort of a simplification. The study arms are compared regularly throughout in case the study needs to be ended one way or the other (Data and Safety Monitoring Committee). (If the vaccine is effective: great, we want to ramp up production and give it to everyone ASAP. If the vaccine is ineffective or has very bad side effects, we also want to conclude the study.)

No, and this is why Phase III trials take a long time, potentially a very long time if we actually get a handle on the virus with measures like masking and social distancing.

Here's the protocol:

1. Volunteers get the vaccine (experimental arm) or a placebo (control arm).

2. They go about their lives.

3. Both study arms report any cases of COVID they develop. Also, any deleterious symptom (potential side effects).

4. If the vaccine arm has a statistically significant reduction in infection rates, and/or severity, everyone wins and the study is concluded.

This process can take years if the background rate of infection is low enough.

Thank you for the explanation.

> This process can take years if the background rate of infection is low enough.

This is why the phase 3 trials tend to be organised in countries with high rates of infection, such as Brazil, South Africa or India. In locations with low rates of infection it's too likely that the people in the experimental group don't get infected simply because they don't get exposed to the virus.

> This is why the phase 3 trials tend to be organised in countries with high rates of infection, such as Brazil, South Africa or India.

Or US (we are still higher than Brazil in cases per million). South Africa or India are actually much lower than us.

I can see why it may take years to determine if the infection rate has been significantly lowered.

But what is the timeline for determining if there are serious deleterious symptoms?

If we get to the point where we know a bunch of vaccines are safe, but not necessarily effective, could these be approved for anyone who understands the risks?

Adverse events are monitored continuously as long as the patient is still a part of the trial (which often extends past approval).

Once the product is approved, the FDA has an adverse event monitoring system that collects reports and analyzes them for signals that might imply a previously-unknown adverse event.

Of course it take more than just one case to for a new signal to be identified (unless it's really obvious like the patient dies right after getting the vaccine), so sometimes it may be a year or more until there is enough data to say "yes, we know nearly all the risks associated with this vaccine".

Sure, that makes sense.

My comment was based on Fauci's recent comments saying approval could happen as soon as next month if there are enough infections in the control group.

It seems to me that what he is implying is that the risk of long-term side effects would not be worth blocking approval of a vaccine if the vaccine proved to be effective in preventing the virus.

Gotcha. Yeah, that timeline seemed really aggressive, but I would hope that the FDA uses it's standard set of evaluating criteria for any new vaccine. Even though the phase 3 might only have a few months of data, you can pool phase 1 + 2 data as well, which would give you a bit more confidence as to potential long term side effects.

It would also depend on what they approve it for. You could see them restricting it to high-risk patients. In that case the risk-benefit is much better, so you'd be willing to take a chance on some hidden adverse event popping up since you'd be looking at avoiding a significant risk of death from Covid).

At least in my experience, there isn't a set formula for evaluating new drugs. The FDA really does look at every piece of data it can find. I've also found the FDA to be pretty conservative - if they are unsure, they lean towards not approving, or approving with significant restrictions.

The FDA has published a detailed guideline on how to handle vaccines against the SARS-CoV-2. Among these, the minimum requirement of a 50% efficacy and mandatory monitoring of the trial participants for at least one year after the trial end (which will not be when authorization requests will be made, in case it works, but later on).

No one will be told to go intentionally infect themselves. There will be no human virus challenge trials in the US as that would obviously never pass a review board. Instead they will vaccinate a study group and then compare infections, symptoms, and deaths versus a control group.

The best estimate of infection fatality rate is 0.65%, not 1%.

https://www.cdc.gov/coronavirus/2019-ncov/hcp/planning-scena...

I think this is the right IFR for the US, maybe a confidence interval is necessary however. In early April, data scientists paid by ARSGE calculated the IFR in france based on the diamond princess and found .7%, +- .2%, and estimated the high early IFR in spain and Italy was due to missing asymptomatic people and mismanagement. This pdf should still be available.

US having a relatively younger population, .65% seems correct.

You can look up those details on clinicaltrials.gov. They will list the timeline for the primary endpoint. That doesn't include recruitment delays though.

Here are the details for the Oxford/Astrazeneca vaccine.[1] It's a 1 year trial. From what I've seen, they vary in length, but have interim analyses scheduled on a regular basis (3-6 months). If they see a strong signal, they can seek approval based off that interim data.

[1]https://clinicaltrials.gov/ct2/show/NCT04536051?term=ChAdOx1...

Potentially years.

According to FDA, phase III trials typically take 1-4 years.

It's worth noting that, if there are any adverse effects that take a while to become apparent, the trial will need at least that long to be able to detect them. To my knowledge, severe vaccine reactions usually happen fairly soon, but a year before onset isn't necessarily unheard of for some vaccines. Also, that's just for vaccines that got approved; there may be some selection effects there.

The bigger one I'm worried about is whether or not the vaccine will confer lasting immunity. If we rush a vaccine to market in six months, everybody gets it, and returns to their pre-pandemic lifestyles, then we'll be in for a nasty surprise on down the road if it turns out that it only confers immunity for a year. It seems to me like we need to consider the possibility that an imperfect vaccine is worse than no vaccine at all.

If the vaccine only confers a few months of immunity, like the yearly flu vaccine, how long does it take to develop, produce and distribute the update?

I think the yearly flu vaccine give you lifetime immunity against the strains you are vaccinated against. However flu strains change every year. (Hopefully that won’t be the case for covid!)

Officially, it gives you at least 6 months' worth of immunity, but, beyond that, there are no guarantees, and it generally fades over time.

That's why the recommendation is to wait until shortly before the onset of flu season to get vaccinated: If you get vaccinated in July, there's no guarantee that the vaccination will carry you through the worst of a (northern hemisphere) flu season.

Good news is that COVID (and coronaviruses in general) don't seem to have the same kind of mutation potential to bypass immune system responses like influenza does. So our best guess is that a COVID vaccine will be like Tdap or MMR, i.e. after the initial course you maybe only need occasional booster shots (if even that), vs influenza where it mutates enough that a new vaccine must be developed and administered every year.

Not widely enough understood. Influenza is a segmented virus and generates new strains by reassorment. Where two different strains of influenza infecting a cell shuffle their RNA segments to produce a third strain.

Best to think of influenza as an ever shifting and recombining family of viruses.

Covid19 has a single strand of RNA and doesn't do that.

>If the vaccine only confers a few months of immunity, like the yearly flu vaccine, how long does it take to develop, produce and distribute the update?

The Pfizer and Moderna vaccines are mRNA based, which means the iteration time is measured in weeks. The production process is massively simplified; it's just a chemical process like any other drug, rather than needing to be incubated in chicken eggs like a flu vaccine. The first mRNA vaccines for SARS-CoV-2 were being administered within 2 months of the outbreak. If these things work (and they do; phase 2 trials have shown immunogenicity 3-4 times higher than COVID convalescent plasma [0]), and they are proven to be safe in widespread usage, it will potentially revolutionize vaccine development. COVID could end up saving lives in the long run for the fact that it sped up the timeline on mRNA vaccines by a decade.

[0] https://www.medrxiv.org/content/10.1101/2020.08.17.20176651v...

They did not actually commit to finishing the clinical trials.

> The companies did not rule out seeking an emergency authorization of their vaccines, but promised that any potential coronavirus vaccine would be decided based on “large, high quality clinical trials” and that the companies would follow guidance from regulatory agencies like the Food and Drug Administration.

https://www.nytimes.com/2020/09/08/world/covid-19-coronaviru...

Does anyone know the dangers of a "bad batch" of vaccines, specifically with Covid?

Here's a bit of digging on some of the dangers of smallpox[1]. Apparently, you can get something called progressive vaccinia which eats away at your skin.[2]

[1] https://www.cbsnews.com/news/the-most-dangerous-vaccine/

[2] https://en.wikipedia.org/wiki/Progressive_vaccinia

"After the program began, the vaccine was associated with an increase in reports of Guillain-Barré Syndrome, which can cause paralysis, respiratory arrest, and death."

This vaccine was rushed which had deadly results.

https://en.wikipedia.org/wiki/1976_swine_flu_outbreak

> "There is not even complete agreement about the causal relationship between the swine flu vaccine and Guillain-Barré syndrome"

> "Studies suggest that it is more likely that a person will get GBS after getting the flu than after vaccination"

In the worst case, about 450 people got Guillain-Barre due to the vaccine. Counterfactually, some thousands or even a million Americans might have died from the swine flu itself.

the Cutter Incident comes to mind. https://en.wikipedia.org/wiki/Cutter_Laboratories#Cutter_inc...

The question of whether the virus or vaccine poses a greater risk seems like a controversial one.

I (28, no health conditions) personally would be willing to take the vaccines that have gone through stage 2 trials. I registered myself as a willing volunteer but have not been selected.

It seems to me that there is a middle ground between approving and recommending a vaccine to all Americans and completely blocking access to vaccines that have been through some baseline safety testing.

What seems like a good solution to me is to have open phase 3 trials that accept anyone willing to waive the risks. This would also accelerate us towards to a point where we are ready to approve a vaccine for everyone.

> have open phase 3 trials that accept anyone willing to waive the risks

If we can quickly train up musicians and waitresses to do the data collection, sure.

The actual pledge is here [1].

There are 4 bullet points, 3 of them are quite generic; the one that made all the waves is:

"[we pledge to] Only submit for approval or emergency use authorization after demonstrating safety and efficacy through a Phase 3 clinical study that is designed and conducted to meet requirements of expert regulatory authorities such as FDA."

I feel there's some weasel wording going on here. They don't pledge to ask for approval after the completion of Phase 3. Instead they use a very convoluted phrasing, that's designed to make people think it's after Phase 3 is completed, but if you read more closely says something quite different.

When is the Phase 3 for Moderna expected to be completed anyway? This is readily available information at clinicaltrials.gov [2]. The estimated study completion date is October 27, 2022. Is the CEO of Moderna saying he will not seek approval prior to that date?

Pfizer's estimated study completion date is November 14, 2022 [3].

Two years from now doesn't sound quite "warp speed" to me. Did they take billions of dollars of public money to deliver a vaccine in 2 years?

[1] https://www.businesswire.com/news/home/20200908005282/en/Bio...

[2] https://clinicaltrials.gov/ct2/show/NCT04470427

[3] https://clinicaltrials.gov/ct2/show/NCT04368728

I agree. They are only saying they will demonstrate safety and efficacy through the trials, not that the trials will be technically completed.

And, I think that's fine. I'm not taking a politician's word for whether that has been achieved, but I agree with it in concept.

'after demonstrating safety and efficacy' is not weasel wording though, it's just a different benchmark than 'completing the study'.

The headline is inaccurate, but that's on Statnews.

When studies go really well, doctors consider themselves ethically obligated to end them early, so that the placebo group can receive the treatment. That these studies have planned end dates well into the future doesn't mean that they must run that long (or that it will take that long to collect sufficient safety data).

Yes, but then the pledge is devoid of content. The act of seeking approval is a submission of evidence that demonstrate safety and efficacy.

The "pledge" is essentially just saying "we'll do everything as we always planned to do it".

Why make this pledge then? What's the value added?

There is value added indeed. In today's climate of general mistrust, simply stating that you will not cut corners (even if there was never any possibility of cutting corners) can allay some fears. But then, who is stoking these fears? Should they know better than doing that?

"82% of Democrats and 72% of Republicans expressed concern that the Covid-19 vaccine approval process would be driven more by politics than by science.

More than 80% of independents, Republicans, and Democrats said they would worry about the safety of a vaccine that was approved quickly."

Wow.

And lest you think this is a Trump thing, the figures are similar in European countries.

A bad COVID vaccine (one that doesn't work), or heaven help us, one that causes harm, could set public healthcare back decades.

It doesn't even have to be a "bad" vaccine. The FDA has already said that 50% effectiveness would be sufficient, which would put it about on par with the seasonal flu vaccine.

Combined with a high baseline infection rate, and an aggressive testing regime (at least compared to flu/other non-pandemic diseases), there will be a lot of people who get vaccinated and proceed to get sick and test positive.

The real evidence of the vaccine working would be by the herd immunity it creates. But that is a population level effect, and people are terrible at understanding population level effects.

> The FDA has already said that 50% effectiveness would be sufficient, which would put it about on par with the seasonal flu vaccine.

I think it’s difficult to quantify how successful the flu vaccine is. I’ve reviewed the numbers and it’s not clear the general flu vaccine does anything. That being said, targeting specific strains can help (problem with flu is the various strains and ability to mutate so easily).

They make a new flu vaccine twice a year and effectiveness is quantified each time.

https://www.cdc.gov/flu/vaccines-work/past-seasons-estimates...

The problem is correlations. The flu naturally varies in severity by region, age, time, etc.

Even the studies you linked, anything prior to 2010 is suspect by participant counts being way too low. More recent studies appear better, BUT we don’t have anything prior to when vaccines started to compare.

I’m not saying the evidence isn’t there, I am arguing it’s circumstantial - aka not definitive how much it helps. Flu itself varies in severity widely.

I’m honestly convinced the entire flu vaccine program / push is to keep the industry active. This is similar to the DOD spending money on new weapons they don’t need to keep manufacturing going

The NIH is attempting to develop a universal influenza vaccine. A clinical trial is currently underway.

https://www.niaid.nih.gov/diseases-conditions/universal-infl...

My understanding is that while prevent infection using the vaccine is a big goal, the other more important goal is that it triggers a better response in people when they do get sick. Specifically, if you get the vaccine and then go on to catch the virus, your body will fight it better and you will have minor symptoms (and hopefully don't go to the ICU).

I will say that everything I've said is just from what I read. If someone with an actual medical background knows more, I would love to hear it.

That is my understanding as well, but it is entirely irrelevant to the point being made. If someone on the anti-vax margins get the vaccine and proceeds to get sick and test positive, the are more likely to say "the vaccine doesn't work" compared with "I would have gotten more sick if I wasn't vaccinated". You also wont here all the stories of people who got the vaccine and proceeded to not get sick; so there is a sampling bias to hearing about cases where the vaccine doesn't work as well.

The concern here is about the longterm PR of vaccinations, not the technical benefits of the vaccine.

> the figures are similar in European countries.

Do you have a source ?

It is a political decision. The kind leaders are supposed to make, the kind they don’t like making.

A leader has to decide on either pushing early and either saving/condemning hundreds of thousand of lives.

Or playing it safe and condemning/saving hundreds of thousands to death while we complete years worth of trials.

Oh because that’s not enough pressure the economy is burning, which will cost many lives as well.

It’s a horrible decision to make anyway you slice it.

Politician is going to be hated no matter what.

If it works, they are bad for taking so long, taking risk. If it goes south...

I think the common understanding of a decision 'driven by politics instead of science' is making the choice in the way that most advantages your own political career, instead of the way that saves lives or the economy.

Aren't those two things essentially the same thing? The best way to advance your career is to make choices that benefit the most people. You're not going to get ahead if your decision fails to save lives or the economy.

The best way to advance your career is to make choices that benefit the most people.

You're not going to get ahead if your decision fails to save lives or the economy.

Is this satire, or simply your first brush with politics?

The subject of the vaccine is a tidy hypothetical example. Approve vaccine (with no actual regard to efficacy or safety). Bolster confidence in the status quo, reopen economy. People feel hopeful, things look up, re-elect current administration. Whoops, turns out the vaccine is actually poison. But it's too late to elect the other guy now, and the administration retains power four more years.

You are, if you manage to blame the other party for sabotaging you.

"political decision" in this context is making a decision to approve something to increase the odds of one candidate winning. It is not "a decision by a politician" but rather "a decision with the primary motivation being political gains only".

Are you sure the polled people interpreted it like that?

I for one read it as politicians pushing for a quick release because the effects of the pandemic are so bad while the risk of side-effects is difficult to predict.

In part.

Politicians pander to their people. Most often by promising take stuff from group A and give it to group B

Killing off your constituents is usually bad for re-election. So mutual self interest.

What you just described is a "policy" decision, one designed to optimize for good results. A "political" decision would be one designed to increase one's support among some sort of collective-decision-making class (voters, in this context). It's sort of the opposite, in context.

Do you really believe polls like this are accurate?

No. It's all propaganda

Not sure how this is an ‘only’ Trump thing. Republicans believe D-politics will delay the vaccine so it doesn’t come out before Nov 3rd, and Democrats believe R-politics will prematurely release a vaccine before Nov 3rd.

This country has become so politically cancerous that I wonder if a WW2 style event were to happen (as if Covid isn’t one already) if the country could unite around it, today.

And before you question the thesis, I’ve had the pleasure of listening to a few doctors lament the possibility of having life-saving therapies or vaccines if it helped Trump get re-elected.

“A bad COVID vaccine (one that doesn't work), or heaven help us, one that causes harm, could set public healthcare back decades.”

I see this a lot (and am not jumping on you), do you mind explaining why you feel this way? To me one of the few things that could restore my faith in public health after how this pandemic has been handled is allowing widespread early access to the vaccine with full access to whatever data has been gathered. In flight is fine.

This “hur dur the masses can’t be trusted to make their own decisions” shit has got to stop. It has become clear public health in the US is more politics than health so any sort of management on an individual level gets zero trust from me.

After hearing Fauci's recent comments on the matter, my understanding is that the phase III trials can be considered for approval once there are enough infections in the control group to do a comparative analysis.

Since the events now needed to confirm the vaccine are in the control group, not the experimental group, it seems that the blocker for approval now isn't SAFETY, as it has been continually suggested, but EFFICACY.

If that is indeed the case, what makes the most sense to me would be to allow an early approval of any vaccine that meets reasonable safety requirement (some x months in stage 3 trial), but the patient must sign a waiver saying that they understand there may be rare side effects and there is no guaranteed immunity.

No, phase III is still examining safety.

For example, they document how a larger number of vaccinated individuals react to infection. A phase II trial might not track any infections.

Phase III examines both the efficacy and safety of the vaccine. These are independent questions.

Just because a trial takes x years to determine efficacy, it doesn't necessarily take the same amount of time to determine safety.

Fauci said certain vaccines could be approved as soon as there were enough events in the control group. Any dangerous side effects would only be in the experimental group and not dependent on events in the control group. If the only blocking factor is number of events in the control group, that to me suggest that the question of safety has already be sufficiently resolved for some of the candidate vaccines.

Yes, I directly addressed that. A potential safety issue with vaccines is making the course of the infection worse. So you have to look at vaccinated people that get infected (an 'event') to check on that.

Phase II checks if the vaccines directly causes problems, but doesn't look at a lot of events.

I see, thanks for the clarification

It's both. The purpose of phase II trials is merely to demonstrate that the new drug is safe enough to proceed to phase III trials. That's typically a much lower bar to clear than demonstrating that it's safe enough to release onto the market.

With (typically) no more than a few hundred participants, phase II trials don't really have the statistical power to detect anything but the most serious of safety problems.

Yes, but figuring out whether something is safe is different than figuring out whether is something is effective.

To answer the efficacy question you would look at the infection and mortality rate of the experimental group and compare it to the rates of the control group. There is a minimum number of infection events needed in the control group for the comparison to be statistically significant, hence the long trial periods.

To answer the safety question I assumed you would wait some X period of time and evaluate the incidence of severe side effects that may have been caused by the vaccine. This analysis wouldn't be dependent on results to the control group. I assume this analysis can be sufficiently done with the current phase 3 trial data we have based on Fauci saying the only thing we are waiting for is events in the control group.

I didn't consider the potential safety issue that the vaccine could potentially make the vaccine worse. This safety analysis would also be dependent on control group events.

Establishing safety also involves a comparison with the control group. Otherwise you can't tell if the outcome in question is significantly more or less likely in the treatment population than in control.

Phase III tests for both safety and efficacy. The efficacy portion is the bottleneck because the experimenters do not a priori know the rate of infection. So rather than waiting for a fixed amount of time, we must wait for a target number of infections.

In contrast, since we know when each person in the treatment group got the vaccine, safety can be measured after a predetermined amount of time.

So, correct me if I'm wrong, but

a) current hypothesis is people with prior exposure to common-cold non-COVID-19 coronaviruses are by and large either asymptomatic or have milder symptoms than those without such exposure

b) presumably it should be possible to test people for these antibodies much as we can test people for COVID antibodies

If people would volunteer for the b) anti-body test in reasonable numbers, and a subset of them who have them would volunteer for a modified trial, we could possibly do a double-blind intentional-exposure test on people to confirm that the vaccine confers BETTER immunity than the existing similar antibodies do, right? Would it be possible to ethically and realistically use that strategy to accelerate effectiveness testing (if not safety testing) of any vaccine candidates? or would the smaller scale of that have only made sense for something more like Phase 2 trials?

Arguably, as long as safety is near perfect, we should be willing to tolerate only moderate (say, 90%) effectiveness (and I'd read one of the vaccines took two doses to get 100% effectiveness but was 90% after a single dose), but I don't know how safety is evaluated and obviously long-term safety and short-term safety are pretty different/I imagine a lot of people will be more concerned about long term safety and I don't know how you can reassure them on that on any kind of accelerated schedule.

What’s your source for (a)? I think virtually every human being on the planet has been infected with some coronavirus common cold strain in the past.

It would also be inversely correlated with age, as the likelihood of having contracted the common cold increases with the amount spend interacting with people throughout your life.

This doesn't reflect reality, as its correlation isnt inverted.

> inversely correlated with age

To some degree. Immunity fades, which is the whole concept of booster shots.

Sorry, forgot to check back here after posting... not 100% sure I have one source but here's one from a quick search: https://www.washingtonpost.com/health/2020/08/08/asymptomati...

Specifically this line: > Or, as a paper published Tuesday in Science suggested, it could trace back to previous encounters with other coronaviruses, such as those that cause the common cold.

Coronaviruses are called so because they look a certain way under an electron microscope. They don't necessarily have common proteins. So you point a does not stand. As for point b,due to the fact that antibodies are specialized and there are tons of viruses that cause the common cold, I wouldn't expect them to match or even exist at any given time in the bloodstream since they only last ~6m and after that memory takes the role of rapid production of new antibodies in case of a new infection.

There is documented cross-reactivity in T-cell responses: individuals who had not come in contact with SARS-CoV-2 developed an immune reaction (T-cell based) against it.

Whether this prevents infection (unlikely) or lessens the symptoms is still an open question. But the phenomenon exists.

Yes my impression was that it lessened infection, not prevented it, otherwise it would basically represent a vaccine or an alternative, at least for otherwise healthy people.

Without fast track approval, in the best case scenario, approximately how long would it take for any of these vaccine candidates to go through phase 3 trials?

Timely: https://www.statnews.com/2020/09/08/astrazeneca-covid-19-vac...

(This may be nothing, of course, but it's a decent illustration that some caution is warranted)

Given that a vaccine may not provide total protection, they should consider how to sell a potential early, safe but only moderately effective vaccination. For instance, calling it a "COVID-19 Immune Booster Shot," and be very transparent that it reduces your protection against the virus but is not total immunity. Then the world won't lose faith in science and medicine when folks who had the shot are testing positive and even dying.

Hopefully either way the amount of news coverage will be enough that most people will get informed about it, in a way that they don't for most issues.

What exactly is this news source doing here? Just repackaging a press release? There are very important questions being asked here about the wording. Journalists should be the one thinking up these questions and asking them. They shouldn't publish these kinds of statements without doing this. Otherwise they are no more than propaganda machines.

Fake news is not only out-right lying, it's journalists not doing their jobs of asking the hard questions.

Sure, who even needs a regulator if pharmaceutical companies will just promise not to bring products to market unless they are "safe and effective".

Looming in the background are torts. If vaccine makers are forced to race ahead of safety in order to get to market and one turns out to be insufficiently safe, the manufacturer may get sued into the ground.

By agreeing not to jump the safety protocol, they are continuing to both limit their liability directly (by ensuring a safer product) and adhere to best-practices (which might help in a future court case).

Shh, if you say that too loud, the presidential administration will just indemnify them.

It's been decades since vaccine makers had any liability for their products in the US. That hasn't changed with COVID-19.

https://en.wikipedia.org/wiki/National_Childhood_Vaccine_Inj...

I signed a waiver for a non-approved yellow-fever vaccine in the US recently (supply of the approved vaccine is either non-existent or very limited); there must be some level of testing/certification required before reaching that threshold?

There are 170+ covid vaccines being developed, 7 of which are in stage 3 trials: https://www.washingtonpost.com/graphics/2020/health/covid-va...

So it's a bit misleading to talk about "the vaccine".

We should have had a serious national discussion about letting low risk volunteers be exposed to the virus to rapidly progress through Phase 3, right?

https://www.nature.com/articles/d41586-020-01179-x

Here in Europe they are freed from legal consequences should the vaccine harm someone. Instead our countries are to pay any occurring damaging. So I don’t quiet get what motivated the vaccine makers to await the approval given that they are practically free from prosecution anyway.

The U.S. has a similar regulatory regime to manage vaccine liability. But it's not a free-for-all; vaccines need to meet certain criteria before they qualify for this program.

This is a huge reason that these companies are concerned. If they are pushed to release a vaccine too early, and it harms a bunch of people, any evidence they bent the rules at all will be used to try to break their immunity from civil liability. It would be a field day for personal injury lawyers.

It should be in everyone's (and certainly the manufacturers') interest that the vaccines actually are safe.

Past has shown that it wasn’t. See swine flu vaccinations.

No vaccine is 100% safe. That doesn't exist.

The real question is the risk/benefit profile. Does the benefit of the vaccine outweigh the risks. That was a "no" for the swine flu vaccine since the outbreak fizzled out quickly.

If tens of thousands were dying every month from the swine flu, then the vaccine may have still be worth it even with the GBS side effect.

Meta observation: The sheer volume of downvoting of reasonable comments in here really speaks volumes about the extent to which the SARS-CoV-2 pandemic is at least as much a political subject as it is a scientific one.

"El sueño de la razón produce monstruos" (The Sleep of Reason Produces Monsters).

Question: is it not a standard procedure to stop a Phase III trial early when the statistics warrant it? Isn't this a pretty cut-and-dried statistical question? Naively I would think that there's nothing controversial about ending a trial early, isn't that the ethical thing to do?

I guess the political maneuvering angle before the election complicates all of that, but if the Trump administration is really willing to actually fabricate Phase III trial data, then why trust anything regardless of whether or not the Phase III trial "completes" or not?

My understanding is that the data has to be overwhelmingly good to stop the trial early.

I suspect the Trump administration's ability to actually fabricate trial data would be pretty limited without collateral damage (i.e. whistleblowing). Their ability to push it out of Phase III prematurely however is more debatable.

I don't think they typically stop the trial as much as they go to the FDA for emergency authorization with data from their midpoints showing overwhelmingly positive effects to get approval to proceed to Phase 4, while still finishing Phase 3. It's meant to compress the timeline, not to skip steps.

If the statistics warrant it then yes, but for a vaccine, even waiting to finish these trials is an incredibly rushed schedule. This isn't even about stopping the trial early - this is about approving it conditionally before the trial is done and then waiting for the trial to end to really approve it. I don't think the concern is about fabricating phase III data. The concern is that extreme political pressures mean no matter what the interim results say, the FDA may feel inclined to approve the vaccine. Considering that we need healthy people to willingly take these vaccines to end the pandemic, losing that trust in the process would be devastating. People need to believe that the FDA approved it because the evidence shows the vaccine is most likely effective without safety concerns. If they don't, then they won't take it, and if the vaccine then fails phase III, its not clear how you regain that trust as a regulatory agency.

> This isn't even about stopping the trial early - this is about approving it conditionally before the trial is done and then waiting for the trial to end to really approve it

I see -- yea totally agree, I thought they were committing to a rigid timetable or something but that's not what's happening here as you say.

Yeah - its some unprecedented stuff for a vaccibe. One important thing to remember is that its impossible to test two important factors for vaccines in a short trial - long term side effects and durability of the immunity. I mean, it's not physically impossible. You could take a few hundred participants, vaccinate them, put them on a ship going at some percentage the speed of light, and then see if they have any side effects and do a challenge study to see if they're still immune. Short of playing with the fabric of space time (and ethics) - you're not really getting that data from any of these trials, which is why as I mentioned even with completed trials this timeline js unprecedentedly short.

The statement does not actually commit these companies to completing the entire Phase III trials regardless of outcome. The relevant paragraph from this article (with quote) is:

> In a statement, the companies pledged to “make the safety and well-being of vaccinated individuals our top priority.” The vaccine developers said they would continue to impose high ethical and scientific standards on the vaccine-testing process, and apply for government authorizations only “after demonstrating safety and efficacy through a Phase 3 clinical study.”

"Through" in that last quote is being taken to mean "at the completion of". But it can also mean "through the use of."

I disagree with the headline that Stat put on their article. To me it seems clear that the commitment from these companies is to the quality of the process, not a particular rigid timetable.

Edit - here is the full statement for those who want to read it.

https://investors.modernatx.com/news-releases/news-release-d...

Ah I gotcha yea, I just misread the article. That makes more sense and seems much more reasonable.

Vaccines are a bit different than "cures" for stopping trials.

If you test drug XYZ and after a while it's clear that far more people in the control group die, you quickly declare XYZ proven effective, stop the trial, and give XYZ to the control group to save as many lives as possible.

For vaccines there are no such dramatic effects. Everyone in the study is healthy, at least to begin with, so there is no tragedy to avert, and you can let the study keep going even after it starts becoming clear that the vaccine is good.

At least in theory. I don't know the actual bureaucratic protocols.

The usual protocols have been well and truly thrown out the window, so I don't know what the comparison point would be. Moderna didn't even finish animal trials before giving their vaccine to humans.

The vaccine hail Mary is weird to me. We've seen that herd immunity can be achieved (see Sweden). People under 65 with sufficient levels of vitamin D have extremely low odds of dying from this disease, less than even the flu. The CDC reported that less than 10% of deaths reported were from Covid alone. We're probably already near herd immunity with hospitalizations plummeting everywhere. Why are we still pinning everything on hopes for a vaccine?

No, we are not at herd immunity. Because if uncontrolled, in US alone 3 million (probably more) would die.

The problem is that the people who back reopening are also against precautions that would make reopening safer. If I could trust the random people I'll encounter to wear their masks correctly and stay home if they're sick, maybe I would feel safe going out again. But instead politics has emboldened these people to behave in ways that put the people around them at more risk than necessary.

Not sure where to start with these statements, but they aren't helpful.

    "We've seen that herd immunity can be achieved (see Sweden)."

No it can't. By the end of July 2020 only 6% of the population was known to have antibodies, according to the Swedish Public Health Agency[1]. It is estimated that 70% to 90% of a population needs such antibodies to achieve herd immunity[2]

    "People under 65 with sufficient levels of vitamin D have extremely low odds of dying from this disease."

Vitamin D has not been scientifically proven as a preventative treatment for COVID-19. The UK National Institute for Health and Care Excellence published a report summarising the research studies on Vitamin D for COVID-19 and found that 'no causal relationship between vitamin D status and COVID‑19 was found after adjustment for confounders such as comorbidity, socio-demographics, ethnicity, BMI and other baseline factors.' [3]

    "We're probably already near herd immunity"

If you are referring to the USA here this is likely not true. No one knows the "true" infection rate, but even if you use the upper estimates of Imperial College modelling[4] this figure is 72 million, or 22% of the population.

    "... less than even the flu"

Again not true. Every age group has worse outcomes from COVID-19 than the flu. If you are 50-64 you are almost 5 times as likely to die[5]

    "... hospitalizations plummeting everywhere"

The hospitalisation rate is down, but not "plummeting". There are still 32,000 people hopsitalised in the U.S. [6] and a number of forecasters predicting a rise over the next 4 weeks[7].

[1] https://bbc.co.uk/news/world-europe-53498133

[2] https://www.jhsph.edu/covid-19/articles/achieving-herd-immun...

[3] https://www.nice.org.uk/advice/es28/chapter/Factors-for-deci...

[4] https://ourworldindata.org/covid-models

[5] businessinsider.com/coronavirus-death-rate-us-compared-to-flu-by-age-2020-6?r=US&IR=T

[6] https://covidtracking.com/data/national/hospitalization

[7] https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/hosp...

Then why are new hospitalizations and new cases nearly non-existent in Sweden? There's only 13 people in serious or critical condition in the entire country, according to: https://www.worldometers.info/coronavirus/country/sweden/ No mask orders or shutdowns of schools or shelter in place ever occurred in Sweden. They achieved comparable results to other European countries like France, Spain, UK as well as the US with no lockdowns whatsoever.

Here is a randomized clinical trial on Vitamin D, released a few days ago:

Effect of Calcifediol Treatment and best Available Therapy versus best Available Therapy on Intensive Care Unit Admission and Mortality Among Patients Hospitalized for COVID-19: A Pilot Randomized Clinical study

"Our pilot study demonstrated that administration of a high dose of Calcifediol or 25-hydroxyvitamin D, a main metabolite of vitamin D endocrine system, significantly reduced the need for ICU treatment of patients requiring hospitalization due to proven COVID-19. Calcifediol seems to be able to reduce severity of the disease, but larger trials with groups properly matched will be required to show a definitive answer."

https://www.sciencedirect.com/science/article/pii/S096007602...

EDIT:

Also, take a look at the Excess Deaths chart: https://www.cdc.gov/nchs/nvss/vsrr/covid19/excess_deaths.htm We are already back to average levels or somewhere near a bad flu season as is. We only had a substantially higher excess death count for 6-8 weeks there, and only by a few thousand. The data is certainly not matching up with the extraordinary disruption of people's lives. It's time to move on.

WTF. This is going to kill people. A lot of people.

Look, the usual situation with vaccines is that we are weighing (1) the danger posed to the few people who get sick while the trials are going on; vs. (2) the risks taken on by everybody who gets the vaccine. The vaccine might have a small likelihood of triggering reactions or otherwise having adverse effects, and spread over the entire population these edge cases can add up to do more damage than the disease itself.

Again, that is for typical vaccine situations. A pandemic is totally different--the number of cases is exponentially increasing and ripping through the entire population. So our options are:

1. Wait the additional 6-12 months it would take (even accounting for the immense investments that have been made) to get a vaccine to go through all the normal regulatory hoops we would demand of vaccine development outside of a pandemic. During which time COVID-19 rips through the population leaving potentially millions dead and hundreds of millions of recovered with disease-related tissue damage.

2. Wait, but stay in lockdown to keep the disease at bay, but in the process massively drive up suicide, domestic violence, and divorce rates, wreck the economy, and force people to spend their savings and/or trigger massive inflation through pandemic relief.

3. Some horrible compromise between the above two extremes.

4. Roll out the vaccines as quickly as they can be manufactured, starting now. Don't wait for Phase III results.

The Phase I and Phase II trials tell us that the vaccine successfully generates antibodies. The group sizes so far have been large enough to know that the risk of fatal interactions is less than the risk of dying from COVID-19 itself--indeed, for the most part there haven't been ANY severe reactions, at least in the major vaccines.

This "wait until the vaccine is proven safe!" is politically generated nonsense. There is no data-driven argument supporting it. Ideologues on the left assume that Trump wants a vaccine ASAP to win reelection, don't trust is understanding of the science, and therefore assume that early administration of a vaccine would be some sort of unsafe political compromise. Ideologues on the right believe COVID-19 is a hoax anyway. But even a broken clock is right twice a day, and the fact that Trump wants a quick vaccine approval has no bearing on whether it is a good idea or not; and in this case it very clearly IS beneficial to distribute a vaccine as quickly as it can be manufactured.

Seems like a smart decision by those businesses to team up (collude?) here both for business and public health reasons. If they all agree to wait post election there will be a higher rate of vaccinations which will benefit everyone (sales and progress towards herd immunity). I'm not sure if this would put them into any odd legal situations for playing politics.

There's no collusion or team up here, the pledge in question carries no obligations and is not legally binding. So this is more of a PR play. Possibly in response to politicians sowing doubt on the efficacy of a vaccine.

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