What if herd immunity can't be reached with a vaccine, as too many refuse to have it?

[corfield]

No - it doesn't have to be as "safe as possible" - it has to be safer than the alternative.

And that would certainly involve having good evidence that it won't actually kill more people than if it's not used.

I don't know there is any intention to remove any of the normal steps in certifying a vaccine anyway, though it looks as if the intention is to get through them a lot more quickly than usual.

The point is that evidence only comes out over time.

So trying to “get through ... more quickly than usual” is exactly that evidence of it being rushed.

Throw in the factors of money and politics and it has the hallmarks of a disaster.

Safe as possible, or rather, practicable, is the test actually. The safety vs an alternative is a subjective measure.

 

[AdamWW]

Are you seriously trying to claim credit for someone considering both sides? The evidence it has nothing to do with you is above...

No I'm not.

 

[AdamWW]

The point is that evidence only comes out over time.

So trying to “get through ... more quickly than usual” is exactly that evidence of it being rushed.

Throw in the factors of money and politics and it has the hallmarks of a disaster.

Safe as possible, or rather, practicable, is the test actually. The safety vs an alternative is a subjective measure.

OK we'll have to disagree on that.

I think that evaluating the risk of an action is meaningless unless you compare it with the risk of inaction.

It's clear that some people here make decisions differently. That's entirely up to them of course.

 

[Bletchleyite]

I think that evaluating the risk of an action is meaningless unless you compare it with the risk of inaction.

This situation is very much like the "points problem", i.e. you have a runaway train and a set of manually controlled points, leaving the points unchanged will cause 2 people tied to the track to be killed, changing the points will cause 1 different person to be killed, do you change the points or not?

 

[bramling]

OK we'll have to disagree on that.

I think that evaluating the risk of an action is meaningless unless you compare it with the risk of inaction.

It's clear that some people here make decisions differently. That's entirely up to them of course.

This is the problem with all this, there’s a large amount of unknown.

Personally I can certainly see some merit in the argument that a vaccine may well have been rushed. Does that risk outweigh the risk of both getting Covid and having a negative outcome from it? The answer is none of us really knows.

 

[corfield]

This situation is very much like the "points problem", i.e. you have a runaway train and a set of manually controlled points, leaving the points unchanged will cause 2 people tied to the track to be killed, changing the points will cause 1 different person to be killed, do you change the points or not?

No of course not, you untie the people from the tracks.

 

[AdamWW]

This is the problem with all this, there’s a large amount of unknown.

Personally I can certainly see some merit in the argument that a vaccine may well have been rushed. Does that risk outweigh the risk of both getting Covid and having a negative outcome from it? The answer is none of us really knows.

Yes I agree - I would be wary of any vaccine.

But in making a decision I would include the latest evidence we have on what contracting coronavirus might do, not just look at the death rates.

 

[Bletchleyite]

No of course not, you untie the people from the tracks.

With regard to COVID, how do you propose to achieve that without many thousands more deaths?

 

[Bantamzen]

No - it doesn't have to be as "safe as possible" - it has to be safer than the alternative.

And that would certainly involve having good evidence that it won't actually kill more people than if it's not used.

I don't know there is any intention to remove any of the normal steps in certifying a vaccine anyway, though it looks as if the intention is to get through them a lot more quickly than usual.

Actually it has to be a lot safer than the alternative, i.e. less risk of serious illness or death, and it has to be shown not to have any other funky side effects.

 

[AdamWW]

Actually it has to be safer than the alternative, i.e. less risk of serious illness or death, and it has to be shown not to have any other funky side effects.

Surely "it has to be shown not to have any other funky side effects" is included in "safer than the alternatives"?

 

[Yew]

This situation is very much like the "points problem", i.e. you have a runaway train and a set of manually controlled points, leaving the points unchanged will cause 2 people tied to the track to be killed, changing the points will cause 1 different person to be killed, do you change the points or not?

I've used the Trolley problem a few times in discussions, and apart from the oversimplification of making it a binary problem, the issues is determining the number of people on each side, as that depends on a persons judgement of the risks.

 

[corfield]

My argument, is that quite frankly the high risk is more than outweighed by the potential vast reward. I think there are several good signs too - the various groups developing a vaccine are all taking different approaches. So it seems unlikely that even if some are malicious or negligent, all the different groups are. And while profits will be a motivating factor, a bigger one will be acclaim. The chances are, the scientists who produce the best vaccine will win Nobel prizes and will become internationally renowned. A scientist who produces a botched vaccine will quite possibly never work again, and will be deeply disgraced. As far as I'm concerned that's a pretty strong motivation for these groups to get it right.

As to mandatory vaccines, personally I think that should be a last resort. But is it really any more dystopian than the current situation? This masked, socially distanced dystopia which is increasingly emerging? If we find a good vaccine, that means no more masks, no more distancing, and a return to the proper normal. I'd argue that's worth the risks a thousand times over.

But what is the vast reward?

So many people will have already had it or been exposed. Arguably it has already taken those most vulnerable.

There is ample evidence from history that for acclaim people will do anything, and then do anything to cover that up. With this so politicised (think Trump’s comments and actions alone) and the money involved vast beyond comprehension - consider how politics and money have conspired to cover up harmful outcomes or even keep harmful things going.

Absolutely and especially in this atmosphere almost religious zeal for “its for yours and our safety” where dissenters are treated as heretics.

We are running into a perfect storm I feel and for the same blind reasons we have in the past.

 

[bramling]

Yes I agree - I would be wary of any vaccine.

But in making a decision I would include the latest evidence we have on what contracting coronavirus might do, not just look at the death rates.

In that case the right answer is undoubtedly to wait and see. At present very little seems to be known about long-term effects on various cohorts of people, so we simply don’t have enough info to even start to make an informed judgement.

Presumably the best, albeit rather selfish, choice for an individual at this moment is to hope for herd immunity whilst not contracting Covid one’s self!

I'm surprised more isn't being said about some of the longer term effects. We've heard snippets on the news about complications like lung damage, but it's only really ever mentioned in passing. Surely at this stage there must be some idea what's going on in this respect?

 

[Bantamzen]

Surely "it has to be shown not to have any other funky side effects" is included in "safer than the alternatives"?

No, the alternative to a covid vaccine is not to have a vaccine. A vaccine needs not only to decrease your chances of contracting covid and/or increase the chances of survival, it must also not produce any other side effects that could cause illness or death.

 

[AdamWW]

No, the alternative to a covid vaccine is not to have a vaccine. A vaccine needs not only to decrease your chances of contracting covid and/or increase the chances of survival, it must also not produce any other side effects that could cause illness or death.

Of course - that's included in the "safer" bit of "safer than the alternative".

 

[Bantamzen]

Of course - that's included in the "safer" bit of "safer than the alternative".

Did you read what I said? The alternative is not to have a vaccine, so "safer than the alternative" in that context is a vaccine that decreases the chances of mortality or illness. But the tests do not just look at that, they look at other side effects to ensure that other unexpected side effects occur that could cause illness or death. Its not enough that it might reduce the impact of covid, it needs to be safe for literally hundreds of millions, billions even.

 

[AdamWW]

Did you read what I said? The alternative is not to have a vaccine, so "safer than the alternative" in that context is a vaccine that decreases the chances of mortality or illness. But the tests do not just look at that, they look at other side effects to ensure that other unexpected side effects occur that could cause illness or death. Its not enough that it might reduce the impact of covid, it needs to be safe for literally hundreds of millions, billions even.

Yes I agree completely.

A vaccine that gives you 100% protection from coronavirus but guarantees that you will drop dead in two years time is not a good thing - and is not safer than the alternative!

 

[Bantamzen]

Yes I agree completely.

A vaccine that gives you 100% protection from coronavirus but guarantees that you will drop dead in two years time is not a good thing - and is not safer than the alternative!

Then you agree that there is no alternative but to test out any potential vaccine the way you would any other medical treatment, regardless of the mortality rate?

 

[jtuk]

It's quite difficult to do a risk benefit analysis if you don't know what the risks actually are, as was the case in March.

We knew quite a lot then actually

 

[AdamWW]

Then you agree that there is no alternative but to test out any potential vaccine the way you would any other medical treatment, regardless of the mortality rate?

No.

I think the approach should be to consider whether any modification to the usual process can be justified by comparing with the alternatives.

For example, compressing the timescale for human trials reduces the ability to determine unexpected long term side-effects.

But getting an effective vaccine out earlier will reduce the number of infections, which also carry an unquantified risk of long term side-effects.

And if it lets you drop lockdown it potentially saves lives by getting people out of financial problems and improving mental health.

And gives greater ability for the health system to treat non-Covid related issues.

I do not agree to a one-size-fits all approach which looks at the risks of a vaccine without considering the benefits, any more than I think that someone wheeled into a hospital for emergency life-saving surgery should then wait several weeks while they go through the procedures they would to ensure they were fit for elective surgery.

 

[Bantamzen]

OK, let's look at these points:

I think the approach should be to consider whether any modification to the usual process can be justified by comparing with the alternatives.

For example, compressing the timescale for human trials reduces the ability to determine unexpected long term side-effects.

But getting an effective vaccine out earlier will reduce the number of infections, which also carry an unquantified risk of long term side-effects.​

Indeed it will, but this is one of the major reasons any kind of testing of treatment or remedies are not reduced. Because if there are serious long term effects, you may not know about them until it is way too late. And in the case of a covid vaccine, way too late could literally mean hundreds of millions of people too late. The whole scale of the requirement means that you have to be more cautious, not less. Can you imagine what would happen a vaccine was administered to millions, only for the discovery to be made that it will have serious, potentially life changing effects on a significant number of those people, many of whom were not considered at risk from covid?

​

And if it lets you drop lockdown it potentially saves lives by getting people out of financial problems and improving mental health.

This is a political decision, and one that politicians do have to consider, but it is not politicians making & testing vaccines. Politics should not be a consideration when developing potential treatment regimes, I invite you again to consider what Trump has been peddling as a "cure".

​

And gives greater ability for the health system to treat non-Covid related issues.

Again a political decision, at least for developed nations. There are potentially plenty of ways that the biggest economies can re-purpose budgets to focus on specialist, and separated care systems to deal with patients with serious illnesses as a result of covid. This is a strategy recommended by many epidemiologists.

​

I do not agree to a one-size-fits all approach which looks at the risks of a vaccine without considering the benefits, any more than I think that someone wheeled into a hospital for emergency life-saving surgery should then wait several week while they go through the procedures they would to ensure they were fit for elective surgery.

And I would agree, different vaccines will go through different lifecycles. In the case covid potentials, it seems that one advantage is being part of a wider viral family, covid shares some types of proteins with it's predecessors meaning that development of potential vaccines is accelerated, and thus getting them to the trial stages quicker than if they were dealing with a whole new type of virus.

However, and I really can't stress this enough in the clamber to get a vaccine, trials still need to go through due process and certification, to ensure that as much risk is assessed as you would with other medical treatments. That covid is spreading across the globe does not mean that we should forgo all or parts of these processes, because once you pass it out for mass use there will be no turning back. You can't undo a bad vaccine, especially if it is terminal.

 

[AdamWW]

OK, let's look at these points:
Indeed it will, but this is one of the major reasons any kind of testing of treatment or remedies are not reduced. Because if there are serious long term effects, you may not know about them until it is way too late. And in the case of a covid vaccine, way too late could literally mean hundreds of millions of people too late. The whole scale of the requirement means that you have to be more cautious, not less. Can you imagine what would happen a vaccine was administered to millions, only for the discovery to be made that it will have serious, potentially life changing effects on a significant number of those people, many of whom were not considered at risk from covid?

Yes of course I can. I am not advocating "rushing" the process but neither do I think decisions on risk should be made in isolation.

This is a political decision, and one that politicians do have to consider, but it is not politicians making & testing vaccines. Politics should not be a consideration when developing potential treatment regimes, I invite you again to consider what Trump has been peddling as a "cure".

Again a political decision, at least for developed nations. There are potentially plenty of ways that the biggest economies can re-purpose budgets to focus on specialist, and separated care systems to deal with patients with serious illnesses as a result of covid. This is a strategy recommended by many epidemiologists.

Well again we disagree. I don't think you should put risks in "medical" and "political" categories and use that as a reason not to make a balanced decision.

And I would agree, different vaccines will go through different lifecycles. In the case covid potentials, it seems that one advantage is being part of a wider viral family, covid shares some types of proteins with it's predecessors meaning that development of potential vaccines is accelerated, and thus getting them to the trial stages quicker than if they were dealing with a whole new type of virus.

However, and I really can't stress this enough in the clamber to get a vaccine, trials still need to go through due process and certification, to ensure that as much risk is assessed as you would with other medical treatments. That covid is spreading across the globe does not mean that we should forgo all or parts of these processes, because once you pass it out for mass use there will be no turning back. You can't undo a bad vaccine, especially if it is terminal.

Agreed. I'm not suggesting we throw all caution to the winds.

But unless we are being lied to, there is a hope of a vaccine being ready far more quickly than has ever been the case before.

Now maybe at lot of the reduced timescale is due to throwing more money at the problem and running stages in parallel. But at the least we won't have the idea of long term side effects that we would for a vaccine tested over 10 years.

I'd argue that this could be justified by the risks of not having the vaccine and people suffering long term effects.

Refusing to look at the risk balance prohibits this approach, and would say that we shouldn't roll the vaccine out for years and years.

 

[87electric]

But unless we are being lied to, there is a hope of a vaccine being ready far more quickly than has ever been the case before.

Would you seriously be happy with stringent trials of vaccines being extensively shortened?

 

[AdamWW]

Would you seriously be happy with stringent trials of vaccines being extensively shortened?

Without knowing what normally drives the timescales and what has been done to shorten them I can't say.

I would want to know more before having one.

For example if they have saved time by running animal trials in parallel with human trials, that has potentially put volunteers at risk but otherwise shouldn't make much difference.

If a large part of the timescales for vaccines is having to wait for enough people to be exposed and we can get that in a much shorter time in this case by doing trials in a country where coronavirus is widespread, again that shouldn't be a problem.

I find it a little hard to imagine that so many people are attempting to produce a vaccine by some time next year if the whole idea is so ludicrously risky that it shouldn't be allowed.

I can however completely understand why people would not want such a vaccine.

But - going back to my original point - I think anyone looking at just the risks of having the vaccine without balancing the risks of not having it and thus contracting Covid-19 isn't making an optimal decision.

 

[yorkie]

Without knowing what normally drives the timescales and what has been done to shorten them I can't say.

I would want to know more before having one.

For example if they have saved time by running animal trials in parallel with human trials, that has potentially put volunteers at risk but otherwise shouldn't make much difference.

If a large part of the timescales for vaccines is having to wait for enough people to be exposed and we can get that in a much shorter time in this case by doing trials in a country where coronavirus is widespread, again that shouldn't be a problem.

I find it a little hard to imagine that so many people are attempting to produce a vaccine by some time next year if the whole idea is so ludicrously risky that it shouldn't be allowed.

I can however completely understand why people would not want such a vaccine.

But - going back to my original point - I think anyone looking at just the risks of having the vaccine without balancing the risks of not having it and thus contracting Covid-19 isn't making an optimal decision.

I do thoroughly agree with this post.

Incidentally the Oxford vaccine is currently undergoing trials in Brazil due to precisely the reason you state, that infection levels are too low in the UK.

It's important to hear in mind that any vaccine that is building on previous work is going to naturally be at a more advanced stage, and therefore may appear to be 'rushed' when it isn't.

We cannot continue living with the current restrictions for much longer; we could wait a few years until more tests have been done, but at what cost?

The vaccine is not going to be mandatory, it does not need to be mandatory, and I would be happy to be vaccinated with the Oxford vaccine as soon as it becomes available.

 

[43066]

But unless we are being lied to, there is a hope of a vaccine being ready far more quickly than has ever been the case before.

Now maybe at lot of the reduced timescale is due to throwing more money at the problem and running stages in parallel. But at the least we won't have the idea of long term side effects that we would for a vaccine tested over 10 years.

Who is throwing money at this problem, and why?

It’s predominantly drug manufacturers (who bankroll most medical research) who have realised that, if they can be the first to develop an effective vaccine, and get it approved for use, they’ll be sitting on an absolute goldmine. A goldmine that will be monetised almost immediately.

I can think of a few (actually a few billion) reasons why they might be keen to shortcut that process by whatever means necessary.

 

[AdamWW]

Who is throwing money at this problem, and why?

It’s predominantly drug manufacturers (who bankroll most medical research) who have realised that, if they can be the first to develop an effective vaccine, and get it approved for use, they’ll be sitting on an absolute goldmine. A goldmine that will be monetised almost immediately.

I can think of a few (actually a few billion) reasons why they might be keen to shortcut that process by whatever means necessary.

Well the UK government is spending on this, e.g. from here:

The UK Government has committed to providing £84m in funding and manufacturing support to researchers working on Covid-19 vaccine programme, said Business Secretary Alok Sharma.

Of the total funding, £65.5m is for the Covid-19 vaccine being developed at the University of Oxford and the remaining £18.5m for Imperial College London.

I think there are good reasons that both governments and industry might be prepared to spend money to safely shorten the timescale that they wouldn't for - say - an Ebola vaccine.

In project management you generally get to trade off between cost, quality and time. Given the strict regulatory framework for medical development, I would have thought trading cost and time is going to be a lot easier to do than quality and time.

Incidentally there is a story here that Astra Zeneca will provide up to 400 million vaccine doses to Europe at no profit. I presume this doesn't mean they won't be looking for profit elsewhere.

 

[MikeWM]

Look what could have happened if Trump and some other world leaders have endorsed hydroxychloroquine as a treatment / cure, and this is a drug that is clinically tested.

I've been looking into this a bit over the past couple of days, and there appears to be something really quite fishy about the debate over HCQ. Not least because mentioning it at all appears to be the quickest way to get banned from social media - or even having your website taken down entirely!

Of the two most mentioned studies that 'showed' it to be dangerous, one was a fake (the Lancet had to retract it) and the other was using over-large doses too late in the disease.

A Yale Professor of Epidemiology published this article last week
https://www.newsweek.com/key-defeat...exists-we-need-start-using-it-opinion-1519535

I am usually accustomed to advocating for positions within the mainstream of medicine, so have been flummoxed to find that, in the midst of a crisis, I am fighting for a treatment that the data fully support but which, for reasons having nothing to do with a correct understanding of the science, has been pushed to the sidelines. As a result, tens of thousands of patients with COVID-19 are dying unnecessarily. Fortunately, the situation can be reversed easily and quickly.

I am referring, of course, to the medication hydroxychloroquine. When this inexpensive oral medication is given very early in the course of illness, before the virus has had time to multiply beyond control, it has shown to be highly effective, especially when given in combination with the antibiotics azithromycin or doxycycline and the nutritional supplement zinc.

On May 27, I published an article in the American Journal of Epidemiology (AJE) entitled, "Early Outpatient Treatment of Symptomatic, High-Risk COVID-19 Patients that Should be Ramped-Up Immediately as Key to the Pandemic Crisis." That article, published in the world's leading epidemiology journal, analyzed five studies, demonstrating clear-cut and significant benefits to treated patients, plus other very large studies that showed the medication safety.

...

On May 27, the Swiss national government banned outpatient use of hydroxychloroquine for COVID-19. Around June 10, COVID-19 deaths increased four-fold and remained elevated. On June 11, the Swiss government revoked the ban, and on June 23 the death rate reverted to what it had been beforehand. People who die from COVID-19 live about three to five weeks from the start of symptoms, which makes the evidence of a causal relation in these experiments strong.

Or there is this from Malcolm Kendrick, a UK doctor who frankly I trust a lot more than most people in the UK medical establishment
https://drmalcolmkendrick.org/2020/07/05/distorting-science-in-the-covid-pandemic/

Evidence that a cheap, over-the-counter anti-malarial drug costing £7 combats COVID-19 gets trashed. Why? Because the pharmaceutical giants want to sell you a treatment costing nearly £2,000. It’s criminal.

...

One issue that has played out over the last few months, has stripped away any remaining vestiges of my trust in medical research. It concerns the anti-malarial drug hydroxychloroquine. You may well be aware that Donald Trump endorsed it – which presents a whole series of problems for many people.

However, before the pandemic hit, I was recommending to my local NHS trust that we should look to stock up on hydroxychloroquine. There had been a great deal of research over the years, strongly suggesting it could inhibit the entry of viruses into cells, and that it also interfered with viral replication once inside the cell.

This mechanism of action explains why it can help stop the malaria parasite from gaining entry into red blood cells. The science is complex, but many researchers felt there was good reason for thinking hydroxychloroquine may have some real, if not earth-shattering benefits, in COVID-19.

...

The other reason for recommending hydroxychloroquine is that it is extremely safe. It is, for example, the most widely prescribed drug in India. Billions upon billions of doses have been prescribed. It is available over the counter in most countries. So I felt pretty comfortable in recommending that it could be tried. At worst, no harm would be done.

...

When things get this messed up, I tend to look for the potential conflicts of interest. By which I mean, who stands to make money from slamming the use of hydroxychloroquine (which is a generic drug that has been around since 1934 and costs about £7 for a bottle of 60 tablets)?

In this case it is those companies who make the hugely expensive antiviral drugs such as Gilead Sciences’ Remdesvir – which costs $2,340 (£1877) for a typical five-day course in the US. Second, the companies that are striving to get a vaccine to market. There are billions and billions of dollars at stake here.

In this world, cheap drugs e.g., hydroxychloroquine, don’t stand much chance. Neither do cheap vitamins, such as vitamin C and vitamin D. Do they have benefits for COVID-19 sufferers? I am sure that they do. Will such benefits be dismissed in studies that have been carefully manipulated to ensure that they do not work? Of course.

Now a vaccine may well not be needed at all if there is a safe, effective treatment available. But as Malcolm Kendrick says, a cheap off-patent drug isn't going to make any money for anyone. And Governments seem very keen to throw money around at vaccine manufacturers (I think we've got over 250 million doses of various vaccines pre-ordered now for the UK...)

I don't know. I'm not saying HCQ works, or not - the evidence seems mixed. But there definitely seems something odd going on when you even try to debate the issue. Maybe it is a knee-jerk reaction to assume anything Trump says is silly, because most of it is. Maybe something else.

 

[43066]

Well the UK government is spending on this, e.g. from here:


I think there are good reasons that both governments and industry might be prepared to spend money to safely shorten the timescale that they wouldn't for - say - an Ebola vaccine.

In project management you generally get to trade off between cost, quality and time. Given the strict regulatory framework for medical development, I would have thought trading cost and time is going to be a lot easier to do than quality and time.

Incidentally there is a story here that Astra Zeneca will provide up to 400 million vaccine doses to Europe at no profit. I presume this doesn't mean they won't be looking for profit elsewhere.

Normally drug companies have a commercial incentive to develop treatments, while governments have a political incentive to ensure they’re safe, so natural checks and balances are in place.

At the moment, in the midst of a global pandemic, there’s both an enormous commercial incentive *and* an enormous political incentive to get a vaccine over the line.

That observation is plenty enough to persuade me that I’m not going to be first in line for this particular vaccine. I’d rather take my chances with the virus.

 

[AdamWW]

Normally drug companies have a commercial incentive to develop treatments, while governments have a political incentive to ensure they’re safe, so natural checks and balances are in place.

At the moment, in the midst of a global pandemic, there’s both an enormous commercial incentive *and* an enormous political incentive to get a vaccine over the line.

That observation is plenty enough to persuade me that I’m not going to be first in line for this particular vaccine. I’d rather take my chances with the virus.

Personally I'd rather spend a bit more time looking into the evidence when or if the time comes, rather than assuming that the presence of vested interests must mean that the vaccine is a greater risk than the disease itself.