plans for mass vaccination at schools in autumn

[pofacedandproud]

here

How do people feel about this?

hi Stuffit....a very important point to put on the table is that in no way are we arguing - we are having (IMO) a balanced, healthy adult debate .

You are spot on about the issue of "background events". It is the way that science works for absolutely everything (be it medicine or research; clinical scenario's or lab based experiments). We measure "the normal" situation and look to see if what we do to "intervene" changes the frequency of a given event. I don't see any other way to do it. And even if all 10 of those cases of encephalitis were investigated and - for the sake of argument - one of them was in some way related to vaccine administration - it would be difficult/nearly impossible to prove as it is only 1 example, and there would always be scientific doubts over cause and effect and indirect effects and nature.

I see what you are saying - but if the frequency of a given event is within the normal range for an untreated population - it won't ever raise concerns...and it will be considered as something that was likely to happpen anyway.

It is just the way science works.

Oh and to answer the risk v benefit thing. It is ABSOULTELY appropriate - if not critical for a new drug/vaccine.

There will be adverse events predicted (from animal studies for example) - which will after a risk v benefit analysis will decide whether those potential risks are worth taking.

Then - there will be potential risks identified during phase 1 testing which will help dictate whether it should pass to phase II etc.

And it doesn't just relate to changing risks. You could take a drug which is highly toxic - and it would never acheive approval for a "relatively mild" condition like flu because the risks (toxicity) far outway the benefits (treatment of a usually mild self limiting disease).

If you took a drug with exactly the same toxicology problems and tried to get approval in cancer patients you are much more likely to be successful because although the risks are higher the benefits are also signicficantly greater (because you may potentaially save lives).

The regulatory authorities can ONLY give a new drug approval if the risk benefit analysis is favourable. However, in the earlier trials and marketing period it is acknowledged that one aspect of risk - the limited characterisation within patient popuation is higher than it is for a drug which has been marketed safely for a number of years.

Of course the outcome of such analysis is not always the right answer.

That's bringing epidemiology into a clinical trial. I don't think most people know that adverse events in drug trials will be dismissed unless greater than normal. Particularly since adverse events outside drug trials and in general use are so often dismissed as coincidence.

The coincidence/normality reassurances seem to go hand in hand. If the timing of an adverse event is always dismissed as coincidence then you have a circular argument. It can't be a reaction because it's coincidence: it must be coincidence because it's not an adverse event. It can't be a reaction because it's "normal": it's must be "normal" because it's not a reaction.

It's a bit like the Wakefield circular argument. Why did you assume Wakefield was wrong about MMR? Because he's a maverick. Why is he a maverick? Because he's wrong about MMR.

You can't make a risk benefit analysis if you don't know the risks. If you don't investigate every adverse event below the background tariff then you cannot know the risks.

It's the difference between the wood and the trees.

TBH I have tried to stay right out of the Wakefield arguments....

Lets take another analogy

You collect 12 eggs from hens and walk back from teh barn to find that 1 or 2 eggs are always broken when you get back to the kitchen.

One day it rains. So you run back. 2 eggs are broken. Would you assume that it was because it is raining and you ran? No you wouldn't because it is "normal" for 1 or 2 eggs to be broken.

What if 3 eggs were broken in the rain? You may not put that down to the rain because it isn't significan;t different from 1 or 2. But you may if you broke 3 eggs in the rain a few times.

In science you ALWAYS have to have a baseline or threshold to compare to. (Whether the group or population that you choose as your baseline is selected appropriately is another question). I am not really sure how you would investigate undesirable events if they are at a "normal" frequency.

Quite a lot of AEs have an unknown mechanism.. So - for example - we know that after agiven drug/vaccine there is a risk of certain side effects - but we don't know why that drug leads to that event - we just know it does. And the reason we know it does is because the event happens at a higher frequency after treatment. If the event has an unknown mechanism, and is at the same frequency as an untreated population how do you know it is an adverse event specifically related to the treatment? How can you prove it or disprove it? You can't? And because it is happening at the same frequency as an untreated population you don't have any evidence what so ever that there is a link between the event and the treatment.

Not to worry, I mentioned Wakefield as an extra example of a circular argument.

"If the event has an unknown mechanism, and is at the same frequency as an untreated population how do you know it is an adverse event specifically related to the treatment? How can you prove it or disprove it? You can't?"

Well I think the thing to do (statement of the bleeding obvious?) is to try to investigate the mechanism by which such a reaction would occur. Rather than just looking at numbers.

For an example again, it's the difference Wakefield was trying to make -- actually taking samples and investigating the mechanism. It's a shame, but lucky for the pharmaceutical companies, that the scientists involved in the trials are neither as conscientious nor as thorough. It's not as if the money is not there.

For another example, when thirteen babies die during a vaccine trial, one would expect each of those deaths to be investigated to ensure that they were not caused by the vaccine.

One would think a great pointer would be the timing of the reaction, but once again we return to circular argument of coincidence. Utterly hollow of course.

I must admit, I would be rather more interested in the death of a baby than the breaking of an egg, but maybe that's not very scientific.

TBH I expected you to state the bleeding obvious that babies are more important than eggs - which is absolutely true. I was just trying to demonstrate the principle.

I hope and think (but can't be sure) that any deaths of patients on a clinical trial would be investigated to confirm that that there is no obvious mechanism that links the trial to the death. And there is of course the post mortem system to review "deaths" that are suspicious circumstances. I am guessing you are thinking of something "deeper".

The problem with the suggesting of investigating the mechanism is that I honestly believe that in the majority of cases where the incidence of the event in after treatment is the same as without treatment there will be no mechanism found. It is like looking for a needle in a haystack if you have no clue what you are looking for in science. If there is no mechanism to be found you could tie up an awful lot of science looking for something that isn't there - which could be spent on studies which advance our understanding in other area's like cancer, heart disease....

What I am NOT saying is that we shouldn't investigate adverse events because they are less important than other area's of science. I am saying where the population data suggests that nothing will be found 90%+ of the time nothing will be found. And therefore scientific investment (which is so hard to come by - even in pharmaceutical industry surprisingly) is better spent in other areas.

Also I still can't get my head around HOW to look for something where the numbers are equal in untreated and treated groups. Because what science would normally do is take the 2 populations. One where 100 events have happened. One where 150 events have happened. So you believe that the treatment is to blame in 50 of them. You then study all 250 "samples", and look for something which is different in about 50 of the affected individuals (because about 50 of them are caused by the treatment). When you find something that is different THEN you can see if it is a potential mechanism. I just can't see HOW you would find something that was different if there isn't a difference in numbers.

In many cases animal studies and knowledge of the drug will explain some AEs. They actively look for some AEs in clinical trials because they know what has happened in animal studies; or because of knowledge of the biology. These AEs will have a mechanism which is more likely to be understood. But TBH if it falls outside of these then the mechanism is a total mystery (even if it is identified as a link through numbers). It really is like looking for aneedle in a haystack.

I know it is a circular argument. But if we come back to the eggs. If you are going to investigate why 2 eggs broken in the rain how would you determine whether they broke for the same reason as they do every day or if they broke because of the rain?

I am trying to explain why it is almost impossible to looking for AEs when the numbers don't add up.

I am not trying to say you are wrong pe se. I just don't see how you could do the sort of studies you suggest where there is no evidence that there is a problem.

Besides.

If you have 100 events in the untreated group and 100 (or even 101/102) the adverse event must be v v v rare and whilst still important to those that suffer as a result it is less important to the population as a whole.

Well for example, if the eggs were babies, then (not being a scientist) I assume that one would look for brain inflammation, take blood samples, examine the possibility of retinal bleeding. I'm afraid your honest belief that deaths in vaccine trials are always investigated is utterly misplaced. But then maybe science has its tenets of faith too.

Your method of operation and belief seems to amount to little more than assumption. Mainly the assumption of coincidence.

Perhaps when initialising a test for a drug or vaccine in children and babies, the trial team should inform the parents that should their baby die during the trial period, they have no way of determining whether the death was due to the vaccine or drug being trialled, and can't even get their heads around the idea of how to find out. I think that would help parents decide whether or not to be involved.

Research investment is, sadly, hard to come by in the pharmaceutical industry and you're right, it is surprising that this is the case when they devote more than eighty per cent of their spending to marketing and profits.

Background deaths are an average. If it is accepted that 13 babies die every month in a particular area in Mexico, then obviously some months there maybe ten, some months maybe sixteen.

So there is absolutely no way you can assume that if 13 deaths occur, that they were not caused by the vaccine.

If the eggs were babies - you would need to look at ALL major organs. It would need to be FAR more extensive than brain, bloods and retina I'm afraid.

I am making assumptions, I am also (I hope) be clear where I am making assumptions because it is outside my field of direct understaning (i.e. that deaths on a clincal trial would be investigated more thoroughly than an unrealted death).

"So there is absolutely no way you can assume that if 13 deaths occur, that they were not caused by the vaccine."

That statement is incorrect. We do assume that they they are unlikely to be related to the vaccine. But we do not know that they weren't caused by the vaccine.

When it comes to clinical trial info up front. The information given up front is pretty thorough (DP is a volunteer). They outline AEs that they predict may happen in detail. They also go into some detail about life insurance policy validity and stuff, and implies that anything has the potential to happen and outlines what will and has been done to prevent it. However, I don't know the specifics about peadiactric paperwork - and you are almost certainly right it won't contain that sort of info.

They were just the first things off the top of my head. It's just that you, as a scientist, did ask me, a laywoman, and I thought they were good places to start.

So, they can do these investigations, and of course they should, but they don't.

And yes, I'm sorry, of course scientists can and do assume whatever they want. I was using "can't" in a rather rhetorical way! as in "how can you possibly assume this" as opposed to "it is impossible to know this to be true".

There is a big difference in making a scietific assumption and a personal assumption though IYSWIM.

The point I was trying to make with the babies is that it isn't as simple as just 1 or 2 organs which have to be investigated. And even if you could say that it was caused by a brain haemorrage (which a PM should do)you then have to work out why there was a brain haemorrage. You just end up answering a question with a question. And then another question.....

And I think that one of my last points is one of the most important.

We assume that there is unlikely to be a link because of the numbers. And that if there is a link - because the numbers are so close to each other it must be v rare event. And if it is a rare event it is less important that a common event.

And I stress the words LESS IMPORTANT (as opposed to NOT important).

Sorry Prefect -- it's just so difficult so let's not bother? Eh?

sorry rl beckons
talk to you later

Prefect.. I think we're well on the way to establishing that when conducting a vaccine trial the scientists involved are unable to tell whether an adverse reaction or death is due to the vaccine.

This is not what I expected you to be saying.

I don't think your last point is the most important at all, I think it's almost irrelevant actually. Because potential adverse reactions are not investigated thoroughly, due to assumptions of coincidence or background, you can't know if it's rare. You don't know what the incidence is.

No I am saying that if the numbers suggest that an event happens 10 times in 1000 without the vaccine AND 10 times in 1000 with the vaccine - statistics (that is statistics NOT science) draws the conclusion that the events have a 99.99+% chance of having happened randomly. In that case if there is less than a 1% chance of the events being as a result of chance. If there is less than a 1% chance of the events being a result of the vaccine then any amount of scientific (and therefore funding) is highly unlikely to demonstrate a cause and effect.

If an event happens - say 12 times. Then there would probably be a 95% chance of the events having occured by chance. If it is a very serious AE and there is a 5% chance of it being caused by the vaccine then it may be investigated (don't know the actual cut - off - and probably is case by case anyway).

If an event happens - say 15 times. Then there would probably be a 60% chance that they occured by chance and 40% chance that it is vaccine related and it would be investigated further. And with such a population to investigate links may be uncovered - so I am not saying links will never be found - just that they are more liekly to be ound with a bigger sample (i.e. the difference between background and treated is bigger).

There are statistical tests that are used to determine what the probability is that things are random (or not). The outcome of the statistical test is what will determine if further work is valuable.

So at the end of the day it is actualy statistics that will drive further investogations. And incidently it is the same mechanism used to decide if a drug is effective.

Anyway - I agree that we are going very much off topic now. It has been an interesting debate, I am not sure that I articulating well.

FGS you two - get a room

...and make sure stuffit does the risk assessment.

In that case we are all DOOMED....there will never be any new medicines ever again

cripes

there go a few pension funds

ok

that's THAT!

trebles all round

with thanks for an interesting conversation and once more prefect you did a lot of research there and I think people might look this thread up when the vaccine comes out and squalene is talked about again

DONT LET THEM VACCINATE YOU OR YOUR FAMILY!
It's imposible for the vaccines to be properly tested in such a short time. No one has any idea what their long-term effects are. E.g. Last year at least 21 people died in Grudziadz, Poland when Novartis tried N5H1 vaccines on them. The preservatives in some of the vaccines contain mercury which causes autism in children. And the virus will mutate anyway, so why bother? Moreover, there is evidence of a crime commited by Baxter - supplier of the vaccine to the UK and its role in spreading the disease around the world. Visit www.theflucase.com and www.birdflu666.wordpress.com to find out more.