Minimal scientific benefit from a single case study.
For it to be meaningful it needs to be a randomised controlled trial, preferably double-blinded.
How does it work for the very rarest illnesses or procedures?
I have a vague awareness that some experimental heart surgeries have to deal with very small sample sizes (in fact I guess they all do, when you first start doing them), with careful statistical rules for discontinuing the procedure if the results to date indicate it's problematic, and obviously there are problems double-blinding heart surgery. But the rarer the condition, the lower the power even the largest studies could attain, and even moderate effect sizes would struggle for statistical significance.
(The hypothetical scenario I was suggesting involved basic research, rather than a clinical trial to seek approval for a purported treatment. Does that make a difference? If all you want to find out to understand the illness a bit more is "Does doing X result in Y for patients with condition Z?" and Z is so rare that we seldom get the opportunity to try X out - in fact by the time we do, we've possibly moved on from wanting to try out X1 to wanting to see the effects of X2 or X3 instead - at what stage do the ethics regulators say "you can't justify your interventions since your research programme simply won't be able to produce a useful evidence base - you will always lack data points, and you can't demonstrate that the X you are trying is likely to have a clinical benefit"?)
There are statistical rules on everything but the regulators are pretty creative where it comes to orphan and ultra orphan diseases (I'm on the board of an orphan company)
From an ethics perspective in ultra orphan, a theoretical rationale for why it might work is a good starting point ("I hope it might cross the blood brain barrier" is not sufficient)
Thanks. And presumably they'd like to see results in an animal model or something first. Does there have to be any realistic hope that the research might actually alleviate the condition in the case of the person undertaking the trial or is it sufficient that the research is investigating a mechanism that is a plausible basis for future, hopefully more useful, interventions?
Needs to benefit the patient. Otherwise they are just a vehicle for experimentation which doesn't work from an ethics perspective.
Essentially all research in humans is a balance of risk, side effects, and potential we may learn something about how to treat the disease.
Animal trials (not least tox studies) are always required before human clinical trials.
' Taxpayers have been left with a £13bn bill for contracts signed by Yorkshire councils to construct and maintain new schools, homes and waste facilities paid for under the controversial Public Finance Initiative, The Yorkshire Post can reveal.
Town hall bosses across the region have entered into a raft of ‘buy now, pay later’ agreements since the turn of the century using PFI, where private firms fund the upfront costs of new buildings and are paid back over the next 25 years or more.
The majority of Yorkshire’s local authorities will be paying back millions of pounds a year in ‘unitary charges’ well into the 2030s, by which time the total spend will dwarf the original construction costs. '
@isam said "Mistaking class prejudice for racism is a mistake that plenty of do gooders have made"
I agree, but the two (and other predjudices on gender, sexuality, religion etc) do intermingle and muddy the situation.
The undererperormance of WWC children educationally relative to most other groups, does feed resentment that often is interpreted as racism for example.
@isam said "Mistaking class prejudice for racism is a mistake that plenty of do gooders have made"
I agree, but the two (and other predjudices on gender, sexuality, religion etc) do intermingle and muddy the situation.
The undererperormance of WWC children educationally relative to most other groups, does feed resentment that often is interpreted as racism for example.
This latest N Korean test is sounding like a very big deal. If the details so far are right that can easily hit all of the US west coast, and it won't need much extra to have Washington & NY in range.
Well we're well within range if that is the case.
I doubt Jong-Un cares about that little backwater off the coast of Europe.
It's dead in the water anyway isn't it? After the Taoiseach told them what to do yesterday? (Though why its the UK with the problem and not the RoI is very far from clear.....I suspect it will be the EU insisting on customs checks...)
The utter destruction of Brussels would make an excellent demonstration of the new weapon system.... said no dictator ever.
As for Ireland, their ire should be directed towards the EU, surely? The UK and Ireland both want the same thing.
The UK and Ireland both want the same thing, and both currently have it. It is the UK that is upsetting the apple cart.
@isam said "Mistaking class prejudice for racism is a mistake that plenty of do gooders have made"
I agree, but the two (and other predjudices on gender, sexuality, religion etc) do intermingle and muddy the situation.
The undererperormance of WWC children educationally relative to most other groups, does feed resentment that often is interpreted as racism for example.
Undoubtedly a tricky area.
Certainly, and a difficult topic to discuss online in particular, as online comments are particularly prone to misinterpretation and misrepresentation.
As I said before, accusations of racism should be tha starting point of discussion rather than a closing down of it. The accusation is a deeply felt one, by both accusser and accused, both of whom are prone to reteat to their fortresses and lob online grenades at each other!
When I worked in NZ there was a policy of biculturism (White and Polynesian*) and there was a great euphemism for racist predjudice: "cultural insensitivity". It dialed down the emotiveness of the accusation and allowed easier discussion than frank accusations of racism.
* Edit: Aotearua, Pakeha and Maori, Pacific Islander respectively! pardon my cultural insensitivity.
@isam said "Mistaking class prejudice for racism is a mistake that plenty of do gooders have made"
I agree, but the two (and other predjudices on gender, sexuality, religion etc) do intermingle and muddy the situation.
The undererperormance of WWC children educationally relative to most other groups, does feed resentment that often is interpreted as racism for example.
Undoubtedly a tricky area.
Certainly, and a difficult topic to discuss online in particular, as online comments are particularly prone to misinterpretation and misrepresentation.
As I said before, accusations of racism should be tha starting point of discussion rather than a closing down of it. The accusation is a deeply felt one, by both accusser and accused, both of whom are prone to reteat to their fortresses and lob online grenades at each other!
When I worked in NZ there was a policy of biculturism (White and Polynesian) and there was a great euphemism for racist predjudice: "cultural insensitivity". It dialed down the emotiveness of the accusation and allowed easier discussion than frank accusations of racism.
couldnt you just apologise to the rest of us for being english and leave it at that ?
The biggest problem this country has is the historical underfunding of pensions - all good reasons, and to be fair people couldn't necessarily have predicted the compression in returns and the rise in life expectancy at the time the schemes were set up.
However, once entrenched the incumbents fought tooth and nail to protect their vested interests - again, perhaps, understandable but it completed screwed the younger generation in the process. There should have been a much more comprehensive deal which cut back benefits into line with what was affordable, increased contributions as well as requiring some funding from the centre.
And they should have converted from guaranteed pension schemes to defined contribution.
@isam said "Mistaking class prejudice for racism is a mistake that plenty of do gooders have made"
I agree, but the two (and other predjudices on gender, sexuality, religion etc) do intermingle and muddy the situation.
The undererperormance of WWC children educationally relative to most other groups, does feed resentment that often is interpreted as racism for example.
Undoubtedly a tricky area.
Certainly, and a difficult topic to discuss online in particular, as online comments are particularly prone to misinterpretation and misrepresentation.
As I said before, accusations of racism should be tha starting point of discussion rather than a closing down of it. The accusation is a deeply felt one, by both accusser and accused, both of whom are prone to reteat to their fortresses and lob online grenades at each other!
When I worked in NZ there was a policy of biculturism (White and Polynesian) and there was a great euphemism for racist predjudice: "cultural insensitivity". It dialed down the emotiveness of the accusation and allowed easier discussion than frank accusations of racism.
couldnt you just apologise to the rest of us for being english and leave it at that ?
I could, but that might be a bit culturally insensitive to my Scottish, Welsh, and Ulster Protestant ancestors...
@isam said "Mistaking class prejudice for racism is a mistake that plenty of do gooders have made"
I agree, but the two (and other predjudices on gender, sexuality, religion etc) do intermingle and muddy the situation.
The undererperormance of WWC children educationally relative to most other groups, does feed resentment that often is interpreted as racism for example.
Undoubtedly a tricky area.
Certainly, and a difficult topic to discuss online in particular, as online comments are particularly prone to misinterpretation and misrepresentation.
As I said before, accusations of racism should be tha starting point of discussion rather than a closing down of it. The accusation is a deeply felt one, by both accusser and accused, both of whom are prone to reteat to their fortresses and lob online grenades at each other!
When I worked in NZ there was a policy of biculturism (White and Polynesian) and there was a great euphemism for racist predjudice: "cultural insensitivity". It dialed down the emotiveness of the accusation and allowed easier discussion than frank accusations of racism.
couldnt you just apologise to the rest of us for being english and leave it at that ?
I could, but that might be a bit culturally insensitive to my Scottish, Welsh, and Ulster Protestant ancestors...
The biggest problem this country has is the historical underfunding of pensions - all good reasons, and to be fair people couldn't necessarily have predicted the compression in returns and the rise in life expectancy at the time the schemes were set up.
However, once entrenched the incumbents fought tooth and nail to protect their vested interests - again, perhaps, understandable but it completed screwed the younger generation in the process. There should have been a much more comprehensive deal which cut back benefits into line with what was affordable, increased contributions as well as requiring some funding from the centre.
And they should have converted from guaranteed pension schemes to defined contribution.
Part of the problem is QE and low returns from gilts.
The biggest problem this country has is the historical underfunding of pensions - all good reasons, and to be fair people couldn't necessarily have predicted the compression in returns and the rise in life expectancy at the time the schemes were set up.
However, once entrenched the incumbents fought tooth and nail to protect their vested interests - again, perhaps, understandable but it completed screwed the younger generation in the process. There should have been a much more comprehensive deal which cut back benefits into line with what was affordable, increased contributions as well as requiring some funding from the centre.
And they should have converted from guaranteed pension schemes to defined contribution.
Part of the problem is QE and low returns from gilts.
It is time the BoE moved on interest rates.
Only for private pensions and deficit funding. I think the pensions regulator should have used a more normal discount rate to determine the deficits that needed to be filled, but they only had a narrow mandate and no politician was willing to get involved.
The biggest problem this country has is the historical underfunding of pensions - all good reasons, and to be fair people couldn't necessarily have predicted the compression in returns and the rise in life expectancy at the time the schemes were set up.
However, once entrenched the incumbents fought tooth and nail to protect their vested interests - again, perhaps, understandable but it completed screwed the younger generation in the process. There should have been a much more comprehensive deal which cut back benefits into line with what was affordable, increased contributions as well as requiring some funding from the centre.
And they should have converted from guaranteed pension schemes to defined contribution.
Part of the problem is QE and low returns from gilts.
It is time the BoE moved on interest rates.
Dumb question on QE (which I have never really been able to get my head around): Is the £445bn the BoE has created effectively just temporary money, i.e. that will be 'erased' when/if the bonds bought by QE are every re-sold? If not, why not just use it to pay off a chunk of the deficit? Or better still, fund growth through tax cuts and higher spending?
The biggest problem this country has is the historical underfunding of pensions - all good reasons, and to be fair people couldn't necessarily have predicted the compression in returns and the rise in life expectancy at the time the schemes were set up.
However, once entrenched the incumbents fought tooth and nail to protect their vested interests - again, perhaps, understandable but it completed screwed the younger generation in the process. There should have been a much more comprehensive deal which cut back benefits into line with what was affordable, increased contributions as well as requiring some funding from the centre.
And they should have converted from guaranteed pension schemes to defined contribution.
Part of the problem is QE and low returns from gilts.
It is time the BoE moved on interest rates.
Dumb question on QE (which I have never really been able to get my head around): Is the £445bn the BoE has created effectively just temporary money, i.e. that will be 'erased' when/if the bonds bought by QE are every re-sold? If not, why not just use it to pay off a chunk of the deficit? Or better still, fund growth through tax cuts and higher spending?
(I said it was a dumb question!)
Yes it is electronic money that will be destroyed once the bonds are returned to the market.
In the year to March 31, USS’s assets rose by 21 per cent to £60bn, but its liabilities increased by 33 per cent to £77.5bn.
Perhaps we are living too long; or taking retirement too early; or young 'uns are opting out?
USS’s eight-member executive committee was paid £3.9m in 2016-17, including bonuses and long-term incentive awards: which equates to an average of £488,000 per person.
In 2016-17, 52 USS employees earned more than £200,000 in salary, up from 51 the year before ..
F1: I was all set to just stick with my No Safety Car bet. But some odds look wrong, so...
Backed Vandoorne to win group C at Ladbrokes (10). It includes Sainz, Kvyat and Grosjean. Kvyat's demoted three places so he and Grosjean start a long way back. Sainz is right behind Vandoorne, both men have 40% DNF rates. I think it's (if they all finish) a two hose race, so 10 is just too long.
Also backed Bottas at 11 each way to win. Strange that he has the longest odds of the top four to win.
Anyway, more rambling and thoughts in the article:
The biggest problem this country has is the historical underfunding of pensions - all good reasons, and to be fair people couldn't necessarily have predicted the compression in returns and the rise in life expectancy at the time the schemes were set up.
However, once entrenched the incumbents fought tooth and nail to protect their vested interests - again, perhaps, understandable but it completed screwed the younger generation in the process. There should have been a much more comprehensive deal which cut back benefits into line with what was affordable, increased contributions as well as requiring some funding from the centre.
And they should have converted from guaranteed pension schemes to defined contribution.
Part of the problem is QE and low returns from gilts.
It is time the BoE moved on interest rates.
Dumb question on QE (which I have never really been able to get my head around): Is the £445bn the BoE has created effectively just temporary money, i.e. that will be 'erased' when/if the bonds bought by QE are every re-sold? If not, why not just use it to pay off a chunk of the deficit? Or better still, fund growth through tax cuts and higher spending?
(I said it was a dumb question!)
Yes it is electronic money that will be destroyed once the bonds are returned to the market.
Except the bonds will never be returned to the market. They will be rolled over in perpetuity.
To link back to university pension scheme woes, one of the side effects of QE is that you have a buyer with effectively (well in theory literally!) limitless money, buying bonds like there's no tomorrow. A huge percentage of all govt bonds are now effectively on the BoE's balance sheet. Now gilt yields move inversely to the price of gilts and if you have a buyer with limitless money in any market, guess what, the price goes up, meaning automatically the yield drops. Why does this matter? Well pension schemes have to value their liabilities by discounting back using high quality corporate bond yields or gilt yields (i.e. Govt bonds). Yields over the past couple of years have been at record lows. The records go back to 1703. Yes, queen Anne's reign.
Therefore QE is a big part of why pension schemes are so royally stuffed at the moment, not that Carney seems to care from what I can see as he pursues biblically low rates.
One grimly bright area possibly, is that life expectancy has stopped increasing at the rate it was and is advancing more slowly. A bit more death might save the survivors' bacon.
Dumb question on QE (which I have never really been able to get my head around): Is the £445bn the BoE has created effectively just temporary money, i.e. that will be 'erased' when/if the bonds bought by QE are every re-sold? If not, why not just use it to pay off a chunk of the deficit? Or better still, fund growth through tax cuts and higher spending?
(I said it was a dumb question!)
It's not a dumb question.
At the moment the Bank has "printed money" through QE which it has used to buy bonds from the government. The Treasury does not pay the interest on these bonds (this changed a couple of year ago).
The intention is that when the circumstances permit, the government will raise funds in the normal markets, repay the bonds and the Bank will cancel the "QE money", thus sterilising the intervention.
If the bonds were written off, or sold by the Bank, then effectively you are making the increase in the money supply permanent and non reversible. If you are a monetarist (as most economists are these days) then an increase in the money supply will lead to inflation and a breakdown of price signals in the market which is bad for the economy as a whole. Over the last 10 years this has shown up in the UK as asset price inflation (houses and equities) which may be less noticeable to the man in the street, but is potentially even more harmful than wage inflation in the long run.
Dumb question on QE (which I have never really been able to get my head around): Is the £445bn the BoE has created effectively just temporary money, i.e. that will be 'erased' when/if the bonds bought by QE are every re-sold? If not, why not just use it to pay off a chunk of the deficit? Or better still, fund growth through tax cuts and higher spending?
(I said it was a dumb question!)
It's not a dumb question.
At the moment the Bank has "printed money" through QE which it has used to buy bonds from the government. The Treasury does not pay the interest on these bonds (this changed a couple of year ago).
The intention is that when the circumstances permit, the government will raise funds in the normal markets, repay the bonds and the Bank will cancel the "QE money", thus sterilising the intervention.
If the bonds were written off, or sold by the Bank, then effectively you are making the increase in the money supply permanent and non reversible. If you are a monetarist (as most economists are these days) then an increase in the money supply will lead to inflation and a breakdown of price signals in the market which is bad for the economy as a whole. Over the last 10 years this has shown up in the UK as asset price inflation (houses and equities) which may be less noticeable to the man in the street, but is potentially even more harmful than wage inflation in the long run.
What I can't understand is why, given that conditions are so historically unusual, pension providers can't be allowed to use a higher discount rate. If they use current rates then most of them are going to look as if they are bust, even though much of the money they have to pay out isn't due for decades, over which period interest rates will recover. All that the current approach does is give the impression that pensions are massively underfunded now, forcing companies to make big contributions and hence reducing money for investment, and then when interest rates / gilt yields rise, suddenly all the pension funds will be in surplus and start taking payment holidays. I'm sure half the problem at BHS was this - being forced to crystallise liabilities at the worst point.
But then I'm only an engineer so I probably have it all wrong!
Dumb question on QE (which I have never really been able to get my head around): Is the £445bn the BoE has created effectively just temporary money, i.e. that will be 'erased' when/if the bonds bought by QE are every re-sold? If not, why not just use it to pay off a chunk of the deficit? Or better still, fund growth through tax cuts and higher spending?
(I said it was a dumb question!)
It's not a dumb question.
At the moment the Bank has "printed money" through QE which it has used to buy bonds from the government. The Treasury does not pay the interest on these bonds (this changed a couple of year ago).
The intention is that when the circumstances permit, the government will raise funds in the normal markets, repay the bonds and the Bank will cancel the "QE money", thus sterilising the intervention.
If the bonds were written off, or sold by the Bank, then effectively you are making the increase in the money supply permanent and non reversible. If you are a monetarist (as most economists are these days) then an increase in the money supply will lead to inflation and a breakdown of price signals in the market which is bad for the economy as a whole. Over the last 10 years this has shown up in the UK as asset price inflation (houses and equities) which may be less noticeable to the man in the street, but is potentially even more harmful than wage inflation in the long run.
What I can't understand is why, given that conditions are so historically unusual, pension providers can't be allowed to use a higher discount rate. If they use current rates then most of them are going to look as if they are bust, even though much of the money they have to pay out isn't due for decades, over which period interest rates will recover. All that the current approach does is give the impression that pensions are massively underfunded now, forcing companies to make big contributions and hence reducing money for investment, and then when interest rates / gilt yields rise, suddenly all the pension funds will be in surplus and start taking payment holidays. I'm sure half the problem at BHS was this - being forced to crystallise liabilities at the worst point.
But then I'm only an engineer so I probably have it all wrong!
They can be allowed to use a higher rate, but it requires politicians to get involved. (Politicians allow greedy companies to cut pension contributions! Fight for your pensions!)
The issue is that the pension trustees have a fiducary responsibility to the pensioners, the regulators have an obligation to force companies to fill the deficits, the companies have little room for manoeuvre, the unions will fight for the maximum benefit for their members regardless of systemic damage and the politicians don;t want to touch the issue
Comments
My immediate reaction on reading this was "what 2014 Uxbridge by-election!!!!!!!!!!!"
Now looked it up and no - there was no by-election. So at least my memory is still intact!
Essentially all research in humans is a balance of risk, side effects, and potential we may learn something about how to treat the disease.
Animal trials (not least tox studies) are always required before human clinical trials.
' Universities face a new blow to their finances after the main pension fund deficit soared to £17.5bn.
The Universities Superannuation Scheme now has the largest pensions deficit of any UK pension fund after it increased by £9bn last year.
One expert said student fees may have to rise or be diverted from teaching. '
http://www.bbc.co.uk/news/uk-40763577
' Taxpayers have been left with a £13bn bill for contracts signed by Yorkshire councils to construct and maintain new schools, homes and waste facilities paid for under the controversial Public Finance Initiative, The Yorkshire Post can reveal.
Town hall bosses across the region have entered into a raft of ‘buy now, pay later’ agreements since the turn of the century using PFI, where private firms fund the upfront costs of new buildings and are paid back over the next 25 years or more.
The majority of Yorkshire’s local authorities will be paying back millions of pounds a year in ‘unitary charges’ well into the 2030s, by which time the total spend will dwarf the original construction costs. '
http://www.yorkshirepost.co.uk/news/13bn-bill-for-yorkshire-councils-buy-now-pay-later-pfi-schemes-1-8675923
I agree, but the two (and other predjudices on gender, sexuality, religion etc) do intermingle and muddy the situation.
The undererperormance of WWC children educationally relative to most other groups, does feed resentment that often is interpreted as racism for example.
As I said before, accusations of racism should be tha starting point of discussion rather than a closing down of it. The accusation is a deeply felt one, by both accusser and accused, both of whom are prone to reteat to their fortresses and lob online grenades at each other!
When I worked in NZ there was a policy of biculturism (White and Polynesian*) and there was a great euphemism for racist predjudice: "cultural insensitivity". It dialed down the emotiveness of the accusation and allowed easier discussion than frank accusations of racism.
* Edit: Aotearua, Pakeha and Maori, Pacific Islander respectively! pardon my cultural insensitivity.
However, once entrenched the incumbents fought tooth and nail to protect their vested interests - again, perhaps, understandable but it completed screwed the younger generation in the process. There should have been a much more comprehensive deal which cut back benefits into line with what was affordable, increased contributions as well as requiring some funding from the centre.
And they should have converted from guaranteed pension schemes to defined contribution.
youve got a potato famine for starters :-)
It is time the BoE moved on interest rates.
I'm also thinking of state pensions.
For those PBers wishing to once again lock horns in the world of fantasy football, I've set up the League again.
All welcome!
The league link is 662822-332043
I am a deferred member of USS and won't be collecting for another ten years or so.
Very worrying and with Jezza and student fees 'reform' looming the universities will be even shorter of cash.
This paper is interesting on whether these valuations actually make good sense:
http://blogs.warwick.ac.uk/files/dennisleech/pensions_regulation.pdf
I didn't follow all the detail but think I understand his basic point on market-based valuations.
(I said it was a dumb question!)
Betting PostF1: I was all set to just stick with my No Safety Car bet. But some odds look wrong, so...
Backed Vandoorne to win group C at Ladbrokes (10). It includes Sainz, Kvyat and Grosjean. Kvyat's demoted three places so he and Grosjean start a long way back. Sainz is right behind Vandoorne, both men have 40% DNF rates. I think it's (if they all finish) a two hose race, so 10 is just too long.
Also backed Bottas at 11 each way to win. Strange that he has the longest odds of the top four to win.
Anyway, more rambling and thoughts in the article:
http://enormo-haddock.blogspot.co.uk/2017/07/hungary-pre-race-2017.html
@Benpointer
To link back to university pension scheme woes, one of the side effects of QE is that you have a buyer with effectively (well in theory literally!) limitless money, buying bonds like there's no tomorrow. A huge percentage of all govt bonds are now effectively on the BoE's balance sheet. Now gilt yields move inversely to the price of gilts and if you have a buyer with limitless money in any market, guess what, the price goes up, meaning automatically the yield drops. Why does this matter? Well pension schemes have to value their liabilities by discounting back using high quality corporate bond yields or gilt yields (i.e. Govt bonds). Yields over the past couple of years have been at record lows. The records go back to 1703. Yes, queen Anne's reign.
Therefore QE is a big part of why pension schemes are so royally stuffed at the moment, not that Carney seems to care from what I can see as he pursues biblically low rates.
One grimly bright area possibly, is that life expectancy has stopped increasing at the rate it was and is advancing more slowly. A bit more death might save the survivors' bacon.
At the moment the Bank has "printed money" through QE which it has used to buy bonds from the government. The Treasury does not pay the interest on these bonds (this changed a couple of year ago).
The intention is that when the circumstances permit, the government will raise funds in the normal markets, repay the bonds and the Bank will cancel the "QE money", thus sterilising the intervention.
If the bonds were written off, or sold by the Bank, then effectively you are making the increase in the money supply permanent and non reversible. If you are a monetarist (as most economists are these days) then an increase in the money supply will lead to inflation and a breakdown of price signals in the market which is bad for the economy as a whole. Over the last 10 years this has shown up in the UK as asset price inflation (houses and equities) which may be less noticeable to the man in the street, but is potentially even more harmful than wage inflation in the long run.
But then I'm only an engineer so I probably have it all wrong!
The issue is that the pension trustees have a fiducary responsibility to the pensioners, the regulators have an obligation to force companies to fill the deficits, the companies have little room for manoeuvre, the unions will fight for the maximum benefit for their members regardless of systemic damage and the politicians don;t want to touch the issue