The bicycle is the technology that I find most useful, enables me to have the whole of London as my neighbourhood, and gives me the greatest pleasure. A day when I don't make at least a small journey on it is the lesser for it. So I am a cycling partisan. I rarely ride on pavements, slow down and stop for pedestrians and stop for red lights. I am a self-confessed middle aged man in lycra (MAMIL) and cycle everywhere I can.
I know if I stop cycling for a while, over a few weeks I pile on the body weight. Cycling allows me to drink beer, eat well and keep my waist measurement below 34. Cycling is my main form of physical activity because I am not disciplined enough to attend a gym regularly, and while I do run sometimes, I don't really like its purposelessness.
Good to see then, in The Lancet that there is evidence that policies that encourage cycling (and walking and use of public transport) increase physical activity (in related research in the journal a substantial minority of ill health - obesity tye 2 diabetes and heart disease of course, but also some cancer - is attributed to a lack of activity).
Twenty mile an hour zones in residential areas, roads designed to limit car speed, intelligent cycle paths that understand how cyclists travel, and incentives to reduce city car use are not only moves that will encourage more people to cast off their Oyster cards, but will prevent some of that chronic disease that causes disability, dependence and eventually death. And you'll lose (or at least not gain) weight. The bicycle is a miracle weight loss technology, and you get the wind in your hair (if you have any: I don't), and the warmth of the sun on your skin, and its light in your eyes, and the vitamin D levels rise, and you see things you don't in a car or a tube, and your manor extends for miles, and...
I could go on, but it might just begin to sound just a bit rabid.
Wednesday, 18 July 2012
Wednesday, 26 January 2011
The honourable role of the muck-raker
Brian Deer's excoriating exposes of the shenanigans behind the dodgy Lancet paper by Andrew Wakefield )and others has been reprised and expanded here and elsewhere in the BMJ.
The first two lengthy pieces in the three-part series the BMJ published attracted huge attention in the press, and numerous comments from readers. The third virtually no attention and just one comment.
The responses to Deer have been critical of Andrew Wakefield, who has been (rightly) struck off by the General Medical Council, and who no longer has any scientific credibility, whatever the support he attracts from desparate parents of autistic children and others. Others, like Ben Goldacre have been hugely critical of what they see as the excesses of the media in their original reporting of the Lancet study, and in their consequent coverage of the issue.
No one has taken up the points made by Deer in his third article about the behaviour of the Lancet's editor Richard Horton who does not emerge well out of Deer's reports. As well as the misjudgment of publishing the paper, adding the cachet of the journal to a highly speculative small case series, Deer reports that the Lancet was involved in a cursory investigation into the quality of the paper, when Deer raised serious issues about the trial's conduct, which the Lancet then used to defend its decision to publish.
One of the strengths of Horton's editorship has been a continuation of the Lancet's history of mischief making in the public interest; stirring things up, for example, by publishing controversial studies about the number killed after the 2003 invasion of Iraq. (paywall).
With the MMR story Horton's nose for a controversial story was on target, but his judgment was not. It has taken the multi-million pound costs of a GMC enquiry for the truth about Wakefield to come out.
Deer does emerge from his own account as someone with a healthy ego, not slow at putting himself at the centre of the story. But his kind of muck-raking hack who gets hold of the documents and tracks down often reluctant interviewees is unlikely to be a shrinking violet, nor a clubbable member of the medical elite. The time and effort Deer has put into exposing the MMR paper scandal justifies his high opinion of himself, even if it does lead him to see medical professional collusion, even among fierce critics of Wakefield, where it did not exist.
What has so far been missing is an adequate explanation from Horton about his apparent role in allowing himself to become a party to a flimsy investigation, and undermining Deer's painstaking investigation.
Asking awkward questions, keeping on asking them long after everyone else has become bored of them, and following all trails of of inquiry should have been part of an inquiry carried out by medical academics as soon as serious concerns were raised about the Lancet paper. Instead it was left to a muck raking hack (and that's a compliment). Medical snobbery about Deer's work did delay the truth emerging. That is the tragedy.
The first two lengthy pieces in the three-part series the BMJ published attracted huge attention in the press, and numerous comments from readers. The third virtually no attention and just one comment.
The responses to Deer have been critical of Andrew Wakefield, who has been (rightly) struck off by the General Medical Council, and who no longer has any scientific credibility, whatever the support he attracts from desparate parents of autistic children and others. Others, like Ben Goldacre have been hugely critical of what they see as the excesses of the media in their original reporting of the Lancet study, and in their consequent coverage of the issue.
No one has taken up the points made by Deer in his third article about the behaviour of the Lancet's editor Richard Horton who does not emerge well out of Deer's reports. As well as the misjudgment of publishing the paper, adding the cachet of the journal to a highly speculative small case series, Deer reports that the Lancet was involved in a cursory investigation into the quality of the paper, when Deer raised serious issues about the trial's conduct, which the Lancet then used to defend its decision to publish.
One of the strengths of Horton's editorship has been a continuation of the Lancet's history of mischief making in the public interest; stirring things up, for example, by publishing controversial studies about the number killed after the 2003 invasion of Iraq. (paywall).
With the MMR story Horton's nose for a controversial story was on target, but his judgment was not. It has taken the multi-million pound costs of a GMC enquiry for the truth about Wakefield to come out.
Deer does emerge from his own account as someone with a healthy ego, not slow at putting himself at the centre of the story. But his kind of muck-raking hack who gets hold of the documents and tracks down often reluctant interviewees is unlikely to be a shrinking violet, nor a clubbable member of the medical elite. The time and effort Deer has put into exposing the MMR paper scandal justifies his high opinion of himself, even if it does lead him to see medical professional collusion, even among fierce critics of Wakefield, where it did not exist.
What has so far been missing is an adequate explanation from Horton about his apparent role in allowing himself to become a party to a flimsy investigation, and undermining Deer's painstaking investigation.
Asking awkward questions, keeping on asking them long after everyone else has become bored of them, and following all trails of of inquiry should have been part of an inquiry carried out by medical academics as soon as serious concerns were raised about the Lancet paper. Instead it was left to a muck raking hack (and that's a compliment). Medical snobbery about Deer's work did delay the truth emerging. That is the tragedy.
Wednesday, 21 July 2010
Changing what you can measure: endpoints and stuff
The Avandia (rosiglitazone)story covered at theheart.org and elsewhere, has been portrayed as a big bad pharma versus heroic meta-analysis contest. While GSK has not covered themselves in glory, the FDA conclusion that there is a defensible case for Avandia remaining on the market - but with higher profile warnings and caveats - seems reasonable.
One major casualty is likely to be the reliance in clinical trials of easy to measure surrogate outcomes, in Avandia's case blood glucose. The glitazones are good at controlling blood glucose levels, and that is in part how they captured such a large part of the diabetes market. But it turned out that their effect on clinical outcomes heart attacks and strokes was more equivocal, and in the case of heart failure had an adverse effect.
The use of surrogate endpoints has, in the past, come up trumps. Treatments to reduce high blood pressure and high blood cholesterol, were licensed, marketed and widely used before there was evidence that they had effects on hard clinical outcomes. Lowering blood LDL as a rationale for using statins was controversial in its day. But large scale clinical trials such as the Heart Protection Study later found important clinical benefits too.
It is at least questionable whether the statins would now have been licensed without showing a reduction in hard endpoints such as heart attacks and strokes. That would have witheld their benefits from thousands of people. So a more cautious approach to the evidence on which drugs are approved for use has drawbacks.
There was criticism of the speed at which glitazones began to be prescribed, particularly in north America, without evidence of benefits in clinical outcomes rather than biochemical outcomes. The speed of uptake of statins was much slower, and really only picked up after the first large scale clinical trials showed benefits, initially in higher risk patients and then more widely.
This is perhaps one lesson. We can choose to accept evidence from surrogate outcome studies in licensing drugs if we accept that it is not then appropriate for treatments to be heavily marketed before they have proved themselves in terms of harder clinical endpoints. Or we can decide not to accept surrogate outcomes, and delay the introduction of treatments possibly by many years (and may prevent the development of some treatments altogether).
It's not an easy choice to make. Either way there are risks - from unexpected adverse events, or from the unavailability of possible treatments.
One major casualty is likely to be the reliance in clinical trials of easy to measure surrogate outcomes, in Avandia's case blood glucose. The glitazones are good at controlling blood glucose levels, and that is in part how they captured such a large part of the diabetes market. But it turned out that their effect on clinical outcomes heart attacks and strokes was more equivocal, and in the case of heart failure had an adverse effect.
The use of surrogate endpoints has, in the past, come up trumps. Treatments to reduce high blood pressure and high blood cholesterol, were licensed, marketed and widely used before there was evidence that they had effects on hard clinical outcomes. Lowering blood LDL as a rationale for using statins was controversial in its day. But large scale clinical trials such as the Heart Protection Study later found important clinical benefits too.
It is at least questionable whether the statins would now have been licensed without showing a reduction in hard endpoints such as heart attacks and strokes. That would have witheld their benefits from thousands of people. So a more cautious approach to the evidence on which drugs are approved for use has drawbacks.
There was criticism of the speed at which glitazones began to be prescribed, particularly in north America, without evidence of benefits in clinical outcomes rather than biochemical outcomes. The speed of uptake of statins was much slower, and really only picked up after the first large scale clinical trials showed benefits, initially in higher risk patients and then more widely.
This is perhaps one lesson. We can choose to accept evidence from surrogate outcome studies in licensing drugs if we accept that it is not then appropriate for treatments to be heavily marketed before they have proved themselves in terms of harder clinical endpoints. Or we can decide not to accept surrogate outcomes, and delay the introduction of treatments possibly by many years (and may prevent the development of some treatments altogether).
It's not an easy choice to make. Either way there are risks - from unexpected adverse events, or from the unavailability of possible treatments.
Monday, 24 May 2010
Why Wakefield became a cause célebre
So, Andrew Wakefield has been struck off by the GMC. Brian Deer has covered the story extensively and uncovered details about the trials that proved to be Wakefield's downfall - details about payments from the legal aid fund, a patent for a vaccine, and the questionable way in which the trials were carried out. His determined investigations show how good journalism can function as a counterbalance to poor judgment by a whole host of agencies from ethics committees to the Lancet which unintentionally promoted the spread of the MMR-autism belief.
But a great deal of blame has also been directed at the newspaper stories that covered the initial findings (based it has to be said on a press conference at the Royal Free Hospital chaired by its professor of medicine, and then on a paper in the Lancet, - both of which most journalists would regard as reasonable sources).
While it would be impossible to defend all the coverage, it is worth noting the historical context.
The UK had recently emerged from the BSE crisis. The medical establishment had been found to be over-sanguine about the threat, ministers had dissembled, and the chief medical officer chose not to correct unfortunate ambiguously reassuring statements. It took much longer than it should have for the real risks to be identified and for preventive action to be taken.
In this context, the pursuit of the MMR-autism hypothesis, in the face of establishment opposition, looks less contrary, and more like the pursuit of the public interest against an orthodoxy that had recently been found to be less than open. What is not defensible is the subsequent highly selective reporting of studies that gave some weight to the hypothesis while ignoring the numerous, better, bigger, more statistically significant studies that did not.
The 'swine flu' pandemic last year shows that an open attitude and a recognition of uncertainty is the right response to take. Most people are sympathetic to the 'damned if you do, damned if you don't' tightrope of a response to a potential health threat. What they find less forgivable is the realisation that information, albeit imperfect information, is being concealed, or finessed.
BSE was a bad enough scandal by itself. The bad taste it left in the mouths of journalists and others was a contributory factor in the wildfire spread of the belief, however unsupported by evidence, that MMR might contribute to autism.
But a great deal of blame has also been directed at the newspaper stories that covered the initial findings (based it has to be said on a press conference at the Royal Free Hospital chaired by its professor of medicine, and then on a paper in the Lancet, - both of which most journalists would regard as reasonable sources).
While it would be impossible to defend all the coverage, it is worth noting the historical context.
The UK had recently emerged from the BSE crisis. The medical establishment had been found to be over-sanguine about the threat, ministers had dissembled, and the chief medical officer chose not to correct unfortunate ambiguously reassuring statements. It took much longer than it should have for the real risks to be identified and for preventive action to be taken.
In this context, the pursuit of the MMR-autism hypothesis, in the face of establishment opposition, looks less contrary, and more like the pursuit of the public interest against an orthodoxy that had recently been found to be less than open. What is not defensible is the subsequent highly selective reporting of studies that gave some weight to the hypothesis while ignoring the numerous, better, bigger, more statistically significant studies that did not.
The 'swine flu' pandemic last year shows that an open attitude and a recognition of uncertainty is the right response to take. Most people are sympathetic to the 'damned if you do, damned if you don't' tightrope of a response to a potential health threat. What they find less forgivable is the realisation that information, albeit imperfect information, is being concealed, or finessed.
BSE was a bad enough scandal by itself. The bad taste it left in the mouths of journalists and others was a contributory factor in the wildfire spread of the belief, however unsupported by evidence, that MMR might contribute to autism.
Thursday, 20 May 2010
Chocolate as part of a healthy diet. Yeah right
There is a kind of news story is‘too good to check’ where the desire for the story to be true over-rides the negative cynicism that is the default state of any decent news room. It’s what hoaxers and pranksters rely on when they persuade reporters and their editors to publish stories that are plainly complete bollocks.
Usually, but not always, these baseless narratives are ‘harmless’ enough and may prompt a weary smile among the media-savvy. The journalists and reader are, arguably, in a conspiracy: ‘we know this is probably crap, but there is a minute chance it might possibly be true, and it’s a laugh, isn’t it?’
Sometimes these stories are ‘what we would like to believe is true, but isn’t’, and one of the best examples is the ‘chocolate is good for you’ meme. Every now and then, some researchers somewhere will have carried out some research on mood and chocolate, or looked at some of the chemicals in cocoa, and found that they are (big fanfare) antioxidants. And we all know from the face cream ads that antioxidants are good for us.
The latest in this Mobius loop of articles are stories suggesting depressed people self-medicate with chocolate. My former colleagues at NHS Choices have done a decent job of picking the study apart here. There’s a story about chocolate and heart disease from the Telegraph; and one here from the Mail about
from the Mail about chocolate reducing stress.
But I’m not really talking about the details of the studies here, more the cumulative effect that might suggest to the nutritionally illiterate that chocolate has significant health benefits.
Now I like chocolate. A lot. Now that my beer consumption is more sporadic, it’s probably the reason that my waistline is what it is. But a food which is 18.5% saturated fat and 56.7% sugar by weight cannot be healthy, not in any universe where Newton’s law on the conservation of energy apply. No marginal antioxidants or mood-enhancing properties make up for the fact that eating chocolate regularly will contribute to, at the least, becoming overweight, and increasing risk of diabetes and heart disease.
I would like chocolate to be good for me, just like other people would like red wine to be good for them. But it isn’t, and the attractive stories are wishful thinking.
What is worrying is the well-known psychological effect of repetition: if you say something often enough 'it becomes true'. But it doesn't, and the repetition encourages out efforts to catch up with US levels of obesity.
Usually, but not always, these baseless narratives are ‘harmless’ enough and may prompt a weary smile among the media-savvy. The journalists and reader are, arguably, in a conspiracy: ‘we know this is probably crap, but there is a minute chance it might possibly be true, and it’s a laugh, isn’t it?’
Sometimes these stories are ‘what we would like to believe is true, but isn’t’, and one of the best examples is the ‘chocolate is good for you’ meme. Every now and then, some researchers somewhere will have carried out some research on mood and chocolate, or looked at some of the chemicals in cocoa, and found that they are (big fanfare) antioxidants. And we all know from the face cream ads that antioxidants are good for us.
The latest in this Mobius loop of articles are stories suggesting depressed people self-medicate with chocolate. My former colleagues at NHS Choices have done a decent job of picking the study apart here. There’s a story about chocolate and heart disease from the Telegraph; and one here from the Mail about
from the Mail about chocolate reducing stress.
But I’m not really talking about the details of the studies here, more the cumulative effect that might suggest to the nutritionally illiterate that chocolate has significant health benefits.
Now I like chocolate. A lot. Now that my beer consumption is more sporadic, it’s probably the reason that my waistline is what it is. But a food which is 18.5% saturated fat and 56.7% sugar by weight cannot be healthy, not in any universe where Newton’s law on the conservation of energy apply. No marginal antioxidants or mood-enhancing properties make up for the fact that eating chocolate regularly will contribute to, at the least, becoming overweight, and increasing risk of diabetes and heart disease.
I would like chocolate to be good for me, just like other people would like red wine to be good for them. But it isn’t, and the attractive stories are wishful thinking.
What is worrying is the well-known psychological effect of repetition: if you say something often enough 'it becomes true'. But it doesn't, and the repetition encourages out efforts to catch up with US levels of obesity.
Monday, 26 April 2010
What's inside the box.: the future of clinical trials
Last week I reported for a newspaper on a huge trial on different approaches to diabetes screening published in the Lancet. It looked at 8 different ways of screening for type 2 diabetes in a population of 325,000 people over 50 years.
Except it didn’t really. It used a computer model, the Archimedes model, built up over many years. The model has had in the past, some fantastic successes, predicting the results of the CARDS trial with great accuracy, for example.
But there are times when for all the hundreds of thousands of data points, and the most sophisticated algorithms in the model, it gets things wrong. The model did not predict the results from the Illuminate trial that resulted in Pfizer stopping development on torcetrapib, its drug to reduce HDL levels, because of unexpected adverse results.
There is still a lot about the complex interaction of treatments and human physiology that we don’t understand and where we have to use empirical evidence.
Developing computer models of human physiology and the likely effects of medicines (or screening strategies) is likely only to increase as computing power grows. The Lancet trial would have been impossible to do in real life. It would have had to have begun before I was born and would have cost tens of millions of pounds to carry out. It came up with some results which should inform public policy on managing the diabetes epidemic.
But there will be fewer and fewer people who can understand what is going on inside the box. What are the assumptions made, what is the integrity of the data? Today a reasonably informed person can, with a little work, read published clinical trials and come to a sensible conclusion about their quality. If the findings come as the result of the workings of arcane formulae, and manipulation of complex datasets, there is much less opportunity for a non-specialist to be able to make any kind of judgement. I have seen the future of clinical trials, and it worries me.
Except it didn’t really. It used a computer model, the Archimedes model, built up over many years. The model has had in the past, some fantastic successes, predicting the results of the CARDS trial with great accuracy, for example.
But there are times when for all the hundreds of thousands of data points, and the most sophisticated algorithms in the model, it gets things wrong. The model did not predict the results from the Illuminate trial that resulted in Pfizer stopping development on torcetrapib, its drug to reduce HDL levels, because of unexpected adverse results.
There is still a lot about the complex interaction of treatments and human physiology that we don’t understand and where we have to use empirical evidence.
Developing computer models of human physiology and the likely effects of medicines (or screening strategies) is likely only to increase as computing power grows. The Lancet trial would have been impossible to do in real life. It would have had to have begun before I was born and would have cost tens of millions of pounds to carry out. It came up with some results which should inform public policy on managing the diabetes epidemic.
But there will be fewer and fewer people who can understand what is going on inside the box. What are the assumptions made, what is the integrity of the data? Today a reasonably informed person can, with a little work, read published clinical trials and come to a sensible conclusion about their quality. If the findings come as the result of the workings of arcane formulae, and manipulation of complex datasets, there is much less opportunity for a non-specialist to be able to make any kind of judgement. I have seen the future of clinical trials, and it worries me.
Tuesday, 20 April 2010
This stuff shouldn't irritate me, but it does
Things reporters get wrong but shouldn't part45...
This report on abdominal obesity on the BBC health news website says 'Excess weight around the middle generates oestrogen and excess chemicals in the stomach, which put people at higher risk of killer diseases.'
I haven't checked the source materials, but I'm pretty sure the excess chemicals they are talking about are inflammatory cytokines. Which would be hydrolysed and destroyed if they were in the stomach, and so not in a position to do any damage. It's when the cytokines produced by the metabolically active fat gets into the blood that the trouble starts (and it's fair enough not to go into too much detail on the immunology...)
The BBC would not let a political or sport story containing such a howler to get through. Its reporters and editors are complete geeks about the different stages of a parliamentary bill or the Liverpool back four from 1974.
Didn't an editor somewhere along the line, wonder how chemicals in abdominal fat cells were transported to the stomach, and how they would then be in a position to increase the risk of heart disease, diabetes and cancer? Did no one in the news room have A level understanding of digestion?
Just looked up the source for the story. It's a churnalism classic: amplifying a badly written and ambiguous phrase in the press release and turning it into an error.
Lazy, careless and ignorant.
This report on abdominal obesity on the BBC health news website says 'Excess weight around the middle generates oestrogen and excess chemicals in the stomach, which put people at higher risk of killer diseases.'
I haven't checked the source materials, but I'm pretty sure the excess chemicals they are talking about are inflammatory cytokines. Which would be hydrolysed and destroyed if they were in the stomach, and so not in a position to do any damage. It's when the cytokines produced by the metabolically active fat gets into the blood that the trouble starts (and it's fair enough not to go into too much detail on the immunology...)
The BBC would not let a political or sport story containing such a howler to get through. Its reporters and editors are complete geeks about the different stages of a parliamentary bill or the Liverpool back four from 1974.
Didn't an editor somewhere along the line, wonder how chemicals in abdominal fat cells were transported to the stomach, and how they would then be in a position to increase the risk of heart disease, diabetes and cancer? Did no one in the news room have A level understanding of digestion?
Just looked up the source for the story. It's a churnalism classic: amplifying a badly written and ambiguous phrase in the press release and turning it into an error.
Lazy, careless and ignorant.
Subscribe to:
Posts (Atom)
