Monday, July 30, 2007

Liberman Proposes a New Commandment About Odds Ratios

Mark Liberman is on a mission to improve the rhetoric and logic of science journalism. He has written some excellent pieces on the topic and his latest is: Thou shalt not report odds ratios.
No, let's make it a commandment: Thou Shalt Not Report Odds Ratios. In fact, I'd like to suggest that any journalist who reports an odds ratio as if it were a relative risk should be fired sent back to school.

Many of you probably don't know what I'm talking about -- that's why dozens of science journalists disobey this commandment every week. But the basic concepts are simple, and nothing more than simple arithmetic is required to understand them.
Liberman puts up a thoroughly readable explanation of one of my recent pet peeves and takes readers through a shocking headline report to show how an arithmetical blunder led to the dissemination of a shocking 60% attention-grabber that should have been reported (more accurately) as the less startling 93.5%.

Liberman includes further discussion and provides some very informative links to allow for further exploration and understanding.

If you have ever wanted to learn about accurate reporting and odds ratios, grab this opportunity, and estimate for yourself just how pleased you were that you did.

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Myth: Autism Omnibus Hearings Have Not Included Evidence About MMR

Recently, there have been several comments, news-stories and posts that disseminate the misunderstanding that the Autism Omnibus Hearings have not included rigorous discussion of the MMR vaccine. A number of the experts testify about their involvement in the UK MMR class action legal case and have included some of that research in this case. It should be noted that the UK legal case was solely concerned with the MMR vaccine; the Autism Omnibus Hearings and the UK case involve many of the same experts as witnesses.

Dr Kinsbourne makes this pertinent comment during his cross examination (pdf) (albeit he is corrected by the Special Master who states that it was the Petitioners Steering Committee who chose to apportion the causation issues into the three categories):
The Special Master designated three questions for us at the beginning of the proceedings. Number one was about the relationship between thimerosal and immune function. The second was the relationship between the measles or MMR vaccination and autism. The third one was about collaboration as it were between thimerosal and the MMR in the causation of autism.

I see myself as addressing number two, the relationship between MMR and autism.
[pg. 150 of 191 or 1172: Day 5]
Many of the experts explictly included discussion of MMR, the presence of measles vaccine virus in the gut and the confidence in the integrity of laboratory findings of measles virus in gut and CSF samples. Mr Matanoski of the legal team for the Secretary of Health and Human Services made MMR part of the second part of his opening comments on Day 6 (pdf):
We want you to be sure in your own mind that MMR vaccine is not causing autism because you've had good evidence to look at and consider on that...[pg 10 of 345]

A serious accusation has been leveled. A serious accusation has been leveled against an important part of the public health arsenal against a preventable disease. An accusation has been leveled that MMR vaccine causes autism. That accusation must be answered, and we will answer it...

This accusation goes against a vaccine that is designed to prevent a killing disease. [pg 11 of 345]

...we are going to put on the evidence this morning and throughout this week that will allow you to effectively deal with that and tto show you that MMR vaccine is indeed safe. [pg 16 of 345]

You heard from Dr. Hepner [one of the petitioners' expert witnesses: Day 3], and frankly, I think the PSC [Petitioners' Steering Committee] may have cringed at one part of her testimony, that is, when she said that MMR vaccine causing autism is an unproven hypothesis. [pg 18 of 345]
Mr Powers, for the Petitioners Steering Committee (PSC), said the following as part of his closing statement on Day 12 (pdf):
You have a case here [the Cedillo case] that is a test case for the theory, the general theory that a combination of exposure to thimerosal-containing vaccines with a significant dose of ethyl mercury early in a child's life, combined then with MMR, can result in a complex system response that prsent symptoms that can get diagnosed as autism.

And in particular a suppressed immune system from the thimerosal in the vaccines, the introduction of the attenuated live measles virus then persists, and the persistence of that virus leading to a complex biological process of disease...
[pg 19 of 49 or 2887]
From the same transcript of Day 12, the following remarks are drawn from the Respondents' legal representative, Mr Matanoski:
You need to find whether Michelle Cedillo's autism occurred before her vaccine. You need to find whether the PSC has proven that autistic spectrum disorders can be caused by MMR.

Whether or not there's inflammation in Michelle's Cedillo bowel or intestines, you need to find whether or not MMR can cause autistic spectrum disorder.
[pg 30 of 49 or 2898]
The following remarks are taken from the same transcript of Day 12 but from wrap-up statement of Special Master Hastings:
the parties for both sides have presented evidence not just about the particulars of Michelle's case, but also about the general causation theory, the first general causation theory of the Petitioners Steering Committee. That is, the general theory that MMR vaccines and thimerosal-containing vaccines can combine to cause autism.
[pg 47 of 49 or 2915]
The following references are all to pdf files. I have included those transcripts that explictly include discussion of: MMR; the impact of the wild measles virus on the brain; the presence of measles vaccine virus in the gut; and the confidence in the integrity of laboratory findings of measles virus in gut and CSF samples.

Day 2: Dr Krigsman

Day 3: Drs Hepner and Kennedy

Day 4: Dr Byers

Day 5: Dr Kinsbourne

Day 6: Matanoski Esq.'s Opening; Drs Fombonne and Cook

Day 7: Dr Witnitzer

Day 8: Drs Ward and Bustin

Day 9: Drs Hanauer and McCusker

Day 10: Drs Chadwick and Brent

Day 11: Drs Fombonne and Griffin

Day 12: Mrs Cedillo and closing statements by Powers Esq. for Petitioners Steering Committee and Matanoski Esq. for Respondents

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Paediatric Grand Rounds 2:8 Is Up

Star - text is Paediatric Grand RoundsPaediatric Grand Rounds 2:8 is up, courtesy of Walter of Highlight Health.

The theme is a creative and delightful use of Deathly Hallows. A mixture of the intriguing, the odd, the humourous, the contentious and the interesting about paediatric healthcare. I commend PGR to you.

Dr. Clark Bartram is looking for hosts for future PGRs. You can consult both the hosting schedule and earlier editions in the Paediatric Grand Rounds archive. Please sign up for hosting.

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Friday, July 27, 2007

Prof. Mawson on Andrew Wakefield: Why Do His Views Need Consideration?

kitten snarls, not want decafDr Crippen has posted a Letter from America. However, it is not a gentle insightful reprint of a favourite Alistair Cooke but a letter from a US epidemiologist, Prof. Anthony R. Mawson. Mawson writes to offer his opinion on Prof. Trisha Greenhalgh's critical analysis of the Wakefield et al. study that was published in The Lancet in 1998. [I shall address these criticisms in another post although I suspect that the comments will deal with these matters in some detail.]

Mawson is a staunch supporter of Dr Andrew Wakefield. Although we may disagree on the quality of Wakefield's research and its significance, I do think it is admirable that Mawson has not only written this supportive letter to the most widely-read medical blog in the UK, but he may also have signed the Nigel Thomas petition that has gained the reputation as being in support of Wakefield and his research. I have emailed Mawson to ask him to confirm that he is currently signatory 2054 and maybe even 3529 (the numbers may be subject to change). If he confirms one or other of those signatures, then I shall discuss the supportive comments that he left there in another post.

Dr. Crippen tells us that:
Professor Mawson’s views need consideration.
He doesn't tell us why he thinks this, although he does then offer a potted summary of Mawson's current positions. However, it is not clear to me why Dr Crippen believes that any of these are more relevant than the opinion of most other commentators. There seems to be some potential for confusion about Mawson's qualifications. Dr RJ makes a robust comment that explores Mawson's reproof to Prof Greehalgh. In passing, he remarks:
Perhaps Professor Mawson hasn't kept up with his continuing medical education?
Having consulted Mawson's CV and various other sources, it's my understanding that he is not an MD or medical doctor. The CV lists an MPH or Masters in Public Health. His alma mater for this offers a 45-credit hour curriculum for this course although I don't know if the requirements were different when he took it. The MPH programme focuses on the
application of management concepts in the public health sector to protect and improve the health of the community. The MPH program consists of a 45-credit hour curriculum, which focus on management at the operating level.
The DrPH seems to be a Doctor of Public Health but it is clear that this is not a PhD programme: in UK terms this seems to resemble an MPhil. Mawson does not list a PhD in any subject. His CV states:
Dr. Mawson obtained his bachelor’s degree in sociology and psychology from McGill University, Canada, his MA degree in sociology from the University of Essex, UK, and both MPH and DrPH degrees in epidemiology from Tulane University’s School of Public Health and Tropical Medicine, New Orleans. He was also a post-graduate student at the London School of Economics and Political Science.
[Edited: 14:00] As several commenters to that letter have pointed out, but Dr RJ summarises:
Prof Mawson is an epidemiologist. He is not a medical doctor, not a virologist, not a pathologist, not an immunologist, not a gastroenterologist and not an autism researcher. There is nothing in Professor Mawsons CV that makes me think that he is qualified to hold an opinion on this paper any more than, say, a nuclear physicist with an interest in the topic.
I fail to understand what added value an epidemiologist without a record of research into autism, MMR, or the prevalence/incidence of paediatric gut-issues brings to a discussion of the appropriate design study for a case-series of 12 children, selected according to criteria that were mostly related to participation in a legal case.

Dr Crippen is notoriously scathing towards the value of PhDs and other higher degrees when nurses comment that they have them. What would his attitude be to those BAs and MAs in sociology and psychology, or the MPH or DrPH if a nurse were to report that s/he had them and was using them as a basis to claim academic credibility or excellence for Wakefield's work? Just why are Mawson's qualifications more relevant and why do they make his opinions more deserving of consideration?

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Tuesday, July 24, 2007

Food for the Brain Promotes an Autism-Gut Seminar

Water vole appears to guide toad into battle: caption reads, Accelerate to ramming speedUnderstandably enough, Food for the Brain updated its homepage to coincide with the broadcast of an update of its project with Chineham Park Primary School on Tonight with Trevor Macdonald, July 13.

Fair enough. It was a little odd, however, that they chose to use that update to promote a seminar, AUTISM AND DEPRESSION - A GUT PROBLEM? with these troubling words:
Dr Andrew Wakefield suggested a link between gut immunity and autism. Was he right? This September we offer a seminar 'The Gut Brain Link in Autism, Depression and Mental Health' for health professionals. For more details and booking a place click here.
Well, that is not quite all that Andrew Wakefield suggested in the aftermath of that discredited Lancet paper and it is a little disingenuous to cherry-pick out one aspect of that work (see related reading). However, I followed the link for more information and learned that the leader of this rigorous investigation into whether Wakefield was right is Michael Ash.
Michael Ash, BSc.DO.ND.Dip ION, is an experienced osteopath, naturopath and nutritionist who specialises in mucosal immunology and its relationship to systemic health problems including neuro-development and psychological health. Anyone interested in the relationship between the Gut, the Brain and Mental Health should attend what will be a fascinating three hour seminar.
A Dip. ION, what were the odds? However, maybe Michael Ash will lead a rigorous examination into Wakefield's work, exploring Prof. Bustin's devastating expert report and testimony to the Autism Omnibus Hearings alongside Dr Chadwick's extraordinary revelations that Wakefield knew that there was no confirmed finding of measles virus in any of the samples at the time of the Lancet publication (more in related reading).

However, I have my misgivings if this is the same Michael Ash who signed the Nigel Thomas petition which has been characterised as supporting Wakefield (currently, signatory 9164) and left this comment:
Dr Wakefields work in the immunological disturbaces in the GIT of individuals with Autism, needs encouragement not derision. This eminent clinician,should be funded to explore this area further. The golden goose in medicine of vaccination is not without risk.
It does seem very much of a piece with one of the articles (pdf) by the Michael Ash who will be running the FFTB seminar. Ash relies heavily upon Wakefield's findings and reports of ileal-lymphoid-nodular-hyperplasia, inflammation and identification of autistic enterocolitis as a novel disorder. However, those findings have been discredited and called into question by many experts with considerable standing in relevant disciplines (see related reading) and have been retracted by the majority of Wakefield's co-authors on that Lancet paper.

I don't know. Maybe Michael Ash will use this seminar as an opportunity to inform concerned health professionals about why Wakefield's work on autistic enterocolitis and related issues can not be relied upon. Perhaps he is announcing a major re-think of some of his own treatment offerings and theories but there is no information about such a significant theoretical overhaul on his own website and it is the sort of thing that anxious parents need to know.

I can't help wondering if Sir Trevor Macdonald knows that FFTB is offering this event or if he is at all concerned that FFTB has strong links with people who are opposed to the recommended vaccination schedule?

Related reading:

Patrick Holford's remarkable ideas about appropriate vaccination strategies for children
Patrick Holford's support for Dr Andrew Wakefield's discredited findings, Part 1, Part 2 and honorary Part 3
Support that extends to exhorting others to sign a petition in support of Andrew Wakefield (and here) but not actually signing it himself (certainly not the last few times I checked).
Wakefield and Why the Edith Piaf Routine Is Baseless Part 1 and Part 2

Click on the image for I can has cheezburger? detail.

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The Independent on the Motivation of Criticism of the Infamous Campbell Articles

Baby with bib that reads, MMR is safe. Tell your friendsStephen Glover of The Independent somewhat magnificently misses the point of Dr Ben Goldacre's criticisms of Denis Campbell's infamous MMR-autism article for The Observer:
It is not often you read an attack in one newspaper on another such as appeared in The Guardian last Wednesday. The oddity here is that the venom of the article's author, Ben Goldacre, was directed at The Guardian's sister paper, The Observer. Mr Goldacre was angry about a front-page piece in The Observer suggesting a possible link between the MMR jab and autism. According to Mr Goldacre, The Observer had wilfully misrepresented research at Cambridge University. His piece was quite persuasive, though I dare say The Observer's case is stronger than he made out. Some may say it is grown-up for one newspaper to be able to attack another in the same group. No doubt it is. Yet, one cannot help wondering whether the publication of this piece in unexpurgated form did not reflect irritation on the part of The Guardian's editor, Alan Rusbridger, at The Observer's distinct populist identity. [My emphasis.]
Oh, I think that one can quite easily avoid that line of thought, if one comprehends the full horror of just why that article and the one that accompanied it are so spectacularly horrible that they will probably end up in textbooks as an Awful Warning to Journalists Who Get Out of Their Depth and Write About Matters that They Don't Understand While Behaving in an Irresponsible and Indefensible Way - and to the Editors Who Back Them.

According to Ginger Yellow, this matter was mentioned in The Guardian's media podcast but, again, missed the point by a country mile.
Tim Radford’s comments about this debacle on the Guardian’s media podcast. He basically took the line that you shouldn’t have scientists or people trained in science in newspapers because only lay journalists would know the questions that readers would want asked, and that we should rely on scientists to give the right answers. But isn’t it the job of an editor to make sure the right questions have been asked? And besides the Observer story had nothing to do with asking the right questions (as far as we can tell they didn’t ask any) and everything to do with basic misunderstandings of science and pushing an anti-scientific agenda. [My emphasis.]
Eh - wasn't one of the most significant points here that Denis Campbell signally failed to contact any of the principal scientists who could have set him straight about his astonishing story? Or was he too busy practising his new signature as Scoop (don't call me Denis) Campbell?

And, frankly, it may be the fact that he knew nothing about the subject, and couldn't assess his sources that led him to repeat the canard by implication that MMR in the US contains thimerosal (UK thiomersal, a mercury-containing preservative) which it does not and never has (he makes this mistake in his interview with Andrew Wakefield* that accompanied the autism scoop article, but he was obviously dazzled judging by the breathless fanfic prose). It may also have led to his inability to understand some of the terminology used and his lack of awareness that it is unwise to report the results of a tool that yield a known false positive rate of 50% without appropriate caveats and qualifications alongside. Those are just a few of the many flaws in Denis Campbell's piece that has now disappeared from The Observer's archive**.

Golf fans would not sit still for reporting by a journalist who didn't know one end of a club from another and flaunted ignorance of the history of the game. Why would anyone think that the public needs science interpreted for them by people whose understanding is worse than their own? Goldacre has described the responsibilities of journalists, acknowledging that the public is expected to rely upon journalists of various media to read and understand studies that are of general interest and to report upon them accurately. However, as Goldacre expresses it, although
newspapers like to fantasise that they are mediators between specialist tricky knowledge and the wider public...I wouldn’t be so flattering.
Scoop Campbell's debacle is a horrible example of this and, yes, An Awful Warning to Others. It is particularly galling that the consequences of correcting his misinformation will not have to be faced by him and The Observer. GPs and health workers in the UK and other countries will face yet more conversations with parents who are alarmed by Campbell's claims and have not heard that there is no foundation to them. Health insurers or the NHS will have to pay for that time. Who knows what the final bill will be if parents are so alarmed by these groundless statistics and claims that they refuse to vaccinate their children against preventable childhood illnesses?

The excellent Language Log posted a thoughtful piece on the Sí se puede surrounding a contretemps that involves language classes and some remarkably simplistic solutions that were offered by people who may not have known better but should have been aware of the appropriate resources that they might have consulted. They quote John Moore and Ana Celia Zentella with approval:
Rarely do politicians think to consult language researchers when dealing with linguistic problems. The governor seems to think that his recollection of his own experience with learning English is enough evidence to know how to deal with complex issues of second-language acquisition and literacy among poor immigrants under very different circumstances. However, we still harbor hope that research and facts might occasionally trump a facile appeal to personal anecdotes, so often invoked in political discourse.
That seems remarkably sensible. If you have an announcement to make that might influence public understanding and even lead to some friction, then it might be worth talking to some experts on the subject. The Science Media Trust comes to mind for Denis Campbell, editors, Correction Offices and anyone else who might regard this as a helpful tip.

*Campbell propagates the myth that the Autism Omnibus Hearings did not discuss MMR but were solely concerned with thiomersal, thimerosal and mercury preservatives
**The Guardian uncritically reproduced some of Campbell's claims in an article that claimed to give a summary background on MMR: Q&A: MMR vaccine row. This article now has the offending paragraph removed pending investigation:
A paragraph regarding concern about MMR overseas, extracted from a piece in the Observer now deleted from the website due to concerns about its accuracy, has been removed from this article until the information can be verified.

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Observer MMR Story Has Disappeared From the Archives: Why?

Ducks with a disembodied hand
Quick update. Dr Ben Goldacre has just posted a note to say that Observer MMR Story Disappears From Archives.
For obvious reasons of propriety I have studiously avoided having an inside track on anything to do with this piece from the beginning, so I have no idea what is going on here.
Were The Observer nibbled to death by ducks in trying to find out where to start for the corrections? Has that desperate email by Dr Fiona Scott convinced them that they had this story badly wrong? Is there going to be a retraction? The Observer badly needs to retract that story albeit the damage is done and those infamous figures have been widely quoted as evidence of an autism epidemic.

Maybe there will be a retraction. Must go, I've just been told that pigs are flying and that there is to be an announcement that Patrick Holford had decided to rethink his treatment programmes that are based on Wakefield's research.

More, as the story unfolds...and there are virtual Jaffa Cakes on offer to the first person who spots a decent conspiracy theory for this disappearance. You know, like the doctors too terrified to speak against vaccines who were given an honorable mention by Halvorsen in his recent Sunday Express extravaganza that blazed, Children 'Used As Guinea Pigs for Vaccines'. Something classy along those lines, or that resembles Sherri Tenpenny's remarkable theory that the reason that Dr Byer's testimony at the Autism Omnibus hearings was so gob-smackingly awful might be more sinister than it reflected Byer's level of knowledge, competence and expertise:
Ya have to wonder if someone got to her or threatened her kids by her response. Absolutely unbelievable and I would suspect was really unexpected by the Chin-Conway team or they wouldn't have put her on the stand.
Of course, it might just be an accurate reflection of the level of actual scientific support for the case...So, something really decent along those lines, please.

Update, July 25: The Guardian's User Help Desk is responding to enquiries thus: "“The article was removed from the website for legal reasons. We are unable to provide a copy.” It is a little sad to reflect that newspapers and such are considerably more responsive to legal actions/discussion than they are to corrections of facts.

Related reading

Wakefield: another triumph for mainstream journalism in the UK
Autism: The Truth Plus Sensitivity, Specificity and All That Is Decent to Reveal About Predictive Values
The British Medical Journal Embarrasses Itself by Reproducing That Notorious 1 in 58 Figure
Ben Goldacre Breaks His Silence on the Media Coverage of the MMR, Autism Stories
Observer Gives A PoMo Clarification: Retract Already
Anthony Cox: How virulent were The Observer’s MMR articles?

For more information about the images used in the illustration, click on it or visit Flickr.

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Autism Diva Gives a PoMo Sting to Wakefield Support Banners

Go and see what Autism Diva has done to some of the banners of Wakefield's bank of supporters outside the GMC Hearings. It is definitely what some of those banners should have said in a disarmingly charming comment on some of the charges.

I don't know whether my favourite is:
  • 1st photo - poster in back says "No time 4 ethics"
  • 2nd photo - "We support Andy Wakefield and his lifestyle ££££"
  • Photo 3 - "Give us bad science"
The sad thing is that these banner-bites resemble so many of the comments made by his supporters that they lack the PoMo sting that should have made their irony more apparent.

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Monday, July 23, 2007

Media Comment on Media Coverage of Wakefield, MMR and Related Matters

It's hats off to Matthew Norman of The Independent's Media Diary who has some astute and wry comments about the schadenfreude enjoyed at the BBC's recent discomforts and ties it in to the ongoing debacle that is the general coverage of autism, MMR and Dr Andrew Wakefield.
Will this wretched appeasement of a tabloid press, whose malevolence is surpassed only by its hypocrisy, never cease?

ALSO CONSIDERING the BBC was Melanie Phillips, who fretted in the Daily Mail about declining standards of objectivity. "With an attitude that regards all challenges to its warped world view as beyond the moral pale," declares the woman who knows Jewish critics of Israeli policy towards the Palestinians as Jews For Genocide, "it follows axiomatically that the truth goes out of the window altogether." Indeed, indeed. Whether Mad Mel will apologise for propagating the dangerous nonsense about a link between MMR and autism should Dr Andrew Wakefield be disciplined by the GMC hearing, we must wait and see.

"He paints a picture of a BBC," declares Mad Mel of Anthony Jay's recent report on wicked BBC liberalism, "in which arrogance and a false sense of moral superiority combine with gross ignorance of the real world, to spread an ideology 'not based on observation and deduction but on faith and doctrine', and into which all events are wrenched to fit".

Uncanny, really, how exquisitely well she puts it.

Of course, I would still like to see the British Medical Journal consider whether or not it would be helpful if they blogged the GMC Hearings.

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Sunday, July 22, 2007

Observer Gives a PoMo Clarification: Retract Already

Cat springs out of birthday cake with suprise notice announcing, You're AdoptedThe Observer deserves sackcloth and ashes for its autism, MMR coverage. The British Medical Journal (BMJ) embarrassed itself by uncritically reproducing that 1 in 58 figure but at least it had the good grace to take a piece by Dr Ben Goldacre that criticised the media coverage of this issue.

Bloggers have offered thoughtful criticism, snarked and ridiculed this on-going story but still it continues because we don't have opinions that should be noted. Baltimore Sun offers an intriguing argument that bloggers are ruining quality mainstream journalism:
the Internet siphons audiences and revenue from the media outlets that can give citizens a voice, causing them to shrink and further impairing the media's democratic power.
Apparently, there is an argument that in a time of contracting revenues, newspapers offload science/environment/health reporters because they don't sell papers and any actual experience/knowledge is not valued.

So, as one of the more respectable representatives of the MSM, The Observer had the opportunity to do the mature, right thing and retract Denis Campbell's New health fears over big surge in autism [Edited: July 24; new URL as original story removed from Observer archive.]for:
  • inappropriate linkage (MMR and autism)
  • spectacular over-emphasis of a particular figure (the 1 in 58, ignoring the particulars of the tool etc.)
  • failing to contact principal parties (shoddy journalistic practice)
  • failing to disclose relevant information (too many examples)
  • plain being wrong.
Instead, they have compounded matters by issuing one of those PoMo clarifications, the sort that reads like an apology if you were offended but the fault lies with you for being offended/picky about the boring science/significance of the statistics. After all, according to Ben Goldacre, Holford Watch, Anthony Cox and Mike Stanton, they were only mostly wrong on most points.

Seriously, The Observer should stop faffing about with this story, they're just compounding the errors and the insult. At the risk of sounding all blogger and undemocratic, their clarifications are inadequate and cannot begin to address the problems with their coverage. As an american friend recently commented to me: Retract already.

Related material

Dr Eric Fombonne delivers a presentation to a conference that addresses the issue of whether there is an epidemic of autism: answer 'No'. 1 hr+ talk, slighly dodgy soundtrack and the slides are tricky to read but it is a good presentation. The site has a lousy interface: you need to load the home page, select conference online and Fombonne is Day 1: Session 2.

The Fombonne presentation is excellent if you can persevere. It discusses prevalence v. incidence; changes in case definition and how this impedes comparison with other studies; changes in the age of diagnosis and its implications for recording figures; and issues relating to statistical power.

If I really can't persuade you that you need to take the time to listen to Fombonne for an hour, Autism Speaks offers interviews with experts who say more or less the same thing in nicely edited 90s to 5min pieces. Both Drs Insel and Volkmar skilfully avoid the loaded, emotive, sensationalist questions lobbed at them by their interviewers and explain that there is no autism epidemic. They both give a good basic overview of the changes in diagnostic criteria (including the development of criteria that embrace a range of IQs); the difference between an educational label of autism (triggers desirable services) and a clinical diagnosis of autism etc.

Dr Insel does a nice job of distinguishing prevalence and incidence in The Increase in Autism Diagnosis.

Dr Volkmar gives a good overview of why there is no autism epidemic in The Increased Rate of Autism Diagnosis.

But, seriously, if you want the inside track on what is so wrong with the figures bruited about by The Observer and precisely why it behoves the researchers to be so careful in evaluating them, listen to the Fombonne presentation.

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Friday, July 20, 2007

Why Can't We Have Single Jabs While There Is Uncertainty?

Baby with bib that reads, MMR is safe. Tell your friendsFollowing recent news stories about Dr Andrew Wakefield, MMR, autism and the vaccination programme in general, I've seen a number of variations on the question:
I want to vaccinate my children but why can't we have single jabs on the NHS while there is uncertainty?
Dr Richard Halvorsen recommends single jabs or individual doses of vaccine, administered one at a time, on separate visits in his recent piece in the Daily Mail.

First and foremost, unless it is contraindicated for a individual (e.g., someone who is immunocompromised), there is no uncertainty about the safety of MMR v. the potential for harm of these preventable illnesses among Public Health Officials and the majority of scientists. The Medicines Control Agency and Dept. of Health issued a useful summary of the safety investigations: it is a clear and well-referenced rebuttal to the flawed claims about the safety record and evaluations studies of MMR that arose from a paper and comments by Drs Andrew Wakefield and Peter Fletcher.
MCA has carried out a review of the licensing of MMR vaccines and can assure the public that the licensing followed normal procedure and was based on robust studies...

Combined MMR vaccines had been extensively tried and tested in Scandinavia and the USA before they were introduced in the UK in 1988. Now MMR is successfully used in over 30 European countries as well as USA, Canada, Australia and New Zealand. In addition, a publication in 1988 lists 30 published studies where combined measles, mumps and rubella vaccines were studied and follow up extended up to ten years. The safety of the combined MMR was studied and shown to be the same as that for the component vaccines...

The Department of Health vaccination programme uses the combined MMR vaccine because it is the safest and most effective means of protecting children from these diseases. The child is put at greater risk of contracting these infectious diseases because of the gap between vaccinations. [pg 1]
More recently, Peltola and colleagues published a 14-year prospective follow-up of MMR vaccination. They reported:
an incidence of serious adverse events with possible or indeterminate causal relation with MMR vaccination of 5.3 per 100,000 vaccinees or 3.2 per 100,000 vaccine doses...Comprehensive analysis of the reported adverse reactions established that serious events causally related to MMR vaccine are rare and greatly outweighed by the risks of natural MMR diseases.
Secondly, there are well-founded concerns that administering individual doses will leave children, and the people with whom they are in contact, exposed to the dangers of preventable illnesses for longer than is necessary. Sense offers a press briefing on why Sense is opposed to single jabs with an excellent summary of the safety and success of MMR with particular emphasis on their principal concern, rubella.
The MMR vaccine was introduced in 1988. Since then, the numbers of children affected by Congenital Rubella Syndrome, and the incidence of rubella in the population at large, has dropped dramatically.

Between 1971 and 1980, 447 children were reported as born with congenital rubella syndrome. Between 1991 and 2000 only 38 cases were reported. Between 1971 and 1980, 5711 terminations were reported as a result of rubella. Between 1991 and 2000, 61 terminations were reported.
Sense provides a fuller briefing paper: MMR - the issues (pdf).
We are aware of calls for making single antigen vaccines available and, having considered the weight of evidence available, conclude that the introduction of single antigen vaccines carries the serious risk of an increased incidence of congenital rubella in addition in the increases in disabilities caused by measles and mumps infections.
Separate vaccinations would mean 6 visits to trips to the GP/Health Clinic and experience shows that a significant number of those opting for this do not attend all of the sessions. These visits would
take from 3-5 years depending on the time span left between each administration of each vaccine. The proportion of children protected at any one time against all three diseases would be reduced.

This would mean more children going uprotected, increasing the risk of infection to themselves and to other children [ref]. Such a decrease in herd immunity would lead to outbreaks of rubella, measles and mumps. [pg 6]
Separate vaccinations encourage a pick-and-mix attitude where some parents decide that, e.g., a boy derives no personal benefit from rubella vaccination and opt to omit this.

Finland has had a 2-dose MMR strategy in place since 1982 and has uptake rates of more than 98%. Finland is the first country to be documented free of indigenous measles, mumps and rubella (Mumps and rubella eliminated; Measles eliminated). In stark contrast, in 1993 Japan stopped giving the MMR and replaced it with individual vaccines for measles and rubella with an optional mumps vaccine. Between 1992-1997 there were 79 deaths related to measles in Japan; for the same period in the UK there was one death. Contrary to the expectations of people who believe in a link between MMR and autism and advocate for single jabs, the rates of autism continued to rise in Japan.

Related posts:
Myth: Measles Is A Trivial Illness, There's No Point to Vaccination
MMR Vaccine Does Not Contain Mercury, Thiomersal, Thimerosal and It Never Has

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Wednesday, July 18, 2007

Ben Goldacre Breaks His Silence on the Media Coverage of the MMR, Autism Stories

Wounded are removed from a battle scene by horse-drawn sledgeI recently complained about the standard of coverage of MMR and autism issues in the UK media alongside the ubiquitous hagiographies of Dr Andrew Wakefield.
The belief in a link between MMR-vaccines-mercury-autism has cultish overtones. Most religions have an act of contrition. UK media collectively need to make an act of contrition and perform an act of reparation. The latter, of course, should take the form of some informed coverage. I would nominate Ben Goldacre (who is uncharacteristically/ominously quiet at present) but then what would somebody who is medically qualified and known for promoting the public understanding of science (awards and everything) have to add to this discussion?
Ben Goldacre has broken his silence with an article in the BMJ: MMR: the scare stories are back (also available on Bad Science). It's a feisty piece (can men be feisty?) and quotes some robust language from an email tirade that happened long ago but is still a stone in the shoe for enraged academic.

One of the interesting nuggets that came out of the article was the background to Prof. Baron-Cohen's widely-reported concerns and consulation of Public Health Officials.
How did the Observer manage to crowbar MMR into this story? Firstly, it cranked up the anxiety. According to the Observer, Baron-Cohen “was so concerned by the one in 58 figure that last year he proposed informing public health officials in the county.”

But Professor Baron-Cohen is clear: he did no such thing and this was simply scaremongering. I put this to the Observer, which said it had an email in which Baron-Cohen did as the paper claimed. Observer staff gave me the date. I went back to the professor, who went through his emails. We believe that I too now have the email to which the Observer refers. It is one sentence long, and it is Professor Baron-Cohen asking if he can share his and the other researchers’ progress with a clinical colleague in the next door office. This dramatic smoking gun reads: “can i share this with ayla and with the committee planning services for AS [autism services] in cambridgeshire if they treat it as strictly confidential?”

Professor Baron-Cohen told me, “That’s not saying I’m concerned, or that we should notify anybody; these are just the people who run the local clinic, who I share a corridor with, who said they were interested to hear how it was going so far. They are not public health officials, and it’s not alarmist, it’s not voicing concern, it’s simply saying: ‘am I allowed to share a paper with a colleague in the next door office?’ It seems very important to me that we discuss clinical research with clinical colleagues, and I only stressed confidentiality because the paper was not yet final.” [My emphasis.]
Now, there is a saying along the lines of "Bring me a dozen words written by any man and there's enough therein to hang him" but the resulting farrago of nonsense seems to rely upon a remarkable over-interpretation of this simple one-liner. If Baron-Cohen had mentioned that he had to dash because he was working to meet a deadline on this report while munching the morning toast, would this have been trailed as a clandestine briefing at a breakfast meeting? Who leaked this email? Why didn't Denis Campbell contact Baron-Cohen to discuss the matter rather than relying upon an over-interpetation by parties who may well have had their own agenda?

The BMJ is one thing. The wider UK media have to step up and start making reparations although that 1 in 58 figure has spread so far that it seems impossible to recall (examples: blogs, here and here; the newspapers who cite this are too many to mention but include, of course, The Observer, the Daily Mail, The Daily Express and even the BMJ). Goldacre concludes, somewhat dismally although accurately:
Whatever one might think about Andrew Wakefield, he was just one man: the MMR autism scare has been driven for a decade now by a media that over-emphasises marginal views, misrepresenting and cherry picking research data to suit its cause. As the Observer scandal makes clear, there is no sign that this will stop.

Related posts

The British Medical Journal Embarrasses Itself by Reproducing That Notorious 1 in 58 Figure
Another Day of Shame for UK Media on Topic of MMR and Autism
Autism: The Truth Plus Sensitivity, Specificity and All That Is Decent to Reveal About Predictive Values
Wakefield: Another Triumph for Mainstream Journalism in the UK
Anthony Cox: How virulent were The Observer’s MMR articles?

Thanks to Wellcome for use of this open access image of the removal of wounded by horse-drawn sledge by Ugo Matania.

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Should the BMJ Blog the GMC Fitness to Practise Hearings?

Matthew Hopkins, witchfinderThere are repeated complaints about the General Medical Council's Fitness to Practise Hearings. Many of the hearings are justifiably closed to the public because they involve close scrutiny of otherwise confidential medical records.

In the case of the current hearing that involve Profs Walker-Smith and Murch with Dr Andrew Wakefield, the medical records of most of the children in the Lancet paper are already partly in the public domain. These hearings are open to the public and will be reported upon by various media. However, so far, much of the coverage is associated with mis-information.

The BMJ has editorial blogs. Would it be interesting to have the blog perspective of relevantly qualified and experienced people on these and other relevant hearings that involve public interest? Would the BMJ be able to offer a less sensationalist view than is seen in the newspapers from time to time?

Both in the UK and various other countries, there are doctors who are known for being, e.g., Lyme Literate or willing to run tests for or treat the conditions such as environmental illness, CFS/ME, thyroid or adrenal problems or controversial diagnoses that cause much frustration for some GPs and patients. Both in the UK and elsewhere, these doctors are being investigated by their licensing bodies or equivalent. Some of the UK doctors have survived various hearings but closed their practices because it is difficult/impossible to obtain insurance to cover GMC Hearings and they couldn't afford to fund a future defence.

I recently attended a wedding where several people discussed the case of Dr. Sarah Myhill, a private GP, who is in just that position. Five years ago, she was scheduled to have a GMC Hearing but it was cancelled without further explanation. However, because of the Hearing that didn't happen, she couldn't obtain insurance against future Hearings and she is now scheduled for a GMC Hearing, later this year. She is asking her patients to help fund her defence.
The complaints against me are all from doctors who do not like my style of practice. No patient has been harmed or even put at risk. The three patients involved have all refused to have their medical records used against me, but their "anonymised" records have been taken anyway by the GMC against their desires and without their permission.
The merits or de-merits of Dr. Myhill's practice and the complaints against her were not under discussion (the charges are not formalised, I don't know the basis for the complaints etc.). There seems to be some unhappiness about the way in which the GMC gathers its evidence and runs its Hearings.

These cases and the way in which they are handled are cited by a number of the doctors who feel that it is a strong indicator that they could not consent to an non-standard test or treatment protocol without running the risk that a colleague might use it as the basis of a complaint. I have no idea whether or not they are being over-sensitive and hyper-cautious or merely prudent in a climate where they feel that their decisions are being consistently second-guessed or questioned. Some GPs are concerned that PCT and NICE dictats along with these concerns are compromising their therapeutic autonomy and not always in the best interests of the patient.

Would decent, informed blog coverage of Fitness to Practise hearings alleviate these misgivings by making them more accessible (assuming that appropriate privacy can be preserved, where necessary)? Or would exposing hearings to more scrutiny make them appear more like the witch-hunts to which they are sometimes (albeit not always appropriately) compared?

Thanks to Wellcome for use of this open access image.

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Tuesday, July 17, 2007

Fitzpatrick and Halvorsen Speak About Vaccines: Whom Do You Trust?

Young infant receives vaccinationDr Michael Fitzpatrick has posted his own version of the recent abysmal UK reporting: The dark art of the MMR-autism panic. What can I say, the man writes with economy and clarity.
Dr Wakefield’s scientific achievements lag far behind his successes in media manipulation: after 10 years (and the expenditure of £15 million in legal aid funding), he has yet to produce credible evidence that MMR has caused autism in a single child (2).

The Observer story contains three features common to the episodic upsurges in media interest in the MMR-autism link provoked by anti-vaccine campaigners over the past decade. These are the leak of an unpublished scientific paper ostensibly supporting the link; the endorsement of the link by some maverick scientist or doctor; the prominent report by a journalist lacking any relevant expertise or experience. By the time that the paper is revealed to be rubbish (or irrelevant), and the maverick is exposed as something less than a reliable authority or to be on the litigation pay roll (or both), the damage to confidence in MMR has been done. While the shabby scaremongering caravanserai moves on in search of its next media opportunity, parents are left with the burdens of anxiety and guilt (and children who miss out on immunisations as a result may be left with even heavier burdens of disease and disability).
Fitzpatrick provides some useful appendices that are a decent guide to the conflict of interest and reporting controversies.

Over in the People's Medical Journal (aka the Daily Mail) Dr. Richard Halvorsen asks the provocative question: Are vaccines a waste of time?


If you think that I should add more, vaccines are a modern medical marvel and, as such, were a strong contender for most remarkable medical innovation in a recent BMJ poll.

Slaving at the altar of balance I should perhaps mention that when Halvorsen tells us about his epiphany, he does himself no favours. He tells us of his dismay at what he learned when he was asked to research the issue. What?!? At no time in his career as a medical student or family doctor had he thought that it might be useful to understand what he was advising people about?
I am now convinced that rather than being a silver bullet in the heart of disease, vaccine programmes could actually be causing some serious health problems, with hundreds if not thousands of children adversely affected every year.
Where did Halvorsen do this astonishing research? Browsing the pages of anti-vax websites or flicking through the books of anti-vax medics such as Dr Stephanie Cave (I don't accept the rhetoric of "I'm not anti-vax, I'm anti-the immunisation schedule)? As for his disingenuous claim for balance:
I repeatedly heard stories of parents being patronised, bullied and forced into a corner when deciding whether to vaccinate their child, so I set out to inform parents, honestly, and without bias, so that they can make their own decisions.
Halvorsen's recommendations are as follows (I've chosen to respond to these with information on the web; there are several books that cover these issues in much greater and more comprehensive detail):
  • MMR: Halvorsen, "However, safety studies were woefully inadequate. To pick up rarer side effects, at least 10,000 children should have been followed up for at least a year.

    However, no children were actively watched for more than six weeks."
    Response: No, there is good quality information about side-effects. Granted, MMR the facts could stand to overhaul its text to improve the present rebuttal of this canard but the Health Protection Agency did a very reasonable job with an elegant and well-referenced rebuttal of Wakefield and Fletcher's claims (pdf) (I would imagine that their paper is the source of Halvorsen's assertion). Suffice it to say that there are studies that recorded data for between 1-10 years in addition to the six-week studies.
    Bandolier does a fine job of discussing the interesting case of Finland which implemented a vaccination catch-up programme in 1982 that also allowed a fascinating, long-term study of MMR and the epidemiology of vaccine-related adverse events.
    The total number of reported vaccine-associated events in 1.8 million people having 3 million vaccinations was 437. Of these, potentially serious adverse events occurred in 169 people, 79 of whom went to hospital. These 169 people were subject to serious scrutiny.

    The details of the potentially serious adverse events are shown in the Table. About half the reported adverse events could be ascribed to other factors (like other vaccinations given with MMR) on clinical, serological and epidemiological analyses. No event had an incidence of more than 1 case per 100,000 doses of vaccine.

    There were no cases of autism, and no cases of ulcerative colitis, Crohn's disease or any chronic disorder affecting the gastrointestinal tract.
  • Measles vaccine: Halvorsen, "May be worth vaccinating against measles with a single vaccine despite the side-effects - on balance, the risks of the disease remain greater than those associated with the vaccine, especially in vulnerable children with chronic illnesses".
    Response: OK, we are agreed on the significant health risk associated with measles although I think that Halvorsen is understating them (for those who contract measles, an estimated 12% of children and 20% of adults are hospitalised as a consequence of measles and its sequelae of vicious secondary bacterial infections).
  • Mumps: Halvorsen, "Not only unnecessary but the vaccine is making this disease worse".
    Response: What? There is not much of a vaccination programme against mumps in Egypt. I wonder if this sheds some light on Egypt's top-of-the-mortality-table rating with 312 deaths from mumps in 2004? The UK doesn't show up in the mortality table for mumps. The other countries that do are reporting very few deaths: this possibly reflects their well-organised vaccination programme. As for the claim about making the disease worse - that is why organisations track the disease strains as they evolve, so they can adapt the strain in the vaccine accordingly. The proposed solution (already adopted in UK and the US amongst others) is to recommend a second dose of the vaccine. WHO Position Paper on Mumps Vaccines, 2007 (pdf). Mumps is a paramyxovirus that has a substantial disease burden:
    Although the disease is usually mild, up to 10% of patients can develop aseptic meningitis; a less common but more serious complication is encephalitis, which can result in death or disability. Permanent deafness, orchitis, and pancreatitis are other untoward effects of mumps.
    We have different definitions of "unnecessary".
  • Rubella: Halvorsen, "Not recommended for children. More effective to screen teenage girls for acquired immunity and vaccinate the few who don't have it".
    Response: Herd immunity? Reservoirs of infection for pregnant women?
  • Polio: Halvorsen, "Still worth having a polio jab now the safer vaccine is available".
    Response: Pleasantly gruntled that we have a point of agreement.
  • Whooping cough: Halvorsen, "One of the least useful childhood vaccines; I'd not now give it to my children".
    Response: fine, but please give it to other people's children. Brian Deer has dealt very thoroughly with most of the Halvorsen canards in Pertussis, DTP-DPT vaccines: it looks like the courts may have got this one wrong. If you are interested in the opinion of a gifted paediatrician and writer, please consult: The Cough of One Hundred Days.
    From 1997-2000, one out of every five children with Pertussis was hospitalized, including more than half of all infants under six months. Ninety percent of Pertussis deaths occurred in infants.

    Younger children are more likely to suffer complications from Pertussis. The most common complication is secondary bacterial infection, most often pneumonia. Most of the infants who die of such complications die of pneumonia.

    Infants are also more likely to suffer seizures and encephalopathy, probably due to the reduction of oxygen supply to the brain.
    Whooping cough may not be a big deal for older children or adults; it is for infants.
  • Human Papilloma Virus (HPV): Halvorsen floats some 'maybes' about auto-immune diseases as a possible side-effect while fauxledging that these "could have happened by chance". However, his overall verdict is: "Wait and see".
    Response: I can't improve on Jo's Trust and their HPV Vaccines Information. HPV vaccines need to be administered before a woman becomes sexually active*.
There is a woeful dearth of accurate information about vaccines in the UK at present; the Daily Mail is not helping by allowing a promotional piece about his own book by an anti-vax doctor**.

Edited: 1 August: *Investigators have discovered non-genital reservoirs of HPV. It does not mean that they are necessarily tranmissable but it does emphasise the need for more research into the mechanism of transmission.

Edited: 18 July: **I haven't been able to verify this but I've seen a claim (Daily Express) that Halvorsen is an NHS GP who acts on his convictions and offers parents single jabs rather than the MMR or 5 in 1. If this is true, I have to assume that the practice is funding this as the NHS does not purchase individual vaccines; if Halvorsen is subsidising this then he is to be commended for acting on the courage of his convictions even if I disagree with his argument for such a practice and the potential for harm of pursuing such a programme.

Thanks to Wellcome for use of this open access image.

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Paediatric Grand Rounds 2:7 Is Up!

Star - text is Paediatric Grand RoundsPaediatric Grand Rounds 2:7 is up, courtesy of Dr. Bryan Vartabedian of Parenting Solved.

A mixture of the intriguing, the odd, the humourous, the contentious and the interesting about paediatric healthcare. I commend PGR to you.

Dr. Clark Bartram is looking for hosts for future PGRs. You can consult both the hosting schedule and earlier editions in the Paediatric Grand Rounds archive. Please sign up for hosting.

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Monday, July 16, 2007

MMR Vaccine Does Not Contain Mercury, Thiomersal, Thimerosal and It Never Has

Bottles of MMR II vaccineMMR has never contained mercury in any form: MMR has never contained thiomersal (UK) thimerosal (US). There are multiple sources for this information. The FDA/CBER has a full report on Thimerosal in Vaccines. The report details the history and use of the mercury-based preservative thiomersal/thimerosal in vaccines with an overview of the reasons for its introduction and the studies on its safety.

The specific information that MMR has never contained thimerosal/thiomersal is Table 1 and Table 3.

If UK readers would prefer a UK source then please consult MMR The facts.

Adding a preservative to MMR would be like adding a preservative to live yoghurt. Some people eat live yoghurt because they want the beneficial bacteria or even specially cultivated probiotics. If you were to pasteurise that yoghurt or add anti-bacterial or anti-fungal preservatives, then you would inactivate those potentially beneficial bacteria so you wouldn't get the benefit. It's a similar story for live vaccines such as MMR and thiomersal/thimerosal.

Kevin Leitch Canards Project is an opportunity to put together a resource that answers FAQ or common concerns; please contribute questions or answers to it.

Related posts:
Measles Is a Trivial Illness and There's No Point to Vaccination: The Myth

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The British Medical Journal Embarrasses Itself by Reproducing That Notorious 1 in 58 Figure

Cat with rifle poised at a window. The caption reads When all else fails, vote from the rooftopsThe deluge of bad reporting flowing from St. Maximilian Kolbe and Blessed Titus Brandsma Day continues. The mojo of this day is so powerful that it has even influenced the British Medical Journal for the worse: GMC hearing against Wakefield and colleagues opens.

After listing some of the charges against Dr Andrew Wakefield, Profs Walker-Smith and Murch but then reporting that the full list of charges won't be announced until today, when the hearing opens, the BMJ concludes this item with a blaze of shame.
Researchers from Cambridge University's autism research centre will conclude in an as yet unpublished study that autistic spectrum disorders are almost twice as common among British schoolchildren as current estimates indicate. The lead researcher, Simon Baron-Cohen, said that this study, which examined some 12 000 primary school children in Cambridgeshire, will conclude that one in 58 children has such a disorder.
No, no, no. Prof. Baron-Cohen has written a letter to The Observer (amongst others) to correct that canard about the 1 in 58 figure.
[Your] article linked MMR and autism.

The research does not...

The best estimate of the prevalence of autism is the 1 per cent figure published in the Lancet in 2006.

My view is that any apparent rise is likely to be driven by better recognition, greater awareness, growth in services, a widening of the definition of autism and a shift towards viewing it as a spectrum rather than a categorical condition.
Once more and with feeling, the researchers used several screening tools on that population. The 1 in 58 figure is the result of the Childhood Asperger Syndrome Test (CAST). When used with a general population such as a mainstream school, the CAST generates 50% false positives but it has a reasonable specificity (the negatives are true negatives) so it might seem reasonable to evaluate its potential usefulness as a comparatively low-cost first pass screening tool for epidemiology research. All of this was quite obvious to anyone familiar with screening who just read the newspaper articles: however, it was up to the journalists to explain this to the general reading public.

If the journalists and BMJ had had any further questions, they might have actually talked with one of the professors at the Cambridge University Autism Research Centre (ARC). They might even have consulted the ARC website and looked at the current research projects where they would have read about: Screening for Asperger Syndrome in primary and secondary schools. Despite the frequent accusations that there is no research into autistic spectrum disorders (ASD), this project is exploring ways of lowering the age at which diagnosis is practical. The researchers are aware that early intervention will help those children who are affected by ASD and they hope that effective screening would "reassure the worried well" (pg 2 of following report).
Currently, AS is picked up far too late. It should be possible to identify AS in children in primary school (age 5-11). We have developed a screening instrument for this purpose, called the CAST (Childhood Asperger Screening Test) and are testing it at a population level.
The team links to some relevant reports, including The CAST (Childhood Asperger Syndrome Test): test accuracy (pdf).

If the journalists or BMJ had done any of that then they would have learned that the researchers do not support that 1 in 58 figure and report it as an artifact of using the CAST. They conclude that although CAST may be useful in epidemiology research, there is not enough evidence to support its use as a general screening tool.
The Childhood Asperger Syndrome Test (CAST) is a parental questionnaire to screen for autism spectrum conditions. In this validation study, the CAST was distributed to 1925 children aged 5-11 in mainstream Cambridgeshire schools. A sample of participants received a full diagnostic assessment, conducted blind to screen status. The sensitivity of the CAST, as a designated cut-point of 15, was 100 percent, the specificity was 97 percent and the positive predictive value was 50 percent, using the group's consensus diagnosis as the gold standard. The accuracy indices varied with the case definition used...The CAST is useful as a screening test for autism spectrum conditions in epidemiological research. There is not currently enough evidence to recommend the use of the CAST as a screening test within a public health screening programme in the general population. [My emphases.]
More relevant quotations from the report are as follows but feel free to page-down through this if you feel that the researchers have already set out their stall.
Currently there is insufficient evidence to recommend screen for autism spectrum conditions as a public health service (National Screening Committee Child Health Subgroup, 2001). One of the gaps in the evidence is the lack of a screening test that has been fully validated and shown to be effective in the general population...

An effective screening test for autism spectrum conditions would also be invaluable for epidemiological research. Due to the resource implications it would not be possible to undertake a detailed assessment of all children in a large population-based study. A screening test can be used in the first phase of an epidemiological survey to sift out the children who require further detailed assessment in a second phase of the study, and hence make large studies feasible.
[pg 2 of 24 or 46.]

Many promising screening tests are being developed, but there is currently no screening test for autism spectrum conditions which has been fully validated in the general population, which has been shown to be effective, and for which information about validation is available in the public domain. The aim in further developing the Childhood Asperger Syndrome Test (CAST) was to validate a test for use in the general population rather than clinical populations, and to develop a test that is sensitive to autism spectrum conditions, including pervasive developmental disorder not other specified (PDD-NOS), not just to typical autism.
[pg 3 of 24 or 47. It is worth noting that the authors acknowledge that the name of the test is a little mis-leading, it has been retained for continuity purposes. They emphasise that CAST is for ASD.]

The consensus diagnosis captured children with wider spectrum conditions. When using the consensus diagnosis, a cut-point of 15 appeared to be appropriate where sensitivity (100 percent; 95 percent CI 74-100 percent) and specificity (97 percent; 95 percent CI 93-99 percent) were high. At higher cut-points, the sensitivity dropped. The positive predictive value was low at a cut-point of 15, at 50 percent (95 percent CI 28-72 percent). Using the assesment diagnosis, a higher cut-point may be more appropriate, such as 18 where sensitivity was 100 percent (95 percent CI 63-100 percent) and specificity 99 percent (95 percent CI 96-100 percent).
[pg 13-15 of 24 or 57-59 (intervening pp of tables).]

The drawback of the CAST is the low positive predictive value, which is a function of low prevalence of the condition in the general population (O'Toole, 2000). There are major resource implications of assessing a large number of children who are false positives. There could be much anxiety associated with false positive screen results, as has been demonstrated with other screening tests (Marshall, 1996). A positive screen results brings uncertainty about health status (Marteau, 1994), in the case regarding the presence of a developmental disorder, until further assessment is under-taken. It should be noted, however, that a child who is a false positive for an autism spectrum condition may have another developmental problem which may be clinically important...
[pg 16 of 24 or 60.]

There is no absolute gold standard test for a developmental disorder...
[pg 18 of 24 or 62.]

If there had been complete response to the screening test, proportionally more respondents with low scores would have been expected and lower prevalence estimates, compariable to those in other studies (e.g. Scott et al., 2002b), could be expected.
[Researchers discuss the type of family that was most likely to have filled out and returned the questionnaire. They missed some known children with ASD because the parents of those with confirmed diagnoses were less likely to participate in the study: to that extent, the prevalence rates might have been higher. However, the rate of participation in the study means that in general, there should probably have been a much greater proportion of low scores, so the prevalence rates were more in line with those reported elsewhere.]

The CAST is demonstrating good sensitivity and specificity but low positive predictive value...As the aim is to develop a screen for the general population, however, a more pragmatic method of increasing the positive predictive value [is needed]. It might be possible to introduce an additional phase prior to using the CAST, such as asking if the parent has concerns over the child's development. The CAST could then be used in a higher-risk population, and the positive predictive value may be considerably increased (O'Toole, 2000).

The CAST can be recommended as a screening test for autism spectrum conditions in epidemiological studies, as the low positive predictive value and subsequent false positives are unlikely to cause anxiety because a range of children from low to high scorers would be invited for further assessment...It is not appropriate, however, to recommend the use of the CAST as a general population screening test in a public health or educational setting...
[pg 19 of 24 or 63.]
[My emphases.]
[Edited: July 18] Simongates commented:
I think I read somewhere that the sample size was actually 116 i.e. there were 2 autistic spectrum children. If this is right the 95% confidence interval around the estimate of 1.7% would be 0.5% to 6.0%, which includes pretty much every value that has ever been claimed. So claiming an autism epidemic (let alone one caused by MMR) from these sorts of figures would be misleading even if the numbers were correct.
As a general point, in the absence of open access journals we rely upon journalists of various media to read and understand studies that are of general interest and to report upon them accurately. However, as Goldacre expresses it, although
newspapers like to fantasise that they are mediators between specialist tricky knowledge and the wider public...I wouldn’t be so flattering. In fact, if you have access to the original journals, you can see just how rubbish things can get.
In this case, the actual report is freely available but the journalists concerned, and those who were subsequently involved in supporting their actions, do not seem to have read it. It's almost as if the source of this figure is of no relevance to the heat and light that can be generated by the mis-reporting.

It was bad enough that this canard of the 1 in 58 prevalence spread like wildfire in the newspapers; it is a new nadir that the BMJ reported it so uncritically.

More when the feeling of sadness goes away.

Update: 15:00 Dr Fiona Scott was one of the implied sources for the MMR-autism connection in the original story that broke the 1 in 58 prevalence figure. A Dr Scott (identity unconfirmed but claimed) has posted this response to The Observer Readers' Editor response. Comment July 16, 2007 11:31 AM.
I feel, given that I was one of the two 'leaders in the field' (flattering, but rather an exaggeration) reported as linking MMR to the rise in autism, that I should quite clearly and firmly point out that I was never contacted by and had no communication whatsoever with the reporter who wrote the infamous Observer article. It is somewhat amazing that my 'private beliefs' can be presented without actually asking me what they are. What appeared in the article was a flagrant misrepresentation of my opinions - unsurprising given that they were published without my being spoken to.

It is outrageous that the article states that I link rising prevalence figures to use of the MMR. I have never held this opinion. I do not think the MMR jab 'might be partly to blame'. As for it being a factor in 'a small number of children', had the journalist checked with me it would have been clear that my view is in line with Vivienne Parry of the JCVI. The 'small number' was misrepresented by being linked inappropriately and inaccurately with 'rise in prevalence', leading readers to arguably infer that it is in fact NOT a small number!

I wholeheartedly agree with Prof Baron-Cohen, and many of the posts and responses received to date, that the article was irresponsible and misleading. Furthermore I reiterate that it was inappropriate in including views and comments attributed to me and presented as if I had input into the article when I had not (and still have not)ever been contacted by the journalist in question. I am taking the matter under advisement.
How many more times will Dr Scott and Prof Baron-Cohen have to issue clarifications?

Update: Denis Campbell's article, New health fears over big surge in autism has been removed from the Observer archive so I have linked to a new URL.

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Sunday, July 15, 2007

Myth: Measles Is A Trivial Illness, There's No Point to Vaccination

child with extensive measles rashI tried to leave this story alone but this horrible reporting of MMR and autism is like some weird vortex that is drawing me in.

Even with the marvellous work of the successful Measles Initiative vaccination programme there were still 345,000 deaths from measles worldwide in 2005. Even in the UK, with comparatively adequate nutrition and abundant medical services, and a baseline of healthier people, the BBC cited some alarming statistics from the medical newspaper Pulse related to measles:
lowering levels of immunity meant as many as 12% of children and 20% of adults could be hospitalised if infected by measles.

Does a hospitalisation rate of 12% of children and 20% of adults sound like what Patrick Holford characterises as "mild and temporary illness"? Does it even vaguely resemble the Peter Hitchen version of measles:
In very rare instances, measles can lead to disastrous complications. In poor countries, where children are hungry and there is no clean water, it can easily be fatal. But in advanced civilisations such as ours, where hunger is extremely rare and clean sanitation universal, it isn't actually a big threat.

Yet the MMR lobby pretend that it is.
If you want to learn about measles from the sort of world authority that I would hope that journalists would quote on the topic if they were seeking to inform rather than polarise then you need to read Dr Diane Griffin's testimony at the recent Autism Ominibus Hearings. Dr Griffin is the editor of the definitive Field's Virology and her status is such that she has contributed the chapter on measles for the last 3 editions.

For a good summary of the testimony, see Autism Diva's Omnibus hearing: Griffin.
[I]f you'd like to know about what happens to children who catch the wild-type measles and do just fine for 7 to 10 years when they
develope subacute sclerosingpanencephalitis or SSPE and then die a horrible death because the measles that had gone into a kind of remission and suddenly reaches a point of replication in their brains that destroys their brains literally eating it up (2785-2790). It's rare among kids who get the wild measles, but not found in kids who have been vaccinated for measles. Autism Diva's typical kid got wild-type measles at age 15 months or so. It was a pretty mild case. That kid was vaccinated on schedule with the MMR a few weeks later. It's frightening to think that kids who get the wild-type measles can end up dead from it 10 years later. That's one of the best arguments Autism Diva has ever seen for vaccinating.

Measles can kill quickly, too, but usually the death comes from a secondary infection. Measles seems to tie up all the immune resources or something and that allows whatever germs are around to come in and run amok and kill the child. So measles can cause a death by pneumonia, for instance, with the pneumonia germ sort of cooperating with the measles to kill the person (2799). Germs can be very scary things. Measles itself can kill people who have advanced AIDS or other severe immune dysfunction. Babies who are infected with the AIDS viruse are vaccinated with measles to take advantage of their still working immune system, after the person's immune system is badly damaged by AIDS they don't vaccinate for measles (2794). Measles is more contagious than many other viruses (2750).
Prof. Bustin wrote to The Observer in response to last week's MMR and autism story: he mentioned his own expert testimony and that of people like Griffin. And The Observer doesn't respond. Other papers hint that public health officials are shroud-waving when they talk about the dangers of a measles epidemic.

Judge this for yourself. Take a look at the records of HPA mortality figures for measles 1940-2006. Look at the figures; follow the trends for the introduction of measles vaccination in the UK and the introduction of the MMR in 1988. Note the downward drift from:
  • high six figure notifications down to low four figure numbers
  • mortality rates in 3 figures to 2 and then single digits.
Who would you place your confidence in? People of the ilk of Bustin and Griffin or the journalists who are shaming their profession and the reputation of the UK media?

Related posts:

MMR Vaccine Does Not Contain Mercury, Thiomersal, Thimerosal and It Never Has

Another Preventable Tragedy

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Another Day of Shame for UK Media on Topic of MMR and Autism

Faustus and the Devil Meet
It's St. Swithin's Day. According to folklore in the UK, if it rains today then it will rain for the next 40 days. It is a little known fact (in fact, known nowhere outside the confines of my imagination) that last Sunday was St. Maximilian Kolbe and Blessed Titus Brandsma Day: once The Observer had published those notorious pieces, it guaranteed abysmal coverage of the issue for the next 100 days.

The Observer publishes some of the many letters that they received, including one apiece from Prof. Baron-Cohen and Prof. Bustin. Baron-Cohen:
[Your] article linked MMR and autism.

The research does not...

The best estimate of the prevalence of autism is the 1 per cent figure published in the Lancet in 2006.

My view is that any apparent rise is likely to be driven by better recognition, greater awareness, growth in services, a widening of the definition of autism and a shift towards viewing it as a spectrum rather than a categorical condition.
Bustin (see Fitzpatrick for a summary of Bustin's devastating testimony):
Remarkably, there is no reference in your story to the fact that on 11 June the first of 4,800 cases in autism proceedings came to trial at the United States Court of Federal Claims in Washington. These are designed to establish whether or not autism can be caused by MMR. For the first time, a succession of highly respected researchers in epidemiology, genetics, virology, molecular biology and other medical and scientific disciplines - the 'medical and scientific establishment' of the Observer article - provided detailed evidence of why, in their opinion, there is no medical or scientific basis for any claim linking the MMR vaccine with autism.
You might have thought that the interventions from these two luminaries might have made it into the Readers' Editor response to the letters and the result of his investigations into the story. The short piece is riddled with self-exoneration. The Head of News says:
'I believe it was legitimate to include the thoughts of two of the authors of the study. We didn't conflate the two issues; the issues are already conflated.

'We worked hard to give a non-incendiary, balanced view. I believe we had to give the readers all the information we had. After all, they would ask, "Could MMR be a factor?"
Sins of omission and commission abound. They seem unrepentant about publishing the inflammatory 1 in 58 figure but grudgingly acknowledge that perhaps they might have included the other figures that were less disturbing and more inline with current estimates (I know, amongst many much-needed corrections, they didn't touch the issue of it being a tool that may generate a 50% rate of false positives which may be acceptable if it has good specificity). It doesn't seem to disturb them that their conclusions are at considerable variance with the contents of of a report about that screening tool (pdf) from Baron-Cohen's research centre (HT to correspondent who sent me this link). The concluding sentiment and sentence are breathtaking for their complete lack of any awareness of the issues that fuelled the strong response of so many readers plus the introduction of a novel definition of accurate.
And the central point, in my view, is that the leaked story of the apparent rise in the prevalence of autism was a perfectly legitimate and accurate story in its own right, which did not need the introduction of the MMR theory.
Oh misery me! Omnes plecum plangite! However, if the Guardian/Observer offered a completely inadequate apologia pro ephermeris sua (HT Kristina Chew) then The Independent is just vox stulti. They offer yet more publicity for the Fletcher family who are caught up in an MMR action against the UK Government (also recently featured in the Daily Mail) and are stalwart supporters of Dr Andrew Wakefield. That is probably understandable and gives the sort of dramatic colour that newspapers favour. It is the coverage of the 'factual information' that is peculiarly irritating.
"There is now overwhelming evidence that MMR does not cause autism," says the DoH in its official guidance and almost every medic and scientist in the country agrees, at least in public. Tomorrow, the one doctor who has been prepared to challenge this universal wisdom will appear before a disciplinary hearing which may lead to his being struck off.

It is nine years since Dr Andrew Wakefield raised doubts about MMR, suggesting it may be linked to bowel disease and – by extension – autism. His paper in The Lancet medical journal – and the media firestorm that followed – triggered one of the great public-health scares of modern times. Who should parents believe? The experts and officials who insisted Dr Wakefield was scaremongering? Or the lone doctor who said the needle might destroy their baby's chance of a healthy life?
The sympathies of the writer seem to surface in the juxtaposition of the acknowledgement that MMR uptake declined with some claims that don't make sense as written (could be bad editing):
Alarmed health experts have warned many times that a deadly measles epidemic may follow. It never has and relentless government information campaigns have slowly regained the trust of some parents. And questions have been asked about Dr Wakefield's methods and his motives. Critics say he is a peddler of bad medicine and hope that the fears he has raised will now be killed off once and for all.
It look like the writer claims that health experts indulged in shroud waving but they have the money to fund information campaigns so some parents trust them because their opinion has been bought; there is no possibility that the parents have been reassured by some decent science arguments? The "peddler of bad medicine" is not a useful way of describing all of the issues involved and I haven't seen any criticisms expressed in that way. By the by, from the paucity of information about Profs Walker-Smith and Murch, either they are keeping a strategically low profile or they lack the money to hire Wakefield's remarkably effective PR team.

Just in case there hasn't been enough dis-information based on the leaked report and that infamous 1 in 58 estimate, The Independent thinks that we need to see it being inappropriately quoted yet again.
The number of autistic children is far higher than previously thought, it emerged last week. One child in 58 may have a related condition, believe researchers at Cambridge University. The previously accepted figure was one in 100. Professor Simon Baron Cohen of the Autism Research Centre, whose team discovered the high rate, does not believe it is due to the jab. "Evidence does not support the idea that the MMR causes autism," he says. The causes are a mystery, but many believe the neurological condition is genetic and the rise in cases is a result of better and wider diagnosis.
No, no, no. The 1 in 58 does not supplant the 1 in 100 estimate but Baron-Cohen doesn't get to rebut that in situ here which just makes this coverage even worse. It looks as if his reference to "the rise in cases" is tacitly accepting the 1 in 58.

The remainder of the piece is just as irritating.
"If Wakefield is struck off," says John Fletcher, "it will discourage any doctor from asking questions about the safety of vaccines and it will leave the policy making to the government and the pharmaceutical industry. Parents who complain will be disregarded, and the research on better treatment for these children will stop. That is unthinkable."
Unlikely. Wakefield, Walker-Smith and Murch are not embroiled in GMC Hearings because they questioned vaccine safety but because of assorted charges relating to serious ethical irregularities and dishonesty. There are many research projects on the topic of improving education and quality of life for children with autistic spectrum disorders.
Government arguments for MMR have always been based on civic responsibility: the jab is the best way to protect society. Yes, there is a "very, very small risk" of some kind of reaction, as one expert put it last week, but that is the case with all vaccines. However, parents act primarily on behalf of their child, not society. For those who visualise a doctor hovering over their baby with a needle, the words "very, very small" can sound like a whisper, and the word "risk" like a warning shout.
MMR: The Facts does make a hidden reference to civic responsibility but it is 1 point in a list of 10 that does include benefits for the individual child (albeit this could be a better list). The fact that we are all given to irrational fears is not a terribly good reason for acting in accordance with them. I think that it is a tad disingenuous of The Independent to affect ignorance that they and other MSM have disseminated so much information that it feeds this irrationality. A few months ago, Orac was discussing Wakefield's financial benefits from involvement in the MMR litigation in the UK. There is a remarkable comment from a parent in the UK:
...deciding to go with MMR, and taking my son to be vaccinated was still one of the most terrifying things I have ever done. I think there is little that is more horrifying to a parent than the idea that your own actions could directly and irreperably harm your child. I am a rational individual, and a strong proponent of the scientific method, and all that I had read on this subject could still not completely eradicate that fear.
The preponderance of coverage of vaccination issues has resulted in some parents feeling that a routine medical procedure is "terrifying" and the MSM (amongst others) shares responsibility for that.

I'll mention the Mail on Sunday farrago of pseudoscience, pseudoepidemiology and, well, generally, pseuds but I refuse to discuss its version of The truth about MMR because I will lose my will to live. I do recommend: Dr Michael Fitzpatrick MMR and Autism: what parents need to know; Arthur Allen Vaccine; Dr Paul Offit The Cutter Incident: How America's First Polio Vaccine Led to the Growing Vaccine Crisis; for an easy web reference, I like the Science Museum's straightforward coverage in the MMR Files although it could stand some updating.

The belief in a link between MMR-vaccines-mercury-autism has cultish overtones. Most religions have an act of contrition. UK media collectively need to make an act of contrition and perform an act of reparation. The latter, of course, should take the form of some informed coverage. I would nominate Ben Goldacre (who is uncharacteristically/ominously quiet at present) but then what would somebody who is medically qualified and known for promoting the public understanding of science (awards and everything) have to add to this discussion? In the absence of such reparations, I would be grateful for suggestions for penances that are rather more colourful and a touch mediaeval. After all, we needn't be superstitious about events on St. Maximilian Kolbe and Blessed Titus Brandsma Day.

Thanks to Wellcome for use of this open access image.

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