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Does autistic enterocolitis exist?

20 Apr

The piece below is from the blog justthevax, where it ran as “Independent” the Wakefield way (really something for the fail blog). I like this piece because, frankly, I wish I had done it. Catherina takes a look at the exact claims made by Dr. Wakefield’s supporters and shows that they are clearly false.

“Independent” the Wakefield way (really something for the fail blog).

One of the claims that keeps reappearing in the comments sections under articles covering the GMC ruling on Andrew Wakefield and colleagues is that

The key finding (chronic colitis found in ASD children) of Dr. Wakefield’s early case report published in The Lancet in 1998 HAS been independently confirmed by medical researchers in five different countries.

That is a very significant claim. After all, independent confirmation of a recent finding, would make the validity of a finding more likely, and if 6 independent laboratories found the same gut changes in autistic children, then then likelihood that this was a) a fluke or b) made up by Andrew Wakefield would be drastically reduced.

Finally, one of those commenters has posted those ‘independent confirmations’ – so I thought it might be worth having a look at them.

Krigsman, A. (Assistant Professor of Pediatrics, New York University School of Medicine Director of Gastroenterology Services), et al.,Ileocolonoscopy in Children with Autistic spectrum Disorder and Chronic Gastrointestinal symptoms. Autism Insights 2010:2 1-11.

Gonzalez, L., et al., Endoscopic and Histological Characteristics of the Digestive Mucosa in Autistic Children with gastro-Intestinal Symptoms. Arch Venez Pueric Pediatr, 2005;69:19-25.

Balzola, F., et al., Panenteric IBD-like disease in a patient with regressive autism shown for the first time by wireless capsule enteroscopy: Another piece in the jig-saw of the gut-brain syndrome? American Journal of Gastroenterology, 2005. 100(4): p. 979-981.

Balzola, F., et al., Autistic enterocolitis: Confirmation of a new infammatory bowel disease in an Italian cohort of patients. Gastroenterology 2005;128(Suppl. 2);A-303.

Galiatsatos, P., et al., Autistic enterocolitis: Fact or fiction. Canadian Journal of Gastroenterology. 2009;23:95-98.

Let’s look at number 1, Krigsman et al. The name sounds vaguely familiar. In fact, anyone who has read a little about the MMR-autism affair will know Arthur Krigsman as the clinical director of Thoughtful House, which happens to be the same Texas Clinic out of which Andrew Wakefield practises. One editor of “Autism Insight”, the journal in which this “independent confirmation” was published, is Andrew Wakefield (another one the senior author of the study, Carol Stott). Gosh, I bet peer review was harsh for this one.

Gonzales et al, number 2, has been published in “Arch Venez Pueric Pediatr” which stands for Archivos Venezolanos de Puericultura y Pediatría. It was a bit tricky to get my hands on the paper, especially since the citation was not quite right, but I did manage and was not surprised to find that indeed the authors cannot replicate Wakefield’s 1998 “findings” of a distinct autistic enterocolitis, although they do report a higher incidence of gastrointestinal problems in their autistic group.

Balzola et al, number 3, is a case report of one adult autistic patient with inflammed bowel.

Similarly, Balzola et al, number 4, is a meeting abstract (if anyone has access, could they email me that abstract, please) that never saw the light of day as a peer reviewed study.

Finally, number 5, Galiatsatos et al., is a case report, featuring two adult patients with gastrointestinal problems and an ASD diagnosis. The authors call for “more investigations” in their discussion.

So what do we have here? Three (3) genuinely published cases of autistic adults who had consulted a doctor for gastrointestinal problems and were found to have gastrointestinal problems. One conference report from April 2005 that has not gone through peer review and has not appeared in a real journal in the 5 years since the conference. One real study looking at over 50 autistic children which does not confirm Wakefield’s findings. And finally, one study by Wakefield’s buddies in a freshly founded journal run by Andrew Wakefield and his buddies, to say that their buddy Andy was really right all along – how is that for “independent” confirmation?!

Brian Deer discusses Andrew Wakefield’s “autistic enterocolitis” in the BMJ

15 Apr

Before the General Medical Council reached a verdict on Dr. Wakefield, Brian Deer was promising that he was going to report on the data Dr. Wakefield used for his now retracted Lancet paper. We were told that he would give a first time ever view of a journalist allowed to check the facts on a scientific research paper.

After the GMC verdict was handed down, I watched the Sunday Times for such an article. I waited. Well, the wait is over. And it isn’t in the Times. Mr. Deer reports his findings in the British Medical Journal (BMJ).

Although much of the attention on Dr. Wakefield’s work has centered on the possible MMR connection, the topic of a “new syndrome” called “autistic enterocolitis” was proposed in that paper. In Wakefield’s “autistic enterocolitis” under the microscope, Mr. Deer takes a closer look at that claim. He does what is very rarely done: he obtained original data used for the study and obtains expert opinions on that data.

In his introduction, he notes the “new syndrome” and the MMR angles of the Lancet paper. Citing the press release from the Lancet paper:

“Researchers at the Royal Free Hospital School of Medicine may have discovered a new syndrome in children involving a new inflammatory bowel disease and autism,” the institution announced in a press release in February 1998. “Their paper . . . also suggests that in a number of cases the onset of behavioural symptoms was associated with MMR vaccination.”

Mr. Deer notes that before any patients were investigated, Dr. Wakefield was already proposing in a submission to the Legal Aid Board that such a new syndrome exists and it is linked to regression in children.

“In contrast to the IBD cases, which have a prima face [sic] gastrointestinal pathology, children with enteritis/disintegrative disorder form part of a new syndrome,” said Wakefield and the lawyer in a confidential submission for legal aid funding for the project in June 1996, before any of the 12 children in the paper had been investigated. “Nonetheless, the evidence is undeniably in favour of a specific vaccine induced pathology.”

For emphasis:

The evidence was “undeniably in favour of a specific vaccine induced pathology”.

Before children were investigated.

That on its own is huge. And, from what I can tell, not consistent with the image Dr. Wakefield is portraying in the alternative media.

That said, was there evidence of this “new syndrome”?

But when the children were brought in to the Royal Free for ileocolonoscopy, between July 1996 and February 1997, a snag in Wakefield’s project emerged. The hospital’s pathology service repeatedly judged colonic biopsy samples to be unexceptional, and thought bowel disease was a possibility in only one child.

The Royal Free’s own pathology service thought that the biopsy samples were unexceptional.

How can Mr. Deer make such a claim? He obtained data from the children’s records from their investigations at the Royal Free. Unfortunately, the actual samples are no longer available, but the reports are, and Mr. Deer submitted these to experts to review:

The biopsy slides are no longer available, according to one of the paper’s authors, Professor Amar Dhillon, but the GMC obtained all but one of the hospital pathology reports, and for the missing case I obtained the discharge summary. I passed the summary and reports to specialists for their reaction. They concluded that most of the 11 children reported as having non-specific colitis in the Lancet paper had been reported by the Royal Free as having normal pathology.

One expert reviewer stated:

“In the present reports and patients, overall, it is my impression that 8 of the 11 [for whom pathology reports were available] were normal,” Karel Geboes, a professor in the gastrointestinal pathology unit of the Catholic University of Leuven, Belgium, told me.

How does this compare to what was reported in the Lancet?

Eleven of the 12 children were said to have “non-specific colitis”: a clinically significant inflammation of the large bowel. In all 11, it was said to be “chronic,” while in four it was reported as both “acute and chronic.”

In other words, the report in the Lancet is not consistent with how experts interpret the pathology reports.

Mr. Deer further notes:

In fact the [Royal Free’s pathology] service identified findings suggestive of possible inflammatory bowel disease in only one of the 12 children. “The mild patchy generalised increase in inflammatory cells with lymphoid aggregates and follicles is not very specific but could be in keeping with low grade quiescent inflammatory bowel disease,” it reported for child 2. But this inflammation resolved after two months’ enteral feeding with a product now marketed as Modulen. A repeat ileocolonoscopy found no abnormality, and a food intolerance was diagnosed.

Yes, it appears that the pathology service, at Dr. Wakefield’s own hospital, at the time of the investigation, didn’t find evidence of abnormalities reported by Dr. Wakefied’s team.

In the GMC hearing, one of the co-authors on the Lancet paper, Dr. Susan Davies, discussed her concerns about the changes in the findings from normal to abnormal at the time of the investigation.

These changes—from normal to abnormal, or from healthy to diseased—had also raised concern in the mind of at least one of the paper’s authors. In September 2007, Davies, the lead histopathologist for the Wakefield project, was examined at length before the panel. “When you were given a draft of the Lancet paper, did you read it?” she was asked by Sally Smith QC, for the doctors’ regulator.
“Yes,” Davies replied.
“What was your overall view of the terminology used in relation to the histology findings in the Lancet paper, just when you read the paper?”
“I was somewhat concerned with the use of the word colitis.”
“First of all, what did you understand that word to mean?”
“I personally use that terminology, ‘colitis,’ when I see active inflammation, or a pattern of changes which suggest a specific diagnosis, and it was not my impression that the children coming through in the spasmodic way that they had, I [sic] had formulated some distinct pattern warranting that terminology.”

If even a co-author was concerned, and the hospital’s pathology reports don’t support the diagnosis of colitis, the obvious question would be: how did the paper reach it’s conclusions?

The answer appears to be that the results underwent a second review. This second review is discussed in the Lancet paper, but there is no mention of the review changing the interpretation of the data,

Mr. Deer poses an important question:

[H]ow many peer reviewers would have felt comfortable approving the paper if they had known that the hospital pathology service reported biopsy specimens as largely normal, but they were then subjected to an unplanned second look and reinterpreted?

Which we are fortunate enough to have answered. Mr. Deer was able to obtain an answer from one of the peer reviewers:

“I’m surprised the GMC didn’t make more of this,” said David Candy, paediatric gastroenterologist at St Richard’s Hospital, Chichester, who reviewed the paper in 1997. “That’s an example of really naughty doing—to exclude the original pathology findings.”

“Really naughty doing”. Not very clinical but I think it tells the story well.

Is it possible that the hospital’s pathology service missed the condition? Apparently at least one author (Dr. Walker-Smith, a co-defendant with Dr. Wakefield in the GMC hearings) noted this in his GMC testimony:

And how bad was this “colitis,” such that the hospital’s pathology service didn’t spot it as the children came through? Walker-Smith told the GMC panel that he had “concerns” about the service and its ability to detect inflammation.

In his report, Mr. Deer counters with:

Yet inflammatory indices that were not reported in the Lancet paper, including serum C reactive protein concentrations and other blood tests, were almost all within normal ranges for the 12 children.6 And as an alternative explanation for any inflammation that was present, nearly all of the children had constipation with megarectum16 (unreported in the paper), which specialists say can cause cellular changes.

Mr. Deer attempted to speak with Dr. Dillhon, a co-author on the Lancet paper. Dr. Dillhon viewed the slides made from the samples taken from the children, and he graded them with Roman numerals to rank the degree of inflammation. At some point, those Roman numerals were translated into “non-specific colitis”.

So who translated these scores on the grading sheet into findings of “non-specific colitis” in the paper? Dhillon says it wasn’t him. He says he would like to see the slides again, but they are missing from the Royal Free laboratory. “He [Dhillon], Andrew Anthony, and Wakefield all looked at them,” I was told, on Dhillon’s behalf, by a senior member of staff at the Royal Free. “Andy [Wakefield] then synthesised their results into what appeared in the paper.”

But still, according to Mr. Deer, “…how the Roman numerical scores, histopathological gradings for a variety of sites in the colon, became the “colitis” findings might, under such circumstances, be anybody’s guess.”

Mr. Deer posits a possible scenario, based on Dr. Wakefield’s complaint to the press complaints commission:

Wakefield wrote: “When the biopsies were reviewed and scored by experts in bowel pathology—namely, Drs Dhillon and Anthony—these doctors determined that there was mild inflammation in the caecum, ascending colon, and rectum,” he said. “This was correctly reported as non-specific colitis in the Lancet.” In other words, it looks like it was Wakefield who translated the scores.

A companion editorial was published in the BMJ by Prof. Sir Nicholas Wright, warden, of Barts and the London School of Medicine and Dentistry, Queen Mary University of London. He lists in his conflict of interest statement: “He has provided expert opinion in the case of Wakefield v GMC and acted as a character witness for Professor John Walker-Smith.”

His editorial:

Does autistic enterocolitis exist?
Despite the retracted Wakefield study, questions remain

His conclusion:

Is autistic enterocolitis a histopathological entity or even an entity at all? In view of the lack of data and the entrenched position of many of the protagonists and antagonists, any firm conclusion would be inadvisable. The expert review, referenced by Deer, concludes that key areas such as the prevalence and best treatment of gastrointestinal disorders in people with autistic spectrum disorders are incompletely understood, and that evidence based recommendations are not yet available. We should remember, as recent experience in several fields has shown, that although science has its defects, it is a self correcting process. Time is, perhaps, the wisest counsellor of all. In the meantime, this case offers a salutary reminder for researchers and journal editors alike that coauthorship means bearing responsibility for what is written.

First, I would submit that Dr. Wright is not being clear on the subject. It is not whether autistics have a greater prevalence of GI issues, or whether there is a difference in the treatment for autistics. The question is whether there is a specific entity which is unique to autistics: autistic enterocolitis. Further, it is also a primary question whether “autistic enterocolitis” is causal in autism. While one can hide behind the “you can’t prove a negative” shield, the answers at present appear to be no to both questions.

Second, the idea that science is a self correcting process is often times true. In this case, it clearly is not. The science, the Lancet paper, was not corrected through science but through investigative journalism. Without the stories in The Sunday Times, Dr. Wakefield’s “science” would likely still be in the official record of The Lancet. Much more, the Lancet study and the presumed expertise of Dr. Wakefield would have likely been key in litigation in the UK and the US. Without Mr. Deer’s continued scrutiny, the facts behind the research into the Lancet paper, specifically that the pathology reports on those children were not consistent with the findings of the paper, would almost certainly not have come to light.

Returning to Mr. Deer’s article, he concludes:

So what should we make of all this? Now the Lancet paper is retracted, its findings don’t officially exist. And, if Dhillon is right in saying the slides can’t be found, the ultimate proof is missing. All we have are the pathology reports, which independent specialists seem to agree are largely unremarkable. “They wanted this bad,” commented Tom MacDonald, dean of research at Barts and the London School of Medicine and coauthor of Immunology and Diseases of the Gut. “If I was the referee and the routine pathologists reported that 8/11 were within normal limits, or had trivial changes, but this was then revised by other people to 11/12 having non-specific colitis, then I would just tell the editor to reject the paper.”

Clearly the Lancet paper should have been rejected. But this isn’t just a scientific paper that made a bad conclusion. This paper impacted multiple families inside the autism communities to believe that their child’s autism was caused by MMR. This paper led many families in the autism communities to apply poorly researched “therapies” to their disabled children. This paper led many families to stop vaccinating their children, leading to outbreaks of measles in the UK and elsewhere.

It is easy to go through Mr. Deer’s paper in the BMJ point by point in a clinical fashion, noting how the research went awry, showing that “autistic enterocolitis” has what appears to be no founding in science. But how does one express the reaction to so much damage caused by Dr. Wakefield’s investigation?

Of course, a further question I have and I bet I share with Dr. Wakefield’s supporters is this: is Brian Deer finished or is there even more yet to be unearthed in this sad tale of research gone awry?

With the facts against them Dr. Wakefield’s supporters appeal to emotion

3 Feb

I should stop being shocked and amazed at how little groups like the Age of Autism blog think of their readership. Sorry to put it so bluntly, but it is pretty clear that they expect us all to just read what they have to say and never go to the original sources and think for ourselves.

Case in point, the GMC hearing on Dr. Andrew Wakefield. Dr. Wakefield was guilty of ethical violations in the treatment of his disabled patients. Not once, not twice but many many times. But you wouldn’t know that to read some of the reports on the blogs and even a couple in newspapers.

We have the NAA SafeMinds and TACA telling us all about how bad this ruling is. We have been told that there was “false testimony”.

OK, take a look at the actual charges. Just for a moment. Here are a few examples

1) Dr. Wakefield took money from the Legal Aid Board (LAB) for procedures paid by the NHS. He then diverted some of the LAB money to other projects.

2) Dr. Wakefield got ethical permission to do his study in December 1996, only on patients enrolled after that date. However, he had already started research on children. Here are two examples:

Child 2 had an MRI, colonoscopy and lumbar puncture in September of 1996.

Child 1 was also a research subject without ethical approval. Tests were performed which were not in the clinical interests of the child.

3) For people who promote the myth that “the only thing he did was start early”, note that Dr. Wakefield’s team did invasive tests that were not called for. For example:

Child 3 was also a research subject without ethical approval, having started before the approval. He underwent a lumbar puncture even though: “The Panel has taken into account the fact that there is no evidence in Child 3’s clinical notes to indicate that a lumbar puncture was required.”

Was this the result of some “false testimony? According to the GMC ruling, experts on both sides stated that the lumbar puncture was not clinically indicated.

Experts on both sides, Professor Rutter and Dr Thomas both considered that such a test was not clinically indicated.

Dr. Thomas is not accused by the defenders of Wakefield as “giving false testimony”.

The above are only a few of the examples of clear misconduct on the part of Dr. Wakefield.

How many times must a man be found guilty of not doing what was in his patients’ clinical interests before we are allowed to consider him as, well, someone who doesn’t always put his patient’s clinical interests first?

Kim Stagliano has taken to the Huffington Post with “The Censorship of Autism Treatment“. No mention of the actual charges. No mention of the fact that Andrew Wakefield was guilty. No mention of the fact that Andrew Wakefield’s research efforts for the past 12 years have centered on repairing his own damaged reputation, not on autism treatment.

Can you find a single mention of the word “ethics” in her post? How about any comment about the actual charges levied against Dr. Wakefield?

You know you are in trouble just with the title from this story: MMR doc’s just guilty of caring . At least that article makes one clear statement:

It [the GMC ruling] focused on the methods of research used, some of which were undoubtedly questionable, but which were performed in the name of finding solace for desperate parents convinced their children had changed for ever following their one-size-fits-all MMR injection.

Yes, you can be unethical if you are “finding solace for desperate parents”.

A blog post by the National Autism Association stated:

“Many parents of children with autism view the GMC investigation as little more than character assassination of a physician brave enough to investigate controversial issues”

Well, not this parent. Anyone who paints the GMC investigation as “character assassination” didn’t read the ruling. Seriously, trying to dismiss this fact-filled ruling as “character assassination” is just plain bizarre.

another post comments, discussing the work Dr. Wakefield’s team performed on his study subjects:

the procedures involved were routine

and

No children were harmed and no parent or guardian has complained about the care these three men provided.

Lumbar punctures are hardly “routine”. Further, there is no reason to do them if not clinically indicated. Colonoscopies are not routine, especially in patients whose symptoms don’t warrant them. Say, as in Child 1.

One child suffered a perforated bowel (in 12 places!). His family won a lawsuit against the Royal Free hospital.

High Court papers alleged that the colonoscopy procedure performed on Jack in 1998 was ‘not clinically indicated or justified’. They also claimed the ‘principal reason’ for the surgery was to further research into links between autism and bowel conditions rather than Jack’s clinical needs.

How does that not count as not “harmed”? Is it because he wasn’t one of the original 12 from the study in The Lancet?

The behavior of the Wakefield supporters is totally predictable. They have no science. They have no first (or second) tier researchers. They rely heavily on Dr. Wakefield. Who else has the perceived stature of Dr. Wakefield for them? When Brian Deer broke the story that Dr. Wakefield may have “fixed” data in his study last year, there was an immediate reaction from the Wakefield supporters: give him faux awards! Make him the keynote speaker at their conventions!

For the past year the message has been “Dr. Wakefield has not been discredited”. They’ve lost that now.

We’ve been warned that they are bringing out their big guns. Yes, David Kirby will blog about this on the Huffington Post. With apologies to Mr. Kirby, but when he’s their “ace in the hole”, you know they don’t have much.

As I finished this, David Kirby came up with his post: “The Lancet Retraction Changes Nothing”. Joining in the style of the times, Mr. Kirby also ignores the actual GMC ruling. Nothing that actually defends Dr. Wakefield against the real charges.

Seriously, go read for yourself. It’s David Kirby with his usual talking points and straw men.

I hope David Kirby is wrong. I hope that things have changed. I hope that the future is a world where the loudest voices in the autism communities fight for a better life for autistics, rather than for a political goal of recognition for bad science, badly done.

I hope.

How Anti-Vaccine ‘Science’ Holds Back Credible Research

4 Jan

An expert panel says there’s no rigorous evidence that digestive problems are more common in children with autism compared to other children, or that special diets work, contrary to claims by celebrities and vaccine naysayers.

This is a totally non contentious piece of work. The panel examined all _credible_ research into the subject and decided there simply wasn’t anything available to support the idea of a things such as autistic entercolitis – a faux syndrome pushed by the section of autism anti vaxxers who believe Andrew Wakefields fake science.

Take careful note though of what they are saying:

1) That there’s no credible evidence. Parental anecdote is not credible evidence.
2) Thats autistic children may well have gut issues and that if they do they should be treated medically.
3) That special diets show no eficacy in _treating autism_ .

The issue for me therefore is that when autistic kids have gut issues they need to be treated properly by medical staff. This means making appointments that allow for the special needs of autistic people (either first in the day or last in the day to avoid waits, quiet waiting rooms with appropriate distractions and most of all well trained staff who won’t say caustic things to parents).

A TACA representative is quoted as saying:

“I’m filled with hope after reading this report,” said Estepp of the support group Talk About Curing Autism. “I wish this report would have come out 10 years ago when my son was diagnosed.”

Ironically, TACA who support the work of Andrew Wakefield probably _could_ have had a report like this ten years ago if the work of Andrew Wakeild hadn’t been so heavily promoted by groups like TACA.

The new report says the existence of autistic enterocolitis “has not been established.” Buie said researchers and doctors have avoided digestive issues in autism because of their connection with Wakefield’s disputed research, which set off a backlash against vaccines that continues to this day.

Quite understandably, researchers didn’t want to get involved in a field tainted by a person like Wakefield and his demonstrably false and disproven idea that MMR causes or contributes to autism. If they did, when they came out with science that contradicted Wakefield they would be subject to the same sort of hate crimes currently perpetrated against numerous other scientists such as Paul Offit who has recieved death threats. Who would want that?

Quite simply – if people like Wakefield admit their error and then shut up, more science will be done that will reveal more results groups like TACA may well support.

Are kids with autism more likely to have gastro issues?

2 Oct

Interesting new paper in Pediatrics:

OBJECTIVE: To determine whether children with autism have an increased incidence of gastrointestinal symptoms compared with matched control subjects in a population-based sample.

So do autistic kids have more constipation, diarrhoea, reflux, bloating or feeding issues? The conclusion was:

As constipation and feeding issues/food selectivity often have a behavioral etiology, data suggest that a neurobehavioral rather than a primary organic gastrointestinal etiology may account for the higher incidence of these gastrointestinal symptoms in children with autism.

Which is self explanatory but (in my opinion) badly worded. Are the authors saying that _all_ the gastro symptoms they looked at have behavioural aetiology or just constipation and feeding issues? And if the latter, whats their conclusions about the others?

The answer can be found in the results section:

Significant differences between autism case and control subjects were identified in the cumulative incidence of constipation (33.9% vs 17.6%) and feeding issues/food selectivity (24.5% vs 16.1). No significant associations were found between autism case status and overall incidence of gastrointestinal symptoms or any other gastrointestinal symptom category.

OK so for the other three no real difference was found between autistic kids and non autistic kids. Thats why they weren’t mentioned in the conclusion.

Constipation (as is bloating and diarrhoea) is regularly quoted by the anti-vaccine/autism lobby as being part of a set of gastro symptoms ’caused’ by vaccines, along with their child’s autism. This paper addresses that fallacy directly and clearly shows that three issues are no different than non autistic kids and two may have a behavioural cause.

What are the allegations against Dr. Wakefield?

16 Sep

Dr. Andrew Wakefield, not of Thoughtful House in the U.S., has recently been called before the General Medical Council for a “fitness to practice hearing”. The allegations stem from activities related to his research of about 10 years ago on children (many autistic).

I recently discussed two of incidents being investigated: a birthday party where blood was drawn from typically developing children (for controls) and activities related to his invention and the subsequent patent his hospital (the Royal Free) applied for. I found it interesting to see these layed out, so I decided to post them here for others to read as well.

These are allegations. The process has not concluded, nor has any decision been reached.

This is a short version. A detailed list (93 pages) can be found on Brian Deer’s website. Note that these 93 pages include allegations against Doctors Murch and Walker-Smith.

Dr Andrew WAKEFIELD GMC Reference number: 2733564

Professor John WALKER-SMITH GMC Reference number: 1700583

Professor Simon MURCH GMC Reference number: 2540201

The GMC’s statutory purpose is to protect, promote and maintain the health and safety of the public by ensuring proper standards in the practice of medicine.

We investigate complaints about individual doctors in order to establish whether their fitness to practise is impaired and whether to remove or restrict a doctor’s registration.

The GMC does not regard its remit as extending to arbitrating between competing scientific theories generated in the course of medical research.

The following is a summary only of the allegations which will be made before the Panel at the forthcoming hearing.

The Panel will inquire into allegations of serious professional misconduct by Dr Wakefield, Professor Walker-Smith and Professor Murch, in relation to the conduct of a research study involving young children from 1996-98.

Dr Wakefield, Professor Walker-Smith and Professor Murch, were at the relevant times employed by the Royal Free Hospital School of Medicine with Honorary Clinical contracts at the Royal Free Hospital.

It is alleged that the three practitioners were named as Responsible Consultants on an application made to the Ethical Practices Committee of the Royal Free Hospital NHS Trust (“the ethics committee”) in 1996 to undertake a research study involving children who suffered from gastrointestinal symptoms and a rare behavioural condition called disintegrative disorder. The title of the study was “A new paediatric syndrome: enteritis and disintegrative disorder following measles/rubella vaccination”. The Panel will inquire into allegations that the three practitioners undertook research during the period 1996-98 without proper ethical approval, failed to conduct the research in accordance with the application submitted to the ethics committee, and failed to treat the children admitted into the study in accordance with the terms of the approval given by the ethics committee. For example, it will be alleged that some of the children did not qualify for the study on the basis of their behavioural symptoms.

It is further alleged that the three practitioners permitted a programme of investigations to be carried out on a number of children as part of the research study, some of which were not clinically indicated when the Ethics Committee had been assured that they were all clinically indicated. These investigations included colonoscopies and lumbar punctures. It is alleged that the performance of these investigations was contrary to the clinical interests of the children.

The research undertaken by the three practitioners was subsequently written up in a paper published in the Lancet in February 1998 entitled “Ileal-Lymphoid-Nodular Hyperplasia, Non-Specific Colitis and Pervasive Developmental Disorder in Children” (“the Lancet paper”).

It is alleged that the three practitioners inaccurately stated in the Lancet paper that the investigations reported in it were approved by the ethics committee.

The Panel will inquire into allegations that Dr Wakefield and Professor Walker-Smith acted dishonestly and irresponsibly in failing to disclose in the Lancet paper the method by which they recruited patients for inclusion in the research which resulted in a misleading description of the patient population in the Lancet paper. It is further alleged that Dr Wakefield gave a dishonest description of the patient population to the Medical Research Council.

The Panel will inquire into allegations that Dr Wakefield and Professor Walker-Smith administered a purportedly therapeutic substance to a child for experimental reasons prior to obtaining information about the safety of the substance. It is alleged that such actions were irresponsible and contrary to the clinical interests of the child.

The Panel will inquire into allegations that Dr Wakefield was involved in advising solicitors acting for persons alleged to have suffered harm by the administration of the MMR vaccine. It is alleged that Dr Wakefield’s conduct in relation to research funds obtained from the Legal Aid Board (“LAB”) was dishonest and misleading. It will be alleged that Dr Wakefield ought to have disclosed his funding from the LAB to the Ethics Committee but did not.

The Panel will inquire into allegations that Dr Wakefield ordered investigations on some children as part of the research carried out at the Royal Free Hospital from 1996-98 without the requisite paediatric qualifications to do so and in contravention of his Honorary Consultant appointment.

The Panel will inquire into allegations that Dr Wakefield failed to disclose his involvement in the MMR litigation, his receipt of funding from the LAB and his involvement in a Patent relating to a new vaccine to the Editor of the Lancet which was contrary to his duties as a senior author of the Lancet paper.

The Panel will inquire into allegations that Dr Wakefield acted unethically and abused his position of trust as a medical practitioner by taking blood from children at a birthday party to use for research purposes without ethics committee approval, in an inappropriate social setting, and whilst offering financial inducement.

We cannot guarantee that all those wishing to attend the hearing will be able to do so, as seating is limited. If you plan to attend the hearing please email the GMC press office press@gmc-uk.org. In the event that we have to allocate seats those people who have notified the press office will be seated before others.
-Ends-

Greater detail can be found in this document, hosted on Brian Deer’s website. It is 93 pages of details of the allegations against Dr. Wakefield, Dr. Walker-Smith and Dr. Murch.

Autism Omnibus: Hazelhurst appeal denied

29 Jul

The Autism Omnibus Proceedings is, for better or worse, one of the big stories in the world of autism news. Hearings have been held, using the best science and arguments that could be brought to bear. The two theories were (1) does MMR cause autism and (2) does thimerosal cause autism.

Each theory was tested using three “test cases”. Essentially, three trials for each theory, each discussing an individual child plus arguments on “general causation”.

So far, the decisions are only in on the MMR question
. The answers were clear and decisive: “this is not a close case”.

The Omnibus decisions are not the end of the vaccine/autism lawsuits. Not by a longshot. The first step was an appeal, and the first appeal has been decided.

Here is the conclusion of the Judge who heard the appeal for the Hazelhurst case:

In hearing this appeal, the court is not without sympathy for Yates, the Hazlehursts, and the other children and families dealing with autism and autism spectrum disorders. And this court, like the special master, acknowledges both the burdens many of these families have faced and the tremendous love and support they have shown their children. The facts, however, do not support petitioners’ appeal and we have no choice but to deny their motion. Accordingly, for the reasons set forth above, the special master’s decision of February 12, 2009, is AFFIRMED.

I.e. the appeal failed. The decision stands. The Court holds that MMR does not cause autism.

The judge’s decision in the appeal gives a good summary of the original case. If you want to read about the Hazelhurst case, it would be the first place I would send you.

From the appeals judge’s ruling, here are the two “cardinal” flaws in the petitioner’s case:

1) First, the special master explained that petitioners’ experts based their opinions on the characteristics of the “wild-type” measles virus rather than on the characteristics of vaccine-strain measles, despite the fact that the measles vaccine is distinguishable from the wild-type measles virus in several key respects.

2) Second, the special master observed that petitioners’ experts further based their opinions on studies (detecting the presence of the measles virus in the gut tissue of autistic children) that the special master found to be unreliable.

The special master considered the presence of the measles virus in the gut to be the “linchpin” of the petitioner’s case. In other words, they needed to show reliable data or studies demonstrating that the virus was still in the tissues of the children long after the vaccination.
The two studies they had to rely on were (a) that by Dr. Wakefield’s team and (b) an unpublished study by Dr. Stephen Walker, presented as a poster at the 2006 IMFAR conference. Well, the Wakefield study was pretty well discredited, and the Walker study was never published.

In the appeal, the Hazelhurst’s lawyer argued that the testimony of Dr. Stephen Bustin should not have been considered. Amongst the arguments were that some of the information was submitted at the last minute.

No arguments were made that Dr. Bustin was wrong in his analysis of the O’Leary laboratory. That was one of those strange moments in law–no one challenged Dr. Bustin on being right. The judge hearing the appeal noted that the rules for the Vaccine Court are different from a typical court of law. Specifially, the rules are designed specifically to allow more information in to inform the Special Master. The judge further noted that under the typical rules of evidence, the Walker study would never be admitted anyway.

If you haven’t read about Dr. Bustin’s testimony, you should consider it now. Dr. Bustin basically discredited the entire “persistent measles in the gut” idea by showing that the O’Leary laboratory that made tests had serious methodological flaws and, basically, couldn’t make the tests at all.

The Hazelhurst’s lawyer then argued that the Special Master failed to include all the relevant evidence., In specific, that the Walker study wasn’t given due weight.

Again, one of those strange moments in law. The laywers moved directly from trying to get the Special Master to exclude evidence that was clearly relevant, to claiming that the Special Master had to include all relevant evidence. I guess that’s why I am not a lawyer. I couldn’t pull that off with a straight face.

As it turns out, even the witness for the Hazelhurts’ side stated that the Walker study wasn’t reliable:

Respondent additionally notes that Dr. Hepner herself acknowledged that the preliminary data from the study was “not useful at this time” (Cedillo Tr. at 682), declined to draw any conclusions about the biological significance of the Walker group’s findings (Cedillo Tr. at 682), and identified what respondent describes as several significant drawbacks to the study, including that the experiments had not been “blinded”28 and had lacked negative controls.

So, it is rather moot as to whether the Walker study was considered, since it doesn’t really provide substantial evidence to support the MMR theory.

The third main argument used in the appeal was that the Special Master failed to decide on a “critical issue”. Namely, whether regressive autism exists as a separate phenotype.

The Special Master wrote in his decision, and the appeals judge agreed: since the decision held that MMR doesn’t cause autism, there was no point in deciding on the question of regressive autism as a separate phenotype.

Given that the expert testimony was against this idea, it is probably better for the petetioners that this question was left unanswered.

The main result is, of course, the original decision was upheld. Looking forward, it doesn’t look good for the MMR theory to win in civil litigation from my perspective. The Bustin testimony is very damning to the little evidence there is, and that will be allowed in a civil case. The Walker study, however, will almost certainly not be allowed as it is unpublished and has severe limitation

Autism and Gastrointestinal symptoms: two new studies

28 Jul

Autism and poop. You hear those two words in the same sentence a lot on the net. People have been asking for studies on whether autistics have a higher incidence of gastrointestinal (GI) problems for a long time. Well, two papers came out in the last week with answers…and many parents are not happy.

The two papers are:


The early stool patterns of young children with autistic spectrum disorder

by B Sandhu, C Steer, J Golding, A Emond of the University of Bristol

and

Incidence of Gastrointestinal Symptoms in Children With Autism: A
Population-Based Study

by Samar H. Ibrahim of the Mayo Clinic.

The Bristol group’s study came out last week. Given that the Mayo Clinic study was on the way, I figured I’d wait and blog them both at the same time. Actually, I considered not blogging them at all. These papers are more nails in the coffin for Andrew Wakefield’s hypothesis that MMR causes “autistic enterocolitis” and the belief by many that this drove much of the “autism epidemic”. But, tired as that story is, the question of whether autistics have GI problems at a higher rate is important and worth discussing.

The Bristol study has free pdf access. Not so the Mayo Clinic study: abstract only, but I have a copy. Rather than go through the studies in detail (if you are that interested you will likely read the paper for yourself), let’s just look at the results and conclusions sections of the abstracts:

Bristol group:

Results: Comparison of the ASD and control group during the first 3.5 years of life showed no major differences in stool colour or consistency, or in frequency of diarrhoea, constipation, bloody stools or abdominal pain. The ASD children had similar stool frequency up to 18 months, but there was a trend for ASD children to pass more stools at 30 months (OR 3.73, 95% CI 1.11 to 12.6; p=0.004) and at 42 months (OR 6.46, 95% CI 1.83 to 22.7; p,0.001), although only three children passed more than 4 stools/day. Repeating the analysis on only those cases diagnosed as having classical childhood autism resulted in very similar findings.

Conclusions: During the first 42 months of life, ASD children had a stool pattern that was very similar to that of other children, apart from a slight increase in stool frequency at 30 and 42 months. There were no symptoms to support the hypothesis that ASD children had enterocolitis.

Mayo Clinic:

RESULTS: Subjects were followed to median ages of 18.2 (case subjects) and 18.7 (control subjects) years. Significant differences between autism case and control subjects were identified in the cumulative incidence of constipation (33.9% vs 17.6%) and feeding issues/food selectivity (24.5% vs 16.1). No significant associations were found between autism case status and overall incidence of gastrointestinal symptoms or any other gastrointestinal symptom category.

CONCLUSIONS: As constipation and feeding issues/food selectivity often have a behavioral etiology, data suggest that a neurobehavioral rather than a primary organic gastrointestinal etiology may account for the higher incidence of these gastrointestinal symptoms in children with autism.

Or, to put in a single sentence: there is no evidence that children with autism have GI problems at a greater rate than the general public.

How about repeating that with emphasis: there is no evidence that children with autism have GI problems at a greater rate than the general public. They are not saying that there are no children with autism and GI issues. Quite the contrary. You wouldn’t know that to read some comments on the internet about these studies.

I’m a little surprised by these results. No, I don’t think that Wakefield was right. But, I wouldn’t be surprised if children with autism have other medical concerns at higher rates. Also, there were two abstracts from IMFAR 2008 that stuck in the back of my mind.

In the first, a team from the University of Connecticut presented a study suggesting that GI issues may be more common in children with children with ASD’s (but at a similar rate to children with other developmental delays).

No evidence for higher rates of gastrointestinal problems in young children with ASDs versus those with other developmental delays

Conclusions: In this sample of young community-based children with ASDs and other developmental delays, no significant group differences in parentally reported feeding problems and gastrointestinal symptoms were found at age two or at age four. Most published research has been conducted at specialty GI or DD/ASD clinics with older children. The results of this study suggest that their findings may not be applicable to young children or to children evaluated in community settings. While GI problems may be increased in children with developmental disorders, we found no evidence that they were specific to autism spectrum disorders.

The second abstract (which later became a paper that was discussed on this blog): David Mandell’s group presented a paper suggesting that a significant fraction of adults hospitalized with schizophrenia diagnoses might actually have autism:

Evidence of autism in a psychiatrically hospitalized sample

Their IMFAR presentation (and later published paper) showed an increased number of GI problems in their adult group. 36% of their adults had GI problems vs. 23% of the general psychiatric hospital population.

Unfortunately, these latest studies are getting the usual “online-autism-parents” community welcome. It follows the same pattern as vaccine/autism research:

a) Ask for studies to be done
b) Studies are done
c) Disagree with the data
d) try to slime the authors

Is it a surprise to anyone that some researchers have opted out of working on autism?

(note: minor edits were made shortly after publishing this article)

Fitzpatrick on the recent Wakefield news

11 Feb

Dr. Michael Fitzpatrick has written the article I wish I could have done–

The MMR scare: from foolishness to fraud?

For anyone looking to understand the timeline and the important questions raised by the Brian Deer investigations, this is a must read.

Dr. Fitzpatrick asks a very important question one must consider–if there is such a big disconnect between what the Wakefield papers report and the actual histories of the children (and the disconnects seem to be very significant), shouldn’t the journals print retractions?

Following Brian Deer’s 2004 revelations about Dr Wakefield’s conflicts of interest arising from undisclosed legal aid funding, 10 of his Lancet co-authors retracted the suggestion of a link between MMR and autism (while upholding the paper’s claim to have identified a distinctive form of bowel inflammation in autistic children). It is now clear that, given the selection bias confirmed by Deer – quite apart from his other allegations – it is not possible to make such a claim on the basis of the Lancet cases. Surely it is now time for the authors to withdraw this paper in its entirety? Perhaps the editor of the Lancet – together with those of the other journals involved – could submit Deer’s allegations to some sort of tribunal, perhaps arranged by the Medical Research Council. For 10 years the world of science has witnessed Dr Wakefield’s foolishness; now it has to ask: has he crossed the line into fraud?

Another good source on the Wakefield studies is in Paul Offit’s book “Autism’s False Prophets“.

You may recall that someone has YouTube’d Autism’s False Prophets. Yes, Story Time with Darwin. If you have problems reading or just want to listen in to the sections on Dr. Wakefield, give “Story Time” a try.

There are a LOT of blogs discussing this. I Speak of Dreams is keeping a running list.

Picking a couple–Respectful Insolence has Why am I not surprised? It looks as though Andrew Wakefield probably falsified his data.

Bad Astronomy has Did the founder of the antivax movement fake autism-vaccine link?

It is worth noting that Dr. Wakefield published a statement of his own as In his desperation, Deer gets it wrong once again.

Dr. Wakefield is in a strange position, since the GMC hearings are still ongoing to determine whether his methods warrant disciplinary action. That said, Dr. Wakefield’s statement responds to a letter that Brian Deer sent prior to publication. It is unclear if this response was sent to Mr. Deer before publication, or if any response was made pre-publication. That said, I wonder why Dr. Wakefield didn’t respond to the specific information from the children’s records which contradicts the story presented in Dr. Wakefield’s papers. What Dr. Wakefield does do is offload responsibility to others–other authors and the parents.

The reporting of the children in the Lancet paper is an accurate account of the clinical histories as reported to Professor Walker-Smith and his clinical colleagues.

One comment that has been made to a blog is worth paraphrasing here. Dr. Wakefield comments in his response:

Finally, I did not “create” a scare but rather, I responded to a scare that parents brought to my attention.

Perhaps Dr. Wakefield didn’t “create” a scare. But, what he did was throw gasoline on a lit match. To stand back and claim no responsibility for burning down the house is quite disingenuous.

Stephen M Edelson gets it wrong, wrong, wrong…

25 Nov

Communication is the members mgazine of the UK’s National Autistic Society. In an issue earlier this year, Mike Fitzpatrick, GP and author had an extract from his latest book published.

The extract touched on chelation and the death of Tariq Nadama.

This prompted a bilious response this month from Stephen M Edelson in this months Communication. The level of ignorance in his response is astounding. I have attached the whole response as a Word document to save me getting accused of taking things out of context. BUt for here, I’ll quote selected parts.

Fitzpatrick has been a longtime, outspoken critic of chelation. (Chelation involves a medication, such as DMPS or DMSA, which removes neurotoxic heavy metals, such as lead and mercury, from the body; it is given under the supervision of a doctor.) If an individual tests with very high levels of one or more heavy metals, chelation is the treatment of choice throughout the medical profession.

If test results indicate very high levels in someone on the autism spectrum, isn’t this person entitled to the same medical care as someone without autism?

This is far too simplistic. Of _course_ if someone on the spectrum has test results that indicate high levels of metals they should have the standard treatment. That is a strawman.

The _point_ is rather more complex that that as Mike mentions in his book and I have blogged about numerous times.

The labs that Mr Edelson and his DAN! colleagues recommend test for levels of metals in people on the spectrum very, very often give false results. Take this extract of the testimony of Dr Jeffrey Brent, a sub-specialty board certified medical toxicologist and the former President of the American Academy of clinical Toxicology.

…I have seen a number of patients now come to me because of these ‘doctor’s data’ type of laboratories which are based on urines – chelated urines – and they always have high leads in their chelated urines and I tell them ‘well, lets just do the gold standard test, lets get a blood/lead level and so far, *100% of the time they’ve been normal*.

So when ‘these Doctors Data’ type of labs do the tests they indicate the need for chelation. When _experts_ in the field such as Dr Brent do the gold standard tests ‘100% of the time they are normal’.

Dr Edelson needs to realise that _that_ is why chelation is an invalid treatment for autism. The fact that when taken to an expert in Chelation and Toxicology, the results usually indicate that chelation is not warranted.

Edelson continues:

In his article, Fitzpatrick brings up the accidental death of Tariq Nadama after chelation treatment. What he does not tell the reader is that Tariq was given the entirely wrong drug, one with a similar name and label that was nearby on the office shelf. Regrettably, these drug errors do
happen in hospitals and doctors’ offices and Fitzpatrick has exploited this unfortunate incident several
times in the past without explaining the complete story. (I have already corrected Fitzpatrick in a previous issue of Communication, and I am disappointed that the editor knowingly allowed such half-truths to be disseminated to NAS’ membership once more.)

Once more, Mr Edelson is quite wrong. Tariq Nadama was not given a drug by mistake ‘with a similar label that was nearby on the office shelf’.

When Dr Roy Kerry (who joined Mr Edelsons loose affiliation of practitioners after the death of Tariq Nadama) was prosecuted for the death of Tariq, the following was admitted by him:

70. Respondent admitted that EDTA is very rare to use on children.

71. Respondent admitted to using Disodium EDTA to chelate Tariq.

72. Respondent stated to Investigator Reiser that Disodium EDTA is the only formula of EDTA he stocks in his office.

73. Respondent admitted that CaNa2EDTA is available but that he has never used this agent.

I would recommend that Mr Edelson reads the entire complaint against Dr Kerry.

Edelson continues again:

Over the past 20 years, scientists have clearly documented immune system dysfunction and gastrointestinal problems associated with autism. Many of these problems can be treated successfully using established medical treatments.

Of course, this is twaddle. I challenge Mr Edelson to provide peer reviewed journal published science to back up these statements. As recently documented by Professor Stephen Bustin, the gastrointestnal ‘link’ to autism is not valid and never was.

I wonder why these treatments that so successfully treat autistic peoples autism have never had one single (that I can find) case study published?

Update 28 Nov 2008

An update from Mike who read some of this thread:

It is true that a number of environmental factors have been identified as causing autism in a small number of cases – these include viral infections (rubella, CMV) and drugs (thalidomide, sodium valproate). What is striking is that ‘over the past decade not a single new environmental factor has been identified as playing a significant role in the causation of autism’ (Defeating Autism: A Damaging Delusion, p 81). Indeed, it would be more accurate to say ‘over the past two decades’. By contrast, over this period there have been dramatic advances in the genetics of autism. Meanwhile intensive researches into alleged vaccine-autism links have failed to confirm any causative relationship.

‘The conviction of the biomedical activists that there must be some environmental explanation for the rising prevalence of autism has grown in intensity in inverse proportion to the emergence of scientific evidence in favour of any particular environmental cause.’