Archive | September, 2007

A bad day for antivaccinationists: Yet another study fails to support an association between vaccines and neurodevelopmental disorders

30 Sep

This blog entry first appeared at Respectful Insolence. It is reproduced here with permission.

A bad day for antivaccinationists: Yet another study fails to support an association between vaccines and neurodevelopmental disorders
By Orac.

I’m almost beginning to feel sorry for the mercury militia.

Think about it. They’ve been claiming for the past several years that the mercury in the thimerosal used as a preservative in childhood vaccines is a cause of autism. If you believe Generation Rescue, A-CHAMP, SAFEMINDS, and various other activist groups, vaccines are the root of all neurodevelopmental evil, culminating in what to them seems to be the most evil of evil condition, autism. Yet, in study after study in the new millennium, no correlation has been found to implicated their favorite bte noire thimerosal, which serves as a surrogate for their general dislike of vaccines in general.

It comes as no surprise, then, that A-CHAMP would want to launch a pre-emptive strike against a large study of thimerosal-containing vaccines that was published in the New England Journal of Medicine today. Blazing out of their website is the headline New CDC Study Falsely Claims Thimerosal is Safe

On September 27, 2007 the New England Journal of Medicine will publish a study entitled, “Early Thimerosal Exposure and Neuropsychological Outcomes at 7 to 10 Years.” For more than two years we at A-CHAMP have been hearing rumors of a new study that “exonerates” thimerosal, despite the fact that the study results were supposed to be kept strictly confidential.

Now the rumors have been turned into hype – another government funded study that tries to spin data and clear thimerosal of any suspicion of causing neurodevelopmental disorders. The study authors claim in their “Conclusions” that “[o]ur study does not support a causal association between early exposure to mercury from thimerosal-containing vaccines and immune globulins and neuropsychological functioning at the age of 7 to 10 years.”

The statement is plainly false. The study’s conclusions do not reflect the study’s data or the limitations of the study,

You’d think that at least A-CHAMP would correct that hanging comma at the end of the sentence there.

Sarcasm aside, the study’s conclusions do reflect the study’s data, quite well, as we will see, and A=CHAMP’s complaints boil down to the usual crank technique of cherry picking the evidence, combined perhaps with sour grapes. Let’s lay the abstract out for all to see before we look at A-CHAMP’s individual points:

Early Thimerosal Exposure and Neuropsychological Outcomes at 7 to 10 Years
William W. Thompson, Ph.D., Cristofer Price, Sc.M., Barbara Goodson, Ph.D., David K. Shay, M.D., M.P.H., Patti Benson, M.P.H., Virginia L. Hinrichsen, M.S., M.P.H., Edwin Lewis, M.P.H., Eileen Eriksen, M.P.H., Paula Ray, M.P.H., S. Michael Marcy, M.D., John Dunn, M.D., M.P.H., Lisa A. Jackson, M.D., M.P.H., Tracy A. Lieu, M.D., M.P.H., Steve Black, M.D., Gerrie Stewart, M.A., Eric S. Weintraub, M.P.H., Robert L. Davis, M.D., M.P.H., Frank DeStefano, M.D., M.P.H., for the Vaccine Safety Datalink Team

Background It has been hypothesized that early exposure to thimerosal, a mercury-containing preservative used in vaccines and immune globulin preparations, is associated with neuropsychological deficits in children.

Methods We enrolled 1047 children between the ages of 7 and 10 years and administered standardized tests assessing 42 neuropsychological outcomes. (We did not assess autism-spectrum disorders.) Exposure to mercury from thimerosal was determined from computerized immunization records, medical records, personal immunization records, and parent interviews. Information on potential confounding factors was obtained from the interviews and medical charts. We assessed the association between current neuropsychological performance and exposure to mercury during the prenatal period, the neonatal period (birth to 28 days), and the first 7 months of life.

Results Among the 42 neuropsychological outcomes, we detected only a few significant associations with exposure to mercury from thimerosal. The detected associations were small and almost equally divided between positive and negative effects. Higher prenatal mercury exposure was associated with better performance on one measure of language and poorer performance on one measure of attention and executive functioning. Increasing levels of mercury exposure from birth to 7 months were associated with better performance on one measure of fine motor coordination and on one measure of attention and executive functioning. Increasing mercury exposure from birth to 28 days was associated with poorer performance on one measure of speech articulation and better performance on one measure of fine motor coordination.

Conclusions Our study does not support a causal association between early exposure to mercury from thimerosal-containing vaccines and immune globulins and deficits in neuropsychological functioning at the age of 7 to 10 years.

It’s noted that a similar study looking at autism will be published next year. Of course, the fact that this study didn’t look at autism leaves the antivaxers a huge opening to say, “Well, yes, but you didn’t look at autism.” Never mind that there are now several studies that did look at autism and found no association between thimerosal-containing vaccines and autism. So what are the main complaints that A-CHAMP has about this study? Let’s take a look, starting with the first one:

The Study’s Claim of No Causality is Contrary to the Study’s Data. The study authors claim that the data disproves causality when in fact, several findings show a negative effect on neuropsychological functioning warranting more study. At least one such adverse association was also found to be associated with low dose thimerosal exposure in other studies. As with earlier studies hyped by vaccine promoters, the study is unable to prove or disprove causality. The blanket dismissal of the troubling neuropsychological outcomes in this study is disingenuous and misleading.

First off, the study didn’t claim that there was “no causality.” What it stated is exactly what you see in the Conclusions section: That the study does not support a causal relationship. There’s a difference there too subtle for the ideologues who wrote this press release to understand. It’s impossible ever to prove “no causality.” It is, however, possible to conclude from the data that the data does not support a causal relationship. Second, A-CHAMP is cherry picking associations here. It is true that there were some negative correlations found that achieved statistical significance. When running 42 tests, it would be shocking if there were not a few anomalous findings. What makes the study authors fairly confident that the findings are anomalous is that they were divided roughly equally in both directions, good and bad. Consequently, if A-CHAMP is going to insist that the correlation, for example, with increasing mercury exposure and poorer performance on the GFTA-2 measure of speech articulation test, then it must also accept the findings of a beneficial association between mercury and identification of letters and numbers on the WJ-III test, as there is no reason to reject it. Naturally, the mercury militia picks on the associations as being true that they want to be true and ignore the other associations, which, if true, would be arguments for including thimerosal in vaccines. It’s far more likely that all of them are just noise. Again, the reason that investigators can reasonably conclude that the associations found are most likely due to random chance is because of their random distribution between positive and negative.

Another complaint:

Children with autism were excluded from this study. The early media contacts we have received suggest that this study shows no association between thimerosal and autism. In fact, the study specifically did not look at children with autism as the sample size was too small and the testing is impossible to complete for the typical child with autism. The exclusion of children with autism from the study may have undermined the power of the study to draw any conclusions about thimerosal.

This is a really, really dumb statement. I’m sorry, but there’s no other way to put it. It just is. It’s like criticizing an apple for not being an orange. The explanation for this is right in the paper, “Since the CDC is conducting a separate case-control study of autism in relation to mercury exposure, a measure of autism was not included in the test battery.” Get it, idiots? A separate study is being done and the results will be reported in a separate paper! That renders this complaint utterly irrelevant. It’s nothing more than a red herring designed to fire up the faithful.

This complaint is not really stupid, but definitely overblown:

The Study’s Methodology has Serious Limitations Negating Any Conclusions Drawn. Major flaws that that causes a large underestimation of neurological adverse effects burden the study: 70% of the families recruited for the study failed to participate. This kind of bias in epidemiological studies is well known to distort even large studies of health effects…It is well established that people who choose to participate in this kind of study are probably very different than those who refuse to participate (the “healthy person” or “complier” effect); especially when the ones who refused to participate said they were too busy.

Simply put: if you have a kid with ADHD or mild ASD or other neurodevelopmental disorders, you are likely to be busier, more stressed, and less available than the mother of a healthy normal child. This phenomenon serves to amplify the effect of the “complier”, the ;healthy families,” – those who do cooperate with the study – confounding or confusing the study’s results. The cooperative parents included in the study were more likely to be those with relatively trouble-free kids

There’s no evidence that this sort of bias existed, and A-CHAMP conveniently omits other biases that might be result from such a selection bias. For example, it is also quite possible to argue that parents who think vaccines may have caused their child’s condition would be even more likely to want to participate in the study (self-selection bias), than parents whose children are normal or who don’t believe vaccines had anything to do with their child’s problems; they might have thought that it wasn’t worth their bother. It’s good of the antivaxers who have been championing the execrable telephone survey done by Generation Rescue to recognize that this sort of bias exists; too bad they only mention it when it suits their purposes (i.e., to trash a study whose results they don’t like) and ignore it when it doesn’t, for example when it calls into doubt the results of the Generation Rescue telephone poll.

In reality, the fact that only 30% of the families who were approached for the study agreed to participate is probably the most significant weakness of the study. The authors don’t try to hide it. Rather, they are right up front with it in the Discussion section, while at the same time pointing out that this is this possible bias was ameliorated by enrolling children on the basis of having received vaccinations without regard to the seeking of health care or having been given a neurodevelopmental diagnosis, as well as noting that many children weren’t enrolled because they couldn’t be located. Moreover, exposure information was obtained from many different sources. It also looked at prenatal exposure to thimerosal-containing vaccinations from vaccines that the mother might have had while pregnant.

Next complaint:

Vulnerable Children Were Excluded from the Study; Early Intervention Was Ignored. Children with a birth weight under 5 lbs. 8 oz. were excluded from the study further skewing the results, as these children are likely more vulnerable to thimerosal than larger babies. In addition, the fact that early intervention may have reduced deficits such as speech delay detected by neuropsychological testing of children aged 7-10 was not accounted for in the study results. There also was no analysis of combined prenatal and postnatal mercury exposures. Only 103 mothers who were exposed to mercury from prenatal immune globulins participated in the study, far too small a group for researchers to draw conclusions regarding the safety of thimerosal in these products.

This is a grab-bag of the specious and semireasonable. The reason for excluding low birthweight children was obvious: Such children are more likely to have neurodevelopmental problems completely independent from any external cause, such as thimerosal. Including preemies and lower birth weight children would only contribute to the background noise and make finding true associations more difficult. A-CHAMP should be glad that the investigators did that, given that it was almost certainly done to make the study more likely to find an association between vaccines and neurodevelopmental disorders. In addition, there is no evidence that low birth weight children are “more vulnerable to thimerosal.” Of course, once again, A-CHAMP fails to point out that the authors themselves pointed out the shortcoming in regard to not being able to account for interventions such as speech therapy. As for the whining about not analyzing combined prenatal and postnatal mercury exposures, that’s just a red herring; the study did test an a priori assumption of interaction between pre- and postnatal mercury exposure.

The rest of the complaints are the standard ones: Conflict of interest, for example, because several of the study’s authors had received funding from pharmaceutical companies. These potential conflicts of interest are clearly stated in the study. A-CHAMP also brings up a totally specious complaint of the study supposedly not accounting for “efflux” disorder (i.e., children who are allegedly “poor excretors” of mercury). Fortunately, Prometheus has provided a good explanation of what a crock that whole myth is, so that I don’t have to.

Of course, there is another reason, besides this study failing to show what the mercury militia wants it to, that there is such hostility here:

The politicization of the thimerosal issue has led researchers to take unprecedented measures. Unlike previous studies, the current study included more than a dozen outside consultants, including at least one advocate for families of children with autism. “We have really tried to make the entire process–from experiment design to manuscript review–as transparent as possible,” says Thompson. But that effort may not have made a difference in the long run. Sallie Bernard, executive director of Safe Minds, a nonprofit parents’ organization that focuses on the role of mercury in neurodevelopment disorders, consulted on the study but still takes issue with its findings. “All the studies, including this one have certain limitations in their design and their methodology,” she says.

Sour grapes, anyone? Ms. Bernard was a consultant on this study and helped contribute to its design! She apparently didn’t like the results that it was producing and decided to drop out and start criticizing it–even jumping the gun on the 5 PM embargo yesterday to do so! Indeed, she is listed on the study in a way that I’ve never seen before: as a “dissenting member.”

How many studies by mercury militia enablers Mark and David Geier include even a note of dissent?

Although this study is not without flaws, it nonetheless does not support a correlation between thimerosal-containing vaccines and the neurodevelopmental problems studied. Even better, the New England Journal of Medicine included two editorials along with the story. One editorial discussed the explosion of vaccine litigation that the now discredited thimerosal “hypothesis” has unleashed, immune to the findings of science. The second editorial is by Paul Offit (the Antichrist to antivaxers) and makes an excellent point about the unintended consequences of taking precautionary measures on the basis of little or no evidence:

On July 9, 1999, after much wrangling, the CDC and AAP decided to exercise the precautionary principle. They asked pharmaceutical companies to remove thimerosal from vaccines as quickly as possible; in the interim, they asked doctors to delay the birth dose of hepatitis B vaccine in children who weren’t at risk for hepatitis. A press release issued by the AAP revealed the ambivalence among its members: “Parents should not worry about the safety of vaccines,” it read. “The current levels of thimerosal will not hurt children, but reducing those levels will make safe vaccines even safer. While our current immunization strategies are safe, we have an opportunity to increase the margin of safety.” Critics wondered how removing something that hadn’t been found to be unsafe could make vaccines safer. But many parents, frightened by a sudden change in policy, reasoned that thimerosal was targeted because it was harmful — and their faith in the vaccine infrastructure was shaken. Doctors were also confused by the recommendation.

I could see how that would confuse parents and doctors. Offit concludes:

Despite several years of reassuring studies, the thimerosal controversy continues to be emotionally charged. Physicians, scientists, government policy advisors, and child advocates who have publicly stated that vaccines don’t cause neurologic problems or autism have been harassed, threatened, and vilified, receiving hate mail and occasionally death threats. The CDC, in response to planned protests at its gates, recently beefed up security and instructed personnel about how to respond if physically attacked.

During the next few years, thimerosal will probably be removed from influenza vaccines, and the court cases will probably settle down. But the thimerosal controversy should stand as a cautionary tale of how not to communicate theoretical risks to the public; otherwise, the lesson inherent in the collateral damage caused by its precipitous removal will remain unlearned.

Exactly. With the best of intentions, trying to be as “safe” as possible, the AAP and CDC unleashed a tsunami of fear of vaccines and laid the groundwork for pseudoscientists like Mark and David Geier to stoke the fears of mercury further with badly designed studies. This was an example of framing science at its worst.

In the end, it is always frustrating to watch how such studies are spun by antivaccinationists. Epidemiology is like that, though. It’s virtually impossible to conduct a cohort study like this without permitting significant shortcomings in it. The reason is that, unlike a bench experiment, the investigators can never control all the variables. Trade-offs are inevitably made, and rarely are there adequate resources to assure sample sizes large enough to be bullet-proof or to be able to account for all potentially confounding variables. No one study is ever sufficient to rule out correlations between undesirable outcomes and various compounds. However, as the weight of several studies starts to bear down on the problem, the preponderance of evidence must at some point be accepted, because we do not have unlimited resources to keep doing studies to answer the same question over and over and over again and every repeated study uses resources that could be used to study other potential causes and treatments for autism. This study happens to be one large and convincing chunk of that evidence, but it is not the only one. Coming next year, when the CDC releases a similar trial about autism, will be another. As Dr. Offit said:

In a new study, Thompson and his colleagues are taking another look at thimerosal exposure and autism. But for many, the question has been resolved. “This study is the third one of its kind. When the autism one comes out, it will be the sixth of its kind. They’ve all shown the same thing–that there is no significant correlation,” says Offit. “Meanwhile, the thimerosal question has diverted attention and resources away from the search for more promising leads on what causes autism. How many more studies will it take?”

That’s the difference between science and crankery. If this study had shown a clear and convincing correlation between thimerosal in vaccines and neurdevelopmental disorders, I would have accepted the results and perhaps started to change my mind. On the other hand, for cranks, no number of studies is ever enough to dissuade them from their beliefs. If God Himself were to come down from on high and design the absolutely perfect study, which when carried out showed no correlation between thimerosal in vaccines and neurodevelopmental disorders, the antivaccinationists would insist that it was flawed, that the investigators had conflicts of interest, and that it needs to be repeated until (although they would never admit this) it shows the results they want it to show.

In fact, expect just that. The CDC has pledged to make the raw data available to other researchers. I predict that, within a few months, a study by Mark and David Geier will use their trademark bad statistics and bad math to cook the numbers to make it look as though there are associations between thimerosal in vaccines and neurodevelopmental disorders that the CDC “covered up.”

Just wait.

ADDENDUM: Some more commentary on this study:

From Left Brain/Right Brain:

No, everything was fine and dandy as long as she [Bernard] was enjoying being fawned over as a “representative of the autism community” and a fellow-scientist instead of the commercial marketer she actually is. Here’s a clue, Sallie: If you’re going to play scientist, you have to follow the rules of science, and that means you stand by your results. You don’t get to say “heads I win, tails you lose” by waiting to see the outcome before deciding whether the study was any good.

And you really don’t get to have CDC at your beck and call, spend hundreds of thousands of taxpayer dollars to do a study to your specifications, then turn around and call them liars when you don’t like how it comes out.

And you, CDC? You’re not just a victim here. Every time you say “let’s do more research” or “we are examining this issue” in order to appease the mercury moms, you increase the chances that kids will go unvaccinated because you failed to give their parents confidence in the safety of vaccines. When you say a study is reassuring and then highlight what is virtually certain to have been a chance finding (a statistical association between higher thimerosal exposure and transient tics in boys) without making it abundantly clear that some false associations were inevitable given the study design, you defeat the purpose of doing the study.

From AutismVox:

Safe Minds, whose Executive Director, Sallie Bernard, was an external consultant and dissenting member of the study, put out a press release stating that the new study’s “draws a misleading conclusion.” But this statement is as “misleading” as the headlines cited above are about the study’s actual contents This only furthers the belief that–no matter how clearly it is stated and shown that there is no causal association between early exposure to thimerasol and later neuropsychological outcomes—a link between these has been firmly established in the public mind. And disputing that link will take more studies, more evidence, more efforts, and more self-scrutiny of why we believe what we believe.

From Autism Natural Variation:

The CDC study looked at 42 different outcomes, and determined multiple confidence intervals in each case, since different levels of exposure were tested. In total, I understand there were over 300 confidence intervals. Consequently, assuming the null hypothesis is correct, you should expect that an RR of 1.0 will be outside the 95% confidence interval in over 15 measures. What the study found was that in 12 measures there was an apparent protective factor, and in 8 measures there was an apparent risk factor. This is completely consistent with the null hypothesis. Therefore, the conclusion of the study, namely that the results of the same do not support a causal association between thimerosal-containing vaccines and neurological outcomes, is absolutely the correct conclusion.

From Arthur Allen on The Huffington Post:

Despite the wealth of data showing that vaccines do not cause autism, many parents continue to believe the theory. Jenny McCarthy, an ex-Playboy Bunny and TV personage, has been making the rounds of the media this week (Oprah, ABC, People magazine) to promote her book, in which she claims that her child was made autistic by vaccines but was “recovered” through alternative therapies.

A large CDC study comparing thimerosal exposure rates in autistic and non-autistic kids is due out around this time next year, as is an Italian study of the question. The data will probably duplicate the many previous studies that have shown no effect. The dogs may bark but the caravan moves on. Or is it the other way around

(The comments from die-hard antivaxers after Allen’s post are scary indeed.)

From Derek Lowe at In the Pipeline:

The director of SafeMinds, a group of true thimerosal believers if ever there was, actually was on the consulting board of this latest study. But she withdrew her name from the final document. The CDC is conducting a large thimerosal-and-autism study whose results should come out next year. Here’s a prediction for you: if that one fails to show a connection, and I have every expectation that it’ll fail to show one, SafeMinds will not accept the results. Anyone care to bet against that?

As a scientist, I’ve had to take a lot of good, compelling ideas of mine and toss them into the trash when the data failed to support them. Not everything works, and not everything that looks as if it makes sense really does. It’s getting to the point with the autism/thimerosal hypothesis- has, in fact, gotten to the point quite some time ago – that the data have failed to support it. If you disagree, and I know from my e-mail that some readers will, then ask yourself what data would suffice to make you abandon your belief? If you can’t think of any, you have moved beyond medicine and beyond science, and I’ll not follow you.

Commenting on David Kirby’s truly idiotic take on this study in The Huffington Post, Steve Novella at Neurologica:

What Kirby does is not just really dumb, it’s despicable. He cherry picks all the negative (meaning bad) neurological outcomes and pretends that the study shows a correlation (it doesn’t, when you look at ALL the data). He then tries to dismiss the positive (good) outcomes as absurd. He mockingly writes:

If they (the CDC) really mean that thimerosal increases IQ levels in males, then sign me up for a double-dose flu shot this year.

No, David, they don’t mean that. Not by any stretch of the imagination. It takes incompetent statistical analysis or the blindness of ideology to write something so ridiculous. What the CDC means is that the study does NOT show that thimerosal increases IQ, nor that it causes motor tics, or improve motor skills, or decrease language skills, or anything else. The study showed no correlations because it all averaged out as noise.

Steve, normally polite to a fault even with cranks, seems to be laying down a bit of the old Respectful Insolence(tm). I like it.

Happiness.

29 Sep

 We sit on the bench, the noise of the people moving around us making it difficult for me to even attempt rudimentary explanations of where we are. Pictures should have been thought of, of course, yet this event seemed to arrive so quickly. I do not know any of the signs, I cannot think of any reasonable substitutions and I conclude that little good would be done of inventing symbols that he has no context for. All that remains is to watch and hope that I can honestly say to the company who donated the tickets how grateful I am and that he enjoyed the show.

    He clambers onto my lap, pressing the back of his head against mine, moving my hands up to cover his ears as the show begins with a flurry of noise and movement. Shouts, cheers and claps surround us. I hug him tightly, feeling him calm and try and persuade him to clap along. He stays still, not moving, not talking, his face betraying no sign of his thoughts. The interval comes and I take him to have his photo taken with the Spiderman acrobat, getting him to look at the camera proves impossible, he sits in front of the acrobat and turns to the side, looking away, one arm raised in front of him, one hand dangling high.

 “Did you like Spiderman?” I ask him. He doesn’t look at me, doesn’t seem to have heard. We go and sit down and the second half commences. This time he is feeling braver, wants to sit on the bench next to me and signs “cow” at the two people dressed in a bull suit. He sits quietly and calmly, a contrast between the children near him who shriek and laugh and roar with approval or disbelief. I take a look at his face, see him staring avidly at the show in front of him, everything seems internal.

 We walk out of the tent and I bend down to him.

 “Did you like that?” I ask him and get no answer. I try a different tactic.

 “Mummy and Tom have been to the …?”

 “Circus!” he informs me. I knew he knew.

 I place my hand inside my coat pocket and look at the photo, see my son, seemingly oblivious to why he is there and then I look more closely at his hand. Raised high, fingers bent and slightly arched, the sign for “spider”.

 “Tom,” I ask him, showing him the picture, “who’s that?”

 “Aaah ‘PiderMan!” he tells me.

  “Spiderman and Tom” I inform him in return. I move to place the picture back and he holds onto it, refusing to release it. One of his hands grabs hold of mine and he grabs one of my fingers, using it to point at part of the photo. His mouth moves into a grin and then he giggles.

 “BLUE!” he shouts out, his face beaming with joy. It’s his favourite colour. “Red! Aaah ‘PiderMan!”

 He’s happy, I’m happy. We walk home and look for spiders’ webs upon the bridge.  

Dore pwned in medical journal: expensive and unproven ‘cure’

29 Sep

The Dore programme is an interesting ‘cure’ for all kinds of things: as Dorothy Bishop puts it, “Dore Achievement Centres are springing up world-wide with a mission to cure cerebellar developmental delay, thought to be the cause of dyslexia, attention-deficit hyperactivity disorder, dyspraxia and Asperger’s syndrome. Remarkable success is claimed for an exercise-based treatment that is designed to accelerate cerebellar development.” Sound great, doesn’t it. Except, as Bishop shows in a new journal article, this is not supported by good evidence and it is therefore the case that “the claims made for this expensive treatment are misleading”. While academic journals are normally pretty restrained, this is about as close as I’ve seen to a thoroughgoing fisking in a journal article: Dore, and their research, are really pwned here. Given that – according to Ben Goldacre in the Guardian – a course of Dore treatment costs around £1,700 (and takes a load of time) I’d want much better evidence of efficacy before splashing out.

Dore is certainly well-promoted. Google “Asperger’s Syndrome” and it brings up an advert for Dore’s “Proven Long Term Drug-Free Solution Relieving the Symptoms of Aspergers”. Google “dyspraxia” and an advert informs one about Dore offering a “Proven Long Term Drug-Free Solution Relieving the Symptoms of Dyspraxia”. Google “dyslexia” and an advert promotes Dore as a “Proven Drug-Free, Exercise Based Dyslexia Remedy”. As a slick Dore promotional DVD puts it: “Now Dore Centres are able to offer real hope to those in despair” due to suffering from ‘learning disorders’. This includes Asperger’s Syndrome, which Dore’s UK site describes as “a problem associated with poor social behaviour.” Dore is apparently “suitable for those with high functioning Asperger’s Syndrome and Autism” (are any alternative treatments nowadays not marketed as suitable for people on the autistic spectrum?).

This marketing might make Dore seem appealing. Bishop notes that, “Although most of the promotion of the treatment is based on personal testimonials, these are backed up by research. Dore pointed to a study showing that treatment led to a nearly fivefold improvement in comprehension, a threefold improvement in reading age, and a 17-fold improvement in writing.” Sounds good, right? But the quality of the research was pretty dismal. Among other problems, while the research did include a control group

there were no data corresponding to a time when the treatment group had had intervention and the control group had not – because the control group had embarked on treatment at the end of the first phase. Accordingly, the authors presented the data only from the treated group.

‘Oops’, is all I can say…Bishop puts it more eloquently, making clear that “The publication of two papers in peer-reviewed scientific journal (Dyslexia) has been presented as giving further credibility to the treatment. However, the research community in this area has been dismayed that work of such poor standard has been published.” I wonder how the researchers justified this poor control to Dyslexia – maybe the good old excuse that ‘the dog ate my control group’?

This might sound bad for Dore, but that’s not the half of it – Bishop also takes apart Dore’s posited mechanism of action:

The gaping hole in the rationale for the Dore Programme is a lack of evidence that training on motor-coordination can have any influence on higher-level skills mediated by the cerebellum. If training eye–hand co-ordination, motor skill and balance caused generalised cerebellar development, then one should find a low rate of dyslexia and ADHD in children who are good at skateboarding, gymnastics or juggling. Yet several of the celebrity endorsements of the Dore programme come from professional sports people.

So, aside from lacking a plausible mechanism of action, and lacking good evidence of efficacy, Dore seems like a great idea. If that leaves anyone rushing to get out their cheque book, Bishop kicks the dead horse a few more times. It’s therefore also worth quoting Bishop’s key points about the Dore treatment:

1 The treatment offered by Dore Achievement Centres is being promoted as a “drug free” alternative to conventional treatment for ADHD, and as a ‘miracle cure’ for dyslexia. It is presented as having a neurological rationale and gains credibility by appearing to be medical treatment.
2 The publication of two papers in peer-reviewed scientific journal (Dyslexia) has been presented as giving further credibility to the treatment. However, the research community in this area has been dismayed that work of such poor standard has been published.
3 The research purporting to show efficacy of the treatment does not show sustained gains in literacy scores in treated vs. control children. Furthermore, the intervention has not been evaluated on the clinical groups for which it is recommended.

Ouch. If only more articles in science journals were like this – clear, well-written, and brutal in a rather entertaining way – they’d make much better weekend reading…

UK Charitable Giving and Spending

29 Sep

Research Autism – a UK website that takes an evidence based view of autism research – discusses a report recently released by New Philanthropy Capital. The report, entitled A Life Less Ordinary, is one of the most thorough and thoughtful pieces of Philanthropy I have read on the subject of autism.

The take home statistic is shocking. People think autism is in vogue at the moment but the money tells the truth: £3.70 per head is spent annually on autism research compared to £1,000 per head for cancer. To me, that says it all.

Please pass on a copy of this report to all your friends, families, employers – anyone you know who makes charitable contributions needs to read this report.

More Evidence for the Safety of Vaccines

29 Sep

This article was originally published at the NeuroLogica Blog and is re-published here with permission.

By Steven Novella, MD
NeuroLogica Blog

A new study just published in the New England Journal of Medicine, Early Thimerosal Exposure and Neuropsychological Outcomes at 7 to 10 Years, does not support a correlation between mercury in vaccines and neurological damage. It adds to the growing evidence that vaccines are safe and they do not cause neurological disorders. This study did not look at autism (a study that will be published next year looks, again, at vaccines and autism), but the mercury-causes-autism crowd are still unhappy with the results.

I have been following this issue closely for several years. Although my awareness of the issue goes back much farther, I started to seriously research the claim that the MMR vaccine, or that thimerosal in other vaccines, causes autism while researching an article on the topic for the New Haven Advocate. As a physician (a neurologist) and a skeptical activist I knew I had to get this issue right. I certainly did not want to falsely stoke the flames of public fear, nor did I want to cast myself in the role of denier.

Early on in my research I really did not know which way I was going to go with the issue. Should my bottom line be that there is real reason for concern here, that there is nothing to the claims, or that we really don’t know and will have to just wait for further research? But after reading through all the claims on both sides, and all the research, it was an easy call – vaccines, and specifically the MMR vaccine and thimerosal, do not cause autism, and the alleged autism “epidemic” is likely just an artifact. Those claiming there is a connection were drowning in conspiracy thinking, logical fallacies, and blatant pseudoscience. Meanwhile every piece of reliable clinical data was pointing in the same direction – no connection.

But still, while I was confident in my final conclusion, a small connection between mercury and autism that eluded the existing data could not be ruled out. Or perhaps there was an angle to the whole story that we were missing but would later come to light. I have had enough experience with scientific medicine to be humble in the face of the complexity of medicine and biology. The only rational position is to remain open to new data and new ideas. On this issue there was sure to be more studies in the future – and the ultimate test of the thimerosal-autism connection, the removal of thimerosal from the vaccine schedule, was yet to be seen. So I confidently plunked my nickel down and waited for the future to unfold.

Everyone likes being right, and sometimes this desire clouds our judgment. I have learned, therefore, how to cheat, which is to say how to always be right. All you have to do is say that your position is based upon the existing data, but is contingent upon the results of future studies. In other words, the “right” position is to change your final answer to accommodate new evidence as it comes in. Therefore the only “wrong” answer is to stick to your original position despite new evidence that contradicts it.

OK – so this is just restating how science is supposed to work, but it is amazing how many people forget to cover their behinds with this simple rule. Usually this is because they are not doing science – they are taking an ideological position, and ideology is inflexible. This is a huge advantage for science over ideology, and why, when science and ideology clash, science is almost always right.

In the case of vaccines and autism, since writing my first major article on the topic, the data has come in all consistent with my original position (so I get to be doubly right). Removing thimerosal from vaccines did not decrease the incidence of autism (or decrease the rate of increase in new diagnoses). And several new major studies came out all showing no association – not counting the utter crap being produced by the Geiers.

Enough had happened to warrant an update, so I jumped at the chance when Ken Frazier of the Skeptical Inquirer asked me to write an article on the topic. My article will be out in the next issue, along with a couple of smaller ones on the same topic, so take a look.

Alas, as is often the way in the world of science, my paper is outdated before it even goes to print. This new study, of course, will not be covered in the article. But that’s what blogs are for – instantaneous news and analysis.

Actually, several of my fellow science bloggers have already beat me to the punch. They cover the article, and the response to the article by the mercury crowd, in great detail, so I will not duplicate it here.

Orac at Respectful Insolence goes over the press release of A-CHAMP (one of the mercury militia) that attempts to dismiss the study. He shows that, while the study (like all studies) has its weaknesses, it does add significantly to the body of evidence showing that vaccines are safe. The complaints of A-CHAMP are either wrong, overblown, or inconsistent with their prior positions and shows that they are just trying to tear down the study at all costs.

For the record, I agree with Orac that the study is good enough that it’s conclusions add to the cumulative data on this topic, and that the weakest element of the study was the 30% compliance rate. In other words, only 30% of the subjects that they looked at for the study made it into the final analysis. This opens up the door for selection bias. Orac is probably correct that this bias would likely overestimate a correlation, not underestimate it, but you can never be sure with such things.

I will add that the 30% figure is not as bad as it first seems. The study reports:

Of 3648 children selected for recruitment, 1107 (30.3%) were tested. Among children who were not tested, 512 did not meet one or more of the eligibility criteria, 1026 could not be located, and 44 had scheduling difficulties; in addition, the mothers of 959 children declined to participate. Most of the mothers (68%) who declined to participate in the study and provided reasons for nonparticipation cited a lack of time; 13% reported distrust of or ambivalence toward research. Of the 1107 children who were tested, 60 were excluded from the final analysis for the following reasons: missing vaccination records, 1 child; missing prenatal records, 5; missing data regarding weight, 7; and discovery of an exclusionary medical condition during record abstraction, 47. Thus, 1047 children were included in the final analyses. The exposure distribution of the final sample was similar to the exposure distribution of the initial 3648 children selected for recruitment in the study.

So about 40% of those that did not make it into the final analysis simply could not be located – this is unlikely to represent a bias. But this is a small point.

Isles from Left Brain/Right Brain points out that Sallie Bernard (a believer in the mercury hypothesis) was consulted on the study design and execution and did not criticize its methods until after the results came back negative. That kind of behavior instantly sacrifices all your credibility in the science club.

Kristina Chew at AutismVox reiterates what I did above – that the mercury-causes-autism ideologues are always asking for more studies, but refuse to change their position when the studies they ask for come out. They are waiting for studies that show what they want them to show – we call that “cherry picking.”

The other side is busy too. David Kirby (a bad journalist who desperately wants to be a bad scientist), who wrote the book Evidence of Harm, published an article online in that absolute rag, The Huffington Post (to be fair, they also published this piece by Arthur Allen defending the paper’s conclusions). Kirby repeats all the same points in the A-CHAMP press release, but he emphasizes the fact that the study found some neurological symptoms that were higher in the subjects who received more thimerosal. Kirby proceeds to completely misinterpret the significance of this.

The study looked at 42 different outcomes, and set the p-value for significance at 0.05. A vague concept of basic math should be sufficient to see that some outcomes will reach significance by chance alone. The researchers arguably should have adjusted their statistics to account for the fact that they were looking at 42 variables – but instead they just looked at all the outcomes that were significant to see if there were any patterns or trends. What they found was that there were a few scores that were worse among those exposed to more thimerosal, but there were also a few scores that were better. There was a random distribution of positive and negative effects that essentially average out to no net effect. It’s all just noise. (Is there a small signal hiding in the noise? There could be – scientists have to be honest about that. But that doesn’t mean there is.)

What Kirby does is not just really dumb, it’s despicable. He cherry picks all the negative (meaning bad) neurological outcomes and pretends that the study shows a correlation (it doesn’t, when you look at ALL the data). He then tries to dismiss the positive (good) outcomes as absurd. He mockingly writes:

If they (the CDC) really mean that thimerosal increases IQ levels in males, then sign me up for a double-dose flu shot this year.

No, David, they don’t mean that. Not by any stretch of the imagination. It takes incompetent statistical analysis or the blindness of ideology to write something so ridiculous. What the CDC means is that the study does NOT show that thimerosal increases IQ, nor that it causes motor tics, or improve motor skills, or decrease language skills, or anything else. The study showed no correlations because it all averaged out as noise.

This is, by the way, the same mistake that astrologers make (remember that crusty pseudoscience?). They look at many variables then cherry pick the outliers. At best what this study might show is a possible correlation, but any such possible correlation would have to be corroborated by a later study (with fresh data) that looked specifically at that one variable.

So the pattern that I found when I first started looking at this issue – that all the reliable data was on the side of no correlation between vaccines or mercury and autism or neurological disorders – continues to hold up to new data. The other pattern I noticed – that those promoting a correlation were relying on bad science, logical fallacies, and ad hoc conspiracy claims – also continues to hold.

In the last few years every new study showed no correlation, and the mercury militia responded with abject nonsense and dismissal. This cycle seems to be repeating itself over and over, and this latest study is no exception.

Bloodletting 101 – an alternative history

29 Sep

Alt-med groupies tell us they are on the cutting edge of medical science, and that fringe providers are somehow protecting patients from the ravages of evidenced-based medicine. They even offer examples, as one austim list serve member did when he wrote “Mainstream medicine used to think bloodletting cured disease. So science doesn’t have all the answers!” I’ve read variations on this statement.

It’s true that doctors once prescribed bloodletting for a wide range of conditions. The ancient Greeks were big into bloodletting, based on a non-empirical view of the natural world which held that blood was composed of four “humours”, symbolizing earth, air, water and fire. Bloodletting was popular for 2,000 years because it seemed to work. Some patients improved after being bled. Doctors just knew it worked, and could point to centuries of precedent.

It’s difficult for the modern mind to grasp why anyone would consider deliberate bloodletting to be a cure for anything. But the answers are quite simple.

First of all, patients have always felt that it’s better to do something than nothing. Before the germ theory of disease, which is only 130 years old, there wasn’t much doctors could do for most diseases short of bed rest and chicken soup. Bloodletting may have been messy and painful, but at least someone was trying something. So, odd as it may seem, bloodletting actually had a placebo effect on some patients.

Since bloodletting wasn’t evidenced-based, it was assumed that those patients that improved after being bled must have benefited by the bleeding. If anybody had thought to do a controlled study 500 years ago, they would have found that the patients who weren’t bled recovered more quickly and in greater numbers than the ones that were. But alas, evidence-based medicine was still a ways off.

I suppose if there was an internet back then, one could have learned the benefits of bloodletting from scores of websites. Bleed Autism Now! practitioners would spread the BAN! protocol far and wide, telling story after story of the children who were rescued from the abyss of mind-blindness and senseless spinning. The more people who signed on to the BAN! protocol, the more self-evident its worth. Heart-shaped Autism Bandages would adorn every donkey cart, testament to the love that parents felt for the children they bled.

And evidence-based skeptics would have been called “hemophobes” and burned at the stake as child abusers.

History teaches: Quackery – hard to kill. People – not so much.

29 Sep

New Scientist had an article recently describing the history of the use of X-rays as a beauty treatment. Who knew that radiation’s ability to make a person’s hair fall out was once exploited as a hair remover?
Histories: The perils of X-ray hair removal

FOLLOWING Wilhelm Roentgen’s discovery of X-rays in 1895, doctors around the world turned their primitive X-ray machines on everything from their own hands to patients with cancer and tuberculosis. To Albert Geyser, a brash German immigrant who graduated from a New York medical school in that heady year of discovery, X-rays were clearly the future of medicine.

Researchers quickly noticed that exposure to X-rays had a remarkable side effect: it made hair fall out. In Austria, physician Leopold Freund recommended it as a treatment for excess body hair, or hypertrichosis. “Hair begins to fall out in thick tufts when lightly grasped, or it is seen on the towel after the patient’s toilet,” he observed in 1899. … Tests followed across Europe and North America with apparent success, … There were already hints that all was not well, however. In France, some doctors reported that their patients had fallen ill. Loath to admit that X-rays were responsible, Freund blamed “the hysterical character” of French patients.

Now working at Cornell Medical College in New York, Geyser embraced X-rays with enthusiasm. Like many others, he paid a high price for his zeal: radiologists were belatedly realising that frequent exposure to X-rays could be dangerous, and Geyser suffered burns that claimed the fingers of his left hand. Undeterred, he invented the Cornell tube – an X-ray vacuum tube of leaded glass with a small aperture of common glass, meant to direct lower-energy, or “ultrasoft”, X-rays directly onto a small area of skin. With the Cornell tube, “the X-ray is robbed of its terrors”, declared The New York Times. By 1908 Geyser had administered about 5000 X-ray exposures with his tube, for a variety of skin ailments. Others remained suspicious of X-rays, and the County Medical Society’s lawyer warned Geyser that “the time is coming soon when if a man is burned, the doctor will be held liable… Don’t use the X-ray unless you know what you are doing with it.”

The article goes on to explain how the use of the Cornell tube’s “ultrasoft” hair-removing rays became known as the “Roentgen therapy for hypertrichosis,.” In 1915, Geyser published an article in, The Journal for Cutaneous Diseases, he assured his readers that “no protection of any kind, either for patient or operator” was needed when using his Cornell tube. In 1924, Dr. Geyser and his son founded Tricho Sales Corporation. They advertised the glories of the Tricho System in hundreds of advertisements that went into newspapers throughout North America. Promises in these ads included: “no injury to skin will result.” Explanations of how it worked noted that it used a “hair starvation process” and that it worked by way of, “radio vibration.” Female relatives of physicians just swore by it, apparently.

Soon there were Tricho clinics in over 75 cities in the U.S.. The process was tidy and painless, the only thing that operators or clients might have noticed was a “faint hum and a whiff of ozone.” The women only need to be exposed to the X-rays for a few minutes, and voila, some time later their hair fell out.

You may be asking, “Approximately, how many women underwent this thoroughly modern beauty treatment?” The New Scientist article says the New York City clinic alone claimed 200,000 clients. These clients would have paid from a “few hundred to over a thousand dollars” for a course of treatments. That’s a huge chunk of change in 1920’s dollars.

OK… so are we all waiting for the other shoe to drop here?

Tricho’s triumph was short-lived.

In 1926, Ida Thomas of Brooklyn sued Frank Geyser (the son) for “a staggering $100,739 – the cost of her facial treatments plus $100,000 in damages.” Ms. Thomas sued because her skin had thickened and wrinkled following the treatments. Two years later Frank Geyser “was arrested following a similar complaint.” Then things got really ugly. Clients now were suffering from “wrinkling, mottling, lesions, ulcers and even skin cancer.” The Journal of the American Medical Association commented on this new health problem, “In their endeavor to remove a minor blemish, they have incurred a major injury.” In July 1929, the AMA condemned the treatment as dangerous.

What was Tricho’s tactical response to all these people–like the AMA–bunch of killjoys–trying to bum them out, bring them down? What action could rescue the Tricho Sales Corporation from losing revenue by the handful, not unlike a radiation poisoning victim losing hair?

Well, if you’ve been following the saga of Defeat Autism Now! and similar groups, and their history of promoting questionable and even plainly dangerous quack therapies, you may have at some point thought to yourself:

“What could rescue autism quackery and it’s adherents from the doldrums induced in part by the death of Abubakar, but also by the criminal charges being brought against the DAN! doctor who killed him, the lack of a promised drop in the numbers of children being diagnosed with autism following the reduction of the use of thimerosal in childhood vaccines, the ridiculous show put on by so-called “expert witnesses” chosen by the Petitioners Steering Committee in the Cedillo vaccine hearing, accumulating evidence tending to exonorate vaccines as not being a cause of autism, and even the exposing of Andrew Wakefield’s seeming ethical problems in his General Medical Counsel hearing in London?”

Or, “What does autism wingnuttery need, right now, to give it life again, you know, fluffliness and bounce and shine, like a good salon-quality shampoo can do for listless hair?” Maybe autism quackery could borrow a page from the Tricho corporation playbook…what DAN! and company needs NOW is and what Tricho Sales Corporation got in their hour of need …

A celebrity endorsement!

Ann Pennington

Ann Pennington, was played as Tricho’s “trump card,” according to the NS article. She was the star of 1929’s hit film, Gold Diggers of Broadway.” The article continues:

And if clients had any lingering doubts, the elder Geyser’s impeccable medical credentials probably reassured them. Yet closer inspection of Geyser’s record would have shown that although he carried out research at a prestigious medical college, some of his work was decidedly dubious: he had used electric shocks to treat all sorts of conditions, from gonorrhoea to asthma, and had made unsubstantiated claims to have found cures for tuberculosis and anaemia.

Inevitably, more Tricho victims appeared in JAMA, including a patient in Washington DC “so depressed as a result of the disfigurement of the X-ray burn that she attempted suicide”. Geyser, it seemed, had either been too greedy to heed any warnings, or had convinced himself that his Cornell tubes really were safe. Whatever his motivation, he had installed poorly regulated X-ray machines across the country, and tens of thousands of women – perhaps even more – were exposed to massive doses of radiation on their faces and arms. They had also received wildly varying doses: some women had as few as four treatments, others as many as 50. And because X-ray exposure rises as an inverse square of distance, even a slight shift in sitting position could double or treble a client’s dose.

With the prospect of being sued for millions of dollars, the Tricho Sales Corporation collapsed in 1930. …

If we all feel a sort of vicarious relief at this point, turns out, it’s premature. Other companies noticing the financial success of the Tricho clinics developed their own “copycat operations.” If the training was miniscule for the Tricho clinicians, it seems that it was even less among these newcomers to the game. Medical and business groups responded by trying to close down these outfits, too. But they just went underground. The article says that in 1940, San Francisco detectives were on the trail of what they thought was an illegal abortion clinic. To their surprise, no doubt, the place in question was instead one of these hair-removal-by-radiation shops. And such shops were still taking in customers “at least” into the 1950’s.

Since all radiation-poisoning “fallout” isn’t noticeable immediately, you can imagine how the story of the customers of the Tricho clinics kept coming up again and again in doctors offices into the 1960’s and 70’s.

One 80-year-old woman arrived with a grapefruit-sized tumour in her head; another refused treatment until she had “a huge and deep crater occupying practically the whole lower half of the breast and the chest wall immediately below it”. By 1970, US researchers were attributing over one-third of radiation-induced cancers in women to X-ray hair removal.

Given cancer’s long latency and the many years that Tricho parlours and their ilk persisted, the procedure may not yet have claimed its final victim. Tricho’s most famous customer, though, had reason long ago to regret her endorsement. After spending her final years as a recluse in a small hotel room off Broadway, Ann Pennington died in 1971. Her cause of death, it was reported, was a brain tumour.

Now, no one is wishing a grapefruit sized tumor on to Jenny McCarthy or anything. For one thing, in the updated case of quack driven nonsense, the gullible celebrity endorser is not the one who is being subjected to questionable therapies. It’s her son. And no one wishes any harm to come to Jenny’s son in the least. He looks like an adorable boy. It’s a shame his mother has been fooled into believing the whole “most of these kids are practically saturated with candida yeast, it’s the reason they go all stimmy … it makes them act crazy…put them on a prescription antifungal and a restrictive diet and you’ll get your kid back,” thing (not to mention the whole anti-vax and autism epidemic thing). If his mom and doc sent a blood sample off to Immunosciences lab before it was closed (this past July) then she likely got a bogus positive result. Then the fool doctor could write a prescription for a toxic antifungal (all drugs are toxic, don’t you know, depends on the dose) that the kid likely didn’t need–just to make mommy feel like she’s doing all she can to “pull her son through a rapidly closing window” and give her something to write about besides.

One really scary lesson from the Tricho debacle is that this deadly quackery hung around for so long. In this case, bad news, the news that these radiation machines could easily cause a client’s slow death, besides creating some really ugly skin, didn’t seem to travel quickly enough. Tricho shut down in 1930, but the technique and hype they developed was still be employed forty years later on new suckers, the ones born every minute. The Candida yeast (as cause of dozens of chronic disorders) business was a stupid health fad in the 1980’s. The fad died for the most part, but apparently Jenny didn’t know about it, or didn’t take a clue from it, and here she is in 2007 promoting it as the thing that stood between her autistic son and being a typical kid.

It was interesting that the Tricho company was founded by an apparently unethical doctor, Albert Geyser, who had a pretty respectible looking CV, and who claimed to have great insights into and treatments for many different diseases. Albert went into business with his son. Hmmm. Who does that remind one of? Someone else with a German name that sounds a bit like Geyser. There’s also a creepy and creepier brother duo in autism quackery with a similarly questionable looking, but less impressive-looking background.

When one compares the seeming safety profile of Mr. and Dr. Yasko’s (and Garry Gordon’s) ridiculous RNA yeast soup, or the homeopathic water drops said to be favored by Katie Wright, with something like Lupron and IV chelation, one can almost be grateful for such benign, if expensive and reprehensibly misrepresented, “cures.” But there are major question-marks hanging over the safety of things like long-term, high-dose methyl B12 injections given to kids who are not deficient in B12. There are questions about high doses of any vitamins for anyone. Some mineral supplements are contaminated with heavy metals, so are some chelators, apparently. Lots of biomedded kids take vitamin and mineral supplements. There are questions about the dangers of hyperbaric oxygen therapy, like what if the kid is susceptible to seizures and you put him in the HBOT tank and the extra oxygen kindles these seizures?

As for the recent Jenny McCarthy road show and it’s effect on the DAN! dox customer base, it’s hard to say who needed whom more–DAN! suffering from a series of bad PR breaks, or Jenny suffering from a sagging career and a failed attempt at making a go with the Indigomom Crystalkid schtick. It’s hard enough for a talented actress to keep getting work at age 35, they say, imagine what it’s like for short-on-talent Jenny with her now famed post-pregnancy stretch-marks “that glow in the dark … for some reason!”.

DAN! and Jenny McCarthy deserve each other. Let’s hope they both quickly skulk out of the limelight and into obscurity and may they take their quack therapies, benign or not, with them.

Paul Collins is the writer of the above mentioned New Scientist article. The writing style would seem to indicate that it’s the same Paul Collins who is the author of the fantastic book, “Not Even Wrong.” If so, this Mr. Collins is the father of a beloved autistic boy.

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