Saturday, December 30, 2006

US$780,000

That's about how much Andrew Wakefield received from anti-vaccination lawyers, according to an article by Brian Deer titled MMR doctor given legal aid thousands. Some of the stuff that goes on in autism "research" is really sickening, isn't it?

Kudos to Brian on some great investigative reporting.

Wednesday, December 27, 2006

What Do Parents Attribute Regression To?

Wakefield et al. (1998), despite having been partially retracted, is the paper considered mostly responsible for an autism-related anti-vaccination scare that started with the MMR vaccine and subsequently evolved to include thimerosal-containing vaccines (TCVs). The MMR vaccine has been the focus of hype mostly in the UK, whereas TCVs are most often blamed for autism in the US.

If you search the VAERS database for reports filed in all of 1997 on MMR-attributed autism, you will find 16 reports of adverse events. If you do the same search in all of 2002, you will find 120 reports. That gives you an idea of the effect of MMR hype on what parents attribute autism to. Thankfully, the number of such reports appears to be declining in recent years, with only 40 in all of 2005.

Lingam et al. (2003) found that not only did the rate of attribution of regression to the MMR vaccine changed post-Wakefield, but some parents apparently changed their story as well.
Widespread public concern about the possible relation between autism and MMR began in August 1997, with the pre-publication release of information about the Wakefield study, which attracted considerable and ongoing media attention. The date at which onset of developmental regression was first recorded in the notes was obtained for the 106 cases. After excluding unvaccinated cases and those vaccinated when aged over 24 months (of whom all but one were children vaccinated in the 1988-89 catch-up campaign), we found MMR was reported as the trigger in 6/30 (20.0%) post-August 1997 compared to 2/46 (4.3%) before August 1997 (p = 0.052).

From August 1997 the reported presence or timing of regression changed in 13 cases. For six of these, regression was mentioned for the first time after August 1997, even though many health professionals had seen these children before this date. In seven cases the recorded timing of onset of regression changed in relation to MMR: six closer, one further away.

But there is some other data of interest in Lingam et al. (2003) which I wanted to go into. They survey parents about triggers thought to cause regression.
In 44 (42%) of the 106 children with detailed information on regression, a specific trigger was mentioned as a possible cause. The most common (13 children) was a household or social change such as the birth of a sibling, then vaccination (12 cases). Other triggers mentioned were: viral and bacterial infections (n = 7), seizures (n = 7), postsurgery (n = 2), and other causes (n = 3). The MMR vaccine was mentioned specifically in eight of the 12 cases where a vaccine was suspected. Although families would not have been directly asked about this possibility, this finding suggests that very few parents (less than 2% in this cohort) considered that MMR vaccine might have triggered their child's autism.

Interestingly, in this post-Wakefield survey, there is one trigger parents seem to attribute regression to more often than vaccination: Household stress, such as the birth of a sibling.

In case there are doubts about this, let's look at another survey on language regression, Shinnar et al. (2001) (full HTML text can be temporarily found here). The following is what they found.
Fifty-two families (29%) reported a trigger to the regression (Table 2). The most common triggers reported included family stresses (n=23), such as the birth of a sibling (n=10) or moving (n=7), seizures (n=13), or infectious/immunologic triggers (n=14).

More specifically, they found that only 8% of parents attributed regression to immunization, compared to 19% who blamed the birth of a sibling, and 44% who blamed family issues in general.

It is often said that autism researchers would do well to pay attention to parental experiences. There is some definite merit to this idea, of course, as there is merit to the notion that researchers should listen to autistics themselves. It follows that there must be a whole subfield of autism science dedicated to studying the link between family stress and autism/regression, right? Well, I'm unable to find much of anything about this link through Google Scholar. But surely, the potential link must have been mentioned as part of the Combating Autism Act, correct? No, apparently not. At least there must be mailing lists established to discuss this link or blogs where it has been mentioned, right? Not that I know of. I actually believe this is the first blog post where the link between stress and regression is the main topic of the post.

Why might this be? I suggest it's because there won't be class-action lawsuits that address the stress caused by the birth of siblings. There aren't specific big corporations that can be blamed for family issues. There is no role for the illuminati to play. And perhaps most importantly, it seems difficult to come up with grandiose promises of cure for stress-induced autistic regression.

Further reading

-Whatever Happened To? (Joel)
-Is the TV Hypothesis more Plausible than the Thimerosal Hypothesis? (Joseph)

Friday, December 22, 2006

On The Validity Of Self-Diagnoses

Via Brett I've learned of an article titled Study: Most Self-Diagnosed "Asperger's" Patients Just Assholes claiming to report on a study published in The Lancet, no less. After checking out the website where the article is posted, www.ridiculopathy.com, it's clear this is just one of their spoofs. Nevertheless, I think there's a reason why someone came up with the idea of making fun of self-identified adult autistics, and this is something that should be addressed and debated by our community.

It surely has to do with the fact that 30 years ago there was no one identified as having Asperger's, yet there is probably nothing biologically new about today's adults. I think most people would prefer to keep the ad-hoc labels of the past ("asshole" being one of them) as opposed to having to deal with (and perhaps even accept) the impairments and peculiarities of others. A similar theme was explored by the TV show House, where the main character was suspected of having Asperger's but was later characterized as having to face the fact that he was merely being a "jerk".

Much of the importance of the issue rests in the fact that opponents of autism self-advocacy attempt to use the existence of self identification to their advantage. Think Lenny Schafer. Never mind that undiagnosing someone over the internet is obviously less valid than any non-professional self-assessment.

The "explosion" in adult diagnoses and self-diagnoses of ASD certainly seems to parallel that of diagnoses in children. That is, they started to occur mostly in the 1990s, and really exploded in the late 90s. I first learned about Asperger's in 1998, which is roughly when the internet was experiencing a substantial boom. Doubts about the validity of ASD diagnostic labels are not restricted to adulthood, mind you, as evidenced by an article by one Katie Grant titled Some 'autistic' children aren't ill, they're just badly behaved (which was not a spoof, sadly).

Before I continue, I think a personal disclaimer is in order. I do have what I consider to be a diagnosis, given to me by my son's psychiatrist. It was a quick diagnosis and it's not in writing, mind you, but I don't really have use for anything beyond that. Plus I have an autistic son, a dad with clear autistic characteristics in early childhood, and my own childhood history which includes hyperlexia. There are many other relevant facts about my family and myself which I won't go into. So I have no doubt I'm autistic, and neither does my wife. My parents seem to be mostly accepting of the fact that I'm autistic at this point.

But in many cases a diagnosis of ASD, particularly a self-diagnosis, might leave room for doubt. The matter is complicated by the fact that there are no medical tests for ASD and it's unlikely there will ever be a simple, accurate test.

Whether self-diagnoses are valid or not is primarily a scientific question in my opinion. Intuitively, it seems to me people would be able to determine what they are most of the time. But while it would not make sense for people to be wrecklessly giving themselves false psychiatric labels (consider the potential impact on any employment, for example) error is always a possibility, as is hypochondria.

I'm aware that professionals warn against self-diagnoses of ASD. But is there a study which documents the inaccuracy of self-diagnoses of ASD specifically? Not that I know of. I think such warnings are based on educated hunches, nothing more.

While studies on the validity of self-diagnoses of ASD don't appear to exist, I wouldn't say nothing is known about them. Let's look at what I believe are the two most often used instruments involved in self-diagnosis.



The owner of the Aspie Quiz makes some relevant claims about that instrument. For example, that the test has been adjusted over time based on the performance of each question. And that self-diagnosed autistics, surprisingly, tend to score slightly higher than diagnosed autistics. Interesting as these claims are, it's important to note there are no published studies on the validity of the Aspie Quiz.

The AQ Test, on the other hand, has been studied on multiple occasions. For example, Woodbury-Smith et al. (2005) found the test to have good discriminative validity at a threshold of 26. What this means is that if you score 26 or lower in the AQ Test, it is very unlikely that you are autistic. This only tells us about the screening properties of the tool, not about its potential use as a diagnostic instrument. But let's look at Baron-Cohen et al. (2001) where 11 students scoring 32 or higher were interviewed. All of the 11 met 3 or more DSM-IV criteria and 7 of the 11 met "threshold" on these criteria. (I believe "threshold" means clinical significance). So it appears that the AQ Test has about 64% accuracy at a cut-off of 32.

I would conclude that if you score higher than about 33 in the AQ Test, you have the 3 major features of autism (impaired socialization, communication difficulties and obsessive interests/repetitive activities), and these cause problems in the areas of employment, education or social/family life, then there is little doubt you are autistic. This is just my opinion, which is that of a non-psychiatrist. Do I expect most psychiatrists to disagree with this conclusion? Of course.

Thursday, December 21, 2006

David Kirby Plays Fast and Loose With Facts

I've discussed fabrications related to autism before. A much more annoying phenomenon occurs when a single individual goes around making up significant claims that simply cannot be substantiated. I'm talking about David Kirby.

An article published by Herald Community Newspapers Online has irresponsibly echoed such claims by Kirby. The most outrageous claim in the article is perhaps the following:

He pointed to Denmark and Sweden to support his theory that there was a connection between an autism increase and Thimerosal. In 1992, both countries removed the mercury preservative from their vaccinations and have seen a remarkable drop in autism.


Not only is there no data to substantiate this claim, but it is known that what actually happened is the opposite of what this claim states. (At least in Sweden that is obvious, and although disputed to an extent in Denmark, there's no reason to think their administrative autism rates have declined at any point in time). I don't know if the paper quoted Kirby correctly, but there are several other direct quotes attributed to David Kirby. For example:

There was a huge spike in autism in 1992 when the Hepatitis B vaccine was added to the regular vaccination schedule for babies.


If you look at a graph of administrative prevalence of autism in the U.S. you will see there is an increase in the prevalence between 1992 and 1993, but it is a very small increase. There is no "huge spike" around 1992. There are no "huge spikes" at any time, but a gradual increase throughout the 1990s and beyond. The growth in prevalence between 2002 and 2003, for example, is much larger than anything that occurred around 1992.

Kirby on historic prevalence:

There were 1 in 10,000 children with autism in 1987 in the United States before the addition of Thimerosal.


This is absolutely not true, and cannot be substantiated by any epidemiological study. It is not clear where this statistic comes from at all, and I do not believe Kirby can produce an original source, nor can JB Handley, who has been asked to source the same claim previously. The first significant epidemiological study of autism was Lotter et al. (1967) which found a prevalence of 4.5 in 10,000 for Kanner autism as operationalized by Lotter. For a prevalence study around the year Kirby cites, see Ritvo et al. (1989), which found a prevalence of 4 in 10,000 in Utah.

There is a comment by one Michelle Soodek in the article which I wanted to note as well:

She reasoned that if there were just as many people with autism when she was a child, than where are the institutions and facilities to house all of these people that would now be adults?


Ms. Soodek is repeating a common mistake in reasoning by those who embrace the autism epidemic concept. She is assuming that most children currently diagnosed with autism would be institutionalized, and that rates of institutionalization for children diagnosed today is the same as that of children diagnosed 20 years ago. As I have shown using CDDS data, the total number of institutionalized developmentally disabled individuals in California has declined a little in the last 14 years. More institutions will not likely be needed in the future. To suggest otherwise is nothing but fear mongering. She is also promoting the idea that autistics naturally belong in institutions, which is a deplorable thing to do even if it was unintentional.

That's enough about that article. Let me now look at some of David Kirby's history of dubious claims. They started early on. For example, an infamous claim from his book, Evidence of Harm, was that Asperger's Syndrome is "also known as idiot-savant syndrome". This is clearly false if you consider the history of the terms.

What about his promotion of Evidence of Harm as the work of an impartial journalist? These days he refers to thimerosal hypothesis skeptics as "mercury defenders".

A more significant example of dishonesty is documented by Kevin Leitch. In an interview with the New York Times in 2005, David Kirby stated that autism rates should drop by the end of 2005. He later established his current goalpost of 2007 when he discussed the California numbers with Citizen Cain. Kev requested a clarification from Kirby, which was the following:

The Times misquoted me. I actually asked for a correction, but did not receive one. What I told the reporter is that "we should know in the next few years."


Kev actually apologized to David Kirby before he contacted the New York Times to verify Kirby's account. The Times replied as follows:

Prior to publication, we read the entire passage relating to this matter to Mr. Kirby. He approved it.


I do not know that Kirby addressed the issue further after Kev caught him lying.

I'm sure there are further examples of dishonesty from Mr. Kirby. Readers can provide additional instances if they wish to.

There will be a public debate between David Kirby and Arthur Allen on January 13 at 10 a.m. in the Price Center, University of California, San Diego. This debate is sponsored by TACA and Generation Rescue, who will no doubt attempt to stack up the audience against Mr. Allen. It would be nice if members of the skeptical community can attend.

I am sure Mr. Kirby will try to introduce some of these "facts" of his in the debate. The problem with a spoken debate format is that it allows such fabrications to occur. In that format it is more difficult to call your opponent on dubious claims and successfully show that the claims cannot be sourced. This is likely one reason why you don't see David Kirby debating in blogs, while accepting to debate in a standard spoken format. It has nothing to do with visibility, in my opinion, considering, for example, that Kev's blog has at least twice the readership size of the Autism Speaks website.

Wednesday, December 13, 2006

Kirby, Olmstead Shoot Selves in Foot

David Kirby is well aware that 2007 is right around the corner. You can tell by the rather unusual tone of his latest post. He's no longer even pretending to be objective. How long before he starts calling anyone who disagrees with him a Big Pharma Shill?

So what is Kirby so worked up about? It appears that he has learned from Dan Olmstead of a NIH report titled "Thimerosal Exposure in Pediatric Vaccines" about potentially serious methodological problems in ecological studies that use the VSD database. I don't know if Kirby read the report, but I did. This is actually a very well thought out report which ideally should have been done 6 years ago. But Kirby seems to think this report is evidence of an association between autism and thimerosal, or at the very least evidence that undermines lack of evidence of an association. Something like that.

Verstraeten et al. (2003), the VSD study in question, found statistically significant associations between thimerosal and a couple neurological outcomes in some HMOs, but the associations were not consistently found in other HMOs. Because of these conflicting findings, the study authors called the results "neutral", meaning that the study can't tell us if thimerosal is associated with neurodevelopmental disorders or not. Now the NIH has come up with a list of methodological problems that put in further doubt any VSD findings by Verstraeten et al. in relation to thimerosal. In other words, the neutrality (or non-informativeness) of the findings has been strengthened.

Surprisingly, Kirby's reading of the report conflicts with his other views, because it completely undermines the foundations of the Simpsonwood conspiracy theory. You see, Verstraeten et al. were supposed to have found significant associations between thimerosal and neurodevelopmental outcomes beyond those that were reported in 2003. But now Kirby is endorsing a NIH report which says that ecological studies on the VSD database, specifically those done by Verstraeten et al., are likely flawed. I'm not sure if Kirby realizes this. If he does, he's being duplicitous. If he does not, he just shot himself in the foot.

Furthermore, there is a quote by Thomas Verstraeten which is often used to argue in favor of the thimerosal association:

Personally, I have three hypotheses. My first hypothesis is it is parental bias. The children that are more likely to be vaccinated are more likely to be picked up and diagnosed. Second hypothesis, I don't know. There is a bias that I have not yet recognized, and nobody has yet told me about it. Third hypothesis. It's true, it's thimerosal. Those are my hypotheses.

(Source)

Verstraeten was likely being honest in his assessment. What the NIH report has done, effectively, is provide many possible "Second hypotheses".

Kirby also believes the Verstraeten et al. study is the cornerstone of the case against the thimerosal hypothesis. It's not clear why he believes that is true. I think one of the best studies on the matter is Fombonne's out of Canada. Even if you don't care to analyze those findings, it's enough to consider that thimerosal was fully removed from pediatric vaccines in Canada in 1994, and the prevalence of ASD among Kindergarten children there is currently around 1%. You don't have to be an epidemiologist to realize what the implications of these facts are. Kirby thinks Fombonne's findings are inconclusive, but again, it is not clear what he bases that on. I imagine it's the very weak rebuttal by SafeMinds, an organization that is apparently no longer even putting minimal effort into arguing its case.

Kirby makes light of the Andrews et al. (2004) study out of the UK. That study found statistically significant negative associations ("protective" effects) between thimerosal and autism. Kirby's interpretation of those findings is either naive or desingenuous. If thimerosal is phased out at the same time the incidence of autism increases, it is obvious that the study will find that children not receiving thimerosal tend to become autistic more often than those vaccinated with it. So the finding of a statistically significant negative association is not surprising. It doesn't mean thimerosal protects against autism, but simply that there were coincidentally divergent trends of thimerosal exposure and autism incidence. Incidentally, if a VSD study were done on the birth year cohort expanding, say, 1998 to 2002, it would also find a "protective effect" of thimerosal, no doubt.

Back to the NIH report. I actually welcome this report, and I'm not just saying this now that it has come out. Back on November 20, I analyzed claims about early drafts by Verstraeten et al. In that post I mentioned several ridiculous negative associations found between various outcomes and thimerosal. I argued that the findings of Verstraeten et al. cannot be taken at face value, and that while VSD has its merits, "this doesn't mean VSD is impervious to confounds beyond random error." I further stated that "VSD still records outcomes based on existing diagnoses, not the results of whole population screenings. In a cohort of children expanding many years, recent diagnoses are not necessarily equivalent to older diagnoses. Surely, things like coincidental trends and left censorship could have an impact on any findings." What does the NIH report say?

The panel identified several serious problems that were judged to reduce the usefulness of an ecologic study design using the VSD to address the potential association between thimerosal and the risk of AD/ASD. These included uncertainties in case ascertainment, heterogeneity of business practices within and across managed care organizations (MCOs) and their systematic changes over time, misclassification of exposure status using comparisons of before vs. after removal of thimerosal from most childhood vaccines, and the inability to control for temporal changes in awareness, diagnostic practices and potential confounding factors.


(Emphasis mine)

I'm glad there are people who think about these things in more professional depth, believe in the self-correcting principle of science, and are willing to criticize existing scientific work, no matter who did it.

The NIH panel makes some interesting proposals for future VSD studies and they are apparently taking suggestions from the autism community. I think the biggest potential problem of a VSD study is that of coincidental trends (specifically, thimerosal exposure rising at the same time as administrative incidence of ASD in the early 1990s). That is why I think a VSD study should not look at a cohort expanding many years, but maybe only one year. This is difficult, nonetheless, because the number of children with a given outcome in an HMO is small. An alternative is to look at a cohort where the average thimerosal exposure was roughly constant over time (e.g. 1995 to 1998).

Other confounds are not as easy to control for I'd imagine. Either way, more studies would be good to have. Matters that appear unresolved don't help things move along.