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The final nail in the mercury-autism hypothesis?

PROLOGUE: BAD LUCK AND BAD TIMING

Two and a half years ago, very early in the history of this blog, I wrote one of my usual logorrheic (although I prefer the word “comprehensive”) posts entitled Mercury in vaccines as a cause of autism and autism spectrum disorders (ASDs): A failed hypothesis. In that post, I characterized the scientifically discredited notion that the mercury in the thimerosal preservative that used to be in several childhood vaccines was the cause of the “autism epidemic” as “one of the most pernicious medical myths of recent years.” And so it is. I like to characterize the notion that thimerosal-containing vaccines (TCVs) cause autism as the American version of the British myth, popularized by Andrew Wakefield and a sensationalistic British press, that the measles-mumps-rubella (MMR) vaccine causes autism and “autistic enterocolitis.”

Both notions were based on confusing correlation with causation, aided and abetted by some truly bad science, and both notions have been painfully difficult to dislodge. Indeed, in the case of Wakefield, only now that Wakefield was stripped of his license to practice in the U.K. by its General Medical Council, leading to The Lancet finally doing what it should have done six years ago and retracting Wakefield’s 1998 study that sparked the MMR frenzy in the U.K. and arguably kickstarted the modern anti-vaccine movement, do I sense that journalists are finally “getting” that science does not support the idea that the MMR vaccine causes autism. Andrew Wakefield may be trying to fight back with his book Callous Disregard after his disgrace was complete, basking in the glow of admiration of die-hard anti-vaccine groups, but, for now, at least, Wakefield and his MMR fear mongering are yesterday’s news, and that’s a very good thing indeed–at least for as long as it lasts.

Perhaps it is the fall of Andy Wakefield that has led to an apparent resurgence of the concept that mercury in TCVs somehow causes autism, after having faded into the background after the CDC and AAP recommended that thimerosal be removed from all childhood vaccines in 1999 and the last TCV having expired towards the end of 2001. After all, if the hypothesis that TCVs cause autism had been correct, we should have expected to see a marked decrease in the incidence of autism and autism spectrum disorders (ASDs) within about 5 years of 2002, given that the vast majority of cases of ASDs are diagnosed between the ages of 2 and 5. We have not, and, even though its adherents have kept moving the goalposts back regarding the date that we should start to see a leveling off and drop in the incidence of ASDs, starting with 2005, then 2007, and now, apparently, 2011 (which is only less than four months away, by the way), even Jenny McCarthy’s anti-vaccine organization originally founded by J.B. Handley and his wife, namely Generation Rescue, began demphasizing mercury in 2007, after having stated flatly on its website that autism is a “misdiagnosis for mercury poisoning” for so long. Since then, “too many, too soon” has been the favored propaganda talking point.

Of course, not every crank is ready to abandon the myth that TCVs cause autism. Indeed, tomorrow two mercury militia “heavy hitters” and bloggers for the anti-vaccine propaganda blog Age of Autism, Mark Blaxill and Dan Olmsted, will be releasing a book entitled Age of Autism: Mercury, Medicine, and a Manmade Epidemic. In anticipation, four weeks ago I actually e-mailed the publicist to send me a review copy of Age of Autism. I have yet to receive the book. I wonder why. Be that as it may, it amuses me that the official release of the release of the not-so-dynamic duo of the mercury militia’s book actually will one day after a study that is arguably the last nail in the coffin of the very dead hypothesis that TCVs cause autism was released. Either the great pharma conspiracy is far more conniving and effective than even J.B. Handley thinks, or Blaxill and Olmsted’s luck is just that bad. As I anticipate the conspiracy mongering posts about this bad timing aside, let’s just take a look at this last coffin nail, which is a study by Price et al that was released today in the journal Pediatrics entitled Prenatal and Infant Exposure to Thimerosal From Vaccines and Immunoglobulins and Risk of Autism.

PRELUDE TO PRICE ET AL

The first thing you need to know about this study is that it is the long-awaited follow-up to a study by Thompson et al published in The New England Journal of Medicine in 2007, which I’ve discussed before. Thompson et al was a study that examined in a rigorous fashion whether there is a correlation between TCVs and adverse neuropsychological outcomes other than autism and ASDs. Basically, this was a case-control study of over 1,000 children tested for 42 different neuropsychological outcomes other than autism and ASDs in which children were subjected to various neuropsychological tests and the results correlated to exposure to TCVs during the neonatal period (days 0 to 28) and the first seven months of life. The results were a classic example of in essence random noise. There were a few neuropsychological measures in which lower scores correlated with TCV exposure, and there were a few neurodevelopmental measures in which higher scores correlated with TCV exposure. However, the detected associations were small and almost equally divided between positive and negative effects; in other words, nothing more than would be expected from random noise in the data.

One aspect of this study that was depressing and amusing at the same time was that the input of anti-vaccine–excuse me, “pro-safe vaccine”–groups was solicited during the design of the study. Indeed, Sallie Bernard, president of SafeMinds, was a consultant to the investigators of Thompson et al and participated in the design of the case-control study, despite the fact that she has no relevant background in science, statistics, or clinical trial design! Yes, in the ultimate case of trying to appease those who cannot be appeased and indulging Ms. Bernard’s arrogance of ignorance, apparently the CDC and the Vaccine Safety Datalink (VSD) team decided to “reach” out to their foes. The result? Sallie Bernard saw the writing on the wall, namely that the study was not showing what she wanted it to show, dropped out of the study, and started attacking it immediately, even jumping the gun on the article embargo in order to post her sour grapes all over the Internet. A blogger by the ‘nym of Interverbal aptly criticized Bernard for this:

Even before this study was released yesterday, there was publicized dissent from advocates from the idea of a mercury etiology of neuropsychological harm. One of them came from a well known advocate, Sallie Bernard, who was invited to be a collaborator in this study. It seems that she was involved in the planning of this study, but the lead author indicated that she withdrew her support after the results began to be circulated.

That is not how science works. If you have a problem with a study design then you dissent before you begin collecting data.

As Joseph aptly put it, sour grapes. As the final draft circulated, qq read it and didn’t like what the results showed. She even went so far as to write a letter to the NEJM listing her complaints, to which the Thompson et al responded, skewering all of her objections quite ably. Bernard’s behavior with respect to her involvement in Thompson et al is one reason why I have come to the conclusion that attempting to “build bridges” to the leaders of the anti-vaccine movement is a fruitless and pointless exercise. That is not to say that we shouldn’t try to build bridges to parents who express fears over vaccines because they’ve heard the message of anti-vaccine leaders like Bernard, but trying to convert or coopt high profile anti-vaccine activists like Bernard is a waste of effort.

The other common reaction of the anti-vaccine movement to this study was to cherry pick all the negative outcomes and ignore all the positive outcomes. Steve Novella caught opportunistic anti-vaccine propagandist David Kirby doing just that at the time of the study. Sadly, this dishonesty continues even today. Indeed, Mark Blaxill himself promoted the very same misinterpretation of Thompson et al just last week. Spin and misinformation promoted by the anti-vaccine movement never truly dies. Once a line of attack is developed, no matter how many times it is soundly refuted by science, it inevitably rises again, much like the zombies in any number of movies that I’ve enjoyed through the years. What that means is that defenders of science-based medicine, in order to outrun the zombies when they inevitably rise again, need to do their cardio.

That, of course, and the double-tap. On the other hand, anyone who’s read my stuff for a while knows that for me the double-tap isn’t enough. I like to deal with anti-vaccine pseudoscience using at minimum a .50 caliber machine gun.

SURPRISE! SURPRISE! THIMEROSAL IN VACCINES ISN’T ASSOCIATED WITH ASDs, EITHER!

When Thompson et al was published three years ago, the authors pointed out that they intentionally did not include autism and ASDs as studied outcomes and that these outcomes would be the topic of a subsequent paper. Price et al is that paper. What one also needs to understand about Price et al and Thompson et al is that these were studies suggested at the time that the CDC and AAP first decided on the precautionary principle to recommend the removal of thimerosal from all childhood vaccines. That it took until 2007 to publish Thompson et al and until now to publish Price et al just goes to show how difficult and time-consuming epidemiological research can be. Finally, given that the data sources and methodology were in essence the same for each of the two studies, we can expect that the anti-vaccine movement will use the same spin and misinformation about Price et al as it did for Thompson et al in order to attack it.

Basically, Price et al is a similar sort of case-control study. A case control study is a type of retrospective trial in which subjects with a certain condition (cases) are matched as closely as possible with subjects without the condition under study (controls), and the two groups compared to look for factors that correlate with the condition. That’s how Thompson et al was performed, and that’s how Price et al was also performed. Being retrospective, such a study can never be as rigorous as a randomized controlled trial or a prospective cohort study. However, given that thimerosal has already been removed from all infant vaccines other than the flu vaccine (and there is a thimerosal-free alternative) and, more importantly, that it would be unethical to conduct a randomized double blind, placebo-controlled clinical trial, this sort of trial is the best evidence that we will be able to come up with.

The specific design of Price et al is summarized in this table (click for a larger version):

design

Basically, the final two groups that were studied consisted of 256 children with ASD and 752 matched controls. One very interesting aspect that looks as though it were almost certainly placed into the experimental design based on concerns of anti-vaccine advocates like Sallie Bernard is a group of children who underwent regression. Basically, the study examined whether there was a correlation between ASD and TCV exposure. It also examined two subsets of ASD, autistic dsorder (AD) and ASD with regression, looking for any indication whether TCVs were associated with any of them. Regression was defined as:

the subset of case-children with ASD who reported loss of previously acquired language skills after acquisition.

Also, when adding up total thimerosal exposure, the investigators also included any thimerosal exposure that might have come prenatally from maternal receipt of flu vaccines during pregnancy, as well as immunoglobulins, tetanus toxoids, and diphtheria-tetanus. In other words, investigators tried to factor in all the various ideas for how TCVs might contribute to autism when designing this study.

So what did the investigators find? I think you probably know the answer to that question. They found nothing. Nada. Zip. There wasn’t even a hint of a correlation between TCV exposure and either ASD, AD, or ASD with regression:

There were no findings of increased risk for any of the 3 ASD outcomes. The adjusted odds ratios (95% confidence intervals) for ASD associated with a 2-SD increase in ethylmercury exposure were 1.12 (0.83–1.51) for prenatal exposure, 0.88 (0.62–1.26) for exposure from birth to 1 month, 0.60 (0.36–0.99) for exposure from birth to 7 months, and 0.60 (0.32– 0.97) for exposure from birth to 20 months.

The last result is a bit of an anomaly in that it implies that exposure to TCVs from birth to 1 month and birth to 7 months actually protects against ASD. The authors quite rightly comment on this result thusly:

In the covariate adjusted models, we found that an increase in ethylmercury exposure in 2 of the 4 exposure time periods evaluated was associated with decreased risk of each of the 3 ASD outcomes. We are not aware of a biological mechanism that would lead to this result.

Of course, two of the most likely explanations for such a paradoxical result would be either that parents of cases, given the genetic component of ASD, might have older children who have already developed ASDs. If these parents have imbibed the anti-vaccine propaganda that is so prevalent, they might be less likely to vaccinate their children according to the recommended schedule. The authors looked for such a correlation between older siblings with ASD and TCV exposure levels and found none. They also asked whether parents of children in the case group may have suspected that their children had an ASD and been influenced in their choice of vaccines by that knowledge, but none of the case children had been diagnosed by 7 months and only a few had been diagnosed by 20 months, which were the two time periods for which cumulative thimerosal exposure was calculated. In light of this, I would tend to interpret this seemingly paradoxical result as meaning, in essence, that there really isn’t even a whiff of a hint of a difference between the two groups.

This study had an additional strength as well, namely that the case and control populations were collected from three managed care organizations (MCOs) that participate in the VSD. Consequently, because of the detailed records maintained by these MCOs, investigators were able to develop a detailed and accurate estimate of total thimerosal exposure from the computerized databases maintained by the MCOs as well as the medical records of the cases, controls, all supplemented by standardized interviews with the parents. In addition, outcomes were measured in clinical settings using standardized assessment tools. In Price et al, the most up-to-date standardized assessment tools used to diagnose ASDs were used to identify cases. In addition, in order to make sure that the controls did not include children with undiagnosed ASD, which would tend to decrease any apparent differences between the groups, controls the lifetime form of the Social Communication Questionnaire was administered as part of the interview with each mother for children who had indications of any neurodevelopmental difficulties. Several children were excluded from the control group in this manner. Finally, the detailed medical records and databases maintained by the MCOs allowed for the detailed determination of and control for many potential confounders. All of these are strengths that were shared with Thompson et al.

So is this study the “last nail in the coffin” of the hypothesis that TCVs cause or contribute to ASDs? Scientifically, I would argue that it’s close, if not actually the final nail. After all, there have been multiple large, well-designed epidemiological studies of varying designs, all of which have come to the same conclusion: There is no detectable correlation between exposure to mercury in vaccines and ASDs. As far as case-control studies go, Price et al is quite good, but it is a retrospective study and the possibility of undetected biases or unidentified confounders can never be completely excluded. Also, it shares one other weakness with Thompson et al, namely a relatively low response rate of around 30%. However, as the authors pointed out in their response to Sallie Bernard, that participation rate was actually higher than predicted as the study was being designed, and it was accounted for in incredible detail in the technical description of how the study was set up.

Even though Price et al provides yet another bit of powerful evidence that, as far as science can tell, mercury in vaccines is not a cause of ASDs, I am under no illusion that this study will put this issue to bed once and for all. After all, if Blaxill and Olmsted are still publishing books based on Olmsted’s laughably poorly researched series Age of Autism. Let’s also not forget that Sallie Bernard was an external consultant for Price et al, as well. No doubt she will make her displeasure known soon, and no doubt it will consist of the same already refuted criticisms that she leveled at Thompson et al.

I can think of one criticism of this study that the anti-vaccine movement will level at it. In the methods, the authors state:

Children were excluded if they had the following medical conditions with known links to ASD traits: fragile X syndrome; tuberous sclerosis; Rett syndrome; congenital rubella syndrome; or Angelman syndrome.

Bernard complained that low birth weight children were excluded from Thompson et al (and presumably also from this study), not understanding that 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. Or perhaps she did understand that and picking up false positives from random noise is what she hoped to see. Be that as it may, the same reasons apply for excluding children with medical conditions with known links to ASD traits. Including them would have added random noise to the current study. Anti-vaccine zealots will no doubt claim that the CDC intentionally excluded them because they are more “vulnerable” to “vaccine injury,” but there is no convincing evidence that this is so, and making such a claim is a shifting of the goalposts from the original claim that autism is a “misdiagnosis for mercury poisoning.” Such a hypothesis will probably eventually have to be studied, but it is a relatively implausible hypothesis given the weight of existing evidence. I also wonder if anti-vaccine activists realize just how much of a shrinking of their hypothesis it is to narrow it down to saying that vaccines cause autism only in children with these conditions. Particularly ironic is congenital rubella syndrome, given that maternal rubella during pregnancy is one of the few known external contributors to the development of autism.

CONCLUSION

In the end, it is always frustrating to watch how studies like Thompson et al and Price et al are spun by anti-vaccinationists. Epidemiology is like that, though. It’s virtually impossible to conduct a case-control study like this without there being significant shortcomings in it. The reason is that, unlike a bench experiment, the investigators can never control all the variables. Trade-offs are inevitable, and rarely are there adequate resources to assure sample sizes large enough to be completely bullet-proof or to be able to account for every single potentially confounding variable.

However, if there’s one rule in science-based medicine, it’s that no one study is ever sufficient to confirm or rule out correlations between undesirable outcomes and various exposures. However, as the weight of several studies starts to bear down on the problem, the preponderance of evidence must at some point be acknowledged, 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. Price et al happens to be one large and convincing chunk of that evidence, but it is not the only one. It builds on multiple other studies and it fits into the confluence of evidence strongly refuting the hypothesis that mercury in vaccines is a cause of autism.

Not that the die-hard cranks will ever accept that result. Blaxill and Olmsted’s book still stands there, thumbing its nose at science.

Posted in: Neuroscience/Mental Health, Vaccines

Leave a Comment (56) ↓

56 thoughts on “The final nail in the mercury-autism hypothesis?

  1. Chris says:

    That is not to say that we shouldn’t try to build bridges to parents who express fears over vaccines because they’ve heard the message of anti-vaccine leaders like Bernard, but trying to convert or coopt high profile anti-vaccine activists like Bernard is a waste of effort.

    One has to be motivated by ideology instead of science to go after a hypothesis several years after the incidence of that hypothesis is no longer valid. Normal people finding out that their particular bug-a-boo no longer existed would stop championing the the removal of that bug-a-boo. or research demonizing that bug-a-boo.

    In 2001 Sallie Bernard was unable to find DTaP vaccines with thimerosal for the the Burbacher vaccine primate study. So Burbacher had to add thimerosal to the vaccine given to the primates.

    Don’t believe me? It is on the public record in the Autism-Mercury Yahoo Archives… make sure to remind anyone telling you that thimerosal in children’s vaccines is still causing autism:

    # Subject: Thimerosal DTaP Needed
    # From: Sally Bernard
    # Date: Wed, 27 Jun 2001 00:01:50 -0400
    # Yahoo! Message Number: 27456
    http://onibasu.com/archives/am/27456.html

    Hi all:

    A group of university-based researchers needs several vials of the older DTaP vaccine formulations which contained thimerosal for a legitimate research study. If anyone knows an MD who might have some of these vaccines or knows where to get them, please email me privately.

    Thank you.

    Sallie Bernard
    Executive Director
    Safe Minds

  2. JKW says:

    Truly, anyone continuing to defend the autism=misdiagnosis for mercury poisoning idea must realize they are fighting reality. I understand their financial and emotional investment, but they really need to give it up.

  3. cervantes says:

    This one didn’t really need a final nail, it’s been dead for a long time. The whole affair is instructive, however, about our flawed nature. People very often get committed to a belief and end up arguing backwards, from their conclusion to whatever evidence they can cherry pick or misunderstand that fits their pre-conceived frame. That’s also called religion. Once it happens to people, it is very hard to shake them free.

  4. theshortearedowl says:

    “In the covariate adjusted models, we found that an increase in ethylmercury exposure in 2 of the 4 exposure time periods evaluated was associated with decreased risk of each of the 3 ASD outcomes. We are not aware of a biological mechanism that would lead to this result.”

    Didn’t the Polish MMR study (comparing the triple vaccine vs the individual ones) find a similar effect? That the triple vaccine was associated with a small but statistically significant decreased risk of ASD? Are we sure that there isn’t some possible cause – say a decreased risk of subclinical measles infection that could produce some neurodevelopmental effects?

    I only ask to annoy AoA.

  5. qetzal says:

    Normal people finding out that their particular bug-a-boo no longer existed would stop championing the the removal of that bug-a-boo. or research demonizing that bug-a-boo.

    The problem with this, IMO, is that it only applies to normal people who care primarily about the truth. Unfortunately, plenty of people care more about getting attention, feeling important, and believing that they’re right. Actually being right doesn’t necessarily matter to such people. And that’s before we even consider the people primarily care about making money off others (again, regardless of what’s actually right.)

    Take Sally Bernard, for example. If her idea is wrong, then there’s not much point for her to be Executive Director of Safe Minds any more, is there? Her important position, the attention she gets from her followers, even her own sense of worth are potentially in jeopardy. Easy to see how she might convince herself that she must be right, regardless of the evidence.

    Like cervantes says, it’s akin to religious belief. For some people, once they’ve decided to believe, evidence is no longer relevant. And unfortunately, that’s pretty normal behavior for humans.

  6. Deetee says:

    David, can I just say how much I appreciate the effort and summation you do to keep on top of all the antivax nonsense. You rock +1

  7. lizditz says:

    I too appreciate the efforts of those keeping on top of the antivax nonsense.

    Here’s a list of blog posts & news reports covering the Price paper

    http://lizditz.typepad.com/i_speak_of_dreams/2010/09/important-new-paper-again-maybe-finally-no-link-between-vaccination-and-thimerosal-in-vaccines-not-c.html

  8. Shortearedowl: You’re not the only one. I think I heard Mark Crislip mention a similar theory for a protective effect in a recent QuackCast.

    Is it wrong that I would absolutely and lingeringly savor the moment such an effect was proven?

  9. daedalus2u says:

    Immune system stimulation might have a protective effect by “exercising” the various parts of the immune system (but this is quite speculative).

    Mild and self-limiting immune system responses would be the “best” (if this mechanism is correct), where the immune system gets turned on, ramps itself up, does what ever it is supposed to do, and then turns itself back down to the pre-stimulus state.

    If that is the mechanism for any protective effect, then allowing the natural course of a disease (provided the disease is mild and self-limiting) might be better than trying to suppress the symptoms (which are actually the immune response). I have said this before, but feeling weak and having a fever are “features”, they compel you to not use metabolic resources for your “lifestyle” while your body is trying to save your life. Yes, you feel crappy when you are sick, that is a “feature” so you don’t do something foolish like try to work when you are sick and should be resting.

    I want to emphasize this idea is highly speculative, and has nothing to do with vaccines. A vaccination is a very safe and mild self-limiting immune system stimulation. TCVs are much safer than a disease because TCVs don’t have any living disease organisms. TCVs can’t cause an infection.

  10. Solandra says:

    My ex-sister in law refuses to vaccinate her children and it drives me CRAZY, especially since she takes them to Israel where they have incidences of wild Polio. She has this “doctor” that tells her that vaccinating is bad. Their excuse can no longer be the mercury since they know that it’s been removed since about 2000, so they come up with other excuses. Now it’s the “toxins” or whatever. These people have no understanding of basic biology or common sense, and they are endangering their children and being lead by “doctors” who promulgate this crap. I don’t know what we can do, since study after study and thousands of real life anecdotes (which you think they would love since much of alternative “medicine” thrives on that) point to vaccines being OK. It’s like we’re fighting something that has become, basically, a religion. And since they don’t listen to science, what can we do??

  11. pmoran says:

    As David has pointed out before, the MMR, thiomerosal, and more recent “too many too soon” hypotheses are attempts to explain something that is just not there. Our job is not done until this is more widely understood.

    e.g. –

    http://www.ic.nhs.uk/statistics-and-data-collections/mental-health/mental-health-surveys/autism-spectrum-disorders-in-adults-living-in-households-throughout-england–report-from-the-adult-psychiatric-morbidity-survey-2007

  12. # Solandra

    “My ex-sister in law refuses to vaccinate her children and it drives me CRAZY, especially since she takes them to Israel where they have incidences of wild Polio. ”

    Firstly, I’m feeling reasonably appalled at someone who would travel internationally without vaccination, much less with children. It’s not just polio and the other routine vaccines, how about Hep A and B which are at much higher levels in many other parts of the world.

    Possibly, the U.S. would be within their rights to inform people traveling abroad (in general or to specific areas) that they must either have the required vaccination, be exempt due to a documented medical condition, or undergo a quarantine when returning to the States.

    I’m sure that would go over well, politically :)

  13. desta says:

    I think homer simpson once pointed out that sometimes you have to ‘double kill that corpse’

  14. MountainHowie says:

    The US federal vaccine court has awarded the family of nine-year-old Hannah Poling $1.5 million, the first such award. The court ruled that vaccination didn’t “cause” her autism, but “resulted” in it by aggravating a pre-exiting condition in the girl. However, 4800 other lawsuits in the federal court.

    Has anyone had a chance to review the evidence from the case? All I can find right now is the court’s decision.

  15. Chris says:

    See:
    http://www.sciencebasedmedicine.org/?p=174

    There is also the links in the Neurologica thread I pointed out to you there.

  16. Chris says:

    Sigh, comment in moderation. It just point you to an article dated July 23, 2008 titled “Autism and Vaccines: Responding to Poling and Kirby”… it does not show the evidence, but kind of explains why the Polings have restricted access to records.

  17. MountainHowie says:

    Thanks for the links Chris.

  18. David Gorski says:

    I think homer simpson once pointed out that sometimes you have to ‘double kill that corpse’

    Note my reference to the “double-tap” in my post. :-)

  19. lizditz says:

    1. Congratulations — this piece got Kottke’d

    http://kottke.org/10/09/vaccines-dont-cause-autism

    2. Fewer than 1% of children <35 months are completely unvaccinated: Wall Street Journal

    http://blogs.wsj.com/health/2010/09/16/toddlers-for-the-most-part-are-getting-vaccinated/

    For all your data needs

    National, State, and Local Area Vaccination Coverage Among Children Aged 19–35 Months — United States, 2009

    http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5936a2.htm?s_cid=mm5936a2_w

  20. Marsha says:

    Keep spreading these lies but they won’t help. Truth’s out & too many are awake now for the cover up to continue.

    The proof is in the numbers & science is on the side of truth no matter how others try to spin it.

    The people who have been duped & those duping them cannot even prove vaccines have ever worked. But we have proved they don’t.

    “Proof That Vaccines Didn’t Save Us”

    http://genesgreenbook.com/content/proof-vaccines-didnt-save-us?page=1

    All the studies done by the foxes guarding the hen house don’t mean a thing. Vaccines cause these neurological disorders we label autism & the people know it. And it’s not just the mercury that’s toxic either. There are many ingredients that are.

    Let’s take aluminum & mercury which are just two of the toxins in most vaccines & see what happens in this experiment;

    http://www.youtube.com/watch?v=Z7Ilxsu-JlY

  21. David Gorski says:

    Marsha, Marsha, Marsha. (Couldn’t resist. I’m of the generation for whom The Brady Bunch was big.)

    I’m way ahead of you. Here’s the intellectual dishonesty of the “vaccines didn’t save us” gambit examining the utter scientific and intellectual vacuity of the very Gene’s Green Book link you provided:

    http://www.sciencebasedmedicine.org/?p=4431

  22. canuck says:

    This study does not prove there is no link between childhood vaccines, thimerosal and ASD. Final nail in the mercury-autism hypothesis? Could not be farther from the truth – though many would like to believe otherwise. Though the study is seemingly well written and follows the design quite well and is carried out well, the design is so flawed that the end result could be predicted before the study took place. Price et al (and others before them) took a group of children with confirmed ASD and documented exposure to mercury. They then established a control group of children without any ASD who all had similar exposures to mercury. Any children in the control group who could have potentially had undiagnosed ASD were also removed. Not surprisingly enough they concluded that because both groups had similar exposures to mercury and there was no appreciable increase in risk from one group to the other that there was no causal link. I am not sure how to categorize this but this is not science based medicine.

    To put this differently, this would be like researchers getting together and putting all people who had upper cervical manipulation and a VBA dissection in a case group and then finding a matching group of individuals based on age, sex, gender etc. who also received upper cervical manipulation but had no VBA dissection for a control. It is obvious to anyone who knows anything about study design and even those who don’t that the results would show no link of manipulation to artery dissection.

    Both studies, the fictitious one and Price et al’s have a fatal flaw. Any study that seeks to look at the causal association between a condition and a potential risk factor should not select and control the risk factor which they are studying. It is the non-risk factors which should be selected and controlled and doing anything else is manipulation at best. Gorksi’s attempts to downplay design, while adding how complex this type of study are diversion. Designing a good epidemiological study to examine mercury as a risk factor is not as complex as he makes out. At this point it is prudent to note that the original study design panel recommended against this study design due to this very reason but were overruled by the CDC and the AHIP, two groups that incidentally funded the study and have some vested interests in finding no link between mercury and autism, to say the least. I am not going to go all ‘conspiracy theorist’ on anyone, but find this conflict of interest troubling to say the least on my validity and bias scale and it is worth pointing out as this conflict of interest is not mentioned in the paper.

    Anyway, this is another ‘study’ which is not worth the paper it is written on. The weight of poor studies on the matter is growing and statements such as the “nail in the coffin” of the mercury autism debate are more than premature. To be clear, I am not an anti-vaxer, so save those attacks for others more deserving please. If anything, I am anti-bs and Gorski’s conclusion, if not so hypocritical, wrong and clearly biased, would be laughable, yet sadly there are too many small minds who will eat it up without question. Perhaps Gorski and others could jump off the bandwagon for a moment and turn their so called evidenced based medicine (or SBM if you prefer) radars on when reading something that is so clearly hype and pseudoscience. Confirmation bias anyone or perhaps something more insidious???

  23. squirrelelite says:

    Marsha,

    You didn’t quite make it to Scopie’s Law territory, but citing a YouTube video as a scientific experiment gets you pretty close.

    Have you read Dr Gorski’s post on the source of your first reference?

    I suggest you give it a detailed and careful reading and post your response here. (It got over 500 comments before finally being laid to rest, so let it be.)

    http://www.sciencebasedmedicine.org/?p=4431#more-4431

    Your genesgreenbook post asserts

    it was better sanitation and hygiene in the cities that prevented the spread of diseases

    Certainly sanitation and hygiene help but they are not sufficient in and of themselves. One fortunate fall-out from all the publicity last year about the new H1N1 variant of the flu virus and recommended hygiene measures may have been (it will take more careful and detailed analysis to get a definitive assessment) a reduction in cases of food poisoning which can certainly be caused by bad hygiene.

    But, if you wish to assert that sanitation and hygiene prevented the spread of infectious diseases without the aid of effective vaccination programs, then I would like to see your answer to Chris’s question from the Gorski article.

    She cited the following data on measles incidence.

    Year…. Rate per 100000 of measles
    1912 . . . 310.0
    1920 . . . 480.5
    1925 . . . 194.3
    1930 . . . 340.8
    1935 . . . 584.6
    1940 . . . 220.7
    1945 . . . 110.2
    1950 . . . 210.1
    1955 . . . 337.9
    1960 . . . 245.4
    1965 . . . 135.1
    1970 . . . . 23.2
    1975 . . . . 11.3
    1980 . . . . . 5.9
    1985 . . . . . 1.2
    1990 . . . . .11.2
    1991 . . . . . .3.8
    1992 . . . . . .0.9
    1993 . . . . . .0.1
    1994 . . . . . .0.4
    1995 . . . . . .0.1

    And then asked:

    What happened between 1960 and 1970 in regards to the incidence of measles?

    Specifically, what major improvements in sanitation and hygiene took place in the 60′s that caused an order of magnitude reduction in the incidence of measles?

    Or was it nutrition, i.e. Tang?

  24. David Gorski says:

    @canuck

    Wow. So many straw men, so little time. No one has said that Price et al “proves” that mercury in vaccines doesn’t cause autism. To wit, here’s part of my conclusion:

    However, if there’s one rule in science-based medicine, it’s that no one study is ever sufficient to confirm or rule out correlations between undesirable outcomes and various exposures. However, as the weight of several studies starts to bear down on the problem, the preponderance of evidence must at some point be acknowledged, 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. Price et al happens to be one large and convincing chunk of that evidence, but it is not the only one. It builds on multiple other studies and it fits into the confluence of evidence strongly refuting the hypothesis that mercury in vaccines is a cause of autism.

    Apparently canuck read the part about “last nail” and then didn’t read much further. For a summary of the other data that represent the prior “nails” in the thimerosal-autism hypothesis, I suggest that canuck read Mercury in vaccines as a cause of autism and autism spectrum disorders (ASDs): A failed hypothesis. Then there’s also our page summarizing the data on vaccines and autism, one part of which is a section on thimerosal in vaccines and autism:

    Vaccines and autism. (Scroll down to the topic “Thimerosal and autism.”)

    No, canuck, your attempt to dismiss the studies as “junk science” notwithstanding, there are copious data indicating that there is no detectable association between mercury in vaccines and autism spectrum disorders. All this post was saying was that Price et al is but the latest chunk of evidence. Given the quantity of evidence upon which Price et al builds, it is not unreasonable to call this study the “final nail” in the thimerosal-autism hypothesis.

    Nice touch with the pharma shill gambit, though. What was that again you were saying about not being a conspiracy theorist?

  25. Chris says:

    canuck, your objections are explained as specious here.

    I would also like to point out that studies on smoking done over fifty years ago followed the same group selection protocol. They were chosen and matched by sex and age, then the level of smoking and what they smoked was compared to rates of lung cancer. This is how they found out that cigarettes were more dangerous than pipes and cigars:

    The cohort studies verified the association between smoking and lung cancer and also found that the lung cancer death rate was substantially higher in cigarette smokers than in smokers who used pipes or cigars; that the strength of the association between smoking and lung cancer increased with the amount of smoking;

  26. canuck on case-control design: “To put this differently, this would be like researchers getting together and putting all people who had upper cervical manipulation and a VBA dissection in a case group and then finding a matching group of individuals based on age, sex, gender etc. who also received upper cervical manipulation but had no VBA dissection for a control. It is obvious to anyone who knows anything about study design and even those who don’t that the results would show no link of manipulation to artery dissection.”

    No. Not like that at all.

    It would be like looking at a group of people with VBA dissections (cases) and another group of people without VBA dissections who are the same age/ sex/ income/ etc. (controls) and then checking to see if there was a difference in visits to the chiropractor between the two groups.

    If twenty-somethings with VBA dissections were more likely to have seen a chiropractor recently than twenty-somethings without VBA dissections, then we deduce that there seems to be a relationship of some kind between chiropracty and dissecting VBAs in young people.

    First you select your groups. Then you look at the factors you have in mind. The factors you are looking at are not controlled in advance, they are investigated afterwards.

  27. canuck says:

    @ Gorski

    To be clear, my statement was the, “study does not prove there is no link between childhood vaccines, thimerosal and ASD”. I never claimed you stated that Price et al proves that mercury in vaccines doesn’t cause autism though you certainly go to great lengths placing this study on a pedestal and as a “large and convincing chunk of evidence” to strongly refute that mercury in vaccines causes autism. Perhaps saying that others have more than proved the opposing view is the same or perhaps it is splitting hairs but I concede you did not make that statement (even though I never claimed it to begin with, though certainly others have). Of course you are not responsible for others.

    Also, please do not assume what I have read or have not read. Certainly there are parts of my post which can easily be misconstrued and examining them now they were not written as clearly as I would have liked. Haste makes waste. That said, I stand by my first statement. There are many people that are using this study as definitively demonstrating the lack of a link and this is a generous interpretation to say the least. Price et al has some severe limitations yet all I hear are largely baseless arguments on one side and glowing adulations on the other. This rhetoric and partisanship passed off as scientific is less than in my opinion. Studies should be objective and above the fray however this latest work is far from this. Also, before someone accuses me of throwing the baby out with the bathwater, I don’t throw out the whole study because they have bias, unlike many, but weigh it appropriately given the strength and condition of that bias. A quick read of the discussion more than shows the author’s hand, especially when compared to the actual results not to mention the admitted selection bias. As well, my issues with this study are not just related to bias but it is a small factor. For once it would be nice to see people apply their keen critical analysis to a study that may otherwise support their bias versus just turning it on only when something doesn’t fit or using it to attack others. Certainly this is made more challenging when the technical reports are several hundred pages in length, the analysis is complex and heavy in statistics etc., but there are more than enough people qualified to make this analysis. Further, so my critics don’t think otherwise, this generalization regarding critical analysis applies to those on both sides of the argument, some more than others.

    For the record and since it seems you have somehow already concluded otherwise, I happen to side with those who believe that the mercury in vaccine hypothesis as a cause of autism has its issues. I am however more measured in my support and am more skeptical in the body of research then clearly you and others are, but nonetheless I believe we largely agree on the basics.

    Also for the record, you seemingly accuse me of being a conspiracy theorist and mention the pharma shill gambit. You certainly spend some effort raising that flag (on this and other blogs) and I find it interesting that one side of this issue can so readily accuse, attack or dismiss those that may have some financial motives in an association of ethylmercury with autism, but seemingly dismiss any self interest of pharmaceutical companies or those organizations who may have supported the safety of vaccinations containing ethylmercury or those who actual deliver those to the public. Surely you recognize that a corporation has many interests, some of which may be contrary to those of the public at large. Without making accusations, and I don’t believe I did in my earlier post either, at least related to pharmaceutical companies, CDC, or AHIP, I cannot dismiss any motive that a pharmaceutical company may have in ensuring one of their products is not implicated, just as I am not going to dismiss the likelihood that there are those that trumpet the evils of vaccines for their own interests. The difference here is that one of these parties has the political means, money, power, know-how and connections to actually do something about it. Again, I am not saying they are actually doing anything devious or doing anything about it – other then of course the well documented cases – but more so I am saying that I rate a study lower on the bias scale if an interested party is involved. We all do or at least should. That is my point. If exercising a critical analysis of any and all research I see based on potential biases makes me a conspiracy theorist then I guess, by that definition, then I am.

    Last, I did not state or attempt to dismiss all the studies as “junk science” nor did I use those words – those are yours. What I said was that the amount of poor studies was growing (on both sides) and that in my opinion this study for all that it was, was not worth the paper it was written on. Given the effort, time and everything invested in this research, I find the study somewhat disappointing and hoped that some of the seemingly fatal flaws were not there. Additionally, the bias and narrative outside the scope of the study are further disappointments. Anyway, what I was hoping to get across and obviously did not do very well was that drawing conclusions that are not supported by the actual results and broader than what the study showed and then building them up for whatever means to me is hype and pseudoscience.

    I hope this helps explain my prior post. Let the diminishments, demonizing and distractions begin.

  28. canuck says:

    @ Chris

    Thanks for the link to the teachable moment treatise (which I had already read) however, I am already aware of the structure, design, strengths, weaknesses etc. of case-controls, cohorts etc. and this does not address my objections to Price et al.

    As for the tobacco study, I am not sure how this relates to Price et al as they are distinctly different studies, done at different times, looking at entirely different variables etc., but thanks for that too – I guess.

  29. David Gorski says:

    For the record and since it seems you have somehow already concluded otherwise, I happen to side with those who believe that the mercury in vaccine hypothesis as a cause of autism has its issues.

    Oh, it has more than “issues.” It’s been about as refuted as a hypothesis can be using epidemiological evidence and basic science. It’s pining for the fjords. Or it would be, if science were all that mattered.

    As for your dodging owning the term “junk science,” OK, fine. You didn’t use the actual term “junk science.” You did, however, characterize the study as “poor” and “not worth the paper it was written on” in the context of insinuating an irreconcilable financial conflict of interest due to pharmaceutical companies. Given that and given that the very definition of “junk science” is ideologically and/or financially motivated bad science designed to show a predetermined result, I do not think I was out of line in summarizing your criticism as calling it “junk science.”

    You say pot-AY-to, I say pot-AH-to. And all that rot. You may not have actually used the actual term “junk science,” but you did, in essence, refer to it as junk science without actually coming out and saying it.

  30. canuck says:

    @ Alison

    I think you are missing my point or at least one of them. I understand how the study was conducted and my example is a gross oversimplification so I apologize. The point I am trying to make with the example is the same one you are making – first you select your groups, then attempt to control for all the variables you are not looking at and then examine the risk factors or variables you do want to look at. The risk factors should not be subject to any selection bias or otherwise controlled.

    If the case and control groups in my example were both selected from a group of patients who were all getting upper cervical manipulation according to a pre-determined schedule then you would be closer to Price et al. Then you could examine the results and see if performing one additional adjustment after having already done ten would significantly increase the risk of VBA dissection. You could also run another survey to see if performing enough adjusments to account for 2 SD’s in a population of people that had already had their neck manipulated at least once had any appreciable increase in risk.

  31. canuck says:

    @ Gorski

    Just a clarification – I did not mention pharmaceutical companies in my original post or any “irreconcilable” conflicts.

  32. Scott says:

    @ canuck:

    Please explain in what way the thimerosal exposure in Price et al. were “subject to any selection bias or otherwise controlled.”

  33. Deetee says:

    Canuck, you are parroting the cries of antivaccine proponents in criticizing this study’s design. If you think the methodology was rigged to ensure there was an identical exposure in both the cases and the controls, then how do you explain away the inconvenient truth that the cases had significantly higher exposures to thimerosal between birth and 20 months?
    Kinda squashes your concept of them “establishing a control group which had similar exposures to mercury”, doesn’t it?

  34. squirrelelite says:

    @canuck

    OK,
    Let’s see what you did say in your original comment on 20 September 12:30 PM.

    You started by stating

    This study does not prove there is no link between childhood vaccines, thimerosal and ASD.

    Yes, but so what? A frequent aphorism about science is that it cannot prove a negative. But, it can place an upper bound on the probability that a tested hypothesis is true. And in this case since a 2 standard dose increase in mercury exposure actually corresponded to a decrease in the probability of developing ASD. In other words, that upper bound is very, very low.

    You then stated

    They then established a control group of children without any ASD who all had similar exposures to mercury.

    Not quite!

    Actually, as the METHODS portion of the abstract states,

    A case-control study was conducted in 3 managed care
    organizations (MCOs) of 256 children with ASD and 752 controls
    matched by birth year, gender, and MCO. ASD diagnoses were validated
    through standardized in-person evaluations. Exposure to thimerosal in
    vaccines and immunoglobulin preparations was determined from
    electronic immunization registries, medical charts, and parent interviews.
    Information on potential confounding factors was obtained from
    the interviews and medical charts. We used conditional logistic regression
    to assess associations between ASD, AD, and ASD with regression
    and exposure to ethylmercury during prenatal, birth-to-1 month, birthto-
    7-month, and birth-to-20-month periods.

    In other words, they established a control group similar to the ASD cases being studied by matching for Birth Year, Gender, and Managed Care Organization (MCO). Mercury/thimerosol exposure was calculated and analyzed as were several other factors, but it was not the basis for matching controls with ASD children.

    You then offered an analogy.

    this would be like researchers getting together and putting all people who had upper cervical manipulation and a VBA dissection in a case group and then finding a matching group of individuals based on age, sex, gender etc. who also received upper cervical manipulation but had no VBA dissection for a control.

    Not quite. This would be like looking at one group who had a VBA dissection and comparing it to a similar group who had no VBA dissection and THEN looking to see who in each had an upper cervical manipulation (and how many) and then analyzing to see if there was an association between the probablity of getting a VBA dissection and the number of upper cervical manipulations.

    Any study that seeks to look at the causal association between a condition and a potential risk factor should not select and control the risk factor which they are studying. It is the non-risk factors which should be selected and controlled and doing anything else is manipulation at best.

    Almost true. It is also necessary to control for other known risk factors.

    the original study design panel recommended against this study design due to this very reason but were overruled by the CDC and the AHIP, two groups that incidentally funded the study and have some vested interests in finding no link between mercury and autism, to say the least. I am not going to go all ‘conspiracy theorist’ on anyone, but find this conflict of interest troubling to say the least on my validity and bias scale and it is worth pointing out as this conflict of interest is not mentioned in the paper.

    An interesting statement. Do you have a reference for this recommendation and overruling?

    As for conflicts of interest and funding sources, Price et al states:

    Dr Marcy received honoraria for
    speaking for Merck and GlaxoSmithKline within the last 5 years
    and grant support for studies on Gardasil and ProQuad from
    Merck within the last 5 years; Mr Lewis received grant support
    from Medimmune, Sanofi Pasteur, Chiron, Wyeth, Merck, and
    GlaxoSmithKline; and Dr Bernal received research funding from
    the CDC, the National Institute of Mental Health, Health
    Resources and Service Administration, and Autism Speaks. The
    other authors have no financial relationships relevant to this
    article to disclose.

    and

    This work was supported by a contract
    from the CDC to America’s Health Insurance
    Plans and via America’s
    Health Insurance Plans subcontracts
    to Abt Associates Inc; Department of
    Population Medicine, Harvard Pilgrim
    Health Care Institute, Harvard Medical
    School; Southern California Kaiser Permanente,
    and Center for Vaccine Research,
    University of California Los Angeles;
    and Division of Research, Kaiser
    Permanente Northern California.

    As I read that, it says that CDC contracted with AHIP to provide access to their medical records so that the data could be studied.

    If that’s a conflict of interest, please explain.

  35. canuck says:

    @ Deetee

    Please do not affiliate me with the antivaccine proponents and their cries. My claims are not theirs and from what I have seen they have been mostly emotional and baseless. Further, I never said the methodology was “rigged” and also don’t think it is my job to explain the results. That said, I will let the authors of Prince et al address your question themselves:

    “The difference between the participant group and full sample estimates of the case control difference…supports the hypothesis that selection bias may have contributed to the participant group difference between cases and controls in mean cumulative exposure” in the birth to 7 month group.

    The authors then go on to say they saw similar results in the birth to 1 month and birth to 20 month group. To be fair, they say the effect of sample bias is small and by itself probably not responsible for the full effect.

    “VSD data may have muddied the picture somewhat”

    Modeling “suggests that controlling for having an older autistic sibling, or omitting records of children that had autistic older siblings, pushed the estimates of the case-control difference in exposure amounts closer to zero.”

    The authors also state repeatedly in the technical reports that the differences in cumulative exposure amounts for the periods spanning birth to 1 month, birth to 7 months or birth to 20 months were not statistically significant among participant and non-participant cases and control.

    I could go on and discuss recall bias, issues associated with maternal flu vaccines, assumptions made related to unknown lot numbers etc. etc. but really, are you asking me to summarize the entire study and technical report when you can read it yourself? Either way, I think I have more than demonstrated that the differences in exposures shown in the study could be in error or due to other factors and are more than likely closer to zero or perhaps even swung in the opposite direction.

  36. Deetee says:

    @Canuck-
    My earlier comment was in error, I of course meant:

    “….You are parroting the cries of antivaccine proponents in criticizing this study’s design. If you think the methodology was rigged to ensure there was an identical exposure in both the cases and the controls, then how do you explain away the inconvenient truth that the cases had significantly LOWER exposures to thimerosal between birth and 20 months? Kinda squashes your concept of them “establishing a control group which had similar exposures to mercury”, doesn’t it?”

    I stand by my comment. I merely said you were saying what the antivaxers say – I am sorry but if anyone is creating the impression you are with them on this one it is you. You clearly have meticulously dissected this study, cherry-picking every nuance that would argue against the careful and considered conclusion of the authors that thimerosal plays no part in the development of autism.

    What about the finding that cases had higher lead exposure? Does anyone in the “toxins cause autism” movement highlight that? No? Why not? Is it because lead is not one of the “toxins” in vaccines? – quite probably.

    In fact there is little indication that anything looked at in this study correlates well with autism, either a lack of thimerosal or an excess of lead (these are quite likely to be , as David Gorski says, merely statistical noise, and this is accepted within the technical report, as you say).

    But I do wonder what the response from the toxic vaccine lobby would have been if the association had pointed in the direction of thimerosal being associated with autism – would any of their objections about the supposed defects in the study be trotted out in what appears to be a concerted effort to smear the study? I doubt it.

    As David has explained, this study is merely one further indication among many that thimerosal has nothing to do with autism, and it should not be viewed in complete isolation. Nor can it be viewed as you characterise it (just using different words), as junk science.

  37. Deetee says:

    Just to say, Marsha would appear to be the same Marsha who lives over on Huffpo, under the moniker “Time4truth”. Her post here is almost identical to one comment she made.
    http://www.huffingtonpost.com/social/time4truthnow/the-age-of-autism_b_716795_61217980.html

    Her posts there are (by her own admission) based entirely upon “Mommy science” – she knows best and she deliberately does not read any scientific papers nor look at scientific evidence, because “there is nothing it can tell me”. Yet strangely she is happy to source antivaccine blogs as “evidence”.

  38. squirrelelite says:

    Thanks, Deetee.

    Evidently, a moderator over there has also decided to ignore her.

    Ignored on the HuffPo. Can you sink much lower than that?

  39. canuck says:

    @ squirrelelite

    “A frequent aphorism about science is that it cannot prove a negative.”

    Yes, but so what? :)

    “But, it can place an upper bound on the probability that a tested hypothesis is true.”

    Agreed and nothing in my post states otherwise.

    “And in this case since a 2 standard dose increase in mercury exposure actually corresponded to a decrease in the probability of developing ASD.”

    Debatable.

    As to your next point and as I stated prior, my description of the study and analogy were gross oversimplifications of the study design and again my apologies. I could certainly have reproduced the methods section but did not for obvious reasons. That said, I agree with your description of how this study was conducted and though my statement was potentially misleading, I did not say that the control group was selected based on mercury exposure levels.

    As for your next point, I stand by my statement made. Again, I agree that the groups were not selected based on exposure levels or vaccinations, but in effect they were based on a study design that chose children from HMOs that had children enrolled from birth and all followed the uniform vaccination schedule etc. It is unlikely that given this and a variety of other factors during selection that those children enrolled in the study would have had any significant variation in their vaccination regimes and thus mercury loads. I give the analogy again that this could be likened to a VBA dissection study wherein the case-control groups were selected from a group of patients who have all had upper cervical manipulation following a routine, standardized and published schedule for the last seven years and none (or at least very few) did not. Confounding indeed and something seemingly overlooked. Anyway, there are several other issues and I am not putting all my eggs in this one basket. Don’t take my word for this. Read the reports and you will find a lengthy discussion about many of these issues related to bias, error etc. Maybe I am missing something but when the authors themselves make the case in the 100’s of pages of supportive info, it is hard to ignore.

    “Almost true. It is also necessary to control for other known risk factors.”

    Of course. They also need to do a bunch of other stuff neither of us stated.

    “An interesting statement. Do you have a reference for this recommendation and overruling?”

    I remember first seeing this statement on some blog and found it curious myself. After a lengthy search I found a link, I believe, someone put in their blog post and less assuredly, perhaps I found it through a basic web search. I looked again and waded through more blogs and comments than I would normally like and all I can find is the troubling Safeminds and AoA references or others repeating them. I seem to remember it being contained in a governmental report related to some meeting but I am not sure. Anyone find this link/resource?

    As for the conflict of interest, providing access to records, funding and support through contract and being implicitly involved are two different things in my mind. Price is quoted as stating that the CDC was involved in the design, analysis, review and final draft of the study. This is the conflict I was referring to, not to mention the specious reference to the CDC/AHIP overrule, which unfortunately I cannot support at this time.

    All this said, I am happy to continue responding to questions and defending my every word, however perhaps some folks can read the technical reports themselves and maybe answer some of their own questions. Perhaps even someone can offer their opinions why they believe this study is as strong as they claim and then we can analyze their every word.

  40. canuck says:

    @ Deetee

    I am not sure how much more clear I can be when I say that I am not an anti-vaxer and that I do not speak for anyone else. These opinions are mine. You may also have read above that I side with Dr. Gorski for the most part on this issue. Siding with Gorski and anti-vaxers at the same time? Is that even possible? Is this just a case of “if you’re not with us, you’re against us” and seeking to otherwise define me/put me in a box, or perhaps it is the all too strong confirmation bias and need to otherwise diminish anything I say. Who knows and really, I don’t care. Either way, you are free to stand by your comment and you should, however you have not acknowledged the quotes and comments I provided from the authors themselves to address your direct question, which I believe does so more than adequately. BTW – I saw your slip and took it as such.

    As to charges of cherry picking, I responded to posters asking for clarification or proof, and I believe I presented each faithfully, acknowledging both strengths and weaknesses as they were. This data is not hidden and anyone who actually reads the technical reports should readily see it. I also did not present every nuance as you state – there are many more. Perhaps I should ask for posters to demonstrate to me how they arrived at their opinions that the study was strong, valid etc. but I have not – yet. Just reading the abstract, the shiny published study or some blog is likely not going to be that helpful in defense but I digress. Back on topic, most of my arguments in response to many of these requests were echoes of those of the study’s authors and in some cases direct quotes. So I guess any beef with me and my assertions is really a beef with Price et al. :)

    Last, though I have stated I have issues with the study, this by no means validates my support for a thimerosal – ASD link – far from it. If the study showed a correlation between mercury and ASD my objections would remain the same. In my opinion, and clearly there are those who disagree for whatever reason, this study does little either way to support or deny any correlation. You may recall my comment about it not worth the paper it was written on.

    Your last comments regarding further indications and my characterization are debatable but I will leave it at that and to what I have said prior.

  41. canuck says:

    @ squirrelelite

    “A frequent aphorism about science is that it cannot prove a negative.”

    I am not of the camp that agrees that science cannot prove a negative – it does it all the time, but I do acknowledge that this is something that is stated all the time. Just wanted to make this small clarification and don’t want to divert this topic away from the issue at hand. There are more than enough conversations out there tackling this issue for those inclined and I will not answer any posts to this regard.

  42. Scott says:

    It is unlikely that given this and a variety of other factors during selection that those children enrolled in the study would have had any significant variation in their vaccination regimes and thus mercury loads.

    Fortunately, we need not speculate on how much variation there was. See Table 2 and the end of page 658 for the numbers on variation. The section “Relationships of ASD Outcomes to Ethylmercury exposure” describes the reasons variation existed.

    Simply put, your complaint is entirely incorrect.

    I remember first seeing this statement on some blog and found it curious myself. After a lengthy search I found a link, I believe, someone put in their blog post and less assuredly, perhaps I found it through a basic web search. I looked again and waded through more blogs and comments than I would normally like and all I can find is the troubling Safeminds and AoA references or others repeating them. I seem to remember it being contained in a governmental report related to some meeting but I am not sure. Anyone find this link/resource?

    So you made the claim, and then find yourself unable to back it up?

  43. squirrelelite says:

    @Canuck,

    Thanks for replying to my comment. Perhaps some of our differences are just due to different writing styles and I will reply at least partly to that.

    However, a few substantive points first.

    Several commenters have replied to the overall tone of your first comment which can be exemplified by these quotes:

    This study does not prove there is no link between childhood vaccines, thimerosal and ASD. Final nail in the mercury-autism hypothesis? Could not be farther from the truth

    Both studies, the fictitious one and Price et al’s have a fatal flaw.

    Anyway, this is another ‘study’ which is not worth the paper it is written on.

    If anything, I am anti-bs and Gorski’s conclusion, if not so hypocritical, wrong and clearly biased, would be laughable, yet sadly there are too many small minds who will eat it up without question.

    Your first statement, that the study does not prove that there is no link, seems to imply this is a problem. I tried to point out that obtaining convincing proof of absolutely no connection is an impractically high goal and that the study’s conclusion that the probability of such a link is extremely low and tenuous provides the medical community with useful information.

    If the fatal flaw mentioned in your second statement is the selection process, evidently we agree that does not exist. Was there some other flaw?

    You may not think the study was worth the paper it was written on, but I thought it was worth the bytes on my hard drive to store the pdf and the pixels on my desktop to show the shortcut.

    The fourth statement, without some clearcut support for its assertions, is merely and ad hominem argument.

    If you are not anti-vaccine, these statements certainly make it hard to tell.

    Some stylistic suggestions.

    If you don’t have a good source to back up your statement, try to be more cautious and guarded in the strength you give to it.

    Try to make a good argument for what you are for.
    Make the statement.
    State the reasons that lead to that conclusion.
    Provide evidence to support those reasons.

  44. canuck says:

    @ Scott

    Ummm, I do not think you are getting what I am talking about, based on your response at least. In the quote you provide I am talking about study design, choice of study populations and selection and you are giving me figures and discussion based on the results of the analysis thereafter which nobody, including me, is speculating upon, except perhaps on their relative strength and validity. As you so astutely point out, those results and discussion are there in black and white. If I can make a recommendation, perhaps you might want to reread my posts and for added benefit, read the actual technical report which goes into much greater detail on all of it. Then we can maybe have an informed and pertinent discussion on the matter, or not. Sorry if I am making assumptions, but I have little to go on based on your written words.

    As to the other item in your post, I reiterate that I DID make the claim and now I AM unable to back it up. I do not like making statements that I cannot back up and my inability to find my corroborative source is troubling but I am not going to lose sleep over it. I looked to confirm the information initially, remember finding confirmation and then I guess shame on me for not linking to it with the foresight that I would make some statement about it in the future, someone would challenge that statement and I would therefore need to find it in my defense and that it might not be easily reproducible. If nobody can find the link/source I have no trouble withdrawing my comment as it really has little bearing on the argument I was making.

  45. canuck says:

    @ squirrelelite

    I have talked at least a couple times about how some of the words in my original post could be mistaken and have offered my apologies for such. It is certainly not my best work. Haste makes waste. Anyway, I believe the remainder of my posts have explained or at least lent some clarity to the original and it is possible this group has dissected every word I wrote as they called me to task – begrudgingly deserved in a couple instances. Thanks for reminding me…

    As for the source issue and stylistic suggestions, thanks. Now if only I did not interpret them as condescending and presumptive. I believe my post to Scott explains what happened with the one source issue it seems there was in the entirety of my posts. I also do not believe I applied a lot of strength to it, but either way can see how someone might interpret otherwise. Again, I have no problem retracting this comment if the source can not be located as it really has little bearing on my base argument.

  46. canuck,

    The source issue: nobody is going to do your sourcing for you. If you can’t back up your statement, just withdraw it. Don’t offer to do it at some vaguely specified future time. This isn’t about whether the issue is substantive, it’s about being careful to make statements for which you have evidence and realizing you’ve learned something when you discover you don’t have the evidence you thought you did. You know, science-like. This applies to everything, not just to cruxes (cruciae?) of arguments.

    The style issue: squirrelelite’s advice is excellent.
    “Try to make a good argument for what you are for.
    Make the statement.
    State the reasons that lead to that conclusion.
    Provide evidence to support those reasons.”

    It’s simple but not easy. Good expository prose takes practice and feedback. You might feel as though you are above learning and that you don’t need advice, but none of us is.

  47. squirrelelite says:

    Canuck,

    If I came across as condescending, I apologize. That was not my intent. I know sometimes when I review one of my comments I think to myself, “did that come out a little too preachy?” So, it’s good to get feedback.

    I did read all your comments, but chose to go back and read and respond to the first one because you had pointed out a discrepancy between what was being responded to and what you had actually stated in that first comment. If I overlooked significant corrections later, again I apologize.

    There are several commenters on this and other blogs whom I don’t always agree with, but which I read carefully anyway because they are trying to explain and support a specific idea.

    I look forward to reading your comments in the future.

  48. Scott says:

    mmm, I do not think you are getting what I am talking about, based on your response at least. In the quote you provide I am talking about study design, choice of study populations and selection and you are giving me figures and discussion based on the results of the analysis thereafter which nobody, including me, is speculating upon, except perhaps on their relative strength and validity.

    Ludicrous. You said, and I quote again,

    It is unlikely that given this and a variety of other factors during selection that those children enrolled in the study would have had any significant variation in their vaccination regimes and thus mercury loads.

    We know for a fact that the children enrolled in the study DID have significant variation in their vaccination regimes and mercury loads. Ergo, we know for a fact that your complaint is entirely unfounded.

    As you so astutely point out, those results and discussion are there in black and white. If I can make a recommendation, perhaps you might want to reread my posts and for added benefit, read the actual technical report which goes into much greater detail on all of it.

    I DID read the paper. I have a hard time believing that you did, however, given that you are making statements diametrically opposed to the facts which are, as you say, right there in black and white.

  49. canuck says:

    @ Alison

    I did not ask people to do my sourcing for me. I looked and could not find it readily and merely asked if someone on this site might have it handy assuming this was collaborative. I don’t think I am wrong in this assumption but I stand to be corrected. Since this seems to be an important issue with you and no source has been presented so far, nor have I bothered to look again, consider my prior statement withdrawn – for now.

    As for the rest of your post, I have not said that I am above learning or advice, far from it. I certainly would not be reading these types of blogs, engaging in discussion, wading through 100′s of pages of a technical report for a single study etc. if I weren’t. I also hope that it is clear that I am not close-minded, dogmatic or ideological as we unfortunately see all the time, stubborn perhaps but acquiescing at the same time. I appreciate any feedback and consider it a gift, if an all too rare one. That said, I would like to note that over the years I have learned that I find I don’t care too much for lectures, especially if they are somewhat hypocritical or misinformed. I am not leveling any accusations at you personally as I don’t know you and your posts at least in this thread don’t bely otherwise, but just commenting in general on feedback given and received. You did include yourself in your last comment, so thanks for that.

  50. canuck says:

    @ squirrelelite

    Thanks and likewise.

  51. canuck says:

    @ Scott

    “We know for a fact that the children enrolled in the study DID have significant variation in their vaccination regimes and mercury loads. Ergo, we know for a fact that your complaint is entirely unfounded.”

    Once again, I present the authors’ own words to refute this statement/claim you make:

    “There were no statistically significant differences between AD cases and controls in cumulative number of vaccines received at ages 28, 214, or 609 days. Nor were there significant differences in cumulative number of vaccines received at these age ranges between controls and any of the other classifications of cases (ASD, ASD with Regression, ASD-no-AD, AD with Low Cognitive Function Excluded, ASD with screened control group, and AD with screened control group).”

    I think this quote alone is sufficient to rebut your first statement of ‘fact’ related to vaccine regimes. Now for mercury loads which I have discussed in a prior post but will put again. Again in the authors’ own words:

    “The difference between the participant group and full sample estimates of the case control difference…supports the hypothesis that selection bias may have contributed to the participant group difference between cases and controls in mean cumulative exposure” in the birth to 7 month group.

    The authors then go on to say they saw similar results in the birth to 1 month and birth to 20 month group. To be fair, they say the effect of sample bias is small and by itself probably not responsible for the full effect.

    Some others:

    “VSD data may have muddied the picture somewhat”

    Modeling “suggests that controlling for having an older autistic sibling, or omitting records of children that had autistic older siblings, pushed the estimates of the case-control difference in exposure amounts closer to zero.”

    “Odds ratios and 95 percent confidence intervals corresponding to a one-unit increase in the exposure measures are shown. In many studies, a one-unit increase in exposure represents the difference between ‘exposed’ and ‘not exposed’, and for those studies this kind of odds ratio has intuitive relevance. However, for the current study a one-unit increase in the postnatal exposure measures correspond to a one microgram per kilogram increase in exposure, which lack intuitive meaning.”

    I could go on and discuss recall bias, issues associated with maternal flu vaccines, assumptions made related to unknown lot numbers etc., etc. The authors also state repeatedly in the technical reports that the differences in cumulative exposure amounts for the periods spanning birth to 1 month, birth to 7 months or birth to 20 months were not statistically significant among participant and non-participant cases and control. I am not sure how much I need to provide but this more than sheds some doubt on the ‘facts’ related to mercury loads. It also means my complaint is not “entirely unfounded”.

    I’ve read the paper, the technical report executive summary and both volumes of the technical report, plus a whole host of the supportive references etc. Reading the abstract and the published study only gives a glimpse and a skewed one at that. You claim you have read the “paper”, but I did not make that recommendation. I figured you had already since you quoted it. My recommendation was that you read the technical reports. Perhaps you are calling the reports the paper, but I think not.

  52. pmoran says:

    Scott’s point is critical to the value of this study, also to what some antivaxers seem to be saying.

    Why, Canuck, did you say that there would be no “significant variation” in “mercury loads” in the “children enrolled in the study”? As Scott points out, that actually varied from zero to many hundreds of micrograms, with a mean suggesting a fairly even distribution over this wide range.

    Surely that makes this a very suitable population for detecting a causal correlation between ASD and thiomerosal in vaccines, if one existed.

    Do you have any criticisms of the study that are likely to swamp the influence of such a variation in exposure, if thiomerosal is an important casue of that illness?

  53. canuck says:

    @ scott (and pmoran)

    Reading pmoran’s post I believe I see why we can’t figure out what the other person is talking about and any frustration therein – for my side of this, I apologize. My prior post, which sat in moderation forever, likely does not answer this question either. Your question was not clear to me until pmoran framed it differently. Agreed, there is a variation in cumulative mercury exposure and number of vaccines received per child in each study group for both the cases and controls. As you point out, the chart clearly shows this and my apologies. That said, the chart also shows the mean values for each group of cases and controls. These mean values show no significant variation from case to control for each group studied, which was part of my point to you.

    pmoran: As for the even distribution over the range, I fail to see how the mean shows that there is a fairly even distribution over the wide min and max range. Perhaps I am misinterpreting your description of an “even distribution”. If anything, one would expect a Gaussian distribution clustered around the mean which is what it appears we have. Further, with 2.9 controls per case and cases and their controls linked by group and each group analyzed according to their mean and cumulative exposures by case or control, the effect of individual differences is lost. Certainly there is a case for saying that there is suitable variation within the study population and I am not sure exactly what that distribution is per group of cases and controls, but I think there is a larger issue with this population and how it is selected that may hinder the results.

    Anyway, if I may start from the beginning and explain why I think this, perhaps this will help.

    One of the problems, in my mind, with doing a study based on vaccinations or any component therein and a disease outcome is the prevalence of confounding variables. Isolating one component of a vaccine while controlling for the others is very difficult and it is very difficult to interpret the results of a study if this is not done or not done correctly. Additionally, an inherent selection bias also exists depending on the study base. In this study, the population consists of children who have been enrolled in medical care since birth, or really before birth, and have remained under active medical care for many years. Part of the medical regimen is vaccination according to a pre-established schedule and each HMO will have their own schedule that will be followed by every physician. As cases were matched by HMO, sex and age there is a very high likelihood that three matched control cases, chosen at random would have a similar mean and cumulative exposure and vaccine regimen as the case based on the uniformity of the established vaccine schedule at that time, uniformity of vaccines used by each HMO at that time, uniformity in the locations where the vaccines were administered etc. The fact that certain cases could not be suitably matched and some sample sizes were very small yet were still included in the study also increases the bias and error. The exclusionary criteria further ensure that this population is less random. The more exclusionary criteria the more manufactured the data set. Overall, the nature of the study, study base and design basically guarantees that controls will have a similar exposure as cases except that they would not have the disease outcome as these would have been part of the exclusionary protocol. To be clear, I am not saying that mercury exposures or vaccines taken were part of the specific selection process, more so that, in effect, they were.

    I have discussed the admitted selection bias in a prior post and as the authors state, the selection bias was in a direction that “supports the hypothesis that selection bias may have contributed to the participant group difference between cases and controls in mean cumulative exposure birth to seven months.” They go on to say that similar results were obtained in the birth to one month and birth to 20 month groups. There is no way of knowing the true magnitude of this bias and though the authors opine that alone it likely does not account for the full effect, there is a possibility that what seemed like a negative correlation between mercury and autism may become a positive one or may have shifted the insignificant already positive associations to that of statistically significant. Again, there is no way of knowing and not to inflate anyone’s sails, but the study doesn’t clearly demonstrate this to me either way.

    Another curious thing for me is the type of measures made to show correlation or lack thereof. The first exposure measure is a reported one unit increase in exposure which corresponds to a one microgram increase (or 1 microgram/kg) in mercury exposure. This measure lacks intuitive meaning and the authors discuss how in many studies the one unit increase represents the difference between the exposed and not exposed and how for those studies this measurement and corresponding odds ratio is intuitive. They continue this discussion and state that in this study this “one unit difference metric for the odds ratio is not ideal.” Further, the use of a one microgram change in exposure is not statistically significant nor particularly meaningful in the context of vaccinations, especially when the difference between getting a vaccination or not getting one is in the magnitude of 0 to 12.75 or 0 to 25 micrograms.

    If the authors wanted to demonstrate an effect based on an exposed versus unexposed population I am curious why they did not look at a subgroup of children from each group that had documented zero mercury exposure. This would have been valuable and given the depth of the analysis in the study looking at a whole host of other factors, covariates etc., I wonder why this was not done or at least discussed. To me it would have been very valuable to compare those with no exposure to those with. For vaccination counts this would have been very difficult as a very small amount of study participants received no vaccinations, but at least for the birth to seven months group there are at least twenty children who have zero cumulative mercury exposure. I stated earlier that I had my issues with the overall ethylmercury equals autism hypothesis and was largely in support of Gorski. If someone would actually produce a reliable study to examine the relationship of the unvaccinated and/or unexposed and assuming it shows no correlation, this would put the nail in the coffin, so to speak, for me. Of course there would be no guarantees at silencing anyone, but again, I am curious why this was not at least tested in Price et al when so many other arguments were seemingly anticipated and tested, the data was there and readily available and the analysis fairly easy. Unfortunate to say the least and disappointing.

    Anyway, I have pointed out several issues prior and of course no study such as this is free from issues with bias and confounding etc. When the bias and confounding significantly interferes with the results however, I do not lend too much weight to the conclusions therein. As well, when the majority of the biases and errors are largely pointing in a single direction, it is also disconcerting. I hope this helps explain some of my issues with Price et al and doesn’t muddy the waters any more than necessary.

    Last, pmoran stated:
    “Surely that makes this a very suitable population for detecting a causal correlation between ASD and thiomerosal in vaccines, if one existed.”

    Just a clarification that a case-control study cannot find a ‘causal correlation’ but only an association. I will assume this was an inadvertent error.

  54. David Gorski says:

    We know for a fact that the children enrolled in the study DID have significant variation in their vaccination regimes and mercury loads. Ergo, we know for a fact that your complaint is entirely unfounded.

    Indeed we do. More reinforcement as to why:

    http://leftbrainrightbrain.co.uk/2010/09/safeminds-comments-on-the-latest-thimerosal-autism-study/

  55. canuck says:

    @ Gorski

    Really?

    “We know for a fact that the children enrolled in the study DID have significant variation in their vaccination regimes and mercury loads. Ergo, we know for a fact that your complaint is entirely unfounded.”

    Indeed you do not.

    Seriously, the link aside from a few comments, particularly wherein the author states that they cannot conduct a study that looks at zero exposure levels for mercury because it cannot be done or it is too difficult, seems largely on target and I happen to agree with a good portion of it. (As an aside, they can conduct these studies, just not in the way they did this one and they are not too difficult.) This said, I don’t see much to refute or counter what I am saying in my post. As I have said earlier, since I am merely quoting many of the statements made within the technical reports themselves, saying my arguments are “entirely unfounded” is not only inaccurate but serves to criticize the study or the authors themselves.

    Perhaps it is just easy to falsely categorize me as one of ‘them’ and thus pave an easier road to diminish or dismiss what I say. That said and to be clear, I read the link and what is being attributed to SafeMinds and what I am saying is not the same as what they are saying. I did not read their source letter or response, but from what I see their complaints are largely not mine. For one, I do not attribute the rise of autism to vaccinations. Two, I don’t bemoan the lack of studies in the unvaccinated and if you actually read what I stated, recognized the difficulty in doing so in my post (as another aside, it is important to note that the incidence of ASD is roughly 30-60 cases out of 10,000 which is 0.3 – 0.6%. The authors state you would need a serious amount of kids given the prevalence of the unvaccinated which lies at 0.4% to conduct a good study, but somehow they were able to find enough case studies in the same population, but I digress). Three, I recognize the modeling done to attempt to demonstrate a high versus low exposure in Price et al. Four, I am not making some complaint about temporal associations. Five, I am not bringing up some historical argument about autism to defend or support anything I state. Last, I recognize that I could be wrong, and if shown, am willing to admit as much – something others seemingly are less inclined to do. I could go on, but I have laid out my opinions for everyone to pull apart, in several different ways – trying to address the comments of those who have called into question what I have said. I have also acknowledged areas and points made by people when we do agree. Since the bulk of this provided link is spent refuting statements that I have not made or claimed, it is largely inconsequential to the discussion at hand. Interesting but definitely not reinforcement.

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