Respectful Insolence

Last week, the Journal of Pediatrics published a study that did a pretty good job of demolishing a favorite antivaccine trope used to frighten parents. In fact, it’s one of the most effective of antivaccine tropes, as evidenced by a large number of parents who are generally pro-vaccine expressing doubts when asked about this particular antivaccine slogan. I’m referring, of course, to the “too many too soon” slogan, in which antivaccinationists try to imply that the current vaccine schedule somehow “overwhelms” an infant’s immune system and leads to autism by some unknown and undemonstrated mechanism. There is no compelling science behind this particular idea, but that doesn’t stop it from being used as an argument against the current vaccine schedule by antivaccinationists and antivaccine-sympathetic doctors like “Dr. Bob” Sears (who created an “alternate” vaccine schedule based on the idea that the current schedule gives babies too many shots too soon) and Dr. Jay Gordon. “Too many too soon” even became the rallying cry of a march on Washington, DC led by the queen of the antivaccine movement herself (at least at the time, anyway), Jenny McCarthy.

So it was that when I wrote about this particular study and what it showed the first time, I couldn’t resist mentioning a few of the antivaccinationists who, predictably, attacked the study, including the aforementioned “Dr. Bob” Sears, whose tantrum on Facebook over the study was burning stupid distilled down to the most powerful stupid known, much as 16 Million Reserve distills down pepper extract to a mixture so hot that it’s painful. “Dr. Bob’s” screed has the same effect on the brain of anyone who has a science-based understanding of vaccines as 16 Million Reserve has on the tongue. So, for that matter, did homeopath Heidi Stevenson’s “scientific critique” of the study.

And so does Brian Hooker’s critique of the study.

The things I do for you! After reading Hooker’s “debunking” of DeStefano et al, I feel the need for many, many gallons of reason and science to wash the pain from my brain, much as a hapless person who ingests 16 Million Reserve will crave gallons and gallons of water to wash the pain from his mouth. Before I get into his “scientific critique,” let’s just remind everyone of who Brian Hooker is. Brian Hooker is a biochemical engineer who works as a consultant in the biotech industry who also, unfortunately, has turned to antivaccine quackery. Specifically, he belongs to the wing of the antivaccine movement that believes against all evidence that the mercury-containing preservative thimerosal that used to be in childhood vaccines until around 2001 to 2002 is a major cause of autism. He’s also somehow managed to beguile a certain budding antivaccine crank by the name of Jake Crosby to the point that Jake turned on his former allies and dished dirt in the form of their private e-mails, publishing them on the even crankier Patrick “Tim” Bolen’s website. Hooker’s claim, channeled through Crosby’s “reporting,” was that he actually had arranged the Congressional hearing on autism in November and that the antivaccine crank group SafeMinds had, through its lobbyist Beth Clay, stepped in and taken it over by misrepresenting themselves as representing Hooker.

I will give Hooker one thing. He did have a mildly funny quip to attack DeStefano et al when he said, “The Destefano et al. 2013 study is to science what the movie Ishtar was to cinema.” Of course, antivaccine quackery is more akin to what Plan 9 From Outer Space was to cinema and has about as much relationship to reality as Plan 9 did in that his complaints against the study nearly all derive from either antivaccine talking points or a complete misunderstanding what a case control study is.

First, however, I can’t resist but insert a brief quote from the editor of Health Impact News, which seems to be quite woo-friendly, introducing Hooker:

Why did we ask Dr. Hooker to comment? There are probably very few people in the world who have spent as much time looking at CDC studies related to vaccines and autism as Dr. Hooker. Dr. Brian Hooker, a PhD scientist, has been fighting the CDC since 2004 in trying to get them to comply with Freedom of Information Acts to see the CDC research that supposedly shows there is no link between mercury in vaccines and autism.

I couldn’t help but laugh at this. A better description is that few cranks have wasted as much of the CDC’s time and effort in pursuit of a scientifically bankrupt idea. Let’s take a look at Hooker’s complaints. First, he complains that the study “is not new,” as this were some sort of revelation. Well, duh. It’s right in the methods (and was discussed in detail by me when analyzing the study) that DeStefano et al uses data from a study by Price et al in 2010, which I also discussed. It’s not as though it were secret or anything. Although I’ve seen a lot of the fallacious antivaccine attacks on Price et al before, Hooker brought out a new one, in which he claims:

Not only was this original study fatally flawed due to a statistical error called “overmatching” (which I’ll discuss further below) but also the study authors hid data regarding the only valid part of the study (i.e., prenatal thimerosal exposure) which showed that children exposed to just 16 microgram mercury in thimerosal in utero were up to 8 times more likely to receive a diagnosis of regressive autism (Price C, et al. Thimerosal and Autism. Technical report. Vol I. Bethesda, MD: Abt Associates Inc; 2009). The study authors instead falsely reported no risk of autism associated with prenatal thimerosal exposure.

This technical report can be found here. It’s 235 pages long, and I was trying to figure out just what the hell he was talking about, given that Price et all was actually quite well controlled, and it was well explained how various risks were calculated. This smells like a bit of cherry picking of results from multiple comparisons. I pored over as much of the technical report as I had time to, and I couldn’t figure out what Hooker was talking about, but it’s certainly possible that I missed it. Every section that I read pointed out things like,” and the odds ratios in the relevant tables were all near 1. Googling for previous articles in which Hooker made this charge was unrevealing, too. He’s going to have to elaborate on this before I see any reason to take it the least bit seriously.

Next up is a complaint that seems to be a major talking point agreed upon by the antivaccine movement, namely that he thinks there are no “true controls in the study,” based on this passage from DeStefano et al:

Of the remaining 752 controls included in the analysis, 186 had an SCQ (Social Communication Questionaire) score <16 but had indications of speech delay or language delay, learning disability, attention deficit hyperactivity disorder or attention deficit disorder, or tics, or had an individual education plan.

Which leads Hooker to conclude:

This clearly shows that the 186 aforementioned controls (25% of the control group) were not controls at all but instead had some underlying developmental deficit (all of which are features of autism or autism spectrum disorder). Unlike the study design described (i.e., where autism cases were matched to neurotypical controls), autism cases were matched with “cases” of other, similar neurodevelopmental maladies. Thus, you would expect to see no difference between the two groups.

I discussed this complaint when I discussed Price et al the first time around and again just this week. But think of how silly Hooker’s complaint is. He once again does not understand what a case control study is. The whole point was to match cases, which means children with the condition under study, namely autism or autism spectrum disorder, or controls, which means children without autism or ASD. The whole point of administering the SCQ was to identify children in the control group who might have an undiagnosed ASD and in fact eliminated 7 children from the control group that way. Again, remember: The hypothesis being tested in Price et al was whether thimerosal-containing vaccines were associated with autism risk, and the hypothesis behind DeStefano et al tested was whether total antigen load due to vaccines is associated with autism.. Here’s another hint for Mr. Hooker: Speech delay is not autism, and, even if his complaint were valid, at worst such matching could only be expected to decrease any apparent difference between the groups, not eliminate it. Basically, Hooker is criticizing the investigators for not picking cases based on more than just autism. Of course, doing that would add heterogeneity to the case group.

Next up, Hooker complains that using the number of antigens as an estimate of vaccine exposure is meaningless. One reason he gives for this is the standard goalpost-moving antivaccine Gish gallop of claiming that it’s not the antigens but the “toxins” (yes, the “toxins gambit” is liberally used, in which Hooker complains about adjuvants, formaldehyde, and polysorbate 80 as the real culprits. As for the rest, the issue of using antigens as a surrogate for vaccines is discussed in this review article, along with a discussion of how children are exposed to far fewer antigens from vaccines today than they were in the past. Yes, it’s a crude estimate, but the argument that not all antigens are equal in evoking an immune response cuts both ways in that using, for example, the number of vaccines as the measure is arguably worse. Not that it probably matters, because autism risk doesn’t correlate with on time administration of vaccines compared to late administration anyway. Of course, the unspoken assumption behind Hooker’s objection is that the immune reaction caused by vaccines is an etiological agent that causes autism. There is no compelling evidence to support that assumption.

Another complaint Hooker has is that a high participation refusal rate led to selection bias. That’s an old complaint leveled against Price et al three years ago by SafeMinds, and it’s as without validity as SafeMind’s complaint was back then. Not that that will stop antivaccinationists from resurrecting it again and again. To them, repetition of a trope makes it true, rather like an incantation.

In fact, the rest of Hooker’s criticisms are basically warmed over SafeMinds criticisms about Price et al. He’s unhappy that there are no unvaccinated children in the study, to which I say: So what? That’s not what the study was studying, and it’s possible to get at the question of whether vaccines are a risk factor for autism without examining an unexposed cohort. The reason, of course, is that if vaccines do something to increase autism risk, there should be a dose-response relationship that can be gleaned from epidemiology. So far, no reputable researcher who’s looked has been able to detect such a relationship.

Even Hooker’s complaint about “overmatching” is warmed over SafeMinds:

The point made by Dr. DeSoto and Dr. Hitlan is that the cases and the controls in this study are too closely matched to each other. Cases were matched with controls of the same age, sex, within the same HMO and essentially the same vaccination schedule using the same vaccine manufacturers. This may be seen in Figures 1 and 2 of the Destefano et al. 2013 paper which indicated that there are almost no differences between the exposure to antigens between the case (autism) and control groups in every exposure group tested. This holds for cumulative antigen levels (Figure 1) as well as single day antigen exposure levels (Figure 2).

This type of error of course precludes “finding a difference” between cases and controls because all differences were matched out case-by-case.

This would be akin to analyzing radiation workers that got the same dosage of gamma radiation within cases and control groups to determine the relationship between gamma radiation and cancer incidence. Of course, since cases and controls got the same dosage, no effect would be seen. However, this is an unfair study. To see the true effect, cases would need to be matched with controls with variable levels of gamma radiation exposure and perhaps a “no exposure” group would be included as a baseline comparison to cancer rates within higher exposure groups.

As I said at the time about SafeMinds, Hooker seems to be criticizing a case control study for not being a cohort study, which is what he is proposing. So I’ll explain again, as it’s been three years since I’ve discussed this specific issue in depth. Here’s how case-control studies work. (Hint: They don’t work the way Hooker seems to think they work.) You take a population and identify the cases. Take a random subset of cases if you can’t examine all the cases. Then you look at the rest of the population and randomly select people who do not have the condition that you are studying. You match them for as many relevant demographic parameters as you can that could potentially confound any correlations that might be observed. Then you look for differences between the groups. If the cases, for instance, have a higher exposure to the substance under study, then the conclusion is that exposure to the substance is associated with the condition and therefore the substance might cause or contribute to the studied condition. If the exposure to the substance under study is lower in the case group than in controls, then the conclusion is that that substance might be protective. If the exposure is the same between the groups, then the conclusion is that that substance probably has no relationship to the condition under study, which is what this case-control study more or less concluded. Hooker looks at an observation that is a conclusion of the study and appears to misunderstand that a failure to find a difference does not mean that the groups were chosen that way, which is what was implied.

Basically, what Hooker is proposing is to match cases to controls on the variable being studied, which is a violation of Epi 101.If Hooker wants to say that a case control study is an inappropriate experimental methodology for the hypothesis being studied, let him make that case. But he’s doing nothing other than betraying ignorance and obfuscating the issue. Basically, what Hooker is proposing is to match cases to controls on the variable being studied, which is a violation of Epi 101. Of course, Hooker seems profoundly confused by the difference between case control studies and cohort studies. He seems to think that somehow the case groups and the control groups were intentionally matched to have equal exposure to vaccine antigens, rather than what really happened: Autism cases were matched with non-autistic controls, and no difference in vaccine antigen exposure was found between the groups. Indeed, he doesn’t even appear to know what overmatching is, of which there are three types. One type refers to matching that harms statistical efficiency, such as case-control matching on a variable associated with exposure but not the condition being studied. The second refers to matching that harms validity, such as matching on an intermediate between exposure and disease. The first form basically just adds noise, which seems to be the form to which Hooker is referring. Of course, the silliest aspect of this criticism is the complaint that the cases and controls were matched by birth year. Here’s a hint: That is not overmatching! For more details, go back to my original deconstruction of SafeMinds’ attack on Price et al.

Perhaps the silliest part of Hooker’s entire screed came when he writes:

The CDC is simply afraid of what they already know – vaccines cause chronic disease and an unvaccinated population will be much healthier, period (as evidenced in the Glanz et al. 2013 study within the Journal of the American Medical Association which stated that unvaccinated children were seen at a lower rate of frequency in emergency room and outpatient visits).

The study to which he refers is this one, and Hooker’s misinterpretation of the study is a perfect example of how he misunderstands case controls. He believes that the study shows that undervaccinated children are healthier. He fails to note that the study didn’t specifically look at unvaccinated children and, indeed, used the same sort of division that he castigated in DeStefano et al, namely between children who received all their vaccines on time and those who didn’t or who were undervaccinated. Apparently doing that is pure pseudoscience when CDC investigators do it but completely hunky dory when the authors of a study Hooker likes do it. (Do I need to repeat again how blatant the double standard is?) In any case, apparently it doesn’t occur to Hooker that perhaps there is a confounder here in that parents who tend not to vaccinate their children also tend to be parents who don’t take their kids to doctors or emergency rooms as much. Another glaring omission from Hooker’s discussion of the study is this inconvenient observation from the study that’s right in the abstract:

In a matched cohort analysis, undervaccinated children had lower outpatient visit rates compared with children who were age-appropriately vaccinated (incidence rate ratio [IRR], 0.89; 95% CI, 0.89- 0.90). In contrast, undervaccinated children had increased inpatient admission rates compared with age-appropriately vaccinated children (IRR, 1.21; 95% CI, 1.18-1.23). In a second matched cohort analysis, children who were undervaccinated because of parental choice had lower rates of outpatient visits (IRR, 0.94; 95% CI, 0.93-0.95) and emergency department encounters (IRR, 0.91; 95% CI, 0.88-0.94) than age-appropriately vaccinated children.

Yes, children who were undervaccinated not because of parental choice had a higher utilization of emergency room and inpatient services than those who were undervaccinated by specific parental choice. The authors even comment on this:

Children who were undervaccinated because of parental choice had lower rates of outpatient visits, lower rates of ED encounters, and no significant difference in inpatient admission rates compared with age-appropriately vaccinated children. These results suggest inherent health care–seeking behavioral differences between the 2 groups of parents. For example, published survey data31- 32 have shown that parents who choose not to have their children vaccinated are less likely to trust health care professionals and more likely to use complementary/alternative medicine providers than are parents who have their children fully vaccinated. It is therefore possible that parents who delay or refuse immunizations are less likely to use the traditional health care system when their children contract minor acute illnesses but will seek medical care when their children become seriously ill. Such differences could create a selection bias in studies that attempt to examine the risk of potential adverse events following vaccination. Future survey work with parents across a range of vaccination concerns could help explain these differences in health care utilization rates.

Emphasis mine.

In other words, this study says nothing about whether undervaccinated children are more healthy and a lot about the health-seeking behaviors of antivaccine parents. Hooker interprets it to mean that undervaccinated children are healthier and have less chronic disease when the study was not designed to show that and in fact says little or nothing about the health of such children relative to vaccinated children. A more willful misinterpretation of a study is hard to imagine.

Finally, Hooker opines:

Finally, this type of study misses the point entirely that children with autism are physiologically different than neurotypical children. Numerous studies have shown genetic (e.g., James et al. 2006), morphological (e.g., Herbert et al. 2005) and biochemical differences (e.g., Waly et al. 2004) between these two populations. To perform a case-control study such as that presented in the Destefano et al. 2013 paper assumes a genetically, morphologically and physiologically homogeneous population, which is simply not the case.

No one is claiming that children with autism or ASD got higher doses of vaccine antigens, thimerosal, MMR or whatever. What we know instead is that when our children received the same vaccines within the ACIP recommended schedule, they reacted differently. The scientists at the CDC are trained in managing infectious diseases with progressions that may be predicted with reasonable certainty. However, these neurological sequelae to vaccines are chronic, multifactorial conditions that cannot be put into the same tiny box as the common cold, influenza or chicken pox.

Ah, yes. Special pleading. You can’t study my hypothesis using your usual methods! Take that, skeptics! It’s also a bit of the old moving of the goalposts as well. Think about it. Back in the 1990s and early 2000s, vaccines were claimed to be The One True Cause of Autism. Indeed, back in the day, Generation Rescue used to say that autism was a misdiagnosis for mercury poisoning. That’s the sort of claim that implies a very high correlation between, in this case, thimerosal-containing vaccines and autism, and, given that mercury seems to be Hooker’s particular bogeyman, I felt obligated to mention Generation Rescue’s hyperbole, which was long ago scrubbed from its website. Indeed, we see this a lot among antivaccine cranks. As scientific evidence fails to find such correlations, it is amusing to me to watch antivaccinationists like Hooker retreat to less and less convincing excuses. In this case, he attacks a straw man, namely that a case control study must assume a morphologically and physiologically homogeneous population. In other words, the hypothesis has shifted from “vaccines cause autism” to “vaccines cause autism only in children with special undefined genetic susceptibilities.”

Same as it ever was. Hooker is, after all, an antivaccine activist. Of course, he misinterprets science, Gish gallops all over the data, confuses case control studies and cohort studies, insinuates dire conflicts of interest, and in general cherry picks the data to support his hypothesis. If he did otherwise, there might be hope that he might realize that he’s devoted his life to pseudoscience and quackery. I see little hope of that.

Comments

  1. #1 Lurking Angel
    Delurking briefly
    April 3, 2013

    Wow. DeStefano et al must really be bugging the antivaxers. Otherwise they wouldn’t be taking so much time to rubbish it. One would think that someone could do a better job. The study is not without its flaws, but Hooker’s “critique” is beyond dumb.

  2. #2 Denice Walter
    April 3, 2013

    Hooker, like many other parents of children with ASDs who buy into the failed vaccines-autism hypothesis, is highly motivated to find fault with studies with which he disagrees. The conclusions of the study threaten the explanatory system he currently uses to cope with his day-to-day travails as a caretaker.

    I recalled that he made an appearance @ PRN some time ago- after a search, I found that he had been shopping his pet theories around various other natural health sites ( published by smaller ones) as well ( early 2011, IIRC); it seems he assoociates with other anti-vax groups ( CoMeD; Focus Autism)

    Not to single him out ( but he is the subject to the post)- many of these parents have spent years battling the consensus and centring their lives upon a-v belief – witness John Stone’s complaints, JABS, AoA’s editors’ hobby-turned-livlihood, TMR’s venomous attacks on medicine amidst the frivolous girltalk. This is how they spend their time, thoughts and effort.

    They steep themselves in pseudoscience and waste their money on alt med nonsense that might better be spent on recreation for themselves and their children. It’s escapism, a fantasy system built to replace a painful reality. Perhaps a way to gain stature as a ‘researcher’/ speaker to make up for the self-esteem lost alongside their other dreams.

    Although I’m an atheist, I do subscribe to the Christian value of concern for others’ welfare: these people are suffering and obviously in need of help. When a person’s focus and *raison d’etre* in not grounded in reality, they probably need to ‘talk to someone’. And not the like-minded, who will drive them deeper into the mucky quagmire of unreasonableness that they are currently floundering in, hopelessly. It can be difficult to show sympathy to those who constantly cast invective upon any criticisms we make and who may despise our very existence- but it would be a great achievement for us if we could somehow communicate that to them.

  3. #3 Orac
    April 3, 2013

    Actually, it occurs to me since this post went live. One thing I would appreciate is if someone would let me know what Hooker is talking about with the prenatal thimerosal exposure bit. I’ll go back to the technical report later and see if I can find it, but maybe someone could point me to what he meant.

  4. #4 Passing Thru
    April 3, 2013

    He sounds very much like that crank ecologist David Lewis who Mr Wakefield dug up to say that Mr Wakefield had found colitis in patients’ ileums.

    The antivaxxers assume anybody who can put “Dr” in front of their names must be an expert, but they so often turn out to be what the Brits call “nutters”.

    It’s real desperation time.

  5. #5 Ren
    April 3, 2013

    You know, if people didn’t start off their arguments against something by swinging their credentials, accusing others of malfeasance, or making some weirdo claims about conspiracies, I’d pay more attention to what they have to say. I tuned out when they started off by writing:

    “There are probably very few people in the world who have spent as much time looking at CDC studies related to vaccines and autism as Dr. Hooker.

    Really? There aren’t people in academia, pharmaceutical companies, health departments, or curious individuals looking at CDC studies? Is he really that unique?

    And then to make the common mistake of claiming “overmatching” in a case-control study! It really is Epi 101. Match as much as possible on everything, except the variable(s) you’re studying, so as to eliminate bias and confounding.

    The typical example was a study back in the 1980s that claimed that coffee drinkers had a higher rate of pancreatic cancer. They took pancreatic cancer patients and asked them about their coffee-drinking habits. Then they took regular people without pancreatic cancer and asked them about their coffee-drinking habits. Guess what they didn’t match the cases and controls on? Smoking! When they were called on it, and other researchers adjusted the study for smoking, the two groups had similar coffee-drinking habits… It was the smoking, stupid.

    If Hooker shows up around here, I’d like to ask him how much training in epidemiology and biostatistics he had, and whether or not he ran this by Jake Crosby. Jake must be done with Dr. Cleary’s Epi 101 class, where Dr. Cleary explained these things very well. If Hooker never learned epi and biostats, or if he never ran this by Jake, then I can understand his error.

  6. #6 Mark
    April 3, 2013

    This is actually one of the best examples of moving goalposts I’ve seen, and illustrative of why I also call it “impossible expectations.” Because it sounds like the only study he’ll accept is to compare the vaccine exposure between genetically-identical/autism prone individuals. Of course, we wouldn’t even know what to measure to identify this group that he insists exists. So maybe we have to do a antigenic exposure/twin study where one twin gets autism and the other doesn’t and they receive different vaccine schedules somehow? I can imagine how recruiting for that would go. Sometime around the year 3000 we’d have a high enough n to power it.

  7. #7 palindrom
    April 3, 2013

    Thank you for the “Plan 9 from Outer Space” reference. I did manage to keep the coffee off my screen, but only just.

  8. #8 Orac
    April 3, 2013

    Heh. Smoking and cigarette smoking actually tend to be correlated, if I remember correctly. But that is an excellent reason why everything possible has to be matched on. Perhaps the silliest complaint about the study, echoed by Hooker, is that they shouldn’t have matched for birth year. Seriously. That’s a complaint I’ve seen by antivaxers elsewhere. It’s also mirrored in Hooker’s apparent belief that the cohort study that showed that undervaccinated children had less ER usage means that they must be healthier. It never occurred to him that perhaps the sorts of parents who are prone to not vaccinating their children might also be the sorts of parents who are less prone to taking their kids to doctors in general.

  9. #9 elburto
    April 3, 2013

    I’d hate to think these people play football (soccer, not handegg) the way they “critique” science. Goalposts that move faster than the speed of light, constantly committing fouls, taking dives.

    As the esteemed DW said upthread, these people have built their entire identities on the foundation of “vaccines turned my neurotypical baby into a soulless changeling”.

    They seem almost convinced that with enough biomeddling, and enough repetition of research until the get the result they want,, that their child will spring up, shout “I love you mummy!” and fulfil their dreams.

    I pity them, but I have infinitely more pity for the children. I know only too well the searing pain of being a disappointment, of not living up to that fantasy child.

    Also, I think empathy and concern for others is a basic human trait, not a christian one. Having been raised in the hell of evangelical christianity, I can honestly say that I wouldn’t have fled so quickly as I did into the arms of “heathen nonbelievers” if they hadn’t been a hell of a lot more concerned about me than the “good christians” in my life.

    Empathy and altruism may be hardwired solely to. propagate the spread of genes, but I’m glad they are!

  10. #10 Gray Falcon
    April 3, 2013

    I’ve said it before and I’ll say it again: The reason we don’t have double-blind studies of vaccines is the same reason we don’t have double-blind studies of parachutes.

  11. #11 rork
    April 3, 2013

    “what Hooker is proposing is to match cases to controls on the variable being studied”
    I don’t get that. My interpretation may be giving him too much credit:
    I thought he was trying to say that if all the subjects (controls and cases) got the same vaccine schedule, then there is no possibility to detect any differences – we need there to be variability in vaccination among the population. That would be correct. The facts are that the distributions are nearly the same, but that’s far different than it being the same for every individual (see figure 1 from the paper). So the problem he is worried about may not be a problem.

    I did not think the number of antigens was an interesting variable to study, and having both DTP with DTap makes for a mess. I wasn’t willing to conclude much.

  12. #12 elburto
    April 3, 2013

    It’s also mirrored in Hooker’s apparent belief that the cohort study that showed that undervaccinated children had less ER usage means that they must be healthier. It never occurred to him that perhaps the sorts of parents who are prone to not vaccinating their children might also be the sorts of parents who are less prone to taking their kids to doctors in general.

    There’s that pesky Earth-logic again. Silly blinking box, using logic against anti-vaxxers isn’t playing fair, you have to level the playing field!

  13. #13 Ren
    April 3, 2013

    “It never occurred to him that perhaps the sorts of parents who are prone to not vaccinating their children might also be the sorts of parents who are less prone to taking their kids to doctors in general.”

    Of course now. If he can’t get the matching right, then he doesn’t know about bias and confounding. This is the same kind of bias that would crash a vax v. nonvax study. Anti-vax parents who think their snowflakes are vaccinated would over-report bad outcomes, or take them to SCAM practitioners. Likewise, parents with a little too much faith on vaccines would not report bad outcomes, but they would probably take them to a qualified healthcare provider.

    Even if we did a blinded, placebo controlled trial, there would be crossover bias, where parents would attempt to vaccinate their kids outside the study if they though the child was randomized into the non-vaccinated group and there was, say, a measles outbreak. Or anti-vax parents would submit their children to chelation and other nonsense if they thought their child was “acting funny” and thus, in their mind, must have been vaccinated.

    These are all things that first-year MPH students are asked to consider in their assignments and second-year students are required to state in their capstone project proposals for IRB review. Which reminds me…

    Does Hooker really think that issues of “overmatching” or, as he alleges, poor study design wouldn’t have come up during the study proposal and IRB approval? Ah, yes, I forget… Obama. Or Big Pharma. Or reptilians. Something other than an IRB allowed this study to proceed. Something evil.

  14. #14 Mel
    April 3, 2013

    He is looking at the table on page 194, which analyses interaction effects of prenatal thimerosal exposure and exposure by 7 months. The line for outcome = regressive autism shows 2SD unit change odds ratio of 8.73 for prenatal thimerosal (p=0.009)

  15. #15 Eric Lund
    April 3, 2013

    One thing I would appreciate is if someone would let me know what Hooker is talking about with the prenatal thimerosal exposure bit.

    I noticed that line, too, but I assumed (probably incorrectly) he was referring to any vaccines (most likely flu) that the mother may have gotten while pregnant. I’m aware that pregnancy is a medical contraindication for some vaccines, but possibly not all.

    I also enjoyed the “Plan 9 from Outer Space” reference. I tried but failed to come up with a suitable comparison in Hooker’s essay to the notorious line, “We are all interested in the future, because that is where you and I are going to spend the rest of our lives.” I concluded that such a comparison would be unfair to Wood and Criswell, because that line isn’t wrong, but merely a vacuous tautology. Hooker is at best wrong (some of that essay doesn’t even rise to that level).

  16. #16 Mel
    April 3, 2013

    I should have made clear that I’m not agreeing with his interpretation of that line of data – I don’t have the expertise to know what it means, if anything.

  17. #17 brian
    April 3, 2013

    Re Prenatal exposure to thimerosal

    http://pediatrics.aappublications.org/content/early/2010/09/13/peds.2010-0309.abstract

    Of course, the Geier’s suggest it all comes down to mercury–even it’s in dental amalgams:

    http://www.ncbi.nlm.nih.gov/pubmed/19593333

  18. #18 Sid Offit
    April 3, 2013

    As I interpret Hooker (and you appear to agree) he seems to be saying something along the lines of “How is this study different from taking one group of smokers with lung cancer and comparing them to a group of smokers without lung cancer and using this to say smoking does not cause lung cancer.” You seem to acknowledge this but accept it as a result of doing this type of study even though that methodology is ill-suited to make any claims about autism and vaccination.

  19. #19 Gray Falcon
    April 3, 2013

    @Sid- If you can definitively prove that vaccines kill more people than diseases, then you can make that interpretation, and not a moment before.

  20. #20 Sid Offit
    April 3, 2013

    I don’t understand how illnesses killing people affects the usefulness of the study we’re addressing. Can you connect the dots for me?

  21. #21 Gray Falcon
    April 3, 2013

    @Sid- Because that’s why the vaccines were given in the first place. Would you jump out of a plane if you were told there was a fifty-fifty chance your pack was a parachute?

    Also, the study in question was on the amount of antigens, not simply whether they were introduced in the first place.

  22. #22 Ren
    April 3, 2013

    “How is this study different from taking one group of smokers with lung cancer and comparing them to a group of smokers without lung cancer and using this to say smoking does not cause lung cancer.”

    It’s in how they did the sampling. They didn’t know the vaccination doses of the cases and the controls until after they picked the cases and the controls. They took cases, matched them with controls (but did not match them on vaccination status) and then looked to see how many vaccines (i.e. antigens) they were given. No difference.

    The error that every single anti-vaccine person keeps making is inferring that the researchers took children with autism, saw how many vaccines they got, then looked to find controls with a similar vaccine level, thus matching them on the variable they were studying. They did not do this, and I don’t know how much clearer to make it than:

    Case-control studies do not match cases and controls on the variable that is in question, e.g. vaccination levels.

    Capisce?

  23. #23 Gray Falcon
    April 3, 2013

    Thanks Ren, that explains everything.

  24. #24 Sid Offit
    April 3, 2013

    Yes, I know all this. But because of such high vaccination rates, we were unlikely to find any differences between cases and controls when it came to vaccination. They didn’t need to know the the doses in each group beforehand because vaccination is basically something everyone does.

    Verstehen sie?

  25. #25 Gray Falcon
    April 3, 2013

    Sid, if you “know all this”, then why did you make that erroneous comparison? Are you admitting to lying?

  26. #26 Sid Offit
    April 3, 2013

    Perhaps my question was not worded perfectly. I was not suggesting at the start of the study they pick one group that smoked and another group that smoked. I was saying what if you wound up with two groups of smokers . If you did it would be hard to get any conclusions regarding smoking’s ability to cause cancer. So in this case we just happen to get high vaccination status in both groups you because of the high rates of vaccination in the childhood population. Immunize.org estimates out of 1000 kids only 2 or 3 are not vaccianted

  27. #27 Dallas
    April 3, 2013

    I’d like to see how Orac criticizes the ~3000 purported number of antigens in the whole cell pertussis vaccine. Moving the goalpost much Orac?

  28. #28 Ren
    April 3, 2013

    “But because of such high vaccination rates, we were unlikely to find any differences between cases and controls when it came to vaccination.”

    Ja. Ich verstehe. Aber lassen Sie mich es erklären ein wenig besser. (But let me explain it a little better.) It’s a common mistake in biostat undegrad students when their gut disagrees with what they’re supposed to do.

    ” Immunize.org estimates out of 1000 kids only 2 or 3 are not vaccianted”

    This is why they picked so many more controls than cases. Ideally, you want a 1:3 to 1:5 ratio of cases to controls exactly to avoid what you’re stating. But back to the ‘splaining.

    Suppose that you had an outbreak of intestinal disease in people who went to a wedding. Your cases are people with diarrhea and your controls are people without. If we were to do the case-control investigation the way you want it, we’d get people who went to another wedding and were not sick to compare to the sick people from our wedding. (Well, not our wedding…) If we did that, the only thing we could definitely conclude is that the sick people have greater odds of being at our wedding than the other one. Period.

    Of course, we want to find out what food made people sick, so we need to be smarter about getting our controls. So we get our controls from people at the wedding, but we stupidly pick controls who are children versus the cases who are mostly adults. I don’t know about your wedding, which I’m sure was fabulous, but kids usually have a different menu at weddings. We do the comparison and we can only say that people who fell ill had greater odds of being adults at the wedding.

    You can see where I’m going with this. See, we need to match the controls to the cases in all respects except the food. We don’t ask about the food in choosing controls. We can’t say, “Hey, if you ate the roast beef, you can’t participate,” because we wouldn’t be able to say anything about the odds of eating roast beef as it relates to the disease. As you can see, both our cases and controls have equal odds of their age, being at the wedding, etc… Except the food. That is the unknown.

    We ask them what they ate and, almost magically, we see that people who were sick had greater odds of having eaten, say, the pasta dish.

    Also, although I covered this before in the Epi Night School, note that we’re not saying that eating the pasta dish increased the risk of diarrhea in the group. We can’t. With case control studies, we can only say that those with diarrhea had greater odds of eating the pasta dish. It may sound like semantics, but it’s important. It doesn’t prove causation. For that, we use the scientific plausibility of pasta causing diarrhea… So we test the pasta for pathogens, bad storage conditions, etc. Ninety-five times out of 100, we’ll be right… And that’s an acceptable p-value.

  29. #29 Answer to Orac #3
    April 3, 2013

    “One thing I would appreciate is if someone would let me know what Hooker is talking about with the prenatal thimerosal exposure bit.”

    Hooker is basing this on documents he obtained from the CDC. Congressman Posey has been helping him obtain documents that he didn’t get through his FOIA. Think of it as his version of the “generation zero” argument from the Verstraeten study of a decade ago. In this case it has to do with the Price study and a claim that they reported an insignificant risk when the risk, according to Hooker, is actually high.

    What was actually stated in the document or email, in what context and how Hooker interpreted it to the way he has I can not say at this point.

  30. #30 Gray Falcon
    April 3, 2013

    @Sid- Learn Statistics 101, then get back to me. If 90% of the population smoked, and 99% of lung cancer patients were smokers, we’d have ways to detect it.

    @Dallas- How about the 10000 or so that we get every minute of every day? The world isn’t a sterile environment.

  31. #31 Captain A
    April 3, 2013

    Sid,

    I agree with your point that nearly all children are going to get fully vaccinated, so a case control study will end up showing both cases and controls getting fully vaccinated.

    It is not true, however, that nearly all children get vaccinated ON SCHEDULE. There is large variability here and this study would have showed a difference if there was any merit to the “Too many too soon” argument.

  32. #32 dingo199
    April 3, 2013

    Come now Sid, don’t pretend you can’t understand a case control study. The outcome is autism, so you select controls without autism, then you go back and compare exposure to the variable you are interested in (vaccine antigen exposure).

    For lung cancer and smoking as you suggest, you get those with cancer and controls without, and compare smoking – but not as a discrete variable (ie yes/no) but as a continuous variable – ie the degree of exposure (eg number of cigarettes per day range 0-100).

    Actually, I just realised – maybe Sid isn’t pretending.

  33. #33 Chris
    April 3, 2013

    Dallas:

    I’d like to see how Orac criticizes the ~3000 purported number of antigens in the whole cell pertussis vaccine. Moving the goalpost much Orac?

    See post where actually discusses the paper, which is linked to on this page:
    http://scienceblogs.com/insolence/2013/04/01/the-death-of-too-many-too-soon-not-a-moment-too-soon/

    Remember the point is that the number of antigens does not matter.

    Some selected quotes: ” The vaccines examined in the study ranged from a single antigen antigen per dose (hepatitis B) to 3,004 antigens per dose (DTP-Hib).”

    “Using a strategy similar to the earlier Price et al study, DeStefano et al examined antigen exposure and compared the number of vaccine antigens to which the controls and the cases were exposed to. What do you think they found? Yes, I know. I already told you what they found from the beginning: Nada, zip, nothing. No correlation between antigen exposure from vaccines and the risk of developing autism or autism spectrum disorder (ASD)—or even ASD with regression.”

  34. #34 dingo199
    April 3, 2013

    I’d like to see how Orac criticizes the ~3000 purported number of antigens in the whole cell pertussis vaccine. Moving the goalpost much Orac?

    Why? Do you think Orac is somehow dischuffed that pertussis vaccination required giving infants antigens?

  35. #35 Sid Offit
    April 3, 2013

    Dingo, you’re not addressing the issue at hand. Why would you see any difference since all these vaccines are administered on a schedule, i.e, the same time at the same does, in the same combination. The reality is everyone in the study is going to have a very similar vaccine profile. It would be if you were looking at maternal obesity as a causal factor for autism when everyone in the study (case and control) was obese.

  36. #36 Dallas
    April 3, 2013

    A vaccine containing ~3000 antigens is ridiculous. There is not a vaccine in the childhood immunization schedule that has or comes anywhere close to that exaggerated number. The year was 1996 when acellular pertussis vaccine came to picture. It has only 2-5 antigens and a Bordetella pertussis species has only 33 toxins! Wherever did Dr Offit get those numbers?

  37. #37 Ren
    April 3, 2013

    “The reality is everyone in the study is going to have a very similar vaccine profile.”

    Let’s look at it with the wedding example: “The reality is everyone in the study is going to have eaten a very similar variety of foods.”

    Ah, but, because of the magic of statistics and math and stuff, we’ll be able to tell even a small-yet-significant difference between cases and controls. That magic is also why pollsters can ask 1,000 people in the US what candidate they like and extrapolate that to a population of 300+ million without having to ask the whole country. And that magic is why some people can win at blackjack without having to see the whole deck of cards.

    It’s math.

  38. #38 Todd W.
    http://www.harpocratesspeaks.com
    April 3, 2013

    As a layperson, understanding the difference between a case control study and a cohort study can be confusing. It isn’t intuitive, so I can understand why Dr. Hooker and others raising a stink about this study are having problems.

    Sid, they started with kids with autism and kids without autism. If the “too many, too soon” argument were valid, then we would expect to see greater and/or earlier exposure among the kids with autism and in the kids without autism (e.g., younger age at first exposure, greater exposure at single visits, greater overall exposure earlier than controls, etc.). If we found, instead, that controls had earlier/greater exposure, then we might suggest that earlier/more antigen exposure is actually protective against autism. The researchers found that there were no significant differences between cases and controls, which means that getting “too many” vaccines “too soon” does not contribute to autism.

    Yes, there is a recommended schedule, but people do not adhere to it to the letter. It is not like every single child is vaccinated on day 0, day 60, etc. You have some vaccinated on day 4, day 56, day 70 and so on. There is variability. Expecting that the reality of vaccine administration is at “the same time at the same does [sic], in the same combination” would be like expecting that infants and toddlers never wander off the sidewalk and onto the grass or dirt (to pay homage to another troll that used to frequent here).

  39. #39 Dallas
    April 3, 2013

    I have also noticed that Dr Offit did not include the smallpox vaccine in the reference table. Does it mean he finally realized that he had mistaken the “200 viable organisms per mL” to be antigenic component of the vaccinia virus vaccine?

  40. #40 Sid Offit
    April 3, 2013

    @Ren
    That magic is also why pollsters can ask 1,000 people in the US what candidate they like and extrapolate that to a population of 300+ million without having to ask the whole country

    @Ren. Thanks for your professional epidemiological views. (I’m being serious.)

    Yes, I understand the power of statistics to compensate for small numbers etc. But this study must also incorporate a large number of covariates (and adjust for the one large antigen dose of the whole cell vaccine), which could make the conclusion more difficult/speculative.(?) Also, would you not concede a study having a more unusual/uncommon variable/s (for example maternal obesity or residence near a freeway) would yield more trustworthy conclusions. Finally what do you make of the wide confidence intervals – for example OR 0.65 (0.16-2.64) in ASD with regression in the birth to 24 month group with 12 000-18 258 antigens [table 2 - bottom - 3rd column]

    I did not link to the study due to spam filter concerns but a link is in the 1st sentence of Orac’s post

  41. #41 Beamup
    April 3, 2013

    @ Sid:

    Let’s do that smoking analogy right. In a case-control study to determine if smoking is associated with lung cancer, one would take a group of people with lung cancer. You would match them with controls who don’t have lung cancer, matching them as closely as possible, but without looking at their smoking status yet.

    Then you compare the rates of smoking in the cases with lung cancer, and the controls without. If smoking is not associated with lung cancer, the controls will have the same smoker/nonsmoker ratio as the cases (within the statistical variation). If smoking IS associated with lung cancer, then the cases will include a greater fraction of smokers than the controls.

    The latter result is what we see with smoking and lung cancer. The former is what we see with vaccines and autism.

    Since there IS variability in the population at large (some kids miss shots, or use Sears’ randomly made-up schedule, or what have you), but there is NOT a difference between cases and controls, we conclude that this study provides evidence against a link.

  42. #42 lilady
    April 3, 2013

    Orac provides a “hint” to Hooker about the inclusion of children who have other diagnoses…

    “(Hooker) once again does not understand what a case control study is. The whole point was to match cases, which means children with the condition under study, namely autism or autism spectrum disorder, or controls, which means children without autism or ASD. The whole point of administering the SCQ was to identify children in the control group who might have an undiagnosed ASD and in fact eliminated 7 children from the control group that way. Again, remember: The hypothesis being tested in Price et al was whether thimerosal-containing vaccines were associated with autism risk, and the hypothesis behind DeStefano et al tested was whether total antigen load due to vaccines is associated with autism.. Here’s another hint for Mr. Hooker: Speech delay is not autism, and, even if his complaint were valid, at worst such matching could only be expected to decrease any apparent difference between the groups, not eliminate it. Basically, Hooker is criticizing the investigators for not picking cases based on more than just autism. Of course, doing that would add heterogeneity to the case group.”

    Hooker also doesn’t realize that both case control studies (thimerosal exposure and antigen exposures), do NOT include children diagnosed with genetic disorders who also have known “causal links to the symptoms of autism” (or autistic-like behaviors) associated with these genetic syndromes:

    http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2788.2009.01197.x/full

    From the original 2010 case control study testing the hypothesis that Thimerosal contained in vaccines causes autism, this statement…

    “…Children were excluded if they had the following medical conditions with known causal links to the symptoms of autism: Fragile X syndrome, tuberous sclerosis, Rett’s syndrome, congenital rubella syndrome, or Angelman’s syndrome….”

    And this statement…

    “…There were two types of secondary research questions specified in the analysis plan. The first type concerned relationships of exposures to subgroups of AD and ASD cases. Questions about the same previously described cumulative exposure measures for five time periods or age ranges were asked about the each of the following subgroups:

    - ASD-not-AD

    - ASD with regression

    - AD with low cognitive functioning excluded

    - ASD w/Screened Controls

    - AD w/Screened Controls

    ASD-not-AD is the subset of cases that met criteria for ASD, but did not meet criteria for AD. ASD with regression is a subset of ASD cases that had a definite loss of language
    skills. Analysis of the subgroup of AD cases where children with low cognitive functioning were excluded was motivated
    by the following concern. Because children who are non-responsive during the assessment process are more difficult to assess, it can sometimes be difficult to determine whether children with severe developmental delay actually have autistic disorder…”

  43. #43 Orac
    April 3, 2013

    The hilarious thing is that some of the critics of DeStefano et al criticize the study for exactly that: Excluding children with conditions that are highly associated with autism and ASD, such a Fragile X syndrome, tuberous sclerosis, Rett’s syndrome, congenital rubella syndrome, or Angelman’s syndrome, thus proving that they really have no clue what a case control study is and how it’s carried out.

  44. #44 Orac
    April 3, 2013

    Let’s do that smoking analogy right. In a case-control study to determine if smoking is associated with lung cancer, one would take a group of people with lung cancer. You would match them with controls who don’t have lung cancer, matching them as closely as possible, but without looking at their smoking status yet.

    Then you compare the rates of smoking in the cases with lung cancer, and the controls without. If smoking is not associated with lung cancer, the controls will have the same smoker/nonsmoker ratio as the cases (within the statistical variation). If smoking IS associated with lung cancer, then the cases will include a greater fraction of smokers than the controls.

    Which is exactly how Sir Richard Doll did one of the earliest epidemiological studies linking smoking with lung cancer in 1947:

    Two of these studies, one in 1947 by Sir Richard Doll and one in 1951 by A.B. Hill, are considered classics. Doll used the case-control study method and compared the smoking history of a group of hospitalized patients with lung cancer with the smoking history of a similar group without lung cancer. Hill used a cohort study, categorizing a group of British physicians according to their smoking histories and then analyzing the causes of death among those who died, to see whether cigarette smokers had the highest incidence of lung cancer.

  45. #45 Ren
    April 3, 2013

    “But this study must also incorporate a large number of covariates (and adjust for the one large antigen dose of the whole cell vaccine), which could make the conclusion more difficult/speculative.”

    Not at all. That’s the magic of matching. It eliminates those “covariates” like randomization does under the cohort or prospective design.

    “Also, would you not concede a study having a more unusual/uncommon variable/s (for example maternal obesity or residence near a freeway) would yield more trustworthy conclusions.”

    No, because it doesn’t matter how common the exposure is. It’s how common the condition (i.e. autism) is. And don’t forget biological plausibility.

    “Finally what do you make of the wide confidence intervals – for example OR 0.65 (0.16-2.64) in ASD with regression in the birth to 24 month group with 12 000-18 258 antigens [table 2 - bottom - 3rd column]“

    The width of confidence intervals has to do with sample size, the statistical analysis being done, and other things in the study design. To make it narrower, you’d have to make your sample get closer and closer to the population. (This is why elections don’t have confidence intervals, because we assume that everyone who could or would vote did.) So, yeah, we could repeat this with a bigger and bigger population until the OR became a point and not a point and a range, but think of how cost prohibitive that is AND the odds are very good that you’ll end up on the south end of 1.0 (showing protection rather than risk) because there are conditions that are vaccine-preventable that cause autism while vaccines do not cause autism.

    But, if we did do that, what would he have to talk about, Sid… er… Bob?

  46. #46 Old Rockin' Dave
    April 3, 2013

    @palindrom & everyone:
    The “Plan 9 from Outer Space” comparison is particularly apt for the whole antivax crowd.
    “Plan 9″ was made by the prolific director Ed Wood. Wood was a passionate filmmaker who had messages and a creative vision that he was passionate about, and he let no obstacles get in his way. He lacked adequate funds, high-quality equipment, accomplished actors and production staff, and a high-powered distribution network.
    All this was because of one more thing he lacked: talent.
    Similarly, antivaxers have a message they passionately believe in and nothing will stop them. The one thing that keeps sabotaging their efforts is their sad lack of facts, which denies them credibility the same way Ed Wood’s lack of talent did him.

  47. #47 Sid Offit
    April 3, 2013

    @Beamup

    My only concern is that while there may be some variability, it is rather slight (especially when you match for education, income, etc. which correlates with vaccination practices) As I asked, Ren, would you concede a study looking at other variables that were less common (maternal obesity/living by a freeway) to both groups would be more reliable?

  48. #48 Gray Falcon
    April 3, 2013

    @Sid- If that’s your concern, then do the work and check to see how much variability there is. If you were really sincere about finding the truth, you wouldn’t just ask questions, you’d look for answers.

  49. #49 Beamup
    April 3, 2013

    @ Sid:

    Moved those goalposts into an entirely different state, I see. If you want to argue that there’s too little variability in the population at large to do a case-control study, you’ll have to demonstrate that the study did the statistics completely wrong… because the analysis captures that. If there were no variability, for instance, the error bars would be infinitely wide.

    As I asked, Ren, would you concede a study looking at other variables that were less common (maternal obesity/living by a freeway) to both groups would be more reliable?

    No I would not. Nor is the question relevant in any way.

  50. #50 Dallas
    April 3, 2013

    So why did you move the goalpost Orac? Why did you dismiss it as “toxin gambit” when we’re actually referring to the “immunogenic proteins and polysaccharides” of the whole cell pertussis vaccine which are mostly toxins (PTx, LPS, AC, DNT, TCT, among others)?

  51. #51 rork
    April 3, 2013

    For folks who can’t see the paper, at age 2 about 40% of the kids have total of antigens at less than 200, and about 25% had more than 12000. So for that variable, there was considerable variation (understatement!).
    Part of that is that DTP and typhoid having about 3000, while for most others it is <20.

    I'm not saying that variable is one I'd be most interested in testing, but if you think that might be close to what matters, then this data-set seems very good (in statistical power).

  52. #52 lilady
    April 3, 2013
  53. #53 Calli Arcale
    April 3, 2013

    Sid, regarding invariability in the vaccine schedule….

    Just go look at the CDC’s schedule for a minute. How wide are the windows for each recommended dose? How many options are provided for “catchup” vaccination? Truth is, there’s quite a bit of variety in what specific vaccines a child gets and when, even if the child is vaccinated in compliance with all state regulations for school entry.

    When you’re done with that, check to see how many of those vaccines are actually required rather than merely recommended; remember, many people will only get the vaccines they need in order to enter school, so optional vaccines are less likely to get compliance. Lots and lots of kids don’t get flu shots; it’s not required. And where varicella vaccine isn’t required, lots of kids skip that too. Part of it’s parental caution, but most of it is money and convenience and just not wanting to poke the kid more than necessary.

  54. #54 Beamup
    April 3, 2013

    @ Dallas:

    Hooker’s talking about the substances like formaldehyde, which is indeed a complete shifting of the goalposts on his part.

    And even if your claim were true, that wouldn’t be Orac shifting the goalposts – it would be a strawman.

  55. #55 Sid Offit
    April 3, 2013

    @Ren – good point on the covariates

    On the confidence interval, it is my impression that (from Cochrane reviews), “intervals that are very wide (e.g. 0.50 to 1.10) indicate that we have little knowledge about the effect, and that further information is needed”

    So even though it [wide interval] is due to a small sample size, are we not left with the problem of a wide interval regardless of the reason and isn’t your conclusion, “odds are very good that you’ll end up on the south end of 1.0,” somewhat speculative? especially with no extant cases of CRS – an accepted cause.

    Finally, I’m having trouble with this:

    “because it doesn’t matter how common the exposure is. It’s how common the condition (i.e. autism) is”

    I know you tried to address this earlier, but I think there is still a little confusion so I’ll ask one last time and leave it at that. Let’s say we had a 100% vaccinated population and vaccination was done under the same conditions (doses, combos, dates, etc. everything is the same) We would then have each group [case and control] fully vaccinated and there would be no way to discover anything in regards to vaccination’s impact on autism. (Do you agree up to this point?) (If so) Is there a point under/less than/lower than the 100% identical vaccine profile I described that would still make vaccination difficult to measure? What if population wide vaccination was the same in 98% of the population. Still too similar? Or at 98% could we still get a control group and an autism group that differed enough in vaccination status that a causative signal regarding vaccines could emerge?

    And would it not be easier to find a signal if we had a population to draw from that had a 50/50 rate of vaxxed/unvaxxed. Then if we saw the an equal antigen distribution between autism/non autism we’d know it wasn’t vaccines. And if we had lots of antigens in the autistic group we’d know the opposite?

  56. #56 Chris
    April 3, 2013

    Dallas, you are not making much sense. Also when the schedule switched from DTP to DTaP the numbers of antigens dropped. So by the “too many too soon” crowd logic, if the total number of antigens fell, then autism rates should go down.

    And do please tell which toxins in the DTaP are more potent than the toxins created by the bacterial infections caused by diphtheria (diphtheria toxin), tetanus (tetanospasmin) and pertussis (pertussis toxin). Be sure to provide verifiable scientific documentation to support your answer.

  57. #57 Ren
    April 3, 2013

    “I know you tried to address this earlier, but I think there is still a little confusion so I’ll ask one last time and leave it at that. Let’s say we had a 100% vaccinated population and vaccination was done under the same conditions (doses, combos, dates, etc. everything is the same) We would then have each group [case and control] fully vaccinated and there would be no way to discover anything in regards to vaccination’s impact on autism. (Do you agree up to this point?) (If so) Is there a point under/less than/lower than the 100% identical vaccine profile I described that would still make vaccination difficult to measure? What if population wide vaccination was the same in 98% of the population. Still too similar? Or at 98% could we still get a control group and an autism group that differed enough in vaccination status that a causative signal regarding vaccines could emerge?”

    No. No. No, and no.

    If we had a 100% vaccinated population, we wouldn’t be looking at vaccines as the cause. In essence, we would have cases and controls matched on vaccine status by the nature of the population alone. There would be no way to look for that “signal.” We’d move on to look at other factors, e.g. genetics. This is why we can’t drinking water to anything, but we can say that drinking water from this or that source, or with this or that concentration of somethings. And that’s what they did… They looked at antigens.

    “And would it not be easier to find a signal if we had a population to draw from that had a 50/50 rate of vaxxed/unvaxxed. Then if we saw the an equal antigen distribution between autism/non autism we’d know it wasn’t vaccines. And if we had lots of antigens in the autistic group we’d know the opposite?”

    You’re looking at it backwards, again. You want to force the case-control methodology into a cohort frame. In that “50/50″ study you suggest, we wouldn’t look to see how many vaccines/antigens the two groups received. We’d look to see which group (vaccinated/unvaccinated) had higher risk of developing autism given the exposure (vaccine). Further, the way you want to do this, we’d start with “normal” children, give vaccine to half, and then look for autism. I hope you remember what we’ve told you about that kind of a study.

    This is why I keep writing that it’s not the commonality of the exposure that dictates the type of study. It’s the commonality of the disease.

    Then you guys (anti-vaccine types) say, “Well, let’s take these kids here who are not vaccinated, and those kids there who are, and check for autism.” Guess what that is? It’s a case-control, except that you’re determining how autism affects vaccination practices, not the other way around. And, because you’re determining vaccination as an inclusion/exclusion factor into the cases or the controls, you can’t analyze it as an exposure with any degree of certainty.

    Really, Bob, there’s a course on statistics on Coursera.org right now.

    Finally…

    “On the confidence interval, it is my impression that (from Cochrane reviews), “intervals that are very wide (e.g. 0.50 to 1.10) indicate that we have little knowledge about the effect, and that further information is needed””

    Believe it or not, that interval is not that wide. The important thing is that it includes the number 1.0, which means that the two groups have no difference at all, let alone significant, in their exposures. To determine if a CI is “too wide,” you have to look at statistical power as well as your aims. If you see a CI of 2.1 – 25.6, then, yes, that’s one wide CI. I would take apart that study with a fine tooth comb to see why that happened.

    This will be my last comment on this matter for the time being. I recommend the books “Intuitive Biostatistics” and “Studying a Study and Testing A Test”, the latter by one of my professors at GW and the man who caught a glitch on one of my graphs in my capstone project presentation.

  58. #58 Dallas
    April 3, 2013

    The rate of autism did not go down because:

    1. The cumulative number of antigens has increased significantly since 1996. The ~3000 purported number of antigens in the whole cell pertussis vaccine was Dr Offit’s reference point for his false claim “that children are exposed to fewer antigens (proteins and polysaccharides) in vaccines today than in the past.” The drop in antigenic load between the old WCPV and APV is only a difference of a couple of toxins (less LPS) but not the absurdly dramatic decrease from ~3000. He may have used the Tohama pertussis strain’s genomic sequence of having ~3000 ORFs in a disengenuous attempt to establish the false premise. That would be a medical travesty.

  59. #59 Passing Thru
    April 3, 2013

    Why would this man Hooker even think he understood epidemiology? It’s like a farmer thinking he can fly an aircraft, or a pharmacist designing a skyscraper.

    Sure, there are gifted amateurs, but doesn’t our society train people up and pay them to do highly specialist jobs for us?

    Who needs this man? Why? What’s the gap that he fills?

  60. #60 lilady
    April 3, 2013

    Orac @ # 43…That’s why I posted that link to genetic syndromes known to be associated with autism…and other genetic syndromes (such as Williams Syndrome), where kids who have been diagnosed with an ASD/autistic-like behaviors, are excluded from case control studies about vaccines and the onset of ASDS/autism.

    One of the AoA groupies, who also posts on the Ho-Po and other blogs, has a child with Williams Syndrome which was diagnosed at age two and then diagnosed with an ASD/autism at age nine. She’s not too pleased with me when I post about my son who was born with a rare genetic disorder, who also had “autistic-like behaviors-not autism”.

    None of the anti-vaccine people I encounter on blogs are too pleased when I state that children who are severely/profoundly intellectually impaired, usually display autistic-like behaviors-not autism.

  61. #61 jre
    Boulder, CO
    April 3, 2013

    Yeah, but let’s get back to the peppers. A very interesting study was presented at this year’s ARO conference: “Oral Capsaicin Prevents Cisplatin Ototoxicity” by Leonard Rybak, Debashree Mukherjea, Kelly Sheehan and Vickram Ramkumar of the
    Southern Illinois University School of Medicine. One conclusion was that “Oral capsaicin (levels equivalent to those when consuming spicy food) can attenuate cisplatin induced hearing loss.”
    Why is this a nifty result? Well, despite the wishful thinking promoted by many altie cancer theorists, the best option for many cancers remains chemotherapy, with all its attendant side effects. Now it would appear that we can mitigate some of those side effects with a nice habanero-mango salsa.
    Hurrah for Southwestern medicine!

  62. #62 JGC
    April 3, 2013

    But because of such high vaccination rates, we were unlikely to find any differences between cases and controls when it came to vaccination.

    Only if vaccination rate has nothing to do with likelihood of developing an ASD. If vaccination rate does predispose to developing ASD we’d instead expect that as a fnction of selecting controls that although matched independently of immunization history we’d have skewed it toward subjects who’d received fewer immunizations.

  63. #63 JGC
    April 3, 2013

    I was not suggesting at the start of the study they pick one group that smoked and another group that smoked.

    But they would not have picked one group that smoked and another that smoked–they’d have picked one group with lung cancer and one without, then compared smoking ahbits between the two (just as in this case they picked one group with diagnosed ASD and one without and compared immunization history between them).

  64. #64 Sid Offit
    April 3, 2013

    Thanks Ren.

  65. #65 Todd W.
    http://www.harpocratesspeaks.com
    April 3, 2013

    @Sid

    Let’s say we had a 100% vaccinated population and vaccination was done under the same conditions (doses, combos, dates, etc. everything is the same) We would then have each group [case and control] fully vaccinated and there would be no way to discover anything in regards to vaccination’s impact on autism.

    You’re getting it backward, again. As Ren said already, you’re trying to fit a case-control study into a cohort format.

    In DeStefano et al., the researchers started with what is known: cases of autism and neurotypical controls, matched on a variety of factors. What was unknown was how much antigenic exposure each group had, as well as the timing of the exposure. The hypothesis was: If “too many too soon” is correct, then we will see greater/earlier antigenic exposure in the cases than in the controls. Or, to put it another way, if a person has autism, then their odds of having earlier/greater antigenic exposure will be greater than controls.

    The question you keep asking is “if a person has more exposure, then their odds of autism will be greater than controls that have less exposure”. Can you see the difference?

  66. #66 Roger
    April 3, 2013

    Sid,

    I think you meant “Verstehen Sie.” A lower-case “sie” implies a different target.

    Remember: this study specifically addressed the “Too many, too soon” argument. This isn’t intended to completely state that vaccines themselves (the “toxins,” thimerosal, whatever) don’t cause autism; that’s been studied, re-studied, and debunked consistently. This is one particular anti-Vax claim.

    As to the range? Statistically significant is the important phrase to keep in mind. As a non-statistician myself, I often find studies (in physics, in medicine, in economics) where the results being statistically significant (or insignificant) are not immediately apparent to me. But do you know what? To the people who do this work for a living, it IS immediately apparent.

    And that’s what this study showed: a statistically significant result (different from an “inherently obvious to laymen” result) that showed no credence to the “Too many, too soon” argument.

    Dallas,

    You’re ridiculous. That is all. (There is no statistical significance nor scientific study that PROVES you’re ridiculous, but it seems pretty evident).

  67. #67 Dallas
    April 3, 2013

    The rate of autism did not go down because:
    1. The cumulative number of antigens has increased significantly since 1996. The ~3000 purported number of antigens in the whole cell pertussis vaccine was Dr Offit’s reference point for his false claim “that children are exposed to fewer antigens (proteins and polysaccharides) in vaccines today than in the past.” The drop in the antigenic load between the old WCPV and APV is only a difference of a couple of toxins (less LPS) but not the absurdly dramatic decrease from ~3000. He may have used the Tohama pertussis strain’s genomic sequence of having ~3000 ORFs in a disengenuous attempt to establish the false premise. That would be a medical travesty.

  68. #68 Denice Walter
    April 3, 2013

    Far be it from me to attempt explaining statistical analyses without a chalkboard – or
    trying to deal with the concept of causality ( whatever that is),
    SO…
    I’ll answer elburto on the value of Christianity instead: it’s far easier.

    elburto:
    of course, I believe that altruism/ sympathy might be natural qualites of humans however, I have to admit that, despite my upbringing ( agnostic/ atheist), I do see value in the basic central concepts of Christianity as a civilising influence over the millenia- perhaps as a bolster for the natural tendency- especially in Europe. As a strong cultural influence underpinning the foundations of the west, those values were pushed towards the forefront AND because Christians have a book, it may have encouraged literacy eventually as well as art and architecture.

    Of course, I realise that it has also brought misery, judgmentalism and interpersonal manipulativeness sanctified in the deity’s name and perhaps has held scientific inquiry back a century or more. I know the results are a mixed bag. I do see value in proselytising that all people are brothers and sisters, to treat the other as yourself, to be responsible for your actions, for being concerned for the least, assisting those weaker than yourself, for not living by the sword, for not overvaluing wealth and for a self-reflective mindset etc.

    If you ever get to California, it’s really awe-inspiring to visit and contemplate the missions and imagine what they have wrought – both for good and ill. Unfortunately, in many cases, it was mostly for ill.

  69. #69 Matt Carey
    April 3, 2013

    those wishing for a study comparing vaccination rates among autistic and non-autistic kids won’t have to wait long.

    “No Differences in Early Immunization Rates Among Children with Typical Development and Autism Spectrum Disorders”

    Is a talk to be presented at IMFAR next month. The researchers are from the MIND Institute, one of those which carries a great deal of weight among those promoting a vaccine-induced autism-epidemic.

  70. #70 Chris
    April 3, 2013

    Dallas,

    Citation needed.

    Oh, and do be sure to post those citations about the “toxins” in the DTaP being more dangerous than the ones created by the actual diphtheria, tetanus and pertussis bacteria.

  71. #71 Narad
    April 4, 2013

    The drop in the antigenic load between the old WCPV and APV is only a difference of a couple of toxins (less LPS) but not the absurdly dramatic decrease from ~3000. He may have used the Tohama pertussis strain’s genomic sequence of having ~3000 ORFs in a disengenuous attempt to establish the false premise.

    Well, I’m out of my depth here, but you seem have advanced two separate premises here. The first begs the question in that it assumes that only the major virulence factors count in assessing antigenic load. The second, that the Tohama proteins may not all be relevant, is fine, but that still doesn’t get you down to a difference of two.

  72. #72 Dallas
    April 4, 2013

    “Immunogenic spots” = epitopes

    And according to the study, it states clearly:

    ” Moreover, the calculations do not take into account the number of epitopes per antigen or the immunologic strength of each epitope.”

    The antigenic load of each vaccine ideally would contain the major virulence factors of the pathogen, which is the basis of immunological memory.

    Dr Offit sadly, is doing a great disservice to humanity and he’s still continues to harm more innocent children with his outright lies and deception.

  73. #73 Julian Frost
    Gauteng East Rand
    April 4, 2013

    Dallas, please highlight what you think are Dr Offit’s “lies and deception”.
    That means quote Dr Offit, don’t take his quotes out of context in any way, show that his comments are false and show that he is wilfully being deceptive.

  74. #74 The Typical Pharma Shill
    Red light district, NWO Underground City
    April 4, 2013

    Please think of the innocent children!!!!11!

    You know, our flagship product, the Toxin™ blend, is a trade secret, but who cares? No one whines about Tuna Surprise in the school lunch except for picky kids (and annoying Grey kids at our schools).

    Now excuse me while I go get a lap dance at Draconubiles Night Club. Maybe I’ll pay for more, I don’t care since Glaxxon Financial has nice interest rates on savings.

  75. #75 Grant
    April 4, 2013

    Dallas,

    So many of your remarks show a lack of understanding. Rather than object, you’d do better to ask for someone to fill you in.

    As one example in comment #39 you wrote “I have also noticed that Dr Offit did not include the smallpox vaccine in the reference table.” The list is of the vaccines given to those in the study – the smallpox vaccine isn’t one of them so it isn’t listed. That’s not surprising – the smallpox vaccine hasn’t been on the routine vaccine schedule in the USA since the early 1970s.

    In your most recent comment your write, “The antigenic load of each vaccine ideally would contain the major virulence factors of the pathogen, which is the basis of immunological memory.” – That’s what the modern (e.g. recombinant) vaccines do.

    The reason for the high antigen count for the typhoid and DTP vaccines will be that these are “whole” organism (bacteria/virus) vaccines. Sure, only a portion of the proteins/polysaccharides/etc will dominate the antigen load, but all of them are foreign molecules present in the body and so all count as potential antigens.

    As for this sort of thing: “Dr Offit sadly, is doing a great disservice to humanity and he’s still continues to harm more innocent children with his outright lies and deception.” – that’s just being silly. Personal attacks on him won’t change the results found.

  76. #76 Krebiozen
    April 4, 2013

    Dallas,

    The cumulative number of antigens has increased significantly since 1996.

    How many antigens were children exposed to in the good old days before vaccination, when almost all of them contracted measles, mumps, rubella and chicken pox? If you think exposure to antigens in vaccines is dangerous, how much more dangerous is a full-blown infection with one of these diseases? These viral infections, particularly measles, also suppress the immune system so that secondary bacterial infections are common, greatly increasing antigen exposure. If exposure to either a few highly virulent or numerous less virulent antigens in infancy causes autism, we would expect to have seen far more cases in the days before routine vaccination for childhood diseases. Wouldn’t we?

  77. #77 Narad
    April 4, 2013

    “Immunogenic spots” = epitopes

    And according to the study, it states clearly:

    ” Moreover, the calculations do not take into account the number of epitopes per antigen or the immunologic strength of each epitope.”

    But then you’re undercounting what is presented to the immune system. This seems to contradict your previous argument regarding Tohama open read frames. This is the upshot of Sheridan et al. and linked epitope suppression.

  78. #78 Narad
    April 4, 2013

    I have also noticed that Dr Offit did not include the smallpox vaccine in the reference table. Does it mean he finally realized that he had mistaken the “200 viable organisms per mL” to be antigenic component of the vaccinia virus vaccine?

    The smallpox entry in this table comes from here.

  79. #79 Science Mom
    http://justthevax.blogspot.com/
    April 4, 2013

    So why did you move the goalpost Orac? Why did you dismiss it as “toxin gambit” when we’re actually referring to the “immunogenic proteins and polysaccharides” of the whole cell pertussis vaccine which are mostly toxins (PTx, LPS, AC, DNT, TCT, among others)?

    They are de-activated toxoids for starters, not active. The ‘toxin gambit’ refers to the ridiculous and ever-shifting assertions of vaccine constituents causing whatever, including constituents that aren’t even in vaccines. Besides, there were no differences between ASD and NT groups for the receipt of DTP.

    The rate of autism did not go down because:

    1. The cumulative number of antigens has increased significantly since 1996. The ~3000 purported number of antigens in the whole cell pertussis vaccine was Dr Offit’s reference point for his false claim “that children are exposed to fewer antigens (proteins and polysaccharides) in vaccines today than in the past.”

    Then you won’t mind supplying actual evidence for this in terms of antigens.

    The drop in antigenic load between the old WCPV and APV is only a difference of a couple of toxins (less LPS) but not the absurdly dramatic decrease from ~3000. He may have used the Tohama pertussis strain’s genomic sequence of having ~3000 ORFs in a disengenuous attempt to establish the false premise. That would be a medical travesty.

    A couple of toxoids less? Why don’t you count them up for us in terms of antigenic sites.

  80. #80 Dallas
    April 4, 2013

    But then you’re undercounting what is presented to the immune system. This seems to contradict your previous argument regarding Tohama open read frames. This is the upshot of Sheridan et al. and linked epitope suppression.

    What part of “virulence factors” do you not understand? If a pertussis infection could kill humans with its toxin would they developed a vaccine containing surface proteins or the toxins? Remember LPS? It was used to be a major component of the old whole cell pertussis vaccine but was eventually removed because of its e side adverse effects. LPS was later founf out to be antigenic but not immunogenic. Epitope suppression is simply a vaccine failure as a result of the lack or incomplete use of virulence factors in the vaccine.

  81. #81 Ren
    April 4, 2013

    “What part of “virulence factors” do you not understand? If a pertussis infection could kill humans with its toxin would they developed a vaccine containing surface proteins or the toxins? Remember LPS? It was used to be a major component of the old whole cell pertussis vaccine but was eventually removed because of its e side adverse effects. LPS was later founf out to be antigenic but not immunogenic. Epitope suppression is simply a vaccine failure as a result of the lack or incomplete use of virulence factors in the vaccine.”

    My, my… Someone can take term definitions and regurgitate them, can’t she?

    *applause*

  82. #82 Dallas
    April 4, 2013

    Tohama open read frames? Where else did Dr Offit get the ~3000 figure?

    Oh look smallpox has 200 antigens? Let’s look at your citation Narad.

    “198 ‘major’ protein-coding regions …

    “Protein-coding” parts [also called "coding sequences" (cds) or "open reading frames" (ORFs)] contain the sequence information needed to create functional protein (polypeptide) chains . Most of the parts presented on this page are protein-coding sequences only — a few of them, however, currently also contain RBS sites.

    Now if Dr Offit is trying to rectify a mistake with another mistake then at least be fair. C. diphtheria was so pissed off after Dr. Offit gave her a count of “1 protein”. C. diphtheria has 2272 ORFs.

  83. #83 Dallas
    April 4, 2013

    They are de-activated toxoids for starters, not active.

    Yeah right. They were so “de-activated” the vaccine was able to cause more cases of acute encephalopathy than the natural disease.

  84. #84 JGC
    April 4, 2013

    What part of “virulence factors” do you not understand?

    What does one need to understand other than ‘virulence factor’ isn’t a synonym for ‘antigen’? That is your argument, that the cumulative exposure to antigens due to routine immunization has increased significantly–right?

    They were so “de-activated” the vaccine was able to cause more cases of acute encephalopathy than the natural disease

    Citation needed.

  85. #85 Dallas
    April 4, 2013

    Then you won’t mind supplying actual evidence for this in terms of antigens.

    Dr Offit has provided the so-called “evidence”:

    1. Study-eligible children were: (1) born between January 1, 1994, and December 31, 1999.

    2. His previous article has the list of vaccines and the number of immunogenic protein and polysaccharides starting with the smallpox vaccine.

    3. 1996- the year acellular pertussis vaccine was first used. “Approximately one-half of the study children never received a whole-cell pertussis containing vaccine”

    4. The false premise. He used the Tohama strain with ORF of ~3000 “proteins” as the beginning count. In order to find an association between autism and antigen exposure, this figure must be overcome.

    False premise leads to junk study..

    A medical travesty.

  86. #86 JGC
    April 4, 2013

    In order to find an association between autism and antigen exposure, this figure must be overcome

    Actually, in order to find an association between autism and antigen exposure, there’d have to be some actual freaking evidence demonstrating an association. To date there is none.

  87. #87 Science Mom
    http://justthevax.blogspot.com/
    April 4, 2013

    Yeah right. They were so “de-activated” the vaccine was able to cause more cases of acute encephalopathy than the natural disease.

    Except they didn’t and unrecognised Dravet’s Syndrome masked that effect.

    4. The false premise. He used the Tohama strain with ORF of ~3000 “proteins” as the beginning count. In order to find an association between autism and antigen exposure, this figure must be overcome.

    Right, the Tahoma B. pertussis strain has more than 3500 proteins, not immunogens. But the comparison is apples to apples as proteins are also being used for all the vaccines. If you want to try and make the argument that DTP is the same or less antigenic (and immunogenic) than DTaP, go ahead and provide evidence.

  88. #88 Science Mom
    http://justthevax.blogspot.com/
    April 4, 2013

    Addendum to above: Polysaccharides are also included where applicable.

  89. #89 Dallas
    April 4, 2013

    What does one need to understand other than ‘virulence factor’ isn’t a synonym for ‘antigen’? That is your argument, that the cumulative exposure to antigens due to routine immunization has increased significantly–right?

    Virulence factors are essentially antigens but not all antigens are immunogenic. Dr Offit was very clear from his last article on “immunogenic proteins and polysaccharides” of each vaccines. The Bordetella pertussis species has about 33 bacterial toxins and they are of course antigenic but some of them are not immunogenic, hence, you would not expect all these antigens included in the final vaccine otherwise, you’ll kill the host. Acellular pertussis vaccine which is devoid of LPS has about 2-5 antigens. Therefore, the whole cell pertussis vaccine cannot contain such huge amount of antigens.

  90. #90 Dallas
    April 4, 2013

    Actually, in order to find an association between autism and antigen exposure, there’d have to be some actual freaking evidence demonstrating an association. To date there is none.

    The existing “evidence” is Children are Exposed to Fewer Antigens in Vaccines Today Than in the Past.

    And we have an autism rate of 1:50

    Something is amiss obviously. Now are you going to look for evidence or are you going to fix the wrong premise first?

  91. #91 Todd W.
    http://www.harpocratesspeaks.com
    April 4, 2013

    Is Dallas trying to argue that we aren’t exposed enough as children, and that causes autism?

  92. #92 Lawrence
    April 4, 2013

    @Dallas – and where is the proof that this “incidence” rate of autism is any different than it was the past?

    You do realize that guidelines for diagnosing autism is in flux, even today? And people who, as adults, are now recognized as autistic, weren’t when they were younger, right?

    Who’s premise is faulty now?

  93. #93 Denice Walter
    April 4, 2013

    Hooker appears to be a rising alt media star with appearances this week on Curt Lindeman (“Unleashed”, Wednesday), Robert Scott Bell ( Thursday) and Gary Null ( Progressive Radio Network). The last is supposed to be today but that outlet often mislabels dates in their archives amongst their other errors. It’ll show up.

  94. #94 Chris
    April 4, 2013

    Dallas:

    What part of “virulence factors” do you not understand?

    What part of “citation needed” do you not understand.

    And we have an autism rate of 1:50

    Which is a more logical explanation: the 1994 introduction of DSM IV, or the 1994-1999 vaccine schedule (which did not include smallpox)?

    And exactly how do you keep antigens from the environment away from your kids? Do you keep them inside a sterile bubble and never let them go outside to play? Do you boil every bit of food to kill everything? Do they breathe sterilized air from a tank?

    Because while you are clutching your pearls over some small numbers of antigens in vaccines, you are exposed to several times more every single day.

    Again, since you are all up in arms over the contents of the pertussis vaccines, please provide the title, journal and dates of the PubMed indexed studies that show the ingredients in the DTaP vaccine are more dangerous than the very real toxins created by the bacteria which cause pertussis, tetanus and diphtheria. Again, the above sentence has the definition of “citation”, because argument by blatant assertion is not going make us believe you.

    I am would be fascinated by what in the few milliliters of that vaccine is more toxic than tetanospasmin, which is only slightly less toxic than the botulism toxin. It is why this little needs to learn to walk again.

  95. #95 Dallas
    April 4, 2013

    ORFs are PROTEIN-coding SEQUENCE.

    Yes PROTEIN-coding SEQUENCE.

    “Protein coding sequences are DNA sequences that are transcribed into mRNA and in which the corresponding mRNA molecules are translated into a polypeptide chain.”

    You got that?

  96. #96 Chris
    April 4, 2013

    Dallas, you still need to provide citations for your claims, that includes Offit quotes. Again, citations are the title, journal and dates of PubMed indexed papers. It is not shouting in all CAPS.

    So, again, please provide the actual citation showing the ingredients in the DTaP vaccine are more toxic than the actual real toxins created when someone actually gets pertussis, diphtheria and tetanus.

  97. #97 Todd W.
    http://www.harpocratesspeaks.com
    April 4, 2013

    You got that?

    Not quite. Could you please say it again, but this time use more caps?

  98. #98 JGC
    April 4, 2013

    Virulence factors are essentially antigens but not all antigens are immunogenic

    Just as not all antigens, immungenic or otherwise, are virulence factors.

    Your argument, however, didn’t take the form of “The cumulative number of virulence factors has increased significantly since 1996″, or even “The cumulative number of antigens which are antigenic has increased significantly since 1996″: it took the form ‘The cumulative number of antigens has increased significantly since 1996″.

  99. #99 novalox
    April 4, 2013

    @dallas

    [citation needed].

  100. #100 JGC
    April 4, 2013

    The existing “evidence” is Children are Exposed to Fewer Antigens in Vaccines Today Than in the Past. And we have an autism rate of 1:50

    Which argues against any association between exposure to antigens and the risk of developing of autism. Agreed?

  101. #101 JGC
    sigh
    April 4, 2013

    Blockquote fail.

    The existing “evidence” is Children are Exposed to Fewer>Antigens in Vaccines Today Than in the Past. And we have an autism rate of 1:50

    Which argues against any association between exposure to antigens and the risk of developing of autism. Agreed?

  102. #102 Dallas
    April 4, 2013

    Sorry I have to go. Just don’t ignore the writings on the wall.

  103. #103 Chris
    April 4, 2013

    Dallas:

    Just don’t ignore the writings on the wall.

    Sorry, we are going to have wash off the graffiti you left on the wall because shouty arguments of blatant assertions are not citations. Do try to find those citations before you come back.

  104. #104 Chris
    April 4, 2013

    Blockquote fail:

    Sorry, we are going to have wash off the graffiti you left on the wall because shouty arguments of blatant assertions are not citations. Do try to find those citations before you come back.

  105. #105 Dangerous Bacon
    April 4, 2013

    Dallas: “Sorry I have to go. Just don’t ignore the writings on the wall.”

    I’m amazed at how often the goings-on here recall great moments from Monty Python.

    http://www.youtube.com/watch?v=KAp9sFVdERQ

  106. [...] this discussion going on over at Respectful Insolence between an anti-vaccine activist and an epidemiologist, like [...]

  107. #107 Narad
    April 4, 2013

    Oh look smallpox has 200 antigens? Let’s look at your citation Narad.

    “198 ‘major’ protein-coding regions …

    Yes, which was the point. It seems to have eluded you, although I quoted your remark, that this was in response to your implicit assertion that “he finally realized that he had mistaken the ’200 viable organisms per mL’ to be antigenic component of the vaccinia virus vaccine”.

  108. #108 Dallas
    April 4, 2013

    The point Mr Narad is Dr Offit’s original claim that the smallpox vaccine has ~200 proteins. So I had to look it up in the package insert and noted that the vaccine actually contains “not more than 200 viable bacterial organisms per mL.” But things could have been a lot easier had Dr Offit not been so dishonest by just simply saying the smallpox vaccine contains “approximately 100 million infectious vaccinators viruses per mL.”

    The 198 “major” protein-coding regions are already pointless so what’s your point?

  109. #109 Dallas
    April 4, 2013

    Damn Auto-correct is a lot smarter:

    Vaccinators = vaccinia

  110. #110 Dallas
    April 4, 2013

    Just as not all antigens, immungenic or otherwise, are virulence factors.

    Like what vaccine does not contain a virulent factor?

  111. #111 Dallas
    April 4, 2013

    “Perhaps the most controversial of all the relations studied was that between DPT and encephalopathy. The committee concluded, “The evidence is consistent with a causal relation between DPT vaccine and acute encephalopathy, defined in the controlled studies reviewed as encephalopathy, encephalitis, or encephalomyelitis” (IOM, 1991, p. 118). The committee concluded that the range of excess risk of acute encephalopathy following DPT immunization was on the order of 0.0 to 10.5 per million immunizations.”http://www.nap.edu/openbook.php?record_id=9814&page=3

  112. #112 Grant
    April 4, 2013

    Dallas re your many comments…

    re #85 – I addressed all the points you make. Either you simply aren’t reading other’s comments or you don’t understand.

    You’ve continued on to make statements that are all over the place. As I wrote earlier, “So many of your remarks show a lack of understanding. Rather than object, you’d do better to ask for someone to fill you in.”.

    Quickly, then, just a few (picked more-or-less randomly to illustrate the point):

    Dr Offit has provided the so-called “evidence”:

    He only provided the antigen counts for each vaccine, not the statistics used in the study. (You’re implying him out to have provided everything.)

    1. Study-eligible children were: (1) born between January 1, 1994, and December 31, 1999.

    Sure. Is there a point to this?

    2. His previous article has the list of vaccines and the number of immunogenic protein and polysaccharides starting with the smallpox vaccine.

    So? As I wrote earlier, “The list is of the vaccines given to those in the study – the smallpox vaccine isn’t one of them so it isn’t listed. That’s not surprising – the smallpox vaccine hasn’t been on the routine vaccine schedule in the USA since the early 1970s.” (Offit’s earlier paper is listing vaccine contents over a wider range in time; the table in the paper lists what the children studied received. No smallpox vaccine listed, because none was given to the children being studied.)

    3. 1996- the year acellular pertussis vaccine was first used. “Approximately one-half of the study children never received a whole-cell pertussis containing vaccine”

    So? As they are counting antigens people taking different vaccines isn’t an issue. (Excepting the case where different manufacturer’s versions of a particular vaccine slightly differ, as noted in the study. The differences there are small.)

    4. The false premise. He used the Tohama strain with ORF of ~3000 “proteins” as the beginning count. In order to find an association between autism and antigen exposure, this figure must be overcome.

    As I wrote earlier, “The reason for the high antigen count for the typhoid and DTP vaccines will be that these are “whole” organism (bacteria/virus) vaccines. Sure, only a portion of the proteins/polysaccharides/etc will dominate the antigen load, but all of them are foreign molecules present in the body and so all count as potential antigens.”

    False premise leads to junk study..

    You haven’t shown anything is false.

    A medical travesty.

    Yes, you’re a laugh a minute. Full of nonsense. (If you don’t like this, consider: why claim things when you clearly don’t know the biology, rather than ask and let people fill you in.)

    re #82

    Now if Dr Offit is trying to rectify a mistake with another mistake then at least be fair. C. diphtheria was so pissed off after Dr. Offit gave her a count of “1 protein”. C. diphtheria has 2272 ORFs.

    The counts presented in the paper are the number of the proteins (or polysaccharides, etc) in the vaccine. The diphtheria vaccine has (had) only one. The organism has many (of course). You’re trying to suggest others are failing: this is colossal goof. If shows, again, that you’re just cut’n’pasting and making loud noises with no understanding.

    re #83 Yeah right. They were so “de-activated” the vaccine was able to cause more cases of acute encephalopathy than the natural disease.

    See Science Mom’s comment #87.

    re #95


    ORFs are PROTEIN-coding SEQUENCE.

    Yes PROTEIN-coding SEQUENCE.

    “Protein coding sequences are DNA sequences that are transcribed into mRNA and in which the corresponding mRNA molecules are translated into a polypeptide chain.”

    You got that?

    Yes, we can see you’re cut’n’pasting something you think you’ve just learnt. Small hint: this is high school biology – some of us have been working in biology for, aw, getting on 30 years, eh?

    (@Todd #97: Hehe!)

    re #107 – this is so all over the place that I don’t know where to start.

    And so on.

    But a point: Even you were were to exclude the “whole”-cell pertussis vaccine it wouldn’t matter a lot: the main results (to my mind) are the second results column in the tables Orac showed, where the children have had twice the number of antigens as those in the reference group, but with no difference in autism rates seen. These results are not affected by whatever anyone says about the “whole”-organism vaccines as those vaccines aren’t present in that data.

  113. #113 Grant
    April 4, 2013

    Dallas #110

    - cut’n’pasting again.

    That was written before it was understood that many (most) of these case were in fact Dravet Syndrome. (See Science Mom at #87.)

  114. #114 Science Mom
    http://justthevax.blogspot.com/
    April 4, 2013

    That was written before it was understood that many (most) of these case were in fact Dravet Syndrome. (See Science Mom at #87.)

    @ Grant, Dallas is Thingy so there will be much persevering on her bailiwick du jour.

  115. #115 Dallas
    April 4, 2013

    The counts presented in the paper are the number of the proteins (or polysaccharides, etc) in the vaccine. The diphtheria vaccine has (had) only one. The organism has many (of course). You’re trying to suggest others are failing: this is colossal goof. If shows, again, that you’re just cut’n’pasting and making loud noises with no understanding.

    Let me give you a little kindergarten session. The C. diphtheria species originally has 2 toxins whereas the final vaccine would only contain 1 toxin. Now the B. pertussis species has 33 toxins, how many toxins do you think are there in the vaccine?

  116. #116 Dallas
    April 4, 2013

    Is Dallas trying to argue that we aren’t exposed enough as children, and that causes autism?

    No. My argument is pretty clear in #67.

  117. #117 Dallas
    April 4, 2013

    Dravet syndrome is clinically distinct from acute encephalopathy. The evidence of causal relation is only between DPT and acute encephalopathy regardless if this adverse would lead to chronic neurologic damage including Dravet Syndrome.

    “Encephalopathy: acute generalized disturbance of brain function requiring hospitalization and consisting of coma or stupor that cannot be attributed to medication or pos- tictal state. Such cases must have altered consciousness, delirium, obtundation and/or confusion.”
    Encephalitis/encephalomyelitis: evidence of acute neuro- logic disease presenting with nonspecific signs such as fever, seizures, altered consciousness, headache, vomiting, meningismus or anorexia. We required multifocal involve- ment of the central nervous system and evidence of cere- brospinal fluid inflammation (

  118. #118 Narad
    April 4, 2013

    The point Mr Narad is Dr Offit’s original claim that the smallpox vaccine has ~200 proteins. So I had to look it up in the package insert and noted that the vaccine actually contains “not more than 200 viable bacterial organisms per mL.” But things could have been a lot easier had Dr Offit not been so dishonest by just simply saying the smallpox vaccine contains “approximately 100 million infectious vaccinators viruses per mL.”

    What on earth are you babbling about? You mistook where the figure of 200 came from. Now, rather than simply admitting this, you’re claiming that your error somehow makes Offit dishonest.

  119. #119 Science Mom
    http://justthevax.blogspot.com/
    April 4, 2013

    Dravet syndrome is clinically distinct from acute encephalopathy. The evidence of causal relation is only between DPT and acute encephalopathy regardless if this adverse would lead to chronic neurologic damage including Dravet Syndrome.

    So now Thing Dong is saying DPT will cause genetic alterations. True to form Thingy.
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3187538/

  120. #120 Dallas
    April 4, 2013

    A drop of a smallpox vaccine could contain approximately 6,666,666.67 infectious vaccinia virus. Does it even come close to ~200, Narad?

    Dr Offit manipulated the data and controlled the researchers in that study. Yes, he is totally dishonest.

  121. #121 Roger
    April 4, 2013

    @Dallas, re: #116: ” No. My argument is pretty clear in #67.”

    Quote, #90: “The existing “evidence” is Children are Exposed to Fewer Antigens in Vaccines Today Than in the Past. And we have an autism rate of 1:50″

    So, yes, you basically DID say that. #90 conflicts with your claim (uncited, of course, and contrary to all actual evidence) in #67 that antigen loads have gone up.

    Which is it, Dallas? Have antigen loads gone up or down? If you think it’s up (as in #67), please cite something other than your caps lock key. If you think it’s down (as in #90), please realize that this completely negates your argument that it could possibly be related to a perceived rising rate in autism.

    Not to mention that you completely ignore every single argument, every time, and instead quote-mine random sources hoping to distract from your ignorance.

    Dallas, I don’t want to be mean, but I find it impossible at this point to believe that you are anything other than a troll.

    Well, I suppose there is one alternative: you could just be a sophisticated spam-bot. Someone replies to you, you respond with a cut-and-paste sentence from a random science page. I don’t quite see how this is going to sell Nike shoes or male enhancement pills, but I see this tactic ALL OVER my spam filter.

    @Grant, #112: “you’re just cut’n’pasting and making loud noises”

    I actually snorted a little bit out loud.

  122. #122 Dallas
    April 4, 2013

    The evidence is consistent with a causal relation between DPT vaccine and acute encephalopathy. Now if you’re going to argue then present the evidence that this was retracted.

  123. #123 Chris
    April 4, 2013

    Dangerous Bacon:

    I’m amazed at how often the goings-on here recall great moments from Monty Python.

    I think this clip is more appropriate:
    Romans Go Home Latin Lesson

    Hey, Dallas that 1991 paper is a bit out of date:

    Pediatrics. 2010 Aug;126(2):263-9.
    Lack of association between acellular pertussis vaccine and seizures in early childhood.

    Pediatr Infect Dis J. 2006 Sep;25(9):768-73.
    Encephalopathy after whole-cell pertussis or measles vaccination: lack of evidence for a causal association in a retrospective case-control study.

    So are going to come up with a citation showing the ingredients in the DTaP are more toxic than the real toxins created by the bacterial infections due to diphtheria, tetanus, pertussis.

  124. #124 Dallas
    April 4, 2013

    Quote, #90: “The existing “evidence” is Children are Exposed to Fewer Antigens in Vaccines Today Than in the Past. And we have an autism rate of 1:50″

    The first sentence was the one I was trying to disprove hence my argument in #67. That existing “evidence” (please mind the quotes) was Dr Offit’s decree he made in 2002 and then again recently.

  125. #125 Narad
    April 4, 2013

    Now if Dr Offit is trying to rectify a mistake with another mistake then at least be fair. C. diphtheria [sic] was so pissed off after Dr. Offit gave her a count of “1 protein”. C. diphtheria [sic] has 2272 ORFs.

    Once again, there was no “mistake.” You can argue with the counting method, something that you have so far failed to do successfully, but the diptheria toxoid vaccine, which is what’s being counted, has one protein with four conjugated antigens. You have one immunogen.

    If you actually had put enough thought into the matter to split hairs, you could have tried it this way.

  126. #126 Chris
    April 4, 2013

    Yeah, it looks like Dallas is Thingy. Totally impervious to reality.

  127. #127 Narad
    April 4, 2013

    A drop of a smallpox vaccine could contain approximately 6,666,666.67 infectious vaccinia virus. Does it even come close to ~200, Narad?

    You’ve lost this one; deal with it.

    Dr Offit manipulated the data and controlled the researchers in that study.

    “Manipulated” how? The sources are cited. You can disagree with the methodology, but again, you have failed to do so cogently and now are simply opting for some random detour.

  128. #128 herr doktor bimler
    April 4, 2013

    Dr Offit [...] controlled the researchers in that study.

    Did he use his state-of-the-art Thought Control Machine? Are the researchers in fact robot dummies which Offit is directing from afar? Inquiring minds would like to know.

  129. #129 Grant
    April 4, 2013

    Science Mom,

    @ Grant, Dallas is Thingy so there will be much persevering on her bailiwick du jour.

    It’s amazing how tangled up Thingy’s thingying is.

    Dallas,

    The C. diphtheria species originally has 2 toxins whereas the final vaccine would only contain 1 toxin. Now the B. pertussis species has 33 toxins, how many toxins do you think are there in the vaccine?

    Not only have you not gotten what your earlier error was, you now shift goalposts to repeat another error you made (one which I didn’t address earlier).

    Let me remind you. Your earlier error was to confuse the number of proteins in the vaccine and the number of proteins in the organism – a pretty basic error. See also #125.

    Now you are repeating some nonsense about vaccines not having the same number of “toxins” as the organism. Same class of error. Generalising, vaccines use surface proteins from the organism. Nothing to do with the bacterial “toxins”.

    You’re only making an ass of yourself by presenting what you’re saying as “facts” y’know. Better to acknowledge you don’t know this stuff well enough to be presenting it to others.

  130. #130 Melissa G
    April 4, 2013

    I think Dallas/Thingy is a Turing test. She sure reads like one.

  131. #131 Orac
    April 4, 2013

    Grant, Dallas is Thingy so there will be much persevering on her bailiwick du jour.

    All the indications are there. Although the IP address is different., there are many other clues.

  132. #132 brian
    April 4, 2013

    Those wishing for a study comparing vaccination rates among autistic and non-autistic kids won’t have to wait long.

    “No Differences in Early Immunization Rates Among Children with Typical Development and Autism Spectrum Disorders” is a talk to be presented at IMFAR next month. The researchers are from the MIND Institute, one of those which carries a great deal of weight among those promoting a vaccine-induced autism-epidemic.

    The University of California, Davis, the home of the MIND Institute, receives federal funds to support research–and each and every researcher there is therefore, like Orac, obviously a cog in the CDC-mandated defense of the ever-expanding vaccine schedule. ‘Nuff said.

    Since a quick search of the 2013 IMFAR abstracts suggests that mercury, thimerosal, and MMR will NOT be discussed at the meeting, it’s obvious that the scientists who have dedicated their lives and careers to studying autism are ALL part of the world-wide cover-up.

  133. #133 Politicalguineapig
    April 5, 2013

    Science Mom: Dallas can’t be thingy. She actually uses punctuation and capitalization. She might be thingy’s older sister.

  134. #134 Narad
    April 5, 2013

    Dallas can’t be thingy. She actually uses punctuation and capitalization.

    Yah, I’m not getting the usual linguistic tip-offs, but I’ve been wrong on this front before. One does, after all, have this:

    Who cares? Well, Offit the Crook does and so his minions. This jackass quack had tried jacking up the numbers to mislead the people. But I do not count the antigens, I count the pathogens and the virulence factors.

    And, further down,

    Offit the Crook counted the genes for WC pertussis vaccine and now you’re telling me he can’t do the same for each polysaccharide capsule of each vaccine strain of Hib and S. pneumoniae? Or is he barking up the wrong tree? Following your method, if CPS is to HiB and S. pneumoniae, the WC pertussis vaccine should only contain 5 antigenic components which are also the virulence factors of the pathogen (Ptx, AC, FHA, AGG, LPS)

    Maybe it’s figured out that some of its catchphrases are dead giveaways, but this would represent an impressive development of restraint.

  135. #135 lilady
    April 5, 2013

    @ Narad: Thingy has been using different names…and different IP addresses as well. She’s been banned on all the science blogs. I suspect she’s undergone AoA’s strict moderation policy and been banned there as well. For cripes sake Thingy…banned by AoA !

    Courtesy of Dachel’s “Media Update”, the press release for the book launch of TMR’s book. Make certain to connect to all the links. Dr. Bob Sears does the book’s Foreword.

    http://finance.yahoo.com/news/thinking-moms-revolution-book-offers-134500277.html

  136. #136 Narad
    April 5, 2013

    Note, however, that it got “S. pneumoniae” correct (although making a really dumb comment about polysaccharides), whereas Dallas got “C. diphtheriae” wrong.

  137. #137 Adam
    April 5, 2013

    What’s the point of an April Fools if people are too smart to fall for it? Sounds like the DJ’s hooked their bait perfectly and reeled the idiots in.

  138. #138 Adam
    April 5, 2013

    Gah – I retract that comment – two articles on a tab each, one comment, wrong tab!

  139. #139 Science Mom
    http://justthevax.blogspot.com/
    April 5, 2013

    Science Mom: Dallas can’t be thingy. She actually uses punctuation and capitalization. She might be thingy’s older sister.

    She starts off coherent, wrong but coherent to avoid immediate detection but then slides downhill.

  140. #140 Gray Falcon
    April 5, 2013

    I stopped listening to Dallas/Th1Th2 the moment she brought up smallpox. How do you make that kind of blunder?

  141. #141 Denice Walter
    April 5, 2013

    Addenum to my # 93 above:
    Hooker shows up on the show labeled as that of the 3rd, April- in the last ten minutes; talks about pre-natal exposure to Hg via flu vax and rhogram etc. Progressive Radio Network; Gary Null Show.

  142. #143 brian
    April 7, 2013

    Well, now Hooker’s submitted his “analysis” of the paper as a Rapid Response in the BMJ:

    http://www.bmj.com/content/346/bmj.f2095/rr/639837

    As Matt Carey pointed out, a UC Davis group is poised to demonstrate that there is no difference between ASD cases and controls with respect to vaccination in a different study population. It’s worth noting that the large CHARGE (CHildhood Autism Risks from Genetics and Environment) study has already contributed a number of case-control studies related to ASD–I wonder if all those studies were “overmatched”?

  143. #144 Grant
    http://sciblogs.co.nz/code-for-life/
    April 7, 2013

    brian – thanks for the heads-up.

  144. #145 Science Mom
    http://justthevax.blogspot.com/
    April 7, 2013

    I notice Hooker failed to mention he has FOIA suits against the CDC and is a petitioner for the NVICP. For someone constantly whining about the supposed conspiracies and conflicts of interest of vaccine researchers, he does a fine job of blatantly hiding his.

  145. #146 Grant
    April 7, 2013

    Science Mom,

    I have to admit one of my quibbles about the BMJ (and other journals’) response sections is that many, particularly non-scientists, do not give their conflicts of interests properly or at all. I’ve seen organisers (i.e. not just “mere” followers) of anti-vaccine forums write responses and not declare their conflicts of interest (as I suspect all of us who have read their have!)

  146. #147 Narad
    April 8, 2013

    Speaking of Th1Th2, check out this Facebook page and tell me that commenter “Athee Ross” is not one and the same.

  147. [...] while the kid is all about rhetoric. They wouldn’t let the PhD guy talk because, frankly, hilarity would ensue. I mean, the guy can’t even tell what’s what in a case-control study, and he wants to [...]

  148. [...] it is based on. In case you’re interested, the article I was pointed to was covered by Orac here. Perhaps Hubbard based this claim on a different article? I can’t say, as he doesn’t [...]

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