Respectful Insolence

There’s a new blog in town that I’ve been meaning to pimp. It’s a blog by a retired epidemiologist who got things started looking at the role of diagnostic substitution in autism diagnoses and argued that the autism “epidemic” is an artifact of changing diagnostic criteria.

The blog is Epi Wonk, and it’s a good one so far.

This week, I’m really glad Epi Wonk exists. The reason is that somehow, another Geier père et fils crapfest of dumpster-diving has somehow slimed its way into the medical literature, just in time to be used in the Autism Omnibus hearings no doubt. The “study” (if you can call it that) is entitled Thimerosal exposure in infants and neurodevelopmental disorders: An assessment of computerized medical records in the Vaccine Safety Datalink, posted as an article in press at the Journal of Neurological Sciences. For reasons that escape me, Pharmalot has a direct link to the PDF and appears to be pimping this execrable exercise in cesspit (I mean data) mining. I understand why Age of Autism is so eager to pimp this article, but why Pharmalot?

In any case, a number of people have pointed this study out to me. However, after diving into the craptacular exercise in bad science known as the “13 monkeys” study being touted by the Age of Autism by Hewitson and Wakefield, the thought of diving into yet another exercise of tortured statistics so soon by the Geiers was about as appealing as diving head first into the Cuyahoga River in 1969, except that likening the Geiers’ “research” to industrial waste is an insult to industrial waste. At least industrial waste comes about as a result of producing goods and products that are useful. Not so anything the Geiers have published in the last decade or two at least.

Fortunately, Epi Wonk is taking on this study so that I don’t have to. She’s far more able to see through the data torturing than I am (although the manipulation of data is so blatant that anyone who’s taken Biostatistics 101 should see through it immediately.) A taste:

This study has a lot of problems, and I predict that it will take me at least five posts to go through the article point by point to explain all the flaws. However, there’s one trick that the authors play that’s so glaring that I have to point it out immediately. In fact, I’ve spent two days in shock that the journal editor and reviewers let the authors get away with it.

See what I mean? I could deconstruct the latest Geier opus, but I couldn’t do it in such ruthless, clinical detail. I know some epidemiology, but I’m not a professional. My first thought when seeing this new study was that it reminded me of the last time the Geiers tried to mine the Vaccine Safety Datalink.

Epi Wonk’s most damning finding is that the Geiers used some statistical sleight-of-hand to impute extra cases of autism to certain birth cohorts that couldn’t be legitimately done:

Let’s quote directly from the Young, Geier & Geier paper to make sure I have this right. “Because of concern that the cohorts from 1995-1996 had only 4-6 years of follow-up, frequency distributions of age at diagnosis were examined for all years. This revealed that for some of the disorders a sizable proportion of children were diagnosed after 4.5 years. Adjustments were made for counts of cases as needed for birth cohorts depending upon the disorder examined to correct for under ascertainment that occurred due to shorter follow-up times. These adjustments were made for all disorders including the control disorders as appropriate based on the age distribution….”

“For example, 37% of autism cases in the study were diagnosed after 5 years old with about 50% diagnosed after 4.5 years old. This is a conservative estimate since it includes the 2 years (1995-1996) that had shorter follow-up times. Examination of the distribution of age of diagnosis by birth year for autism revealed that only about 15% of cases were diagosed after 5 years of age in the 1995 birth cohort while the 1996 birth cohort had no cases diagnosed after 5 years of age and only 3.5% of cases diagnosed between 4.5 and 5 years of age. Based on the average age at diagnosis for all cohorts the 1995 count of autism cases was increased by 45 cases with the assumption that all of these would have been added in the 5 year+ age group (bringing this percentage close to the overall average of of 37% diagnosed after 5 years of age.) The same was done for 1996, but the number of cases was augmented by 80 because it was assumed that these would be diagnosed in the 4.5 to 5 and 5+ groups essentially bringing the percentage after age 4.5 close to the overall average of 50% diagnosed after 4.5 years of age. The new augmented frequency counts of cases in 1995 and 1996 birth cohorts were then use as new case counts in the analysis.”

This is just not done. It’s not valid. It’s not ethical. Adding imaginary cases into a data set borders on scientiific fraud. I’ve been trying to wrap my mind around some sort of rationale for the authors “imputing” extra cases and to me it’s just fudging the data. What they’ve done bears some relationship to a procedure called “direct age standardization,” but age standardardization might be useful in a situation where invesigators were comparing birth cohorts — not where the birth cohorts are the units of analysis (more on this “units of analysis” concept later). I don’t think this is downright scientific fraud for two reasons. First, they carried out this procedure of “imputing” imaginary cases for the control disorders, as well as autism and five other neurodevelopmental disorders. (I’ll explain this in more detai in upcoming posts.) Second, they come right and admit that they cooked the data by adding imaginary cases — it’s not as if they’re trying to hide anything.

The Geiers doing something unethical? Imagine that. I urge you to go and read Epi Wonk’s entire post. I look very much forward to seeing the rest of her deconstruction of this study.

The Geiers’ fudging data to make it show what they want it to show I can understand. After all, that’s just what the Geiers do. It’s like a dog rolling in excrement or a dead and decaying bird. They just can’t help themselves, as it’s natural to them. But what about Heather Young, an Assistant Professor of Epidemiology and Biostatistics at the George Washington University School of Public Health? Does she realize that she’s committing academic suicide to be associating with the Geiers? Surely she doesn’t think that a tenure committee will look favorably on a publication record that includes articles like this, does she? More importantly, surely she must have known that the methodology she used is dubious.

I will give the Geiers that the VSD database is a much better source of data for studies than the VAERS, their previous favorite stomping ground. The reason VAERS is so crappy for incidence and prevalence data is because anyone can submit a report to it and blame anything on a vaccine reaction. This is good for looking for early warnings of problems. However, it’s bad for any useful data about correlations. Indeed, Dr. Laidler once famously demonstrated how ridiculous reports to the VAERS database can be when he submitted a report claiming that vaccines had turned him green and large; i.e., had turned him into The Incredible Hulk:

The chief problem with the VAERS data is that reports can be entered by anyone and are not routinely verified. To demonstrate this, a few years ago I entered a report that an influenza vaccine had turned me into The Hulk. The report was accepted and entered into the database.

Because the reported adverse event was so… unusual, a representative of VAERS contacted me. After a discussion of the VAERS database and its limitations, they asked for my permission to delete the record, which I granted. If I had not agreed, the record would be there still, showing that any claim can become part of the database, no matter how outrageous or improbable.

Another problem with the VAERS database is that vaccine litigants have been urging people to report any and all perceived vaccine reactions, particularly cases of autism, to the VAERS database. As I discussed two years ago, this has hopelessly distorted the database.

In contrast, the VSD database is a collaborative passively collected database managed by the CDC with several large HMO. It was last used to demonstrate that neurodevelopmental disorders other than autism are not associated with vaccines. Medical professionals are entering data, and there is a system for monitoring. However, individual-level data takes work to derive, and the Geiers probably didn’t have access to individual-level data because they had been busted for trying to merge datasets in such a way that would have compromised patient confidentiality. Instead, they used average estimated levels of exposure for each of the seven birth cohorts, a point that I had planned on emphasizing heavily when I got around to analyzing the study in more detail. Given that, it might as well Epi Wonk tells us why this is inherently a bad way to analyze such data:

Aside from the fact that a regression analysis based on an N of 7 is unstable and not robust at all, it has been known in the social sciences since 1950 and in epidemiology since about 1973 that in general, regression estimates from ecological analyses tend to be hugely magnified compared to individual-level analyses. (By individual-level analysis I simply mean the type of study where individual exposure data and individual level outcome data is used in the analysis for every study participant.)

Indeed, compare how the Geiers mined the VSD to the way that a similar sort of analysis was done in the other use of the VSD:

We determined the mercury content of vaccines and immune globulins that the study children received when they were infants (1993-1998) from published data and the FDA (Table B of the Supplementary Appendix). We identified vaccines and immune globulins that children had received from HMO computerized immunization records, paper medical records, personal immunization records, and maternal interviews. Prenatal exposure to mercury included all known exposures of the mother to thimerosal-containing vaccines and immune globulins during pregnancy. We defined postnatal exposure as micrograms of mercury divided by the weight of the child in kilograms at the time of administration of each vaccine or immune globulin. Individual exposures were summed during the period of interest: birth to 1 month and birth to 7 months (1 to 214 days).

In other words, in that study, the investigators estimated each child’s exposure to mercury to the best of their abilities based on the data in VSD. Moreover, children enrolled in the study then underwent neuropsychological testing to seek out any diagnoses that could be correlated with vaccination status.

Of course, to magnify the regression estimates is exactly what the Geiers wanted to do. What I find it hard to believe is that an epidemiologist like Dr. Young would go along with this. If she is unware, perhaps it was naïveté that led her to trust the Geiers. At least, I hope that’s the case, because the other possibilities (that she’s either incompetent, intentionally cooked the data, or both) are ones that I would prefer not to contemplate. I also hope that her career doesn’t spiral downwards into autism crankery after this.

The other thing that I can’t figure out is how this sort of blatantly obvious crap got through peer review. The only explanation I can think of is that most peer reviewers also aren’t aware of the limitations of the database. In a way, this does provide a lesson for lay people who assume that peer reviewed studies are reliable, namely that there is a lot of crap out there, even in the peer-reviewed literature. The journal in which a study appears can give a reader an idea of the probability that an article within is lousy, low for high quality, high impact journals, and higher for lower quality, lower impact journals, but appearance of an article in a peer-reviewed journal, even a good one, is no guarantee that the science is solid. (That’s why when I see something in non-peer-reviewed ideological journals like the Journal of American Physicians and Surgeons, I know right away that it’s almost certainly garbage; if the authors could have gotten it into a peer-reviewed journal, even a dumping ground of a journal, rather than JPANDS they almost certainly would have.) Each study has to be evaluated on its own according to methodology. Sadly, the appearance of this article in the Journal of Neurological Sciences represents a failure of peer review for which the editors should be deeply ashamed.

I look forward to the next installment of Epi Wonk’s deconstruction of this article, and I’m going to add her blog to my blogroll the next time I update it. In the meantime, please head on over and check out Epi Wonk. Tell ‘em Orac sent you.

ADDENDUM: Here’s an acknowledgment from the paper:

This study received funding from the Autism Petitioners’ Steering Committee of the no-fault National Vaccine Injury Compensation Program (NVICP). Dr. Heather Young has been a consultant in vaccine cases before the no-fault NVICP. David Geier has been a consultant in vaccine/biologic cases before the no-fault NVICP and in civil litigation. Dr. Mark Geier has been a consultant and expert witness in vaccine/biologic cases before the no-fault NVICP and in civil litigation.

Lovely. This means this study was almost certainly funded as part of the Autism Omnibus. Talk about our government bending over backwards to give the petitioners every benefit of the doubt; it’s even funding “studies” for them to use!

Comments

  1. #1 Blake Stacey
    May 22, 2008

    Is there any plan afoot to get a comment on the paper published in the Journal of Neurological Sciences? That’s a common enough occurrence, and it looks like the hard work has already been done.

    Oh, and while we’re talking about supposed “toxins”, the question must be asked: can vodka get them out of hair?

  2. #2 Susie
    May 22, 2008

    You are my hero of the day for your commentary on the use of VAERS “data.” The anti-vax wackjobs always cite VAERS entries as proof of the harm caused by vaccines, and then get angry when I point out that at least one of the Gardasil deaths they tout was a girl whose car crashed on her way home from the clinic. If you’re telling me I’m going to crash my Toyota because I got a vaccine jab, then I’m gonna tell you you’re a tool!

  3. #3 Joseph
    May 22, 2008

    I think it’s fair to say that both the “13 monkeys” study and this one by the Geiers are litigation-generated research. I imagine we might see a few more of these before the Omnibus is over.

  4. #4 Don't Panic
    May 22, 2008

    Susie,
    I don’t think that crashing one’s car after a vaccine jab is completely is inconceivable.
    Cases of vasovagal syncope aren’t unheard of. This was recently discussed over at
    Effect Measure: fainting after a vaccination. That isn’t to say that I think it’s the vaccine itself that causes the syncope — I don’t. At least for me (see the comments there) it’s a psychological reaction to the needle.

    So, please, I don’t think I’m being a “tool”. In the case in question I’d suspect that the cause wasn’t the Gardasil itself. Go ahead and continue pointing out that there are problems with these reporting databases, just please point out that in some cases there’s a reasonable explanation for some egregious sounding ones.

  5. #5 Don't Panic
    May 22, 2008

    Sorry about the double post. I should know by now that when scienceblogs reports an error on posting that one should check to see if the post went through anyway. Mea culpa.

  6. #6 DLC
    May 22, 2008

    Okay, so… if I am reading Orac right, the idea here is that the Geiers added imaginary cases to their (bunch of crap)
    study. So, allow me to ask the Geiers : If I come to your (frankenstien)laboratory and fix the plumbing, it’ll be okay if I add some imaginary work hours to the bill ?

    PS: For “Don’t Panic” and others who may have had difficulty posting. I have found that posts go through more often without error if I hit preview before posting.

  7. #7 ed
    May 23, 2008

    Dear RI,

    Thanks for pointing out Epi Wonk’s post. I don’t pretend to be an epidemiologist and find the info very interesting and helpful. And I’m curious to see what else Epi Wonk writes and, in particular, if anything comes of the issues raised.

    To address your question, though, I posted an item about the study because the topic remains controversial and I gathered this study would likely fall into that category, given the recent and ongoing news about litigation (and yes, I noted the consulting work by the authors).

    But in case it wasn’t clear, I take no sides in the matter. The issue, in my view, is for others to debate, dismiss or decide, as the case may be. I appreciate the concerns you raised, but you’re remiss to suggest I’m ‘pimping’ for anyone. I posted news of a study for others to chew over.

    And I will be happy to post again. Perhaps the Journal of Neurological Sciences will take some action in response to the criticisms leveled by Epi Wonk or whomever. Or perhaps some other sort of shoe will drop. The ensuing debate is, itself, quickly becoming interesting fodder.

    So I will do my best to stay tuned. Meanwhile, though, I would respectfully request that you refrain from making assumptions about my motives.

    Cheers,
    Ed at Pharmalot

  8. #8 Craig
    May 23, 2008

    Ed, don’t worry. Orac does that to everyone who disagrees with his point of view. He is, after all (in his mind, anyway), always right and by golly, you are a complete idiot if you have a different point of view because, hey, didn’t he tell you what to think already? I appreciate your objective view on the subject, and I, for one, enjoy your posts and your point of view. Keep up the good work.

    And don’t let these vaccine-thugs get you down.

  9. #9 SM
    May 23, 2008

    For the Nth time:

    There is no controversy.

    There is no scientific basis to assert that vaccines in general or thimerosol in particular cause autism.

    Any claim of controversy regarding that assertion is entirely manufactured by people with ulterior motives regarding it and an interest in maintaining this nonexistent controversy.

    I say this as the parent of an autistic child and as someone who reported that child’s former pediatrician to the State Medical Board for lying to us about whether or not the child received vaccines containing thimerosol. I take the situation very, very seriously, I assure you, and whether or not the thimerosol caused the problem, our doctor had a responsibility to give us accurate information and they did not do so. I am not giving anybody a free pass when it comes to my child’s health.

    But since I am not a mathematical illiterate, I know a result of no significant correlation when I see one. Kindly stop being outraged on my child’s behalf over their nonexistent poisoning. I would appreciate it if instead you became outraged about wasting time on this nonsense instead of working for development of therapies to improve their quality of life. Thank you.

  10. #10 SM
    May 23, 2008

    For the Nth time:

    There is no controversy.

    There is no scientific basis to assert that vaccines in general or thimerosol in particular cause autism.

    Any claim of controversy regarding that assertion is entirely manufactured by people with ulterior motives regarding it and an interest in maintaining this nonexistent controversy.

    I say this as the parent of an autistic child and as someone who reported that child’s former pediatrician to the State Medical Board for lying to us about whether or not the child received vaccines containing thimerosol. I take the situation very, very seriously, I assure you, and whether or not the thimerosol caused the problem, our doctor had a responsibility to give us accurate information and they did not do so. I am not giving anybody a free pass when it comes to my child’s health.

    But since I am not a mathematical illiterate, I know a result of no significant correlation when I see one. Kindly stop being outraged on my child’s behalf over their nonexistent poisoning. I would appreciate it if instead you became outraged about wasting time on this nonsense instead of working for development of therapies to improve their quality of life. Thank you.

  11. #11 SM
    May 23, 2008

    Sorry for the double post. I think my tags messed up the input server. Feel free to delete the extra one.

  12. #12 Craig, I fixed it for you
    May 23, 2008

    And don’t let these proponents of gravity and reality get you down.

  13. #13 Dr Aust
    May 23, 2008

    It is disturbing that this passed the peer review process at the Journal of Neurological Sciences. It makes one wonder about the Journal, although they do list “neuroepidemiology” as one of their areas.

    It is hardly a secret that after the first half-dozen to a dozen journals in any “subject category”, peer review gets increasingly less stringent the further down the journal food chain you get, finishing up with the various “Journals” of Alternative Reality, oops, I mean Alternative Medicine.

    J Neurol Sci’s blurb says that it is:

    “Ranked 50th out of the 146 journals in the ISI Clinical Neurology category and 102nd out of the 199 journals in the ISI Neurosciences category! Journal Citation Reports® 2007.”

    - admittedly it is a huge field, but 50th sounds a little bit far down the list for my taste, although J Neurol Sci has an impact factor over 2.0 which suggests it is definitely not bottom-feeder fodder. The journal is linked to the World Federation of Neurology and the WHO. The editorial board is very multi-national, reflecting the journal’s parent organisation I would guess.

    Given the vast subject area the journal says it covers:

    Its scope includes neuromuscular diseases, demyelination, atrophies, dementia, neoplasms, infections, and disturbances of consciousness, stroke and cerebral circulation, growth and development, plasticity and intermediary metabolism.

    The fields covered are neuroanatomy, neurochemistry, neuroendocrinology, neuroepidemiology, neurogenetics, neuroimmunology, neuroophthalmology, neuropathology, neuropharmacology, neurophysiology, neuropsychology, neuroradiology, neurosurgery, neurotoxicology, restorative neurology, and tropical neurology.

    - one might wonder how easy they find it to come up with real expert referees for everything. I guess it would depend critically on the editorial board and the manuscript handlers. Although I would hazard a guess that a fair predictor of who their referees are might be “the folk who publish a lot in the journal”.

    Incidentally, the Editor in Chief is from one of Orac’s fave states: Robert P. Lisak of the Department of Neurology at Wayne State University.

    The above is all general surmise, of course – what we really need is a neuroepidemiologist or neurologist to tell us where the journal really stands in the pecking order for this kind of work.

  14. #14 John Best
    May 26, 2008

    While Epi Wonk tries to dazzle us by playing games with stat’s, Mark Geier is curing kids by removing the mercury from their brains.

    How many kids has Mr Wonk cured?

    Case closed.

  15. #15 Prometheus
    May 27, 2008

    John,

    Data, please? When can we expect to see the Geiers publish the results of their “study”? Any hints?

    They certainly can’t claim – as so many of the “alties” do – that they are too busy saving lives (or was it “cashing cheques” ?) to publish their results, since they’ve been publishing like mad fools ever since the Autism Omnibus hearings started.

    Until they do publish their results, I’ll play it safe by assuming that they don’t have any data supporting their “therapies” and that you – as usual – are simply repeating what you’ve read on the Internet.

    Prometheus

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