Let’s say that you think food A caused disease B. To test your theory, you get cases of people who got B and controls of people who did not get B. Then you compare the odds of exposure to A. The ratio between the odds is called the odds ratio, and anything significantly different from 1.0 means there’s some sort of an association (if both ratios are equal, two equal odds divided by each other are equal to one). For these case-control studies, it is very important to choose your cases and controls carefully. If you are not careful, you mess up the odds of exposure, messing up the odds ratio. When that happens, you make it look like two things are associated when they’re not.
This is what we in the biz call “bias.”
Now, let’s say that you’re dead-set on blaming A for B. But, as you get older, you’re more likely to be exposed to A, and you only get diagnosed with B as you get older. Can you see where, even if there is no association between A and B, you could see one because time moves forward? You see an example of this in real life with Nobel Prize awards. You would think that only older adults get Nobel Prizes, or that being old is associated with getting a Nobel Prize. The problem is that all the work you need to do to earn the prize takes time, so you can only get it after working in your field a long time. Very rarely will someone very young get it.
So why am I writing all this? I got a tip from Todd W. (you should go read his blog) of a study by some known anti-vaccine luminaries. The study, published in Brain Sciences (an online and open source journal) attempts to link the Hepatitis B vaccine given at a young age (usually between birth and six months in American children, but available to people of any age) and Hyperkinetic Syndrome of Childhood (HKSoC). Guess what the anti-vaccine activist “researchers” found?
Go ahead and guess. I’ll give you a few seconds.
Surprise! They found an association between getting the dreaded “mercury” (aka thimerosal) in Hepatitis B vaccines to a diagnosis of HKSoC later. My guess is that they would have published nothing if there was no observed association, given that at least one of the authors — Brian S. Hooker — has an ongoing case in the vaccine court. In my opinion, it is essential for BS Hooker to find an association between vaccines and almost anything so that his case can have a little more heft to it. A couple of the other authors bill themselves as vaccine experts, although they have some questionable credentials. So let’s start there.
Not too long ago, David Geier (“The Son”) and Mark Geier (“The Father”) got into hot water in Maryland because of The Father’s medical misadventures. For a while, The Father and The Son diagnosed children with autism as having an overabundance of testosterone and treated them accordingly. That is, mistreated them. There is no evidence that testosterone causes any aggravated symptoms of autism. As Todd W. reports:
“Dr. Geier, through his Institute of Chronic Illness and Genetic Centers of America, misdiagnosed autistic children with precocious puberty so he could claim that he was using Lupron on label, rather than for an unapproved, experimental indication (i.e., autism). This also allowed him to bill insurance companies for the lupron. His actions got him into hot water with various state medical boards, starting with his medical license in Maryland being suspended on April 27, 2011. Since then, one by one, 11 of his 12 medical licenses were suspended, an application for a thirteenth license in Ohio was denied, and some of those suspensions became complete revocations. The last actions I wrote about were the revocation of his license in Missouri and suspension of his Illinois license. At the time, the only state left in which Dr. Geier could practice was Hawaii.
As of April 11, 2013, that is no longer the case.
Although his license listing on the Hawaii state Professional and Vocational Licensing search has yet to be updated as of this writing, searching the state’s RICO Complaint History database reveals that the board revoked his license last month. The case number is MED 2011-79-L (if the link to the PDF doesn’t work, go to the OAH Decisions web site, click on OAH Final Orders and search for “Geier”). According to the Final Order, a petition for disciplinary action against Dr. Geier was filed on July 17, 2012, Geier was notified on November 19, and a hearing was held on February 5 of this year. Dr. Geier failed to appear for the hearing and did not file for exceptions or extensions to delay the hearing.”
Not only that, but The Son (David Geier) was charged with and found guilty of practicing medicine without a license.
In other words, the authors have more conflicts of interests than what they led on in the study’s COI statement:
“All of the investigators on the present study have been involved in vaccine/biologic litigation.”
To say the least.
But what about the study? Is it any good? No, it’s not good. Before I tell you why it’s not good, let’s talk about their conceptual framework. These anti-vaccine luminaries’ theory is that exposure to the Hepatitis B vaccine and the thimerosal therein leads to HKSoC. To test their theory, they used the Vaccine Safety Datalink (VSD), a database maintained by the Centers for Disease Control and Prevention (CDC) where vaccine outcomes are tracked. Basically, if you are part of a healthcare system that reports to VSD, the vaccines you get (their lot numbers, dose, etc.) are reported to the database. If you ever get sick and go to the same healthcare system, those following visits (for whatever cause) are also reported to VSD. Anyone with the time and money can then “dumpster dive” through the data and try to come up with something to publish.
This is not to say that the VSD is a bad idea or a waste of time. Serious scientists who account for all possible sources of bias — and thus all possible confounders — can get a lot from the data in it. It’s actually the reason we know that HPV doesn’t cause all the horrible things that anti-vaccine people attribute to that vaccine, or any vaccine. There are millions of doses given to millions of people and reported in the VSD, and there is yet to be any credible sign of anything really bad coming from all those vaccinations. There is also no evidence of autism rising from increased vaccination. (Note that I didn’t lump autism with “anything really bad” because autism is not bad. I know. I know. Antivaxxers won’t believe this.)
Anyway, as I told you in the opening paragraph, when you choose your cases and controls, you have to choose them at random is possible, and without any kind of bias as to how to classify them, except for whether or not they’re cases or controls. You don’t say, “Okay, you are a case if you have the disease and…” There is no “and.” You’re a case if you have the disease. You’re a control if you don’t have the disease. Injecting any more requirements triggers a bias. Again, if I think that A causes B, and I only choose cases who have been exposed to A, how do I know that B isn’t caused by something else if I left anyone exposed to that something else outside of my study?
But that is exactly what these people did. From their methods section, with my emphasis:
“To locate the initial cases of a diagnosis that fell within the HKSoC spectrum (ICD-9 code: 314.xx), including the following subtypes: attention deficit disorder without mention of hyperactivity (314.00), psychiatrically known as ADD; attention deficit disorder with hyperactivity (314.01), psychiatrically known as ADHD; hyperkinesis with developmental delay (314.1); hyperkinetic conduct disorder (314.2), and other specified manifestations of hyperkinetic syndrome; (314.8) and unspecified hyperkinetic syndrome (314.9), the outcome files were examined. This included both outpatient and inpatient diagnoses. When multiple cases of HKSoC umbrella in a child were discovered, only the initial one was used. Table 1 summarizes the year of birth of the children diagnosed with HKSoC identified in the present study. Among those children diagnosed with an HKSoC identified in Table 1, only children where the HKSoC diagnosis came after they received a HepB vaccine were allowed in the analyses. This step was incorporated to be sure of the necessary temporal cause and effect relationship.”
Read that again. Only children where the diagnosis came AFTER the exposure were allowed into the analysis.
“But Hepatitis B vaccine is given immediately after birth, of course the diagnosis will come after the exposure?” you ask. Well, not for everyone. And even if those numbers are relatively small, it is important to know if and how many cases of HKSoC are occurring in the yet-to-be-vaccinated or unvaccinated.
Then this is how they got their controls (children without the HKSoC diagnosis), with my emphasis:
“To find control children who did not have an HKSoC diagnosis and only a low probability of getting that diagnosis later as they were followed-up, the control children had to be enrolled continuously from after birth up until they were at least 7.55 years old (mean age of initial HKSoC diagnosis + SD of mean age of initial HKSoC diagnosis). When this rule was applied, it left a group of control children numbering 20,584, with males = 10,303, females = 10,281, and male/female ratio = 1.002. Their year of birth ranged from 1991 to 1993. Thus, the exclusion criteria for the control children (those without a diagnosis of HKSoC) were lack of continuous enrollment, lack of record of the child’s gender, and an age of less than 7.55 years. The year of birth of the control children used in the analyses are summarized in Table 1.“
Reading how they got cases and how they got controls, do you think that they’re cases and controls are comparable in their chances of making it into the study? No. The answer is no. Then, if you remember what I said about the Nobel Prize, and what I’ve told you about the vaccine, and what we see about HKSoC diagnosis… What can you conclude about the vaccine and the chances of diagnosis?
Yes, the older you are, the more likely you are to have been diagnosed if you were going to develop HKSoC. And, the older you are, the more likely you are to have been exposed to more thimerosal because you’re more likely to have all three doses of the vaccine. But these “researchers” didn’t control for that. They didn’t even take into account that maybe there were cases out there who were vaccinated post-diagnosis. By inserting that requirement that you had to be diagnosed AFTER AND ONLY AFTER being vaccinated, they wiped out an entire universe of possible cases that we don’t get to know in this “research.”
So, do exposed cases and unexposed cases have an equal chance of making it into the study? No, because of the requirement of being vaccinated before the diagnosis. And do exposed controls and unexposed controls have an equal chance of making it into the study? No, because most children will be vaccinated (exposed) by age 7, raising the chances of the exposed to be in the study more so than the unexposed.
To seal the deal of doing epidemiology and biostatistics in a really weird way, the only statistical analysis the authors report doing is a Fisher’s Exact Test, which is fine for 2×2 tables, but it’s not really as good as linear regression, especially with all the possible covariates that exist in the databases (e.g. age, gender, ethnicity, location). They did a Fisher’s on the gender strata, but that is as far as they controlled for covariates.
Really sloppy work.
So what do we have in this new anti-vaccine piece of propaganda disguised as “research”? We have:
- Authors with serious conflicts of interest.
- An author whose previous “research” has been retracted because it was just as bad as this one.
- An author who conducted very questionable “medicine” on children and lost his medical license for it.
- An author who was found guilty of practicing medicine without a license.
- And funding by an anti-vaccine foundation, the Dwoskin Family Foundation.
So does the Hepatitis B vaccine cause HKSoC? Not according to this analysis, and using this analysis to say that it does is irresponsible at best and dangerous at worse due to the seriousness of a hepatitis B infection if the vaccine is not taken/given. I cannot tell you what the intentions of the authors were in writing this and submitting it to publication. I can also not tell you why it got published. But I can tell you that, based on the authors’ previous and current anti-vaccine projects, my money’s on them trying to associate yet another vaccine with yet another neurological condition. There’s money in it, after all.
René F. Najera, DrPH
I'm a Doctor of Public Health, having studied at the Johns Hopkins University Bloomberg School of Public Health.
All opinions are my own and in no way represent anyone else or any of the organizations for which I work.
About History of Vaccines: I am the editor of the History of Vaccines site, a project of the College of Physicians of Philadelphia. Please read the About page on the site for more information.
About Epidemiological: I am the sole contributor to Epidemiological, my personal blog to discuss all sorts of issues. It also has an About page you should check out.