Tuesday, August 26, 2014

Brian Hooker's Hooked Hoax: Measles-Mumps-Rubella (MMR) Vaccination and Autism Spectrum Disorder

I always get the best stuff from Google+ to look at, don't I? This post is stemming from my last post on autism spectrum disorder (ASD), which was a response to a prompt by C0nc0rdance on YouTube. If you're interested in this topic, I would recommend reading it just to be familiarized with some of the literature, and then read the post-publish discussion in the comments section and on Google+. It's not necessary for this post, however.

Uh-oh.
In February of 2004, DeStefano et al. published a study entitled Age at first measles-mumps-rubella vaccination in children with autism and school-matched control subjects: a population-based study in metropolitan atlanta. This was a case-control study collected in Atlanta, comparing age of first MMR vaccination between children with autism (N=624) and the control children (N=1824), collecting data on maternal and birth factors from immunization forms and birth certificates, in order to determine risk of ASD at different age cutoffs of MMR immunization. The findings were that with the exception of vaccination before 36 months being more common in case children than control children (which was attributed to immunization requirements in early intervention programs, and was a modest 2.8% difference), there was no significant association between the age cutoffs and the risk of autism. This is one of many pieces of evidence which show that the MMR vaccine does not confer an increased risk in ASD.

However, 10 years after the initial study was conducted, famous anti-vaccine alarmist Brian Hooker, along with Andrew Wakefield, are talking about a "whistleblower" in the CDC claiming that the original data was fraudulent, and was masking a 336% increased risk in ASD in African American boys receiving the MMR vaccine "on time." Hooker published his own findings in the Journal of Translational Neurodegeneration, titling it Measles-mumps-rubella vaccination timing and autism among young african american boys: a reanalysis of CDC data. He claims that according to the "whistleblower," Dr. William Thompson, the CDC intentionally manipulated the data to bury this increased risk.

Here we go again.
To people who are familiar with the anti-vaccine movement, Hooker and Wakefield are household names. Wakefield has become famous for his scientific fraudulence, and Hooker has recently become the new big name, most likely taking pointers from Wakefield himself; thus making Dr. Hooker's name very apt.

But what exactly is going on here? Was the CDC fraudulent? Did they intentionally manipulate the data to hide this increased risk? Before we get to that, there are a few things we need to make note of.

It's always good to remain skeptical when someone proposes that they have reanalyzed already published data. In my experiences, although limited, this never amounts to anything good, and the arguments are usually pretty weak. On that same note, when someone reanalyzes data, they most likely have a chip on their shoulder. Keep in mind this isn't true for all reanalyses -- in fact, such reanalysis is what called Wakefield out for his fraudulence in the first place -- but I'm speaking from personal experience.

These a priori contentions not withstanding, Hooker's reanalysis just didn't seem right at all when I first looked at it. Let's just quote the conclusions from the abstract for a moment:
"The present study provides new epidemiologic evidence showing that African American males receiving the MMR vaccine prior to 24 months of age or 36 months of age are more likely to receive an autism diagnosis."
And from the results:
"Relative risks for males in general and African American males were 1.69 (p=0.0138) and 3.36 (p=0.0019), respectively."
Hooker went through all this trouble just to show that only African American males are at a higher risk for ASD from the MMR jab? That's certainly not going to do anything for Jenny McCarthy. Color me unimpressed by the so called coverup by the CDC, because it leaves the overwhelming majority of evidence that shows there is no link between the MMR vaccine and ASD untouched. In fact, even if he'd shown the whole study was fraudulent from its conception, he still would've left the overwhelming majority of research to the contrary untouched. Even better, a 3.36 increase in ASD isn't 336%. It's 236%.

Booker accuses DeStefano et al. (2004) of intentionally leaving out African American males in their sample in order to manipulate the results, but that's just not what happened. Subjects that were inappropriate, given age requirements and necessity of medical information, were excluded from the study because they wouldn't be able to control for the important things mentioned earlier: maternal and birth factors, as well as actually comparing something useful in this particular study. DeStefano et al. weren't manipulating the data, they were legitimizing it.

But the burning question here is: did Hooker even manage to show what he claimed he did? Are African American males at a higher risk for ASD from the MMR jab at ages younger than 24 or 36 months? Let's take a look inside the paper to find out.
"The relationship between the MMR vaccine and autism was first hypothesized by Wakefield et al. [7] in 1999 after the observation of a regressive phenotype of autism that appeared in general after the administration of the first MMR vaccine. Although several studies have affirmed such a relationship between the MMR vaccine and neurodevelopmental disorders including autism [8,9], many other studies purport no statistical relationship between the MMR vaccine and autism incidence."
This is only the third paragraph in, mind you, and Hooker cites Wakefield, and then two studies by the Geier duo. Don't make me laugh. Hooker is partaking in a classic "teach the controversy" grasp at straws to make it seem like there's even some doubt that the MMR vaccine isn't linked to ASD. No matter. Let's just skip to the methodology:
"Cohort data were obtained directly as a “restricted access data set” from the Centers for Disease Control and Prevention (CDC) via a Data Use Agreement. Data were deidentified by the CDC in accordance with Family Education Rights and Privacy Act (FERPA) and the Health Insurance Portability and Accountability Act (HIPAA) prior to receipt by the study authors."
Wait what? Cohort data? But the original study by DeStefano et al. was case-control. Oh, there we see it.

I know I have some readers who aren't too fond of statistical babble, so I'll sum up what the issue is here. The original study by DeStefano et al. used something called a case-control model. In a case-control model, you compare a group of case subjects (subjects with the disease) and control subjects (without the disease) and determine how frequently another variable occurs for either group of subjects while controlling for confounders and effect modifiers. Hooker, on the other hand, used a cohort model, which doesn't quite do the same thing. Regardless, using data that was arranged to be analyzed in a case-control model and then analyzing it in a cohort model is just screaming problems; especially when you chop up the data into multiple subcohorts so that any small effect will be magnified.

The funny thing is, even with the skewed methodology, the results aren't even impressive. Table 2 below from Hooker's paper shows the age group cutoffs and their risk for ASD:


So what's wrong here? Not much, except for the fact that the relative risk only sees a modest increase at the 24 month cutoff. The true increase is seen at 36 months. So why is this important? Because symptoms of autism are most noticeable starting at age 3. This isn't anything new Hooker. That's why DeStefano et al. controlled for age in their original study. Because they're not stupid.

But why was there an increase in exclusively African American male children? The answer is simple again. Table 4 from the study shows us this:


Hooker reveals that he had to use a 31 month cutoff because he was limited in terms of sample size. This, also, isn't anything new in the realm of statistics, Hooker. Smaller sample sizes are going to potentially yield misleading results because the smaller the sample, the greater its susceptibility to statistical noise. Funny enough, Hooker didn't even provide his sample size. The very lack of transparency in Hooker's paper, after being prompted by accusations of a lack of transparency in the CDC, is absolutely egregious.

This didn't take very long to research and debunk; in fact, I was surprised at how little exposure this study got. Perhaps we're all learning something from these types of studies: they provide nothing informative, and are only reflections of someone's ideologically grinding teeth and hand waving. In doing so, Hooker hooked a hoax: his own.

Thank you all very much for reading.

UPDATE: Translational Neurodegeneration has taken Hooker's article off public domain for concerns about the validity of its findings. You can find it in full here.

(8/28/2014) Yesterday, Dr. Thompson released a statement via his lawyers clearing the air of any doubts: Wakefield is just as disingenuous and manipulative as he's always been.

(10/3/2014) Brian Hooker's paper was retracted from the journal of Translational Neurodegeneration after concerns were expressed of its validity. The PubMed link still works.

*I would also highly recommend looking at this infographic from Healthcare Management Degree.
Sources are at the bottom of the page.*



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ResearchBlogging.org
References:

DeStefano, F., Bhasin, T., Thompson, W., Yeargin-Allsopp, M., & Boyle, C. (2004). Age at First Measles-Mumps-Rubella Vaccination in Children With Autism and School-Matched Control Subjects: A Population-Based Study in Metropolitan Atlanta. PEDIATRICS, 113 (2), 259-266 DOI: 10.1542/peds.113.2.259

Hooker, B. (2014). Measles-mumps-rubella vaccination timing and autism among young african american boys: a reanalysis of CDC data. Translational Neurodegeneration, 3 (1) DOI: 10.1186/2047-9158-3-16

11 comments:

  1. I think it would be useful to respond to a reply I received on G+ here, so that people can see what's going on:

    "What do you require a break on?"

    All of this stupidity.

    "Thompson admitted in an available video there was suppressed and covered up data showing higher rates of autism after vaccinations."

    You mean that audio recording that Wakefield took without Thompson knowing, and took him completely out of context? Yeah, Thompson already made a statement via his lawyer here:

    http://www.morganverkamp.com/august-27-2014-press-release-statement-of-william-w-thompson-ph-d-regarding-the-2004-article-examining-the-possibility-of-a-relationship-between-mmr-vaccine-and-autism/

    "In a 2002 email Thompson authored and CC many others at CDC, states there was data being held back (and now known subsequently suppressed and covered up) and that he others were hiring attorneys for this reason."

    The email said nothing of the sort. http://www.naturalnews.com/images/CDC-DOJ-Investigation-MMR-Vaccine-Autism-NN-Watermark.jpg

    "Thompson has made a statement he regrets suppressing and covering up the data."

    No, he made statement saying he regrets that the CDC data isn't as transparent as he'd like it to be.

    "So, what do you want to be given a break on?"

    See the responses above.

    ReplyDelete
  2. "3.36 increase in ASD isn't 336%. It's 236%" - why? how?
    please, explain it to me, thanks in advance

    ReplyDelete
    Replies
    1. Gladly! A 3.36 fold increase means you multiply the original number by 3.36. I'll use an example of money: let's say you start off with $100. Then, let's say your money increases 3.36 fold. That means multiply 100 by 3.36, which equals $336. $336 is a 236% from $100.

      Basically, your starting point is always a 1 fold "increase." A 1 fold increase actually means no increase at all: multiplying the original number by 100% yields the same number.

      I hope this helped!

      Delete
  3. oh yeah, I got it..

    but here is anther think: the 3.36 dose not come from table 4, but 3, and there is 36 cutoff, no 31

    anyway, I think, it is because of age, like You said. But I think, that the number is higher in African American more than in general population because of a hidden factor, confounding.

    I guess the key is here: "Destefano et al. [14] study, the coauthors interpreted this result as an artifact of “healthcare seeking behavior” citing that autistic children would receive their vaccines earlier in order to enroll in State of Georgia early intervention programs. However, it is highly unlikely that this type of behavior would be seen exclusively in African American males and thus, alternative hypotheses must be explored, including the possibility that the MMR vaccine may be causally linked to autism in African American males." so accordng to Hoooker, it is unlikely, but he does not have (yet) an evidence for it. Destefano pointed out, that if You look at the African american, who keep some "rules" (programs in Georgia) and African american without it, it reveals the hidden factor, that is why he interpreted that it is the factor, not connection between autism and vaccines. So it is "unlikely" against "a kind of proof". That is not manipulating, like the antivax says.

    ReplyDelete
    Replies
    1. Oh, I know. I was merely citing Table 4 in order to show that the sampling was off. Hooker hypothesizes that something having to do with higher vitamin D in AA males results in this higher vulnerability to the vaccines, or something, but it's unfounded. As I said in my post, I'm at a bit of a loss for why Hooker would be so obnoxiously loud about this finding in the first place. It's a single study, and it only shows a link in AA males -- his own reanalysis verifies that there's no link between the MMR vaccine and ASD in any other race or gender. I don't see why he's so proud of that.

      Delete
  4. What exactly is relative risk? That 3.36 number, what does it mean exactly? Is that a percentage?

    ReplyDelete
    Replies
    1. Relative risk is the probability of something happening to the affected group, relative to the unaffected group. In this scenario, a relative risk of 3.36 would mean that compared to AA males unexposed to the MMR vaccine, AA males who are exposed have a 3.36 relative risk of having ASD.

      3.36 can be represented as a percentage, which would be 336%. What this means is that AA males who have received the MMR vaccine at 36 months have a 3.36 fold increase in ASD, or a 236% increase from the original 100%.

      Delete
  5. "using data that was arranged to be analyzed in a case-control model and then analyzing it in a cohort model is just screaming problems; especially when you chop up the data into multiple subcohorts so that any small effect will be magnified."

    could You explain me a little bit more - how can using cohort study design instead of case-control study design make the reanalysis wrong? I know the differences, You have also write them a tried to explain, but can be made an argument based on this that the reanalysis is bullshit?

    ReplyDelete
    Replies
    1. Actually, in general, cohort studies are of substantially superior quality to other studies. The issue here is that Hooker used a cohort model for data that were collected for case-control analysis. This is significant, however, because it means that Hooker compared exposures in cohorts retrospectively, which leaves room open for selection/identification bias. At the same time, certain risk factors (i.e. maternal/birth factors) aren't controlled for. To make matters worse, Hooker sliced and diced the data with multiple subcohorts, leaving the study even more prone to false positives.

      So yes, based on this alone, one can dismiss this study as bullshit. There are actually many ways you can dismiss the study as bullshit. Point out that he cited a retracted paper. Point out that he cited a paper by Geier, who had his medical license revoked. Point out that he didn't have an epidemiologist or statistician on his team. Point out that the results disprove Wakefield.

      All in all, changing the study design is suspect, whether or not it's obvious where the biases may lead. Case-control data should be analyzed via case-control methods.

      Delete
  6. In fall 2012, my husband received his annual flu vaccine. The next day, he had arthritic (RA) like symptoms: swollen joints, pain, required a cane for mobility, and was off work for 2.5 months. We were considering disability, and at that time, he was only 38 years old. Being pro-vaccine, my hubby saw the timing of the vaccine to the symptoms as mere coincidence. In fall 2014, he received his flu vaccine. The next day, wham, all symptoms were back with a vengence. He and his doctors now concede a correlation.

    LIke it or not, vaccines do cause adverse reactions. Dr. Wm Thompson backs this in his press release. Though he mentions vaccines do save lives, he states that there are risks associated. Note he does not say vaccines are safe. Nor does he say the vaccine-autism link is debunked, as there are "still more questions than answers."

    Here is the biggest problem with this situation, in my opinion. To be pro-vaccine means to deny or minimalize the adverse reactions. To fully acknowledge there are problems though, means change can occur. Pharmaceutical companies need to be held accountable to develop safe alternatives to those preservatives or combination of viruses in one vaccine which continually are deemed suspect. These companies at least have the deep pockets to try.

    To demand change from the pharmaceutical industry is not anti-vaccine; in reality, change can remove or reduce the justified reasons from those who are.

    ReplyDelete
    Replies
    1. I'm sorry that all of this happened to you. People can have adverse reactions to different vaccines; in fact, this is why some people need to consult their doctor before getting the influenza vaccine if they have an egg allergy. This doesn't mean, however, that because one person has serious reactions to the influenza vaccine, that the vaccine itself is dangerous. It means some people can't receive it because of its contents, just like some people can't eat a tuna salad.

      So if this is your case for why vaccines are dangerous, with emphatic consideration, then it's rather weak. Just because some people can have reactions to mayonnaise doesn't mean there is anything universally wrong with mayo. The same goes for vaccines. Dr. Thompson, however, does say:

      "I would never suggest that any parent avoid vaccinating children of any race. Vaccines prevent serious diseases, and the risks associated with their administration are vastly outweighed by their individual and societal benefits."

      That seems pretty safe to me.

      "To be pro-vaccine means to deny or minimalize the adverse reactions."

      Then you would be unaware of what "pro-vaccine" actually means. Being pro-vaccine would mean supporting the usage of vaccines, encouraging people to protect themselves and their children. I acknowledge that there are many possible reactions to all kinds of vaccines. I also acknowledge the many possible reactions to taking ibuprofen, leaving the seat up and eating buffalo chicken wings. Just because there are some side effects to something doesn't mean it's bad. If that were the case, you should be advocating against living in Philadelphia.

      "To fully acknowledge there are problems though, means change can occur."

      You're right, and I never disagreed with this. I just don't think there's a link between the MMR vaccine and autism, since the link hasn't been well established, and Hooker's study design was flawed.

      "Pharmaceutical companies need to be held accountable to develop safe alternatives to those preservatives or combination of viruses in one vaccine which continually are deemed suspect."

      Only if those suspicions are legitimate; in which case, they do (see the egg allergy). Wakefield's data was fraudulent. So was Hooker's. This doesn't make suspicions of MMR vaccines causing autism legitimate.

      "These companies at least have the deep pockets to try."

      I don't know where you get that idea. The CDC is a non-profit organization, and their research needs funding. Pharmaceutical companies are also not as profitable as one may think.

      "To demand change from the pharmaceutical industry is not anti-vaccine; in reality, change can remove or reduce the justified reasons from those who are."

      It's anti-vaccine if you're irresponsibly pushing associations that aren't there, or are incredibly rare (like the association between the influenza vaccine and death). There's no established link between the MMR vaccine and autism. All attempts to establish it have failed. There's no reason, then, to demand that the relevant organizations look into the association, or to demand that pharmaceutical companies change their methods.

      Delete

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