A Scientist’s Rebuttal to the Danish Cohort Study

Brian S. Hooker, PH.D., P.E.

Brian S. Hooker, PH.D., P.E.

Guest Contributor | BIO

Clipboard with vaccine list, MMR checked offThe MMR vaccine study recently published by Hviid et al. (2019, Annals of Internal Medicine) entitled, “Measles, Mumps, Rubella Vaccination and Autism: A Nationwide Cohort Study,” leaves many more serious questions than definitive answers.

The authors claim that their work, “strongly supports that MMR vaccination does not increase the risk for autism, does not trigger autism in susceptible children, and is not associated with clustering of autism cases after vaccination.”

This is an extremely broad claim that unfortunately is not supported by the evidence they present. There are eight fundamental flaws in the research study that lead to questions about the accuracy of the conclusions.

1. Children were notably missing from the study sample:

First and foremost is the underascertainment of autism cases within their data sample.  The study authors used Denmark population registries of children born in Denmark of Danish-born mothers which should reflect the current reported autism incidence in Denmark at 1.65% (Schendel et al. 2018, JAMA).  However, the autism incidence within the sample of the Hviid et al. paper is 0.98%, meaning that approximately 4,400 autistic children are missing from this study.  The authors do not discuss the discrepancy in the number of cases. 

2. Many of the children in the sample were too young for an autism diagnosis:

The most probable reason for the discrepancy in cases is that the sample in the Hviid et al. paper is too young to completely ascertain autism diagnoses.  The average age of sample is 8.64 years with a standard deviation of 3.48 years.  Age of autism diagnosis on average is reported as 7.22 years with a standard deviation of 2.86 years.  Assuming that the age of diagnosis follows a standard bell curve, this would mean that 31.5% of the sample was too young to get an autism diagnosis.  This could account for as many as 3,400 additional cases not included in the analysis, which would bias the outcomes to favor not finding a relationship between the MMR vaccine and autism.

3. Failure to eliminate those with autism related to genetic conditions from the sample:

In addition, individuals who were diagnosed with genetic comorbidities (known to lead to autism) after age 1 were “censored,” meaning that they were followed until the time of diagnosis, but not removed from the study.  Thus, they were counted among the sample with many of them most likely autistic due to a genetic condition.  These should have appropriately been eliminated from the sample.

4. Use of two (2) different MMR vaccines:

Also, two different MMR vaccines were used in this study.  The GlaxoSmithKline Prolix® formulation was used from 2000 to 2007 and Merck’s MMR®II formulation was used from 2008 to 2013.  Prolix® contains the Schwarz measles strain and MMR®II contains the Ender’s Edmonston measles strain.  Thus, children using the Merck formulation were much too young to receive an autism diagnosis as the oldest they would be at the time of study is 6 years of age or younger.  This is important for comparison to the experience in other countries, especially the U.S. where the Merck formulation was used exclusively for the entire study period.

5. Failure to control for the “dosage effect”:

In addition, the age at which Danish children in the sample received their second dose of MMR vaccine was dropped from 12 years to 4 years in 2008.  This means that children born after 2004 would get two MMR vaccines prior to the average age of an autism diagnosis, whereas children born prior to 2004 would have received only one MMR vaccine.  If indeed there is a “dosage effect” of the MMR (i.e., where both doses were causally related to autism), this could not be elucidated in the sample and again, this would bias the results erroneously to not find a relationship.

6. Statistical method failed to capture those children with a delayed diagnosis of autism:

The authors also used a non-transparent statistical method where “person-years” were considered following the MMR vaccine to an autism diagnosis where children who received a diagnosis soon after receiving their first MMR vaccine would be weighted more heavily than children with a delay in diagnosis. This makes no sense given that the age of autism diagnoses varies widely among populations based on access to services and severity of the autism case, among other factors.  This type of method is “borrowed” from infectious disease epidemiology where an exposure directly leads to a disease state rather quickly, for example, chicken pox.  However, the method has no place in evaluating chronic sequelae to vaccination which may take a period of years to receive an accurate diagnosis.

7. Vaccinated male siblings of children with autism show more autism diagnoses:

Doctor giving vaccine injection to a childIt is interesting to note the increased incidence of autism in boys with autistic siblings in the vaccinated group shown in Figure 2 of the article’s supplement. The increase towards the end of the “survival curve” shows that more boys vaccinated with MMR (with autistic siblings) are diagnosed with autism than unvaccinated boys. The difference is not statistically significant but this may be an artifact of the very small subset of boys considered in this analysis.

The study authors also cite the CDC’s Destefano et al. 2004 study which actually shows a statistically significant relationship between MMR timing and autism incidence. This is discussed further in a reanalysis of CDC’s data in the Journal of American Physicians and Surgeons (Hooker, 2018).

8. Conflict of interest of the study authors

It should be noted that three of the study authors are currently employed at the Statens Serum Institut which is a for-profit vaccine manufacturer in Denmark.  In addition, this work was funded by a grant from the Novo Nordisk foundation. Novo Nordisk is a Danish multinational pharmaceutical manufacturer. These are two serious conflicts of interest.

The lead author, Anders Hviid was the second author on the New England Journal of Medicine MMR autism paper from 2002 (Madsen et al. 2002). This research was completed despite the fact that the study authors had never received proper ethics approval to complete the studyA detailed analysis of this is featured by Children’s Health Defense.

With these issues, this paper cannot be relied upon as evidence that the MMR vaccine does not cause autism. 

Brian S. Hooker, PH.D., P.E.

Guest Contributor

Brian has been a member of the Focus for Health Team since 2012 and has more recently joined the Board. He is an Associate Professor of Biology at Simpson University in Redding, California, where he specializes in chemistry and biology coursework. Additionally, Hooker was a Senior Process Consultant at ARES Corporation until 2013, where he worked closely on process design for the environment restoration industry. His design efforts focus on industrial biotechnology and chemical engineering principles. He has a teenage son with autism and has been active in the autism community since 2004.

28 Comments

Kim Thiehoff

Thank you so much for looking at this study and giving us your learned opinion.

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Vasileios S.

The study is flawed by design and mostly from what and how they choose to ‘study’
I agree with all your remarks and I want to add the following.

1st. They choose to stop the follow up (08/2013) and that is the reason the autism prevalence at first birth cohort is 1.70% and at the last cohort only 0.2%. One explanation for that choice maybe is because in Denmark they incorporate the PCV7 vaccine (3 doses same as pentavalent) at October 2007. That mean 3 doses of a heavily adjuvanted vaccine before 1st MMR for the last cohort.

2nd. They choose to ”include and study” only 5 from 8 sub-categories of «F84 Pervasive developmental disorders» – International Statistical Classification of Diseases and Related Health Problem (ICD-10) – https://www.ncbi.nlm.nih.gov/books/NBK92974/

«F84.0 (autistic disorder – 1997 cases)
«F84.1 (atypical autism – 537 cases)
«F84.5 (Asperger syndrome – 1098 cases)
«F84.8 (other pervasive developmental disorder – 576 cases) –
«F84.9 (unspecified pervasive developmental disorder – 2309 cases).
”F84.9 PDD unspecified has a description saying that it is a residual category for PDD where there is either inadequate information or contradictory findings regarding diagnosis. F84.8 has no description at all. No description but present!!!!!!!”

But they did’t include at the study from the main ICD-10 category «F84 Pervasive developmental disorders» the 3 following subcategories.

-F84.2. Rett’s syndrome – – so far reported only in girls (they leave out that subcategory and probably that’s why at their flawed analysis it appear that ”Receipt of MMR vaccination reduced the risk for autism in girls” with a statistical significance)
-F84.3. ”Other childhood disintegrative disorder” – «A pervasive developmental disorder (other than Rett’s syndrome) that is defined BY A PERIOD OF NORMAL DEVELOPMENT BEFORE ONSET,AND BY DEFINITE LOSS OVER THE COURSE OF A FEW MONTHS, of previously acquired skills in at least several areas of development, together with the onset of characteristic abnormalities of social, communicative, and behavioural functioning» …. That definition fall exactly under their 3rd objective, … and they CHOOSE to leave all cases under that definition outside of their study
> Objective: ”To evaluate whether the MMR vaccine increases the risk for autism in children, subgroups of children, or time periods after vaccination … We evaluate the risk for autism after MMR vaccination in specific periods in detail.”
-F84.4. ”Overactive disorder associated with mental retardation and stereotyped movements”

So intentionally 1/3 of «F84 Pervasive developmental disorders» subcategories was not included in their BIASED study (and they did’t even explain that decision).

3rd. MMR vaccination status for all the children that ”appear” no-vaccinated in the registries should had been confirmed by their medical cards since a previous study ’danish mEdical JOURnal- Dan Med J 2017:64(2):A5345 proved that up to 55% of no-vaccinated (as per registries) was actually vaccinated.

4th. They should analyze the time relation between MMR vaccination and «”the manifest time of autism” or ”time of first symptom appeared” or ”the day of onset”» which could be obtained from children medical cards (which they didn’t review – ” Limitation:No individual medical charts were reviewed”), since they didn’t use the ”time of first symptom appeared” then all the aHR (for time relation between autism and MMR) analysis is complete WRONG.

Conclusion: The bias and flaws of that study strongly support that health authorities and vaccine promoters don’t want actually to RESEARCH if there is any link between autism and vaccine (or vaccines) thus actually they don’t care for the safety of their products since they are the authority and no one can question them.

My best wishes to you and your family Dr Brian, please correct me if I am wrong at any of my remarks for that study

Reply
Brian Hooker

Dear Vasileios – Thanks so much for your additional comments. I concur with your findings! All my best,

Brian Hooker

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saskia

Wooooo, thanks, Brain & Vasileios, for all your effort! With lots of appreciation from Holland!

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Andrei

Numbers on Figure 3 show that not getting DTaP-IPV/Hib vaccine decreases ASD chances from 8% to 0,9% , am I reading it correctly?

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dr. J. Marieke Buil

Just for my information. Was this written as a personal opinion, or as Associate Professor of Biology at Simpson University in Redding, California? In other words: is this rebuttal backed by Simpson University?

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Brian Hooker

Dear Dr. Buil – This is my own personal opinion and does not represent the opinion of Simpson University.

Brian Hooker, Ph.D.

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DEB S

To Brian Hooker PhD.
Is your degree of “P.E.” mean public education? Does this qualify you to do retrospective analysis of scientific studies- I honestly don’t know. Public education is important- but no one is an expert on everything.

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saskia

Be cause people used to think that one needed to be a chemist to understand what the effect of neonicotinoids could be, insects and bees are now dying on a large scale.
To your information..Deb. S., there’s a growing belief that non-chemists have the right to read studies and co-decide whether or not to use certain poisons on our crops. The same counts for nuclear power, tobacco and other stuff that weren’t handled very well by the “experts”…. The same could count for vaccination… Something with “Once bitten, twice shy.”

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Don

From now on, Saskia, fix your car yourself, fly your own airplane, have the school social studies teacher fill your cavities, and gather your own herbs to treat every malady you or your family may have. You just can’t trust experts.

Robert L Wachsmuth SR

AUTISM is a 5 trillion dollar a year profit-making scam AND GROWING medical scam you’ll never going to be able to stop it doctors making a living by killing New World Order Healthcare

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Jeff

I haven’t read the study but didn’t Del Bigtree mention this was not vaccinated vs unvaccinated, it was fully required Denmark vaccinations vs fully required Denmark vaccinations plus MMR. The CDC’s whole premise is that contraindications cause adverse reactions ie autism. Why not do a study and screen all children for contraindications prior to vaccinations? Lets let the CDC tell us what testing every parent should have done to prevent adverse reactions and make vaccinations safe. When that fails too, then the conclusion can only be vaccinations are unsafe and your rolling the dice when you vaccinate your children.

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Brian Hooker

Thanks for the comment, Jeff. I’ve been pushing for methods for screening children vulnerable to vaccine injury for years. Many of the genetic susceptibilities to such injury have already been elucidated. It would save many lives to implement such a program.

All my best,

Brian Hooker

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Chana E

Can someone explain why #3 (Failure to eliminate those with autism related to genetic conditions from the sample) is reducing the autism cases in the study? I found everything else clear and compelling, I was just confused by this one. Thanks!

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Rachel S.

#3 argues in favor of good research. If this Danish study is truly trying to elucidate if there is a connection specifically between the MMR vaccine and autism, then the study needs to separate children genetically disposed and children that aren’t genetically disposed. Why? Because it could show how many autism cases are related (or not) to the MMR vaccine even when there’s no genetic predisposition. To group all those children together is to confound these variables.

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Jaromir

I see the published data of no early DTaP-IPV/Hib group the most interesting. It can actually proof that every seventh child with ASD can have it after vaccination with MMR because not beeng early vaccinated rises risk of MMR vaccination by 17%. ( Figure3 1.17 =1.09/0.93). It actually tells that early DTaP-IPV/Hib vaccination has also increase risk by 19% (1.19=1.09/0.92). I think that it would be much more if the data were not censored. I also wonder how can be published study like this where risk of vaccination is below one. It means that compared groups are not comparable. It really is meat seriously that girls are protected by 21% if they ase vaccinated? So few shots and we will solve girls autism? No hurra cry? We solved it! Isn’t it insane?

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Anthony Newcomb

Thank you Dr. Hooker.

It’s also worth noting the danish schedule.
They don’t start vaccinating until 3 months. Further, they don’t administer HepB, flu, or chicken pox vaccines.

If you compare the 2 schedules, US 4month old infants get as many shots/ doses as a 1year old danish infant.

When I mentioned following the danish schedule to my pediatrician, she said they wouldn’t accept us asd patients.

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Al Scott

It seems that point#2 clarifies the underreporting of autism cases relative to the general population–some of the kids have try to be diagnosed. Ok, but the strongly worded conclusion in point#2 is wrong. If some of the children are too young to have been diagnosed it does not bias the results. It merely decreases the statistical significance of the null result. Please correct your statement.

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Zack M

One very important thing that wasn’t mentioned in this article is that the MMR vaccines DOES NOT CONTAIN AN ALUMINUM ADJUVANT – which is probably the main culprit that causes autism and other forms of brain damage. All of these BS meta-analysis studies only consider vaccines (generally MMR vaccine) that don’t contain aluminum nanoparticles.

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Ed

Regarding your first point “1. Children were notably missing from the study sample:” Why do you assume that the autism rate in the study (1999- 2010) MUST be the same current 2017?/2018? autism rate in Denmark. Has Denmark not experienced an increase is autism prevalence since 2010?

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Dr. Jones

Dr. Hooker,

You claimed that Hviid et al used a sample with 31.5% of their subjects too young to be diagnosed with autism. But with their sample, mean age 8.64, sd = 3.48, hence the 95% CI for age in their sample was 1.68-15.9 years. But you claim that the average age of autism diagnosis is 7.22, s.d. 2.68, so the 95% CI is 1.5-12.94 years. The bottom 31.5% (z = -1.865) of the latter would be under 1.88 years, while the bottom 31.5% of the Hviid et al (2019) sample was 2.15 years. Can you explain, especially given the Schendel (2018) data showing that autism proportions rising from age 4 to 16, why you think that Hviid et al. (2019) sampled children who were too young to be diagnosed. Arguably, they had a very good range in terms of age.

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dreamer

There are some very basic things nobody seemed to notice….

in figure 3, there is a (non statistically significant) relative risk of 2.69 in a sub group.

but as this cohort is non randomized, the huge imbalance of the size of unvaxx/vaxxed groups represents a major selection bias (if some children were unvaxxed, why ?) In the end the complete unvaxxed group represent 0,72% of the global size o the cohort. It just means that any result of this study can’t be interpreted if you don’t know why those children were fully unvaccinated.

The funniest thing : as this happens with nearly all linked-database cohort studies, there is no validation of the content.

As per the following paper : “Dan Med J 2017:64(2):A5345 – Danish MMR vaccination coverage
is considerably higher than reported” we can have very serious doubts about the quality of the original data source if only on this small extract, more than half of the “unvaxxed” children were actually vaccinated…. Also how many children were “vaccinated” while they actually weren’t…

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Donald Probst

A scientist’s rebuttal to Hooker’s rebuttal.

1 – the study was controlled as well as possible for genetic and environmental differences by strictly limiting it to children of Danish-born mothers. It is doubtful the incidence reporting you reference used that same criteria. Of course, this would also mean an unusually high incidence among non-Danes, also a ludicrous assumption (more on those later)

2- you state that as many as 3400 children were too young to have been diagnosed. Using your incidence rate from point 1 of 1.65%, that extrapolates to at most 57 additional cases, not statistically significant.

3- why should those genetically predisposed be eliminated? Presumably they are vaccinated at an identical rate to other children. Determination of whether the MMR vaccine affects their prognosis is entirely within the scope of this study.

4, 5, 6 – First, as an epidemiologist, you should know better than to invoke something like “causally related”. You are also making the assumption that the “causal agent” is the strain of Measles virus, while, no consensus has remotely been reached, even among the staunchest of Wakefield worshippers, as to what the causative agent may be.
Also, the greater the temporal difference, the more tenuous the causality becomes. Six years is pretty tenuous to begin with. It is entirely appropriate to give items with temporal similarity a heavier weight.

7 – this shouldn’t have been discussed at all. As you said, it is not statistically significant. In addition, your own conflict of interest and bias are showing more when you mention the CDC study, but link your own analysis of it rather than the original study.
Which brings us to 8.

8- The authors fully disclosed their places of employment, etc. Any conflict is tenuous at best, since the two vaccines in this study were manufactured by GSK and Merck, respectively. You failed, however, to disclose your conflicts. Were you paid to write this article? By whom? It wasn’t until the comments that you acknowledged the article was your personal opinion, despite your credentials being fully visible from the beginning.

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