There have been a lot of studies on the hypothesis that the MMR vaccine causes autism. In view of the well-proven fact that immune activation is a cause of autism, this is a reasonable and biologically plausible hypothesis. There are many credible accounts of children suffering neurodevelopmental regression and acquiring autistic behaviors immediately after receipt of the MMR vaccine. In view of this circumstantial evidence and the case reports, it is surprising that an MMR-autism association is almost completely absent in the scientific literature.
The studies on the MMR-autism hypothesis generally do not find evidence for it. Some of these studies are garbage, like the well-known Madsen 2002 study (see our review here). Another well known study by scientists at the CDC (DeStefano, Pediatrics, 2004) reported misleading/fraudulent results by not following the predetermined study protocol. This study deliberately omitted a positive association between MMR receipt and autism in boys (especially in black boys). This positive association was explored by Dr Hooker using the CDC data in this paper, which was retracted. Dr Hooker’s results are almost exactly the same as what the CDC scientists (DeStefano et al.) found and deliberately removed from their paper. I consider the retraction of Hooker’s paper to be completely unjustified and obviously political. So I accept Hooker’s results. Here are the reasons why Dr Hooker’s results should be accepted. And here is a presentation by Dr Hooker explaining this story (analysis starts at about 10:00).
The deliberate removal of the positive MMR-autism association by CDC scientists is important because it proves the CDC is motivated to conceal evidence of vaccine injury. The CDC is not impartial. The CDC will lie to promote vaccines.
Several MMR-autism papers funded by CDC were performed by Dr Poul Thorsen as lead investigator. Today Dr Thorsen is a fugitive criminal wanted for embezzlement of about $2 million in research funds. This does not necessarily mean that his results are fraudulent; but in science, reputation is important. The CDC has an obvious strong desire to conceal vaccine dangers. A dishonest, greedy scientist like Dr Thorsen is likely to fabricate results to advance the CDC’s political agenda. So I am not accepting of studies led by Dr Thorsen. Criminality or dishonesty in combination with motivation to lie is fatal for a scientific study, in my opinion (especially in highly controversial subjects). The story of Dr Thorsen is explained here in the Huffington Post.
But some of the MMR-autism studies are apparently good quality and free of fraud, conflicts of interest, or criminality, such as Smeeth 2004 Lancet. This was a large case-control study from the UK and it found no association between MMR receipt and autism. I looked at this study closely, corresponded with the author, and find it to be free of obvious flaws. I accept the results of Smeeth 2004, which are in apparent contradiction with Hooker’s results.
This was the state of the MMR-autism controversy at the time Jain’s paper was published in April 2015.
Jain et al. JAMA 2015
Full paper (Jain et al): Autism occurrence by MMR vaccine status among US children with older siblings with and without autism.
The Jain et al study received a lot of media attention when it was published April 21, 2015. It was promoted as the “final nail in the coffin” for the MMR-autism hypothesis. I disagree with this assessment.
The Jain study looked at autism and exposure to the MMR vaccine by age (at 2, 3, 4, and 5 years). Separate analyses were performed for children with and without older siblings diagnosed with autism. The idea here being that children with an autistic older sibling may be more sensitive to MMR. This is a good hypothesis.
A substantial problem with the Jain study is that parents observing developmental delays or autism symptoms will avoid MMR vaccination. Consequently, sick children (e.g. vaccine-injured children) will be concentrated in the MMR-unvaccinated control group, even if the problems are caused by vaccines (i.e. non-MMR vaccines). This of course will conceal an association between MMR and autism. If parental MMR-avoidance is large enough, it will create a negative association (i.e. the incidence of autism will be higher in the MMR-unvaccinated group). Jain et al report this negative association (since all but one risk ratio is <1.0).
In other words, there are two possible causal links between MMR vaccination and autism, and they interfere with one another:
Causal Link #1: MMR vaccination causes autism (the hypothesis under investigation)
Causal Link #2: Autism (or vaccine injury) causes MMR avoidance (due to parental concern that vaccines may cause autism. Mere indicators suggestive of autism, not enough for autism diagnosis, will also impact parental vaccination decisions)
For link #2 I use the term “healthy user bias”, or HUB. Its also known as “healthy vaccinee effect”. It occurs because sick people avoid vaccines. Its a terrible confounder for many vaccine studies, including studies of the flu vaccine. See this article on healthy user bias: http://vaccinepapers.org/healthy-user-bias-why-most-vaccine-safety-studies-should-not-be-trusted/
Above: Vaccine injury from first-year vaccines cause healthy user bias (HUB) in MMR-autism studies. Children injured by first-year vaccines are less likely to receive the MMR, and hence are used as “unvaccinated controls” in MMR-autism studies. These so-called “unvaccinated” subjects receive lots of vaccines, just not MMR. Of course, this is extremely misleading and conceals the damage caused by MMR.
To measure only link #1, there must be a way to avoid HUB, or eliminate it from the data. In a population partially accepting the possibility that vaccines may cause autism, HUB is probably impossible to avoid. There is great awareness of the vaccine-autism controversy. A 2014 survey by the National Consumers League found that about 33% of parents believe vaccines can cause autism. These parents will avoid vaccinating a child showing signs of autism or experiencing neurodevelopmental problems.
Also, its expected that parents with one autistic child may be more cautious regarding vaccination of their second child. Hence, we should expect HUB to be stronger in children that have an autistic older sibling.
Jain et al. acknowledge HUB , but they make no effort to control for it. Jain states:
“It is possible, for example, that this pattern is driven by selective parental decision making around MMR immunization, i.e., parents who notice social or communication delays in their children decide to forestall vaccination. Because as a group children with recognized delays are likely to be at higher risk of ASD, such selectivity could result in a tendency for some higher-risk children to be unexposed. To be consistent with observed data, this would need to happen more often at younger ages. This seems feasible because by the time the child is older, developmental concerns are more likely to have been confirmed or ruled out and parents may then be less worried about a new exposure, such as a vaccination, influencing a child’s developmental trajectory. Estimates at older ages would thus be less susceptible to bias related to selective parental decision making, which also aligns with the pattern observed here.” (Emphasis Added)
Jain et al, 2015
I agree with the above description of the problem. Jain says that HUB will be stronger at younger ages, and I agree.
However, I want to go further. Is it possible to estimate the strength of HUB? If so, we will be able to determine if HUB is large enough to influence the study outcome. If HUB is strong enough, it could completely reverse the study outcome.
How Strong is HUB (link #2)?
The data provided by Jain (see Table 2 in the Jain paper) enables a calculation of an estimate of the strength of HUB. Jain correctly assert that “estimates at older ages would thus be less suceptible to bias related to parental decision making…”. In other words, HUB will be strongest at younger ages, and weakest at ages 4-5. Accordingly, in order to obtain a conservative estimate of HUB, we will use the data for the oldest ages (4-5) in the Jain study.
So, lets determine the strength of HUB. We do this by calculating the use of the MMR vaccine between age 4 and age 5, and comparing vaccine usage for autistic and normal children. Specifically, this is done by looking at the number of unvaccinated at age 4 and age 5.
Having sibling with ASD:
Age 4 unvaccinated: 25/387 (25 with ASD, of 387 total. Number without ASD = 387-25=362)
Age 5 unvaccinated: 23/269 (23 with ASD, of 269 total. Number without ASD = 269-23=246)
The change in these numbers indicates the number that received the MMR vaccine between age 4 and 5.*
2/25 autistics were vaccinated, a rate of 8%.
116/362 non-autistics were vaccinated, a rate of 32%
So, non-autistics were vaccinated at a rate 32/8= 4 times greater than autistics. Parents with one ASD child strongly avoid giving the MMR vaccine to a second child with autism. Obviously this will bias the study results by concentrating autistics in the “unvaccinated” group (i.e. MMR-unvaccinated).
Since only 2/25 autistics were vaccinated, there is substantial statistical uncertainty. The 4X ratio will have a wide confidence interval. This issue is ignored in this simple analysis.
Lets repeat the calculation for the non-ASD sibling group.
Having sibling without ASD:
Age 4 unvaccinated: 65/11957 (65 with ASD, of 11957 total. Number without ASD = 11957-65=11892)
Age 5 unvaccinated: 56/7735 (56 with ASD, of 7735 total. Number without ASD = 7735-56=7679)
9/65 autistics were vaccinated, a rate of 13.8%
4213/11892 non-autistics were vaccinated, a rate of 35.4%
So, non-autistics were vaccinated at a rate of 35.4/13.8=2.6 times greater than autistics. Parents without an autistic older child are also avoid giving the MMR in a second child with autism.
As expected, parents that already have one autistic child (the older sibling) more strongly avoid the MMR vaccine in their second child (since 8% < 13.8% and 32% < 35.3%). This occurs whether the second child has autism or not. This is a clear demonstration that autism in the family leads parents to avoid MMR vaccination.
Rate ratios of 2.6 and 4 are rather strong effects. We will choose the more conservative rate ratio of 2.6 for further analyzing the results. And remember that Jain asserted that parental vaccine avoidance will be weakest at age 4-5, compared to younger ages. So at younger ages, the rate ratio is likely to be even greater than 2.6, according to Jain et al.
The rate ratio gives us the information we need to remove the effect of parental vaccine avoidance due to autism. It allows an approximate correction for HUB, and thereby produces a more accurate estimate of link #1.
Removing HUB
The question now is: what effect will an avoidance rate ratio of 2.6 have upon data at the other ages? Will this be enough to change the outcome of the study?
To answer this question, we calculate risk ratios of autism for the other age groups, corrected by a factor of 2.6.
We combine all the data for each age (non-ASD sibling and ASD sibling). This makes the calculation more conservative, since the parental avoidance is stronger in the ASD older sibling group.
Autistics are 1/2.6 (38.5%) as likely to be vaccinated as non-autistics, due to autism-motivated parental behavior (i.e. HUB). Removing this effect requires increasing the number of vaccinated, autistic subjects by a factor of 2.6. Alternatively, the same correction can be obtained by reducing the number of unvaccinated autistics by a factor of 2.6 (i.e. removing the autistics that were unvaccinated due to parental observation of autism). Either choice has the same effect on the risk ratio calculation.
Results of the corrected calculation are shown in the table below.
Above: The risk ratios are corrected by a factor of 2.6 to remove the effect of HUB. The resulting corrected risk ratios are now greater than 1, suggesting that MMR vaccination is indeed associated with autism.
The important thing to notice is that the corrected risk ratios are greater than 1. This means that HUB is strong enough to account for the finding of no association by Jain et al. In fact, HUB appears to be so strong as to conceal a positive association between MMR and autism. In other words, when the effect of HUB is removed, the Jain et al study data shows that MMR is associated with autism.
However, I am not arguing that Jain et al. provides evidence for a positive MMR-autism association. I think there are too many assumptions for such a claim. Rather, I assert that HUB is strong enough to make the Jain et al study unreliable. The Jain et al results are essentially meaningless. The reason why Jain et al. find no MMR-autism association is simply because of the effect of autism on parental vaccination choices, not the other way around. When parents observe autism or autism traits, they avoid vaccination, and the result is that autistic children wind up in the “unvaccinated” group. Obviously, this is a highly misleading effect that conceals an autism-causing effect of MMR.
HUB is why MMR-autism studies are wrong
Many vaccines, including MMR, cause autism. Vaccines cause autism if they stimulate interleukin-6 or interleukin-17a production in the brain. The autism effect is not observed in Jain et al due to its failure to control for HUB.
There are profound difficulties in studying health outcomes in a population that is aware of the hypothesis under investigation. Many people are aware of the vaccine-autism controversy and believe in the link. When they adjust their behavior accordingly, the direction of causation is reversed and the phenomenon becomes almost impossible to observe.
HUB biases every MMR-autism study. Unfortunately, the other MMR-autism studies do not provide the data necessary to calculate the strength of HUB. Jain et al. is the only study I am aware of that provides data sufficient to estimate the strength of HUB.
HUB is a good reason to be skeptical of all human vaccine-autism studies, and instead look at controlled animal studies. Animal studies always have better controls and do not suffer from biases due to behavior of study subjects. And many animal studies prove beyond any doubt that activation of the immune system during brain development causes autism, schizophrenia, epilepsy, seizure disorders and other brain injury. Animal studies also prove beyond doubt that aluminum adjuvant in vaccines can cause brain injury, at dosages routinely given to human infants.
Researchers at the CDC published an important paper in 1992 on HUB, showing that it can be strong enough to completely reverse the outcome of vaccine safety studies. See this article for a detailed explanation: http://vaccinepapers.org/healthy-user-bias-why-most-vaccine-safety-studies-should-not-be-trusted/
Final Word
The Jain study only looked at MMR. Media reports about this study have falsely and deceptively asserted that the Jain study shows that “vaccines” in general do not cause autism. In reality, the Jain study says nothing about other vaccines. The MMR vaccine is the only vaccine that has been much studied in relation to autism, and all of the MMR-autism studies suffer from HUB. The other likely more dangerous aluminum-containing vaccines, given at younger ages, have hardly been studied at all. It is a blatant lie to claim that the science shows “vaccines” in general do not cause autism.
The science actually shows the opposite. Controlled animal experiments overwhelmingly prove that immune activation (i.e., interleukin-6) in the developing brain causes autism. Animal experiments also prove that aluminum adjuvant causes brain damage, at dosages human infants routinely receive from vaccines. There is also evidence that aluminum and the Hepatitis B vaccine stimulate interleukin-6 production in the brain. Hep B vaccine evidence: http://vaccinepapers.org/two-vaccines-opposite-effects-brain/
NOTES:
* I have made two assumptions here: that the 269 are all derived from the 387, and the 23 were all derived from the 25. However, this is not necessarily true (some of the 387 could have become part of the 23 autistic at age 5). I believe any resulting error is small. Also, I believe this error will not likely affect the ratio calculation, because it likely affects both autistics and non-autistics similarly (we are calculating a ratio, after all). I would need more detailed data from Jain to know for sure (Jain has not responded to this request).