Oliver vaccine injury case – Court denies appeal of NVICP ruling

On January 9, 2019, the Federal Circuit’s Court of Appeals decided not to rehear an appeal by Laura and Eddie Oliver of a decision of a vaccine injury case (referred to as “Oliver”) by a special master of the National Vaccine Injury Compensation Program (NVICP) who ruled that the NVICP would not award compensation to their son for his developmental delays and seizure disorder.

Circuit Judge Pauline Newman dissented to the Court of Appeals decision, joined by Judge Jimmie V. Reyna. Although Judge Newman’s dissent carries no legal authority, it can be offered as persuasive materials in other cases. It should not, however, carry much weight, because Judge Newman’s dissent mischaracterizes the Oliver vaccine injury case, mischaracterizes the relevant science, and makes numerous other errors.

This article will examine the Oliver vaccine injury case along with the scientific issues involved.

The Oliver vaccine injury case

Mr. and Mrs. Olivers’ son – E.O. – was born on October 2, 2008. In April 2009 E.O. received vaccines against diphtheria, tetanus, and pertussis (DTaP), hepatitis B, polio, pneumococcal disease, and rotavirus – the routine six months vaccines at the time. That evening E.O. experienced his first seizure.

The parents called 911 and E.O. was rushed to ER, where he was found to have 101.3 fever, red eyes and “discharge” from one eye, and a runny nose. The ER doctor described E.O. as “happy, playful, smiling and active.” The next day he was seen by his pediatrician and found to only have a tearing eye.

Nothing happened for the next two months, but in June of 2009, the child’s mother noticed he was not interacting and not moving his right side. She took him to the hospital, where he was diagnosed with a possible seizure. In follow up with a pediatric neurologist, she described E.O. as “alert, playful, interactive, very socially engaging,” and in a letter as having normal development.

Unfortunately, E.O. continued to have seizures, which increased in severity. He did not respond – or did not respond enough – to seizure-controlling medications. In June of 2010, E.O. underwent genetic testing and was found to have the SCN1A gene mutation (see more below).

On July 19, 2010, he was seen by a pediatric neurologist – Dr. James Wheless – again, and that was the point his developmental delays were noted. E. O. was diagnosed with:

Intractable, symptomatic childhood absence and complex partial seizures of independent hemisphere origin secondary to SCN1A gene defect (borderline SMEI syndrome),” and “encephalopathy characterized by speech delay.

As explained in the Special Master’s decision,

The SCN1A gene encodes for a sodium channel, which is “a portion of a channel that allows the transport of sodium molecules across cell membranes in the neurons.” Resp’s Ex. A at 6-7. The flow of sodium molecules permits appropriate transmission of information from one cell to another. Id. at 6. SCN1A gene mutations affect neuron cells in various ways, depending on the particular mutation, and how the mutation affects the structure and function of the sodium channel. Id. So far, several neurological conditions have been associated with the SCN1A gene mutation, including familial hemiplegic migraines, several epilepsy syndromes, Generalized Epilepsy with Febrile Seizures plus (“GEFS+”), and E.O.’s condition, Dravet syndrome. Id. at 5-7.

In other words, this is an important gene that gives instructions for creating a channel controlling the flow of sodium into cells, especially brain cells. Mutations in it can mean the protein necessary for the channel will be formed incorrectly, with negative effects.

Mutations in the SCN1A gene have been associated with a variety of seizure disorders, including Dravet Syndrome. The effect depends, in part, on where in the gene the mutation is, and what type of mutation it is.

The gene in question has over 6,000 base pairs which code for a relatively large protein – an average protein is around 1,000 base pairs. A mutation at the beginning of the gene sequence would make it a lot less likely that a viable, functional protein will be formed. A frameshift mutation dramatically changes the translation of the DNA code, and it can affect the next steps of it – such a mutation in the SCN1A gene increases the chances of Dravet mutation by eightfold.

As the Special Master in the Oliver vaccine injury case explained, Dravet Syndrome is a severe form of epilepsy in which a previously healthy infant develops recurrent seizures, generally resistant to drug treatment, in which by the second year of life usually includes “encephalopathy with cognitive, behavioral and developmental delays.” 70-80% of cases of Dravet syndrome are caused by SCN1A mutations.

E.O.’s parents petitioned NVICP for compensation, alleging that E.O.’s problems were the result of his six months vaccination.

In a lengthy decision that examined in detail the testimony and scientific evidence provided by both sides of the case, Chief Special Master Nora Beth Dorsey rejected the claim, finding that E.O.’s seizure disorder and epilepsy were caused by his genetic mutation.

The parents appealed the claim, first to the United States Court of Federal Claims where Judge Kaplan, in a 15-page decision, rejected the appeal, and then to the Federal Circuit Court of Appeals, where, in a 2-1 decision, a panel rejected the appeal, over a dissent by Judge Pauline Newman. The parents asked for a rehearing, and the Federal Circuit Court of Appeal voted and denied the request. Again, Judge Newman wrote a dissent from the denial. Her arguments in both dissents are similar, and in both cases, highly problematic.

Judge Newman’s arguments on the vaccine injury case

Judge Newman relied on two main contentions. First, she stated that developing science did not support a view that the SCN1A mutation by itself could lead to E.O.’s medical issues because the genetic aspect is only one part of Dravet’s etiology.

Second, she disagreed with the ruling in the lower court, which she characterized as denying compensation because “E.O. has a genetic mutation that might injure him at some time.” In the background of the decision appears to be her view that serious harms from vaccines are more common than the data shows.

Bad science on Dravet Syndrome and vaccines

Insofar as Judge Newman’s decision says that genetic issues may have environmental triggers, that’s uncontroversial. But if her argument is that problems cannot be solely genetic in origin, that’s simply incorrect. Similarly, if her argument is that genetics alone cannot lead to Dravet Syndrome, or that vaccines play a major role in its development, that does not fit the evidence.

Judge Newman reviews the early literature on Dravet. Then she mentions an important study by McIntosh. She describes the study in these terms:

The authors, reviewing the scientific literature, state that about 70–80% of children with Dravet syndrome have the SCN1A gene mutation, and about 20–30% do not have the mutation. Id. at 592. They report that about one-third of children with Dravet syndrome exhibited onset in less than 3 days after vaccination. The authors state that “[v]accination might trigger earlier onset of Dravet syndrome in children who, because of an SCN1A mutation, are destined to develop the disease.

But McIntosh was discussed in detail by the Special Master in Oliver. And the Special Master repeated what McIntosh actually concluded, which was that there was:

no difference between the two groups, vaccination-proximate and vaccination-distant’, with regard to ‘intellectual disability’ or ‘occurrence regression. …the results of the study show that children with Dravet syndrome experience regression and developmental delays regardless of whether they receive a vaccination.

Omitting the conclusion of the study and leaving in place just one carefully chosen quote is not a legitimate way to use a scientific study.

Similarly, discussing another study by Zamponi et al., Judge Newman describes the study as follows:

The authors are cautious about extrapolating vaccination recommendations from their results, although they state that “patients who experienced seizures close to vaccination had an earlier seizure onset and a higher frequency of status epilepticus during development.”

What Judge Newman omitted is the remainder of the sentence and the paragraph. Here is the full paragraph from Zamponi et al.:

We found that patients who experienced seizures close to vaccination had an earlier seizure onset and a higher frequency of status epilepticus during development, but no different clinical and cognitive evolution. Moreover, vaccination regimen completion did not determine a different cognitive evolution. From the present data, it seems that vaccination suspension might be associated with a higher risk of status epilepticus. However, this last result has to be considered with caution because of the small subgroup size (only 14 patients suspended vaccination).

In other words, not only did the article not find that vaccines led to more harm, it said the opposite in the very same paragraph Judge Newman quoted. This omission is highly problematic from a scientific evidence standpoint.

Judge Newman appeared to be strongly influenced by an article by Centica et al. that came out after the Special Master decision, an article she saw as changing the data. In that study, after studying 182 people, the authors found that age at first seizure and frameshift mutations were predictive of Dravet. Judge Newman quoted the study thus:

… that they “could not predict with high confidence Dravet syndrome vs milder phenotypes” and “outcome is not predetermined by genetic factors only.”

Judge Newman is partly right in that the study did suggest that age of first seizure matters. But she is incorrect in seeing the study as suggesting that genetic factors do not matter, that E.O.’s genetic factors did not, and is missing some of the limits of the study.

Here is the full sentence for the first quote:

Our estimation through ROC analysis of the value of different mutation types to predict the risk of developing Dravet syndrome sets the best cutoff grouping truncating mutations vs splicing and missense mutations but could not predict with high confidence Dravet syndrome vs milder phenotypes (sensitivity = 48.61%, specificity = 80.85%). Therefore, localization and type of SCN1A mutations are, on their own, less accurate predictors of outcome than assessment based on age at seizure onset. Combining mutational data with clinical parameters did not significantly improve the discrimination performance of the test.

In other words, it’s not that genetic factors did not matter. It’s that they had limited predictive value in this specific study, though the type of mutation was still relevant. Further, Judge Newman is ignoring the other part of the findings, under which “frameshift mutations and rearrangements confer a significantly higher risk of developing Dravet syndrome” –  in other words, certain types of mutations do come with a dramatically elevated risk of Dravet – and E.O., in this case, has a frameshift mutation.

Further, the causal connection may go the other way than where the authors end up. It may well be that children already predestined to have Dravet have earlier seizures.

Other research discussed in detail in the initial Oliver decision supports that. For example, the initial decision discussed animal research – pp. 20-22 in the initial decision – make the genetic contribution clear. The animal research shows that seizures will start irrespective of the presence or absence of external triggers.

The same data also shows that the seizures start within the first year in “rodent years”, and why the seizures do not start at birth – at birth, a different gene codes the sodium channel, one that was in place during fetal development. That channel is replaced by SCN1A subunit protein in the first 6 months of life. Dravet syndrome becomes clinically evident only after the SCN1A subunit protein is needed by cells to regulate sodium.

It is also not clear whether preventing seizure in the first year of life is at all possible, given the many potential triggers, or would have a real effect on cognitive impairment.

For all these reasons, this paper is not a good counter to studies directly looking at vaccines and clinical outcomes. It raises an interesting question about age and seizures, but it does not change the data directly on vaccines and Dravet.

Finally, assuming that vaccines are the main source of fever in the first year, or that not vaccinating will decrease the chances of fever, is unsupported.

For all these reasons, using Cetica et al. to argue that vaccines cause Dravet is unconvincing. Using it to argue that E.O.’s problems are vaccine-related rather than Dravet-related is even less convincing because E.O. does fall into the other category of risk mentioned by Cetica et al. – frameshift mutations.

Judge Newman Mischaracterizes the Decision in E.O.’s case

The Special Master decision in E.O.’s case did not assume that an SCN1A would automatically predestine him to seizures and developmental delays (though it did draw heavily on the science to link the mutation and Dravet). The decision, in 36 pages, focused on E.O.’s specific situation as well as on the science.

Among the factors that led the Special Master to reject the claim of compensation was the development of the problem – E.O. had a transitory seizure at six months, after his vaccinations, but appeared to have recovered with little issue, along with no additional seizers for the subsequent two months. There were no vaccines associated with his subsequent seizures, and his encephalopathy was not diagnosed until 21 months. The Special Master concluded that this pattern fits better into the typical development of the genetic-based Dravet syndrome than to harm caused by “a brief seizure following immunization.”

Further, much of the decision addressed E.O.’s specific mutation. E.O. had a splice site mutation with deletion of four base pairs: a frameshift mutation. It is in the 264th nucleotide of a 6,000 base pair gene – almost at the beginning, which is the most problematic. And because it’s a frameshift mutation everything after it would not be functional – the abnormal gene, with such a deep change at an early stage, will not manufacture a viable protein in the cell

However, the decision did not say “any SCN1A gene automatically means the child is predestined to have Dravet Syndrome.” But it said that a child with this specific mutation, which means the gene cannot make the protein, will have Dravet. In fact, looking at the data, another child with an identical mutation was found, and that child, too, had Dravet syndrome.

In other words, this child’s specific genetic situation made the development of Dravet syndrome certain. It is certainly a hard situation for the family, and in an ideal world, they should receive support for the child’s needs. But it is a genetic problem – and not an inherited one, generally called a de novo mutation. It’s not anyone’s fault, and it is not vaccine-related.

Moreover, the Special Master did not automatically assume any SCN1A mutation predestined a child to Dravet – the case looked closely at E.O.’s specific mutation, specific pattern, and found that for him, the evidence did not support a link between his problems and vaccines, but it did support a link between E.O.’s specific genetic mutation and Dravet.

Other issues in the decision

There are other problematic statements in the decision. For example, Judge Newman claimed that Congress found that “about one half of one percent of children each year experience vaccine-related injury; and with four million births each year in the United States, this is about 20,000 vaccine injuries per year,” referencing this report.

I’m not quite sure where Judge Newman found that number. I have searched the report in multiple ways and have not found it. P. 21, referenced by her, has a table of reported events, but there is nothing close to 0.5% of all children who experience long-term or serious harm there.

vaccine injury case

There are certainly not 20,000 children per year seriously harmed by vaccines today. In fact, serious harms from vaccines are extremely rare.

And while Judge Newman is certainly correct that there are those working on identifying genetic factors that may make children more vulnerable to vaccine harms, and also correct in saying that in some cases there is an interaction between genes and environment, those points do not change the evidence related to Dravet syndrome, genetics and vaccines specifically, or E.O.’s case (even more specifically).

Similarly, when Judge Newman says that “E.O’s vaccine injury is typical of the vaccine injury that necessitated the Vaccine Act” she is right as a historical matter – concerns about encephalopathy following DTP, the precursor of DTaP, were a main driver in leading to the act, the evidence is that these initial concerns were unfounded, and DTaP has never been convincingly linked to such issues. If Judge Newman argues that the program should continue compensating for things disproven, I disagree.

Conclusion

Judge Newman’s opinion on the Oliver vaccine injury case mischaracterizes the science on Dravet and vaccines, incorrectly described the decision in E.O.’s case and makes other errors. It has no legal authority, being a dissent from an appeal and a dissent from refusal to rehear the case. It should also have no persuasive authority because it is ill-reasoned and ill-founded.

Notes

This article is by Dorit Rubinstein Reiss, Professor of Law at the University of California Hastings College of the Law (San Francisco, CA), who is a frequent contributor to this and many other blogs, providing in-depth, and intellectually stimulating, articles about vaccines, medical issues, social policy, and the law. 

Professor Reiss writes extensively in law journals about the social and legal policies of vaccination. Additionally, Reiss is also a member of the Parent Advisory Board of Voices for Vaccines, a parent-led organization that supports and advocates for on-time vaccination and the reduction of vaccine-preventable disease.

Below are pdf files for each of the key documents in this case and its appeals:

 

Dorit Rubinstein Reiss
This article is by Dorit Rubinstein Reiss, Professor of Law at the University of California Hastings College of the Law (San Francisco, CA), is a frequent contributor to this and many other blogs, providing in-depth, and intellectually stimulating, articles about vaccines, medical issues, social policy and the law. 

Professor Reiss writes extensively in law journals about the social and legal policies of vaccination. Additionally, Reiss is also member of the Parent Advisory Board of Voices for Vaccines, a parent-led organization that supports and advocates for on-time vaccination and the reduction of vaccine-preventable disease.