CHRISTIAN J. MORAN, Special Master.
This case presents a tragic story. When Nicholas Copenhaver was four months and, by all accounts, healthy, he was seen by his pediatrician. The pediatrician administered a set of vaccinations. In the early morning hours three days later, Nicholas died. After an autopsy discovered no other reason for Nicholas's death, the medical examiner classified it as a case of sudden infant death syndrome ("SIDS").
Nicholas's parents, Dillon and Amanda Copenhaver, are the petitioners. They claim that the vaccinations that he received within 72 hours of his death caused his demise. The Copenhavers seek compensation through the National Childhood Vaccine Injury Compensation Program, codified at 42 U.S.C. § 300aa-10 through 34 (2012).
To support their claim, the Copenhavers rely upon the opinions presented by Doctors Douglas Miller, a neuropathologist, and David Axelrod, an immunologist. Dr. Miller and Dr. Axelrod opine that the vaccinations prompted the production of cytokines and that these vaccine-induced cytokines prevented Nicholas from rousing himself during an episode of respiratory distress.
In opposition, the Secretary also presented testimony from two experts: Doctors Brent Harris, a neuropathologist, and Christine McCusker, a pediatric immunologist. Dr. Harris and Dr. McCusker stated that it is less likely than not that the vaccinations stimulated the production of cytokines that interfered with Nicholas's brain function, causing him to die.
These four doctors testified at a hearing held on July 30-31, 2015. Other witnesses were Ms. Copenhaver and the person caring for Nicholas the night he died, Janice Schoneboom. Following the hearing, each party submitted one brief.
The case is ready for adjudication. For the reasons discussed at length below, the Copenhavers have not presented a persuasive case. The simplest explanation is that Dr. McCusker, one of the Secretary's experts, possesses greater training and experience to discuss the critical issues. Therefore, Dr. McCusker's opinion — that vaccines, given in the periphery, are unlikely to stimulate the production of cytokines that interfere with the brain's function — is given a greater amount of weight than the contrary opinions.
Everything below expands upon the above summary. To facilitate this expansion, the discussion is divided into four sections: background, standards for adjudication, analysis, and conclusion.
To appreciate the analysis below, it is necessary to have background on SIDS, the facts of the case, and the petitioners' theory of how vaccination caused Nicholas's death.
The age of four months is when the American Academy of Pediatrics recommends that babies receive a set of vaccinations. The age of four months is also a peak time period in which currently healthy babies are found dead after being asleep. When that death remains unexplained after a thorough clinical analysis, autopsy, and investigation of the death scene, doctors classify the death as one of sudden infant death syndrome. Exhibit 29 (Hannah C. Kinney et al.,
In the United States in 2001, the incidence of SIDS was 0.8 per 1000 live births. Exhibit 29 (Kinney) at 228;
Given these devastating deaths, researchers have been attempting to determine why SIDS happens. In 1994, James J. Filiano and Hannah C. Kinney co-authored an article that proposed that three separate factors coincide in cases of SIDS. Exhibit 28 (James J. Filiano and Hannah C. Kinney,
The vulnerable period for development of homeostatic control usually begins at approximately two months and continues until approximately six months. In this time, "major changes occur in virtually all physiologic systems as infants attain adaptive mechanisms enabling them to maintain homeostasis. These changes include dramatic transitions in homeostatic systems regulated by the brain notably autonomic control, ventilation, sleep-waking state organization, temperature regulation, and circadian rhythms." Id. at 195-96.
For the intrinsic defect, Dr. Kinney and other researchers have focused on a part of the brain that controls respiration known as the medulla oblongata. Tr. 125;
The third factor in the triple-risk model is an extrinsic stressor. Tr. 126-28 (Dr. Miller), 356-57 (Dr. McCusker). In Dr. Filiano's and Dr. Kinney's 1994 article, they proposed that prone sleeping could contribute to SIDS deaths. Relying upon epidemiological studies, they also identified minor respiratory or gastrointestinal illnesses, fever, and over-blanketing as other external stressors. Exhibit 28 at 196. The ensuing "Back-to-Sleep" campaign, which encouraged parents to place their babies to sleep in the supine, or face up, position, reduced the incidence of SIDS by approximately 50 percent. Tr. 127-28;
Dr. Kinney's articles have not included vaccinations among external stressors that could precipitate a SIDS death. Tr. 160-61 (Dr. Miller), 427-28 (Dr. McCusker). The Secretary's expert, Dr. McCusker, interprets Dr. Kinney's work as focusing on impediments in the mechanical aspects of breathing. Tr. 380-81. According to Dr. Miller, Dr. Kinney has told him that she is consciously staying away from the issue of whether vaccines cause SIDS. Tr. 189.
However, other researchers have explored a possible connection between vaccination and SIDS using large databases.
The Vennemann group's suggestion that vaccinations may decrease the incidence of SIDS is consistent with a finding the Institute of Medicine made in 1991. The IOM stated that "All controlled studies that have compared immunized versus nonimmunized children have found either no association or a decreased risk of SIDS among immunized children." Exhibit 48 (Institute of Medicine,
Thus, no articles reliably demonstrate that vaccines increase the risk of SIDS.
With respect to Nicholas's medical history, the parties have relatively little, if anything, in dispute. The medical records and testimony showed the following:
On July 12, 2013, Nicholas went to his pediatrician for a four-month well baby appointment. Nicholas appeared to be healthy. He received a second round of vaccinations, including Pentacel, Prevnar 13, and Rotateq. Exhibit 5 at 24, 30.
According to his mother, prior to his second set of vaccinations, Nicholas was a very active baby who liked to smile. Tr. 20. In contrast, after the July 12, 2013 vaccinations, Nicholas was unsettled, restless, fussy, and lethargic. Tr. 23; exhibit 1 at ¶ 5. Two to three hours after vaccination, Nicholas vomited extensively. Tr. 22-23, 34-35;
In the evening of Sunday, July 14, 2013, the Copenhavers dropped Nicholas off with Ms. Schoneboom. Tr. 26-27. At approximately 1:00 AM, Nicholas awoke and was unhappy. To help him fall back to sleep, Ms. Schoneboom swaddled him in a blanket and held him up on her shoulder as she sat on a sofa watching television. Tr. 42-44.
At approximately 4:00 AM, Ms. Schoneboom woke up and discovered that Nicholas was not breathing. Resuscitation was attempted and 911 was called. Sadly, efforts to revive Nicholas were unsuccessful. Exhibit 10 at 1-5; exhibit 11 at 1; Tr. 48.
On August 13, 2013, Karl Christopher Stacy conducted a general autopsy on Nicholas. Exhibit 2 at 1-6; Tr. 79.
Dr. Miller's neuropathologic examination was also significant for what was not found. Dr. Miller stated that a brain abnormality commonly found in SIDS cases, a defect in the arcuate nuclei, was not present. Exhibit 2 at 11;
At the hearing, Dr. Miller testified that when he performed the neuropathology work on Nicholas he did not know that Nicholas had been vaccinated within three days of his death. Tr. 81-82. In the absence of information about Nicholas's recent vaccination, Dr. Miller's August 2013 neuropathology report proposed that Nicholas may have had a seizure. Exhibit 2 at 11. In this litigation, Dr. Miller has changed his position. He now states that the vaccinations contributed to Nicholas's death.
With support from their experts, Dr. Axelrod and Dr. Miller, the Copenhavers present a theory that builds upon the triple risk model. To restate, the triple risk model proposes that SIDS episodes can occur (1) during a vulnerable time, (2) in a vulnerable infant, such as one with an intrinsic neurological defect, and (3) after the introduction of an extrinsic stressor.
The Copenhavers most clearly express their theory on page 10 of their posthearing brief. There they state: "Vaccination acts as the exact same mechanism of injury as infection does in serving as an extrinsic risk factor through cytokine expression." Pet'rs' Posth'g Br., filed Oct. 1, 2015, at 10. Cytokines are biological molecules that signal other cells to do things. Cytokines were first identified as components of the innate immune system, and can be either pro-inflammatory or anti-inflammatory, depending on the type of cytokine. Tr. 88. They add more detail to their theory when they elaborate: "During infection, peripherally produced cytokines can cross the blood-brain barrier, bind to endogenous cycle receptors on neuronal populations that mediate stress responses in the hypothalamus and/or brainstem, and thereby determine sickness behavior, including blunted arousal and depressed respiration." Pet'rs' Posth'g Br. at 10.
The Secretary's recitation of the Copenhavers' theory is slightly different. Quoting Dr. Miller's initial report, the Secretary summarizes the theory as the vaccinations "`induced cytokine production, and those cytokines then acted in the brainstem which was already deficient in serotoninergic drive for respiratory effort, leading to an apneic episode from which he did not recover, i.e. SIDS.'" Resp't's Posth'g Br., filed Nov. 3, 2015, at 2, quoting exhibit 13 at 10.
Although petitioners could have presented their theory more clearly, it appears that they are not maintaining that the vaccine-induced cytokines caused an "apneic episode."
Because cytokine-induced apnea appears not to be part of the Copenhavers' theory, the undersigned is not entirely certain as to how their theory proceeds. After reviewing all the expert reports, the medical literature associated with the reports, the pretrial briefs, the testimony, and the posttrial briefs, the undersigned has determined that the Copenhavers are contending that (1) vaccinations induce the production of cytokines just as infections induce cytokines, (2) the cytokines travel through the blood stream and cross the blood-brain barrier to reach the part of the brain responsible for auto-resuscitation, (3) for some unknown reason, Nicholas stopped breathing, and (4) Nicholas's brain could not initiate the normal autoresuscitation process because cytokines, which were induced by the vaccination, impaired the brain's functioning. See Tr. 148 (Dr. Miller: "the cytokine IL-1 beta has an inhibitory effect on the 5-HT network . . . and in a situation where there's apnea during sleep, then there will be a failure to recover from it"); Tr. 301 (Dr. Axelrod: "he had the vaccination, the cytokine levels increased, just as they do with infection; . . . they had a reason to cross the blood-brain barrier and to be elevated in the cerebrospinal fluid, just as they were in the Rognum study; and the rest is, . . . as described by Dr. Miller"); Tr. 471-72. With respect to step 3 — for some unknown reason, Nicholas stopped breathing — the undersigned emphasizes that the Copenhavers are not arguing that the vaccinations caused an apneic episode. With this clarification, the undersigned will assess the persuasiveness of this theory and its applicability to Nicholas's case in the sections below.
In the analysis section below, evidence in this case will be analyzed according to the following standards of adjudication.
A petitioner is required to establish her case by a preponderance of the evidence. 42 U.S.C. § 300aa-13(1)(a). The preponderance of the evidence standard requires a "trier of fact to believe that the existence of a fact is more probable than its nonexistence before [he] may find in favor of the party who has the burden to persuade the judge of the fact's existence."
Distinguishing between "preponderant evidence" and "medical certainty" is important because a special master should not impose an evidentiary burden that is too high.
Special Masters are fact finders that use their accumulated expertise to judge the individual merits of claims. See Hodges, 9 F.3d at 961;
The elements of the Copenhavers' case are set forth in the often cited passage from the Federal Circuit's decision in
The analysis below applies the above standards of adjudication. It focuses first on overall weaknesses in the petitioners' case, and then moves on to discuss petitioners' case within the Althen framework.
After considering all the evidence, the undersigned finds that the petitioners have failed to meet their burden of presenting a persuasive case that the vaccinations contributed to Nicholas's unfortunate death. Three reasons support this overall conclusion. First, the Secretary's expert, Dr. McCusker, was much better qualified to discuss cytokines. Second, the articles do not support the opinions Dr. Miller and Dr. Axelrod expressed. Third, there are gaps in the medical record for Nicholas that Dr. Miller fills with assumptions. Of these three reasons, the most significant are the first and second.
In considering the value of opinion testimony, special masters may consider the offeror's expertise.
The greatest weakness in the Copenhavers' case was the disparity in the credentials among the expert witnesses (Dr. Axelrod, Dr. Miller, and Dr. McCusker) in immunology.
The Copenhavers argue that testimony about the causes of SIDS should be reserved for neuropathologists who have performed autopsies in SIDS cases. Pet'rs' Posth'g Br. at 19. In their view, their theory "sound[s] in neuropathology, not immunology."
The Secretary answers that Dr. McCusker was qualified to address immunologic topics, such as whether the response to vaccination is the same as the response to infection. The Secretary adds that if anyone testified outside his or her area of specialty, it was Dr. Miller. Resp't's Posth'g Br. at 5-6.
The Secretary's argument is well-founded. The Copenhavers have proposed a theory in which vaccinations lead to the production of cytokines and the cytokines impair the brain's function. The Copenhavers essentially concede this point when they acknowledge that "part of [their] causation theory in this matter deals with cytokine expression following vaccination." Pet'rs' Posth'g Br. at 20. There is no doubt that questions about cytokines (What type? How many are produced? Are they present in the brain? Do cytokines cause damage or do cytokines respond to damage?) dominated the hearing. The Copenhavers' attempt to minimize the significance of immunology is not persuasive.
In terms of the medical education that he received, Dr. Axelrod is roughly comparable to Dr. McCusker, discussed below. After graduating medical school, Dr. Axelrod was a resident for three and a half years. Tr. 281. He completed two fellowships, the first at McGill University in the Department of Clinical Immunology, and the second at the United States National Institutes of Health from 1980-82. Tr. 281; exhibit 16 (curriculum vitae) at 1.
At the beginning of Dr. Axelrod's medical career (1979), he received board certification in internal medicine and, three years later, received additional certification in rheumatology. In 1988, he became board certified in medical laboratory immunology. In 2011, he received his most recent board certification, which is in allergy and immunology. Exhibit 16 at 3; Tr. 282, 303.
For teaching, Dr. Axelrod was an associate professor in the division of rheumatology at the Medical College of Ohio from 1989-91. Exhibit 16 at 2; Tr. 283.
For research, Dr. Axelrod's curriculum vitae lists 12 articles that appeared in peer-reviewed journals. From their titles, none seem to involve cytokines.
Since 2012, Dr. Axelrod has been working as a private practitioner in York, Pennsylvania. His patient population is "mostly older." Most have allergies, including some adverse reactions to drugs. Tr. 315. In the course of his employment, he reads journals that publish articles about cytokines. Tr. 316.
The Secretary did not object to Dr. Axelrod's expertise in the field of immunology. Tr. 286. However, the Secretary attempted to impeach his trustworthiness by eliciting testimony on cross-examination that he advertised his services as an expert witness in the Vaccine Program on the internet. Tr. 302-03. He also wrote letters to attorneys whose names appear on a list maintained by the Court of Federal Claims Clerk's Office. Most of his participation in the Vaccine Program derived from his letters, rather than the website. Tr. 317. Dr. Axelrod stated that he also communicated with the government but the government has not retained him. Tr. 302.
Dr. Axelrod's advertising of his services as an expert witness raises some concern. An advertisement could be construed as a willingness to provide an opinion that is helpful to the retaining party for the correct fee. However, after observing Dr. Axelrod's demeanor, the undersigned did not find that Dr. Axelrod was offering opinions simply to be paid. In other words, Dr. Axelrod appeared to be providing opinions that he held sincerely.
Although sincerity was not a problem with Dr. Axelrod, his lack of expertise in cytokines was. Dr. Axelrod was retained to opine about "cytokine production with vaccination." Tr. 287. Yet, on direct examination, his answers to questions were relatively short because the Copenhavers' attorney was asking leading (or narrow) questions. Consequently, Dr. Axelrod did not explain critical articles on immunology very well. The lack of persuasive testimony from Dr. Axelrod is most evident with respect to an article the Copenhavers were using to support their argument that the cytokine response to vaccination is similar to the cytokine response after infection.
The undersigned concurs that the field of cytokines was outside the bounds of Dr. Axelrod's expertise. As previously noted, his knowledge about cytokines appears to stem largely, if not entirely, from reading journal articles. He has not published any articles on cytokines or conducted research on them. This relative lack of expertise diminishes the value of Dr. Axelrod's opinions.
Consequently, for all these reasons, the undersigned gives Dr. Axelrod's testimony about cytokines relatively little weight. This finding means that the Copenhavers' remaining expert witness, Dr. Miller, must be considered.
Preliminarily, it is important to emphasize that this portion of the decision is weighing the experts' qualifications to discuss immunology.
The basic definition of neuropathology is "the branch of medicine dealing with morphological and other aspects of disease of the nervous system."
The Copenhavers have not presented an easily understood basis for finding that Dr. Miller's expertise in neuropathology gives him a basis for explaining immunology. Dr. Miller is familiar with SIDS as he has conducted the neuropathological aspects of an autopsy in approximately 100 cases. Tr. 188. This experience provides him a basis for identifying structural defects in the arcuate nucleus. However, to identify cytokines as affecting any structural defect is another step. Dr. Miller may have training and experience to take this step, but the Copenhavers have not made this aspect of his background readily apparent.
On cross-examination, Dr. Miller stated that he is not board certified in immunology and he does not hold himself to be an expert in immunology. Tr. 154. Among his numerous publications, he has written one article involving cytokines. It was written in the late 1980's or early 1990's. Tr. 187.
Regardless of whether the topic was neuropathology or immunology, Dr. Miller testified without any objection from the Secretary. In other words, his lack of experience in immunology did not preclude the admissibility of his testimony. The question is about the weight to be given to his testimony.
To be clear, as shown in sections 1.B, 1.C, and 2, below, the undersigned is considering all the testimony and weighing the value of that testimony.
Dr. McCusker possesses an excellent background in immunology. Before attending medical school, she earned a master's degree in molecular virology and completed three years of study in a Ph.D. program for immunology. Tr. 330. After medical school, she did a residency in pediatrics and then a post-doctoral fellowship in allergy and immunology.
She holds the Canadian equivalents of board certification in the field of pediatrics as well as the field of allergy and immunology. Tr. 331. As a clinician, she works at the McGill University Health Center, Montreal Children's Hospital, where she sees patients with problems in their immune system and with allergies. Tr. 333.
Dr. McCusker works at McGill University as an associate professor in the division of allergy and immunology within the department of pediatrics. Tr. 331; exhibit D (curriculum vitae) at 3. She teaches all the first year medical school students immunology and other topics. Tr. 333. She also teaches undergraduate students basic immunology and graduate students advanced immunology. Tr. 334. Her experience in teaching probably contributed to her ability to explain complicated topics and scholarly articles in a way that made them understandable.
Dr. McCusker conducts research in immunology. She operates her own laboratory, focused on developmental immunology. Tr. 331. Her curriculum vitae lists more than 30 articles published in peer-reviewed journals. Exhibit D at 21-25. Of these, approximately 15 publications involved cytokines. Tr. 335.
The Copenhavers did not object to Dr. McCusker's being recognized in the field of pediatrics and pediatric immunology, although the Copenhavers maintained that she could not testify in the field of neuropathology. Tr. 335. Although they did not challenge her credentials or experience, the Copenhavers attempted to portray Dr. McCusker as being biased in favor of companies that manufacture pharmaceuticals including vaccines.
The undersigned did not perceive any bias from Dr. McCusker. She remained a superb witness. As the Secretary noted, many special masters have praised Dr. McCusker's testimony. Resp't's Posth'g Br. at 5 n.3 (citing
Dr. McCusker's testimony was largely, but not exclusively, about immunology generally, and cytokines specifically.
The strongest endorsement about Dr. McCusker's abilities came in the rebuttal phase of the case. During Dr. McCusker's testimony, the Copenhavers objected to portions of her testimony as being outside her area of expertise. The undersigned allowed her testimony and stated that "either Dr. Axelrod or Dr. Miller [can] explain why [Dr. McCusker's testimony] is wrong." Tr. 360. In rebuttal, the undersigned asked Dr. Axelrod whether any portion of Dr. McCusker's testimony was erroneous, and Dr. Axelrod replied: "I think I agree with most of what she had to say." Tr. 451. That endorsement is telling.
Along with the disparity in the experts' qualifications, the other major reason for finding the Copenhavers' claim unpersuasive is that the medical articles are more consistent with the Secretary's description of them.
According to binding precedent, petitioners may establish that they are entitled to compensation without presenting any medical literature.
The Copenhavers' claim seems inconsistent with the submitted articles in two respects.
Dr. Kinney proposes that during a vulnerable time, children with a defect in their brain who encounter an external stressor may suffer a SIDS death. To date, the list of external stressors includes prone sleeping, co-sleeping, and infections. Exhibit 28 (Filiano and Kinney) at 196; exhibit J (Kinney and Thach) at 4, 7.
Through Dr. Miller and Dr. Axelrod, the Copenhavers extend the list of external stressors to include vaccinations. As mentioned earlier, none of Dr. Kinney's articles have included vaccinations.
As Dr. McCusker discussed extensively, almost all the external stressors in Dr. Kinney's work are factors that impair the mechanics of breathing. Tr. 380-81, 384-87. From her experience as a pediatrician working in an emergency room, Dr. McCusker knows how infants breathe. Tr. 431-32.
An impairment in breathing serves as the immediate trigger that leads to SIDS in the triple risk model. One example of a cause for problems in respiration is an upper respiratory infection. The upper respiratory infection interferes with the infant's breathing and, during a critical age when the infant's brain is developing, the brain lacks the ability to arouse the infant. This sequence is easily understood.
The Copenhavers' theory alters the triple risk model.
The Copenhavers are not persuasive because, at the most basic level, they have not presented any evidence that cytokines trigger problems in breathing. Infections, co-sleeping, and prone sleeping can all interfere with how the respiratory system functions. There is very little evidence, and certainly no persuasive evidence, that cytokines obstruct ventilation.
The Secretary distinguished the mechanical aspects of respiration from the neurochemical effects of vaccination. Resp't's Posth'g Br. at 3-4. It would have been helpful for the Copenhavers to have answered this argument in a reply brief. However, the Copenhavers did not file a reply, leaving the Secretary's argument unaddressed. Dr. Kinney's triple risk model sensibly includes as extrinsic risks factors that impair breathing. Dr. Axelrod's and Dr. Miller's attempt to expand the group of extrinsic risk factors to something (vaccination) that does not impair breathing is not sensible.
The Copenhavers' unpersuasive attempt to extend the extrinsic risk factor from Dr. Kinney's triple risk model stems from a difference in opinion about the factors that influence an infant's respiration. As a board-certified pediatrician, Dr. McCusker was much more qualified to explain how infants breathe and what can interfere with respiration than the Copenhavers' experts, who lacked similar expertise in pediatrics. The next topic also is based upon a field in which Dr. McCusker possesses excellent qualifications ___ immunology.
The second significant problem in the Copenhavers' case is that they propose that cytokines damage the brain, reducing its ability to respond to stoppages in breathing. This assertion is based upon an incomplete and outdated understanding of cytokines, one that Dr. McCusker effectively refuted.
Before exploring the shortcomings in the Copenhavers' case regarding the damage that cytokines might cause, the undersigned will first discuss one idea that the Copenhavers did establish persuasively. The Copenhavers showed that the immune system can produce roughly the same quantity of a cytokine known as IL-6 in response to the influenza vaccination as it produces in response to an influenza infection.
The body's encounter with an outside substance, known as an antigen, leads to a response from the immune system.
For the general proposition that vaccines and infections prompt a comparable amount of cytokines to be produced, Dr. Miller and Dr. Axelrod rely upon the Kashiwagi article. Tr. 135-36, 172, 204, 291, 304. The Kashiwagi researchers, in part, determined "whether cytokines were produced in the serum after immunization," including IL-1β, IL-6, and TNF-α. Exhibit 17 at 680. In the portion of the experiment on which Dr. Miller and Dr. Axelrod rely, the Kashiwagi researchers presented the cytokine measurements, in picograms/milliliter (pg/mL), of four groups of people: (1) those immunized without a febrile reaction, (2) those immunized with a febrile reaction, (3) those infected with 2009 H1N1 pandemic influenza who were outpatients, and (4) those infected with 2009 H1N1 pandemic influenza who were admitted patients.
In consolidated chart form, the data appear as follows:
The Kashiwagi researchers stated "no significant difference was observed in the IL-6 and TNF-03b1 levels between the influenza outpatients and immunization groups with febrile or non-febrile illness after vaccination."
That specific proposition, however, cannot be generalized to establish that the vaccines in this case resulted in production of a comparable amount of a different cytokine (IL-103b2) as would have resulted from an infection.
At this more sophisticated level of analysis, information about how individual cytokines act becomes critical, and Dr. McCusker's superior background in immunology showed through.
In the triple risk model, a SIDS victim can have an inherent defect in some part of his brain, and oftentimes this defect is in the arcuate nucleus.
Years ago, some research provided support for this idea. Dr. Kinney and other researchers discovered the presence of certain cytokines in the brains of infants who died from SIDS. See exhibit 38 (Hazim Kadhim et al.,
However, more recent research contradicts that hypothesis. Some cytokines occur in the brain normally.
The cytokines may be present in the brain because they are responding to an injury, that is, the cytokines are beneficial, not harmful. Dr. Kinney and colleagues asserted in 2009 that elevated levels of IL-6 "may reflect a compensatory mechanism whereby defective arcuate 5-HT neurons require excessive cytokine stimulation to respond to infection-induced hypercapnia." Exhibit 32 (Hannah C. Kinney et al.,
Dr. McCusker concisely explained how Dr. Kinney was using IL-6. She stated that IL-6 was a message, like words being spoken into a telephone. The telephone in this analogy is the part of the brain that normally receives the cytokine signals, for example the arcuate nucleus. With SIDS, the arcuate nucleus does not work. To continue Dr. McCusker's analogy, the telephone is unplugged and therefore cannot receive the message the IL-6 is trying to transmit. Tr. 442;
At the hearing, the undersigned was impressed with Dr. McCusker's interpretation of the 2009 Kinney article. Thus, the undersigned specifically inquired about the Kinney article in Dr. Axelrod and Dr. Miller's rebuttal testimony. When asked about whether IL-6 was compensatory, Dr. Axelrod stated that he did not have the expertise to answer any questions. Tr. 454. Dr. Miller stated: "I don't disagree that it's [IL-6 is] not causative." Tr. 471. Thus, the rebuttal testimony essentially leaves Dr. McCusker's opinion that IL-6 responds to damage, rather than causes the damage, unrebutted.
The foregoing reasons explain why the Copenhavers have failed to present a persuasive case that vaccinations can cause SIDS. Even if they had succeeded, they would still be required to establish that Nicholas responded to the vaccinations in a way their theory predicted.
With respect to Nicholas, the Copenhavers' case contains two assumptions that make crediting their case difficult. The first assumption concerns his brain, and the second assumption concerns his cytokine levels.
One of the factors in Dr. Kinney's triple risk hypothesis is that infants are vulnerable to SIDS when they have an intrinsic defect in their brains. Dr. Kinney's group has focused attention on the arcuate nucleus, which is located in the medulla portion of the brain stem.
As part of the autopsy for Nicholas, Dr. Miller analyzed Nicholas's brain. He obtained tissue samples that he looked at under a microscope. Tr. 189-93. Dr. Miller's neuropathological report states: "Examination of the medulla reveals a robust arcuate nucleus." Exhibit 2 at 11;
In this litigation, Dr. Miller assumes that Nicholas had some defect in his brain. This assumption is based upon two factors. First, Dr. Kinney has identified defects in the arcuate nucleus in approximately 70 percent of SIDS cases when she used advanced receptor autoradiography techniques. Dr. Miller did not use any advanced technique in Nicholas's case. Thus, this leaves open the possibility that more sophisticated screening would have found a defect that Dr. Miller's routine work did not. Tr. 168-69. Second, during the neuropathologic portion of the autopsy, Dr. Miller identified a problem in Nicholas' cerebellum. Exhibit 2 at 10. From this finding, Dr. Miller reasoned that Nicholas probably suffered some injury in utero and this injury could have produced other lesions that have not been identified. Tr. 167.
Dr. Harris was not willing to assume that Nicholas suffered from an unfound defect in his brain. In his view, Nicholas's case should not be classified as SIDS (meaning sudden infant death syndrome), but rather sudden unexpected death syndrome. Tr. 241, 269. Dr. Harris could not offer any explanation for why Nicholas died. Tr. 263.
Overall, Dr. Miller's determination that Nicholas's medulla was robust (exhibit 2 at 11) is a matter of some concern. The lack of an abnormality appears to have led Dr. Miller to think that Nicholas did not die from SIDS. Exhibit 2 at 11. Dr. Miller's colleague, Dr. Stacy, described Nicholas as suffering from "sudden unexpected death[,]" which is similar to the wording Dr. Harris proposed.
A second aspect of the Copenhavers' theory is that cytokines degraded the function of Nicholas's brain. Pet'rs' Posth'g Br. at 10. When asked whether Nicholas produced any cytokines, Dr. Miller stated that he did not know because routine autopsies do not include an investigation for cytokines. Tr. 90.
Dr. Miller predicted that if a test were done, it is "plausible" that IL-6 would be found in Nicholas's brain. Tr. 178-79. Dr. Miller and Dr. Harris agreed that a type of immunohistochemical testing described in the Rognum article could still be performed on the tissues from Nicholas's testing. Tr. 193-94, 268-69.
Overall, the lack of evidence showing that Nicholas actually responded in a way that Dr. Miller and Dr. Axelrod predicted is an obstacle to awarding the Copenhavers compensation.
To restate, the undersigned finds that the Copenhavers failed to carry their burden of presenting a persuasive case for three reasons. First, Dr. McCusker's superior experience in immunology make her opinions about immunology more reliable than the opinions from either Dr. Axelrod or Dr. Miller on immunology. Second, the literature does not support the opinions Dr. Axelrod and Dr. Miller presented. Third, the Copenhavers filled gaps in knowledge about Nicholas with assumptions. These reasons underlie an analysis of the
The required elements for the Copenhavers' case set forth in
The first prong from Althen requires the petitioners to establish "a medical theory causally connecting the vaccination and the injury."
Largely for the reasons explained in section 1A and 1B, above, the Copenhavers have failed to present a persuasive theory. To Dr. Kinney's triple risk model, the Copenhavers have added vaccination to the list of extrinsic risk factors. However, vaccinations are unlike the other extrinsic risk factors because the ones Dr. Kinney proposes interfere with breathing. The Copenhavers have failed to persuade the undersigned that vaccinations are the equivalent of upper respiratory infections.
In finding that the Copenhavers have failed to meet their burden of proof, the undersigned has considered the testimony of Dr. Harris that the Copenhavers cited twice in their brief. The Copenhavers argue that Dr. Harris admitted the reliability of their theory. Pet'rs' Posth'g Br. at 11, 15-16. The relevant portion of Dr. Harris's testimony on cross-examination is:
Tr. 262 (emphasis added).
This portion of Dr. Harris's testimony and the persuasiveness of the Copenhavers' argument about it turn on the meaning of "consider." In a dictionary, "consider" has different meanings. Definitions include:
However, Dr. Harris's demeanor while testifying suggested that he was using "consider" in its first sense, meaning that he would contemplate whether vaccines could serve as an extrinsic risk factor. The idea that Dr. Harris would reflect carefully and seriously is consistent with the Copenhavers' attorney's use of the word "possible" in the preamble to the question. Moreover, in another place in his testimony, Dr. Harris unambiguously discounted the vaccinations as contributing to Nicholas's death. Tr. 225.
In any event, even if Dr. Harris's statement served as an admission on his part, the Copenhavers would still be required to grapple with Dr. McCusker's opinion. Dr. McCusker persuasively refuted the assertion that IL-6 cytokines are likely to damage the medulla. Dr. McCusker explained that IL-6 cytokines are more likely part of the restorative process. This finding removes another aspect of the Copenhavers' theory, making their theory unpersuasive.
The second prong of Althen requires "a logical sequence of cause and effect showing that the vaccination was the reason for the injury."
Here, as a matter of logic, because the Copenhavers have not presented a persuasive basis for finding that vaccinations can cause SIDS, they have also not presented any persuasive basis for finding that the vaccinations caused Nicholas to die from SIDS.
In connection with prong 2, the Federal Circuit has instructed special masters to consider carefully the views of treating doctors.
When the treating doctors do not know about the vaccination, any lack of connection between the vaccination and injury should not be held against the petitioners. Dr. Stacy's autopsy is not given probative weight, although it has been considered.
After Dr. Miller joined the litigation and learned about the vaccination, he rendered an opinion favorable to the Copenhavers' position. His opinion is not persuasive for the reasons set forth above.
The third prong of Althen requires "a showing of a proximate temporal relationship between vaccination and injury."
Here, the parties devoted relatively little attention to this prong. Before the hearing, Dr. Miller appeared to suggest that vaccinations could cause an increase in cytokines for approximately 48 hours after vaccination. Exhibit 13 (Dr. Miller's report) at 8;
The Secretary did not contest Dr. Miller's proposed timeframe. Consequently, the Copenhavers have carried their burden regarding prong 3, meaning that they established Nicholas died within the time predicted by the theory.
As explained above, however, the Copenhavers have not presented a persuasive theory explaining how vaccines can cause an infant to die unexpectedly. In the absence of a persuasive theory, the finding that the temporal sequence of events is appropriate does not advance the Copenhavers' case in any meaningful sense.
Moreover, establishing that an injury occurred shortly after vaccination, by itself, does not mean that the petitioners are entitled to compensation.
Finally, if the Copenhavers had prevailed on all three Althen prongs, then the Secretary would bear the burden of establishing some factor, other than the vaccinations, caused Nicholas's death. When the petitioners have not met their burden, as in this case, the Secretary does not bear a burden of presenting an alternative cause.
Thus, the Secretary's apparent abandonment of two potential alternative factors (co-sleeping and pneumonia) (see footnotes eight and nine above) does not affect the outcome of this case. The problem with the Copenhavers' case is that the evidence, taken as a whole, does not support the theory that vaccinations can serve as an extrinsic risk factor by stimulating the production of cytokines that impair the brain's functioning. The relative strength or weakness of any argument that something else caused Nicholas to die is irrelevant to assessing whether the vaccinations can contribute to a case of SIDS.
As demonstrated in the moving testimony from Ms. Copenhaver, Nicholas's death has caused his parents a terrible grief. Their suffering is understandable, and they deserve much sympathy for losing a child so mysteriously.
However, sympathy cannot be a basis for deciding cases in the Vaccine Program. To be entitled to compensation, the Copenhavers are required to establish that the vaccinations contributed to Nicholas's death. They have failed to meet this burden. Therefore, the Clerk's Office is instructed to enter judgment in accord with this decision.
Consequences for Interendothelial Adherens and Tight Junctions, 9:7 Plos One (2014)) at 6; Tr. 309.
