CHRISTIAN J. MORAN, Special Master.
K.O. filed a petition on behalf of her minor son, A.F., alleging that the pneumococcal conjugate ("PCV") vaccine caused him to develop opsoclonus myoclonus syndrome ("OMS"). K.O. is seeking compensation pursuant to the National Childhood Vaccine Injury Compensation Program, codified at 42 U.S.C. § 300aa-10 through 34 (2012).
To connect the PCV vaccine and A.F.'s OMS, K.O. relied upon the opinion of a pediatric neurologist, Spencer Weig. Dr. Weig opined that A.F. developed OMS on August 25, 2010, asserting that the PCV vaccination A.F. received on July 14, 2010, provoked the condition under the theory of molecular mimicry.
The Secretary disagreed with K.O.'s claim. The Secretary presented the opinion of neurologist Eric Lancaster. Dr. Lancaster opined that the onset of A.F.'s OMS was August 28, 2010, and asserted that the medical evidence did not support the theory proposed by Dr. Weig.
K.O.'s case falters for two independent reasons. First, the theory she presents, molecular mimicry, is far too general to be persuasive. She has not offered sufficient evidentiary justification for a finding that Dr. Weig's opinion is reliable. Second, the onset of A.F.'s OMS occurred outside the time that both Dr. Weig and Dr. Lancaster accepted as medically acceptable. Because K.O. did not prove, by a preponderance of the evidence, that the PCV vaccine can cause OMS, and did not show A.F.'s OMS arose in the acceptable time, K.O. did not meet her burden of proof. Thus, she is not entitled to compensation.
Section A provides a brief overview of OMS. Section B summarizes the experts' qualifications. Section C delineates the relevant events in A.F.'s medical history.
OMS is a rare neurological condition defined by acute onset of rapid and chaotic eye movements (opsoclonus) and jerking of the limbs and trunks (myoclonus) in conjunction with other conditions, including ataxia and behavioral irritability. Exhibit 18, tab C (Katherine K. Matthay,
OMS is diagnosed upon the presentation of a patient with various prodromal
K.O. relies upon the expert opinion of Spencer Weig. Dr. Weig is a board-certified pediatrician and neurologist with a special qualification in child neurology. Exhibit 18 at 1; exhibit 19 at 2. He graduated from Mt. Sinai School of Medicine in 1973 and, after practicing for several years, completed residencies and a fellowship in child neurology. He practiced child and adult neurology continuously for 24 years. Exhibit 18 at 1. Dr. Weig has treated 10 to 12 patients with opsoclonus myoclonus syndrome over the course of his career. Exhibit 18 at 1; Tr. 10. He remains active in the Departments of Neurology and Pediatrics at the University of North Carolina at Chapel Hill School of Medicine. Exhibit 18 at 1.
The Secretary relies upon the expert opinion of Eric Lancaster. Dr. Lancaster completed his PhD focused on neuroscience and MD degrees at the University of Maryland in 2002 and 2003, respectively. He completed a residency in neurology and multiple fellowships in neuromuscular study. He is the author of 22 peer-reviewed publications with many concerning autoimmune neurological disorders. Exhibit A at 1; exhibit B at 3-4. Dr. Lancaster's current practice primarily focuses on research of autoimmune brain and nerve diseases. Tr. 101. Dr. Lancaster has treated one patient with opsoclonus myoclonus syndrome. Exhibit A at 1. He currently serves as an assistant professor of neurology at the University of Pennsylvania. Exhibit B at 1.
A.F. was born on July 15, 2009, and developed normally for the first year.
A few weeks later, on August 11, 2010, A.F. was seen by pediatrician Meredith Saillant presenting with a carbuncle
K.O. recalled A.F. experiencing constipation on August 25, 2010. She gave him prune juice and noted some improvement. Exhibit 13 at ¶ 4. A.F. had an eye exam on August 27, 2010, with unremarkable results and Dr. Rebecca Maida concluding that "[A.F.'s] eyes are healthy." Exhibit 8 at 7. The normal eye exam, Dr. Weig opined, indicated that A.F. was not experiencing opsoclonus at the time. Tr. 37. Dr. Lancaster asserted that a normal eye exam rules out opsoclonus and he further asserted that a doctor would not miss opsoclonus during an eye exam. Tr. 151.
The day after his eye examination, A.F. was taken to the emergency room due to increased fussiness, crying, drooling, unsteadiness, and lack of bowel movement. Exhibit 4 at 8. An abdominal x-ray revealed a "large amount of stool." A.F. was discharged in good condition with instructions for the family to use glycerin suppositories and prune juice.
The following day, on August 29, 2010, A.F. was taken to the emergency room again for being "inconsolable of late" and complaints that he "[c]ried inconsolably for 4 [hours]" when being put down for a nap. Exhibit 6 at 282, 287; Tr. 19. The family reported that A.F. was more uncoordinated than usual, wobbling and flopping, and that he had been constipated for several days. Exhibit 6 at 287. The family also reported that A.F. was no longer constipated or fussy as he had been the previous night.
Dr. Weig opined that the irritability and inconsolable crying were prodromal symptoms of OMS. Dr. Weig also asserted that A.F.'s irritability and inconsolable crying started no later than August 25, 2010, based on the affidavit of K.O. and the medical records of Dr. David Coulter. Tr. 39-41. Dr. Lancaster disagreed, asserting that the medical records and histories provided by K.O. indicate that A.F. was constipated on August 25, 2010, and did not experience any OMS-like symptoms until later on August 28. Tr. 107-08.
During a consultation on August 29, 2010, neurologist David Coulter documented the concerns of lethargy, inconsolability, and coordination issues. Exhibit 6 at 290. Dr. Coulter noted some weakness attributing it to "the setting of constipation or mild illness (though he has had no evidence of recent illness)."
A.F. saw a physician with Dr. Saillant's practice, Marshall Reiner, on August 30, 2010, for a follow-up after the emergency room visit. While the parents complained that A.F. had regressed and been "unsteady" for the past two days, Dr. Reiner's impression was that "the child's actions are normal for age." The diagnosis was ataxia with a referral to a neurologist. Exhibit 5 at 25. Dr. Saillant saw A.F. on August 31, 2010, with continued complaints of irritability, constipation, and unsteadiness that had not improved. Exhibit 5 at 26. Dr. Saillant noted that A.F. was "markedly different from the last time I saw him a few weeks ago" and that his balance was "severly [sic] compromised."
Upon review of the past medical history and examination on September 1, 2010, Dr. Coulter diagnosed A.F. with acute cerebellar ataxia. Exhibit 6 at 279-80. Dr. Coulter's notes state that the family had reported to him that A.F. had been fine on August 27, 2010, with an onset of symptoms on August 28 and worsening on August 29.
On September 7, 2010, during the hospital stay, Kara Smith noted that A.F. had lost the ability to "sit independently, pull to stand and to cruise, all of which he had previously." Dr. Smith diagnosed A.F. with opsoclonus myoclonus syndrome stating "[A.F.'s] history and exam is quite concerning and he offers opsoclonus as well as myoclonus." Dr. Smith coordinated further imaging studies with A.F.'s neuroimmunologist, Mark Gorman, to rule out a neural crest tumor, such as a neuroblastoma. Exhibit 6 at 269-70, exhibit 17 at 4. A.F. was discharged the following day.
Under the supervision of Dr. Gorman, A.F. was readmitted on September 14, 2010, for MRI and MIBG
A.F. returned to Dr. Gorman for a follow up visit on November 5, 2010, when Dr. Gorman noted that A.F. had "idiopathic OMS" being treated with immunosuppressive therapy that was going well. Exhibit 6 at 201-02. Dr. Lancaster opined that Dr. Gorman's impression that the OMS was "idiopathic" is an indication that a cause or triggering event was sought, but one was not found. Tr. 142-43.
Several months after Dr. Gorman's follow up appointment, pediatric neuro-ophthalmologist Gena Heidary evaluated A.F. on June 2, 2011. Dr. Heidary's impression of A.F.'s OMS was that while the etiology was unclear, "there is a question of a reaction to the pneumococcal vaccine number 13 as this was the only thing that antedated the onset of his symptoms." Exhibit 6 at 143. A.F. returned to Dr. Heidary on September 15, 2011, and she noted that the OMS had resolved and he was "doing extremely well."
On July 12, 2013, K.O. filed a petition on behalf of her minor son, A.F., alleging that the PCV vaccine caused him to develop OMS. K.O. filed medical records, exhibits 1-12, on October 28 and 30, 2013. Affidavits were filed on December 17, 2013 and outstanding medical records filed on December 20, 2013. Exhibits 13-15.
On January 7, 2014, the Secretary filed her report pursuant to Vaccine Rule 4. The Secretary maintained that K.O. had failed to demonstrate causation. Resp't's Rep. at 13. The Secretary argued that K.O. did not offer reliable scientific evidence that demonstrated a causal relationship between the PCV vaccination and OMS. Although the Secretary noted that pediatric neuro-ophthalmologist Gena Heidary stated that she "thought" the PCV vaccination was secondary to A.F.'s OMS, the Secretary asserted that Dr. Heidary's opinion was contradicted by all of A.F.'s treating physicians who did not mention such an association, but merely noted the temporal relationship.
During a January 13, 2014 status conference to discuss the Rule 4 report, K.O. stated that she would retain an expert to opine on her case after the parties discussed the possibility of settlement. K.O. filed additional medical records and a response to the Rule 4 report on January 29, 2014. K.O. answered questions presented regarding medical records asserting that all requests made by respondent were satisfied. Pet'r's Resp., filed Jan. 29, 2014.
On February 4, 2014, K.O. filed a status report proposing a May 5, 2014 deadline for her expert report. The undersigned issued draft Instructions to Witnesses Offering Opinion Testimony (hereinafter "proposed instructions") on February 12, 2014. The undersigned explained that expert reports are filed in advance of the hearing and provide all parties and the special master notice of the contents of the testimony. Therefore, the proposed instructions ordered that any expert's report would, most likely, constitute the expert's testimony on direct examination. The undersigned further explained that the purpose of this requirement was two-fold: 1) to ensure a complete report that presented the expert's opinions and bases for those opinions, and 2) to decrease time spent in hearings repeating the content of the expert report.
The undersigned ordered K.O. to file any comments to the proposed instructions by February 28, 2014, and her expert report by May 5, 2014. On March 7, 2014, K.O. filed her Opposition to the Court's Proposed Instructions to Witnesses Offering Opinion Testimony. Presenting several objections to the proposed instructions, K.O. relied primarily upon Vaccine Rule 8. K.O. asserted that Rule 8(b)(2) allows petitioners to present evidence in the manner in which they choose and that there is no authority given to special masters to require evidence be presented in a specific format. Pet'r's Opp. at 4. K.O. further asserted that expert reports are evidence as governed by Vaccine Rule 8(b) and therefore cannot be limited to the written report.
Additionally, K.O. argued that expert testimony in complex cases warranted oral presentation and cited two previous cases where the undersigned has stated that "oral testimony may be more persuasive than written records."
The undersigned issued an order for expert reports and addressed K.O.'s objections on April 17, 2014. This order mandated that the expert reports comply with the proposed instructions previously set forth and that the reports would constitute direct testimony. The undersigned drew from other instances where written direct testimony had been used in non-jury cases by similar courts with the most instructive instance being the Tax Court. The undersigned analogized the Court of Federal Claims and the Office of Special Masters to the Tax Court in three ways. First, both are Article I tribunals. Second, both are devoted to one subject matter. Third, both hear cases without a jury. The undersigned noted that the Tax Court Rules of Practice and Procedure, specifically Rule 143(g), provided that testimony need not be presented orally. Additionally, FRCP 43(a) removed the oral testimony requirement. The undersigned reasoned that this was instructive because Court of Federal Claims Rule 43 is identical to FRCP 43. The undersigned cited cases in which the Court of Federal Claims and the Tax Court had received direct testimony from experts in the form of written reports.
The undersigned further observed that there is no statutory restriction prevents the Office of Special Masters from using expert reports as direct testimony. In addressing K.O.'s fairness objections, the undersigned determined that they were unpersuasive as the order applied to both parties and was designed to facilitate flexibility in the presentation of evidence allowing experts weeks to draft comprehensive reports with assistance of counsel for development.
K.O. filed her expert report, supporting literature, and the curriculum vitae from Dr. Weig on July 11, 2014. Exhibits 18-19. On July 16, 2014, K.O. filed a Renewed Opposition to the Court's Orders dated February 12, 2014 and April 17, 2014 and Motion to Vacate the Orders. K.O. renewed her objections that special masters lacked authority to require expert reports as direct testimony, precluding oral testimony was a detriment to petitioners being able to present the opinion of the expert fully, and that the special master had gone beyond his duties in mandating the instructions.
During the ensuing status conference to discuss Dr. Weig's report, the undersigned determined that most of petitioner's outstanding motions were moot due to Dr. Weig answering the questions posited by the instructions in his report. Order, issued July 25, 2014. The Secretary filed an expert report with supporting literature, following the same instructions as K.O., as well as a curriculum vitae, from Dr. Lancaster on October 1, 2014. Exhibits A-Q. In the ensuing status conference to discuss Dr. Lancaster's report, the undersigned ordered Dr. Lancaster to provide the basis for his assertion that "PCV contains no antigens expressed in a normal brain." Reminding K.O. that Dr. Weig's reports may constitute his direct testimony, the undersigned ordered a supplemental report to respond to Dr. Lancaster. At that time, the parties discussed exploring settlement.
The Secretary filed Dr. Lancaster's supplemental expert report with supporting literature on November 5, 2014. Exhibits R-T. On December 12, 2014, K.O. filed Dr. Weig's responsive expert report with supporting literature. Exhibit 20. On January 13, 2015, the Secretary filed a status report indicating that, despite settlement efforts, she desired to defend the case. During a January 23, 2015 status conference, the undersigned questioned whether a fact hearing would be needed to settle the question of onset.
The Secretary filed a supplemental expert report from Dr. Lancaster on February 9, 2015. Exhibit U. The parties proposed mutually convenient dates for an expert hearing on entitlement and a one-day hearing was set for August 13, 2015. Pet'r's Status Rep., filed Mar. 2, 2015. The undersigned issued a pre-hearing order setting the dates for pre-hearing submissions and the pre-hearing status conference. Order, issued Apr. 23, 2015;
On July 9, 2015, K.O. filed a supplemental statement asserting that oral direct testimony from Dr. Weig was required to present the dispute regarding onset of OMS symptoms, complex theories, a logical sequence of cause and effect showing that the vaccination was the reason for the injury, and showing a proximate temporal relationship between the vaccination and injury. On July 13, 2015, the Secretary filed her pre-hearing brief.
An expert hearing was held on August 10, 2015, in Washington, DC. Both Dr. Weig and Dr. Lancaster testified at the hearing. Both testified in accord with their reports.
Dr. Weig testified that the onset of symptoms was late August 2010, opining the date to be August 25, 2010, based on K.O.'s affidavit and the August 29, 2010 medical records from Dr. David Coulter. Tr. 74-75. He stated that K.O. noticed the irritability in late August which is consistent with the timing of OMS symptom onset. Tr. 18-19, exhibit 13 (K.O.'s affidavit) at 1-2. The medical records from the hospital then provided a documented parental statement of the symptoms presenting since three days prior to that August 28 visit. Tr. 19-20, exhibit 18 (Dr. Weig's report) at 7. Dr. Weig stated that the irritability noticed by the parents and crying at night, supported an onset date of August 25 because these behaviors were the early symptoms of the disease. Tr. 19-20, 23; exhibit 18 at 4.
Dr. Weig explained that A.F.'s normal eye exam results on August 27 were unremarkable because, in his professional experience, a patient could be asymptomatic for opsoclonus and later exhibit symptoms. Tr. 38-39, 94. Dr. Weig ruled out constipation as the cause of A.F.'s irritability due to the duration and prolonged period of crying. The duration of the irritability instead pointed to a typical prodromal symptom of OMS. Tr. 39-41, exhibit 18 at 7.
Dr. Weig opined that it was more likely than not that A.F.'s OMS was vaccine-induced because extensive testing ruled out possible alternate causes, such as neuroblastoma, or alternate theories. Tr. 95, 169; exhibit 18 at 9.
K.O. had approximately 30 minutes of direct examination with Dr. Weig. K.O. was also able to ask Dr. Weig any additional questions or gain clarification on re-direct examination after the Secretary cross-examined and the undersigned examined Dr. Weig.
The Secretary presented the testimony of Eric Lancaster at the hearing. Dr. Lancaster testified that, based on the totality of the medical records, the irritability A.F. experienced on August 25, 2010, was due to constipation with which he was diagnosed and for which he was treated. Tr. 108, exhibit A at 12. He opined that the onset of OMS was three days later, on August 28, as confirmed by the contemporaneous medical records. Tr. 107, exhibit A at 13.
Dr. Lancaster acknowledged Dr. Heidary's records possibly linking the vaccination to OMS as K.O. suggested, but asserted that her notes indicated obscurity regarding causation and an inability to understand her thought process fully. Tr. 141-42. In contrast to Dr. Weig's opinion, Dr. Lancaster stated that A.F.'s normal eye exam was "very helpful for ruling out opsoclonus" as it would be "very unlikely, for any eye doctor to miss that." The normal exam and physician indication that A.F. was negative of any symptoms weighed against onset prior to August 28. Tr. 150-51, exhibit A at 3, 12; exhibit U at 2.
Dr. Lancaster opined that the furuncle present prior to the onset of A.F.'s neurological symptoms provided a better temporal fit as a potential triggering infection. Tr. 146-47, exhibit A at 13. He further explained that while the cause of A.F.'s OMS was more likely idiopathic, the furuncle was a more plausible trigger than the vaccination. Tr. 155-56, exhibit A at 13.
Overall, the process of expert reports as direct testimony worked well. Both Dr. Weig and Dr. Lancaster presented their opinions (in writing and orally) thoughtfully. When the undersigned asked Dr. Weig his opinion regarding the instructions issued to him for preparing his expert reports, Dr. Weig testified that the instructions "helped me organize my — my thoughts, my analysis of the records. I didn't think it was artificial either. I mean, I found it helpful." Tr. 171.
On August 21, 2015, the undersigned issued an order for post-hearing briefs. While the case was still pending, K.O. filed a motion for attorneys' fees and costs on an interim basis with the Secretary filing a response shortly thereafter. K.O. filed her post-hearing brief on October 22, 2015. The Secretary submitted her post-hearing brief on November 18, 2015, with K.O. filing a reply on December 3, 2015. K.O. filed an additional motion for interim fees and costs on June 20, 2016. The case is now ripe for a decision.
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.
The elements of K.O.'s case are set forth in the often cited passage from the Federal Circuit's decision in Althen: "(1) a medical theory causally connecting the vaccination and the injury; (2) a logical sequence of cause and effect showing that the vaccination was the reason for the injury; and (3) a showing of a proximate temporal relationship between vaccination and injury."
As mentioned in the introduction of this decision, K.O.'s case fails to be persuasive with respect to two of the
The second problem with K.O.'s case is that the timing does not fit. Both Dr. Weig and Dr. Lancaster opined that an acceptable interval between vaccination and the onset of OMS would encompass 42 days. Neither expert offered opinions that an onset of more than 42 days would be medically acceptable. As explained in section B below, the records created in August and September 2010, are much more consistent with a finding that A.F. started to experience OMS 45 days after vaccination.
K.O.'s failure to establish either a persuasive medical theory (
K.O.'s burden is to present "a medical theory causally connecting the vaccination and the injury."
To establish the first prong of Althen, K.O. must provide "a reliable medical or scientific explanation."
Collectively, the parties' evidence relating to the proposition that PCV vaccines can cause OMS via molecular mimicry falls into five broad categories: (a) literature about vaccines and OMS, (b) an article by Pranzatelli, (c) studies on homology, (d) an admission by Dr. Lancaster, and (e) an admission by the Secretary in other cases.
In support of their respective positions, the parties submitted medical articles discussing vaccines and disorders of the central nervous system, including OMS. The medical articles fall into two groups: an epidemiologic study and four case reports.
Because these articles are part of the record, they must be considered. 42 U.S.C. § 300aa-13(a);
In weighing the relative value of the articles, the undersigned follows the guidance of the Federal Judicial Center. The Federal Judicial Center has published a series of guides designed "to assist judges . . . in reaching an informed and reasoned assessment concerning the basis of expert evidence." Jerome P. Kassirer and Gladys Kessler, Reference Manual on Scientific Evidence,
According to the Federal Judicial Center, "[e]pidemiologic studies have been well received by courts deciding cases involving toxic substances." Michael D. Green et al., Reference Manual on Scientific Evidence,
Consistent with the instruction from the Federal Judicial Center, the Federal Circuit has long endorsed special masters' consideration of epidemiologic evidence.
Here, the record contains one epidemiologic study. Exhibit K (Hung Fu Tseng et al.,
In their reports, first Dr. Lancaster and then Dr. Weig commented on the Tseng study.
At hearing, Dr. Lancaster changed his position. He stated "Dr. Weig has a good point, that the disease is very rare, which makes it very hard to fully power to detect it." Tr. 133-34. Nevertheless, without citing any authority, the Secretary argued that the Tseng study remains "evidence to be considered." Resp't's Posth'g Br. at 11 n.3. In contrast, K.O. contended that the only value of the Tseng study is to call into question Dr. Lancaster's credibility. Pet'r's Resp. at 8-9.
It is important to remember that K.O. has the burden to show that the PCV vaccine can cause OMS.
Unlike Tseng, which the Secretary's expert introduced, K.O. relied upon a set of four case reports.
Again, the undersigned follows the lead of the Federal Judicial Center. A pertinent guide states "[a]necdotal evidence usually amounts to reports that events of one kind are followed by events of another kind. Typically, the reports are not even sufficient to show association, because there is no comparison group." David H. Kaye and David A. Freedman, Reference Manual on Scientific Evidence,
The only Federal Circuit case to discuss the value of case reports in the Vaccine Program found no error in a special master's giving the case reports little weight. In a series of five cases involving auto-immune hepatitis, the undersigned special master rejected case reports as evidence of causation.
When the Federal Circuit reviewed the special master's decision, the Federal Circuit stated that "[t]he special master found that the remaining two articles, both describing single case studies, did not contain any meaningful analysis about causation."
It is interesting to juxtapose case reports with epidemiologic studies. Case reports are generally seen as holding less evidentiary value than epidemiologic studies.
The foregoing assessment describes the limited value of case reports generally. Here, the case reports K.O. and Dr. Weig identify have even less value because they report a sequence in which a vaccine, but not a vaccine against pneumococcus, precede the onset of OMS. Exhibit 18, tab B (Kinsbourne); Exhibit 18, tab L (Nicholas Christoff,
An expert may "extrapolate from existing data,"
After considering the case reports, the testimony about the case reports, and the briefs containing arguments about the case reports, the undersigned chooses to give the four case reports negligible weight.
Dr. Michael Pranzatelli is considered one of the leading researchers for OMS. Tr. 24. When Dr. Weig was asked to identify the articles that most strongly supported his opinion regarding molecular mimicry, Dr. Weig cited a review article that Dr. Pranzatelli wrote in 1996. Tr. 53, citing exhibit 18, tab G (Michael R. Pranzatelli,
In that lengthy article, Dr. Pranzatelli proposes molecular mimicry as one among several possible etiologic theories. Exhibit 18, tab G at 21-22. In this context, Dr. Pranzatelli states that "Cross-reactivity between neural crest-derived tumors and brain antigens . . . in paraneoplastic cases is also very plausible, given their shared embryology."
Dr. Weig's assessment that Dr. Pranzatelli was "open" to the idea that immunizations may contribute to the onset of OMS appears accurate. Dr. Pranzatelli also discussed vaccinations in another part of his long article. Dr. Pranzatelli's list of environmental factors that are "likely to be very important in OMS" includes viruses, bacteria, and immunizations. Yet, Dr. Pranzatelli recognized that "Assessment of the potential effects of immunization on the onset of OMS is not simple."
At hearing, K.O. referenced Dr. Pranzatelli's statement that a reaction to a tumor and virus producing OMS "presented both a puzzle and a clue." Dr. Weig explained that the puzzle is determining what a virus or bacterium have in common with a form of cancer. The clue would be that the body responds to fight a tumor in the same manner it responds to fight a virus or bacterium. Tr. 57-58.
Dr. Pranzatelli made this statement as part of his thesis for his research into the mechanism of action of current therapy. Exhibit 18, tab G at 2. Dr. Pranzatelli ultimately stated that the virus was not directly encephalogenic in OMS cases associated with viral infection.
In the Secretary's post-hearing brief, she challenged K.O.'s reliance on the Pranzatelli article in several respects. First, the Secretary observes that Dr. Pranzatelli did not state "that vaccines in general (let alone the PCV vaccine specifically) can cause OMS" via molecular mimicry. Second, Dr. Weig's conclusion that Dr. Pranzatelli was "open" to vaccines as a causative factor "is insufficient for petitioner to meet her burden." Third, the Secretary argues that the lack of validation of molecular mimicry outside the context of a neuroblastoma in the 20 years since Dr. Pranzatelli wrote the article is "telling." Resp't's Posth'g Br., filed Nov. 18, 2015, at 12. K.O.'s reply brief did not answer these specific criticisms of the Pranzatelli article.
Whether developments in the last two decades have supported the proposal that vaccines can cause OMS via molecular mimicry is considered next.
A premise for molecular mimicry is that a particular antigen (say, a vaccine) shares that molecular structure with some part of the human body such that the immune system's attack on the antigen is misdirected to the host's own tissue. Exhibit 18, tab G (Pranzatelli) at 21. The medical term for similarity in structure is homology.
The degree of homology between two proteins can be determined using a method known as blast sequencing according to an article Dr. Weig submitted. Exhibit 18, tab H (Paul M. Candler et al.,
The Secretary's expert, Dr. Lancaster, explained the experiment the Candler group conducted. Dr. Lancaster also criticized the experiment in certain respects, but these perceived flaws are not particularly important to the outcome of K.O.'s case. Tr. 118-22. More significantly, K.O.'s expert, Dr. Weig, struggled to explain the Candler experiment. Tr. 53-55. When asked to explain what a blast sequence is and whether it could be used on the pneumococcal vaccine, Dr. Weig said that he did not have the background to answer those questions. Tr. 55-56.
On cross-examination, Dr. Weig was asked whether he was aware of any homology between the PCV vaccine and brain cells. Dr. Weig stated that he did not know. Dr. Weig was also asked whether he knew of any homology between the pneumococcal bacteria (the target of the PCV vaccine) and brain cells, Dr. Weig again stated that he did not know. Tr. 85. Dr. Weig's lack of knowledge creates a considerable gap in K.O.'s case.
Special masters may consider whether the expert's opinion can be and has been tested.
K.O. argued that a showing of homology between the PCV vaccine and brain tissue is not needed because Dr. Lancaster has accepted molecular mimicry as a theory to explain how neuroblastomas can lead to OMS. Pet'r's Posth'g Br., filed Oct. 22, 2015, at 20; Pet'r's Posth'g Resp., filed Dec. 3, 2015, at 7. To review, a neuroblastoma is a tumor of embryonic cells that develop into a nerve cell or neuron.
The frequency of cases in which neuroblastomas precede OMS has led to a conclusion that neuroblastomas cause OMS. How neuroblastomas cause OMS has not been elucidated. Tr. 42-44, 112. Dr. Pranzatelli's 1996 article proposes that: "While the initial immune response is appropriately directed to eradicating virus or tumor, the immune response becomes secondarily pathological." Exhibit 18, tab G at 21. Dr. Pranzatelli, as discussed above, suggested molecular mimicry as one theory to explain the harmful response of the immune system.
Dr. Lancaster stated, "in the case of patients with neuroblastoma, [I think] that molecular mimicry is — is close to the correct concept." Tr. 116. Later, Dr. Lancaster clarified that molecular mimicry in cases with a neuroblastoma is "not yet firmly established because we don't have the specific antigen." Tr. 135.
While Dr. Lancaster accepted molecular mimicry as a "highly likely" link between neuroblastomas and OMS, Dr. Lancaster distinguished viruses as a potential source of cross-reactivity. "Given how very different viruses are from human beings, it would be unusual for some component of the virus to very closely resemble some component of the brain." Tr. 117. Dr. Lancaster's opinion was that viruses might cause OMS through some process other than molecular mimicry. Tr. 117-18, 135.
K.O. charges Dr. Lancaster with being inconsistent in two respects. First, K.O. argues that Dr. Pranzatelli proposed molecular mimicry as a theory by which neuroblastomas (tumors) and infections could lead to OMS. Pet'r's Posth'g Br. at 20; Pet'r's Posth'g Resp. at 7. In this respect, K.O. is only partially correct. It is true that Dr. Pranzatelli suggested molecular mimicry for tumors as well as infections. Exhibit 18, tab G at 21. However, molecular mimicry is not the only theory that Dr. Pranzatelli proposed.
Second, K.O. argues that Dr. Lancaster is being inconsistent because science has not found the pathway for either neuroblastomas or infections. Under K.O.'s logic, because the lack of knowledge about the target antigen does not prevent Dr. Lancaster from accepting molecular mimicry as a method to explain the connection between neuroblastomas and OMS, this same lack of knowledge should not prevent Dr. Lancaster from accepting molecular mimicry as a method to connect infections and OMS. Pet'r's Preh'g Br. at 22; Pet'r's Posth'g Resp. at 7.
Here, too, K.O.'s argument misses its mark. Because neuroblastomas are essentially malignant nerve cells, it is easy to see how the immune system's response to neuroblastomas could be misdirected against other nerve cells, such as those found in the brain.
In short, K.O. is not persuasive in arguing that because molecular mimicry may be valid in some situations not involving vaccines, molecular mimicry also should be accepted as a reliable theory in a situation involving vaccines.
Finally, K.O. argues that her theory is reliable because the Secretary has agreed to settle other cases involving OMS. Pet'r's Resp. at 3-4. Procedurally, the argument was raised too late. K.O. could have offered this same argument in either her pre-hearing brief or her initial post-hearing brief. But, she did not. Non-jurisdictional arguments that are raised for the first time in a reply brief are typically considered waived.
More significantly, settlements are not considered admissions that can be used to establish a fact based upon a settlement.
Through Dr. Weig, K.O. has presented a theory to explain how the PCV vaccine can cause OMS. However, K.O. has not presented a reliable basis for finding this theory persuasive. Consequently, K.O. has not established her burden of proof regarding
K.O. must establish a "proximate temporal relationship" between the PCV vaccination and the onset of A.F.'s opsoclonus myoclonus.
The first part of the third prong of
Here, the parties generally agree that an interval from which inferring causation is acceptable is from one to six weeks. Dr. Weig provided this estimate in his report, exhibit 18 at 7, and based his estimate on a 1994 report from the Institute of Medicine ("IOM") that considered whether vaccines against tetanus, diphtheria, and pertussis could cause demyelinating diseases. When asked during the hearing if he could explain the 42 day limit, Dr. Weig stated: "I don't know. It's just there." Tr. 65.
Dr. Lancaster also relied upon the 1994 IOM report but stated that the IOM report states that onset is more likely to occur within seven to 21 days of vaccination. Tr. 137-38; exhibit A at 12. Thus, Dr. Lancaster explained that while the IOM provides 42 days within the range for onset, it is the upper limit of plausibility. Tr. 140.
Based upon entire record, the undersigned finds that an acceptable interval extends to 42 days. The record does not contain any persuasive basis for extending this period past 42 days. As Dr. Lancaster explained, the IOM found that vaccines might produce a demyelinating disease within seven to 21 days. The IOM, then, further extended the 21 days to 42 days to account for any outliers. Tr. 140; exhibit Q (Institute of Medicine,
Therefore, to establish the third prong of
Unlike the agreeing opinions that an acceptable interval was up to 42 days, the parties have considerable dispute about when A.F. first began to manifest problems of his OMS. As previously discussed, the onset of OMS is sometimes marked by the presentation of prodromal symptoms such as irritability, behavioral disturbances, and ataxia. K.O. asserts that the prodromal symptoms were present on August 25, 2010 (42 days after vaccination). The Secretary disagrees and proposes August 28, 2010, as the onset date (45 days after vaccination).
Dr. Weig first opined an onset date as far back as August 20, 2010. Exhibit 18 at 7. When asked how he determined this date, he answered "Well, not directly in the medical record. That was working backwards from . . . K.O.'s report of late August and then knowing, in my mind, that the symptoms began on the — you know, the first mention we have in there is August 25th, that I thought it was probably started a few days earlier." Tr. 73. Dr. Weig agreed that the medical records did not support this onset date.
In the absence of a reliable foundation for his opinion that A.F. started to experience OMS on August 20, 2010, Dr. Weig came up with another date. He proposed August 25, 2010. Tr. 19-20. The medical records show A.F. was irritable and constipated. Exhibit 4 at 8-9, 12-13, 15;
In K.O.'s post-hearing brief, she asserts that determining the onset of OMS in children of A.F.'s age is difficult. For this argument, she relies on her expert, Dr. Weig, who stated that behavioral issues, which can be prodromal symptoms of OMS, are more difficult to assess in a child one-year to two-years old. Pet'r's Posth'g Br. at 16; Tr. 17. Dr. Weig states that while "exact timing of onset of symptomatology is frequently quite difficult to ascertain with absolute precision," the sleep disturbances and irritability that A.F. experienced made it "evident that by 8/25/2010" these were symptoms consistent with the onset of OMS. Exhibit 18 at 7.
The Secretary's expert, Dr. Lancaster, stated that A.F. was experiencing constipation based on the totality of the medical records on August 25, 2010. He stated that K.O. reported several times in the record that the symptoms of irritability subsided once A.F. passed a hard stool. Tr. 107-08. The resolution of A.F.'s irritability after he moved his bowels suggested that constipation was causing the irritability. If a brain-based neurologic disorder had been causing A.F.'s irritability, then the irritability would have continued after the bowel movement. Thus, August 25, 2010 is not the date of onset of A.F.'s OMS.
Here, the persuasive evidence indicates that the onset of A.F.'s OMS was on August 28, 2010. Dr. Lancaster provided an onset date of August 28 based on the medical records. Exhibit A at 13; Tr. 150. Several medical records point to an onset of August 28, 2010. These include: exhibit 6 at 282-86 (Dr. Shrivastava's notes on August 29, 2010, stating "Mom noted his coordination seemed to be off a little yesterday."); exhibit 6 at 286-89 (Dr. Coulter's notes on August 29, 2010, stating "[A.F.] . . . presents today with a one day [history] of `wobbliness and floppiness'. . . Of note: five days prior to presentation, when he was `constipated' with mom noting that he had increased straining, and needed prunes to pass a hard stool."); exhibit 6 at 290-91 (Dr. Viccari's notes on August 29, 2010, stating "The patient is a 13-month-old male crying inconsolably on and off since yesterday. History of being constipated."); exhibit 5 at 25 (Dr. Reiner's notes on August 30, 2010, stating "Unsteady, different sense of balance, past 2 days."); exhibit 5 at 26-7 (Dr. Saillant's notes on August 31, 2010, stating "3 days ago was irritable and had some constipation and thought to have imbalance/dizziness."); exhibit 6 at 279-80 (Dr. Coulter's notes on September 1, 2010, stating "When I saw [A.F.] on September 1st, his parents again noted that [A.F.] had been pretty normal on Friday, August 27th, and in fact had seen the eye doctor that day and had a normal examination."); exhibit 8 at 4 (phone call from A.F.'s father to Bennet Family Eye care stating "since after appt [A.F.'s] leg's wobbly, trouble sitting more clumsy").
This abundant evidence, which K.O. did not address in her reply brief, supports a finding that the onset of OMS was August 28, 2010. This finding means that 45 days elapsed after the vaccination. Because K.O. offered no basis for extending the accepted interval past 42 days (
The remaining prong from
Here, the parties rely upon different views expressed by two doctors. K.O. cites pediatric neuro-ophthalmologist Gena Heidary's June 2, 2011 report. Pet'r's Posth'g Br. at 32-33. Dr. Heidary wrote: while the etiology was unclear, "there is a question of a reaction to the pneumococcal vaccine number 13 as this was the only thing that antedated the onset of his symptoms." Exhibit 6 at 143.
The Secretary, in contrast, mentions the November 5, 2010 report of pediatric neuro-immunologist Mark Gorman. Dr. Gorman's early history showed that he was aware of A.F.'s receipt of the PCV vaccine. Exhibit 6 at 247. Yet, on November 5, 2010, Dr. Gorman described A.F.'s OMS as "idiopathic," meaning Dr. Gorman did not know the cause of the OMS. Exhibit 6 at 201-02.
Dr. Heidary's report does not assist K.O. in any significant way. Dr. Heidary received a history that A.F. had received that PCV vaccination three weeks prior to symptom development. Exhibit 6 at 143. But, this history is erroneous. The actual interval between vaccination and onset was longer than Dr. Heidary understood. When a treating doctor receives an inaccurate history, the special master is not required to defer to that doctor's opinion regarding causation.
Moreover, Dr. Heidary's actual words are "there is a question of a reaction." This wording does not indicate that Dr. Heidary believes, on a more-likely-than-not basis, that the vaccination caused A.F.'s OMS.
In addition to the problems with Dr. Heidary's report, other evidence suggests that there is not a logical sequence between A.F.'s vaccination and his OMS. As discussed above, K.O. has not presented a reliable basis for crediting the theory that PCV vaccine can cause OMS. As a matter of logic, if there is no showing that the vaccine can cause an injury, there cannot be a basis for finding the vaccine did cause the injury. Similarly, K.O. has not established an acceptable temporal relationship. Again, as a matter of logic, if the injury occurs outside of the time expected, then a finding of causation would not be logical.
Finally, some precedent suggests that special masters, in considering whether petitioners have met their burden regarding prong two, should consider whether petitioners have ruled out any other potential causes for the injury.
Here, Dr. Lancaster proposed that A.F.'s OMS was "idiopathic." Exhibit A at 13; Tr. 156. Alternatively, between the two factors that were considered as possible causes (the furuncle and the vaccination), Dr. Lancaster ranked the furuncle as more likely than the vaccination. In Dr. Lancaster's opinion, the furuncle was a stronger candidate than the vaccination (but still less likely than an unknown cause) because A.F. experienced the furuncle in closer temporal proximity than the vaccination. Tr. 147.
K.O.'s brief addresses only the Secretary's contention that the most likely cause of A.F.'s OMS was an unknown cause. K.O. makes a creditable argument that assuming she has met her burden of proof regarding the three
To the extent that the presence of potential alternative causes bears on the petitioner's burden regarding
For the furuncle, K.O. essentially places all her eggs in one basket — an argument that because Dr. Lancaster could not say that the furuncle was the likely cause of the injury, his opinion is "wholly irrelevant." Pet'r's Reply at 20. However, K.O. has not cited any precedent that the Secretary must establish an alternative cause as more likely than not before a petitioner must address the proposed alternative cause.
K.O.'s expert, Dr. Weig, offers little assistance to her. (K.O. did not cite any testimony about the furuncle from him in her post-hearing briefs.) At hearing, when asked why the bacteria that is the source of the furuncle was not a trigger for molecular mimicry leading to A.F.'s OMS, Dr. Weig stated that "it's more likely than not that the vaccine would be the cause." He went on to state that he discounted the bacteria because he knew of no known associations between skin infections and opsoclonus myoclonus syndrome. Tr. 169-70. This argument essentially undercuts K.O.'s assertion that the PCV vaccine caused A.F.'s OMS as she presented no evidence of known associations between the PCV vaccine and OMS.
Thus, the analysis has come full circle. The first problem with K.O.'s case is that she has not demonstrated, at a preponderance of the evidence level, that the PCV vaccine can cause OMS. As discussed at length above, the cause of OMS is not known in approximately 50 percent of the cases. In these non-neuroblastoma cases, there is a lack of supporting evidence for any proposed causes, including viruses, bacteria, and vaccines. The fact that bacteria have not been established as a cause of OMS is analytically distinct from whether the PCV vaccine can cause OMS.
K.O. claimed that the PCV vaccine caused A.F. to develop OMS. The evidence was not sufficient to establish the causal relationship between the vaccination and OMS. Consequently, K.O. is not entitled to compensation on behalf of her minor son, A.F.
The Clerk's Office is instructed to enter judgment in accord with this decision.
