O'Malley v. Secretary of Health and Human Services ( 2017 )

In the United States Court of Federal Claims
OFFICE OF SPECIAL MASTERS
*********************
K.O., parent of * No. 13-472V
A.F., a minor, * Special Master Christian J. Moran
Petitioner, *
* Filed: July 7, 2016
v. * Reissued: January 3, 2017
*
SECRETARY OF HEALTH * Entitlement; Pneumococcal Conjugate
AND HUMAN SERVICES, * (“PCV”) Vaccine; Opsoclonus
* Myoclonus Syndrome (“OMS”).
Respondent. *
*********************
Ronald C. Homer and Meredith Daniels, Conway, Homer & Chin-Caplan, P.C.,
Boston, MA, for petitioner;
Heather L. Pearlman, United States Dep’t of Justice, Washington, DC, for
respondent.
PUBLISHED DECISION DENYING COMPENSATION1
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
1
After this decision was issued, the petitioner filed a motion to redact her name to initials
pursuant to Vaccine Rule 18(b). That motion was granted. Order, filed Nov. 30, 2016.
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.
I. Background2
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.
2
The undersigned has considered all the evidence. Cf. Moriarty v. Sec’y of Health &
Human Servs., No. 2015-5072, 2016 WL 1358616 (Fed. Cir. Apr. 6, 2016) (stating special
master erred in not considering the entire record). Although the undersigned does not discuss all
the evidence, the undersigned discusses the evidence (documentary and testimonial) that the
undersigned finds most relevant. The process of determining the relevancy of any piece of
evidence is informed by the undersigned’s experience as a special master generally. The
undersigned has reviewed the expert reports several times, beginning when they were initially
filed. In preparing the order requesting briefs before the hearing, the undersigned reviewed the
expert reports and the articles cited in those reports. The parties provided their views of the
relevance of the articles in their pre-hearing briefs. The parties’ briefs, in turn, provided a
foundation for asking questions at the hearing. The witnesses’ testimony further refined and
highlighted the most important articles that the parties discussed in their briefs after the hearing.
The undersigned is reasonably confident that this process has brought to his attention any piece
of evidence that would significantly contribute to analyzing K.O.’s claim. See Vaccine Rule
8(b)(1).
2
A. Opsoclonus Myoclonus Syndrome
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, Opsoclonus myoclonus
syndrome in neuroblastoma: a report from a workshop on the dancing eyes
syndrome at the advances in neuroblastoma meeting in Genoa, Italy, 2004, 228
Cancer Lett. 275 (2005)) at 276; exhibit D (Barbara Hero, Update on Pediatric
Opsoclonus Myoclonus Syndrome, 44 Neuropediatrics 324 (2013)) at 324; exhibit
18, tab D (K. Ki Pang, A prospective study of the presentation and management of
dancing eye syndrome/opsoclonus–myoclonus syndrome in the United Kingdom,
14 European J. of Pediatr. Neurol., 156 (2010)) at 156. Most, but not all, pediatric
patients with OMS also have a diagnosis of a neuroblastoma. 3 The etiology of
OMS is believed to be autoimmune in nature. Exhibit 18, tab B (M. Kinsbourne,
Myoclonic encephalopathy of infants, 25 J. Neurol. Neurosurg. Psychiatr. 271
(1962)) at 276; exhibit 18, tab C at 276-77; exhibit D at 324; Tr. 52-53, 61, 154.
OMS is diagnosed upon the presentation of a patient with various
prodromal 4 symptoms with irritability being the most common. Neurologic
symptoms of ataxia, falling, and myoclonus are most often experienced with
behavioral problems becoming more prevalent. OMS is commonly misdiagnosed
as acute cerebellitis. Exhibit J (Elizabeth D. Tate, Neuroepidemiologic Trends in
105 US Cases of Pediatric Opsoclonus-Myoclonus Syndrome, 22 J. of Pediatr.
Oncol. Nurs., 8 (2005)) at 10.
B. Expert Qualifications
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
3
A neuroblastoma is a sarcoma consisting of malignant neuroblasts, usually arising in the
autonomic nervous system or in the adrenal medulla. It is considered a type of neuroepithelial
tumor and affects mostly infants and children up to 10 years of age. Dorland’s Illus. Med.
Dictionary at 1263 (32d ed. 2012).
4
A prodrome is a premonitory symptom or precursor; a symptom indicating the onset of
a disease. Dorland’s at 1522.
3
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.
C. A.F.’s Medical History
A.F. was born on July 15, 2009, and developed normally for the first year.
See generally exhibit 5 at 1-24. At his one-year child health check on July 14,
2010, A.F. received the PCV vaccine. Id. at 23.
A few weeks later, on August 11, 2010, A.F. was seen by pediatrician
Meredith Saillant presenting with a carbuncle5 that she eventually diagnosed as
“furuncle of face.”6 Id. at 25. In Dr. Lancaster’s opinion, the presence of the
furuncle within a month before onset of OMS was a better temporal fit for an
“autoimmune encephalitis after immune stimuli” as the mechanism of A.F.’s OMS
than the PCV vaccination. Tr. 147. Dr. Weig disagreed, stating that between the
furuncle and vaccine, the vaccine more likely than not triggered the OMS. Tr. 156.
5
A carbuncle is a necrotizing infection of skin and subcutaneous tissue composed of a
cluster of boils (furuncles), usually due to Staphylococcus aureus, with multiple formed or
incipient drainage sinuses. Dorland’s, at 289; Tr. 146, 169.
6
A furuncle is a painful nodule formed in the skin by circumscribed inflammation of the
dermis and subcutaneous tissue after staphylococci enter through the hair follicles. Dorland’s, at
751; Tr. 146, 169.
4
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. Id. at 9-10.
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. Id. at 282. The doctor’s neurologic exam was
normal, noting that A.F. was “[f]ussy with exam but consolable.” Id. at 283. A
consultation with a neurologist was arranged. Id. at 284-86.
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).” Id.
at 289. Dr. Coulter concluded that the neurologic exam was normal with follow up
suggested in two weeks. Id.
5
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.” Id. She confirmed the
diagnosis of ataxia and expressed her concerns for closer neurological evaluation
and an MRI with Dr. Coulter, scheduling an appointment for the following day.
Id. at 26-27.
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. Id. at 280-82. Five days later, on September 6, 2010, A.F. was taken
back to the emergency room due to concerns that he was “losing motor skills.” Id.
at 262. He was admitted for further evaluation. Id. at 264.
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 MIBG7 scanning. Exhibit 6 at 259. There was no evidence
of a neuroblastoma. Id., Tr. 95-96, 160. The notes from Dr. Gorman summarized
A.F.’s medical history including his receipt of the PCV vaccine. Dr. Gorman
7
An MIBG scintiscan is a type of imaging test. It uses a radioactive substance (called a
tracer) and a scanner to find or confirm the presence of pheochromocytoma and neuroblastoma.
These are types of tumors that affect nerve tissue. “MIBG scintiscan,” A.D.A.M. Medical
Encyclopedia, (June 21, 2016, 10:45 AM),
https://www.nlm.nih.gov/medlineplus/ency/article/003830.htm.
6
stated developmental changes began “[o]n 8/28.” Exhibit 6 at 247. Dr. Gorman
confirmed the OMS diagnosis, stating “[t]he presentation is [entirely] consistent
with OMS and meets 2004 Genoa criteria for the diagnosis.” Id. at 249; see
generally exhibit 18, tab C. Dr. Gorman recommended immunosuppressive
therapy. Exhibit 6 at 250.
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.” Id. at 119.
II. Procedural History
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. Id. at 13.
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
7
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. Id. at 5.
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.” Id. at 6-7.
K.O. asserted that the proposed instructions were in conflict with Federal Rules of
Civil Procedure (“FRCP”) 26(a)(2)(B) and the role of a special master as outlined
in Vaccine Rule 3(b)(2) because they would lead to a “more rigid, less flexible,
and more adversarial process” contrary to Congress’s intent. Id. at 9-10. K.O. also
made a general objection to the fairness of the proposed instructions as they
applied to petitioners. Id. at 10-11.
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
8
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. See generally Pet’r’s Renewed Opp., filed July 16,
2014. K.O. also introduced specific objections to the instructions. Id. at 10-12.
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.
9
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; see also order, issued Apr. 6, 2015.
K.O. filed her pre-hearing brief on June 24, 2015. In an order issued June 29,
2015, the undersigned reiterated that the reports of the experts, upon careful
review, would constitute direct testimony due to any oral direct testimony likely
being duplicative. The undersigned allowed K.O. to submit a supplemental
statement identifying the portions of Dr. Weig’s opinion that she believed should
be presented orally due to her requests for oral presentation. The Secretary was
also afforded the opportunity to submit a responsive supplemental statement from
Dr. Lancaster.
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.
10
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.
11
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.
III. Standards for 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.” Moberly v. Sec’y of
Health & Human Servs., 592 F.3d 1315, 1322 n.2 (Fed. Cir. 2010) (citations
omitted). Proof of medical certainty is not required. Bunting v. Sec’y of Health
&Human Servs., 931 F.2d 867, 873 (Fed. Cir. 1991).
Distinguishing between “preponderant evidence” and “medical certainty” is
important because a special master should not impose an evidentiary burden that is
too high. Andreu v. Sec’y of Health & Human Servs., 569 F.3d 1367, 1379-80
(Fed. Cir. 2009) (reversing special master’s decision that petitioners were not
entitled to compensation); see also Lampe v. Sec’y of Health & Human Servs.,
219F.3d 1357 (Fed. Cir. 2000); Hodges v. Sec’y of Health & Human Servs., 9 F.3d
958, 961 (Fed. Cir. 1993) (disagreeing with dissenting judge’s contention that the
special master confused preponderance of the evidence with medical certainty).
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.” Althen v. Sec’y of Health
& Human Servs., 418 F.3d 1274, 1278 (Fed. Cir. 2005).
12
IV. Analysis
As mentioned in the introduction of this decision, K.O.’s case fails to be
persuasive with respect to two of the Althen prongs. First, K.O. has not presented
evidence of sufficient quantity or quality that supports a finding that molecular
mimicry is a reliable mechanism persuasively explaining how the PCV vaccine can
cause OMS. This shortcoming is addressed in section A below.
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 (Althen prong
1) or an acceptable temporal relationship (Althen prong three) resolves her case.
Because either finding is dispositive, the analysis of the remaining Althen prong (a
logical sequence of cause an effect) is relatively short. See section C. Finally,
section D considers a potential cause for A.F.’s OMS that is unrelated to the PCV
vaccine.
A. Theory
K.O.’s burden is to present “a medical theory causally connecting the
vaccination and the injury.” Althen, 418 F.3d 1274, 1278.
13
1. K.O. must prove causation by a preponderance of the evidence.
To establish the first prong of Althen, K.O. must provide “a reliable medical
or scientific explanation.” La Londe v. Sec’y of Health & Human Servs., 110 Fed.
Cl. 184, 201 (2013), aff’d sub nom. LaLonde v. Sec’y of Health & Human Servs.,
746 F.3d 1334, 1339-40 (Fed. Cir. 2014). A special master may require additional
evidence supporting a theory of molecular mimicry to find that the theory is related
to the petitioner. W.C. v. Sec’y of Health & Human Servs., 704 F.3d 1352, 1360
(Fed. Cir. 2013); Hunt v. Sec’y of Health & Human Servs., 123 Fed. Cl. 509, 524-
25 (2015) (special master properly followed W.C. and was not arbitrary in finding
molecular mimicry not persuasive); Crutchfield v. Sec’y of Health & Human
Servs., 125 Fed. Cl. 251, 263 (2014) (special master was not arbitrary in finding
that the petitioner’s expert failed to demonstrate any similarities between the
vaccine and a relevant part of the body).
2. Evidence relating to theory
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. 8 These topics are explored below.
a. Literature
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); Moriarty, 2016 WL 1358616 at *9-10. An assessment of
these articles is consistent with Terran’s endorsement of the flexible Daubert test,
which authorizes special masters to consider, among other factors, whether an
8
Some of this evidence originated with the Secretary because the Secretary “is permitted
to offer evidence to demonstrate the inadequacy of the petitioner's evidence on a requisite
element of the petitioner's case-in-chief.” Bazan v. Sec’y of Health & Human Servs., 539 F.3d
1347, 1353 (Fed. Cir. 2008).
14
expert’s opinion appears in peer review literature and whether the opinion has been
tested. Terran v. Sec’y of Health & Human Servs., 195 F.3d 1302, 1316 (Fed. Cir.
1999), citing Daubert v. Merrell Dow Pharmaceuticals, 509 U.S. 579, 593-94
(1993).
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, Preface, (3d ed.
2011). The guidance from the Federal Judicial Center translates to the Vaccine
Program because the burden of proof in an off-Table case, like K.O.’s case, is “the
traditional tort standard.” Moberly, 592 F.3d at 1322.
1) Epidemiology
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, Reference Guide on
Epidemiology, 549 n.2 (3d ed. 2011) (citing cases). “Epidemiologic evidence
identifies agents that are associated with an increased risk of disease in groups of
individuals, quantifies the amount of excess disease that is associated with an
agent, and provides a profile of the type of individual who is likely to contract a
disease after being exposed to an agent.” Id. at 552. The authors of this guide
from the Federal Judicial Center emphasize that “an association is not equivalent to
causation.” Id. “In evaluating epidemiologic evidence, the key questions, then, are
the extent to which a study’s limitations compromise its findings and permit
inferences about causation.” Id. at 553.
Consistent with the instruction from the Federal Judicial Center, the Federal
Circuit has long endorsed special masters’ consideration of epidemiologic
evidence. W.C., 704 F.3d at 1361; Grant v. Sec’y of Health & Human Servs., 956
F.2d 1144, 1149 (Fed. Cir. 1992) (“epidemiological studies are probative evidence
relevant to causation”). However, special masters may not go so far as to require
petitioners in off-Table cases to present epidemiologic evidence to establish that a
15
particular vaccine can cause a particular injury. Capizzano v. Sec’y of Health &
Human Servs., 440 F.3d 1317, 1325 (Fed. Cir. 2006).9
Here, the record contains one epidemiologic study. Exhibit K (Hung Fu
Tseng et al., Postlicensure surveillance for pre-specified adverse events following
the 13-valent pneumococcal vaccine in children, 31 Vaccine 2578 (2013)). The
researchers relied upon information held in the Vaccine Safety Datalink.10 The
authors compared the number of adverse events following approximately 600,000
doses of the PCV-13 vaccine with the number of adverse events following
administration of PCV-7. After reviewing medical records, the researchers found
that PCV-13 was not associated with an increased risk of encephalopathy. Id. at
2580.
In their reports, first Dr. Lancaster and then Dr. Weig commented on the
Tseng study. 11 Based on Tseng, Dr. Lancaster concluded that the “medical
literature therefore does not support any association between PCV13 and OMS.”
Exhibit A at 10. Dr. Weig challenged Dr. Lancaster’s reliance on the Tseng study.
Dr. Weig’s starting points were that the incidence of OMS is approximately one
case per five million children and that the non-neuroblastoma incidence is
approximately one case per ten million children. From here, Dr. Weig argued: “In
a sample size of 500,000, we would only expect to see .1 child (1/10 of a child)
with OMS. Given the incredibly low incidence rate of OMS, the sample size of
[the] Tseng study is underpowered to detect even one incidence of OMS.” Exhibit
20 at 2.
9
If a petitioner presented reliable epidemiologic evidence that a vaccine is associated
with a statistically significant increased risk of developing a disease, the Secretary would likely
agree to resolve the case. See National Injury Compensation Program: Revisions to the Vaccine
Injury Table, 80 Fed. Reg. 45132-01 (proposed July 29, 2015) (to be codified at 42 C.F.R.
§ 100.3) (discussing epidemiological studies supporting modifications to the list of injuries
presumptively caused by vaccines).
10
For more information regarding the Vaccine Safety Datalink, see Parsley v. Sec’y of
Health & Human Servs., No. 08-781V, 2011 WL 2463539, at *10 n.33 (Fed. Cl. Spec. Mstr.
May 27, 2011); Werderitsh v. Secʼy of Health & Human Servs., No. 99-319V, 2005 WL
3320041 (Fed. Cl. Spec. Mstr. Nov. 10, 2005) (denying motion for production of documents).
11
Dr. Weig has no training or experience in epidemiology. Tr. 12. Dr. Lancaster has
taken one course on epidemiology and biostatistics while obtaining his medical degree. Tr. 103.
16
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. Pafford v. Sec’y of Health & Human Servs., 451 F.3d
1352, 1355 (Fed. Cir. 2006). In finding no increased risk of OMS after PCV-13,
the Tseng study does not help K.O. meet her burden. Whether the Tseng study
would be a reliable basis for an opinion that PCV vaccinations cannot cause OMS
is another question and a question that is not germane to this case’s outcome. The
Secretary does not bear the burden of establishing that it is impossible for PCV
vaccinations to cause OMS.
2) Case Reports
Unlike Tseng, which the Secretary’s expert introduced, K.O. relied upon a
set of four case reports. See Pet’r’s Preh’g Br. at 14, 20; Pet’r’s Posth’g Br. at 25-
28; Pet’r’s Resp. at 9-10. In her view, “case reports . . . supplement and bolster her
other evidence of causation.” Pet’r’s Resp. at 10.
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,
Reference Guide on Statistics, at 218. These authors also state “some courts have
suggested that attempts to infer causation from anecdotal reports are inadmissible
as unsound methodology under Daubert.” Id. at 217 n. 14 (citing cases).
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. Porter v. Sec’y of
Health & Human Servs., No. 99–639, 2008 WL 4483740, at *13 (Fed. Cl. Spec.
Mstr. Oct. 2, 2008). Under the caption of a different case, a judge at the Court of
Federal Claims disagreed with this weighing of evidence. Rotoli v. Sec’y of
Health & Human Servs., 89 Fed. Cl. 71, 86-87 (2009).
17
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.” Porter v. Sec’y of Health & Human Servs., 663 F.3d 1242, 1253 (Fed.
Cir. 2012). The Federal Circuit also stated that the “decision reveals a thorough
and careful evaluation of all the evidence including ... medical literature.” Id. at
1254. Admittedly, the discourse on case reports in Porter is indirect and there may
come a time when the Federal Circuit addresses the evidentiary value of case
reports in the Vaccine Program more directly. Until that future Federal Circuit
case, the undersigned relies upon Porter, which endorsed a view that single case
studies did not contain any meaningful analysis of causation.
It is interesting to juxtapose case reports with epidemiologic studies. Case
reports are generally seen as holding less evidentiary value than epidemiologic
studies. Campbell v. Sec’y of Health & Human Servs., 97 Fed. Cl. 660, 668
(2011).12 Here, what is more useful — an observational study involving more than
a half million people or a handful of anecdotes? As discussed above, K.O. and Dr.
Weig present an insightful criticism of the Tseng study: it was not sufficiently
powered to detect increases in OMS. Yet, with regard to the case reports, K.O. and
Dr. Weig have not presented any persuasive argument why the case reports rise
even to the level of circumstantial indicia of causation. Tr. 44-45; exhibit 18. As
the Court of Appeals for the Eleventh Circuit stated, case reports “do not offer the
underlying toxicological data in a scientifically reliable form to satisfy Daubert.”
McClain v. Metabolife Int’l, Inc., 401 F.3d 1233, 1253-54 (11th Cir. 2005).
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, Myoclonic encephalopathy of infants: A
report of two cases and observations on related disorders, 21 Arch Neurol. 229
(1969)); Exhibit 18, tab N (James McCarthy & James Filiano, Opsoclonus
myoclonus after human papilloma virus vaccine in a pediatric patient, 15
Parkinsonism and Related Disorders 792 (2009)); Exhibit 18, tab M (F. Lapenna et
12
Although Campbell recognized that case reports have less value, Campbell continued:
“Nevertheless, the fact that case reports can by their nature only present indicia of causation does
not deprive them of all evidentiary weight. See, e.g., Rotoli, 89 Fed. Cl. 86-87.” After Campbell
was issued, the Federal Circuit reversed Rotoli. Porter, 663 F.3d at 1245.
18
al., Post-vaccinic opsoclonus- myoclonus syndrome: a case report, 6 Parkinsonism
and Related Disorders 241 (2000)).
An expert may “extrapolate from existing data,” Snyder v. Sec’y of Health
& Human Servs., 88 Fed. Cl. 706, 743 (2009), and use “circumstantial evidence,”
Althen, 418 F.3d at 1280. But, the reasons for the extrapolation should be
transparent and persuasive. Here, Dr. Weig did not offer any persuasive reasons
for extrapolating from the rubella vaccine, HPV vaccine, DTP vaccine, and polio
vaccine, to the PCV vaccine.
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. See Whitecotton v. Sec’y of Health &
Human Servs., 81 F.3d 1099, 1108 (Fed. Cir. 1996) (“Congress desired the special
masters to have very wide discretion with respect to the evidence they would
consider and the weight to be assigned that evidence”). They are not a reliable
basis for finding causation. Consequently, the evidence relating to the reliability of
the theory of molecular mimicry will be explored in detail. The following three
sections (the Pranzatelli article, homology, and Dr. Lancaster’s admission) concern
molecular mimicry.
b. Pranzatelli article
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, The immunopharmacology of the opsoclonus-myoclonus syndrome,
19 Clin. Neuropharmacology 1 (1996)).
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.” Id. at 22.13 Dr. Pranzatelli returns to molecular
mimicry in his conclusion. “A peripheral induction mechanism involving
13
K.O. frequently cited these pages of the Pranzatelli article. Pet’r’s Preh’g Br., filed
July 9, 2015, at 12, 19; Pet’r’s Posth’g Br. at 19; Pet’r’s Posth’g Resp. at 8; see also Tr. 25.
19
molecular mimicry or one of several other possible mechanisms leads to immune
system dysregulation, which transiently allows otherwise for hidden
autoaggression against cross-reactive brain antigens. Although immunizations are
logical candidates for costimulation in peripheral induction in children, if there is
an adult counterpart, it is unknown.” Id. at 36. Dr. Weig interpreted this passage
as indicating that Dr. Pranzatelli was “certainly… open to the idea of immunization
as a potential initiating factor in children.” Tr. 26.
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.” Id. at 18-19. Dr. Weig understood Dr. Pranzatelli as
wanting to avoid the logical pitfall known as “post hoc ergo propter hoc.” In other
words, it is wrong to conclude that because a second event occurs after a first
event, the first event caused the second event. Tr. 60. In his article, Dr. Pranzatelli
recommended an epidemiologic study. Exhibit 18, tab G at 19.
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. Id. at 4. Specifically on vaccinations, he states that
molecular mimicry is a “possible mechanism.” Id. at 21, 36.
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
20
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.
c. Homology
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. Dorland’s at 868.
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., Post-streptococcal opsoclonus-
myoclonus syndrome associated with anti-neuroleukin antibodies, J. Neurol.
Neurosurgery Psychiatry 507 (2006)) at 509; see also Wirt v. Secʼy of Health &
Human Servs., No. 11-118V, 2014 WL 1911421, *8 (Fed. Cl. Spec. Mstr. April
18, 2014). The article cites to a website maintained by the National Institutes of
Health.
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. Terran, 195 F.3d at 1316, citing Daubert, 509 U.S. at 593-94. Here,
Dr. Weig is assuming that there is homology between the PCV vaccine and brain
21
tissue. However, Dr. Weig lacks a background to determine the accuracy of his
assumption. This lack of testing constitutes a reason for finding Dr. Weig
unpersuasive. See Caves v. Sec’y of Health & Human Servs., 100 Fed. Cl. 119,
135 (2011) (“Without any empirical evidence that the theory [of molecular
mimicry] actually applies to the influenza vaccine and [transverse myelitis], the
first prong of Althen would be rendered meaningless”), aff’d without opinion, 463
F. App’x 932 (Fed. Cir. 2012).
d. Admission by Dr. Lancaster
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. See Dorland’s at 1263 (defining neuroblast and neuroblastoma),
1668 (defining sarcoma). Neuroblastomas are found in approximately 50 percent
of OMS cases.
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.
22
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. Id. at 16 (“Response to Viruses”), 19-22.
Thus, Dr. Pranzatelli’s article can accommodate molecular mimicry for
neuroblastomas and some other theory for infectious agents.
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. See Tr. 51 (Dr. Weig). That step is relatively short. In
contrast, the PCV vaccine does not contain nerve cells. Thus, an attempt to join
the PCV vaccine and brain cells affected in OMS requires a much longer jump. 14
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.
14
K.O. could have shortened the gap between the PCV vaccine and brain cells by
presenting evidence that they are homologous. However, as discussed above, K.O. did not
narrow the gap.
23
e. Admission by the Secretary
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. See Demodulation, Inc. v. United States, 103 Fed.
Cl. 794, 808 (2012). As attorneys experienced in the Vaccine Program, K.O.’s
counsel should have known that raising an argument this late is improper.
More significantly, settlements are not considered admissions that can be
used to establish a fact based upon a settlement. See Woods v. Sec’y of Health &
Human Servs., 105 Fed. Cl. 148, (2012) (settlement of cases cannot equate to the
finding of reasonable basis); R.V. and E.V. v. Secʼy of Health & Human Servs.,
No. 08-504V, 2015 WL 1396357 (Fed. Cl. Spec. Mstr. March 6, 2015) (rejecting
argument that the Secretary was judicially estopped from litigating an argument
based upon a settlement of another case), mot. for rev. denied, 127 Fed. Cl. 136(2016). Thus, the resolution of other cases involving OMS does not meaningfully
change the analysis of the evidence K.O. and the Secretary presented in this case.
f. Synopsis
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 Althen prong one.
B. Timing
K.O. must establish a “proximate temporal relationship” between the PCV
vaccination and the onset of A.F.’s opsoclonus myoclonus. Bazan, 539 F.3d at
1352. This formulation implies that the third prong from Althen actually contains
two parts. First, there must be a showing that a range of time is “acceptable” to
infer causation. Second, there must be a showing that the vaccinee’s disease arose
in this acceptable time. Shapiro v. Sec’y of Health & Human Servs., 101 Fed. Cl.
532, 542-43 (2011), recons. denied after remand on other grounds, 105 Fed. Cl.
353 (2012), aff’d per curiam, 503 F. App’x 952 (Fed. Cir. 2013).
24
1. Medically Acceptable Interval
The first part of the third prong of Althen requires K.O. to show a time
which is “medically acceptable” for an injury to appear after a vaccination,
assuming that the vaccination caused the injury. Bazan 539 F.3d at 1352.
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, Adverse Events of Vaccines Evidence and
Causality (Kathleen Stratton et al. eds. (2011))) at 535; exhibit P (Institute of
Medicine, Adverse Events of Vaccines Evidence and Causality (Kathleen Stratton
et al. eds. (1994))) at 26.
Therefore, to establish the third prong of Althen, K.O. must establish that
A.F.’s OMS developed within 42 days of his PCV 13 vaccination.15
15
Although a finding of 42 days (and not 43) may appear arbitrary, the persuasive
evidence does not go further than 42 days. “At the margins of any judgment call, reasonable
minds may differ as to the judgment reached. Such is the natural consequence of regulatory line-
drawing, much as the natural consequence of judicial line-drawing will permit of marginal
dispute. But that is not to say that the line-drawing exercise lacks reason or is arbitrary.” Haggar
Apparel Co. v. United States, 222 F.3d 1337, 1342 (Fed. Cir. 2000).
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2. Onset of OMS
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).16
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. Id. K.O. recalled that in “late August
2010” A.F. experienced difficulty sleeping and sensitivity to light. Exhibit 13 ¶ 3.
She stated on August 25, 2010, A.F. was constipated but this improved with after
giving him prune juice. Id. at ¶4.
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; see also Tr. 18. Dr. Weig
agreed that A.F. was constipated, but contended that the degree of irritability
described made it prodromal. Tr. 39-40. K.O. did not address the constipation
otherwise.
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
16
This difference of three days is significant because it changes the onset from 42 to 45
days, which then falls outside of the accepted range as established by the IOM report.
26
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 (see Pet’r’s Posth’g Br. at 37), the
timing for A.F. does not work. See Bazan, 539 F.3d 1352 (a petitioner fails to
satisfy the third prong of Althen when too much time elapses between vaccination
and onset).
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C. Logical Sequence of Cause and Effect
The remaining prong from Althen is “a logical sequence of cause and effect
showing that the vaccination was the reason for the injury.” Althen, 418 F.3d at
1278. Evidence particularly relevant to this inquiry is the view of any treating
doctor. Capizzano, 440 F.3d at 1326.
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.
Dobrydnev v. Sec’y of Health & Human Servs., 566 F. App’x 976, 992-83, reh’g
denied, (Fed. Cir. 2014), cert. denied, 135 S. Ct. 1560, 191 L. Ed. 2d 639 (2015).
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. See Paterek v. Sec’y of Health
& Human Servs., 527 F. App’x 875 (Fed. Cir. 2013) (indicating that a treating
doctor’s statement that vaccine-causation was “not impossible” does not establish
causation).
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
28
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.
D. Alternate Causes
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. See
Doe 11 v. Sec’y of Health & Human Servs., 601 F.3d 1349, 1358 (Fed. Cir. 2010);
Contreras v. Sec’y of Health & Human Servs., 107 Fed. Cl. 280, 296 (2012), mot.
for rev. granted after remand, 116 Fed. Cl. 472 (2014), mot. for rev. denied after
third remand, 121 Fed. Cl. 230 (2015), appeal docketed, No. 15-5097 (Fed. Cir.
June 15, 2015).
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 Althen prongs,
the Secretary cannot rely upon an idiopathic cause to defeat the claim for
compensation. Pet’r’s Posth’g Br. at 42-43, citing Knudsen v. Sec’y of Health &
Human Servs., 35 F.3d 543, 547-48 (Fed. Cir. 1994). However, the predicate of
this argument — that K.O. established the three Althen prongs with preponderant
evidence — is not correct for the reasons explained above. Therefore, the burden
of proof did not shift to the Secretary. LaLonde, 746 F.3d at 1340.
To the extent that the presence of potential alternative causes bears on the
petitioner’s burden regarding Althen prong two, K.O. errs when she states
“respondent has offered no evidence of an alternative cause leading to the onset of
A.F.’s OMS.” Pet’r’s Reply at 19 (emphasis in original). As just mentioned, Dr.
Lancaster proposed that the furuncle was a more likely cause than the vaccination.
Thus, it is not correct to say the Secretary has “no evidence.” Similarly, K.O.
argues “Respondent’s ‘ranking’ of the potential causes from most likely to least
likely as 1) idiopathic, 2) skin infection and 3) PCV vaccine is baseless.” Pet’r’s
29
Reply at 20. The Secretary’s argument is not “baseless” because it is based on Dr.
Lancaster’s opinion.
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.17 The case law seems to be heading in the opposite
direction. See Stone v. Sec’y of Health & Human Servs., 676 F.3d 1373, 1380
(Fed. Cir. 2012) (causation cannot be evaluated without addressing the “elephant in
the room” of evidence indicating a separate cause for the injury). Once the
argument about relevancy is passed, K.O. says nothing about the furuncle. She
cannot challenge the fact that A.F. had a furuncle on August 11, 2010, which is 17
days before August 28, 2010.
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. See Caves, 100 Fed. Cl. at 140-41. The second problem with K.O.’s case is
17
Knudsen’s comments arose in a case in which the petitioners had established their child
suffered an on-Table injury, meaning the petitioners were presumptively entitled to
compensation. Here, K.O. has not met her burden of proof.
30
that the timing between A.F.’s vaccination and the onset of OMS is not a match.
The timing problem is also completely independent of the furuncle. Thus, the
outcome of K.O.’s case would be the same regardless of whether Dr. Lancaster had
mentioned the furuncle. Overall, K.O.’s case is not persuasive.
V. Conclusion
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.
IT IS SO ORDERED.
s/Christian J. Moran
Christian J. Moran
Special Master
31