                  In the United States Court of Federal Claims
                                                  No. 15-1333V

                                 (Filed Under Seal: December 28, 2018)
                                      (Reissued: January 15, 2019) 1

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                                    *
MARSHA DOUGHERTY,                   *
                                    *
                    Petitioner,     *                           National Childhood Vaccine Injury Act;
                                    *                           Review of Special Master’s Decision
v.                                  *                           Denying     Relief   for    Narcolepsy;
                                    *                           Application of Althen Test; Assessment
SECRETARY OF HEALTH                 *                           of     Expert       Testimony      and
AND HUMAN SERVICES,                 *                           Epidemiological Studies.
                                    *
                     Respondent.    *
                                    *
*************************************

David P. Murphy, David P. Murphy & Associates, P.C., Greenfield, Indiana, for Petitioner.

Voris E. Johnson, Jr., with whom were Chad A. Readler, Acting Assistant Attorney
General, C. Salvatore D’Alessio, Acting Director, Torts Branch, Civil Division, Catharine
E. Reeves, Deputy Director, Torts Branch, Civil Division, Gabrielle M. Fielding, Assistant
Director, Torts Branch, Civil Division, U.S. Department of Justice, Washington, D.C. for
Respondent.

                                           OPINION AND ORDER

WHEELER, Judge.

       This vaccine case is before the Court on Petitioner’s Motion for Review of the
Special Master’s July 5, 2018 decision denying compensation and dismissing the petition
due to insufficient proof. Dougherty v. Sec’y of Health & Human Servs., No. 15-1333V,


1
 Pursuant to Rule 18(b) of the Court’s Vaccine Rules, this opinion and order was initially filed under seal. As required
under the Rules, each party was afforded 14 days from the date of issue, until January 11, 2019, to object to the public
disclosure of any information furnished by that party. Neither party submitted any proposed redactions. The only
changes to the original opinion and order are the addition of keywords and correction of minor typographical errors.
2018 WL 3989519 (Fed. Cl. Spec. Mstr. July 5, 2018). For the reasons explained below,
the Court affirms the Special Master’s dismissal decision.

       On November 6, 2015, Marsha Dougherty (“Petitioner”) filed a petition with this
Court under the National Vaccine Injury Compensation Program, 42 U.S.C. §§ 300aa-1—
34 (“Vaccine Act”). She seeks compensation for the narcolepsy with cataplexy2 she claims
to have developed as a result of a Fluzone influenza vaccine she received on November 7,
2012. In March 2016, Respondent filed the requisite Rule 4(c) Report, arguing that
Petitioner had not met her burden of proof to show a causal connection between the flu
vaccination and her narcolepsy. Dkt. No. 20. Petitioner and Respondent both filed expert
reports and medical literature supporting their positions. An entitlement hearing before the
Special Master was held on November 30 and December 1, 2017. On July 5, 2018, the
Special Master issued her Decision denying compensation.

                                                   Background 3

       Petitioner’s medical history prior to receiving the flu vaccine included complaints
of abdominal pain, migraines, anxiety, hypertension, and neck pain. She had neck and
spine surgery following an all-terrain vehicle accident in October 2008. On November 7,
2012, the day she received her flu vaccination, she was seeing her primary care physician,
Dr. Neumann, for help with neck pain, anxiety, and hypertension. On December 4, 2012,
Petitioner again visited Dr. Neumann’s office complaining of increasing fatigue, having
difficulty staying awake at times during the day. Her medications were adjusted. In a
follow-up visit to Dr. Neumann on January 11, 2013, she reported continuing fatigue, and
that she had pulled over while driving due to drowsiness. Dr. Neumann ordered a sleep
study and again adjusted her medications. The sleep study performed on January 29, 2013,
revealed “moderate mild to moderate obstructive sleep apnea (OSA).”

       In April 2013, Petitioner made a follow-up visit to Dr. Neumann, who noted that
Petitioner’s migraines had not improved, and that she continued to have a lot of stress at
home due to her living situation. Petitioner visited Dr. Neumann again on August 29, 2013,
to discuss her experience while driving the day before when she passed out. She also
reported that she had been having “staring episodes,” noted by Dr. Neumann to be loss of
consciousness and seizure. Dr. Neumann recommended she restrict driving.

      Dr. Neumann referred Petitioner to a neurologist, Dr. Hemelt, whom Petitioner saw
on September 10, 2013. The neurologist’s notes show that Petitioner reported an episode

2
  Narcolepsy is described as “a chronic neurological disorder that affects the brain’s ability to control sleep-wake
cycles.” Cataplexy is a “sudden loss of muscle tone” while awake, which results in a loss of voluntary muscle control.
Narcolepsy Fact Sheet, National Institutes of Health, National Institute of Neurological Disorders and Stroke,
https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Narcolepsy-Fact-Sheet.
3
    Facts are drawn from the Special Master’s Decision.

                                                          2
of losing consciousness while driving and waking up to find her car in a ditch. Her husband
described times when Petitioner acted “differently,” and sometimes confused. Dr. Hemelt
noted that Petitioner’s awareness problems were likely due to disordered sleep and maybe
medication. She also wrote that the sleep problems could be caused by snoring and sleep
apnea, perhaps combined with narcolepsy. She recommended further tests, medication
adjustment, and continued driving restriction.

       Two days after seeing Dr. Hemelt, Petitioner went to the emergency room at her
local hospital because she had had two “trancelike seizures.” She was discharged the same
day, and the ER physician recommended that she expedite her further neurological tests.
The next day Petitioner had another sleep study, again showing sleep apnea. A day later
Petitioner underwent a multiple sleep latency test, which is used to diagnose narcolepsy.
The test results were seen as consistent with narcolepsy, and Dr. Hemelt prescribed
medication in light of that diagnosis. On September 30, 2013, Petitioner visited her
primary care doctor, Dr. Neumann, who noted her recent diagnosis of narcolepsy and also
observed that Petitioner told him she had done some research and found a link between the
flu vaccine she had received and narcolepsy. At that time he noted that he had not heard
of this connection before (although he later wrote two letters on Petitioner’s behalf
supporting her claim of a link between her flu vaccination and her narcolepsy). Two weeks
later Petitioner visited Dr. Hemelt, whose notes also show that Petitioner spoke of a link
with her flu vaccination. Dr. Hemelt noted that she was not aware of this association.

          During the next years Petitioner continued treatment for narcolepsy and in March
2015, also began treatment for sleep apnea, starting use of a Continuous Positive Airway
Pressure (CPAP) machine at night to help her breathing. In April 2015, she reported to her
neurologist that the CPAP treatment for sleep apnea improved her symptoms of fatigue and
sleepiness. However, she continued to suffer the effects of daytime sleepiness and was
unable to work. Petitioner had a genetic test in December 2016, which showed she carries
the gene associated with narcolepsy. In August 2017, she was granted Social Security
disability benefits due to her diagnosis of narcolepsy with cataplexy.

                                   Evidence Presented

Petitioner’s Expert

         Petitioner’s expert, Dr. Marcel Kinsbourne, received his medical degree at Oxford
University in the United Kingdom and is licensed in North Carolina, Massachusetts, and
Virginia. He is board certified in pediatrics. The Special Master noted that Dr. Kinsbourne
has had a long career in pediatrics and neurology starting in 1955, including serving on the
staff at several hospitals as well as holding academic positions in pediatrics, neurology,
and psychology in various universities. The Special Master observed that it has been
“many years since Dr. Kinsbourne has regularly seen patients.” Dougherty, 2018 WL
3989519 at *9. She stated further that while Dr. Kinsbourne is qualified as an expert in

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neurology, he does not claim expertise specifically in narcolepsy outside his testimony in
Vaccine Program cases.

        Dr. Kinsbourne submitted an initial expert opinion, Dkt. No. 36, and followed it
later with two supplemental reports. Kinsbourne Report, Dkt. Nos. 54 and 90. In his initial
report, Dr. Kinsbourne described significant increases in the rate of narcolepsy in Western
Europe and China after use of H1N1 vaccines, most frequently a formulation called
Pandemrix, during a 2008-2010 pandemic. While H1N1 vaccines are also used in the
United States under brands such as the Fluzone vaccine given to Petitioner, their
formulation is different, notably in the absence of the adjuvant which is in the Pandemrix
vaccines. Dr. Kinsbourne argued that flu vaccines themselves, with or without adjuvants,
initiate an autoimmune attack in genetically susceptible individuals. In his first Report, he
maintained that this autoimmune reaction is likely created by molecular mimicry which
causes the body to attack and diminish its own hypocretin receptors regulating
wakefulness, thereby causing narcolepsy. To support this theory, he cited a study known
as the De La Herrán-Arita article 4. He noted that the presence of adjuvants in a vaccine is
irrelevant under this theory. He concluded that Petitioner’s flu vaccination caused her
narcolepsy with cataplexy “to a reasonable degree of medical probability.”

Respondent’s Experts

       Dr. Thomas Scammell is a Professor of Neurology at Beth Israel Deaconess Medical
Center, Boston Children’s Hospital, and Harvard Medical School. He is board-certified in
neurology, psychiatry, and sleep medicine, and for the last twenty years, has practiced as a
neurologist, a clinical and basic researcher in sleep medicine, and a lecturer on narcolepsy
and the neurobiology of sleep and wakefulness. He also has authored over one hundred
publications, mostly focused on narcolepsy and sleep disorders, and is currently treating
about sixty patients with narcolepsy. Scammell CV, Dkt. No. 47-2. After reviewing
Petitioner’s medical records, Dr. Scammell expressed doubts about Petitioner’s diagnosis.
He also stated that he reviewed the medical literature relating to the Fluzone vaccine and
narcolepsy and found “little evidence that the Fluzone vaccine can cause narcolepsy.”
Scammell Report at 5, Dkt. No. 47-1. He pointed out that the association between H1N1
vaccines and narcolepsy has only been made for vaccines used outside the U.S., with
different formulations. Id. at 9. He emphasized that the De La Herrán-Arita study cited
by Dr. Kinsbourne to support a molecular mimicry theory had been retracted soon after
publication.

       Dr. Andrew MacGinnitie also provided an expert report on behalf of Respondent.
MacGinnitie Report, Dkt. No. 47-3. He is an attending physician and Clinical Director for
the Division of Immunology at Boston Children’s Hospital, and a Professor of Pediatrics
4
 Alberto K. De la Herrán-Arita et al., CD4+ T cell autoimmunity to hypocretin/orexin and cross-Reactivity to a
2009 H1N1 influenza A epitope in narcolepsy, 5 Sci. Translational Med. 1 (2013), Dkt. No. 50-BB (hereinafter De
La Herrán-Arita).

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at Harvard Medical School. He is board-certified in both allergy/immunology and
pediatrics. He sees “more than 1,500 patients” each year for a variety of immunologic
diseases, including reactions to vaccines. MacGinnitie CV, Dkt. No. 47-4. Dr.
MacGinnitie observed that there is “strong” epidemiological evidence linking narcolepsy
with the Pandemrix vaccine used outside the U.S. in 2009, but that this is likely related to
the adjuvant added to the Pandemrix. He noted that “[n]o increase in narcolepsy has been
observed in individuals receiving influenza vaccines not containing adjuvants.” He cited
epidemiological studies of a possible link between seasonal flu vaccines (including
Fluzone) and narcolepsy, including what is referred to as the Duffy study 5. MacGinnitie
Report at 8, Dkt No. 47-3. Those studies found no association with narcolepsy. He also
pointed out that the De la Herrán-Arita article cited by Dr. Kinsbourne to support his
molecular mimicry theory had been retracted.

Experts’ Responses

        Both Dr. Kinsbourne for Petitioner, and Dr. MacGinnitie for Respondent, filed
supplemental reports in response to expert reports in opposition. Dr. Kinsbourne’s second
Expert Report, Dkt. No. 54, was addressed to Dr. Scammell’s Report, and introduced a
different theory by which a non-adjuvanted H1N1 vaccine such as Fluzone could have
caused Petitioner’s narcolepsy. Dr. Kinsbourne described an autoimmune reaction caused
by the nucleoprotein in the influenza vaccine itself regardless of the presence of an
adjuvant. He did not specifically address the De La Herrán-Arita study which had been
retracted, but did offer literature to support this newly-presented theory, including the
Ahmed study (2015) 6. He concluded that even though this theory is “incomplete,” it is a
sufficient basis for “reasonable medical probability” that Petitioner’s vaccination caused
her narcolepsy.

        Dr. MacGinnitie, Respondent’s Expert, filed a response to Dr. Kinsbourne’s second
report, MacGinnitie Report, Dkt. No. 58-1. He described and then summarized the data in
Ahmed supporting a link between the vaccine nucleoprotein and narcolepsy as
“preliminary, resting on [a] single peer reviewed report that lacks appropriate controls and
does not provide evidence” that antibodies are involved in causing the disease. Id., at 4.
He repeated his opinion that Petitioner’s narcolepsy was not the result of vaccination.

       Dr. Kinsbourne filed a third Expert Report, Kinsbourne Supplementary Report, Dkt.
No. 90-1, in which he discussed the Duffy epidemiological study finding no link between
Fluzone and narcolepsy. This had been cited by both Dr. Scammell and Dr. MacGinnitie
to support their opinions. Dr. Kinsbourne pointed out that Duffy and colleagues limited

5
 Duffy, J. et al. Narcolepsy and influenza A(H1N1) pandemic 2009 vaccination in the United States. 83 Neurology
1823-30 (2014), Dkt. No. 50-Z.
6
  Ahmed SS, Volkmuth W, Duca J et al. Antibodies to influenza nucleoprotein cross-react with human hypocretin
receptor-2. 2 Sci Translational Med. 294ra105 (2015), Dkt. No. 51-LL.

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their study to an age range below 30, and since Petitioner was 44 years old at the time she
received the flu vaccine, Duffy “casts no light” on vaccine causation in her case. Id. at 2.
At the same time as the third Report was filed, Petitioner also submitted an expert report
by a new contributor, Dr. S. Stanley Young. Statement of October 24, 2017, Dkt. No. 89-
3. Dr. Young is an adjunct professor of statistics and biostatistics. He argued that flu
vaccines cause the body to make antibodies which can damage the brain and cause
narcolepsy in a person carrying the narcolepsy gene. He pointed out that this theory is
supported by the work of Ahmed and colleagues. He discounted the significance of the
Duffy study, claiming that study found it was neither the vaccine nor the adjuvant causing
narcolepsy, but did not posit a cause. He argued that the Ahmed studies, which came out
after Duffy, do show the cause: “antibodies to the nuclear protein, which is the current last
man standing.” Id. at 6.

        Dr. MacGinnitie then addressed both Dr. Kinsbourne’s third report and Dr. Young’s
report. MacGinnitie Third Expert Report, Dkt. No. 92-1. He observed that Ahmed’s work
does not show how the antibodies described cause brain damage leading to narcolepsy. He
stated that while adjuvant may not be “sufficient by itself to cause narcolepsy, it does not
change the fact that adjuvant is required.” Id. at 1. And he defended the Duffy study:
“Duffy remains strong evidence against a relation between non-adjuvanted vaccination and
narcolepsy.” Id. at 2.

      The Special Master held an evidentiary hearing on November 30 and December 1,
2017, at which time she heard testimony from Petitioner and her family regarding her
diagnosis, as well as from some of the parties’ experts. She issued her opinion denying
compensation on July 5, 2018.


                                      Burden of Proof

       Petitioner seeks recovery in this case for an “off-Table” injury, that is, an injury
caused by a vaccine other than those injuries listed on the Vaccine Injury Table, 42 U.S.C.
§ 300aa-14(a). In off-Table injuries, claimants must show causation in fact by a
preponderance of the evidence. 42 U.S.C. §§ 300aa-11(c)(1)(C)(ii), 300aa-13(a)(1)(A);
see also Moberly v. Sec’y of Health & Human Servs., 592 F.3d 1315, 1321 (Fed. Cir.
2010). The U.S. Court of Appeals for the Federal Circuit summarized the claimant’s
evidentiary burden associated with off-Table cases in Althen v. Sec’y of Health & Human
Servs., 418 F.3d 1274, 1278 (Fed. Cir. 2005), holding that the claimant must establish by
preponderant evidence:

       (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 proximate temporal relationship between vaccination and injury.

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These factors are now commonly referred to as the three Althen prongs.


                                   Special Master’s Decision

       The Special Master first found that Petitioner had established that she “more likely
than not” suffered from narcolepsy with cataplexy. She then turned to Althen Prong One
which requires proof of a medical theory showing the vaccination caused Petitioner’s
condition. She summarized the parties’ expert arguments, and found Respondent’s experts
more persuasive in their position that there is no reliable evidence showing that
nonadjuvanted flu vaccines such as Fluzone cause narcolepsy. She discussed two recent
cases, both decided by the same Special Master, addressing this issue: McCollum v. Sec’y
of Health & Human Servs., No. 14-790V, 2017 WL 5386613 (Fed. Cl. Spec. Mstr. Sept.
15, 2017), review denied, 135 Fed. Cl. 735 (2017), appeal docketed, No. 18-1623 (Fed.
Cir. 2018), and D’Tiole v. Sec’y of Health & Human Servs., No. 15-85, 2016 WL 7664475
(Fed. Cl. Spec. Mstr. Nov. 28, 2016), review denied, 123 Fed. Cl. 421 (2017), aff’d, 726
Fed.App’x. 809 (Fed. Cir. 2018).

        In D’Tiole, which involved FluMist, a vaccine similar to Fluzone, the Petitioner’s
expert made arguments akin to those presented in the instant case. The expert maintained
that the vaccine caused an autoimmune reaction through molecular mimicry, citing studies
of Pandemrix for support. Respondent’s experts, including Dr. MacGinnitie, focused on
the differences between Pandemrix and the vaccine at issue, as has been done in this case.
They also cited the Duffy study to show there is no connection between narcolepsy and the
flu vaccines used in the U.S. The Special Master in that case dismissed Petitioner’s claim,
finding that Petitioner had not shown a reliable theory applicable to FluMist.

       In McCollum, Dr. Kinsbourne also served as an expert for Petitioner and offered the
same causation theory he presented here. The Special Master in McCollum again
dismissed the claim, citing the Duffy study as “the sole relevant epidemiologic evidence
regarding . . . the flu vaccine administered in the U.S.” 2017 WL 5386613 at *17.

       In the instant case the Special Master determined that Petitioner’s experts were not
able to refute the arguments presented by Dr. Scammell and Dr. McGinnitie, and for that
reason found that Petitioner failed to satisfy her burden under Althen Prong One. As to
Prong Two, the Special Master noted that without a reasonable medical theory shown under
Prong One, an analysis of Prong Two is not very meaningful, but the Special Master
pointed out that Petitioner did not present any evidence supporting an autoimmune reaction
in her case. In sum, the claims of her expert were insufficient to “meet the preponderant
standard in the face of relevant and credible epidemiological studies, well-versed opposing
experts, and Petitioner’s reliance on a retracted article.” Dougherty, 2017 WL 3989519 at
*47.


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                                    Motion for Review

        Petitioner argued in her Motion for Review that the Special Master improperly
increased Petitioner’s burden of proof to show a causation theory. Dr. Kilbourne’s opinion,
that “a nucleoprotein in Fluzone caused Marsha, a genetically predisposed person, to
develop narcolepsy” should have been enough, since “[n]either the Act nor Althen requires
Marsha to identify the specific protein . . . .” Mot. for Review at 5, Dkt. No. 101. Rather,
all Petitioner need show is a “scientifically reasonable theory.” Id. In Petitioner’s second
objection to the Decision, she argued that the Special Master ignored an abstract from the
journal SLEEP, submitted by Petitioner in Dkt. No. 89-10. Petitioner maintained that this
article rebuts the conclusions of the Duffy article and provides “stronger proof” that
nonadjuvanted flu vaccines can cause narcolepsy. Id. at 8.

       Respondent answered Petitioner’s Motion by emphasizing Petitioner’s failure to
present adequate proof of her expert’s theory, a theory that had been deemed unpersuasive
in two recent Vaccine Program cases, D’Tiole and McCollum, as noted by the Special
Master in this case. Resp’t Resp. to Mot. for Review, Dkt. No. 105. With regard to
Petitioner’s claim that the Special Master ignored the SLEEP abstract, Respondent pointed
out that the abstract was filed as an attachment to Dr. Young’s Expert Report and only
briefly mentioned in his Report. In addition, Petitioner did not call Dr. Young to testify at
the evidentiary hearing and Dr. Kinsbourne did not mention this study at all. Further, it is
not clear whether this abstract was ever published, which can add to the significance of
studies.


                                    Standard of Review

       This Court has jurisdiction to review decisions of the special masters in accordance
with provisions of the National Childhood Vaccine Injury Act, 42 U.S.C. § 300aa-12(e)(1)
- (2). Under those provisions, this Court will only set aside findings of fact or conclusions
of law found to be “arbitrary, capricious, an abuse of discretion or otherwise not in
accordance with law.” 42 U.S.C. § 300aa-12(e)(2)(B). With respect to findings of fact,
the special masters have broad discretion to weigh evidence and make factual
determinations. As to questions of law, the legal rulings made by a special master in
connection with a vaccine claim are reviewed de novo, under a “not in accordance with the
law” standard. The Special Master’s findings of fact receive deferential review under an
“arbitrary and capricious” standard, while the Court reviews legal conclusions under the
“not in accordance with law” standard and discretionary rulings for an “abuse of
discretion.” Munn v. Sec’y of Health & Human Servs., 970 F.2d 863, 870 n.10 (Fed. Cir.
1992). “Weighing the persuasiveness of particular evidence often requires a finder of fact

                                             8
to assess the reliability of testimony, including expert testimony, and we have made clear
that the special masters have that responsibility in Vaccine Act cases.” Moberly ex rel.
Moberly v. Sec’y of Health & Human Servs., 592 F.3d 1315, 1325 (Fed. Cir. 2010).

                                          Conclusion

        The Court has carefully considered the parties’ arguments, the evidence of record,
and the Special Master’s decision on entitlement, and is satisfied that the Special Master
set forth a reasonable basis for her decision. The Special Master reasonably found here
that there was insufficient evidence to support Petitioner’s claim that the Fluzone
vaccination was the cause of her narcolepsy. She addressed two recent cases addressing
this issue, and reasonably explained why Petitioner’s arguments in this case failed to
establish any persuasive differences from those cases. She reiterated the strength of the
Duffy study at this stage of narcolepsy research. As the Federal Circuit noted in D’Tiole,
nothing in prior Vaccine Program case law “requires the Special Master to ignore probative
epidemiological evidence that undermines petitioner’s theory.” 726 Fed.App’x. 809, 811.


       For these reasons the Special Master’s Decision is AFFIRMED and accordingly,
Petitioner’s Motion for Review is DENIED.


      IT IS SO ORDERED.

                                                s/Thomas C. Wheeler
                                                THOMAS C. WHEELER
                                                Judge




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