F. v. Secretary of Health and Human Services ( 2023 )

In the United States Court of Federal Claims
OFFICE OF SPECIAL MASTERS
No. 19-446V
(to be published)
*************************
* Chief Special Master Corcoran
*
A.F., *
* Filed: October 11, 2022
Petitioner, *
*
v. *
*
SECRETARY OF HEALTH AND *
HUMAN SERVICES, *
*
Respondent. *
*
*************************
Edward Kraus, Kraus Law Group, LLC, Chicago, IL, for Petitioner
Mitchell Jones, U.S. Department of Justice, Washington, DC, for Respondent.
DECISION DENYING ENTITLEMENT1
On March 26, 2019, A.F. filed a Petition under the National Vaccine Injury Compensation
Program (the “Vaccine Program”2), alleging that as a result of receiving the human
papillomavirus (“HPV”) in December 2017, she developed Postural Orthostatic Tachycardia
Syndrome (“POTS”). Petition (ECF No. 1) (“Pet.”) at 1. After the filing of multiple expert
reports, I set a schedule to rule on the record, and the matter is now fully briefed. Petitioner’s
1
This Decision will be posted on the United States Court of Federal Claims’ website in accordance with the E-
Government Act of 2002, 44 U.S.C. § 3501 (2012). This means the Decision will be available to anyone with access
to the internet. As provided by 42 U.S.C. § 300aa-12(d)(4)(B), however, the parties may object to the published
Ruling’s inclusion of certain kinds of confidential information. Specifically, under Vaccine Rule 18(b), each party has
fourteen (14) days within which to request redaction “of any information furnished by that party: (1) that is a trade
secret or commercial or financial in substance and is privileged or confidential; or (2) that includes medical files or
similar files, the disclosure of which would constitute a clearly unwarranted invasion of privacy.” Vaccine Rule 18(b).
Otherwise, the entire Decision will be available to the public in its current form. Id.
2
The Vaccine Program comprises Part 2 of the National Childhood Vaccine Injury Act of 1986, Pub. L. No. 99-660,
100 Stat. 3755 (codified as amended at 42 U.S.C. §§ 300aa-10–34 (2012)) (hereinafter “Vaccine Act” or “the Act”).
All subsequent references to sections of the Vaccine Act shall be to the pertinent subparagraph of 42 U.S.C. § 300aa.
Case 1:19-vv-00446-UNJ Document 49 Filed 10/11/22 Page 2 of 39
Motion, filed Dec. 13, 2021 (ECF No. 37) (“Mot.”); Respondent’s Opposition Brief, filed
Mar. 21, 2022 (ECF No. 42) (“Opp.”); Petitioner’s Reply Brief, filed Apr. 22, 2022 (ECF
No. 43) (“Reply”).
Having reviewed the record and all associated filings, I hereby deny an entitlement award.
The theory that the HPV vaccine can cause POTS has been routinely rejected in numerous prior
Program cases as lacking reliable scientific support sufficient to meet the preponderant burden of
proof. Nothing offered in this case suggests new, or more persuasive grounds, for finding
otherwise.
I. Factual Background
Vaccination and Initial Symptoms
A.F. was born on January 14, 1993. Ex. 1 at 1. She was 24 at the time of
vaccination, and had been prescribed a “beta blocker” 3 to address feelings of anxiety. Ex. 3 at 1.
On December 26, 2017, Petitioner saw her primary care provider (“PCP”), Janet Mullins, M.D.,
for an annual physical. Id. During this visit, Dr. Mullins advised A.F. to undergo
vaccination for HPV, and she accordingly received her first HPV vaccine dose four days later
(December 30, 2017) at a Walgreen’s Pharmacy. Ex. 7 at 2. There is no record evidence of any
immediate reaction or malaise-like symptoms.
A few days later (January 3, 2018), Petitioner hit her hip against the sink while washing
dishes, began feeling dizzy, and eventually passed out. Ex. 2 at 3. After experiencing similar
symptoms while in the shower the following day, A.F. decided to consult a physician. Id. She
subsequently saw Jane McCort, M.D., an internist at the University of Michigan Health
Services, on January 4, 2018. Ex. 2. at 3–6. After an assessment, Dr. McCort advised A.F. that she
had likely experienced a vasovagal episode after hitting her hip, and further instructed A.F. to
reach out if she was not feeling better by the next day. Id.
Petitioner returned to Dr. McCort the next day (January 5, 2018), complaining that her
symptoms had not improved, and noting that she continued to suffer from lightheadedness despite
her efforts to rest and to maintain proper intake of fluids and food. Ex. 2 at 13. A.F. also
informed Dr. McCort that she had received her first dose of the HPV vaccine the week before. Id.
Dr. McCort reviewed A.F.’s lab work and noted that the results evidenced borderline
leukocytosis but were otherwise normal. Id. at 15. Additionally, Petitioner’s blood
pressure
3
Beta blockers (also known as beta-adrenergic blocking agents) reduce blood pressure by blocking the effects of the
hormone epinephrine, also known as adrenaline. They resultingly cause the heart to beat more slowly and with less
force, lowering blood pressure, and can also widen veins and arteries for improved blood flow. Mayo Clinic, Beta
Blockers, https://www mayoclinic.org/diseases-conditions/high-blood-pressure/in-depth/beta-blockers/art-20044522
(last visited Oct. 11, 2022).
2
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readings did not raise concerns for orthostatic intolerance, although Dr. McCort observed a
slightly-abnormal heart rate increase of twenty to thirty beats per minutes following positional
changes. Id. Although Dr. McCort expressed uncertainty as to why Petitioner continued to feel
unwell, she allowed for the possibility that a number of contributory factors—the HPV vaccine,
anxiety about her current symptoms, or stress related to school—could be relevant. Id. Dr. McCort
recommended that A.F. rest over the weekend, take extra care when standing, and return again
should her symptoms not improve. Id.
Suspicion of POTS
Several days later (January 9, 2018), A.F. visited Dr. McCort a third time,
reporting extreme fatigue, mental fogginess, and difficulty focusing. Ex. 2 at 21. She also stated
she felt as though her heart rate was going up, and that she was having heart flutters. Id. Dr.
McCort noted that A.F.’s orthostatic measures from the January 4th visit had suggested the
presence of POTS, and speculated that an immune reaction to the HPV vaccine could be causal.
Id. Dr. McCort advised the Petitioner to undergo additional testing for cardiac issues and POTS.
Id. at 23. To that end, Dr. McCort ordered testing in which A.F. was fitted with a 48-hour
Holter monitor4 on January 12, 2018. Ex. 4 at 4. The monitor revealed a single instance of
tachycardia during a period where Petitioner reported feeling lightheaded. Id. at 4–6; 18–20.
A.F. also underwent an echocardiogram which indicated the presence of an elongated anterior
mitral valve leaflet without prolapse. Id. at 4–6. However, the results were otherwise deemed
normal. Id. at 6.
On January 17, 2018, Petitioner saw cardiologist Dr. Frank Pelosi. Ex. 4 at 39–40; Ex. 9 at
1–2. She provided Dr. Pelosi with her recent medical history, which included feeling lightheaded
at times and occasional heart palpitations, although these events were not consistently correlated
with each other. Id. Dr. Pelosi opined that Petitioner had suffered at least one instance of syncope,
along with “a vague, but profound fatigue.” Id. He acknowledged the HPV vaccine might be
associated with her symptoms, although it was also possible that Petitioner’s susceptibility to
syncopal events might render her prone to their repetition. Id. Dr. Pelosi’s treatment
recommendations echoed what Dr. McCort had proposed (e.g., increase fluid intake, get sufficient
rest, maintain a proper diet, etc.). Id.
Two days later, on January 19, 2018, Petitioner was seen in the Emergency Department at
the University of Michigan due to complaints of lightheadedness, diaphoresis, and nausea. Ex. 4
at 52–55. By this point, Petitioner deemed her fatigue so profound that she had withdrawn from
4
A Holter monitor is a portable electrocardiogram (ECG) that continuously records the electrical activity of the
heart for 24 hours or longer. Johns Hopkins Medicine, Holter Monitor,
https://www.hopkinsmedicine.org/health/treatment-tests-and-therapies/holter-monitor (last visited Oct. 11, 2022).
3
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school for the semester. Id.5 A physical examination, cortisol levels, and head CT scan all produced
normal results, however, and A.F.b2 was discharged and advised to follow up with her PCP.
Id.
The following week (on January 25, 2018), A.F. saw a different cardiologist— Marwan
Bahu, M.D.—for an evaluation for syncope. Ex. 8 at 1–2. The medical history recounted
Petitioner’s recent symptoms, along with her receipt of the HPV vaccine—but it also noted
an instance in which Petitioner had “a year ago fainted with needle stick.” Id. at 1.
Orthostatic readings taken in what appears to be a “sit-stand” test revealed an increase of only
20 bpm from sitting to standing (although from supine to sitting to standing was a larger range of
54 bpm), and Dr. Bahu took note of the prior Holter test findings as well, and the exam identified
no other issues beyond reported dizziness. In light of all of these factors, Dr. Bahu proposed
that Petitioner had experienced “syncope and collapse.” Id. Petitioner was (again) advised to
increase her salt and fluid intake and prescription medicine was contemplated in the event
improvement did not occur. Id.
Further Efforts at Treatment
Six weeks later, on March 5, 2018, A.F. went to see neurologist Brent Goodman at a
Mayo Clinic satellite office in Arizona. Ex. 1 at 1–2. It was reported at this time that Petitioner
had developed symptoms of orthostatic intolerance beginning four days after receipt of the HPV
vaccine. Id. Upon examination, Petitioner displayed signs of hypermobility, scoring eight out of
nine on the Beighton6 scoring system. Id.
Dr. Goodman opined that Petitioner was suffering from POTS as well as a hypermobile
form of Ehlers-Danlos syndrome,7 attributing the former to the vaccine. Ex. 1 at 2. He ordered
autonomic testing and lab work, and recommended certain lifestyle measures. Id. Dr. Goodman
also noted that Petitioner might be a good candidate for certain kinds of drug therapies. Id.
5
On January 22, 2018, Dr. McCort wrote a letter regarding Petitioner’s request for a leave of absence from
school. Ex 4 at 94–95. In it, she explained that a “medical condition” was interfering with A.F.’s ability to meet her
academic obligations. Id. at 94. The letter did not, however, identify a cause of this alleged condition, and made no
reference to the HPV vaccine.
6
“Beighton Score Test” is defined as “a test that detects joint hypermobility syndrome. The test uses a nine-point
scoring system that measures the flexibility of certain joints. A positive Beighton score means you likely have joint
hypermobility syndrome. Joint hypermobility syndrome may indicate other health problems that need further testing.”
Beighton Score Test, Cleveland Clinic, https://my.clevelandclinic.org/health/diagnostics/24169-beighton-score (last
visited Oct. 11, 2022).
7
“Ehlers-Danlos syndrome” is defined as “a group of inherited disorders of connective tissue . . . [p]rominent
manifestations include hyperextensible skin and joints, easy bruisability, and friability of tissues with bleeding and
poor wound healing, with additional symptoms specific for individual types.” Ehlers-Danlos syndrome, Dorland’s
Medical Dictionary Online, https://www.dorlandsonline.com/dorland/definition?id=110561 (last visited Oct. 11,
2022).
4
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On March 13, 2018, A.F. underwent an autonomic reflex study, which included a
QSART8 and tilt table test.9 Ex. 1 at 30. Although there was no evidence of generalized
autonomic failure, the tilt testing revealed evidence of orthostatic intolerance with postural
tachycardia. Id. at 47. Seeing Petitioner about two weeks later (on March 23, 2018), Dr. Goodman
reviewed these results and deemed them consistent with POTS. Id. at 4, 45, 47. He took special
note of the fact that Petitioner had experienced an episode of vasodepressor near-syncope toward
the end of the tilt test. Id. Now, in addition to the previously-proposed lifestyle changes, Petitioner
was also prescribed medication. Id.
Limited records were filed in this case for subsequent time periods. On June 7, 2019, A.F.
again saw Dr. McCort, reporting continued fatigue, light headedness, and palpitations with some
frequency. Ex. 16 at 20. She was referred to cardiology for follow-up regarding her POTS
diagnosis. Id. In 2020, Petitioner underwent testing for eleven categories of autoantibodies,
including many proposed in this case (as discussed in greater detail below) to be causal of some
forms of POTS. See CellTrend Result Report, dated September 10, 2020, filed as Ex. 48 (ECF No.
20-1). Petitioner was negative for every single identified autoantibody except two - anti ETAR 10
and anti-Muscarinic Cholinergic Receptor-3 Antibodies—with her measured levels deemed “at
risk” for both (although in each case the amounts measured were barely above what would have
constituted a negative reading). 11
8
“Quantitative Sudomotor Axon Reflex Test” measures nerves that control sweating, and can assist in identifying
whether an individual possesses a disorder of the autonomic nervous system. QSART, Cleveland Clinic,
https://my.clevelandclinic.org/health/diagnostics/16398-quantitative-sudomotor-axon-reflex-test-qsart (last visited
Sept. 30, 2022).
9
A “tilt test” is a “measurement of various bodily responses while the patient is tilted to different angles on a tilt table,
usually head up, such as monitoring of circulatory, cardiac, and neurologic responses.” Tilt test, Dorland’s Medical
Dictionary Online, https://www.dorlandsonline.com/dorland/definition?id=113022&searchterm=tilt+test (last visited
Sept. 27, 2022).
10
Anti-ETAR antibodies are antibodies against the endothelin receptor. A. Hineno et al., Autoantibodies Against
Autonomic Nerve Receptors in Adolescent Japanese Girls after Immunization with Human Papillomavirus Vaccine,
2 Annals of Arthritis and Clinical Rheumatology 1–6 (2019), filed as Ex. 82 (ECF No. 30-7), at 2. Endothelin is an
amino acid polypeptide that acts as a potent vasoconstrictor, with the capability of affecting blood pressure. Dorland’s
Illustrated Medical Dictionary 614 (33d ed. 2020).
11
Thus, the anti-ETAR antibodies were determined to be present at a level of 11.6 units/ml—below the 17 units/ml
level to test positive, and only slightly above the 10 units/ml level to test negative. And the anti-Muscarinic Cholinergic
Receptor-3 antibodies were present at a level of 6.5 units/ml, well below the 10.0 units/ml required to test positive.
Ex. 48.
5
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II. Expert Reports
A. Petitioner’s Expert – Mitchell Miglis, M.D.
Dr. Miglis, a neurologist specializing in autonomic nervous system disorders, prepared
three reports in support of Petitioner’s claim. Report, filed as Ex. 17 on February 27, 2020 (ECF
No. 16-1) (“Miglis First Rep.”); Report, filed as Ex. 73 on November 30, 2020 (ECF No. 26-2)
(“Miglis Second Rep.”); Report, filed as Ex. 85 on September 16, 2021 (ECF No. 34-1) (“Miglis
Third Rep.”).
Dr. Miglis obtained his undergraduate and medical degrees from the University of North
Florida. See Curriculum Vitae, filed as Ex. 47 on September 15, 2022 (ECF No. 45-1) (“Miglis
CV”) at 1. He is a Clinical Assistant Professor in the department of Neurology at Stanford
University. Miglis CV at 1; Miglis First Rep. at 1. During his time in practice, he has managed
over 300 patients with POTS. Miglis First Rep. at 1. Dr. Miglis is licensed to practice medicine in
New York, Massachusetts, and California, and is board certified in neurology and sleep medicine.
Miglis CV at 2; Miglis First Rep. at 1. Dr. Miglis has also lectured and published in peer-reviewed
scientific literature on POTS and sleep disorders. Miglis CV at 2–7, 9–10; Miglis First Rep. at 1.
First Report
Dr. Miglis began with a discussion of POTS, deeming it generally “a disorder of the
autonomic nervous system.” Miglis First Rep. at 2. POTS is characterized by sustained
tachycardia, or increased heart rate, upon a postural change (like standing), along with sustained
orthostatic hypotension (a drop in blood pressure) leading to feelings of dizziness due to decreased
blood flow to the brain. Id. at 2–3. POTS has many secondary associated symptoms (e.g., shortness
of breath, fatigue), and is not coterminous with vasovagal syncope, even though the latter can be
a symptom of POTS. Id. 12
Dr. Miglis acknowledged that POTS has “no single established etiology.” Miglis First Rep.
at 3. Indeed, literature he offered maintains that it is often the product of “cardiovascular
deconditioning (i.e., cardiac atrophy and hypovolemia 13),” which would not be prompted by an
aberrant immune response. Q. Fu & B. Levine, Exercise and Non-Pharmacological Treatment of
POTS, 215 Auton. Neurosci. 20 (2019), filed as Ex. 19 (ECF No. 46-2) (“Fu & Levine”) at 21. But
he maintained there existed reliable evidence associating it with autoimmunity as well. As a
12
Although Dr. Miglis also defined Ehlers-Danlos syndrome and discussed its POTS associations, Petitioner has not
alleged that her Ehlers-Danlos was vaccine-caused.
13
“Hypovolemia” is defined as “abnormally decreased volume of blood circulating in the body.” Hypovolemia,
Dorland’s Medical Dictionary Online,
https://www.dorlandsonline.com/dorland/definition?id=24456&searchterm=hypovolemia (last visited Oct. 11, 2022).
6
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general matter, some POTS patients reported a viral illness before their symptoms, and women
(who as a group experience autoimmune disease more frequently) also make up a large percentage
of POTS patients. Miglis First Rep. at 3.
More specifically, Dr. Miglis observed that several specific autoantibodies had been
identified as present in individuals suffering from POTS. In particular, Dr. Miglis represented that
“several publications” have discussed instances in which “autoantibodies to G-protein-coupled
receptors (GPCRs)” were measures in POTS patients. Miglis First Rep. at 3. This included
autoantibodies to adrenergic receptors associated with the “fight or flight” response within the
sympathetic nervous system—a physiologic, non-voluntary response to stress that would implicate
autonomically-controlled biologic functions like heart rate or blood pressure. Id. at 3–4; H. Li et
al., Autoimmune Basis for Postural Tachycardia Syndrome, 3 J. Am. Heart Assoc. 1–10 (2014),
filed as Ex. 30 (ECF No. 47-3) (“Li I”); A. Fedorowski et al., Antiadrenergic Autoimmunity in
Postural Tachycardia Syndrome, 19 European Soc’y of Cardiology 1211–1219 (2017), filed as
Ex. 31 (ECF No. 47-4) (“Fedorowski”).
Li I’s authors, operating from the hypothesis that (because POTS often followed a viral
illness) it might be an autoimmune-mediated condition, tested the blood of 14 POTS patients,
finding that they possessed specific autoantibodies that might interfere with receptor functioning,
producing postural tachycardia by causing “an inability of the peripheral blood vessels to fully
constrict on standing,” or simply by enhancing/exaggerating the tachycardia response. Miglis First
Rep. at 4; Li I at 2. However, it was also noted that the cause of the autoantibody production was
unknown. Li I at 8. Fedorowski had also observed the anti-adrenergic autoantibody presence in
the 17 POTS patients considered, and concluded it was likely they played a role in POTS’s
pathogenesis (although its authors noted that POTS likely had “multiple causes,” and that for the
“vast majority of patients” there was little concrete evidence upon which causation theories
involving autoantibodies could be based). Fedorowski at 1217.
Although Dr. Miglis admitted that the studies he cited for this point were small in scale
(deeming their conclusions “preliminary” as a consequence), he also stressed that their findings
were not recent (noting specifically that Li I had first observed the potential association in 2014).
Miglis First Rep. at 4. In fact, he observed that these autoantibodies had been associated with other
kinds of autonomic dysfunction, such as general orthostatic hypotension. See, e.g., X. Yu et al.,
Autoantibody Activation of Beta-adrenergic and Muscarinic Receptors Contributes to an
"Autoimmune" Orthostatic Hypotension: Reception Autoantibodies in Orthostatic Hypotension, 6
J. Am. Soc’y Hypertension 40–47 (2012), filed as Ex. 36 (ECF No. 47-9) (finding several
activating autoantibodies, based on blood testing for six individuals, capable of contributing to the
pathophysiology of orthostatic hypotension).
7
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More recently-published articles had reached comparable conclusions. See, e.g., W.
Gunning et al., Postural Orthostatic Tachycardia Syndrome is Associated with Elevated G-Protein
Coupled Receptor Autoantibodies, 8 J. Am. Heart Assoc. 1–10 (2019), filed as Ex. 83 (ECF No.
30-8) (“Gunning”); H. Li et al., Adrenergic Autoantibody-Induced Postural Tachycardia
Syndrome in Rabbits, 8 J. Am. Heart Assoc. 1– 9 (2019), filed as Ex. 38 (ECF No. 48-1) (“Li II”).
Gunning, for example, observed high titers of autoantibodies similar to the kinds previously noted
in a cohort of 55 POTS patients whose blood was tested. Gunning at 5. But although Gunning
speculates that viral infections (or vaccination) could explain the presence of the relevant
autoantibodies, it also stated that “[t]he significance of autoantibodies against the adrenergic . . .
receptor . . . is unknown,” Gunning at 7–8. 14
Li II, utilizing an animal model, purports to show that immunization with the
autoantibodies “induced a POTS-like phenotype in rabbits.” Miglis First Rep. at 5; Li II at 7.
Specifically, Li II’s authors directly immunized eight rabbits with peptides from the relevant
adrenergic receptors believed to be interfered with by autoantibodies, found that the rabbits on a
tilt test displayed a POTS-like heart rate increase at six weeks post-vaccination. Li II at 6–7. But
Li II’s authors admitted that demonstrated cardiovascular changes had some problems when
compared to humans, since rabbits are quadrupeds. Id. at 6, 8 (“[t]here are currently no animal
models that exhibit the characteristic postural or cardiovascular manifestations of POTS seen in
humans”). And the article acknowledged otherwise that “POTS is likely a heterogeneous disorder
with more than one underlying pathophysiology.” Id. at 1. Dr. Miglis ultimately admitted that these
more recent studies still left it underdetermined whether the tested autoantibodies are likely
causative of POTS or simply reflect “immune dysregulation” in response to POTS. Miglis First
Rep. at 5.
Next, Dr. Miglis proposed how the HPV vaccine might be generally associated with POTS.
He started by referencing a number of articles that are often cited in cases involving the HPV
vaccine and claims it can cause dysautonomia. Miglis First Rep. at 5–6; S. Blitshteyn, Postural
Tachycardia Syndrome Following Human Papillomavirus Vaccination, 21 Eur. J. Neurol. 135–
39, 138 (2014), filed as Ex. 40 (ECF No. 48-3) (“Blitshteyn I”); T. Kinoshita et al., Peripheral
Sympathetic Nerve Dysfunction in Adolescent Japanese Girls Following Immunization with the
Human Papillomavirus Vaccine, 53 Internal Med. 2185–200, 2185 (2014), filed as Ex. 41 (ECF
No. 48-4) (“Kinoshita”); L. Brinth et al., Orthostatic Intolerance and Postural Tachycardia
Syndrome as Suspected Adverse Effects of Vaccination against Human Papilloma Virus, 33
Vaccine 2602–2605, 2603 (2015), filed as Ex. 42 (ECF No. 48-5) (“Brinth”).
14
As support for a vaccine-autoantibody association, Gunning references one article also filed in this case—S.
Blitshteyn, Autoimmune Markers and Autoimmune Disorders in Patients with Postural Tachycardia Syndrome
(POTS), 24 Lupus 1364–1369, 1367 (2015), filed as Ex. 29 (ECF No. 47-2) (“Blitshteyn II”).
8
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But the deficiencies of these items of literature are fairly self-evident (as has been observed
in prior decisions). Blitshteyn I, for example, is a six-patient case series report with explanatory
analysis, but which sheds little light on the nature of how the HPV vaccine could cause POTS,
since it only observes a temporal association for the sample patients. Blitshteyn I at 138. And (like
some of the more recent articles referenced by Dr. Miglis) Blitshetyn I notes that POTS “may arise
from various mechanisms and etiologies,” with an autoimmune explanation as only one possible
cause. Id.
Kinoshita involved a larger cohort (44 Japanese patients) but presented self-selection bias
circumstances (since the cohort members specifically sought treatment, as Dr. Miglis noted, based
on the belief their vaccination was causal of the symptoms they were then experiencing) and thus
did not reflect randomly-chosen patients. Kinoshita at 2185–86. Moreover, the symptoms reported
were wide-ranging, with only a subset involving the kind of orthostatic features common to POTS–
and only 13 of the total sample of patients had received the HPV formulation at issue in this case.
Id. at 2186. Finally, an unidentified subset of 14 patients who purportedly had displayed
“sympathetic dysfunction” (although only four of these subjects met the criteria for POTS) were
tested for autoantibodies comparable to what are alleged herein to be driving POTS in some
cases—and all were negative for them. Id. at 2194, 2199.
Brinth also relied on self-selected cohort populations. Brinth at 2603. There, 35 females
“consecutively referred to our syncope unit,” and based on a suspicion of an HPV vaccine-
associated adverse event, were evaluated. Id. While the majority of them (60 percent) were found
to meet the diagnostic criteria for POTS, no connection between vaccination and symptoms
beyond a mere temporal association was observed, and indeed Brinth’s authors noted that “[o]ur
findings do not confirm or dismiss a causal link to the HPV vaccine.” Id. at 2604.
Dr. Miglis himself ultimately admitted that these kinds of case series were “relatively small
and admittedly observational,” but he deemed them the next-best alternative to an absence of large-
scale independent studies. Miglis First Rep. at 6. As an example of a purportedly non-independent
study, he referenced an otherwise large-scale observational study that has often been discussed in
cases involving the HPV vaccine. Id.; C. Chao et al., Surveillance of Autoimmune Conditions
following Routine Use of Quadrivalent Human Papillomavirus Vaccine, 271 J. Intern. Med. 193–
203, 202, (2012), filed as Ex. 44 (ECF No. 48-7) (“Chao”) (following administration of the HPV4
vaccination in routine clinical use, no safety signal for a variety of autoimmune conditions existed
within a large and mostly female population). Chao considered more than 180,000 instances of
administration of an HPV vaccine dose in a patient sample which was almost wholly (99 percent)
made up of women aged 9–26, although it did not explicitly look for POTS or instances of
purported autoimmune-caused dysautonomia. Dr. Miglis nevertheless deemed the fact that Chao
was funded by a pharmaceutical company to cast doubt on its veracity, given the inherent conflict
of interest. Miglis First Rep. at 6.
9
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Dr. Miglis also referenced an article that relied on an online survey to suggest an HPV
vaccine-POTS relationship. Miglis First Rep. at 5; B.H. Shaw et al., The Face of Postural
Tachycardia Syndrome—Insights from a Large Cross-Sectional Online Community-based Survey,
286 J. Internal Med. 438–448 (2019), filed as Ex. 39 (ECF No. 48-2) (“Shaw”). Based on a sample
of nearly 5,000 survey participants reporting they had been diagnosed with POTS, 1,933
participants claimed their symptoms manifested within three months of a trigger, with six percent
of that group identifying vaccination as the believed trigger. Shaw at 440. Shaw did not, however,
determine the specific vaccines in question—and even noted its own methodologic weaknesses,
such as the fairly significant fact that “we cannot verify that the diagnoses of POTS are correct in
each case.” Id. at 445.
The remainder of Dr. Miglis’s first report was a detailed review of Petitioner’s medical
history. See generally Miglis First Rep. at 7–9. Overall, he emphasized that the record supported
the POTS diagnosis, and that the three days from vaccination to onset were consistent with what
relevant literature would consider medically acceptable. Id. at 10.
Second Report
Dr. Miglis’s second report was filed around the time of Dr. Ahmed’s (his co-expert) first
report, and largely sought to respond to the contentions of Respondent’s expert, Dr. Christopher
Gibbons. First, Dr. Miglis questioned whether A.F.’s POTS could be deemed to have predated
her receipt of the HPV vaccine, noting that she appeared overall quite active in that
timeframe, and that her intermittent fainting episodes after blood draws (and while fasting,
moreover) were more reflective of vasovagal syncope (which “commonly occurs in healthy young
adults”). Miglis Second Rep. at 1. He also discounted Petitioner’s Ehlers-Danlos syndrome as
causal, characterizing it as potentially demonstrating that she was predisposed to POTS, but not
undermining the likelihood that the HPV vaccine triggered it. Id.
Second, regarding whether POTS is generally associated with autoimmune conditions, Dr.
Miglis discussed an item of literature criticized by Respondent’s expert. Miglis Second Rep. at 2;
S. Blitshteyn, Autoimmune Markers and Autoimmune Disorders in Patients with Postural
Tachycardia Syndrome (POTS), 24 Lupus 1364–1369, 1367 (2015), filed as Ex. 29 (ECF No. 47-
2) (“Blitshteyn II”). Blitshteyn II involved blood testing for 100 POTS patients, in an attempt to
identify certain kinds of known autoimmune markers, like a positive ANA. 15 Blitshteyn II at 1364–
65. Approximately 25 percent of the tested group were positive for ANA (although titer levels
were deemed primarily low), and other individuals were found to have distinguishable
autoimmune disease-specific antibodies or had been diagnosed with a specific kind of autoimmune
15
“ANA” refers to antinuclear antibodies. Antinuclear Antibodies, Dorland’s Medical Dictionary Online,
https://www.dorlandsonline.com/dorland/definition?id=56804 (last visited Oct. 11, 2022).
10
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disorder. Id. at 1365. Dr. Miglis deemed these findings significant, despite Dr. Gibbons’s argument
that a positive ANA titer was not uncommon as a general matter (even in individuals not suffering
from autoimmune conditions).
Dr. Miglis also re-emphasized the existence of a number of newer studies that associated
POTS with the presence of specific kinds of anti-adrenergic receptor antibodies, observing that
many had been undertaken since the HPV vaccine’s administration became more prevalent (while
admitting that these same studies “do not specify if Gardasil-vaccinated patients were included in
their study population”). Id; Fedorowski at 4–5; Gunning at 2. A 2020 study, in fact, had provided
support for the proposition that the levels of these autoantibodies in POTS patients correlated with
the severity of orthostatic intolerance experienced. I. Kharraziha et al., Serum Activity against G
Protein-Coupled Receptors and Severity of Orthostatic Symptoms in Postural Orthostatic
Tachycardia Syndrome, 9 J. Am. Heart Assoc. 1–9, 8 (2020), filed as Ex. 74 (ECF No. 26-2)
(“Kharraziha”) (finding that the sera from 48 patients with POTS displayed more activation in four
anti-adrenergic receptors compared to the sera from controls). But Kharraziha focused on receptor
activity rather than autoantibody levels, assuming without confirmation that “the increased activity
in the specific receptors is a consequence of autoimmune disease.” Kharraziha at 8.
Dr. Miglis also noted that Petitioner had (nearly three years after onset) displayed slightly
elevated titers of the purportedly-causal kinds of autoantibodies—and Dr. Miglis viewed the
passage of time as supportive of the inference that her levels had likely waned since onset (although
arguably testing results two-plus years after onset might not say anything at all about antibody
levels in the past). Miglis Second Rep. at 3. Moreover, Dr. Miglis admitted not only that these
autoantibodies could not be seen as biomarkers for POTS, but also that whether they were
causative “or a bystander effect of dysimmunity” remained undetermined. Id.
Dr. Miglis took issue with some of the evidence that Respondent’s expert marshalled
against causation. Dr. Gibbons had noted, for example, that a large-scale report conducted by the
European Medicines Agency (the “EMA”) 16 had identified no POTS-HPV vaccine association.
Miglis Second Rep. at 3; Pharmacovigilance Risk Assessment Committee, Assessment Report:
Review under Article 20 of Regulation (EC) No. 726/2004, 1–40, 38–39 (2015), filed as Ex. A Tab
6 (ECF No. 18-7) (the “EMA Report”). But Dr. Miglis questioned whether the EMA Report had
accurately identified instances of POTS based on the database codes it relied upon, and given how
difficult POTS was generally to diagnose. Miglis Second Rep. at 3–4. And although he agreed that
the counter-evidence he largely relied on came from case reports or case series articles, like Brinth
and Kinoshita—a class of evidence “admittedly of weaker scientific merit”—they reflected the
16
A decentralized agency of the European Union (EU), the European Medicines Agency (EMA) is responsible for the
scientific evaluation, supervision, and safety monitoring of medicines within the EU. European Medicines Agency,
Who We Are, https://www.ema.europa.eu/en/about-us/who-we-are (last visited Oct. 11, 2022).
11
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observations of different nations, involving uncommon symptoms, and thus stood as “a signal of
concern.” Id. at 4.
By contrast, Dr. Miglis noted that a more recent, independent meta-analysis 17 (combining
data from vaccine trials and clinical studies) had suggested that many HPV studies were “at a high
risk of bias,” due to comparison of vaccinated patients with controls who had also received
adjuvant-containing vaccines, and that adverse occurrences that could be POTS-related were
incompletely reported (but still more common in the context of receipt of the HPV vaccine). Miglis
Second Rep. at 5; L. Jorgenson et al., Benefits and Harms of the Human Papillomavirus (HPV)
Vaccines: Systematic Review with Meta-Analysis of Trial Data from Clinical Study Reports, 9
Systematic Reviews 1–23, (2020), filed as Ex. 75 (ECF No. 26-4) (“Jorgenson”). But Jorgenson’s
focus is far more on whether large-scale safety testing of the HPV vaccine is reliable, comparing
overall claimed benefits for the vaccine (which it deemed uncertain) against a lack of emphasis on
possible risks—and it referenced the same articles (Kinoshita and Brinth) as evidence of a POTS
association, despite their lack of reliable findings on that front (as discussed above). Jorgenson at
2 nn. 27–28.
In similar fashion, Dr. Miglis attempted to vouch for other articles he offered in support of
his contentions. For example, one article claimed to observe “clusters of symptoms” that could be
POTS, but which could also simply reflect “availability bias,” based on heightened awareness of
the possibility of an HPV-associated injury. T. Ward et al., A Cluster Analysis of Serious Adverse
Event Reports after Human Papillomavirus in Danish Girls and Young Women, 24 Euro
Surveillance 1–10 (2019), filed as Ex. A-8 (ECF No. 18-9) (“Ward”). But Dr. Miglis maintained
that this “increased awareness” might simply reflect better understanding of the diagnosis itself
(and hence its existence, as opposed to a mistaken correlation). Miglis Second Rep. at 5.
Another study from Finland (which Dr. Gibbons had proposed showed that POTS
diagnoses were already increasing prior to the widespread use of the HPV vaccine) did not, Dr.
Miglis contended, involve the HPV vaccine, but relied (as Jorgenson observed) on inaccurate
classification criteria to identify true instances of POTS, and ultimately could not reliably compare
POTS incidence pre versus post-vaccination. Id. at 5–6; O. Skufca et al., Incidence Rates of Guillain
Barré (GBS), Chronic Fatigue/Systemic Exertion Intolerance Disease (CFS/SEID) and Postural
Orthostatic Tachycardia Syndrome (POTS) prior to Introduction of Human Papillomavirus (HPV)
Vaccination among Adolescent Girls in Finland, 3 Papillomavirus Res. 91–96 (2017), filed as Ex. A
Tab 9 (ECF No. 18-10) (“Skufca I”).
17
“Meta-Analysis” is defined as “a method for systematically combining pertinent qualitative and quantitative study
data from several selected studies to develop a single conclusion that has greater statistical power.” Himmelfarb Health
Sciences Library, Meta-Analysis, https://himmelfarb.gwu.edu/tutorials/studydesign101/metaanalyses.cfm (last visited
Oct. 11, 2022).
12
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Dr. Miglis concluded by arguing that the position statement put out by the American
Autonomic Society (the “AAS”)—which expressly (and contrary to his fundamental opinion)
disavowed an HPV vaccine-POTS association—could not be verified as reliable science, since it
appeared more the opinion of certain “AAS senior members” than a replicable study with verifiable
methodology, and also had been signed by biased individuals who has previously acted as
witnesses for the Government in other litigation involving the HPV vaccine. Miglis Second Rep.
at 6; A. Barboi et al., Human Papillomavirus (HPV) Vaccine and Autonomic Disorders: A Position
Statement from the American Autonomic Society, 223 Autonomic Science: Basic and Clinical
102550 (2020), filed as Ex. A Tab 11 (ECF No. 18-12) (the “AAS Statement”). The AAS
Statement—while expressly not a scientific study itself—reflects the views of 22 neurologists with
expertise on autonomic conditions (including Dr. Gibbons himself), and highlights the fact that
the overall benefits of the HPV vaccine outweigh the views expressed in articles like Brinth or
Blitshteyn I, since they reveal “only weak temporal associations between events,” and otherwise
cannot be relied upon for causality given their “small sample sizes, inherent selection biases, and
lack of control populations.” AAS Statement at 3.
Third Report
The third report prepared by Dr. Miglis mostly attempted to analogize “autonomic
complications” from COVID-19 infections to the circumstances at issue in this case. See generally
Miglis Third Rep. at 1–4. Among the observed post-infectious symptoms and complications has
been POTS —something Dr. Miglis deemed “not surprising,” since POTS could also occur in the
wake of other respiratory infections. Id. at 1–2. In fact, a case of POTS after receipt of the COVID-
19 vaccine has been reported in one article. Id. at 2. 18 Other literature has suggested homology
between the protein components of the COVID-19 coronavirus and human protein components,
suggesting a “correlation of COVID-19 and autoimmunity.” Id. Moreover, some recent studies
demonstrated that individuals suffering from “long COVID” possessed the kind of anti-adrenergic
autoantibodies that Dr. Miglis was contending herein could cause POTS. Id. at 3–4. Based on the
foregoing, Dr. Miglis maintained that evidence of autoimmune processes driving POTS in the
wake of a COVID-19 infection (or vaccination for that matter) had relevance to the contentions in
this case as well. Id. at 4.
18
Although Dr. Miglis has provided literature citations for these assertions, I do not reference them herein—for the
simple, if obvious, reason that the effects of the COVID-19 vaccine (or wild infection) are not in contention in this
case whatsoever. The general points Dr. Miglis sought herein to assert (about the role viruses can play in potentially
causing POTS, and what that says about vaccines or an autoimmune-mediated form of POTS) can be understood and
evaluated without consideration of the secondary support he offers for them, given the degree to which it strays far
from the core questions presented by this claim.
13
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B. Petitioner’s Expert — S. Sohail Ahmed, M.D.
Dr. Ahmed, a clinical immunologist and rheumatologist with specific academic expertise
in the study of vaccines and autoimmune conditions, prepared two additional reports for the
Petitioner, offering an opinion proposing the biologic processes for how the HPV vaccine could
produce the autoantibodies theorized in this case to cause POTS. Report, filed as Ex. 50 on
November 28, 2020 (ECF No. 23-1) (“Ahmed First Rep.”); Report, filed as Ex. 77 on March 17,
2021 (ECF No. 30-2) (“Ahmed Second Rep.”).
Dr. Ahmed attended Johns Hopkins University for his undergraduate degree, and the
University of Texas at Houston for his medical degree. See Curriculum Vitae, filed as Ex. 51 on
November 28, 2020 (ECF No. 23-2) (“Ahmed CV”) at 5; Ahmed First Rep. at 2. Dr. Ahmed has
over 20 years of experience in academic and clinical research that facilitates translational
approaches to drug development. Ahmed CV at 1; Ahmed First Rep. at 2. He currently serves as
a medical and scientific consultant for pharmaceutical and vaccine-producing companies. Ahmed
CV at 2; Ahmed First Rep. at 2–3. He has published several peer-reviewed articles on multiple
topics including immune-meditated diseases, vaccine adjuvant safety, autoimmune diseases,
immune mechanisms triggered by vaccination, autoantibodies linked to autoimmune diseases, and
genetic susceptibility in patients developing autoimmune diseases. Ahmed CV at 6; Ahmed First
Rep. at 3. He is licensed to practice medicine in Italy and Massachusetts and is board certified in
rheumatology and internal medicine. Ahmed CV at 4–5; Ahmed First Rep. at 3.
First Report
Dr. Ahmed’s first report highlighted his professional expertise and listed the materials he
had considered in reaching the conclusions it contained, before going into the specific aspects of
his opinion. Ahmed First Rep. at 1–4. He noted initially that the medical record confirmed that
A.F. had not likely been experiencing POTS pre-vaccination. Id. at 5–7. He discounted the
significance of her pre-vaccination syncopal events, observing that they had occurred in the
context of blood draws, when she had fasted (presumably in preparation for the testing), and that
otherwise she had not shown any clinical evidence of the diagnostic criteria for POTS. Id. at 7.
By contrast, the same record strongly established Petitioner’s post-vaccination POTS
diagnosis. Ahmed First Rep. at 8. In fact, Drs. Miglis and Gibbons so agreed. Id. Dr. Ahmed also
(and relying on Dr. Gibbons’s review of the medical history) proposed that Petitioner’s POTS
onset occurred within four days of vaccination. Id. He deemed such a timeframe consistent with
how long an immune response leading into a pathologic autoimmune reaction would take post-
vaccination, adding that corroboration for this putative process could be discerned from testing
evidence of an elevated white blood cell count in early January 2018—confirming the presence of
systemic inflammation. Id.
14
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Dr. Ahmed then reached the heart of his report: that the HPV vaccine can cause POTS (as
well as other immune-mediated diseases). Ahmed First Rep. at 9–12. But he heavily relied on
arguments contained in Dr. Miglis’s first report, as well as the literature cited therein, for this
opinion. Thus, a whole page of Dr. Ahmed’s report was devoted to a brief recapitulation of the
findings in articles like Kinoshita, Brinth, and Blitsheyn I. 19 See, e.g., Ahmed First Rep. at 9. He
did the same in offering a potential biologic explanation for how the HPV vaccine would cause
autoimmunity leading to POTS. Id. at 10; See e.g., Blitshteyn I at 138; Li II at 8.
Dr. Ahmed proposed a biologic mechanism he deemed to be likely implicated in the
pathogenic course of post-HPV vaccine POTS. Ahmed First Rep. at 10–11. Molecular mimicry,
he explained, could occur when antigens in an infectious agent or vaccine could display “self-like
peptides” (amino acid sequences that constitute the building blocks of proteins), generating
antibodies that in turn would (due to antigenic similarity) attack not just the presenting antigen but
the self-structure as well—an autoimmune cross-reaction. Id. at 11. Other common autoimmune
diseases, like Guillain-Barré syndrome (“GBS”) or lupus, were thought to be mediated by
molecular mimicry due to the influenza vaccine—and the same was possible with POTS.
For direct support regarding the latter aspect of this contention, Dr. Ahmed offered a 2018
paper. Y. Segal & Y. Shoenfeld, Vaccine-induced Autoimmunity: The Role of Molecular Mimicry
and Immune Cross-reaction, 15 Cellular & Molecular Immunology, 586–594 (2018), filed as Ex.
69 (ECF No. 25-3) (“Segal”). Dr. Ahmed maintained that Segal noted a “vast peptide overlap”
between HPV amino acid sequences and “the human proteome,” thus allowing for at least a
speculative possibility of molecular mimicry. Ahmed First Rep. at 11. More specifically, Segal
had itself cited a study (Li I) in which the sera of 14 POTS patients were shown to possess the anti-
adrenergic antibodies that Dr. Miglis had proposed could be causal—and molecular mimicry, Dr.
Ahmed argued, explained how they would come into existence. See e.g., Segal at 591; Li I at 2.
A connection between the HPV vaccine and possible autoantibodies mediating POTS had
also been explored in a different article, although it focused more on an autoantibody theorized to
interact with cardiac myosin (a putative target for an autoimmune attack that could result in
19
Dr. Ahmed also referenced a review paper based on data derived from the Vaccine Adverse Event Reporting System
(“VAERS”). Ahmed First Rep. at 8–9; Miglis Rep. at 6 (citation omitted). VAERS is a national warning system
designed to detect safety problems in U.S.-licensed vaccines. See generally Carda v. Sec’y of Health & Hum. Servs.,
No. 14-191V, 2017 WL 6887368, at *6 (Fed. Cl. Spec. Mstr. Nov. 16, 2017). I provide no detailed consideration of
this item, however—for the simple reason that (as has been often observed in prior Program cases) VAERS data is
unreliable proof of causation entitled to little probative weight. See Thompkins v. Sec’y of Health & Hum. Servs., No.
10-261V, 2013 WL 3498652 at *9 n.25 (Fed. Cl. Spec. Mstr. June 21, 2013). The fact that an individual reports a
particular reaction post-vaccination does not make it more likely that the reaction was vaccine-caused—and VAERS
diagnoses cannot necessarily even be confirmed as accurate in many cases. (Of course, I would reach the same
conclusion about a study that attempted to undermine a vaccine-injury association by assembling VAERS data to
show individuals were not routinely claiming the injury as a post-vaccination adverse event).
15
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arrhythmias). Ahmed First Rep. at 11, S. Dahan et al., Postural Orthostatic Tachycardia Syndrome
(POTS)—A Novel Member of the Autoimmune Family, 25 Lupus 339–342 (2016), filed as Ex. 70
(ECF No. 25-4) (“Dahan”). Dahan claimed to have observed homology between sequences in one
of the HPV vaccine antigens and relevant human antigens associated with arrhythmias, allowing
in turn for the possibility that the vaccine’s spurring of an immune response involving the
production of antibodies could spark the necessary cross-reaction to cause POTS. Dahan at 341.
Thus, Dr. Ahmed was able to conclude that the HPV vaccine could more likely than not cause
POTS. However, Dahan is (by its own title) an editorial, rather than a study, relying on other
publications for the proposed amino acid homologies, and largely assuming (without a showing)
that the sequential identifies result in cross-reactive pathogenicity.
Second Report
Dr. Ahmed’s second report was prepared almost a month after Dr. Gibbons’s responsive
report, and consisted of a litany of rejoinders to points made by Dr. Gibbons. Dr. Ahmed initially
offered some general contentions about the difficulty in identifying a post-vaccination
“epidemiological signal,” especially since vaccines are intentionally designed to be as safe as
possible. Ahmed Second Rep. at 1. But evidence of “signals” supporting causation still exists,
proving at least causality for “certain genetically predisposed subjects in the population.” Id. at 2.
Only if a study was especially large could such signals ever be reliably detected; thus, GBS (a rare
disease generally) was causally associated with the flu vaccine as a result of “a mass immunization
campaign” in 1976 (allowing for subsequent epidemiologic data to be gathered that would
otherwise not have been available). Id.Regarding the mechanism for how the HPV vaccine could cause POTS, Dr. Ahmed
defended the legitimacy of Blitshteyn I’s endorsement. Even if the article did not provide specific
scientific support evidencing the mechanism in the context of POTS, its author is “an autonomic
specialist,” and it references case report examples of individuals whose POTS was argued to have
been vaccine-caused, based on clinical evaluation of alternative explanations. Ahmed Second Rep.
at 3; Blitshteyn I at 138. The same author noted in a different article (Blitshteyn II) that there was
an association between POTS and the existence of ANA, a likely autoimmunity biomarker.
Blitshteyn II at 1367.
Moreover, other literature corroborated a POTS-autoimmunity link. Ahmed Second Report
at 2–3; Dahan at 3 (proposing immune cross-reaction causing arrhythmia, based on HPV peptide
sequences having some kind of homologous similarity with human proteins). Some articles also
establish that POTS can occur after viral infections (including COVID-19 infections), further
underscoring the likelihood of an autoimmune basis for the condition. Ahmed Second Rep. at 3;
M. Thieben et al., Postural Orthostatic Tachycardia Syndrome: The Mayo Clinic Experience, 82
Mayo Clin. Proc. 308–313, 308, (2007), filed as Ex. 79 (ECF No. 30-4) (“Thieben”) (suggesting
16
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that there is a neuropathic basis for roughly half of the cases of POTS, and of those cases, a
substantial percentage may be autoimmune). All of the above provided support for the hypothesis
that molecular mimicry leading to a cross-reaction might explain how a vaccine (like a virus) could
result in POTS. Dr. Ahmed also argued that the animal study from Li II was reliable, and provided
substantiation for an association between anti-adrenergic autoantibodies and POTS. Ahmed
Second Rep. at 4–5; Li II at 8.
In addition, Dr. Ahmed attempted to rebut Dr. Gibbons’s contention that the testing
performed on Petitioner in August 2020 was unreliable or unsupportive of her argument that she
did likely possess the autoantibodies alleged to be causal of POTS. First, he cited an additional
item of literature from Japan, in which 55 young girls who had received the HPV vaccine were
tested (using the same European testing company utilized for Petitioner (see Ex. 48)) for the
relevant autoantibodies (including the “anti-ETAR” autoantibodies that Dr. Gibbons had identified
as likely irrelevant, but which Petitioner tested for in 2020 as “at risk”). Ahmed Second Rep. at 5;
A. Hineno et al., Autoantibodies Against Autonomic Nerve Receptors in Adolescent Japanese Girls
after Immunization with Human Papillomavirus Vaccine, 2 Annals of Arthritis and Clinical
Rheumatology 1–6 (2019), filed as Ex. 82 (ECF No. 30-7) (“Hineno”). Hineno found that the
tested subjects (all of whom had reported a variety of symptoms after receipt of an HPV vaccine)
possessed higher levels of the relevant autoantibodies than controls, concluding that autoantibodies
were likely associated with “orthostatic dysregulation.” Hineno at 4. The capacity of these
autoantibodies to cause POTS was confirmed by articles like Thieben, which showed that viral
infection could cause their presence as well. Thieben at 310. Like other articles attempting to
connect these autoantibodies to POTS, however, Hineno allowed that “the exact pathogenesis of
orthostatic deregulation . . . after HPV vaccination remains unclear,” and also that (a) POTS can
develop in unvaccinated individuals, and (b) some of the Hineno control subjects also possessed
the purportedly-causal autoantibodies without developing POTS. Hineno at 2, 4. In addition,
Hineno possesses the same self-selection bias limitations as articles like Kinoshita, since the tested
subjects had all self-reported post-vaccination symptoms after vaccination. Id. at 2.
Second, Dr. Ahmed vouched for the reliability of the specific testing that Petitioner
received in 2020 (and which studies like Hineno relied upon). He disputed Dr. Gibbons’s argument
that the testing only identified non-specific autoantibodies not shown to be relevant to a particular
disease, noting that other kinds of comparable non-specific testing (such as testing for rheumatoid
factor) was available in the U.S. Ahmed Second Rep. at 6. And he maintained that the
autoantibodies tested by the European testing center had in fact been demonstrated as relevant to
POTS. Id. The location of the testing center did not bear on whether the results were reliable or
relevant.
17
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C. Respondent’s Expert – Christopher Gibbons, M.D.
Dr. Gibbons, a neurologist with expertise in autonomic-oriented conditions such as POTS,
served as Respondent’s sole expert, preparing three reports. Report, filed as Ex. A on June 18,
2020 (ECF No. 18-1) (“Gibbons First Rep.”); Report, filed as Ex. C on March 2, 2021 (ECF No.
29-1) (“Gibbons Second Rep.”); Report, filed as Ex. D on October 27, 2021 (ECF No. 36-1)
(“Gibbons Third Rep.”).
Dr. Gibbons attended Dartmouth College for his undergraduate degree, and Albert Einstein
College of Medicine for his medical degree. See Curriculum Vitae, filed as Ex. B on June 18, 2020
(ECF No. 18-15) (“Gibbons CV”) at 1–2; Gibbons First Rep. at 1. Thereafter, Dr. Gibbons
completed a neurology residency at Johns Hopkins Hospital in Baltimore, Maryland, and a
fellowship in clinical neurophysiology (with a subspecialty in autonomic disorders) from Beth
Israel Deaconess Medical Center in Boston, Massachusetts. Gibbons CV at 1. He is an Associate
Professor of Neurology at Harvard Medical School and is a board-certified neurologist, with
subspecialty qualification in Clinical Neurophysiology. Gibbons CV at 1; Gibbons First Rep. at 1.
Currently, Dr. Gibbons serves as Co-Director of the Autonomic Disorders Clinic at Beth Israel
where he teaches resident and autonomic disorders fellows about autonomic testing and the
treatment of autonomic disorders. Id. In addition to the above, Dr. Gibbons has also served as the
President of the American Autonomic Society and Chair of the Autonomic Section of the
American Academy of Neurology. Gibbons CV at 3; Gibbons First Rep. at 1.
Over the course of his career, Dr. Gibbons has repeatedly in his clinical practice evaluated
and treated patients with POTS and has tested approximately 100 POTS patients per year in the
autonomic laboratory. Gibbons First Rep. at 1. In addition to his clinical work, Dr. Gibbons has
given numerous national and international lectures on the topic of autonomic disorders and POTS,
and has published over 100 research articles, chapters, and books on the subject matter. Id. Dr.
Gibbons does not have specific expertise in immunologic issues.
First Report
Dr. Gibbons provided his own overview of A.F.’s medical history as revealed by the filed
records. Gibbons First Rep. at 1–2. He specifically noted that there was in the record some
reference to pre-vaccination syncopal events, although he acknowledged it was vague in nature.
Id. at 2–3. He then provided a definition of POTS largely consistent with what Dr. Miglis had
proposed (including its characteristics and diagnostic factors)—although he gave more emphasis
to the wide variety of explanations for it (for example, astronauts often experienced POTS after
space voyages due to deconditioning they experienced “in the absence of gravity”). Id. at 2; R.
Freeman et al., Consensus Statement on the Definition of Orthostatic Hypotension, Neurally
Mediated Syncope, and the Postural Tachycardia Syndrome, 161 Autonomic Neuroscience: Basic
18
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and Clinical 46 (2011), filed as Ex. A Tab 1 (ECF No. 18-2) (“Freeman”), at 48 (deeming POTS’s
etiology “likely to be heterogeneous,” and “associated with deconditioning, recent viral illness,
chronic fatigue syndrome and a limited or restricted autonomic neuropathy”). POTS could also
manifest in the presence of other disorders, like thyroid issues, anxiety, dehydration, or as a side-
effect of certain medications. Id. 20
Dr. Gibbons accepted Petitioner’s POTS diagnosis. Gibbons First Rep. at 3. But he denied
any causal relationship between POTS and the HPV vaccine. First, he took issue with the extent
to which POTS could be considered reliably associated with autoimmunity. Id. at 3–4. He noted
that one article relied upon by Dr. Miglis to establish a general POTS/autoimmunity connection,
Blitshteyn II, emphasized the degree to which a large percentage of POTS patients had a specific
ANA titer—a measure Dr. Gibbons denied was clinically significant, especially since many
individuals also possessed that titer level. Id. at 3; Blitshteyn II at 1367.
More specifically, Dr. Gibbons questioned the probative value of the articles referenced by
Dr. Miglis for the proposition that POTS patients often tested positive for certain kinds of anti-
adrenergic autoantibodies believed to potentially be associated with some instances of POTS. He
emphasized the small sample sizes at issue in such articles, and lack of “validated” testing
methodologies to confirm the presence of such autoantibodies in the first place. Gibbons First Rep.
at 4. He further denied the existence of “reliable or persuasive evidence that these antibodies are
pathogenic,” adding that the patient sample groups in some instances were not even comparable
to Petitioner—since they involved patients far older, and who likely had not received an HPV
vaccine pre-testing (given that the studied samples were pre-2013, when the HPV vaccine became
more prevalent). Id; Fedorowski at 1212. The relevant autoantibodies were also detected in other
non-comparable patients with different diseases (dementia or ocular disease, for example), further
diminishing the likelihood that they were as specific to POTS as alleged. A. Miller & T. Doherty,
Hop to It: The First Animal Model of Autoimmune Postural Orthostatic Tachycardia Syndrome, 8
J. Am. Heart Assoc. 1–3, 2 (2019), filed as Ex. A Tab 5 (ECF No. 18-6) (“Miller”) at 3 (editorial
commenting on Li II animal model, and noting questions about “how well this rabbit model of
POTS represents the heterogeneous patient population and whether it will contribute to further
advancements toward novel therapeutics for POTS”). Dr. Gibbons echoed Miller’s concern that
“it is unclear whether the presence of adrenergic autoantibodies in participants with POTS is a
bystander effect of the primary disease process or whether they are centrally pathogenic”). Miller
at 2.
20
Dr. Gibbons also discussed Ehlers Danlos syndrome, explaining that it too could often result in POTS as a secondary
symptom—and might even explain Petitioner’s POTS. Gibbons First Rep. at 2–3. Although a credible case could
be made based on the evidence filed herein that A.F.’s POTS was attributable to her diagnosed Ehlers Danlos
syndrome, I am resolving the case based on the more fundamental finding that the HPV vaccine does not likely cause
POTS.
19
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The case report series articles Dr. Miglis cited as connecting POTS to the HPV vaccine
were in Dr. Gibbons’s view equally deficient. As discussed above, Dr. Gibbons emphasized that
the sample groups in articles referenced were often subject to selection/referral bias, since only
patients who sought care for suspected vaccine reactions were considered, and without
unvaccinated controls. Gibbons First Rep. at 4. Another article found that reported increases of
post-HPV vaccination POTS “were likely related to increased attention on the diagnosis of POTS
in the setting of medical reports,” rather than a causal relationship. Gibbons First Rep. at 5; Ward
at 8.
Dr. Gibbons also cited two large-scale observational studies that he maintained undermined
any POTS/HPV vaccine association. One was prepared by the EMA. Gibbons First Rep. at 4;
EMA Report at 38 (concluding that “[o]verall, available data do not provide support for a causal
relationship between HPV vaccines and POTS,” and criticizing Brinth for conflating POTS with
chronic fatigue syndrome). Another, from Finland, considered the incidence of POTS, among
other illnesses, after receipt of the HPV vaccine over a ten-year period (2002-12), with no evidence
that POTS was increasing after the vaccine was becoming widespread in use (while confirming
Ward’s finding that mere awareness of the diagnosis of POTS was producing speculation that post-
vaccination causation was a possibility). Skufca I at 94–95. Indeed, at least one article observed a
decrease in incidence of POTS after introduction of the vaccine (compared to years when it was
not utilized). J. Skufca et al., The Association of Adverse Events with Bivalent Human
Papillomavirus Vaccination: A Nationwide Register-based Cohort Study in Finland, 36 Vaccine
5926–5933 (2018), filed as Ex. A Tab 10 (ECF No. 18-11) (“Skufca II”).
Ultimately, the most reliable scientific authorities on the topic (in Dr. Gibbons’s
estimation) had expressly discounted any reliable causal relationship between POTS and receipt
of the HPV vaccine. Gibbons First Rep. at 5; AAS Statement at 3. Dr. Gibbons was a co-signer of
the AAS Statement, which maintained that “[l]arge population studies and exposure of over 270
million people to the HPV vaccine have not resulted in an identifiable pattern of adverse events,
and no evidence of an increase in dysautonomia or POTS with use of the vaccine.” AAS Statement
at 3.
Second Report
Dr. Gibbons’s second report endeavored to succinctly respond to objections leveled against
the contents of his initial opinion by Drs. Miglis and Ahmed. Dr. Miglis, he maintained, placed
too much emphasis on the mere fact that there was a temporal association between the HPV
vaccine and Petitioner’s POTS—an insufficient basis for a finding of causality. Gibbons Second
Rep. at 2. Petitioner’s possession of the purportedly-causal anti-adrenergic autoantibodies was in
20
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fact not confirmed on testing from August 2020 (two and one-half years after vaccination), 21 and
otherwise the results were not reliable. Ex. 48 at 1. The testing at issue, he noted, is not available
within the U.S. Moreover, the two types of autoantibody that the testing suggested were even
slightly elevated, such as “anti ETAR” autoantibodies, had not been shown under the Petitioner’s
causation theory to be possibly pathogenic in the context of POTS. Id.Dr. Gibbons also reiterated his prior argument questioning whether the purportedly
pathogenic autoantibodies identified in Dr. Miglis’s theory could actually initiate POTS. These
kinds of autoantibodies “are not specific for any disease,” and have been identified in association
with a broad number of other conditions. Gibbons Second Rep. at 3; S. Vernino & L. Stiles,
Autoimmunity in Postural Orthostatic Tachycardia Syndrome: Current Understanding, 215
Autonomic Neuroscience: Basic and Clinical 78 (2018), filed as Ex. C Tab 1 (ECF No. 29-2)
(“Vernino”). Although Vernino emphasized (consistent with other general articles) that “POTS
likely has a heterogeneous pathophysiology,” it discussed the existing state of scientific
understanding of potential autoimmune factors in some cases of POTS—and specifically the
GPCR/anti-adrenergic autoantibodies proposed as causal in this case. Vernino at 80. But the article
notes that these autoantibodies “are not novel,” and have been observed in connection with general
cardiovascular disorders, thyroid issues, and specific known autoimmune diseases. Id. Ultimately,
Vernino proposed that because these autoantibodies are seen in so many diverse illnesses or
conditions, “they may represent an immune response to tissue injury or some sort of physiological
regulatory response to cardiac stress.” Id. This is not consistent with this class of autoantibodies
being initially causal of POTS.
In addition, Dr. Gibbons made several observations about weaknesses in various items of
literature offered to support Petitioner’ causation theory. Fedorowski, for example, likely had a
sample of patients not comparable to A.F. in age. Gibbons Second Rep. at 3; Fedorowski at 2.
Gunning, by contrast, likely included a population that had not even received the vaccine,
based upon their age at the time of the study. Gibbons Second Rep. a 3; Gunning at 2. And Dr.
Gibbons rejected Dr. Miglis’s argument that the AAS Statement was unreliable because it did not
include all AAS members as signatories, noting that dissenting members could have made their
views known had they objected to its contents.
Dr. Gibbons also commented on Dr. Ahmed’s attacks. 22 He did not find that studies
involving very small patient samples, like Kinoshita (44 patients) and Blitsheyn I (six patients),
21
Dr. Gibbons also expressed skepticism toward Dr. Miglis’s argument that “maybe the antibody titers have declined”
for Petitioner in the time since vaccination more than two years before (which might explain why certain relevant
autoantibodies were undetected, or only deemed to be at levels considered “at risk”). Gibbons Second Rep. at 3.
22
Dr. Gibbons initially reiterated the view (mentioned in footnote 11 above) that Shaw is nothing more than an online
survey that lacks core methodologic reliability. Gibbons Second Rep. at 1. I do not expand on this attack, however,
since I consider the fundamental deficiency of Shaw’s methodology deprives it significant scientific reliability, and
hence it merits little weight in my analysis.
21
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that purported to identify “very modest temporal associations” between the HPV vaccine and
POTS, were especially probative of a causal association. Gibbons Second Rep. at 2. He also noted
a variety of omissions in Dr. Ahmed’s logical causation chain. Comparisons to GBS, for example,
were unavailing, since it is a “well characterized autoimmune disorder” with reliably-researched
characteristics that bear on vaccine causation. Id. POTS, by contrast, “is a poorly defined series of
symptoms . . . that can be due to any number of” causes, “and has only been hypothesized to be
due to autoimmune disease.” Id. And the very limited amount of case report evidence, in
comparison to the number of vaccine doses given, suggested a lack of probative evidence
connecting the two. Id.Another challenge Dr. Gibbons raised to Dr. Ahmed’s opinion was the proposition that the
HPV vaccine could mediate POTS via molecular mimicry. Dr. Ahmed relied on Blitshteyn I for
this aspect of his theory—even though the article itself was (a) penned by “a general neurologist
with no training in immunology,” and (b) contained no independent evidence that POTS could in
fact be mediated through this specific autoimmune mechanism. Gibbons Second Rep. at 2;
Blitshteyn I at 138. Dr. Ahmed also cited Li II’s animal model, but the heart rate increase that had
been observed was only a ten percent increase—not sufficient to meet a POTS diagnosis. Gibbons
Second Rep. at 2. In addition, the tested rabbits in Li II are quadrupeds that do not typically face
the orthostatic stress of standing upright, and hence the tested heartrate changes observed in Li II
“are of unclear relevance to the human condition.” Gibbons Second Rep. at 2.
Third Report
Dr. Gibbons’s final report responded only to the third, short report offered by Dr. Miglis
(which as noted above sought solely to analogize some recent studies about COVID-19 and its
association with POTS to the present case). He characterized the general state of scientific study
of COVID-19 and its secondary symptomatic features as “dynamic and unsettled,” maintaining
the view that not enough was known about how the coronavirus can impact the nervous system
generally to draw the conclusions Dr. Miglis proposed. Gibbons Third Rep. at 1. He also noted
that there were competing mechanistic theories for how COVID-19 might produce neurologic
manifestations, with molecular mimicry serving as only one possibility that had yet to be fully
embraced or confirmed. Id. Dr. Gibbons also noted that one of the articles referenced by Dr. Miglis
as evidence of a COVID-19 relationship with the relevant autoantibodies was too limited in sample
scope (an “N of 1” trial, rather than a study with many sampled subjects), and also involved
evidence of the relevant autoantibodies long predating the COVID-19 diagnosis. Id. He thus
concluded that this evidence, while interesting, could not be persuasively marshaled to support the
causation theory in this case.
22
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III. Procedural History
As noted above, the case was initiated in March 2019. In lieu of a Rule 4(c) Report,
Respondent filed a status report stating their initial reaction to the claim. ECF No. 15. Following
the filing of pertinent medical records and an affidavit, Petitioner offered Dr. Miglis’s first expert
report in February 2020. ECF No. 16. Thereafter Respondent filed his first expert report from Dr.
Gibbons in June 2020, and Petitioner filed an expert report from Dr. Ahmed in November 2020.
ECF Nos. 18, 23. Respondent’s expert filed two supplemental reports, and Petitioner’s expert Dr.
Ahmed filed an additional supplemental report with Dr. Miglis filing two supplemental reports.
ECF Nos. 26, 29, 30, 34, 36. The parties fully briefed the matter by April 2022, and it is now ripe
for resolution.
IV. Parties’ Arguments
Petitioner
Petitioner argues that she has established causation under the three-prong test set by the
Federal Circuit in Althen v. Sec'y of Health and Hum. Servs., 418 F.3d 1274, 1278 (Fed. Cir. 2005).
Mot. at 1. As Petitioner’s experts emphasized, there is a growing consensus within the medical
community that POTS can be immune-mediated for genetically predisposed individuals. Mot. at
2; Reply at 2, 5. Many studies have identified GPCR/anti-adrenergic autoantibodies believed to
play a role in the pathogenesis of the immune-mediated form of POTS. Mot. at 2; Reply at 2, 4.
Molecular mimicry is a biologically plausible mechanism linking the HPV vaccine to POTS (just
as it has applicability in the context of other known autoimmune disease processes). Reply at 2–3.
In particular, the HPV vaccine could initiate “an immune response that triggers an autoimmune
response that progresses to an autoimmune condition.” Reply at 4, 6; Ahmed First Rep. at 8, 71.
To support her causation theory, Petitioner highlighted some of the more recently-
published articles or studies her experts had discussed. Reply at 2, 4. Federowski, for example,
indicated autoantibodies play a role in the pathophysiology of POTS, and Gunning supported the
theory that POTS could actually be an autoimmune disorder. Reply at 5; Federowski at 1214–15;
Gunning at 9. Moreover, an animal study, Li II, had more directly linked adrenergic autoantibodies
and POTS. Reply at 6; Li II at 8. And Hineno suggested some symptoms following vaccination
might be attributed to an abnormal autoimmune response. Reply at 5; Hineno at 5. Respondent, by
contrast, relied heavily on less-contemporaneous articles. Reply at 7. Thus, the many new scientific
developments (including studies about COVID-19’s link to POTS) provided the kind of reliable
evidence lacking from prior cases. Reply at 4, 7–9.
Petitioner also argued that the record supported the conclusion that the HPV vaccine likely
had caused her POTS. She had never experienced the symptoms that were later diagnosed as POTS
until after she received the vaccine, and several of her treaters deemed an association credible.
23
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Mot. at 2; Reply at 2, 9. And her four-day post-vaccination onset fell within a medically acceptable
timeframe “for a vaccine to generate an immune response and then lead to an autoimmune
response.” Mot. at 3; Reply at 1, 6; Ahmed First Rep. at 8.
Respondent
Respondent did not dispute Petitioner’s POTS diagnosis, but argued that she had failed to
satisfy the three Althen prongs necessary to establish entitlement. Opp. at 1. Respondent denied
the existence of reliable evidence linking the HPV vaccine to POTS, and emphasized that no claim
alleging such an association has been successful in the Vaccine Program (at least to date). Id. at 2.
Respondent in particular highlighted Petitioner’s failure to address the lack of evidence suggesting
POTS is an immune mediated disease, even in part. Id. at 12, 17.
Regarding some of the specific components of Petitioner’s causation theory, Respondent
disputed that the articles suggesting many POTS patients possess certain autoantibodies were
compelling, noting that there is no “approved and validated test for these antibodies,” let alone
reliable proof that they are in fact pathogenic. Opp. at 13–14, 17. Respondent also maintained that
Dr. Miglis had assumed POTS patients displaying these autoantibodies had received an HPV
vaccine, even though neither Fedorowski nor Gunning established that to be the case. Id. at 15.
Indeed, given the ages of the sample populations in such articles, it was unlikely that the
participants had received the HPV vaccine. Opp. at 15. In addition, Respondent maintains that
Blitshteyn II only showed the same rates of autoimmunity that would be expected in the general
population. Opp. at 13. And it was “premature” to offer studies relating to COVID-19’s alleged
association with POTS, especially given their lack of direct relevance to the HPV vaccine. Opp. at
17; Ex. 85 at 2–4.
In counter to Petitioner’s literature, Respondent invoked Vernino, arguing that it raised
compelling questions about autoimmune causes for POTS. Opp. at 13; Vernino at 79–80. Vernino
also found that no antibody is specifically understood to be likely causative of POTS, and thus
there was “insufficient proof of an autoimmune cause for POTS based on the current research.”
Opp. at 14–15. And the autoantibodies proposed to be mediating post-HPV vaccine POTS are
frequently found in healthy individuals, “have not been demonstrated as antigenic in any context,”
and have not even been shown to be pathogenic in any regard, despite being “described in many
disorders”. Opp. at 14. Respondent also maintained that there exist some large-scale epidemiologic
evidence undermining the contention that the HPV vaccine can cause POTS. Id. at 15–16; Skufca
II at 1.
Otherwise, Respondent argued, Petitioner could only demonstrate a temporal association
between the vaccination at issue and Petitioner’s POTS. Opp. at 18–19. She failed to offer
medically-acceptable proof of a “metric establishing a timeframe that could be temporally
appropriate.” Id. at 20.
24
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V. Applicable Legal Standards
A. Petitioner’s Overall Burden in Vaccine Program Cases
To receive compensation in the Vaccine Program, a petitioner must prove either: (1) that
he suffered a “Table Injury”—i.e., an injury falling within the Vaccine Injury Table—
corresponding to one of the vaccinations in question within a statutorily prescribed period of time
or, in the alternative, (2) that his illnesses were actually caused by a vaccine (a “Non-Table
Injury”). See Sections 13(a)(1)(A), 11(c)(1), and 14(a), as amended by 42 C.F.R. § 100.3; §
11(c)(1)(C)(ii)(I); see also Moberly v. Sec’y of Health & Hum. Servs., 592 F.3d 1315, 1321 (Fed.
Cir. 2010); Capizzano v. Sec’y of Health & Hum. Servs., 440 F.3d 1317, 1320 (Fed. Cir. 2006). 23
In this case, Petitioner does not assert a Table claim, nor does there exist such a claim for POTS
(or autonomic disfunction generally) as the injury.
For both Table and Non-Table claims, Vaccine Program petitioners bear a “preponderance
of the evidence” burden of proof. Section 13(1)(a). That is, a petitioner must offer evidence that
leads the “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, 592 F.3d at 1322 n.2; see also Snowbank Enter. v. United States, 6 Cl. Ct.
476, 486 (1984) (mere conjecture or speculation is insufficient under a preponderance standard).
Proof of medical certainty is not required. Bunting v. Sec’y of Health & Hum. Servs., 931 F.2d
867, 873 (Fed. Cir. 1991). In particular, a petitioner must demonstrate that the vaccine was “not
only [the] but-for cause of the injury but also a substantial factor in bringing about the injury.”
Moberly, 592 F.3d at 1321 (quoting Shyface v. Sec’y of Health & Hum. Servs., 165 F.3d 1344,
1352–53 (Fed. Cir. 1999)); Pafford v. Sec’y of Health & Hum. Servs., 451 F.3d 1352, 1355 (Fed.
Cir. 2006). A petitioner may not receive a Vaccine Program award based solely on his assertions;
rather, the petition must be supported by either medical records or by the opinion of a competent
physician. Section 13(a)(1).
In attempting to establish entitlement to a Vaccine Program award of compensation for a
Non-Table claim, a petitioner must satisfy all three of the elements established by the Federal
Circuit in Althen, 418 F.3d at 1278: “(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 proximate temporal relationship between vaccination and
23
Decisions of special masters (some of which I reference in this ruling) constitute persuasive but not binding
authority. Hanlon v. Sec’y of Health & Hum. Servs., 40 Fed. Cl. 625, 630 (1998). By contrast, Federal Circuit rulings
concerning legal issues are binding on special masters. Guillory v. Sec’y of Health & Hum. Servs., 59 Fed. Cl. 121,
124 (2003), aff’d 104 F. Appx. 712 (Fed. Cir. 2004); see also Spooner v. Sec’y of Health & Hum. Servs., No. 13-159V,
2014 WL 504728, at *7 n.12 (Fed. Cl. Spec. Mstr. Jan. 16, 2014).
25
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injury.” Each Althen prong requires a different showing and is discussed in turn along with the
parties’ arguments and my findings.
Under Althen prong one, petitioners must provide a “reputable medical theory,”
demonstrating that the vaccine received can cause the type of injury alleged. Pafford, 451 F.3d at
1355–56 (citations omitted). To satisfy this prong, a petitioner’s theory must be based on a “sound
and reliable medical or scientific explanation.” Knudsen v. Sec’y of Health & Hum. Servs., 35 F.3d
543, 548 (Fed. Cir. 1994). Such a theory must only be “legally probable, not medically or
scientifically certain.” Id. at 549.
However, the Federal Circuit has repeatedly stated that the first prong requires a
preponderant evidentiary showing. See Boatmon v. Sec'y of Health & Hum. Servs., 941 F.3d 1351,
1360 (Fed. Cir. 2019) (“[w]e have consistently rejected theories that the vaccine only “likely
caused” the injury and reiterated that a “plausible” or “possible” causal theory does not satisfy the
standard”); see also Moberly v. Sec'y of Health & Hum. Servs., 592 F.3d 1315, 1321 (Fed. Cir.
2010); Broekelschen v. Sec'y of Health & Hum. Servs., 618 F.3d 1339, 1350 (Fed. Cir. 2010). This
is consistent with the petitioner's ultimate burden to establish his overall entitlement to damages
by preponderant evidence. W.C. v. Sec'y of Health & Hum. Servs., 704 F.3d 1352, 1356 (Fed. Cir.
2013) (citations omitted). If a claimant must overall meet the preponderance standard, it is logical
that they be required also to meet each individual prong with the same degree of evidentiary
showing (even if the type of evidence offered for each is different).
Petitioners may offer a variety of individual items of evidence in support of the first Althen
prong, and are not obligated to resort to medical literature, epidemiological studies, demonstration
of a specific mechanism, or a generally accepted medical theory. Andreu v. Sec'y of Health & Hum.
Servs., 569 F.3d 1367, 1378–79 (Fed. Cir. 2009) (citing Capizzano, 440 F.3d at 1325–26). No one
“type” of evidence is required. Special masters, despite their expertise, are not empowered by
statute to conclusively resolve what are essentially thorny scientific and medical questions, and
thus scientific evidence offered to establish Althen prong one is viewed “not through the lens of
the laboratorian, but instead from the vantage point of the Vaccine Act's preponderant evidence
standard.” Andreu, 569 F.3d at 1380. Nevertheless, even though “scientific certainty” is not
required to prevail, the individual items of proof offered for the “can cause” prong must each
reflect or arise from “reputable” or “sound and reliable” medical science. Boatmon, 941 F.3d at
1359–60.
The second Althen prong requires proof of a logical sequence of cause and effect, usually
supported by facts derived from a petitioner’s medical records. Althen, 418 F.3d at 1278; Andreu,
569 F.3d at 1375–77; Capizzano, 440 F.3d at 1326; Grant v. Sec'y of Health & Hum. Servs., 956
F.2d 1144, 1148 (Fed. Cir. 1992). In establishing that a vaccine “did cause” injury, the opinions
and views of the injured party's treating physicians are entitled to some weight. Andreu, 569 F.3d
26Case 1:19-vv-00446-UNJ Document 49 Filed 10/11/22 Page 27 of 39
at 1367; Capizzano, 440 F.3d at 1326 (“medical records and medical opinion testimony are favored
in vaccine cases, as treating physicians are likely to be in the best position to determine whether a
‘logical sequence of cause and effect show[s] that the vaccination was the reason for the injury’”)
(quoting Althen, 418 F.3d at 1280). Medical records are generally viewed as particularly
trustworthy evidence, since they are created contemporaneously with the treatment of the patient.
Cucuras v. Sec'y of Health & Hum. Servs., 993 F.2d 1525, 1528 (Fed. Cir. 1993).
However, medical records and/or statements of a treating physician's views do not per se
bind the special master to adopt the conclusions of such an individual, even if they must be
considered and carefully evaluated. Section 13(b)(1) (providing that “[a]ny such diagnosis,
conclusion, judgment, test result, report, or summary shall not be binding on the special master or
court”); Snyder v. Sec'y of Health & Hum. Servs., 88 Fed. Cl. 706, 746 n.67 (2009) (“there is
nothing . . . that mandates that the testimony of a treating physician is sacrosanct—that it must be
accepted in its entirety and cannot be rebutted”). As with expert testimony offered to establish a
theory of causation, the opinions or diagnoses of treating physicians are only as trustworthy as the
reasonableness of their suppositions or bases. The views of treating physicians should also be
weighed against other, contrary evidence also present in the record—including conflicting
opinions among such individuals. Hibbard v. Sec'y of Health & Hum. Servs., 100 Fed. Cl. 742,
749 (2011) (not arbitrary or capricious for special master to weigh competing treating physicians'
conclusions against each other), aff'd, 698 F.3d 1355 (Fed. Cir. 2012); Veryzer v. Sec'y of Health
& Hum. Servs., No. 06–522V, 2011 WL 1935813, at *17 (Fed. Cl. Spec. Mstr. Apr. 29, 2011),
mot. for review den'd, 100 Fed. Cl. 344, 356–57 (2011), aff'd without opinion, 475 F. App’x. 765
(Fed. Cir. 2012).
The third Althen prong requires establishing a “proximate temporal relationship” between
the vaccination and the injury alleged. Althen, 418 F.3d at 1281. That term has been equated to the
phrase “medically-acceptable temporal relationship.” Id. A petitioner must offer “preponderant
proof that the onset of symptoms occurred within a timeframe which, given the medical
understanding of the disorder's etiology, it is medically acceptable to infer causation.” de Bazan v.
Sec'y of Health & Hum. Servs., 539 F.3d 1347, 1352 (Fed. Cir. 2008). The explanation for what is
a medically acceptable timeframe must also coincide with the theory of how the relevant vaccine
can cause an injury (Althen prong one's requirement). Id. at 1352; Shapiro v. Sec'y of Health &
Hum. Servs., 101 Fed. Cl. 532, 542 (2011), recons. den'd after remand, 105 Fed. Cl. 353 (2012),
aff'd mem., 2013 WL 1896173 (Fed. Cir. 2013); Koehn v. Sec'y of Health & Hum. Servs., No. 11–
355V, 2013 WL 3214877 (Fed. Cl. Spec. Mstr. May 30, 2013), mot. for review den'd (Fed. Cl.
Dec. 3, 2013), aff'd, 773 F.3d 1239 (Fed. Cir. 2014).
B. Law Governing Analysis of Fact Evidence
The process for making determinations in Vaccine Program cases regarding factual issues
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begins with consideration of the medical records. Section 11(c)(2). The special master is required
to consider “all [ ] relevant medical and scientific evidence contained in the record,” including
“any diagnosis, conclusion, medical judgment, or autopsy or coroner's report which is contained
in the record regarding the nature, causation, and aggravation of the petitioner's illness, disability,
injury, condition, or death,” as well as the “results of any diagnostic or evaluative test which are
contained in the record and the summaries and conclusions.” Section 13(b)(1)(A). The special
master is then required to weigh the evidence presented, including contemporaneous medical
records and testimony. See Burns v. Sec'y of Health & Hum. Servs., 3 F.3d 415, 417 (Fed. Cir.
1993) (determining that it is within the special master's discretion to determine whether to afford
greater weight to contemporaneous medical records than to other evidence, such as oral testimony
surrounding the events in question that was given at a later date, provided that such determination
is evidenced by a rational determination).
As noted by the Federal Circuit, “[m]edical records, in general, warrant consideration as
trustworthy evidence.” Cucuras, 993 F.2d at 1528; Doe/70 v. Sec'y of Health & Hum. Servs., 95
Fed. Cl. 598, 608 (2010) (“[g]iven the inconsistencies between petitioner's testimony and his
contemporaneous medical records, the special master's decision to rely on petitioner's medical
records was rational and consistent with applicable law”), aff'd, Rickett v. Sec'y of Health & Hum.
Servs., 468 F. App’x 952 (Fed. Cir. 2011) (non-precedential opinion). A series of linked
propositions explains why such records deserve some weight: (i) sick people visit medical
professionals; (ii) sick people attempt to honestly report their health problems to those
professionals; and (iii) medical professionals record what they are told or observe when examining
their patients in as accurate a manner as possible, so that they are aware of enough relevant facts
to make appropriate treatment decisions. Sanchez v. Sec'y of Health & Hum. Servs., No. 11–685V,
2013 WL 1880825, at *2 (Fed. Cl. Spec. Mstr. Apr. 10, 2013); Cucuras v. Sec'y of Health & Hum.
Servs., 26 Cl. Ct. 537, 543 (1992), aff'd, 993 F.2d at 1525 (Fed. Cir. 1993) (“[i]t strains reason to
conclude that petitioners would fail to accurately report the onset of their daughter's symptoms”).
Accordingly, if the medical records are clear, consistent, and complete, then they should
be afforded substantial weight. Lowrie v. Sec'y of Health & Hum. Servs., No. 03–1585V, 2005 WL
6117475, at *20 (Fed. Cl. Spec. Mstr. Dec. 12, 2005). Indeed, contemporaneous medical records
are often found to be deserving of greater evidentiary weight than oral testimony—especially
where such testimony conflicts with the record evidence. Cucuras, 993 F.2d at 1528; see also
Murphy v. Sec'y of Health & Hum. Servs., 23 Cl. Ct. 726, 733 (1991), aff'd per curiam, 968 F.2d
1226 (Fed. Cir. 1992), cert. den'd, Murphy v. Sullivan, 506 U.S. 974 (1992) (citing United States
v. United States Gypsum Co., 333 U.S. 364, 396 (1947) (“[i]t has generally been held that oral
testimony which is in conflict with contemporaneous documents is entitled to little evidentiary
weight.”)).
However, the Federal Circuit has also noted that there is no formal “presumption” that
28
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records are accurate or superior on their face when compared to other forms of evidence. Kirby v.
Sec’y of Health & Hum. Servs., 997 F.3d 1378, 1383 (Fed. Cir. 2021). There are certainly situations
in which compelling oral testimony may be more persuasive than written records, such as where
records are deemed to be incomplete or inaccurate. Campbell v. Sec'y of Health & Hum. Servs., 69
Fed. Cl. 775, 779 (2006) (“like any norm based upon common sense and experience, this rule
should not be treated as an absolute and must yield where the factual predicates for its application
are weak or lacking”); Lowrie, 2005 WL 6117475, at *19 (“[w]ritten records which are,
themselves, inconsistent, should be accorded less deference than those which are internally
consistent”) (quoting Murphy, 23 Cl. Ct. at 733)). Ultimately, a determination regarding a witness's
credibility may be required when determining the weight that such testimony should be afforded.
Andreu, 569 F.3d at 1379; Bradley v. Sec'y of Health & Hum. Servs., 991 F.2d 1570, 1575 (Fed.
Cir. 1993).
When witness testimony is offered to overcome the presumption of accuracy afforded to
contemporaneous medical records, such testimony must be “consistent, clear, cogent, and
compelling.” Sanchez, 2013 WL 1880825, at *3 (citing Blutstein v. Sec'y of Health & Hum. Servs.,
No. 90–2808V, 1998 WL 408611, at *5 (Fed. Cl. Spec. Mstr. June 30, 1998)). In determining the
accuracy and completeness of medical records, the Court of Federal Claims has listed four possible
explanations for inconsistencies between contemporaneously created medical records and later
testimony: (1) a person's failure to recount to the medical professional everything that happened
during the relevant time period; (2) the medical professional's failure to document everything
reported to her or him; (3) a person's faulty recollection of the events when presenting testimony;
or (4) a person's purposeful recounting of symptoms that did not exist. La Londe v. Sec'y of Health
& Hum. Servs., 110 Fed. Cl. 184, 203–04 (2013), aff'd, 746 F.3d 1334 (Fed. Cir. 2014). In making
a determination regarding whether to afford greater weight to contemporaneous medical records
or other evidence, such as testimony at hearing, there must be evidence that this decision was the
result of a rational determination. Burns, 3 F.3d at 417.
C. Analysis of Expert Testimony
Establishing a sound and reliable medical theory often requires a petitioner to present
expert testimony in support of his claim. Lampe v. Sec’y of Health & Hum. Servs., 219 F.3d 1357,
1361 (Fed. Cir. 2000). Vaccine Program expert testimony is usually evaluated according to the
factors for analyzing scientific reliability set forth in Daubert v. Merrell Dow Pharm., Inc., 509
U.S. 579, 594–96 (1993). See Cedillo v. Sec’y of Health & Hum. Servs., 617 F.3d 1328, 1339 (Fed.
Cir. 2010) (citing Terran v. Sec’y of Health & Hum. Servs., 195 F.3d 1302, 1316 (Fed. Cir. 1999).
Under Daubert, the factors for analyzing the reliability of testimony are:
(1) whether a theory or technique can be (and has been) tested; (2) whether the
theory or technique has been subjected to peer review and publication; (3) whether
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there is a known or potential rate of error and whether there are standards for
controlling the error; and (4) whether the theory or technique enjoys general
acceptance within a relevant scientific community.
Terran, 195 F.3d at 1316 n.2 (citing Daubert, 509 U.S. at 592–95).
However, in the Vaccine Program the Daubert factors play a slightly different role than
they do when applied in other federal judicial settings—e.g., the district courts. Typically, Daubert
factors are employed by judges (in the performance of their evidentiary gatekeeper roles) to
exclude evidence that is unreliable or could confuse a jury. By contrast, in Vaccine Program cases
these factors are used in the weighing of the reliability of scientific evidence proffered. Davis v.
Sec'y of Health & Hum. Servs., 94 Fed. Cl. 53, 66–67 (2010) (“uniquely in this Circuit, the Daubert
factors have been employed also as an acceptable evidentiary-gauging tool with respect to
persuasiveness of expert testimony already admitted”). The flexible use of the Daubert factors to
evaluate the persuasiveness and reliability of expert testimony has routinely been upheld. See, e.g.,
Snyder, 88 Fed. Cl. at 742–45. In this matter (as in numerous other Vaccine Program cases),
Daubert has not been employed at the threshold, to determine what evidence should be admitted,
but instead to determine whether expert testimony offered is reliable and/or persuasive.
Respondent frequently offers one or more experts in order to rebut a petitioner’s case.
Where both sides offer expert testimony, a special master's decision may be “based on the
credibility of the experts and the relative persuasiveness of their competing theories.”
Broekelschen v. Sec'y of Health & Hum. Servs., 618 F.3d 1339, 1347 (Fed. Cir. 2010) (citing
Lampe, 219 F.3d at 1362). However, nothing requires the acceptance of an expert's conclusion
“connected to existing data only by the ipse dixit of the expert,” especially if “there is simply too
great an analytical gap between the data and the opinion proffered.” Snyder, 88 Fed. Cl. at 743(quoting Gen. Elec. Co. v. Joiner, 522 U.S. 146 (1997)); see also Isaac v. Sec'y of Health & Hum.
Servs., No. 08–601V, 2012 WL 3609993, at *17 (Fed. Cl. Spec. Mstr. July 30, 2012), mot. for
review den'd, 108 Fed. Cl. 743 (2013), aff'd, 540 F. App’x. 999 (Fed. Cir. 2013) (citing Cedillo,
617 F.3d at 1339). Weighing the relative persuasiveness of competing expert testimony, based on
a particular expert's credibility, is part of the overall reliability analysis to which special masters
must subject expert testimony in Vaccine Program cases. Moberly, 592 F.3d at 1325–26
(“[a]ssessments as to the reliability of expert testimony often turn on credibility determinations”);
see also Porter v. Sec'y of Health & Hum. Servs., 663 F.3d 1242, 1250 (Fed. Cir. 2011) (“this court
has unambiguously explained that special masters are expected to consider the credibility of expert
witnesses in evaluating petitions for compensation under the Vaccine Act”).
D. Consideration of Medical Literature
Both parties filed numerous items of medical and scientific literature in this case, but not
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every filed item factors into the outcome of this Decision. While I have reviewed all the medical
literature submitted in this case, I discuss only those articles that are most relevant to my
determination and/or are central to Petitioner’s case—just as I have not exhaustively discussed
every individual medical record filed. Moriarty v. Sec’y of Health & Hum. Servs., 844 F.3d 1322,
1328 (Fed. Cir. 2016) (“[w]e generally presume that a special master considered the relevant record
evidence even though he does not explicitly reference such evidence in his decision”) (citation
omitted); see also Paterek v. Sec’y of Health & Hum. Servs., 527 F. Appx. 875, 884 (Fed. Cir.
2013) (“[f]inding certain information not relevant does not lead to—and likely undermines—the
conclusion that it was not considered”).
E. Disposition of Case Without Hearing
I am resolving Petitioner’s claim on the filed record. The Vaccine Act and Rules not only
contemplate but encourage special masters to decide petitions on the papers where (in the exercise
of their discretion) they conclude that doing so will properly and fairly resolve the case. Section
12(d)(2)(D); Vaccine Rule 8(d). The decision to rule on the record in lieu of hearing has been
affirmed on appeal. Kreizenbeck v. Sec’y of Health & Hum. Servs., 945 F.3d 1362, 1366 (Fed. Cir.
2020); see also Hooker v. Sec’y of Health & Hum. Servs., No. 02-472V, 2016 WL 3456435, at *21
n.19 (Fed. Cl. Spec. Mstr. May 19, 2016) (citing numerous cases where special masters decided
case on the papers in lieu of hearing and that decision was upheld). I am simply not required to
hold a hearing in every matter, no matter the preferences of the parties. Hovey v. Sec’y of Health
& Hum. Servs., 38 Fed. Cl. 397, 402–03 (1997) (determining that special master acted within his
discretion in denying evidentiary hearing); Burns, 3 F.3d at 417; Murphy v. Sec’y of Health &
Hum. Servs., No. 90-882V, 1991 WL 71500, at *2 (Fed. Cl. Spec. Mstr. Apr. 19, 1991).
ANALYSIS
I. POTS Has Not Previously Been Found to be Caused by the HPV Vaccine
The parties agree A.F. was appropriately diagnosed with POTS—leaving primarily
the question of whether POTS can be caused by the HPV vaccine.
There are no persuasive reasoned Program decisions finding that the HPV vaccine can
interfere with any aspect of the nervous system sufficiently to cause any form of orthostatic
intolerance—whether manifesting as vasovagal syncope, POTS, or some other comparable
autonomic dysfunction. See, e.g., E.S. v. Sec'y of Health & Hum. Servs., No. 17-480V, 2020 WL
9076620, at *42 (Fed. Cl. Spec. Mstr. Nov. 13, 2020), mot. for review den’d, 154 Fed. Cl. 149(2021) (“[a]lthough I am considering a large number of alleged injuries [specifically, headaches,
chronic fatigue syndrome, POTS, and small fiber neuropathy] . . . I universally find that Petitioner
has not in any instance established [in this case] that the HPV or flu vaccines “can cause” the
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relevant injury”) (emphasis in original); Balasco v. Sec’y of Health & Hum. Servs., No. 17-215V,
2020 WL 1240917, at *34 (Fed. Cl. Spec. Mstr. Feb. 14, 2020) (articulating that the special master
“[did] not find preponderant evidence of a reliable medical theory causally connecting petitioner’s
HPV vaccinations to either POTS generally or her own fibromyalgia and/or vestibular migraines
in particular”); Johnson v. Sec'y of Health & Hum. Servs., No. 14-254V, 2018 WL 2051760, at
*24 (Fed. Cl. Spec. Mstr. Mar. 23, 2018) (discussing how the petitioner failed to establish a reliable
medical causation theory that the HPV vaccine established autonomic nervous system or
orthostatic intolerance conditions); Combs v. Sec’y of Health & Hum. Servs., No. 14-878V, 2018
WL 1581672, at * 1 (Fed. Cl. Spec. Mstr. Feb. 15, 2018) (“[p]etitioner's causation theory—that
the HPV vaccine could damage the autonomic nervous system—was scientifically unreliable and
unpersuasive . . . .”); K.L. v. Sec'y of Health & Hum. Servs., No. 12-312V, 2017 WL 1713110, at
*15 (Fed. Cl. Spec. Mstr. Mar. 17, 2017) (noting that respondent demonstrated more persuasively
that there was “no link between a number of neurological events, including epilepsy, and receipt
of the HPV vaccine”), mot. for review den’d, 134 Fed. Cl. 579 (2017); L.A.M. v. Sec'y of Health
& Human Servs., No. 11–852V, 2017 WL 527576 (Fed. Cl. Spec. Mstr. Jan. 31, 2017) (concluding
that the HPV vaccine not found to cause POTS); Turkupolis v. Sec'y of Health & Human Servs.,
No. 10–351V, 2014 WL 2872215 (Fed. Cl. Spec. Mstr. May 30, 2014) (finding that the HPV
vaccine not shown to cause neurocardiogenic syncope).
In almost all such prior cases, arguments akin to what are advanced herein were considered
but rejected, often based on record evidence findings establishing the existence of POTS or some
other form of orthostatic intolerance. See, e.g., Balasco, 2020 WL 1240917, at *13, 28, 34 (noting
that petitioner (unlike in the present case) had a “positive tilt table test and tested positive for anti-
alpha-1-adrenergic antibodies, anti-beta-2 adrenergic antibodies, and the anti-muscarinic
cholinergic receptor 4 antibodies. . .”, but unsuccessfully established that this raised the likelihood
of autonomic dysautonomia, since there was not enough evidence to support the reliability or
significance of the results); McKown, 2019 WL 4072113, at *50 (stating that molecular mimicry
was not reliably invoked to explain vaccine association with syncopal symptoms); see also Yalacki
v. Sec'y of Health & Hum. Servs., No. 14-278V, 2019 WL 1061429, at *34 (Fed. Cl. Spec. Mstr.
Jan. 31, 2019), mot. for review den’d, 146 Fed. Cl. 80 (2019) (commenting on petitioner’s theory
that the Hep B vaccine could trigger a pathogenic process resulting in an autoimmune attack
leading to an injury, but finding that it was “not enough for a claimant to invoke the concept of
molecular mimicry” as petitioner needed to “cite to evidence, circumstantial or otherwise,
suggesting reason to find it plausible that the proposed autoimmune cross-reaction triggered by
the relevant vaccine does occur”) (emphasis in original).
In addition, these unsuccessful petitioners have commonly cited to many of the same items
of literature offered herein, like Blitshteyn I and II, Brinth, and Kinoshita. But the articles have
been criticized as unreliable or unpersuasive. See, e.g., E.S., 2020 WL 9076620, at *45 (“. . .
evidence offered to suggest a case study-oriented association, like Kinoshita, is weak, dependent
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on self-selected patient populations rather than scientifically-reliable studies.”); McKown, 2019
WL 4072113, at *29, 51 (noting that although Brinth was used to suggest an association between
the HPV vaccine and POTS, it revealed selection bias in the studied patients in its sample, and
otherwise suffered from a lack of reliable scientific basis); Johnson, 2018 WL 2051760, at *17, 24
(articulating that Kinoshita and Brinth both involved self-selection and lacked scientifical
reliability); Combs, 2018 WL 1581672, at *7 n.12, 18 (stating that the European medical
institutions evaluated Kinoshita but determined that the figure supposedly showing a correlation
between HPV vaccination and autonomic conditions was actually attributable to overreporting
rather than a scientifically-based association). Literature filed by Respondent that provides an
overview of these kinds of studies confirms their unreliable and unpersuasive character. B. Butts
et al., Human Papillomavirus Vaccine and Postural Orthostatic Tachycardia Syndrome: a Review
of Current Literature, 32 J. Child Neurol. 11, 956 (2017), filed as Ex. A Tab 12 (ECF No. 18-13),
at 958–59, 962 (no conclusive evidence to establish causal relationship between POTS and HPV
vaccine; discussing Blitshteyn I, Brinth, Kinoshita, and Dahan).
All of the above bears heavily on the outcome in this case—and for good reason. Special
masters are directed to rely on their expertise in deciding vaccine injury cases. Hodges v. Sec’y of
Health & Hum. Servs., 9 F.3d 958, 961 (Fed. Cir. 1993). In performing their tasks, they gain
experiential insight into what kinds of evidence are more or less probative of causation—but they
also develop an understanding of the kinds of claims that do, or do not, have merit. When faced
with a claim that offers the same sorts of causal theories that have been repeatedly found wanting,
they reasonably apply their prior knowledge.
I have had multiple opportunities in the past to consider a comparable causal theory, and
have heard numerous experts propose in prior cases that components of the HPV vaccine can
initiate an autoimmune cross-reaction sufficient to impact the autonomic nervous system and cause
syncopal-like symptoms. See, e.g., McKown, 2019 WL 4072113, at *54; Johnson, 2018 WL
2051760, at *24; Combs, 2018 WL 1581672, at *18–19; K.L., 2017 WL 1713110, at *14–15. Such
cases, like this one, have attempted to invoke the general concept that a form of POTS could be
autoimmune, citing available literature (like Thieben) 24 that suggests some kind of potential
autoantibody association. But I have noted in reaction that POTS cannot properly be understood
to be primarily autoimmune in etiology (as numerous items of literature filed in this case admit)
—and that even if a rare form that is autoimmune exists, its connection with the HPV vaccine has
not been preponderantly established. McKown, 2019 WL 4072113, at *48 (noting the existence of
24
Thieben is in fact one of the older items of literature allowing for the possibility of an autoimmune form of POTS,
since it was published in 2007. And yet in a prior case relevant herein, one of Thieben’s authors (testifying as
Respondent’s expert) expressly disclaimed the article’s findings on this point, observing that his own experience
clinically, since the time of Thieben’s publication, had suggested to him that the proposed autoimmune link was far
weaker than originally theorized. Yalacki, 2019 WL 1061429, at *18. Such evidence is of course not part of this
record—but the finding in Yalacki underscores the extent to which Dr. Gibbons’s expressed skepticism of
autoimmunity as a driver of POTS has support in the relevant medical community.
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“literature support … for the idea that one particular variant of autonomic neuropathy” producing
POTS symptoms might be associated with a particular autoantibody, thereby suggesting
autoimmunity as a plausible pathologic mechanism” in some cases of orthostatic
intolerance/dysautonomia, but that it is extremely uncommon and not likely vaccine-caused). This
stands as the backdrop for Petitioner’s claim.
II. Petitioner Has Offered Insufficient New Evidence to Support
A Determination that POTS Can be Caused by the HPV Vaccine
I acknowledge that Petitioner’s experts have offered a number of more recently-published
items of medical or scientific literature relevant to her causation theory. She maintains that newer
studies better support a POTS-autoantibody association than was substantiated in the
aforementioned older cases. Indeed, some articles filed herein more expressly propose that POTS
is likely autoimmune. See, e.g., Gunning at 9. Do these more recently-published articles provide a
basis to find that POTS could be vaccine-caused, despite the outcome of so many prior cases?
Having reviewed them closely, along with the expert reports filed in this case, I answer that
question in the negative.
First, the newer items of medical/scientific literature largely supplement only one aspect
of Petitioner’s case: the attempt to establish the existence of a type of autoantibody that might
drive some subset of POTS cases. This is an intriguing scientific development, and it has been the
animal model created in Li II that gives it some support—although (as also noted in items like
Miller) that model does not provide a robust comparison to how humans (bipedal rather than four-
legged, like rabbits) experience orthostatic change upon standing. I certainly have no grounds for
questioning the specific reliability of many of these articles and studies, even though Dr. Gibbons
raised some fair objections about how reliable the testing used to identify the presence of these
autoantibodies may be—and some, like Hineno, replicate the kind of selection bias that has caused
me to give less weight to previously-published articles like Kinoshita.
What I reasonably question, however, is the scope of these articles—and the extent to
which they “add up” to a preponderant showing, in the context of a claim that has repeatedly been
unsuccessfully advanced. For too many unresolved issues remain to conclude it is more likely than
not that these autoantibodies explain POTS in enough circumstances to meet the preponderant test
applicable to the first Althen prong. A foundational issue is whether the anti-adrenergic
autoantibodies would trigger the proposed autoimmune process leading to POTS, or whether they
simply arise in connection with an existing, ongoing disease process. This is a significant question
in the context of a vaccine injury claim, where the petitioner hopes to show that vaccination of
some kind caused the autoantibodies to come into existence and initiate disease. If POTS has had
some other initiating etiology, the significance of the presence of such autoantibodies decreases,
even if they theoretically play some role in the subsequent disease process.
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A related matter is whether POTS mostly occurs due to autoimmunity, as opposed to some
physiologic deficit. Gunning’s assertion to the contrary, it is far from agreed upon by medical
science that POTS can be fully deemed an autoimmune condition, with ample explanations for
POTS having nothing to do directly with an immune response. See generally Freeman at 48; Fu &
Levine at 21. As noted above, I have in prior cases observed that at best, POTS might in a subset
of instances be autoimmune in nature, but is not commonly (and cannot be defined to be an
autoimmune disease, in the way other injuries in the Program, like GBS, are understood). Reliance
on the autoimmune form herein may be a product of the Petitioner’s awareness that the best way
to show causation is to implicate an autoimmune process that a vaccine might plausibly initiate.
But the rarity of vaccine injuries generally does not mean that more often than not, POTS occurring
after vaccination will also be the rare, autoimmune form.
This raises the second deficiency presented by these newer articles. Even if a subset of
POTS has an autoimmune character and origin, the more recent literature largely does not suggest
the HPV vaccine can cause these autoantibodies to generate in the first place. Indeed, articles like
Hineno or Gunning say little to nothing about how the autoantibodies might come into being.
Certainly the wild human papillomavirus infection itself has not been demonstrated to have
anything to do with POTS—something that need not be demonstrated to prevail, but which can
serve as the bedrock for arguments involving the vaccine. See Deshler v. Sec’y of Health & Hu.
Servs., No. 16-1070V, 2020 WL 4593162, at *18 (Fed. Cl. Spec. Mstr. July 1, 2020). (finding such
proof to be unquestionably assistive of arguments that a particular vaccine might also cause the
same injury, although it certainly is not a prerequisite to so arguing). Rather, for this aspect of her
theory, Petitioner mostly falls back onto older items of literature that purportedly show a general
association with the vaccine, like Brinth or the Blitshteyn articles, but which have been rejected as
unreliable on repeated occasions, as discussed above. Otherwise, case series evidence of POTS
occurring after receipt of the HPV vaccine does not merit significant weight. See Campbell v. Sec’y
of Health & Hum. Servs., 97 Fed. Cl. 650, 668 (2011) (“[c]ase reports do not purport to establish
causation definitively, and this deficiency does indeed reduce their evidentiary value”).
In addition, arguments about molecular mimicry driving the purported autoimmune
process herein do not rise beyond plausibility and are not otherwise bulwarked by reliable
scientific or medical evidence establishing that antibodies produced in response to components of
the HPV vaccine might in turn initiate an autoimmune cross-reaction sufficient to adversely
interact with adrenergic receptors. Much of the literature offered on this point, such as Blitshteyn
I, Segal, or Dahan, 25 proposes homologous similarities between HPV vaccine components in
25
I note also that Dahan and Segal (as well as Hineno for that matter) all have a common co-author: Dr. Yehuda
Shoenfeld. Dr. Shoenfeld has not only repeatedly testified in prior Program cases, but he has offered the express
opinion that POTS and/or orthostatic intolerance more generally is caused by the HPV vaccine, or others. See, e.g.,
Johnson, 2018 WL 2051760, at *7–12. I have not, however, found him persuasive on this subject. Id. at *24-27; see
also Yalacki, 2019 WL 1061429, at *33 (Hepatitis B vaccine and POTS; observing that “time and again, when
testifying in Vaccine Program cases, Dr. Shoenfeld has readily voiced his belief about the prevalence of autoimmunity
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conclusory fashion, or simply based on non-substantiated contentions about amino acid
sequencing that have not been independently verified in the relevant items of literature. More
broadly (and as I am forced to say over and over again in Vaccine Program cases) molecular
mimicry is not a “one size fits all” theory that can reasonably be applied to any Program case (even
if some experts wield it as such). In fact, it is relatively easy for an expert to show (using database
searches) 26 that amino acid sequences in a vaccine’s protein components match self-sequences
found within the relevant human protein. But this does not mean that invocation of molecular
mimicry in a particular case carries the day for purposes of proving a persuasive causal theory.
McKown, 2019 WL 4072113, at *50 (citing Devonshire v. Sec'y of Health & Hum. Servs., No. 99-
031V, 2006 WL 2970418, at *15 (Fed. Cl. Spec. Mstr. Sept. 2006)) (“[b]ut merely chanting the
magic words ‘molecular mimicry’ in a Vaccine Act case does not render a causation theory
scientifically reliable, absent additional evidence specifically tying the mechanism to the injury
and/or vaccine in question”) (emphasis in original), mot. for review den’d, 76 Fed. Cl. 452 (2007)).
In finding as I do, I am not determining that the evidence against Petitioner’s theory is all-
encompassing. As noted, some of the more recent literature offered herein bulwarks the possibility
that some cases of POTS are autoimmune in etiology, and that some autoantibodies that interfere
with cardiac functioning might be involved, even if their precise role remains unelucidated.
Petitioner’s experts also made a number of credible points about weaknesses in Respondent’s
defense. For example, although I give some weight to the fact that the AAS Statement reflects a
reasoned view of autonomic experts casting doubt on the strength of the HPV vaccine-POTS
association, Dr. Miglis persuasively noted that this is not itself a study that can be evaluated, but
more of an opinion piece (although ultimately Respondent’s point that the majority of the relevant
medical community is unpersuaded by a POTS-vaccine connection merits some weight).
But in the end, the evidence Petitioner relies on to prove the HPV vaccine can “more likely
than not” cause POTS is subject to the same deficiencies and limitations I have repeatedly noted
plague comparable cases—even with the more recently-published literature. It is not likely that
POTS is most commonly caused by an autoimmune process, even if certain autoantibodies have
been shown to exist in the presence of POTS; not enough is known about the limited circumstances
in which such causality is even plausible to deem anti-adrenergic autoantibodies to likely drive
and its unerring connection to vaccination—a view so deeply entrenched and unshakable that it often defies the very
legal standards I am called to apply (especially when he is asked about the timeframe over which such autoimmunity
might germinate”). While Petitioner’s experts in no way displayed this level of outcome-oriented testimony that so
discredited Dr. Shoenfeld, his authorial role in articles aimed at supporting contentions about vaccinations and
autoimmunity provides a small additional reason to question their larger validity.
26
In many cases, claimant’s experts attempt to make this kind of showing as part of the causation theory. Yet even
though it alone does not make it more likely than not that the vaccine causes the relevant cross-reaction to occur,
Petitioner’s experts in this case have not made any attempt to establish homology between HPV vaccine components
and any self-structure where POTS might be proposed to begin (let alone that the latter was itself a reliable possibility).
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pathogenesis of it, by harming the autonomic nervous system (or at least interfering with its
function); and, most importantly, it has not been preponderantly demonstrated that the HPV
vaccine likely causes such autoantibodies to come into existence in the first place. Petitioner’s
theory simply does not rise about a level of baseline plausibility—and does not add enough
additional, and/or new, science to suggest otherwise. There is thus simply not enough in this record
different from what has been presented to me so many times before to accept Petitioner’s
contentions about causation herein. 27
III. The Record Does Not Support the Conclusion that Petitioner’s POTS was
Vaccine-Caused
Even if I had found that the HPV vaccine can cause POTS, the circumstances of this case
would not allow me to conclude as well that Petitioner’s POTS was likely caused by the
vaccination. The most obvious weakness in this aspect of Petitioner’s showing is the fact that she
tested negative for virtually all of the anti-adrenergic or other autoantibodies deemed causal. See
generally Ex. 48. Although I take note of the testing lag (occurring so long after vaccination) as
potentially explaining a diminishment in the alleged relevant autoantibodies over time, the fact
remains that under Petitioner’s theory, her ongoing POTS should be corroborated by the presence
of these autoantibodies—and they are absent. Indeed, there is no evidence of Petitioner ever
possessing these autoantibodies at any prior time in her medical history.
In addition, while there is some treater speculation (in particular from Dr. Pelosi) of a
vaccine relationship to Petitioner’s onset of symptoms, the overall record does not suggest that
treater views have ever coalesced around that idea. Otherwise, Petitioner’s experience has not been
shown to be consistent with an autoimmune form of POTS, unfolding due to an aberrant response
to the HPV vaccine, as opposed to some other form attributable to a physiologic issue, which
undoubtedly explains most cases of POTS. Indeed, Petitioner has not established how, or whether,
an autoimmune-caused form of POTS would differ in clinical presentation from POTS attributable
to deconditioning, making it further difficult on this record to say that the purportedly-autoimmune
form that is the basis of Petitioner’s theory occurred in this case. At bottom, other than the fact that
Petitioner experienced POTS symptoms temporally after vaccination, the record does not suggest
the vaccine likely caused it in this case.
27
My determination that a preponderant showing on causation was not made is not equivalent to “raising the burden”
and requiring medical certainty. There are, rather, too many holes in the existing theory to conclude that vaccination
can trigger POTS. Noting these evidentiary absences is not concurrent with a demand that Petitioner prove beyond a
shadow of a doubt that the HPV vaccine can cause POTS—even if these holes had been filled, it would remain
uncertain that POTS is vaccine-caused, but I would have at least enough to go on to conclude the vaccine likely causes
it. The evidence overall as offered (and bulwarked with more recent publications) does not cross the “more likely than
not” line.
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IV. This Case Was Appropriately Decided on the Papers
In ruling on the record, I am choosing not to hold a hearing. Determining how best to
resolve a case is a matter that lies generally within my discretion, and although the parties have
not objected to my choice of this method of adjudication, I shall explain why a hearing was not
required.
Prior decisions have recognized that a special master’s discretion in deciding whether to
conduct an evidentiary hearing “is tempered by Vaccine Rule 3(b),” or the duty to “afford[] each
party a full and fair opportunity to present its case.” Hovey, 38 Fed. Cl. at 400–01 (citing Rule
3(b)). But that rule also includes the obligation of creation of a record “sufficient to allow review
of the special master’s decision.” Id. Thus, the fact that a claim is legitimately disputed, such that
the special master must exercise his intellectual faculties in order to decide a matter, is not itself
grounds for a trial (for if it were, trials would be required in every disputed case). Special masters
are expressly empowered to resolve fact disputes without a hearing—although they should only
so act if a party has been given the proper “full and fair” chance to prove their claim.
The present claim could be, and was, resolved fairly without the need for live testimony
from the experts. The parties agreed on A.F.’s diagnosis, obviating the need for testimony
on that topic. The question of the HPV-POTS association has been considered multiple times in the
Program, and I personally have decided many prior such cases. As a result, resolution of that
matter as well could be accomplished based upon the briefs and written reports. This was not a
case where live expert testimony was necessary to explain a concept, and holding a hearing would
not have affected or altered the outcome. I was otherwise able to read the expert reports and
filed literature, and to comprehend the theory presented, giving specific attention to some of the
more recently-published items of literature.
CONCLUSION
The record does not support Petitioner’s contention that the HPV vaccine she received
caused her to develop POTS. I therefore must DENY entitlement in this case.
In the absence of a motion for review filed pursuant to RCFC Appendix B, the Clerk of the
Court SHALL ENTER JUDGMENT in accordance with the terms of this Decision. 28
28
Pursuant to Vaccine Rule 11(a), the parties may expedite entry of judgment if (jointly or separately) they file notices
renouncing their right to seek review.
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IT IS SO ORDERED.
/s/ Brian H. Corcoran
Brian H. Corcoran
Chief Special Master
39