Bishara v. Secretary of Health and Human Services

In the United States Court of Federal Claims
OFFICE OF SPECIAL MASTERS
**********************
LAURIE BISHARA, *
* No. 19-115V
Petitioner, * Special Master Christian J. Moran
*
v. * Filed: January 27, 2023
*
SECRETARY OF HEALTH * Entitlement, scleroderma,
AND HUMAN SERVICES, * tetanus, diphtheria, acellular
* pertussis (Tdap), molecular
Respondent. * mimicry, case reports
**********************
Edward Kraus, Kraus Law Group, LLC, Chicago, IL, for petitioner;
Voris Edward Johnson, United States Dep’t of Justice, Washington, D.C., for
respondent.
PUBLISHED DECISION DENYING COMPENSATION1
Ms. Laurie Bishara alleges that the tetanus-diphtheria-acellular-pertussis
(Tdap) vaccine that she received at her annual physical appointment caused her to
suffer scleroderma. The Secretary disputed this allegation, contending that Ms.
Bishara failed to prove that there is a causal link between her Tdap vaccination and
her scleroderma. The parties developed their positions by retaining experts who
wrote reports, arguing through legal memoranda, and presenting testimony.
The evidence, viewed in its entirety, does not preponderate in favor of
finding that the Tdap vaccine caused Ms. Bishara’s scleroderma. The evidence is
not persuasive to demonstrate that molecular mimicry is a reliable basis for
causally connecting the Tdap vaccine to scleroderma. Accordingly, Ms. Bishara is
not entitled to compensation.
1The E-Government Act, 44 U.S.C. § 3501 note (2012) (Federal Management and
Promotion of Electronic Government Services), requires that the Court post this decision on its
website. This posting will make the decision available to anyone with the internet. Pursuant to
Vaccine Rule 18(b), the parties have 14 days to file a motion proposing redaction of medical
information or other information described in 42 U.S.C. § 300aa-12(d)(4). Any redactions
ordered by the special master will appear in the document posted on the website.
I. Facts
Ms. Bishara was born in 1972. She could not produce medical records
created in the three years before the allegedly causal vaccination. 2
According to two medical histories obtained after the vaccination, Ms.
Bishara experienced some symptoms, which could be associated with scleroderma,
in 2015. See exhibit 5 at 78-84; Exhibit 4 at 24. However, Ms. Bishara contested
the accuracy of those histories and the inference that she was suffering from
scleroderma before the vaccination. See exhibit 16 (affidavit, signed May 22,
2020).
Ms. Bishara saw her primary care physician, Sharon Morris, M.D. on
February 8, 2016 for an annual physical. Exhibit 4 at 1-4. Ms. Bishara did not
report any problems with her skin at this appointment. She received the Tdap
vaccination during this appointment.
Ms. Bishara averred that within two days of the vaccination, she felt
exhausted and achy. Exhibit 16 at 2. She returned to the office of her primary care
physician and saw Kamaljit Kaur, M.D. on February 23, 2016. Exhibit 4 at 17.
Ms. Bishara complained that her fingertips were swollen and changing colors from
white to blue. Id. Dr. Kaur diagnosed her with Raynaud's phenomenon and
ordered a lab test for antinuclear antibodies (“ANA”). Id. at 19. Dr. Kaur also
referred Ms. Bishara to a rheumatologist. Id.
Ms. Bishara’s blood was drawn for the ANA test on February 24, 2016, and
the results, which became available two days later, revealed that Ms. Bishara had
an elevated antibody level. Id. at 22.
Ms. Bishara consulted the rheumatologist to whom she had been referred,
Hossam Elzawawy, M.D. on March 14, 2016. Id. at 24-30. Dr. Elzawawy was
aware of Ms. Bishara’s positive ANA results and history of Raynaud’s
phenomenon. Dr. Elzawawy ordered additional lab tests to rule out scleroderma
and other autoimmune diseases. Id. at 30.
2 According to Ms. Bishara’s attorney, when Ms. Bishara’s primary care physician died,
her medical records were not transferred to another doctor because she did not transfer her care.
See Pet’r’s Mot. for Extension of Time, filed Apr. 24, 2019. To ameliorate the lack of medical
records, Ms. Bishara submitted information from her medical insurance companies. These lists
of claims did not suggest that she was having significant health problems before the vaccination.
See Exhibits 14&15. In the January 31, 2020 status conference, the Secretary accepted the
completeness of the records.
2
In April 2016, swelling in Ms. Bishara's fingers prompted her to resize her
rings. Exhibit 50 at 1. Around this time, she began an anti-inflammatory diet to
try to minimize swelling. Exhibit 16 at 2.
Ms. Bishara consulted a second rheumatologist, Eric Greidinger, M.D. who
was affiliated with the University of Miami Hospital and Clinics., reporting
“feeling generally well until receiving a vaccination booster approximately six
months ago, with subsequent onset of fatigue and cold-induced color changes in
her fingers, [primarily] with blue attacks with tingling.” Exhibit 3 at 1 (July 7,
2016). Dr. Greidinger assessed her as having “diffuse cutaneous scleroderma with
Scl-70 positivity.” Id. at 2. He discussed treatment options for her and planned a
return visit in three months. Id.
Ms. Bishara periodically returned for appointments with Dr. Greidinger over
the next one and a half years. See exhibit 3, passim. Reports from these visits
show the ups and downs of Ms. Bishara's scleroderma, but do not provide any
meaningful information about the cause of the scleroderma.
On December 19, 2017, Ms. Bishara consulted her third rheumatologist,
Ami Shah, M.D., who is affiliated with Johns Hopkins Medicine, for an initial
evaluation of “diffuse cutaneous systemic sclerosis.” Exhibit 5 at 78-86. Dr. Shah
obtained medical history from Ms. Bishara in which Ms. Bishara recounted, among
other points, that she was having difficulty removing her rings in March 2015.” Id.
at 78. Dr. Shah diagnosed Ms. Bishara as suffering from systemic sclerosis and
formulated a care plan for Ms. Bishara. Id. at 85-86.
After the December 19, 2017 appointment with Dr. Shah, Ms. Bishara
continued to seek treatment from her doctors for her scleroderma. However, the
parties and the experts whom they retained, agreed that the more recent medical
records do not contribute to determining whether the Tdap vaccination caused Ms.
Bishara’s scleroderma. Thus, these records are not summarized here.
Ms. Bishara testified how the scleroderma was affecting her. Tr. 9-63.
II. Procedural History
Ms. Bishara alleged that the Tdap vaccination caused her to suffer
scleroderma. Pet., filed Jan. 22, 2019. She filed medical records and then assessed
the record as complete on July 17, 2019.
3
The Secretary expressed an interest in defending the case. Resp’t’s Status
Rep., filed Jan. 21, 2020. Thus, to advance the case, Ms. Bishara intended to
obtain a report from an expert. To assist in the process of presenting reports from
experts, a set of instructions were proposed and then made final. Orders, issued
February 7, 2020 and February 26, 2020.
Ms. Bishara filed a report from a rheumatologist whom she had retained,
Samar Gupta, M.D. on June 5, 2020. Exhibit 17. Dr. Gupta asserted that before
the vaccination, Ms. Bishara “was in excellent health with no acute conditions.”
Id. at 2. In Dr. Gupta’s view, after the vaccination, Ms. Bishara developed
scleroderma, which is a rare condition. Id. at 4, 8. Dr. Gupta generally opined that
the Tdap vaccination caused Ms. Bishara's scleroderma. He maintained that
molecular mimicry “may serve to explain potential development of autoimmune
phenomena post vaccination." Id. at 7. Dr. Gupta acknowledged “a paucity in
literature of vaccine induced Scleroderma cases due to its rare nature.” Id. at 8.
However, Dr. Gupta analogized scleroderma to another condition, morphea. Id.
Dr. Gupta’s opinion regarding when Ms. Bishara began to manifest
symptoms of scleroderma was conclusory. See Exhibit 17 at 9. Therefore, Ms.
Bishara was directed to obtain a more detailed opinion. Order, issued June 24,
2020. Ms. Bishara did so. In Dr. Gupta’s supplemental report, he stated that the
positive ANA test from February 23, 2016 was the first diagnostic feature of
scleroderma and Ms. Bishara “displayed the full spectrum of Scleroderma disease”
by March 14, 2016. Exhibit 35 at 1-2.
The Secretary responded by submitting a report from a rheumatologist
whom he had retained, Chester Oddis, M.D. and a report from an immunologist
whom he had retained, You-Wen He, M.D., Ph.D. Exhibit A&B. Dr. Oddis began
his summary of medical events by noting that Dr. Shah had recorded that Ms.
Bishara developed swollen fingers in March 2015. Exhibit A at 2; see also id. at 6-
7 (acknowledging a discrepancy in the evidence that Dr. Oddis cannot resolve).
On the other hand, when Dr. Oddis presented his opinion regarding the onset of
Ms. Bishara’s scleroderma, he does not refer to this history. Instead, Dr. Oddis
maintains that the positive ANA, which was detected two weeks after vaccination,
could not have been produced in response to vaccination because the body takes
more than two weeks to produce antibodies. Id. at 7-8, 10.
Apart from the question of onset, Dr. Oddis agreed that Ms. Bishara suffers
from scleroderma. Exhibit A at 6. Dr. Oddis did not address the theory of
molecular mimicry. See Id. at 8-9. But, Dr. Oddis challenges Dr. Gupta’s opinion
that an antibody can be developed and detected two weeks after vaccination. Dr.
4
Oddis also indicated that morphea is not analogous to scleroderma. Id. at 8-9. He
stated the “etiology of scleroderma . . . is unknown.” Id. at 11.
The Secretary’s second expert, Dr. He, also opined that the “etiology of
Scleroderma is currently unknown” and the “pathogenesis of Scleroderma is very
complex.” Exhibit B at 3. Like Dr. Oddis, Dr. He recognized that the history from
Dr. Shah raised a question as to whether Ms. Bishara “had some levels of
autoimmune disease prior to her Tdap vaccination.” Id. at 3, 8.
Dr. He challenged the theory of molecular mimicry. He stated that recent
scientific evidence shows that “viral and human proteomes have massive peptide
sharing.” Exhibit B at 4, citing three articles.3 Dr. He maintained that Dr. Gupta
had not demonstrated that molecular mimicry could explain how vaccines can
cause an autoimmune disease. Further, Dr. He also asserted that the “fact that not
a single published report described Tdap vaccine and Scleroderma indicates that
Tdap vaccine is highly unlikely to cause Scleroderma." Id. at 7.
The Secretary incorporated the assessments of Dr. Oddis and Dr. He in
recommending against compensation. Resp’t’s Rep., filed Jan. 21, 2021. The
Secretary maintained that despite Dr. Gupta’s reports, Ms. Bishara had failed to
present a persuasive medical theory to explain how the Tdap vaccine can cause
scleroderma. Id. at 7-10. With respect to the onset of Ms. Bishara’s scleroderma,
the Secretary did not directly address that issue. Id. at 12.
After reviewing the reports from Dr. Oddis and Dr. He, Dr. Gupta authored
another report. Exhibit 40. Dr. Gupta defended his opinion that Ms. Bishara’s
scleroderma started after the vaccination and explained why he did not accept the
history Dr. Shah created. Id. at 1. Dr. Gupta also defended the reliability of
molecular mimicry as a theory, noting molecular mimicry was suggested as a way
that the Covid virus could cause damage to the nervous system. Id. at 1. 4 Dr.
Gupta explained why antibodies could develop within two weeks of the
vaccination. Id. at 2.
3 Dr. He cited D. Kanduc et al., “Massive peptide sharing between viral and human
proteomes,” 29(10) Peptides 1755 (2008), filed as Exhibit B.4; Trost et al., “Bacterial peptides
are intensively present throughout the human proteome,” 1(1) Self Nonself 71 (2010), filed as
Exhibit B.5; and A. Kusalik, et al., “Widespread and ample peptide overlapping between HCV
and Homo sapiens proteomes,” 28(6) Peptides 1260 (2007), filed as Exhibit B.6.
4 Dr. Gupta cited A. Gammazza et al., “Molecular mimicry in the post-COVID 19 signs
and symptoms of neurovegetative disorders,” 2(3) The Lancet Microbe Correspondence E94
(2021), filed as Exhibit 43.
5
Dr. Gupta’s report appeared to complete the disclosure of expert opinions.
The parties were, accordingly, directed to advocate for their positions in written
submissions. Order, issued April 19, 2021.
Ms. Bishara submitted her materials, including a brief, on June 25, 2021.
About three months later, the Secretary submitted his materials, which also
included a brief. Ms. Bishara replied on October 25, 2021.
It appeared that the parties disagreed about the significance of the history
that Dr. Shah recorded on December 19, 2017. The Secretary expressed an interest
in calling Dr. Shah as a witness, either during a hearing or at a remote video
deposition. Resp’t’s Status Rep., filed Jan. 14, 2022. To clarify Ms. Bishara’s
health before vaccination, the parties were directed to attempt to obtain additional
evidence. Ms. Bishara described her activities around the time of the February
2016 Tdap vaccination. Exhibit 56 (affidavit, filed Mar. 11, 2022). The parties
also informally sought more information from Dr. Shah through a letter but did not
receive any response from her. Pet’r’s Status Rep., filed June 27, 2022. In a July
18, 2022 status conference, the Secretary was offered an opportunity to compel the
testimony of Dr. Shah because the Secretary was relying upon a history that she
obtained and to which Ms. Bishara contested. The Secretary declined this
opportunity. Order, issued July 19, 2022.
A hearing was held on November 17-18, 2022. Ms. Bishara testified. Dr.
Gupta, Dr. Oddis, and Dr. He testified in accord with their reports. With the
submission of this testimony, the case is ready for adjudication.
III. Standards for Adjudication
A petitioner is required to establish her case by a preponderance of the
evidence. 42 U.S.C. § 300aa-13(1)(a). The preponderance of the evidence
standard requires a “trier of fact to believe that the existence of a fact is more
probable than its nonexistence before [he] may find in favor of the party who has
the burden to persuade the judge of the fact’s existence.” Moberly v. Sec’y of
Health & Hum. Servs., 592 F.3d 1315, 1322 n.2 (Fed. Cir. 2010) (citations
omitted). Proof of medical certainty is not required. Bunting v. Sec’y of Health &
Hum. Servs., 931 F.2d 867, 873 (Fed. Cir. 1991).
Distinguishing between “preponderant evidence” and “medical certainty” is
important because a special master should not impose an evidentiary burden that is
too high. Andreu v. Sec’y of Health & Hum. Servs., 569 F.3d 1367, 1379-80 (Fed.
6
Cir. 2009) (reversing a special master’s decision that petitioners were not entitled
to compensation); see also Lampe v. Sec’y of Health & Hum. Servs., 219 F.3d
1357 (Fed. Cir. 2000); Hodges v. Sec’y of Health & Hum. Servs., 9 F.3d 958, 961
(Fed. Cir. 1993) (disagreeing with the dissenting judge’s contention that the special
master confused preponderance of the evidence with medical certainty).
When pursuing an off-Table injury, a petitioner bears a burden “to show by
preponderant evidence that the vaccination brought about [the vaccinee’s] injury
by providing: (1) a medical theory causally connecting the vaccination and the
injury; (2) a logical sequence of cause and effect showing that the vaccination was
the reason for the injury; and (3) a showing of a proximate temporal relationship
between vaccination and injury.” Althen v. Sec’y of Health & Hum. Servs., 418
F.3d 1274, 1278 (Fed. Cir. 2005).
IV. Analysis
Ms. Bishara and her expert, Dr. Gupta, advance the theory of molecular
mimicry to explain how a Tdap vaccination could cause scleroderma. Thus,
appellate cases regarding molecular mimicry are reviewed in section A. Section B
contains an assessment of the evidence that Ms. Bishara put forward in an effort to
demonstrate the persuasiveness of molecular mimicry as a theory in this context.
A. Appellate Guidance regarding Molecular Mimicry
Because special masters are often called upon to evaluate the persuasiveness
of the theory of molecular mimicry, the Court of Federal Claims and the Court of
Appeals for the Federal Circuit have considered molecular mimicry in their
appellate role opinions from special masters. In December 2019, the undersigned
identified the leading precedents as W.C. v. Sec’y of Health & Hum. Servs., 704
F.3d 1352 (Fed. Cir. 2013), and Caves v. Sec’y of Dep’t. of Health & Hum. Servs.,
100 Fed. Cl. 119 (2011), aff’d sub nom., 463 F. App’x 932 (Fed. Cir. 2012).
Tullio v. Sec’y of Health & Hum. Servs., No. 15-51V, 2019 WL 7580149, at *12-
14 (Fed. Cl. Spec. Mstr. Dec. 19, 2019), mot. for rev. denied, 149 Fed. Cl. 448(2020). While Tullio describes those cases in more detail, their essence appears to
be that although molecular mimicry is accepted in some contexts, special masters
may properly require some empirical evidence to show that a particular vaccine
can cause a particular disease.
In the next approximately three years, appellate authorities reviewing
decisions involving molecular mimicry have generally endorsed the approach of
looking for some evidence that persuasively shows that a portion of a vaccine
resembles a portion of human tissue, which contributes to causing the disease, and
7
that the immune system will respond to the relevant amino acid sequence.5
Chronologically, the list of more recent appellate cases begins with the opinion in
Tullio, which denied the motion for review. 149 Fed. Cl. 448, 467-68 (2020).
Another example in which the Court of Federal Claims held that the special
master did not elevate the petitioner’s burden of proof in the context of evaluating
the theory of molecular mimicry is Morgan v. Sec’y of Health & Hum. Servs., 148
Fed. Cl. 454, 476-77 (2020), aff’d in non-precedential opinion, 850 F. App’x 775(Fed. Cir. 2021). In Morgan, the Chief Special Master found that petitioner had
not presented persuasive evidence about a relevant antibody. Id. at 477. The Chief
Special Master also noted that the articles about the relevant disease do not list the
wild flu virus as potentially causing the disease. Id. When examining this
analysis, the Court of Federal Claims concluded: “the Chief Special Master did not
raise the burden of causation in this case; petitioner simply failed to meet it.” Id.The Federal Circuit also evaluated the Chief Special Master’s approach in
Morgan. The Federal Circuit concluded: “We discern no error in the special
master’s causation analysis.” 850 F. App’x 775, 784 (Fed. Cir. 2021).
Most other recent appellate cases follow this path. See, e.g., Duncan v.
Sec’y of Health & Hum. Servs., 153 Fed. Cl. 642, 661 (2021) (finding the special
master did not err in rejecting a bare assertion of molecular mimicry); Caredio v.
Sec’y of Health & Hum. Servs., No. 17-79V, 2021 WL 6058835, at *11 (Fed. Cl.
Dec. 3, 2021) (indicating that a special master did not err in requiring more than
homology and citing Tullio); Yalacki v. Sec’y of Health & Hum. Servs., 146 Fed.
Cl. 80, 91-92 (2019) (ruling that special master did not err in looking for reliable
evidence to support molecular mimicry as a theory); but see Patton v. Sec’y of
Health & Hum. Servs., 157 Fed. Cl. 159, 169 (2021) (finding that a special master
erred in requiring petitioner submit a study to establish medical theory causally
connecting flu vaccine to brachial neuritis).
Based upon this guidance, a relevant question is whether Ms. Bishara has
presented any evidence that makes the theory of molecular mimicry a reliable
theory in the context of a Tdap vaccine causing scleroderma. The evidence is
taken up in the following section.
5 The term “homology” is used when discussing molecular mimicry. “Homology” is
defined as “the quality of being homologous; the morphological identity of corresponding parts;
structural similarity due to descent from a common form.” Dorland’s at 868.
8
B. Evidence regarding Tdap Vaccine and Scleroderma
Ms. Bishara’s evidence with respect to the first Althen prong can be placed
into two categories. First, Dr. Gupta asserts an unidentified homology between the
Tdap vaccine and tissues affected in scleroderma supports a causal connection.
Second, Dr. Gupta relies upon case reports.
1. Homology
The primary sources of support for Ms. Bishara’s proposal of molecular
mimicry are Dr. Gupta’s May 31, 2020 report and his March 15, 2021 report.
Exhibits 17&40. In his earlier report, Dr. Gupta asserts that a person with genetic
susceptibility could develop an autoimmune disease when the person is exposed to
foreign peptides homologous to human peptides. Exhibit 17 at 7; see also Tr. 160.
He further asserts that scleroderma resembles morphea and case reports have
associated the receipt of Tdap vaccine as occurring before instances of morphea.
Id. at 8; Tr. 102-05. 6
In response to Dr. Gupta’s May 31, 2020 report, the Secretary presented a
contrary opinion from Dr. He. Dr. He questioned the value of the molecular
mimicry theory because, according to Dr. He, recent scientific studies on viral and
human proteomes have shown “massive peptide sharing.” Exhibit B at 4. To
support his opinion regarding the significant degree of overlap, Dr. He cited three
articles: Kanduc, Trost, and Kusalik. With regard to the case reports, Dr. He
emphasized that he could not locate any case reports about Tdap vaccine and either
scleroderma or systemic sclerosis. Dr. He stated: “Tens of millions of Tdap
vaccine doses have been administered to the general population worldwide. The
fact that not a single published report described Tdap vaccine and Scleroderma
indicates that Tdap vaccine is highly unlikely to cause Scleroderma.” Id. at 7;
accord Tr. 274-75. The Secretary’s challenge to the usefulness of the case reports
was reinforced by Dr. Oddis, who opined that morphea is not comparable to
scleroderma. Exhibit A at 9; Tr. 187-88.
In Dr. Gupta’s final report, he defends the value of molecular mimicry as a
theory. He asserts: “To date, molecular mimicry is the most widely accepted
theory for autoimmune disease development.” Exhibit 40 at 1. For this
6Dr. Gupta also discusses adjuvants and cites some articles discussing autoimmune
syndrome induced by adjuvants (“ASIA”). Exhibit 17 at 7-8. However, Ms. Bishara did not
advance a theory based upon adjuvants. See Pet’r’s Br. at 7-13. In any event, special masters
have consistently rejected a theory based upon ASIA.
9
proposition, Dr. Gupta cites one article about how inflammatory bowel disease
might cause arthritis and one article about how the Covid virus might cause
neurovegetative disorders. Dr. Gupta also contends that morphea and scleroderma
“share[] the same histopathology.” Id. at 2.
Here, Ms. Bishara has presented little, if any, persuasive evidence to
demonstrate that molecular mimicry is a reliable basis for causally connecting the
Tdap vaccine to scleroderma. At a fundamental level, Dr. Gupta did not identify
any homology between any component of the Tdap vaccine and any tissue that has
been linked to scleroderma. Tr. 126. Without this basic step, Ms. Bishara’s case is
on par with Caves and Duncan in which appellate judges ruled that the special
master did not err in declining to credit molecular mimicry. In Caves, “[w]hile the
special master acknowledged that [] [petitioner’s] submitted articles supported the
general theory of molecular mimicry . . . he [] held that the articles do not provide
any support for the more specific theory that the influenza vaccine can serve as the
antigenic trigger that sets that autoimmune process into motion.” 100 Fed. Cl. at
129. Furthermore, in Duncan, while “[t]he Special Master acknowledged that
medical literature submitted by [petitioner] indicated that strep infections can lead
to PANDAS through the process of molecular mimicry, [] [petitioner]’s experts did
not identify any link between the molecular structures of strep bacteria and the
HPV vaccine.” 153 Fed. Cl. at 653.
Moreover, a showing of homology alone does not meaningfully advance a
petitioner’s support for molecular mimicry as the Kanduc, Trost, and Kusalik
articles demonstrate. Special masters have, on occasion, discussed these Kanduc
and Trost articles and found that they show homology is common. See, e.g.,
Nifakos v. Sec’y of Health & Hum. Servs., No. 14-236V, 2021 WL 1345218, at
*12, *20-21 (Fed. Cl. Spec. Mstr. Mar. 4, 2021); McKown v. Sec’y of Health &
Hum. Servs., No. 15-1451V, 2019 WL 4072113, at *36, *50 (Fed. Cl. Spec. Mstr.
July 15, 2019); Tarsell v. Sec’y of Health & Hum. Servs., No. 10-251V, 2016 WL
880223, at *10-12 (Fed. Cl. Spec. Mstr. Feb. 16, 2016), mot. for rev. granted after
an intervening remand, 133 Fed. Cl. 782 (2017). Ms. Bishara submitted an article
expressing the idea: “the presence of cellular mimicry does not guarantee the
clinical manifestations of autoimmune conditions.” Exhibit 65 (Daniil Hammoudi
et al., “Induction of Autoimmune Diseases Following Vaccinations: A Review,”
1(3) SM Vaccine Vaccin. 1011 (2015)) at 2. It bears repeating that the discussion
of homology and cellular mimicry is merely academic because Ms. Bishara has not
actually presented any evidence showing that a portion of the Tdap vaccine is
homologous with tissue involved in the pathogenesis of scleroderma. In other
words, Ms. Bishara presented an abstract theory but failed to present evidence on
how this theory applied to her in the instant case.
10
Shortly before the hearing, Ms. Bishara submitted an article to offer some
support for the opinion that vaccines can cause scleroderma. 7 Three researchers
discussed environmental factors that could trigger systemic sclerosis. Exhibit 64
(Hana Alahmari, “Environmental Risks for Systemic Sclerosis,” 48 Rheum Dis
Clin N Am 845 (2022)). They focused on occupational exposures, such as epoxy
resin, asbestos, and heavy metals. But, they also considered the possibility that
infectious agents, such as herpes viruses, parvovirus B19, retrovirus, and
Helicobacter pylori could lead to systemic sclerosis. In doing so, the authors listed
more than 75 articles about systemic sclerosis.
Alahmari has limited, if any, relevance in determining whether the Tdap
vaccination can cause scleroderma. First, the article does not discuss vaccines or
immunizations at all. Tr. 133. Second, to the extent that the article’s list of
infectious agents might be extended to a vaccine against those infectious agents,
the article does not discuss tetanus, diphtheria, or pertussis. Tr. 135.
2. Reliance on Case Reports
Without any evidence that directly connects the Tdap vaccine with
scleroderma, Ms. Bishara relies upon case reports about a tetanus vaccine
preceding the onset of morphea to support the claim that a Tdap vaccine can cause
scleroderma. See Pet’r’s Br. at 11-12; Pet’r’s Reply at 4-5; Tr. 168-70. This
position is flawed because case reports provide little, if any, meaningful
information about causation. At best, they show temporal data but not necessarily
that a Tdap vaccine can cause scleroderma.
Various authorities have commented on the value of case reports. To start,
the Federal Judicial Center has published a series of guides designed “to assist
judges . . . in reaching an informed and reasoned assessment concerning the basis
of expert evidence.” Jerome P. Kassirer and Gladys Kessler, Reference Manual on
Scientific Evidence, Preface (3d ed. 2011) (“Reference Manual”). The guidance
from the Federal Judicial Center translates to the Vaccine Program because
causation for off-Table injuries in the Vaccine Program is the same as traditional
causation. See Moberly, 592 F.3d at 1322-23; Shyface v. Sec'y of Health &
Human Servs., 165 F.3d 1344, 1351 (Fed. Cir. 1999) (“The absence of elaboration
of the law of causation in the legislative history leads us to conclude that the
Vaccine Act's requirement of causation in non-Table cases was not viewed as
distinct from causation in the tort law.”). For examples in which appellate
7 The Secretary did not oppose the submission of this article shortly before the hearing.
11
authorities within the Vaccine Program have cited the Reference Manual, see
Germaine v. Sec’y of Health & Hum. Servs., 155 Fed. Cl. 226, 228-29 (2021), and
Hart v. Sec’y of Health & Hum. Servs., 60 Fed. Cl. 598, 607 n.20 (2004).
A pertinent guide in the Reference Manual states “[a]necdotal evidence
usually amounts to reports that events of one kind are followed by events of
another kind. Typically, the reports are not even sufficient to show association,
because there is no comparison group.” David H. Kaye and David A. Freedman,
Reference Manual on Scientific Evidence, Reference Guide on Statistics, at 218.
These authors also state “some courts have suggested that attempts to infer
causation from anecdotal reports are inadmissible as unsound methodology under
Daubert.” Id. at 217 n. 14 (citing cases)."
Within the Vaccine Program, the Federal Circuit has endorsed, albeit
indirectly, a view that case reports merit little weight. In a series of five cases
involving auto-immune hepatitis, the (undersigned) special master rejected case
reports as evidence of causation. Porter v. Sec’y of Health & Hum. Servs., No.
99–639V, 2008 WL 4483740, at *13 (Fed. Cl. Spec. Mstr. Oct. 2, 2008). Under
the caption of a different case, a judge at the Court of Federal Claims disagreed
with this weighing of evidence. Rotoli v. Sec’y of Health & Hum. Servs., 89 Fed.
Cl. 71, 86–87 (2009). When the Federal Circuit reviewed the special master's
decision, the Federal Circuit stated that “[t]he special master found that the
remaining two articles, both describing single case studies, did not contain any
meaningful analysis about causation.” Porter v. Sec’y of Health & Human Servs.,
663 F.3d 1242, 1253 (Fed. Cir. 2012). The Federal Circuit also stated that the
“decision reveals a thorough and careful evaluation of all the evidence including
. . . medical literature.” Id. at 1254.
Similar indirect support from the Federal Circuit is found in W.C. W.C. v.
Sec’y of Health & Hum. Servs., No. 07-456V, 2011 WL 4537877, at *13 (Fed. Cl.
Spec. Mstr. Feb. 22, 2011), mot. for rev. denied on this point, 100 Fed. Cl. 440,
456 (2011), aff’d, 704 F.3d 1352 (Fed. Cir. 2013). At the trial level, the
(undersigned) special master declined to rely upon case reports because, among
other reasons, “case reports cannot distinguish a temporal association from a causal
relationship.” Id. at *13. At the Federal Circuit, the appellate court focused
primarily upon epidemiologic studies, which undermined the claim that the vaccine
significantly aggravated the petitioner’s illness. W.C. v. Sec’y of Health & Hum.
Servs., 704 F.3d 1352, 1360-61 (Fed. Cir. 2013). However, at the end of its
opinion, the Federal Circuit stated that it “cannot say that the special master’s . . .
weighing of the scientific evidence was arbitrary or capricious.” Id. at 1361.
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Without citing either Federal Circuit case (Porter or W.C.), Ms. Bishara
asserts that “case reports are an important contribution to supporting the
understanding of the pathogenesis of autoimmune disease.” Pet’r’s Br. at 10. For
this proposition, Ms. Bishara cites Paluck v. Sec’y of Health & Hum. Servs., 104
Fed. Cl. 457, 475 (2012).
Paluck generally supports Ms. Bishara’s assertion as Paluck states “case
reports ‘do not purport to establish causation definitively, and this deficiency does
indeed reduce their evidentiary value. Nonetheless, the fact that case reports can
by their nature only present indicia of causation does not deprive them of all
evidentiary weight.’” Paluck, 104 Fed. Cl. at 475, quoting Campbell v. Sec’y of
Health & Hum. Servs., 97 Fed. Cl. 650, 668 (2011). The case Paluck quotes,
Campbell, cites to Rotoli v. Sec’y of Health & Hum. Servs., 89 Fed. Cl. 71, 86-87
(2009). However, the value of the opinion by the Court of Federal Claims seems
questionable as the Federal Circuit, as noted above, reversed the outcome in Rotoli,
and reinstated the special master’s decision, which gave little weight to the case
reports. Porter, 663 F.3d at 1253. 8
Much of the foregoing analysis regarding case reports was set forth in K.O.
v. Sec’y of Health & Human Servs., No. 13-472V, 2016 WL 7634491, at *11-12
(Fed. Cl. Spec. Mstr. July 7, 2016). After K.O., the Federal Circuit has not
discussed case reports in a precedential opinion, leaving Porter and W.C. as the
leading, although muted, words on the subject. Consequently, judges from the
Court of Federal Claims have tended to defer to the special master’s assessment of
case reports. See, e.g., Kelly v. Sec’y of Health & Hum. Servs., 160 Fed. Cl. 316,
319 (2022) (indicating that the special master was not arbitrary in finding that case
reports have limited or nonexistent value); Rus v. Sec’y of Health & Hum. Servs.,
129 Fed. Cl. 672, 682 (2016) (noting the special master could reasonably afford
little weight to the medical literature, including case reports). An exception to this
trend is Patton v. Sec’y of Health & Hum. Servs., 157 Fed. Cl. 159 (2021). In
Patton, the Court ruled that the special master “erred in his prong one analysis by
discounting the evidentiary value of the case reports [petitioner’s expert]
submitted.” Id. at 168. But, Patton does not discuss Porter or W.C. Instead,
Patton relies upon Paluck, which has a questionable value as discussed above.
Outside of the Vaccine Program, district courts have examined the value of
case reports in the context of claims that drugs or a medical device harmed a
person. Recent examples include: In re: Abilify (Aripriprazole) Products Liability
Litigation, 299 F.Supp.3d 1291, 1309 (N.D. Fla. 2018) (“The difficulty with case
8 Paluck, which cited Rotoli, was issued before the Federal Circuit reversed Rotoli.
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reports is distinguishing between association and causation”); In re Tylenol
(Acetaminophen) Marketing, Sales Practice, and Products Liability Litigation, 198
F.Supp.3d 446, 461 (E.D. Pa. 2016) (“It is true that case reports and anecdotal
evidence alone may not be sufficient support for a causation opinion. . . . However,
case reports considered in conjunction with other evidence may be an appropriate
basis for an expert’s causation opinion.”); In re Mirena IUD Products Liability
Litigation, 169 F.Supp.3d 396, 451 (S.D.N.Y. 2016) (“Case reports are generally
disfavored by courts as evidence of causation because they merely describe
‘reported phenomena without comparison to the rate at which the phenomena
occur in the general population or in a defined control group; [they] do not isolate
and exclude potentially alternative causes; and [they] do not investigate or explain
the mechanism of causation.’”) (citation omitted).
Through Dr. Gupta, Ms. Bishara has presented case reports. See Tr. 102-05.
As these case reports are part of the record, the undersigned must consider them
and has considered them. See 42 U.S.C. § 300aa–13(a)(1) (requiring a special
master to evaluate the “record as a whole”). As Dr. Gupta testified, “a lot of case
reports don’t add up to making a well designed data.” Tr. 114. Thus, the
evidentiary value of case reports is negligible, at best. See Whitecotton v. Sec’y of
Health & Human Servs., 81 F.3d 1099, 1104 (Fed. Cir. 1996) (indicating that
special masters have discretion in how they weigh evidence).
Moreover, the case reports submitted here are further removed because the
subjects of the case reports did not develop the same condition, scleroderma, as
Ms. Bishara did. Tr. 131, 170. Dr. Oddis testified that morphea is different from
scleroderma. Tr. 187-88. When case reports do not match the alleged vaccine-
injury combination, special masters may further discount the value of the case
reports. Temes v. Sec’y of Health & Hum. Servs., 151 Fed. Cl. 448, 462-63
(2020). Thus, resolving the controversy as the degree to which scleroderma does
(or does not) resemble morphea is not needed.
In sum, Dr. Gupta essentially proposes molecular mimicry with little, if any,
persuasive evidence to make that theory reliable in the context of Tdap vaccine as
potentially causing scleroderma. Dr. Gupta has not identified any homology.
Medical articles have not listed tetanus, diphtheria, and/or pertussis as infections
often preceding the onset of scleroderma. Case reports, strictly speaking, do not
link Tdap vaccine to scleroderma. Under these circumstances, Ms. Bishara has
failed to meet her burden regarding Althen prong one. As such, the other Althen
prongs do not need to be addressed.
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V. Conclusion
For the foregoing reasons, Ms. Bishara has not presented sufficient evidence
to show that the Tdap vaccine caused her to develop systemic scleroderma.
Accordingly, her claim for compensation is DENIED.
The Clerk's Office is instructed to enter judgment in accord with this
decision unless a motion for review is filed. Information about filing a motion for
review, including the deadline, can be found in the Vaccine Rules, which are
available on the website for the Court of Federal Claims.
IT IS SO ORDERED.
s/Christian J. Moran
Christian J. Moran
Special Master
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