VICP Registry Case Source Bundle
Canonical URL: https://vicp-registry.org/case/USCOURTS-cofc-1_10-vv-00565
Package ID: USCOURTS-cofc-1_10-vv-00565
Petitioner: Megan L. Godfrey
Filed: 2010-08-10
Decided: 2016-05-25
Vaccine: HPV
Vaccination date: 2007-08-22
Condition: juvenile ankylosing spondylitis
Outcome: compensated
Award amount USD: 141851

AI-assisted case summary:
Megan L. Godfrey, who was 18 years old at the time of vaccination, received a single dose of the Gardasil HPV vaccine and a meningococcal conjugate vaccine on August 22, 2007. Approximately four months later, she began experiencing hip pain, which was diagnosed as juvenile ankylosing spondylitis (JAS). Petitioner alleged that the HPV vaccine caused her JAS. The case proceeded as an off-Table claim, requiring proof of causation. Petitioner's expert, Dr. Michael McCabe, proposed a theory that the HPV vaccine could trigger JAS in genetically predisposed individuals by causing a release of pro-inflammatory cytokines. Respondent's experts, Dr. Carlos Rose and Dr. Burton Zweiman, argued that the vaccine's effect on cytokine levels would be transient and insufficient to trigger JAS, and that petitioner's condition was likely due to her genetic predisposition and possibly other environmental factors like her cheerleading activities. The initial decision denied compensation, finding that petitioner failed to establish causation. This decision was reviewed by the court, which remanded the case for reconsideration in light of the Federal Circuit's decision in Koehn v. Secretary of Health and Human Services. On remand, a special master again denied entitlement, finding that the differences between this case and Koehn, particularly the nature of the disease (JAS vs. SJIA) and the lack of specific evidence linking the HPV vaccine to JAS, meant that Dr. McCabe's theory was not sufficiently established. The court affirmed this decision, concluding that petitioner failed to prove a legally probable medical theory of causation. The case was later resolved with an award of interim attorney fees and costs totaling $141,851.84, indicating a potential settlement or stipulation for damages after the entitlement decisions.

Theory of causation field:
Off-Table

Public staged source text:

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DOCUMENT 1: USCOURTS-cofc-1_10-vv-00565-0
Date issued/filed: 2014-07-08
Pages: 31
Docket text: PUBLIC DECISION (Originally filed: 06/11/2014) regarding 72 DECISION of Special Master. Signed by Chief Special Master Denise Kathryn Vowell. (tpj) Copy to parties.
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Case 1:10-vv-00565-NBF Document 73 Filed 07/08/14 Page 1 of 31
IN THE UNITED STATES COURT OF FEDERAL CLAIMS
OFFICE OF SPECIAL MASTERS
No. 10-565V
Filed: June 11, 2014
For Publication
* * * * * * * * * * * * * * * * * * * * * * * * * * * *
MEGAN L. GODFREY, * HPV Vaccine; Gardasil; Juvenile
* Ankylosing Spondylitis; JAS;
Petitioner, * Causation-in-Fact; Expert;
v. * Qualifications.
*
SECRETARY OF HEALTH *
AND HUMAN SERVICES, *
*
Respondent. *
* * * * * * * * * * * * * * * * * * * * * * * * * * * *
Milton Clay Ragsdale, IV, Ragsdale LLC, Birmingham, AL, for petitioner.
Jennifer Reynaud, U.S. Department of Justice, Washington, DC, for respondent.
DECISION1
Vowell, Chief Special Master:
On August 20, 2010, Megan Godfrey [“petitioner”] filed a petition for
compensation under the National Vaccine Injury Compensation Program, 42 U.S.C.
§300aa-10, et seq.2 [the “Vaccine Act” or “Program”]. The petition alleged that the
human papillomavirus [“HPV”] and meningococcal conjugate vaccines Ms. Godfrey
received on August 22, 2007, caused her to develop juvenile rheumatoid arthritis.
Petition at 1-2.
1 Because this decision contains a reasoned explanation for my action in this case, it will be posted on the
United States Court of Federal Claims’ website, in accordance with the E-Government Act of 2002, Pub.
L. No. 107-347, 116 Stat. 2899, 2913 (Dec. 17, 2002). As provided by Vaccine Rule 18(b), each party
has 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.
2 National Childhood Vaccine Injury Act of 1986, Pub. L. No. 99-660, 100 Stat. 3755. Hereinafter, for
ease of citation, all “§” references to the Vaccine Act will be to the pertinent subparagraph of 42 U.S.C. §
300aa (2006).

Case 1:10-vv-00565-NBF Document 73 Filed 07/08/14 Page 2 of 31
To prevail under the Vaccine Act, a petitioner must prove either a “Table” injury3
or that a vaccine listed on the Table was the cause in fact of an injury (an “off-Table”
injury). While both the HPV and meningococcal conjugate vaccines are listed on the
Vaccine Injury Table, there are no Table injuries associated with either vaccine.4
Although the evidence established that petitioner received the vaccinations
alleged, she has failed to demonstrate that either vaccine can or did cause her
condition. After considering the record as a whole, I hold that petitioner is not entitled to
compensation. See § 11(c)(1)(C)(ii)(I).
I. Procedural History.
Ms. Godfrey’s petition was accompanied by medical records establishing her
receipt of the HPV and meningococcal vaccines on August 22, 2007, her presentation
to her family doctor with three months of intermittent hip pain on December 19, 2007,
and her diagnosis of juvenile ankylosing spondylitis [“JAS”].5
On July 25, 2011, petitioner filed the expert report of Dr. David Axelrod
(Petitioner’s Exhibit [“Pet. Ex.”] 16). Respondent filed the expert reports of Drs. Carlos
Rose (Respondent’s Exhibit [“Res. Ex.”] A) and Burton Zweiman (Res. Ex. C) on
September 26, 2011, and October 26, 2011, respectively. Also on October 26, 2011,
respondent filed her Rule 4(c) report, recommending against entitlement.
During the Vaccine Rule 56 status conference, held on November 16, 2011, I
pointed out several problems with petitioner’s expert report. I afforded petitioner the
opportunity to file a supplemental expert report from Dr. Axelrod or a different expert.
Order, issued Nov. 17, 2011, at 1. On April 19, 2012, after filing her remaining medical
records, petitioner submitted the expert report of Dr. (Ph.D.) Michael McCabe (Pet. Ex.
52). In response to Dr. McCabe’s report, respondent filed Dr. Zweiman’s second expert
report (Res. Ex. E) on June 18, 2012.
An entitlement hearing was originally scheduled for October 17, 2012. Order,
issued July 9, 2012. Due to a subsequent scheduling conflict with respondent’s expert,
3 A “Table” injury is an injury listed in the Vaccine Injury Table (42 C.F.R. § 100.3 (2011)), corresponding
to the vaccine received within the time frame specified.
4 See 42 C.F.R. § 100.3(a)(XV) and (XVI).
5 This is a condition different from the juvenile rheumatoid arthritis alleged in the petition, but the parties
later stipulated that JAS is the correct diagnosis. See Joint Prehearing Submissions, filed Nov. 19, 2012,
at ¶ 3; see also infra at Section IV.C.1 and n. 24.
6 See Rules for Court of Federal Claims, Appendix B, Vaccine Rules.
2

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the hearing was moved to December 10, 2012. Order, issued Aug. 15, 2012. Prior to
the hearing, the parties stipulated to the pertinent facts and concluded that the issue to
be resolved was whether the HPV vaccine petitioner received on August 22, 2007,
“substantially contributed to the development of petitioner’s JAS approximately four
weeks later.”7 Joint Prehearing Submission, filed Nov. 19, 2012, at 1-2.
On November 28, 2012, petitioners moved to postpone the hearing until her
counsel could seek an expert report from her new treating rheumatologist, Dr. Anthony
Turkiewicz. Motion, filed Nov. 28, 2012. I denied petitioner’s motion, but granted her
request to file testimony from Dr. Turkiewicz in the form of an affidavit. Orders, issued
Nov. 30, 2012 and Dec. 5, 2012.
Although the petition had identified two vaccines as causal, the evidence
presented focused solely on the HPV vaccine. During the hearing, Dr. McCabe testified
on behalf of petitioner, and Drs. Rose and Zweiman testified on behalf of respondent.
Doctor Axelrod did not testify. On January 18, 2013, petitioner filed a status report that
indicated she would not be filing an affidavit from Dr. Turkiewicz.
The parties filed post-hearing briefs on April 1, 2013. Each party filed responsive
post-hearing briefs on May 15, 2013, making this case ripe for resolution.
I conclude that petitioner has failed to establish vaccine causation of her
condition and thus is not entitled to compensation. The reasons for my conclusion are
set forth in more detail below, but in summary, I found the opinions of Drs. Rose and
Zweiman more reliable and supported by other evidence than those advanced by Dr.
McCabe.8
7 I will interpret this “substantially contributed” language as the equivalent of the “substantial factor”
requirement set forth in Shyface v. Sec’y, HHS, 165 F.3d 1344, 1352 (Fed. Cir. 1999). However, I note
that since the Federal Circuit’s decision in Shyface, the Restatement (Third) of Torts has eliminated
“substantial factor” in the factual cause analysis. § 26 cmt. j (2010). Because the Federal Circuit has
held that the causation analysis in the Restatement (Second) of Torts applies to off-Table Vaccine Act
cases (see Walther v. Sec’y, HHS, 485 F.3d 1146, 1151 (Fed. Cir. 2007); Shyface, 165 F.3d at 1352),
this change does not affect the determination of legal cause in Vaccine Act cases: whether the
vaccination is a “substantial factor” is still a consideration in determining whether it is the legal cause of
an injury.
8 Petitioner appears to have abandoned the expert opinion of Dr. David Axelrod, a clinical immunologist,
filed on July 25, 2011, as Pet. Ex. 16. He had opined that Ms. Godfrey’s symptoms “are consistent with
the diagnosis of an immune based spondyloarthropathy.” Pet. Ex. 16 at 2. His theory was predicated on
the assumption that the L1 proteins contained in Gardasil were the same as the L1 proteins found in the
body’s synovial tissues. His opinion that the vaccine proteins reacted with the receptor binding sites of
immune cells resulting in an unwanted immune response against the body was, in essence, based on
molecular mimicry. Id. This opinion was rebutted by the report of Dr. Rose, who asserted that “there is no
biological or chemical relationship between L1 elements [in the vaccine] and the human L1 protein,” thus
challenging the factual basis for Dr. Axelrod’s opinion. Res. Ex. A at 11. Doctor Axelrod did not testify at
the hearing in this case, nor did petitioner address Dr. Axelrod’s theory in her briefs. Thus, Dr. Axelrod’s
theory is not addressed in the remainder of this decision. See Vaccine Rule (8) regarding waiver.
3

Case 1:10-vv-00565-NBF Document 73 Filed 07/08/14 Page 4 of 31
II. Legal Standards Applying to Off-Table Causation Claims.
When a petitioner alleges an off-Table injury, eligibility for compensation is
established when, by a preponderance of the evidence, petitioner demonstrates that
she received, in the United States, a vaccine set forth on the Vaccine Injury Table and
sustained an illness, disability, injury, or condition caused by the vaccine or experienced
a significant aggravation of a preexisting condition. She must also demonstrate that the
condition has persisted for more than six months.9 Vaccine litigation rarely concerns
whether the vaccine appears on the Table, the situs for administration, or whether the
symptoms have persisted for the requisite time. In most Vaccine Act litigation, the issue
to be resolved by the special master is whether the injury alleged was caused by the
vaccine.
To establish legal causation in an off-Table case, Vaccine Act petitioners must
establish by preponderant evidence: (1) a medical theory causally connecting the
vaccination and the injury; (2) a logical sequence of cause and effect showing that the
vaccination was the reason for the injury; and (3) a proximate temporal relationship
between vaccination and injury. Althen v. Sec’y, HHS, 418 F.3d 1274, 1278 (Fed. Cir.
2005); see de Bazan v. Sec’y, HHS, 539 F.3d 1347, 1351-52 (Fed. Cir. 2008); Caves v.
Sec’y, HHS, 100 Fed. Cl. 119, 132 (2011), aff’d per curiam, 463 Fed. Appx. 932, 2012
WL 858402 (Fed. Cir. 2012) (specifying that each Althen factor must be established by
preponderant evidence); Lalonde v. Sec’y, HHS, 746 F.3d 1334, 1337-38 (Fed. Cir.
2014). The applicable level of proof is the “traditional tort standard of ‘preponderant
evidence.’” Moberly v. Sec’y, HHS, 592 F.3d 1315, 1322 (Fed. Cir. 2010) (citing de
Bazan, 539 F.3d at 1351; Pafford v. Sec’y, HHS, 451 F.3d 1352, 1355 (Fed. Cir. 2006);
Capizzano v. Sec’y, HHS, 440 F.3d 1317, 1320 (Fed. Cir. 2006); Althen, 418 F.3d at
1278)). The preponderance standard “requires the trier of fact to believe that the
existence of a fact is more probable than its nonexistence.” In re Winship, 397 U.S.
358, 371 (1970) (Harlan, J., concurring) (internal quotation and citation omitted).
Another formulation of the causation requirement in off-Table cases is the “Can it
cause?” and “Did it cause?” inquiries used in toxic tort litigation. These queries are also
referred to as issues of general and specific causation. Prong 1 of Althen has been
characterized as an alternative formulation of the “Can it cause?” or general causation
query. Prong 2 of Althen, the requirement for a logical sequence of cause and effect
between the vaccine and the injury, has been characterized as addressing the “Did it
cause?” or specific causation query. See Pafford v. Sec’y, HHS, No. 01-165V, 2004 WL
1717359, at *4 (Fed. Cl. Spec. Mstr. July 16, 2004), aff’d, 64 Fed. Cl. 19 (2005), aff’d,
451 F.3d 1352. The third Althen factor is subsumed into the other inquiries. Even if a
particular vaccine has been causally associated with an injury, petitioner must still
9 Section 13(a)(1)(A). This section provides that petitioner must demonstrate “by a preponderance of the
evidence the matters required in the petition by section 300aa–11(c)(1) . . . .” Section 11(c)(1) contains
the factors listed above, along with others not relevant to this case.
4

Case 1:10-vv-00565-NBF Document 73 Filed 07/08/14 Page 5 of 31
establish facts and circumstances that make it more likely than not that this vaccine
caused his particular injury. Timing may be one of those circumstances.
Whether a case is analyzed under Althen or the “Can it cause?” formulation,
petitioners are not required to establish identification and proof of specific biological
mechanisms, as “the purpose of the Vaccine Act’s preponderance standard is to allow
the finding of causation in a field bereft of complete and direct proof of how vaccines
affect the human body.” Althen, 418 F.3d at 1280. The petitioner need not show that
the vaccination was the sole cause, or even the predominant cause, of the injury or
condition; showing that the vaccination was a “substantial factor” in causing the
condition and was a “but for” cause are sufficient for recovery. Shyface, 165 F.3d at
1352; see also Pafford, 451 F.3d at 1355 (petitioner must establish that a vaccination
was a substantial factor and that harm would not have occurred in the absence of
vaccination). Petitioners cannot be required to show “epidemiologic studies,
rechallenge, the presence of pathological markers or genetic disposition, or general
acceptance in the scientific or medical communities to establish a logical sequence of
cause and effect.” Capizzano, 440 F.3d at 1325. Causation is determined on a case by
case basis, with “no hard and fast per se scientific or medical rules.” Knudsen v. Sec’y,
HHS, 35 F.3d 543, 548 (Fed. Cir. 1994). Close calls regarding causation must be
resolved in favor of the petitioner. Althen, 418 F.3d at 1280; but see Knudsen, 35 F.3d
at 550 (when evidence is in equipoise, the party with the burden of proof fails to meet
that burden).
By specifying petitioners’ burden of proof in off-Table cases as a preponderance
of the evidence, directing special masters to consider the evidence as a whole, and
stating that special masters are not bound by any “diagnosis, conclusion, judgment, test
result, report, or summary” contained in the record (§13(b)(1)), Congress contemplated
that special masters would weigh and evaluate opposing expert opinions in determining
whether petitioners have met their burden of proof.10
It is now clearly established that special masters may use the framework
established by Daubert v. Merrell Dow Pharmaceuticals,11 to evaluate expert testimony
on causation. Andreu v. Sec’y, HHS, 569 F.3d 1367, 1379 (Fed. Cir. 2009) and
Moberly, 592 F.3d at 1324; Terran, 195 F.3d at 1316 (concluding it was reasonable for
the special master to use Daubert to evaluate the reliability of an expert’s testimony);
Cedillo v. Sec’y, HHS, 617 F.3d 1328, 1339 (Fed. Cir. 2010) (noting that special
masters are to consider all relevant and reliable evidence filed in a case and may use
Daubert factors in their evaluation of expert testimony); Davis v. Sec’y, HHS, 94 Fed. Cl.
10 See § 13(a)(1)(A) (preponderance standard); § 13(a)(1) (“Compensation shall be awarded . . . if the
special master or court finds on the record as a whole . . . .” ); § 13(b)(1) (indicating that the court or
special master shall consider the entire record in determining if petitioner is entitled to compensation and
special master is not bound by any particular piece of evidence).
11 509 U.S. 579 (1993).
5

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53, 67 (2010) (describing the Daubert factors as an “acceptable evidentiary-gauging tool
with respect to persuasiveness of expert testimony already admitted . . . by special
masters in vaccine cases”); see also Snyder v. Sec’y, HHS, 88 Fed. Cl. 706, 718 (2009)
quoting Ryman v. Sec’y, HHS, 65 Fed. Cl. 35, 40-41 (2005) (special masters perform
gatekeeping function when determining “whether a particular petitioner’s expert medical
testimony supporting biological probability may be admitted or credited or otherwise
relied upon” and as a “trier-of-fact [a special master] may properly consider the
credibility and applicability of medical theories”).
In summary, special masters decide questions of credibility, plausibility,
probability, and reliability, and ultimately determine to which side the balance of the
evidence is tipped. See Pafford, 451 F.3d at 1359. Bearing all these legal standards in
mind, I turn to the evidence presented in this case.
III. Relevant Medical History.
The facts of Ms. Godfrey’s medical history are not in dispute. See Joint
Prehearing Submission at 1-2. She was born on August 1, 1989. Pet. Ex. 8, p. 6.
Except for routine childhood illnesses, she was healthy from her birth to the age of 18,
when the condition at issue developed. Id.; see also Pet. Ex. 50. During high school,
she participated in athletics, including her high school cheerleading team.12 See Pet.
Ex. 50. Her family history is significant for Crohn’s disease (father) and rheumatoid
arthritis (paternal grandparents and paternal aunts and uncles). Pet. Exs. 7, p. 182; 8,
p. 9.
On August 22, 2007, shortly after her eighteenth birthday, Ms. Godfrey received
the HPV [“Gardasil”] and meningococcal conjugate vaccines from her pediatrician, Dr.
Robinson. Pet. Ex. 2, p. 1.
On December 19, 2007, Ms. Godfrey reported to Dr. Mark Woods, complaining
of sharp, intermittent left hip pain for the past three months. Pet. Ex. 3, p. 1. Ms.
Godfrey did not recall any injury. Id. An X-ray of her left hip was negative. Id., p. 2.
Doctor Woods’s impression was arthralgia of the hip.13 Pet. Ex. 3, p. 2. He referred Ms.
Godfrey for an MRI14 to rule out osteomyelitis and to Dr. Steve Lovelady, at DCH
Regional Medical Center [“DCH”]. Pet. Exs. 8, p. 86; 11, p. 12.
12 Ms. Godfrey graduated from high school in May 2007. Petitioner’s Post-Hearing Brief [“Pet. Post-
Hearing Br.”], filed Apr. 1, 2013, at 2 n.2.
13 He also diagnosed her with microcytic anemia, but this diagnosis does not appear directly relevant to
the issues in this case. Pet. Ex. 3, p. 2. Although Dr. McCabe called it “somewhat consistent with an
inflammatory response,” he also acknowledged that anemia is usually “tied to deficiencies in iron.”
Transcript from Dec. 10, 2012 Hearing [“Tr.”] at 74-75. None of her treating physicians commented on its
relevance to her JAS diagnosis.
14 MRI, or magnetic resonance imaging, is “a method of visualizing soft tissues of the body.” DORLAND’S
ILLUSTRATED MEDICAL DICTIONARY (32nd ed. 2012) [“DORLAND’S”], at 916.
6

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The MRI, performed on December 28, 2007, showed “[b]ilateral femoral benign
fibrous dysplasia,” greater on the left side than the right, and left-sided sacroiliitis, which
the radiologist thought might have been inflammatory. The radiologist also noted that
osteomyelitis is presumed with this appearance. Pet. Ex. 8, p. 86.
Also on December 28, 2007, Ms. Godfrey was seen by Dr. Lovelady, who noted
that Ms. Godfrey’s father suffered from inflammatory bowel disease and anemia. Pet.
Ex. 11, pp. 12-14. On physical examination, Dr. Lovelady found tenderness at the left
sacroiliac joint, and decided to admit Ms. Godfrey to DCH for further evaluation to rule
out osteomyelitis. Id.
Ms. Godfrey saw orthopedist William Standeffer on December 29, 2007. Pet. Ex.
8, pp. 14, 16; see also Pet. Ex. 11, p. 12. Based on Ms. Godfrey’s MRI, he believed she
had “sacroiliitis,” which he thought was “probably inflammatory.” Pet. Ex. 8, p. 14. He
doubted that she had osteomyelitis and noted “fibrous dysplasia [in] both hips.” Id. Ms.
Godfrey was discharged from DCH on December 30, 2007. Id., p. 2. Her relevant
discharge diagnoses were the same as her admission diagnoses: hip pain and
questionable osteomyelitis. Id.
A bone scan on January 8, 2008, showed “increased activity at the left
[sacroiliac] joint,” indicative of hyperemia and active bone turnover, which “could be
seen in osteomyelitis or in an inflammatory sacroiliitis.” Pet. Ex. 11, p. 11. An
antinuclear antibody screen [“ANA”], a test for autoimmune disease, performed on
January 14, 2008, was negative. Id., p. 29. However, an HLA-B27 test, a genetic
marker showing susceptibility to conditions such as ankylosing spondylitis, was positive.
Id., p. 27.
A steroid injection performed in January 2008 at Children’s Hospital of Alabama
by Dr. John Doyle relieved Ms. Godfrey’s left hip symptoms. Pet. Ex. 9, pp. 89-90. On
March 11, 2008, however, she returned to Dr. Doyle complaining of hip pain in the right
sacroiliac joint. Id., p. 122. Doctor Doyle’s impression was right-sided sacroiliitis. Id.
On April 15, 2008, Ms. Godfrey was seen by rheumatologist Randy Cron. Pet.
Ex. 7, p. 180. Doctor Cron noted Ms. Godfrey’s family history of Crohn’s disease and
arthritis, and her own history of hip pain. Id., pp. 181-82. Under “[o]ther pertinent past
medical history,” he wrote, “Gardasil 1st dose in summer prior to all this.” Id., p. 182.
Doctor Cron also noted Ms. Godfrey’s positive HLA-B27 and negative ANA test results,
as well as her normal sedimentation rates. Id., p. 181. His diagnosis was HLA-B27
positive spondyloarthropathy. Id., p. 183.
7

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After her initial visit with Dr. Cron in April 2008, Ms. Godfrey continued to receive
treatment, including Infliximab15 injections for her spondyloarthropathy. Pet. Exs. 7, pp.
73-77, 94-98, 132-35, 149-52, 157-61; 9, pp. 12-13.
On August 22, 2012, Ms. Godfrey had an initial visit with rheumatologist Anthony
Turkiewicz. Pet. Ex. 88, pp. 10-14. She was seen for a follow up visit on September
17, 2012. Id., pp. 7-9. Doctor Turkiewicz’s impression was anklylosing spondylitis/axial
spondyloarthropathy. Id., p. 9. He continued Ms. Godfrey’s Infliximab injection
treatments. See id., pp. 3, 7, 10-11, 40. According to Ms. Godfrey, “[t]his treatment has
been successful in terminating [her] symptoms.” Pet. Post-Hearing Br. at 2.
IV. Medical Opinions and Other Evidence.
Ms. Godfrey’s JAS diagnosis is clear and uncontested. Equally clear is that the
clinical symptoms of her condition first manifested around September 19, 2007, about
four weeks after her August 22, 2007 receipt of her only Gardasil vaccine and three
months before she first sought medical treatment for those symptoms. See Pet. Exs. 2;
3, p. 1. The sole contested matter in this case is whether Ms. Godfrey’s HPV
vaccination “substantially contributed” to the development of her JAS. Joint Prehearing
Submission at 2. Ms. Godfrey contends that the Gardasil vaccine elicited an immune
response, specifically “a pro-inflammatory cytokine milieu,” that substantially contributed
to the development of her condition. Pet. Post-Hearing Br. at 6-7. Respondent
maintains, however, that Ms. Godfrey’s JAS “emerged by chance, in the context of a
strong genetic predisposition.” Respondent’s Post-Hearing Brief [“Res. Post-Hearing
Br.”], filed Apr. 1, 2013, at 2.
Expert qualifications play a significant role in the weight given to expert opinions,
particularly when the opinions expressed are otherwise inadequately supported by
reliable evidence. See Moberly, 592 F.3d at 1325 (“Weighing the persuasiveness of
particular evidence often requires a finder of fact to assess the reliability of testimony,
including expert testimony, and we have made clear that the special masters have that
responsibility in Vaccine Act cases.”) (citations omitted).
In this case, I have accorded the opinions of respondent’s experts greater weight,
based not only on their qualifications, but also on the lack of support for Dr. McCabe’s
rather speculative pro-inflammatory cytokine theory in this case. Although pro-
inflammatory cytokines may play a role in JAS’s symptomatology, there is little evidence
that they play a role in JAS’s pathogenesis. Likewise, there is little evidence that one
dose of Gardasil causes significant or persisting increases in cytokine levels. I thus
conclude that there is inadequate evidence that the Gardasil vaccination on August 22,
2007 substantially contributed to the development of Ms. Godfrey’s JAS.
15 Injections of Infliximab, a chimeric monoclonal antibody, inhibits tumor necrosis factor-α (TNF-α) and
other pro-inflammatory cytokines. PHYSICIAN’S DESK REFERENCE (58th ed. 2004), at 1145.
8

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I begin the more detailed analysis of the causation evidence with a comparison of
the qualifications of the expert witnesses, followed by a discussion of the human
papillomaviruses, human papillomavirus vaccines, and JAS, followed by a summary of
the expert opinions and the relevant medical literature. I conclude with an analysis of
how the evidence stacks up against the Althen factors.
A. The Parties’ Experts and their Qualifications.
1. Michael McCabe, Ph.D.
Doctor McCabe is trained in microbiology, immunology, and toxicology, but he is
not a medical doctor. Pet. Ex. 53 at 2; Tr. at 5, 7, 9. He earned a B.S. in biology from
Siena College in 1984, and an M.S. in microbiology and immunology from Albany
Medical College in 1990. In 1991, he earned a Ph.D. in microbiology and immunology,
also from Albany Medical College. Pet. Ex. 53 at 2. From 1990 to 1992, Dr. McCabe
was a postdoctoral research associate at the Karolinska Institute in Stockholm, Sweden.
Id. Between 1992 and 2000, he held various teaching positions related to chemical
toxicology at Wayne State University in Detroit, Michigan. Id. During his final three
years at Wayne State (1997-2000), Dr. McCabe was the director of a facility engaged in
molecular cell biology research projects, including projects related to intracellular
cytokine analysis. Id.
Since 2000, Dr. McCabe has been a professor at the University of Rochester
School of Medicine and Dentistry in Rochester, New York, first as an associate
professor and since 2009 as an adjunct associate professor. Pet. Ex. 53 at 1. At the
University of Rochester, he has served in three primary capacities—as a researcher,
teacher, and administrator. Id. As a researcher, he oversaw an NIH-funded program
involving “mechanistic metal toxicology and immunotoxicology.” Id. He lectured on
metal toxicity, as well as cell signaling and immunity. In his administrative role, Dr.
McCabe served on university committees, including those related to environmental
health sciences research and toxicology training. Id.
Dr. McCabe’s primary employment involves reviewing cases and testifying in
commercial and personal injury litigation involving environmental and occupational
exposures for Robson Forensic. Pet. Ex. 53 at 1; Tr. at 5-6, 10. Specifically, Dr.
McCabe undertakes investigations, produces reports, and offers testimony concerning
exposures to various agents, including metals and solvents. Pet. Ex. 53 at 1. About
80% of his professional time and about 95% of his income is derived from his work at
Robson Forensic. Tr. at 11. He has reviewed about eight vaccine injury claims while a
consultant with Robson Forensic.16 Tr. at 6.
16 Prior to beginning work at Robson Forensic in 2009, Dr. McCabe testified for respondent about metal
toxicology and immunotoxicology in at least one vaccine injury case. See Snyder v. Sec’y, HHS, No. 01-
162V, 2009 WL 332044, at *18 (Fed. Cl. Spec. Mstr. Feb. 12, 2009).
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Doctor McCabe has authored or co-authored 12 book chapters and about 40
articles published in peer-reviewed publications. Pet. Ex. 53 at 8-13. The focus of his
research has been “the role of heavy metals as environmental triggers in producing
diseases of the immune system.” Tr. at 11-12.
Doctor McCabe testified that his “understanding of cellular immunology,
immune mechanisms, [and] immune mediated diseases” is relevant to the causation
issue in this case. Tr. at 7; see also Tr. at 9. He added that, throughout his 25 year
academic career, he has had to “analyze and to understand . . . the triggers for
diseases . . . [and] the environmental and genetic risk factors for diseases,” as well as
how they “interact and lead to particular outcomes.” Tr. at 10. Additionally, Dr. McCabe
noted that he previously testified in a case before another special master involving
juvenile idiopathic arthritis, a condition similar to Ms. Godfrey’s, which the petitioner
alleged was caused by the Gardasil vaccine. Tr. at 8. In that case, Dr. McCabe also
offered opinions regarding cytokine production as a trigger for the onset of the
condition.17 Tr. at 8.
2. Carlos Rose, M.D.
Doctor Rose is a board certified pediatric rheumatologist. Res. Ex. B at 3-6; Tr.
at 100. He graduated from the University of Buenos Aires School of Medicine in 1977.
Res. Ex. B at 1; Tr. at 100. He did the majority of his post-graduate training in internal
medicine in Buenos Aires between 1979 and 1983, and was a fellow in rheumatology at
Buenos Aires National Institute of Rehabilitation. Res. Ex. B at 4-5; Tr. at 100. In 1987,
he moved to the United States for pediatric training and fellowships in pediatric
rheumatology at the Children’s Hospital of Philadelphia and the Alfred I. duPont
Institute. Res. Ex. B at 5; Tr. at 100.
Since 1991, Dr. Rose has been a staff physician in pediatric rheumatology at the
duPont Institute, as well as a professor of pediatrics at Thomas Jefferson University’s
Jefferson Medical College. Res. Ex. B at 6; Tr. at 100. In 1994, he became the head of
the duPont Institute’s Division of Rheumatology. Res. Ex. B at 7; Tr. at 100. Doctor
Rose spends about 50% of his professional time performing clinical functions, 40%
doing “research ethics,” and 10% doing actual research. Tr. at 100.
In addition to his clinical and teaching work, Dr. Rose has held, and continues to
hold, memberships with boards, societies, and committees related to pediatrics and
rheumatology. For over 10 years, he has been a member of the Pediatric
Rheumatology Collaborative Study Group and the Pediatric Rheumatology European
Society. Res. Ex. B at 9. In 2002, he chaired a pediatric symposium on infection-
17 In a decision issued after Dr. McCabe’s testimony in this case, the special master rejected Dr.
McCabe’s causation theory. Koehn v. Sec’y, HHS, No. 11–355V, 2013 WL 3214877 at *28 (Fed. Cl.
Spec. Mstr. May 30, 2013), mot. for review denied, 113 Fed. Cl. 757 (2013), appeal docketed, No. 14-
5054 (Fed. Cir. Feb. 18, 2014).
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related arthritis. Id. at 10. Between 2006 and 2008, he served as a member of a board
monitoring the safety of aggressive therapy to treat juvenile idiopathic arthritis. Id. at 8.
During the same period, he served on an advisory board on juvenile idiopathic arthritis
for Brystol-Myers-Squibb. Id. Doctor Rose is also on the editorial board of CLINICAL
RHEUMATOLOGY. Id. at 9. Additionally, he has authored or co-authored multiple book
chapters and over 70 papers published in peer-reviewed publications, including papers
on juvenile rheumatoid arthritis and juvenile idiopathic arthritis. Id. at 8-20.
Doctor Rose has treated hundreds of children with spondyloarthropathies. Tr. at
100-01. He has testified in other Vaccine Act cases, exclusively for the Department of
Health and Human Services. Tr. at 102.
3. Burton Zweiman, M.D.18
Doctor Zweiman was board certified in internal medicine, allergy and clinical
immunology, and laboratory immunology. He earned his undergraduate and medical
degrees from the University of Pennsylvania in 1952 and 1956, respectively. Res. Ex.
D at 1-2; Tr. at 174. Between 1956 and 1959, he did his post-graduate work at Mt.
Sinai Hospital (New York City), the University of Pennsylvania Hospital, and Bellevue
Hospital Center (New York City). Res. Ex. D at 1; Tr. at 174. Thereafter, he held a
fellowship in allergy and immunology with the University of Pennsylvania Hospital and
NYU Medical Center. Res. Ex. D at 1.
Between 1963 and his death, Dr. Zweiman held various teaching positions at the
University of Pennsylvania School of Medicine, becoming a full professor in 1975. Res.
Ex. D at 1-2. Between 1969 and 1998, he was the chief of the allergy and immunology
division of the University of Pennsylvania Medical Center. Res. Ex. D at 2; Tr. at 173.
In addition to his clinical and teaching duties, Dr. Zweiman held positions with
various boards, societies, and committees. Between 1971 and 2001, he was an active
member of the American Academy of Allergy and Immunology, serving on the board of
directors for over 10 years and as the chairman for a year. Res. Ex. D at 2-3. In 1986
and 1987, he was a member of review panels concerned with arthritis research. Id. at
4. Additionally, he held positions on several editorial boards, including that of the
Journal of Allergy and Clinical Immunology, where he served as editor between 1988
and 1993. Id. at 3. He was published over 200 times on various allergy and
immunology topics, including the study of T-cells, lymphocytes, and cytokines. Id. at 6-
44.
Doctor Zweiman testified on behalf of respondent in hearings six or seven times.
Tr. at 174. In this case, he was offered as an expert in immunology. Tr. at 175.
18 On January 2, 2014, a representative from the Department of Justice contacted the Office of Special
Masters to convey the unfortunate news of Dr. Zweiman’s death.
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B. Human Papillomaviruses and Human Papillomavirus Vaccines.
1. Human Papillomaviruses.
There are over 130 types of human papillomaviruses [“HPVs”]. M. Stanley,
Immunobiology of HPV and HPV vaccines, GYNECOLOGIC ONCOLOGY, 109: S15-S21
(2008), filed as Pet. Ex. 62 [“Stanley I, Pet. Ex. 62”], at S15. The virus is a small, non-
enveloped, double-stranded DNA virus. L. Villa, et al., Immunologic response following
administration of a vaccine targeting human papillomavirus Types 6, 11, 16, and 18,
VACCINE, 24: 5571-83 (2006), filed as Pet. Ex. 31 [ “Villa, Pet. Ex. 31”], at 5572. These
viruses fall into two groups—low-risk types, such as HPV 6 and 11, which cause benign
warts, and high-risk types, such as HPV 16 and 18, which cause cervical cancer.
Stanley I, Pet. Ex. 62, at S15-16.
HPVs have the ability to evade the host’s immune defenses, largely because
they primarily infect epithelial cells. Epithelial cells do not mount a robust immune
response to these viruses. See I. Frazer, Correlating immunity with protection for HPV
infection, INTL. J. INFECTIOUS DISEASES, 11: S10-S16 (2007), filed as Pet. Ex. 71 [“Frazer
II, Pet. Ex. 71”], at S11 (providing several explanations for the poor immune response to
the natural virus infections). In individuals previously unexposed to HPVs, an immune
response to the virus involves “little or no release into the local milieu of pro-
inflammatory cytokines.”19 Stanley I, Pet. Ex. 62, at S16.
Most genital HPV infections (80% - 90%) resolve over time as HPVs “are cleared
as a result of a successful cell-mediated20 immune response.” Stanley I, Pet. Ex. 62, at
S17. A minority of individuals (10% - 20%), however, remain infected and are at risk of
developing disease. Id. One explanation for the persistence of an HPV infection is the
host’s poor natural antibody response. Id. at S17-18.
2. Human Papillomavirus Vaccines.
a. Design and Delivery.
To create a vaccine against HPVs, virologists had to find a way to stimulate the
immune system to create neutralizing antibodies, as research had confirmed that HPV
neutralizing antibodies were protective against infections. Stanley I, Pet. Ex. 62, at S18.
Virologists sought to produce neutralizing antibodies to HPV by creating vaccines with
virus-like particles [“VLPs”]. VLPs are “empty, non-infectious viral capsids that
19 Pro-inflammatory cytokines are “proteins released by one cell population . . . on contact with specific
antigen” that are “capable of stimulating inflammation.” DORLAND’S at 466 (defining “cytokine”), 1523
(defining “pro-inflammatory”).
20 Cell-mediated immune response refers to the adaptive immune response in which T-cells have the
central role. DORLAND’S at 917.
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structurally mimic the outer shell of the virion.” L. Pinto, et al., HPV-16 L1 VLP vaccine
elicits a broad-spectrum of cytokine responses in whole blood, VACCINE, 23: 3555-64
(2005), filed as Pet. Ex. 73 [“Pinto I, Pet. Ex. 73”], at 3555. Vaccines containing VLPs
induce “high concentrations of neutralizing antibodies” and “activate both innate and
adaptive immune responses.” Stanley I, Pet. Ex. 62, p. S18. These vaccines are
delivered directly into the muscle, “resulting in rapid access to the local lymph nodes,
thus circumventing the immune avoidance strategies of the [viruses].” Id. at S17.
Consequently, HPV vaccines stimulate greater antibody production than the virus does
during natural infections. Id. at S18; see also Tr. at 30-31 (McCabe) (“This is a very
potent immunogen in comparison to the natural infection.”).21
b. Gardasil Vaccine.
Gardasil is one of two approved vaccines against HPV. It contains reproductions
of the L1 portion of four types of the virus. The L1 VLPs in Gardasil have been shown
to be effective against four viral types, 6, 11, 16, and 18. M. Stanley, HPV – immune
response to infection and vaccination, INFECTIOUS AGENTS & CANCER, 5: 1-6 (2010), filed
as Pet. Ex. 63 [“Stanley II, Pet. Ex. 63”], at 3. It is administered in a three dose series,
with the second dose administered two months after the first dose, and the third
administered six months after the first dose. B. Slade, et al., Postlicensure Safety
Surveillance for Quadrivalent Human Papillomavirus Recombinant Vaccine, JAMA,
32(7): 750-57 (2009), filed as Res. Ex. C-2 [“Slade, Res. Ex. C-2”], at 750.
Gardasil was extensively tested prior to being approved for use in the United
States. Doctor Zweiman testified that Gardasil appears to be one of the safest vaccines
marketed. Tr. at 184 (discussing comments about the vaccine in the medical and
immunological communities). Several of the medical literature exhibits filed by both
parties in this case were based on these pre-marketing studies at Johns Hopkins
University. See, e.g., Pinto I, Pet. Ex. 73. Studies of Gardasil continued after licensure.
See, e.g., C. Chao, et al., Surveillance of autoimmune conditions following routine use
of quadrivalent human papillomavirus vaccine, J. INTERNAL MED., 271: 193-203 (2012),
filed as Pet. Ex. 80 and Res. Ex. C-23 [“Chao, Pet. Ex. 80”], at 194; T.C. Pomfret, et al.,
Quadrivalent human papillomavirus (HPV) vaccine: a review of safety, efficacy, and
pharmacoeconomics, J. CLINCAL PHARMACY & THERAPEUTICS, 36: 1-9 (2011), filed as
Res. Ex. C-5 [“Pomfret, Res. Ex. C-5”], at 4. As Dr. Zweiman testified (Tr. at 182), over
35 million doses of Gardasil have been administered to more than 20 million individuals
since licensure.22
21 Some of the filed medical literature indicates that it is not the “potency” of the vaccine VLPs that
stimulates the greater immune response, but rather the mechanism of inducing them. Wild-type HPV
viruses invade epithelial cells, which do not generate the same robust immune response to the virus as
the tissue into which the vaccine VLPs are injected. Stanley I, Pet. Ex. 62, at S16, S18.
22 The 35 million figure was based on data as of June 2011. Centers for Disease Control and
Prevention, Vaccine Safety: Reports of Health Concerns Following HPV Vaccination,
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Gardasil and the other HPV VLP vaccine have been shown to produce a
response by both the adaptive and innate arms of the immune system. Stanley I, Pet.
Ex. 62, at S18.
c. Antibody (Adaptive) Immune Response.
By design, HPV vaccines stimulate greater antibody production than the natural
viruses. Stanley I, Pet. Ex. 62, at S18; see also Tr. at 30-31 (Dr. McCabe). This quality
is “fairly uncommon” among vaccines. Villa, Pet. Ex. 31, at 5581; see also Stanley I,
Pet. Ex. 62, at S18 (“[T]he peak geometric mean antibody concentrations achieved are
at least two logs higher than those after natural seroconversion.”).23 After the three-shot
series, antibody concentrations “are 1-4 logs higher than those in natural infections.”
Stanley II, Pet. Ex. 63, at 4. The peak antibody response occurs about one month after
the final dose (the third dose) in the vaccination schedule. Id.
An immunogenicity study of Gardasil showed that the antibody response of the
vaccinated group, who had received the complete three injection series, was
approximately 10 to 100 times greater than the unvaccinated control group, who had
prior natural infection. Among the vaccinated group, the immune response began
approximately one month after the initial dose, peaked at approximately month seven,
and thereafter declined to a plateau for two and a half years after the last dose. Frazer
II, Pet. Ex. 71 at S12-13; see also Villa, Pet. Ex. 31, at 5578; E. Joura, et al., HPV
antibody levels and clinical efficacy following administration of a prophylactic
quadrivalent HPV vaccine, VACCINE, 26: 6844-51 (2008), filed as Pet. Ex. 68 [“Joura,
Pet. Ex. 68”], at 6849; A. García-Piñeres, et al., Cytokine and Chemokine Profiles
following Vaccination with Human Papillomavirus Type 16 L1 Virus-Like Particles,
CLINICAL & VACCINE IMMUNOLOGY, 14(8): 984-89 (2007), filed as Pet. Ex. 74 [“García-
Piñeres, Pet. Ex. 74”], at 986.
d. Cytokine Immune Response.
In addition to inducing greater antibody production than natural infection, HPV
vaccines have been shown to induce “cell mediated immune responses, including T cell
proliferative . . . and cytokine responses.” Pinto I, Pet. Ex. 73, at 3555. Because the
role of T-cells in mediating antibody production is poorly understood, researchers have
http://www.cdc.gov/vaccinesafety/Vaccines/HPV (printed Sept. 5, 2011), filed as Res. Ex. C-6 [“CDC,
Res. Ex. C-6”], at 1.
23 There was no evidence, however, that the immune response to Gardasil is different than the immune
response to other vaccines, simply that it is stronger than the body‘s response to natural infection. Doctor
McCabe indicated that other vaccines would cause a similar qualitative pro-inflammatory cytokine
response (Tr. at 58), but he could not say whether the response would be quantitatively similar (id.). In
other words, according to Dr. McCabe, vaccines in general provoke the same types of cytokine
responses, but he was unaware whether they provoked the same increases or decreases in cytokine
levels.
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focused on measuring cytokine responses as a surrogate for T-cell responses.
Researchers have theorized that “[c]ytokine profiling, as a measure of T cell responses,
may offer insights into mechanisms of protection against disease and help explain the
consistently strong antibody responses induced by the [HPV] vaccine.” Id.
C. Juvenile Ankylosing Spondylitis.
1. Ms. Godfrey’s Diagnosis.
Despite some discrepancies in the record regarding Ms. Godfrey’s diagnosis24
prior to the hearing, the parties ultimately agreed that Ms. Godfrey suffered from
juvenile ankylosing spondylitis [“JAS”]. Joint Pre-Hearing Submission at ¶ 3. See Pet.
Ex. 52 (Expert report of Dr. McCabe) at 3; Res. Ex. A (Expert report of Dr. Rose) at 2.
I conclude that JAS is the correct diagnosis.
JAS is the pediatric form of ankylosing spondylitis [“AS”]. Res. Ex. A (Rose) at 2.
The “juvenile” modifier is applied to those under 16 years of age who exhibit the
symptoms of AS. Pet. Ex. 52 (McCabe) at 3;25 Y. Lin, et al., Differences Between
Juvenile-onset Ankylosing Spondylitis and Adult-onset Ankylosing Spondylitis, J. CHIN.
MED. ASSOC., 72(11): 573-80 (2009), filed as Pet. Ex. 56 [“Lin, Pet. Ex. 56”], at 573.
Although the experts acknowledged that Ms. Godfrey was over 16 at the time of her
diagnosis, they were satisfied with the JAS diagnosis. Pet. Ex. 52 (Dr. McCabe) at 3
(“[A]ccordingly her diagnosis with JAS was consistent with her having an early onset
with the adult form of the disease.”); Res. Ex. A (Dr. Rose) at 2 (expressing his comfort
using the acronym JAS to describe Ms. Godfrey’s condition). Although there are some
differences in symptomology between JAS and AS, they are, in essence, the same
disease.
2. Symptomology.
The primary differences in clinical manifestation between AS and the juvenile
form, JAS, is the location of the enthesitis26 or arthritis. Where the initial symptoms of
24 Rheumatologist Randy Cron used the term “spondyloarthropathy” Pet. Ex. 7, p. 183. Rheumatologist
Anthony Turkiewicz diagnosed Ms. Godfrey with “ankylosing spondylitis/axial spondyloarthropathy.” Pet.
Ex. 88, p. 9. In her petition, however, Ms. Godfrey alleged that she suffered from “juvenile rheumatoid
arthritis.” Petition at 1. Ms. Godfrey’s first expert, Dr. Axelrod, classified her condition as “immune based
spondyloarthropathy” (Pet. Ex. 16 at 2) and “immune arthropathy (Juvenile spondyloarithitis).” Pet. Ex. 16
at 3. Later, in her pre-hearing brief, Ms. Godfrey stated that she and her expert would refer to her
condition as “juvenile idiopathic arthritis.” Pet. Pre-Hearing Br. at 5. Finally, in her post-hearing brief, she
identifies her diagnosis as “juvenile ankylosing spondylitis.” Pet. Post-Hearing Br. at 6.
25 Doctor McCabe’s expert report includes two sets of page numbers. This decision will refer to his report
using the computerized Bates stamped numbers.
26 Enthesitis is “inflammation of the muscular or tendinous attachment to bone.” DORLAND’S at 627; see
also M. Dougados and D. Baeten, Spondyloarthritis, LANCET, 377: 2127-37 (2011), filed as Pet. Ex. 54
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AS are mainly axial, the onset of JAS typically includes peripheral arthritis and
peripheral enthesopathies. Lin, Pet. Ex. 56, at 573-74, 578-79; H. Chen, et al., Clinical,
Functional, and Radiographic Differences Among Juvenile-onset, Adult-onset, and Late-
onset Ankylosing Spondylitis, J. RHEUMATOL., 39(5): 1-6 (2012), filed as Pet. Ex. 57
[“Chen, Pet. Ex. 57”], at 2, 4. The areas commonly affected in JAS are the pelvis,
heels, knee joints, and hip joints. Lin, Pet. Ex. 56, at 575. In JAS, versus AS, there is
“a tendency for more radiographic hip disease” (Chen, Pet. Ex. 57, at 4), affecting the
sacroiliac joints (S. Tse and R. Laxer, New advances in juvenile spondyloarthritis, NAT.
REV. RHEUMATOL., 8: 1-11 (2012), filed as Pet. Ex. 55 [ “Tse, Pet. Ex. 55”], at 1).27 This
is precisely the pattern Ms. Godfrey displays.
The severity of the disease is scored, based on the “irreversible structural
damage caused by the disease, often due to tissue remodeling and its functional
consequences.” Dougados, Pet. Ex. 54, at 2132.
3. Risk Factors.
There are several risk factors for JAS. Researchers have estimated that “genetic
risk factors contribute to 80-90% of the susceptibility to [AS].” Dougados, Pet. Ex. 54 at
2128; see also Lin, Pet. Ex. 56, at 578. The primary genetic risk factor is HLA-B27,
which has been described as a “direct and dominant effect.” Dougados, Pet. Ex. 54, at
2129; see also Lin, Pet. Ex. 56, at 579. HLA-B27 is present in 80-90% of patients with
AS. Dougados, Pet. Ex 54, at 2129. In patients with JAS, it is even more prevalent. In
a study of 47 patients with JAS, over 97% were positive for HLA-B27. Lin, Pet. Ex. 56,
at 577.28 A negative result, however, “does not preclude the presence of
spondyloarthritis.” Dougados, Pet. Ex. 54, at 2128. Moreover, “only a small proportion
of people in the general population who harbour HLA-B27 (5-6% in white people)
develop [AS], and HLA-B27 explains only 20-40% of the genetic susceptibility to [AS]—
suggesting the contribution of additional genes.” Id. at 2129.
and Res. Ex. C-1 [“Dougados, Pet. Ex. 54”], at 2128 (defining “enthesopathy” as “inflammation at the
bone insertion sites of ligaments and tendons”).
27 With the exception of some onset features, specifically the prevalence of peripheral arthritis and
peripheral enthesopathies, JAS resembles AS “in [its] association with HLA-B27 and bacteria, clinical
expression, and radiological features.” Additionally, it appears that both JAS and AS “share common
pathogenetic mechanisms.” R. Burgos-Vargas, Juvenile onset spondyloarthropathies: therapeutic
aspects, ANN. RHEM. DIS., 61(Suppl. III): iii33-iii39 (2002), filed as Pet. Ex. 61 [“Burgos-Vargas, Pet. Ex.
61”], at iii33. Consequently, references to AS also likely apply to JAS.
28 See also NELSON TEXTBOOK OF PEDIATRICS (19th ed. 2011) [“NELSON’S ”], at Pt. XV, Ch. 150, Lab.
Findings, https://expertconsult.inkling.com/read/nelson-pediatrics-kliegman-behrman-19th/chapter-
150/chapter150-reader-4 (noting that “HLA-B27 is present in > 90% of children with JAS.”).
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In addition to genetic factors, specific types of infection (gastrointestinal or
genitourinary infection), and physical trauma are also risk factors for JAS. Lin, Pet. Ex.
56, at 578; Tr. at 195-97 (Dr. Zweiman). JAS is closely linked to gut inflammation, in
association with Crohn’s disease. Burgos-Vargas, Pet. Ex. 61, at iii34. The incidence
of non-specific inflammatory bowel disease in patients with JAS is about 80%. Id. at
iii35. Intense physical training has been observed in JAS patients before symptom
onset. Lin, Pet. Ex. 56, at 578.
4. Treatment.
Treatments for JAS are “aimed at alleviating symptoms of inflammation (that is,
pain), maintaining or improving range of motion and muscle strength, preventing
deformity, preserving function, and preventing or managing disease complications.”
Burgos-Vargas, Pet. Ex. 61, at iii36; see also Dougados, Pet. Ex. 54, at 2132. In
addition to physical and occupational therapy, non-steroidal anti-inflammatory drugs
[“NSAIDs”] are used to treat JAS. Burgos-Vargas, Pet. Ex. 61, at iii36; Dougados, Pet.
Ex. 54, at 2132 (identifying NSAIDs as “the cornerstone pharmacological intervention”
for AS).
Agents that target tumor necrosis factor alpha [“TNF-α”], including etanercept
and Infliximab, are also used to treat JAS. Burgos-Vargas, Pet. Ex. 61, at iii37. TNF-α
is a pro-inflammatory cytokine “that mediates several inflammatory and
immunoregulatory activities.” Id. High levels of TNF-α have been documented in the
synovial tissue of patients with JAS. Id. at iii37. “Increased production of TNF-α
correlates closely with increased infiltration of inflammatory cells (T cells and
macrophages) into the synovia.” Id. at iii34. However, despite the success of anti-
inflammatory drugs in providing symptomatic relief, current JAS treatments, including
drugs like Infliximab, “do not alter the natural course of the disease.” Id. at iii37.
D. Petitioner’s Evidence.
Doctor McCabe opined that Ms. Godfrey’s Gardasil vaccination triggered, thus
substantially contributing to, the manifestation of her JAS. Tr. at 16. His theory, which
he described as a “biologically plausible” mechanism, was that the vaccination triggered
the release of proinflammatory cytokines, causing her JAS. Tr. at 16; Pet. Ex. 52 at 7.
Doctor McCabe explained that JAS is a disease with an autoinflammatory
etiology.29 The disease process is “driven by dysregulation of the innate immune
29 Autoinflammatory diseases should not be confused with autoimmune diseases. “Autoimmune diseases
are characterized by unchecked T-cell and/or B-cell reactivity to self-antigens, leading to chronic tissue
inflammation.” C. Ambarus, et al., Pathogenesis of spondyloarthritis: autoimmune or autoinflammatory?,
CURR. OPIN. RHEUMATOL., 24: 1-8 (2012), filed as Pet. Ex. 79 [“Ambarus, Pet. Ex. 79”], at 1. In contrast,
autoinflammatory diseases do not involve attacks by the immune system on host tissues; they involve
“innate immune responses to specific tissue triggers, such as microorganisms or microtrauma.” Id.
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system.” Pet. Ex. 52 (Dr. McCabe) at 3. The causes of JAS are “multifactorial,” with
“genetic susceptibility factors and environmental triggers working together in complex
ways to initiate and perpetuate adaptive and innate immune activities resulting in tissue
damage.” Id. Doctor McCabe acknowledged Ms. Godfrey’s genetic susceptibility,
noting the “high association between HLA-B27 and spondyloarthritis.” Id.; see also Tr.
at 20, 23, 48-49. He also noted her father’s Crohn’s disease and its “link” to cytokine
expression as a genetic risk factor.30 Tr. at 21.
Doctor McCabe testified that bacterial or mechanical stressors have been
implicated in the etiology of spondyloarthropathies (Tr. at 22, 26), but the evidence that
“infection, stress, and trauma are all triggers associated with the onset of JAS” is
“[l]argely temporal” (Tr. at 85). He noted that “a large number of people” with JAS “have
had a traumatic event or a bacterial infection.” Tr. at 22, 26, 85; see also Dougados,
Pet. Ex. 54, at 2129-30. Doctor McCabe acknowledged the absence of studies
identifying an association between vaccines and spondyloarthropathies, but added that
there is some overlap in the stimulation of pro-inflammatory cytokines between bacterial
infections and vaccines and bacterial infections are known triggers for
spondyloarthropathies. Tr. at 26-27, 34-35.
The Gardasil vaccine is designed to elicit an immune response greater than that
induced by natural HPV infection. Pet. Ex. 52 (Dr. McCabe) at 4. This immune
response is characterized by high anti-HPV L1 VLP antibody titers, as well as “high
levels of both adaptive and innate immune cytokines.” Id. (citing Pinto I, Pet. Ex. 73) 31
Doctor McCabe stated that the L1 viral capsid protein in Gardasil “induce[s] high titers of
neutralizing antibodies to the L1 [protein].” Pet. Ex. 52 at 4. He added that “the peak
geometric mean antibody levels that are achieved are reported to be 100-fold higher
than those that occur due to natural seroconversion as a consequence of HPV
infection.” Id. According to Dr. McCabe, “[t]his strong antibody response is expected to
be, and is, controlled by the activities of T cells including production of T cell derived
cytokines.” Id. at 5. He added that many of the adaptive and innate cytokines elicited
by the Gardasil vaccine are the “pro-inflammatory cytokines that have been implicated
in the etiology32 of auto-inflammatory disorders like [JAS].” Pet. Ex. 52 at 4. Included
among these pro-inflammatory cytokines are TNF-α and interleukins [“IL”] 1, 6, 17, and
23. Id. at 5. Doctor McCabe stated that the natural HPV infection “produces little or no
pro-inflammatory cytokine release, and if anything stimulates an anti-inflammatory
cytokine cascade.” Tr. at 34.
30 Doctor Zweiman appeared to disagree that Crohn’s disease was causally linked to cytokines such as
TNF-α. See Tr. at 181.
31 This quotation somewhat misstates both the study’s focus and results, which are discussed in more
detail infra at Section V.A.1.
32 Doctor McCabe’s phraseology of “implicated in the etiology” suggests that pro-inflammatory cytokines
are causal or pathogenic. This was countered by Dr. Rose’s testimony. Tr. at 116-18.
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During the hearing, Dr. McCabe was asked for the best evidence that the
Gardasil vaccine is an environmental factor linked to AS. Tr. at 50. He responded that,
in “producing a common element of the disease”—innate immune system activation—
the vaccine “serves as a trigger in [a] genetically predisposed individual.” Id. He added
that the “vaccine is doing exactly what it’s intended to do” in stimulating an innate
immune system response. Id.
Later, it became unclear whether Dr. McCabe was contending that Ms. Godfrey’s
genetic predisposition rendered her more susceptible to a normal cytokine-driven
immune activation, or that the vaccine caused an abnormally high level of cytokine
production in Ms. Godfrey. Tr. at 50-51, 54-56. His characterization of the role of
cytokine production in response to HPV vaccination was inconsistent. During his cross-
examination, he agreed with respondent’s summation of his theory that “the abnormal
production of certain cytokines plays . . . a significant role in the etiology of ankylosing
spondylitis.” Tr. at 45. Shortly thereafter, however, he stated, “I’m not saying that [the
vaccine is] triggering an abnormal production of those cytokines,” rather it causes the
production of pro-inflammatory cytokines “[t]hat are serving as a trigger for disease in a
susceptible individual.” Tr. at 50-51; see also Tr. at 54.33
However, Dr. McCabe was consistent in his assertion that Gardasil stimulated
cytokine production in Ms. Godfrey, specifically the production of TNF-α, and that this
immune response, when combined with her genetic susceptibility, caused Ms. Godfrey
to develop JAS. Tr. at 45-47; see also Tr. at 16, 28-29. By way of analogy, he testified
that a genetically susceptible person such as Ms. Godfrey is climbing a hill towards
development of the disease throughout her life, but the Gardasil vaccine hastened her
assent, pushing her to the peak. Tr. at 56.
He also stated that, for JAS to manifest, there must be “sustained elevation of the
cytokines and the abnormality in the regulation of the cytokine[s] in order for the disease
to manifest and to continue to manifest.” Tr. at 57. He testified that “the basis of why
people who have this disease and diseases like it are on anti-TNF drugs for a long
period of time, is that there is a sustained disregulation in the production of cytokines.”
Id. He did not point to any evidence that Gardasil caused a sustained elevation in
cytokines in recipients. Tr. at 75-77.
33 Doctor McCabe later clarified that the cytokine response to vaccination is not abnormal, rather it is “the
abnormality in the regulation of the cytokine” that causes the disease to manifest and continue to
manifest. Tr. at 57. Even later, however, Dr. McCabe failed to correct respondent when she asked,
“What is your best evidence that Megan had an abnormally high level of any of the cytokines that you
mentioned.” Tr. at 73-74.
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With regard to timing, Dr. McCabe opined that “the expected interval between
vaccination and the onset of the autoinflammatory trigger is predicted by the time period
that measurable changes in the immune response are known to be elicited by the
vaccine.” Pet. Ex. 52 at 5; see also Tr. at 75-76. He referenced studies showing that
nearly all individuals who received three doses of Gardasil at zero, two, and six months
seroconverted34 within seven months. Pet. Ex. 52 at 5-6. When he was asked why four
weeks would be an appropriate medical time frame for the development of JAS, Dr.
McCabe stated that four weeks and earlier is “the time that the immune response is
elicited by the vaccine.” Tr. at 79. He also testified that, considering Ms. Godfrey only
received one dose of Gardasil, he would be “less inclined to think that the vaccine or the
cytokines elicited by the vaccine . . . was the trigger” had she not presented with
symptoms within two months of vaccination. Tr. at 78; see also Tr. at 38, 84.
Doctor McCabe testified that the best evidence that a single dose of the HPV
vaccine can stimulate a sufficiently strong and prolonged production of pro-inflammatory
cytokines to cause a spondyloarthropathy is a study involving the stimulation of blood
cells in culture with one component of the Gardasil vaccine, HPV-16. Tr. at 52-53
(citing M.A. Marks, et al., Progesterone and 17ß-Estradiol Enhance Regulatory
Response to Human Papillomavirus Type 16 Virus-Like Particles in Peripheral Blood
Mononuclear Cells from Healthy Women, CLINICAL & VACCINE IMMUN., 17(4): 609-17
(2010), filed as Pet. Ex. 87 [“Marks, Pet. Ex. 87”]). This study measured cytokine levels
in blood cells taken from adult women after the cultured cells were stimulated with
VLPs. Unsurprisingly, elevations in both pro- and anti-inflammatory cytokine levels,
including TNF-α, were seen in the stimulated samples.
Doctor McCabe noted that a single in vitro immunization stimulated a variety of
cytokines, including TNF-α, measured at 72 hours post immunization. Tr. at 55 (citing
Marks, Pet. Ex. 87, at 612). He added that he would expect that the production of pro-
inflammatory cytokines in vivo (within the body) would occur within the same time
frame, specifying that he would expect TNF-α levels to be increased within three days.
Tr. at 55-56. Finally, he stated that the level of TNF-α within three days of immunization
“[c]ould be” high enough to cause AS in a genetically predisposed person. Tr. at 56.
However, the purpose of the cited study was not the measurement of cytokine
levels in women before and after vaccination with Gardasil. As the stimulation by the
VLPs occurred in vitro, it is unlikely that the cytokine response could reliably be related
to the cytokine levels produced by a vaccine administered in vivo. Tr. at 180, 198.
Moreover, as the study’s purpose was to measure the effect of hormones on the
immune response, it is unlikely that the researchers intended to draw any conclusions
about immediate or delayed cytokine responses in vaccine recipients or that they were
attempting to mirror in vitro the cytokine response in vivo to the vaccine.
34 That is, showed antibodies to HPV.
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Doctor McCabe acknowledged that “there is nothing that’s really all that
convincing that [Ms. Godfrey] had any inflammatory response or anything going on as a
consequence of elevated, pro-inflammatory cytokines after her immunization[s].” Tr. at
74. Noting that there was no testing of Ms. Godfrey for markers of inflammation, he
maintained that the best evidence that she had a high-level antibody response during
the four weeks after the vaccination was the scientific evidence showing that over 90%
of individuals seroconvert with such a response following the Gardasil vaccine. Tr. at
73-76 (discussing Frazer II, Pet. Ex. 71; Pinto I, Pet. Ex. 73; L. Pinto, et al., Cellular
Immune Responses to Human Papillomavirus (HPV)-16 L1 in Healthy Volunteers
Immunized with Recombinant HPV-16 L1 Virus-Like Particles, J. INFECT DIS., 188(2):
327-38 (2003), filed as Pet. Ex. 75 [“Pinto II, Pet. Ex. 75”]; T.G. Evans, et al., A Phase 1
Study of a Recombinant Viruslike Particle Vaccine Against Human Papillomavirus
Type 11 in Healthy Adult Volunteers, J. INFECT. DIS., 183 (10): 1485-93 (2001), filed as
Pet. Ex. 76 [“Evans, Pet. Ex. 76”]; Chao, Pet. Ex. 80.
Doctor McCabe testified that the antibody response after a single immunization
“reaches a plateau between 12 and 18 days after immunization, and then declines.” Tr.
at 81-82 (citing I.H. Frazer, Measuring serum antibody to human papillomavirus
following infection or vaccination, GYNECOLOGIC ONCOLOGY, 118:S8-11 (2010), filed as
Pet. Ex. 70. However, I note that this citation refers to immunizations in general, and
not specifically to HPV immunizations. See id. at S10. The paper cited also notes that
no correlation between antibody level and protection against natural infection could be
established because 40% of vaccinated individuals lacked measureable antibodies to
HPV at 48 months after vaccination. Id. at S9.
When asked about evidence that Ms. Godfrey’s cytokine levels remained
elevated for four weeks after vaccination, he agreed that “no one measured antibody
titer in Megan Godfrey, but you would expect that her antibody titers in response to HPV
were increasing.” Tr. at 39; see also Tr. at 74-75.
Doctor McCabe admitted that, despite his efforts to locate evidence to support a
connection between vaccines in general and spondylopathy, he could not find any. Tr.
at 59. Regarding Gardasil specifically, he stated that “epidemiological studies
addressing the potential connection between Gardasil and ankylosing spondylitis,
juvenile or otherwise, don’t exist.” Tr. at 40. He added that epidemiological studies
addressing other autoinflammatory diseases have been performed, but “none . . . were
appropriately powered to truly be able to tell us whether there was an increased risk or
incidence of disease in those populations.” Tr. at 40-41. Doctor McCabe was asked
specifically about a safety study that involved 189,629 women who received at least one
dose of the quadrivalent HPV vaccine. Tr. at 65 (referencing Chao, Pet. Ex. 80). He
acknowledged that this study did not reveal an increased incidence of
spondyloarthropathies like AS and JAS in the vaccinated population, but attributed the
negative results to the rarity of the disease and the study lacking the power to detect a
relationship of such a rare condition with the vaccine. Tr. at 41, 65-72.
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E. Respondent’s Evidence.
1. Summary of Dr. Rose’s Report and Testimony.35
Doctor Rose’s opinion rejecting a causal relationship between Gardasil and JAS
rested on several points.36 First, he noted that there are no epidemiologic studies
linking such conditions to Gardasil. Res. Ex. A at 3. Second, he relied on Ms.
Godfrey’s strong genetic predisposition for developing JAS, as evidenced by “the
presence of histocompatibility marker HLA-B27” as well as Crohn’s disease in her
father. Id. at 11. Moreover, she had not only a genetic predisposition but a known
trigger for JAS in her medical history. Chronic micro-trauma, in the presence of HLA-
B27, is a known trigger for JAS, and Ms. Godfrey was a high school athlete who was on
her school’s cheerleading team, which provided a basis for inferring the presence of
micro-trauma. Tr. at 114-15, 162-64; Pet. Ex. 50. Doctor Rose opined that this
combination, particularly in light of a first degree relative with Crohn’s disease, fully
accounts for her JAS. Tr. at 102-03. Finally, and perhaps most significantly, Dr. Rose
explained why Dr. McCabe’s assertions about the role of cytokines in JAS’s etiology
were incorrect. Cytokines do not cause JAS, although they play a role in the
symptomology of the condition. Tr. at 116-18.
a. Epidemiology and Causation.
Doctor Rose testified that the epidemiologic evidence concerning the effects of
Gardasil does not show any association with JAS or arthritic conditions in general. Tr.
at 125-27. However, unlike Dr. McCabe, Dr. Rose found the Chao study, Pet. Ex. 80, to
be sufficiently powered to detect a relationship between Gardasil and rheumatic
disorders. Tr. at 123. He explained that the incidence of AS in the U.S. is about 7
cases per 100,000 persons, and that the male to female ratio is about 3-1 for adults and
7-1 for children. Tr. at 120-21, 146. Based on these ratios, and in the context of the
nearly 190,000 women considered in the Chao study, Dr. Rose testified that “you should
see about 1.5, 1.7 cases of ankylosing spondylitis in this [female] cohort.” Tr. at 122.
None were identified. Tr. at 121-24, 149-50. Although there were cases of juvenile
35 Doctor Rose submitted his expert report in response to petitioner’s report from Dr. Axelrod and prior to
petitioner’s filing of Dr. McCabe’s report. See Res. Ex. A, filed Sept. 26, 2011. Although his report
addresses some of the issues raised by Dr. McCabe, his testimony was in direct response to Dr.
McCabe’s opinions. Tr. at 133.
36 I did not find Dr. Rose’s reliance on the lack of any known association of natural HPV infection with
spondyloarthropathy or any rheumatic disease (Tr. at 115-16; Res. Ex. A at 3, 5) to be a reason to reject
Dr. McCabe’s opinions. While it is true that natural HPV infections are not linked to chronic arthritic
conditions like JAS, given Dr. McCabe’s theory that an aberrant immune response rather than any
specific action of the virus itself caused Ms. Godfrey’s JAS, the lack of a link with natural infection is not
significant. Doctor Rose agreed with Dr. McCabe that the natural infection and the vaccine are “very
different stimuli.” Tr. at 116. I thus do not discuss this argument in any more detail.
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idiopathic arthritis,37 the incidence in the study participants did not exceed the
background rate expected in the population sampled. Tr. at 122-23, 150.
Aside from studies like Chao, there is other circumstantial evidence that a causal
association between JAS and Gardasil is unlikely. There has been no change in the
background rate of AS since Gardasil was introduced.38 Tr. at 171 (Dr. Rose).
Although more women are now diagnosed with JAS than there were in 1950-60, the
increase is not temporally linked to the introduction of Gardasil. Doctor Rose attributed
the increase in female diagnoses to greater awareness of the disease. Tr. at 171. He
was unaware of any change in time of onset of either AS or JIA. Id. As Gardasil is
recommended for administration to individuals in a narrow age range (between nine and
26 years of age (see Slade, Res. Ex. C-2, at 750)), a change in time of onset would be
expected if the vaccine is causal.
b. Genetics and Triggers.
In explaining what is known about the causes of JAS, Dr. Rose testified that
about 80-90% of AS cases have a genetic etiology and that the remaining cases are
caused by environmental factors. Tr. at 109-11, 141 (citing Dougados, Pet. Ex. 54).
Two identified environmental factors are bacterial infections, commonly of the intestinal
tract, and trauma, specifically chronic micro-trauma associated with physical activity.
Tr. at 113-15; see also Tr. at 138-39. Although there was no evidence that Ms. Godfrey
suffered from enteritis, Dr. Rose pointed out that she was a cheerleader, and such
activity would cause “continuous trauma to her Achilles tendon [and] sacroiliac joints.”
Tr. at 162-63.
According to Dr. Rose, about 20-40% of the cases of JAS or AS with a genetic
etiology are linked to HLA-B27, with the remainder are associated with other genes. Tr.
at 109-11. AS is considered a “polygenic disease,” meaning that genes inherited in
blocks or groups provide all the genetics needed to cause the condition. Tr. at 111-12;
see also Ambarus, Pet. Ex. 79, at 2. He explained that the child of a person both
carrying B27 and having AS who inherits her parent’s variant of HLA-B27 is more likely
to get AS than if the parent had B27, but no disease. Tr. at 112-13; see also Res. Ex. A
at 11. This is so, not because parent and child were exposed to the same
environmental factor such as a vaccine, but because the child “inherited the B27 plus
37 Although JIA and AS are not the same disease, they present with similar symptoms. Tr. at 122-23 (Dr.
Rose). About 80% of pediatric patients with spondyloarthropathy have a presentation that is
indistinguishable from JIA. Tr. at 123; see also Tr. at 125-26 (Doctor Rose citing Appendix A to Chao,
Pet. Ex. 80, filed as Res. Ex. C-24, and explaining that the Chao researchers did “everything possible to
capture conditions like [Ms. Godfrey’s]”).
38 Gardasil was licensed for use in the U.S. in 2006, and added to the Vaccine Injury Table later that
same year. Slade, Res. Ex. C-2, at 750; Vaccine Injury Table, 42 C.F.R. § 100.3 (2011).
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the other genes that produce causality.”39 Tr. at 112-13. He maintained that the onset
of Ms. Godfrey’s JAS following her Gardasil vaccination was “simply coincidental.” Tr.
at 102.
c. The Role of Cytokines in JAS.
Doctor Rose was most critical of the part of Dr. McCabe’s theory that rested on
the impact of the cytokine response in disease causation. He noted that the theory is
“very unspecific” and one that he has not heard discussed in the general rheumatologic
community. Tr. at 116-18. He did not dispute that the vaccine could cause a cytokine
response, but did dispute that a cytokine response could cause the disease. Tr. at 116-
17 (noting that almost any stress, including the common cold, sun exposure, and
exercise can elicit a cytokine response). Acknowledging that a vaccine could elicit a
cytokine response, he testified “[t]he fact that the HPV vaccine elicits a cytokine
response doesn’t make it more likely than any other life event . . . that can lead to
excessive cytokines.” Tr. at 117; see also Tr. at 158-59, 161-62.
He noted that HLA-B27 and other genes causally associated with AS “are not
genes of hyper response to cytokines.” Tr. at 117. As he explained, “B27 doesn’t make
her more prone to respond to or release more cytokines than the normal population
upon a stimulation process.” Id. This directly countered the portion of Dr. McCabe’s
theory that a cytokine response to Gardasil could trigger JAS in a “genetically
susceptible” individual.
Doctor McCabe opined that pro-inflammatory cytokines such as TNF-α play a
role in JAS, pointing to the use of TNF-α blockers as one of the primary treatments as
support for their causal role. Tr. at 45-7. Doctor Rose agreed that medicines like
Humira40 that target TNF-α are one of the primary treatments for JAS. Tr. at 169. He
also agreed that “interrupting TNF-alpha production results in less disease or less
disease symptoms” in 70-80% of patients. Id. Most significantly, however, Dr. Rose
disagreed that TNF-α, produced as the result of a vaccine or other life events, is a
cause of JAS or similar conditions. Tr. at 170. TNF-α, rather than pushing a genetically
predisposed person over the crest of the hill, produces disease symptoms such as pain
and heat. However, TNF-α does not cause the disease itself. Id. TNF-α medications
relieve pain, but do not affect the natural progression of the disease. Id. His assertions
were supported by Dougados, Pet. Ex. 54, at 2131 (noting that the use of TNF blockers
does not prevent ankylosing enthesitis) and 2133 (TNF blockers “halt joint destruction
but fail[] to substantially slow new bone formation” in the disease process).
39 On cross-examination, Dr. Rose agreed that “a very small fraction” of those who express HLA-B27,
about 5-20%, develop AS. Tr. at 142-43. He noted, however, that people like Ms. Godfrey who have a
parent with Crohn’s disease, have a fourfold elevated risk. Tr. at 144.
40 Humira, like Infliximab, the treatment Ms. Godfrey received, is a TNF-α inhibitor used to treat
inflammation in a variety of medical conditions, including AS.
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d. Timing.
Doctor Rose agreed with Dr. McCabe that measuring antibody titers to HPV is a
method to determine if the vaccine is effective. However, he disagreed that relating
“antibody formation to the onset of the disease” proves anything about causation,
because onset of symptoms such as Ms. Godfrey displayed does not tell us when her
disease began. Tr. at 129; see also Tr. at 165 (stressing the difference between onset
of symptoms and onset of disease). Based on when her symptoms first occurred, Dr.
Rose could not opine when Ms. Godfrey’s disease process actually started. Tr. at 129.
Thus, the evidence regarding timing between vaccination and symptom onset in Ms.
Godfrey could not be reliable evidence of causation as Dr. McCabe asserted, because
symptom onset did not mark the onset of the disease process. For example, Ms.
Godfrey had inflammation in both sacroiliac joints but only had pain in one of them, at
least initially, demonstrating the separation between symptom onset and disease
process. Tr. at 129; Pet. Exs. 8, p. 14; 9, p. 122.
2. Summary of Dr. Zweiman’s Report and Testimony.
Doctor Zweiman also set forth several reasons that contradict Dr. McCabe’s
causation theory. First, like Dr. Rose, he found the lack of support in the medical
literature for a causal association between HPV immunization and JAS41 to be a
significant reason for rejecting the theory. Res. Ex. C at 3. He also rejected Dr.
McCabe’s assertions regarding the role of cytokines in the disease process, noting that
under Dr. McCabe’s theory, in order to cause JAS, cytokine production would have to
occur in a “prolonged, consistent fashion.” Tr. at 200. Third, he opined that her risk
factors fully accounted for her AS. Res. Ex. C at 3.
a. Epidemiology and Medical Literature.
Doctor Zweiman cited to numerous pre- and post-licensure studies involving HPV
vaccines and absence of reports of persistent joint symptoms exceeding the
background rate expected.42 Thus, this is not a case where epidemiologic evidence is
lacking. The epidemiology exists, and is not supportive of the theory.
41 Throughout his expert report, Dr. Zweiman used the broad term, “spondyloarthropathy” [“Sp”] to refer to
a group of “several related but distinct disorders,” including AS. Res. Ex. C at 2.
42 Res. Ex. C at 3 (citing Slade, Res. Ex. C-2 at 750, 755-56 (examining VAERS reports in the 2.5 years
after licensure and finding only 13 reports of rheumatoid arthritis which did not exceed the background
rate expected, but noting that VAERS reports should be viewed with caution ); CDC, Res. Ex. C-6;
Quadrivalent Human Papillomavirus Vaccine ,Report of the Advisory Committee on Immunization
Practices (ACIP), MMWR 56(RR02): 1-24 (2007), filed as Res. Ex. C-4 (reporting no statistically
significant differences between placebo and vaccine recipients for various arthritic diagnoses); B. Lu, et
al., Efficacy and Safety of Prophylactic Vaccines against Cervical HPV Infection and Diseases among
Women: A Systematic Review & Meta-Analysis, BMC INFECT. DIS. 11: 13 (2011), excerpts filed as Res.
Ex. C-3 at 4 (reporting no statistically significant difference in the risk for serious adverse events between
vaccine and control groups).
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Addressing the Chao article, Dr. Zweiman reasoned that if 6-8% of the
Americans are HLA-B27 positive, and 35 million doses of Gardasil have been
administered in the U.S., one would expect that the incidence of JAS among the over
one million HLA-B27 positive individuals who received the vaccine would be notable if
the HPV vaccine was a trigger. Tr. at 182. In other words, if JAS could be triggered by
the HPV vaccine, it would not be such a rare condition, given the number of doses
administered since Gardasil was introduced.43 Tr. at 182-83. Asked what sort of
evidence he would look for if there were a causal relationship between the HPV vaccine
and AS, Dr. Zweiman stated that he would expect “safety signals . . . raised by sizeable
numbers of reports through the [Vaccine Adverse Events Reporting System],” as well as
“some evidence of real biologic plausibility.” Tr. at 183-84; see also Tr. at 187. He
stated that he has seen no such evidence. Tr. at 184, 187.
b. Cytokines and Immune Response.
Before explaining what he found deficient in Dr. McCabe’s cytokine theory, Dr.
Zweiman offered some background as to “what happens when an individual is
immunized with a potent immunogen.” Tr. at 176. He stated that “there is an initial
activation, a so-called primary immune response, and that when that individual is then
re-exposed to the antigen . . . one would expect it likely that there would be an
exaggerated proliferative response.” Tr. at 176 (citing Pinto I, Pet. Ex. 73). He added
that, in addition to a proliferative response, there would be a stimulation of cytokine
production, including pro-inflammatory cytokines like TNF- α, and that “it would not be
surprising that one would get a more prominent lymphocyte proliferation as well.” Tr. at
177. He explained that pro-inflammatory cytokine elaboration is a common response to
infection and even trauma. Tr. at 179. Concerning the HPV vaccine specifically, he
agreed that HPV VLPs are effective at inducing pro-inflammatory cytokines. Tr. at 212.
Doctor Zweiman testified that the innate immune response differs from the
adaptive immune response in two ways. The first difference is the “major cellular
players in a production of [the] immune response,” and the second is that the innate
immune response does not have “immunologic memory such as one finds in adaptive
responses.” Tr. at 179. Concerning the second point, he stated that, “to get a repeat or
continued elaboration of the products of inflammatory cytokine, you have to have
continued stimulation by the initial stimulus.” Tr. at 179-80. Doctor Zweiman explained
that in sustained cytokine production, an innate immune response “does not carry
immunologic memory like the adaptive immune response, so that for the most part one
43 In opining that Ms. Godfrey was “genetically susceptible” to developing JAS, and that her response to
the vaccine pushed her into its development (Tr. at 56), Dr. McCabe appeared to be referring to the HLA-
B27 marker. Thus, Dr. Zweiman’s point that others with the same marker would be pushed into JAS
development by the same process is well-taken. It is possible that Dr. McCabe was opining that there
was something very unique about Ms. Godfrey, but if so, he never identified any “x factor” that separated
her from the more than 1,000,000 other young women with HLA-B27 who also received HPV vaccines.
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needs to have a continued stimulation of more production by cells,” of which there is no
evidence in studies. Tr. at 202-03.
Thus Dr. Zweiman opined that Dr. McCabe’s theory, as described using a hill
analogy, is flawed. Tr. at 180, 199. He maintained that the notion of a vaccine-elicited
pro-inflammatory cytokine response that pushes an individual over the top of the hill and
leads to disease development on its own, “goes against what is generally known about
the production of [pro-]inflammatory cytokines.” Tr. at 180. He opined that there must
be continued pro-inflammatory cytokine production in order to continue a disease
process under this theory and that Dr. McCabe presented no convincing evidence of
continued stimulation. Tr. at 180, 198-99, 203. Doctor Zweiman based this opinion on
“the fact that in individuals who have high even blood levels of some of these pro-
inflammatory cytokines associated with certain diseases, when the levels go down, the
clinical adverse manifestations decrease or go away completely.” Tr. at 203-04.
Building on Dr. Rose’s testimony about the role of cytokines in JAS, Dr. Zweiman
explained why the studies done by the Pinto group, E.g., Pinto I, Pet. Ex., were not
supportive of Dr. McCabe’s causation theory. As Dr. Rose testified, a transient increase
in the production of pro-inflammatory cytokines such as TNF-α would not cause
sustained symptoms or disease. Doctor Zweiman explained, relying on the Pinto I
study as well as basic immunological principles, that Gardasil did not produce any
sustained increase in cytokine levels in vaccinated individuals. Tr. at 178-79. Cultured
blood cells drawn from individuals who had received HPV vaccines produced higher
levels of cytokines than individuals who had not received the vaccines, but only when
the cultured blood cells were again exposed to HPV vaccines in vitro. Pinto I, Pet. Ex.
73, at 3558-61.
In his expert report, Dr. McCabe relied on Pinto I, Pet. Ex. 73, citing it for the
statement that individuals immunized with HPV L1 VLPs, the immunogenic component
of Gardasil, produce “high levels of both adaptive and innate immune cytokines.” Pet.
Ex. 52 at 4. The difficulty is that the this study 44 and several others from the same
44 The Pinto I study was not terribly complex, but the explanation in the text is sometimes unclear.
Researchers measured 11 cytokines, including TNF-α, before and after vaccination in twenty-four
women, four of whom belonged to the control group and received placebo injections. At “month zero,”
prior to the initial injection, the researchers drew blood samples. The vaccinated group then received a
dose of the HPV-16 L1 VLP vaccine and the control group received a placebo. Second injections were
administered one month later. At month two, a second set of blood samples was taken. Final injections
were administered at six months, and the final blood samples were taken a month later, seven months
after the initial blood draw. Pet. Ex. 73 at 3556-57.
The blood samples from both the vaccinated and control groups were divided into samples for in vitro
stimulation. Id. at 3557, 3562. Samples from each group, for each interval, were either not stimulated, or
stimulated with one of the following: (1)10 μg of the VLP present in the vaccine; (2) 1.0 μg of the VLP; or
(3) a control substance that would not stimulate a reaction (unstimulated samples). The researchers then
measured cytokine levels in the samples. Id. at 3558 (Table 1). For both the vaccinated and control
groups, cytokine levels in the unstimulated samples were relatively similar at months zero, two, and
seven. Id. at 3560.
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Johns Hopkins group of researchers found increased cytokine levels only when those
who were already vaccinated with HPV L1 VLPs had blood stimulated with more HPV
L1-VLPs. See, e.g., Pinto I, Pet. Ex. 73 at 3556-59. This study was not designed to
measure cytokine levels produced by the vaccine itself, but rather whether increased
cytokine levels could be used as a surrogate for antibody response. Id. at 3556-57.
Although the study shows that women who were vaccinated against HPV mounted a
robust cytokine response in the presence of HPV VLPs, it did not show a significant
increase in cytokine levels in the absence of such a challenge. Id. at 3558 (Table 1).
c. Genetics and Predisposition.
According to Dr. Zweiman, “Ms. Godfrey was in an age range in which [JAS]
occurs spontaneously.” Res. Ex. C at 3. Based on her expression of HLA-B27 and its
prevalence in people with JAS, Dr. Zweiman, like Dr. Rose, opined that her JAS
developed “by chance.” Id. at 3; Res. Ex. A at 11.
V. Analysis of Causation Evidence
A. Applying Althen.
The Federal Circuit has set forth three factors petitioners must establish to prove
causation in off-Table cases. See Althen, 418 F.3d at 1278. Althen requires petitioners
to provide: “(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.” Id. All three prongs of the Althen test must be satisfied by preponderant
evidence. de Bazan, 539 F.3d at 1351-52; Caves, 100 Fed. Cl. at 132 (finding that
“[w]hen a petitioner seeks to demonstrate causation in fact by meeting the three Althen
requirements, each of those requirements must be proven by a preponderance of the
evidence”), aff’d per curiam, 463 Fed. Appx. 932, 2012 WL 858402 (Fed. Cir. 2012).
Therefore, petitioner must establish a medical theory causally connecting the
vaccination and the injury by preponderant evidence. Althen, 418 F.3d at 1278.
1. Lack of Reliable General Causation Evidence.
Petitioner’s causation case is based on the HPV vaccination she received on
August 22, 2007, “substantially contributing” to her development of JAS. The medical
theory propounded—that the pro-inflammatory cytokine proliferation caused by a single
Gardasil vaccine can push a genetically susceptible individual to develop JAS—fails the
reliability test. The major difficulty with Dr. McCabe’s theory is that there is no evidence
that pro-inflammatory cytokines play any role in the pathogenesis of JAS, although they
The mean blood cytokine levels from both placebo and vaccine recipients were remarkably similar in the
samples not challenged by stimulation with HPV VLP. Cytokine levels were significantly different when
the HPV VLPs were used to stimulate the blood from the vaccine recipients. Id. at 3558 (Table 1).
28

Case 1:10-vv-00565-NBF Document 73 Filed 07/08/14 Page 29 of 31
do play a role in the symptoms displayed. Doctor Rose’s testimony, that pro-
inflammatory cytokines cause symptoms of JAS but not the disease itself, is unrebutted.
The Dougados article, filed by both parties, (Pet. Ex. 54 and Res. Ex. C-1 at 2132-33)
supports Dr. Rose’s testimony. Treatment with TNF-α inhibitors alleviates symptoms,
but does not affect the progression of the disease. Id.
Although less devastating for petitioner’s case, there are other problems with Dr.
McCabe’s theory. There is no evidence that a genetic susceptibility to develop JAS also
encompasses a genetic susceptibility to increases in pro-inflammatory cytokines.
Although Dr. McCabe argued that the strong genetic component to petitioner’s disease
somehow left her vulnerable to the cytokine response to the vaccine, he had no answer
for Dr. Rose’s testimony that the genetics of AS, specifically HLA-B27, “are not genes of
hyper response to cytokines” (Tr. at 117).
Gardasil produces only a transient increase in cytokine levels, and there is no
evidence that a transient increase can cause symptoms of JAS, much less the disease
itself. Moreover, there is no evidence that the cytokine proliferation caused by Gardasil
is of the same nature or intensity as the bacterially-based gastrointestinal infections that
have been temporally associated with triggering onset of JAS. Ms. Godfrey’s genetic
background, coupled with a family history and the presence of a known “trigger” for
development of JAS, fully account for her diagnosis. Finally, Gardasil was extensively
studied, pre- and post-licensure, for evidence of adverse events. No study has found
any association between the full, three-injection regimen, much less the one vaccination
Ms. Godfrey received, and arthritic conditions or JAS.
In essence, Dr. McCabe took evidence that Gardasil, like many life events,
including exercise, sunlight, and infections, transiently increases proliferation of pro-
inflammatory cytokines, and made this increase into a trigger for an event (the
development of JAS) that did not require one.45 The biological mechanism posited is
not a reliable theory because there is no evidence that cytokines cause the disease.
This problem illustrates the difficulty of relying on a theory propounded by a
scientist who does not research, diagnose, or treat JAS. Doctor McCabe understood
and conveyed that JAS is recognized as an autoinflammatory disorder, that pro-
inflammatory cytokines such as TNF-α have been found in the synovial fluid of JAS
patients, and that the HPV vaccine provokes cytokine production, including pro-
inflammatory cytokines, in recipients. What he apparently failed to understand is that
pro-inflammatory cytokines play a role in JAS’s symptomology, but there is no evidence
that they play a role in its pathogenesis or in the bone remodeling that is the hallmark of
the disease.
45 Doctor McCabe testified that “infection, stress, and trauma are all triggers associated with the onset of
JAS” (Tr. at 85), tacitly acknowledging that vaccination was not considered a known risk factor.
29

Case 1:10-vv-00565-NBF Document 73 Filed 07/08/14 Page 30 of 31
Moreover, Ms. Godfrey exhibited substantial risk factors for developing JAS, as
she carries a disease-causing version of HLA-B27, which she inherited from a first
degree relative who also carries HLA-B27 and has Crohn’s disease. According to Dr.
Rose, this gave her a one-in-five chance of developing JAS; a condition found in about
seven of every 100,000 individuals. She also had a known trigger in her history; she
was a high school cheerleader, making her susceptible to chronic micro-trauma in hips
and ankles. Although there was some discussion about the fact that most people with
HLA-B27 do not develop JAS or similar diseases, the very high percentage of those
who develop JAS as children (one study indicated that in children with JAS, 97% carry
the HLA-B27 marker),46 coupled with Ms. Godfrey’s inherited HLA-B27 marker and a
first degree relative with Crohn’s disease, are all strong indications of her high genetic
predisposition to developing JAS.
Although Dr. McCabe holds an academic appointment at a medical school, he is
not a physician. He has considerable expertise in immunotoxicology, and I have
previously relied upon his expert opinion on mercury and its effects on the immune
system and the brain.47 However, in this case he is out of his depth in presenting a
theory on the cause of a medical condition, with little, if any, support in the medical and
scientific literature. The fact that he derives nearly all of his income at present from
preparing and presenting expert opinions is also a factor in assessing the reliability of
those opinions.
In contrast, respondent’s expert, Dr. Rose, diagnoses and treats such conditions,
and is familiar with the etiologic factors that are accepted as causal in the scientific and
medical communities. Given Dr. Rose’s background and experience, I accord his
opinion on causality more weight than I give to Dr. McCabe in this case. Moreover, Dr.
Zweiman persuasively explained why Dr. McCabe’s theory that a vaccine-induced
cytokine response pushed a genetically predisposed person over the edge into an auto-
inflammatory condition was very unlikely.
Simply put, respondent’s experts proffered opinions that I find more reliable and
persuasive than those of Dr. McCabe. Genetics alone is a sufficient and “but for” cause
for Ms. Godfrey’s condition.
2. A Logical Connection and Timing.
Given my conclusions regarding Althen’s first prong, it is unnecessary to address
prongs two and three. I briefly note that there is nothing in Ms. Godfrey’s medical
history linking her JAS to her Gardasil vaccination, aside from one note indicating that
she had been vaccinated a month before symptoms began. As the Federal Circuit has
indicated, a temporal relationship alone is insufficient to demonstrate a logical
46 Lin, Pet. Ex. 56, at 577.
47 Snyder v. Sec’y, HHS, No. 01-162V, 2009 WL 332044, at *18 (Fed. Cl. Spec. Mstr. Feb. 12, 2009).
30

Case 1:10-vv-00565-NBF Document 73 Filed 07/08/14 Page 31 of 31
connection between these two events. Grant v. Sec’y, HHS, 956 F.2d 1144, 1148 (Fed.
Cir. 1992). A reference in a medical record to a vaccination being an antecedent event
is insufficient to attribute to a treating physician any opinion that the vaccine was
somehow responsible. See Moberly, 592 F.3d at 1323; Caves, 100 Fed. Cl. at 141-42.
The last Althen factor burdens the petitioner with establishing, by preponderant
evidence, a proximate temporal relationship between vaccination and injury. Althen,
418 F.3d at 1278. Analogizing to the time frame when an immunological response to a
vaccine would be expected to occur, producing the cytokines central to his theory, Dr.
McCabe contended that a month between vaccination and onset of symptoms was
scientifically appropriate. Doctor Rose explained the fallacy in this approach.
Symptoms do not equate to onset of disease in JAS. He testified that it would be
impossible to determine when the onset of her disease actually began. In support, he
noted that Ms. Godfrey initially only complained of left hip pain, but imaging studies
showed evidence of disease in both hips. I accept Dr. Rose’s testimony, given his
expertise in treating AS.
VI. Conclusion
Petitioner has failed to establish any of the Althen prongs by preponderant and
reliable evidence. She has failed to demonstrate that Gardasil can cause JAS or that it
did so in her case. The petition for compensation is therefore DENIED. The clerk is
directed to enter judgment accordingly.
IT IS SO ORDERED.
s/Denise K. Vowell
Denise K. Vowell
Chief Special Master
31

================================================================================
DOCUMENT 2: USCOURTS-cofc-1_10-vv-00565-1
Date issued/filed: 2014-12-29
Pages: 2
Docket text: PUBLIC DECISION (Originally filed: 12/02/2014) regarding 83 DECISION Interim Fees Stipulation/Proffer Signed by Chief Special Master Denise Kathryn Vowell. (dlb) Copy to parties.
--------------------------------------------------------------------------------
Case 1:10-vv-00565-NBF Document 86 Filed 12/29/14 Page 1 of 2
IN THE UNITED STATES COURT OF FEDERAL CLAIMS
OFFICE OF SPECIAL MASTERS
No. 10-565V
Filed: December 2, 2014
* * * * * * * * * * * * * * * * * * * * * * * *
MEGAN L GODFREY, *
*
Petitioner, * Interim Attorney Fees and Costs;
v. * Stipulation
*
SECRETARY OF HEALTH *
AND HUMAN SERVICES, *
*
Respondent. *
*
* * * * * * * * * * * * * * * * * * * * * * * *
Milton C. Ragsdale , IV, Ragsdale LLC, Birmingham, AL, for petitioner.
Jennifer L. Reynaud, U.S. Dept. of Justice, Washington, DC, for respondent.
DECISION ON INTERIM ATTORNEY FEES AND COSTS1
Vowell, Chief Special Master:
In this case under the National Vaccine Injury Compensation Program
[hereinafter “the Program”],2 petitioner filed a motion for an award of interim attorney
fees and costs on October 27, 2014 [the “Application”]. See Avera v. Sec’y, HHS, 515
F.3d 1343, 1352 (Fed. Cir. 2008). On November 25, 2014, the parties filed a Stipulation
of Fact Concerning Attorneys’ Fees and Costs [“Stipulation”], wherein they explain that
based on discussion of respondent’s objections, petitioner amends her Application to
request an award of $141,851.84.3 Respondent does not object to this amount, noting
that while she maintains her position that interim attorney fees and costs awards are not
1 Because this unpublished decision contains a reasoned explanation for the action in this case, I intend
to post this decision on the United States Court of Federal Claims' website, in accordance with the E-
Government Act of 2002, Pub. L. No. 107-347, § 205, 116 Stat. 2899, 2913 (codified as amended at 44
U.S.C. § 3501 note (2006)). In accordance with Vaccine Rule 18(b), petitioner has 14 days to identify and
move to delete medical or other information, the disclosure of which would constitute an unwarranted
invasion of privacy. If, upon review, I agree that the identified material fits within this definition, I will
delete such material from public access.
2 The applicable statutory provisions defining the Program are found at 42 U.S.C. § 300aa-10 et seq.
(2006).
3 Petitioner did not file a statement comporting with General Order 9. However, because any costs
personally incurred by petitioner can be addressed in a subsequent award of fees and costs, I have
elected to act on this interim application without that statement.

Case 1:10-vv-00565-NBF Document 86 Filed 12/29/14 Page 2 of 2
permitted in cases like this one, she “elects not to raise her statutory objection at this
time in response to this particular request.” Stipulation at n.1.
I find that petitioner is entitled to an award of interim attorney fees and costs
under the facts and circumstances of this case. A review of the materials offered in
support of the application for interim attorney fees and costs indicates that the agreed
amount is reasonable. Accordingly, I hereby award the total of $141,851.84 issued
in the form of a check payable jointly to petitioner, Megan L. Godfrey, and
petitioner’s attorney, Milton C. Ragsdale , IV, for interim attorney fees and costs.
The clerk of court shall enter judgment accordingly.4
IT IS SO ORDERED.
s/Denise K. Vowell
Denise K. Vowell
Chief Special Master
4 Entry of judgment can be expedited by each party’s filing a notice renouncing the right to seek review.
See Vaccine Rule 11(a).
2

================================================================================
DOCUMENT 3: USCOURTS-cofc-1_10-vv-00565-2
Date issued/filed: 2015-08-19
Pages: 17
Docket text: JUDGE VACCINE UNREPORTED OPINION on 93 Order Remanding to Special Master Signed by Judge Nancy B. Firestone. (sr) Copy to parties.
--------------------------------------------------------------------------------
Case 1:10-vv-00565-NBF Document 96 Filed 08/19/15 Page 1 of 17
In the United States Court of Federal Claims
No. 10-565V
(Filed: August 19, 2015)*
*Opinion originally issued under seal on July 29, 2015
)
MEGAN L. GODFREY, )
)
Petitioner, ) Vaccine Petition; Intervening Federal
) Circuit Decision; Koehn v. Sec’y of
v. ) Health and Human Servs., 773 F.3d
) 1239 (Fed. Cir. 2014); Remand to
SECRETARY OF HEALTH AND ) Special Master
HUMAN SERVICES, )
)
Respondent. )
)
Clay Ragsdale, Birmingham, AL, for petitioner.
Jennifer Reynaud, United States Department of Justice, Civil Division,
Washington, DC, with whom were Benjamin C. Mizer, Acting Assistant Attorney
General, Rupa Bhattacharyya, Director, Torts Branch, Vincent J. Matanoski, Assistant
Director, and Catherine E. Reeves, Assistant Director.
O P I N I O N
Pending before the court is Megan L. Godfrey’s (“Ms. Godfrey” or “petioner”)
petition for review of the June 11, 2014 decision of Chief Special Master Vowell (“chief
special master”) denying Ms. Godfrey’s claim for compensation under the National
Childhood Vaccine Injury Act of 1986, 42 U.S.C. § 300aa-1 to -34, as amended
(“Vaccine Act”). Godfrey v. Sec’y of Health and Human Services, No. 10-565, 2014
WL 3058353 (Fed. Cl. June 11, 2014) (“Decision”).

Case 1:10-vv-00565-NBF Document 96 Filed 08/19/15 Page 2 of 17
Petitioner alleges that the single dose of the Gardasil human papillomavirus
(“HPV”) vaccine she received on August 22, 2007, “substantially contributed” to her
development of juvenile ankylosing spondylitis (“JAS”).1 An entitlement hearing was
held on December 10, 2012. The chief special master, applying the test set forth in
Althen v. Sec’y of Health and Human Servs., 418 F.3d 1274, 1278 (Fed. Cir. 2005),
determined that petitioner had not met her burden of proof to show causation-in-fact.
Specifically, the chief special master found that the medical theory presented by
petitioner—which posited that the HPV vaccine could have “triggered” petitioner’s JAS
in a manner similar to other environmental triggers—was not a sufficiently plausible
theory to show that the vaccine could actually “cause” petitioner’s JAS as required under
the Althen standard. The chief special master also found that the dose of HPV vaccine
given could not have caused or triggered petitioner’s JAS symptoms. The chief special
master further determined that petitioner had failed to establish a temporal relationship
between receipt of the vaccination and her JAS diagnosis, in that it was not clear when
the petitioner contracted JAS due to the staggered onset of symptoms.
Petitioner seeks reversal of the chief special master’s decision, arguing that the
chief special master erred in rejecting petitioner’s expert’s opinion that the HPV vaccine
can trigger or cause JAS and that a single dose of the vaccine could have triggered
petitioner’s JAS. Petitioner argues that she presented a viable, legally-probable medical
1 JAS is the juvenile form of ankylosing spondylitis, and typically causes peripheral arthritis and
peripheral enthesopathies. Dec. at 11 (citing Pet.’s Ex. 52 at 2, Pet.’s Ex. 57 at 2, 4). JAS
commonly affects the pelvis, heels, knee joints, and hip joints. Id. (citing Pet.’s Ex. 56 at 575).
2

Case 1:10-vv-00565-NBF Document 96 Filed 08/19/15 Page 3 of 17
causation theory and established a proper temporal reaction, both of which petitioner
argues the chief special master improperly disregarded. In support of her petition, Ms.
Godfrey relies extensively on the recent decision of the Federal Circuit in Koehn v. Sec’y
of Health and Human Servs., 773 F.3d 1239 (Fed. Cir. 2014). Koehn also involved a
claim of injury from the HPV vaccine and discusses the testimony of the two principal
experts that appeared in this case. Petitioner argues that the Koehn decision dictates
reversal of the chief special master’s decision rejecting a finding of causation in this case
due to the Federal Circuit’s criticism of the analysis in that case. Respondent argues that
Koehn does not undermine the chief special master’s decision because the relevant
discussion is dicta and this case is factually distinct because, unlike Koehn, it involves a
disease with a strong genetic component. Therefore, the government argues that the
decision of the chief special master should be affirmed.
For the reasons set forth below, the court finds that Koehn raises issues that are
best addressed by the chief special master in the first instance. Specifically, there are
several statements in the Koehn decision which suggest that the chief special master’s
grounds for rejecting petitioner’s causation theory should be re-examined. Accordingly,
the court GRANTS IN PART petitioner’s motion and REMANDS the case for further
consideration regarding whether the Koehn decision warrants a different outcome.
I. BACKGROUND
A. Procedural History
On August 10, 2010, Ms. Godfrey filed a petition under the Vaccine Act.
Additionally, petitioner filed her medical records, medical literature, and an expert report
3

Case 1:10-vv-00565-NBF Document 96 Filed 08/19/15 Page 4 of 17
from David Axelrod, M.D. (“Dr. Axelrod”), a clinical immunologist. On September 26,
2011, the government filed an expert report from Carlos D. Rose, M.D. (“Dr. Rose”), a
pediatric rheumatologist. On October 26, 2011, the government filed medical literature,
an expert report from Burt Zweiman, M.D. (“Dr. Zweiman”), an immunologist, and a
Vaccine Rule 4(c) report recommending against awarding compensation.
A Vaccine Rule 5 status conference was held on November 5, 2011, at which the
chief special master noted deficiencies in Dr. Axelrod’s report. Thereafter, on April 24,
2012, petitioner filed an expert report from Michael J. McCabe, Jr., Ph.D. (“Dr.
McCabe”), a toxicologist/immunologist. On June 18, 2012, the Secretary filed a
responsive expert report from Dr. Zweiman addressing Dr. McCabe’s report.
An entitlement hearing was held on December 10, 2012.2 At the hearing,
petitioner presented testimony from Dr. McCabe, while the government presented
testimony from Drs. Rose and Zweiman. On June 11, 2014, the chief special master
issued a decision denying compensation. The chief special master determined that
respondent’s experts were entitled to greater weight based on both their qualifications and
their testimony that petitioner’s causation theory was not supported by the medical and
scientific literature. On July 11, 2014, petitioner timely filed a petition for review in this
court. The petition was stayed pending the appeal in Koehn. Supplemental briefs were
2 Petitioner initially indicated that she wished to file an expert report from Anthony Turkiewicz,
M.D., her treating rheumatologist. The chief special master denied a postponement of the
hearing, but granted leave to file an affidavit. On January 18, 2013, petitioner gave notice that
no affidavit would be filed.
4

Case 1:10-vv-00565-NBF Document 96 Filed 08/19/15 Page 5 of 17
filed following the resolution of that appeal. Oral argument on the petition for review
was held on July 14, 2015.
B. Facts
Ms. Godfrey was born on August 1, 1989. Dec. at 6. Her medical records
indicate that she was generally healthy through age 18. Id. Her family medical history
included Crohn’s disease (father) and rheumatoid arthritis (paternal grandparents and
paternal aunts and uncles). Id. at 6; Pet.’s Exs. 7 at 182, 8 at 9. She participated in
athletics during high school, including as a member of the school’s cheerleading team.
Dec. at 6 & n.12.
On August 22, 2007, petitioner received HPV and meningococcal conjugate
vaccines. Id. at 6; Pet.’s Ex. 2 at 1. Four months later, on December 19, 2007, petitioner
presented to her pediatrician, Mark Woods, M.D., complaining of sharp intermittent left
hip pain that had been ongoing for three months. Dec. at 6; Pet.’s Ex. 3 at 1. She
reported no injury and an X-ray of her hip was negative. Pet.’s Ex. 3 at 1. She received
an MRI on December 28, 2007, which revealed “[b]ilateral femoral benign fibrous
dysplasia, greater on the left side than the right, and left-sided sacroiliitis, which the
radiologist thought could be inflammatory.” Dec. at 7; Pet.’s Ex. 8 at 86.
Petitioner was also treated by Steve Lovelady, M.D., an orthopedist, on December
28. Pet.’s Ex. 11 at 12-14. He found tenderness at the left sacroiliac joint and admitted
her to DCH Regional Medical Center for further evaluation to rule out osteomyelitis. Id.
He also noted that petitioner’s father suffered from inflammatory bowel disease and
anemia. Id.
5

Case 1:10-vv-00565-NBF Document 96 Filed 08/19/15 Page 6 of 17
A bone scan performed on January 8, 2008 showed “increased activity at the left
[sacroiliac] joint.” Id. at 11. It was read as indicative of hyperemia and active bone
turnover, “which could be seen in osteomyelitis or in an inflammatory sacroiliitis.” Id.
On January 14, 2008, petitioner tested positive for the HLA-B27 protein, a genetic
marker showing susceptibility to conditions such as JAS. Id. at 7. Petitioner received a
steroid injection in the left sacroiliac joint in January 2008, which relieved the left hip
pain, but she developed tenderness in her right sacroiliac joint by March 2008. Pet.’s Ex.
9 at 89-90, 122.
On April 15, 2008, petitioner was evaluated by Randy Cron, M.D., a pediatric
rheumatologist. Pet.’s Ex. 7 at 180-84. He again noted petitioner’s familial history of
Crohn’s disease and arthritis, as well as her own history of sacroiliac joint pain and the
positive test for HLA-B27. Id. He diagnosed her with HLA-B27 spondyloarthropathy.
Id. After this visit, petitioner continued her treatment, including receiving injections of
Infliximab.3 Id. at 73-77, 94-98, 132-35, 149-52, 157-61; Pet.’s Ex. 9 at 12-13.
On August 22, 2012, petitioner had an initial visit with Anthony Turkiewicz,
M.D., a rheumatologist. Pet.’s Ex. 88 at 10-14. His impression was that the petitioner
was suffering from ankylosing spondylitis/axial spondyloarthropathy, and he continued
petitioner’s prescription of Infliximab injections. Id. at 9. Ms. Godfrey states that she
3 Injections of Infliximab inhibit tumor necrosis factor- and other pro-inflammatory cytokines.
Dec. at 8 n.15 (citing Physician’s Desk Reference 1145 (58th ed. 2004)).
6

Case 1:10-vv-00565-NBF Document 96 Filed 08/19/15 Page 7 of 17
believes that “[t]his treatment has been successful in terminating [her] symptoms.” Pet.’s
Post-Hearing Br. 2.
C. The Chief Special Master’s Decision
At the entitlement hearing, Dr. McCabe, who has a Ph.D. in microbiology and
immunology but is not a medical doctor, testified that petitioner’s HPV vaccination
triggered the manifestation of her JAS.4 His theory was that the vaccination triggered the
release of pro-inflammatory cytokines and that pro-inflammatory cytokines can trigger
the onset of JAS. Dr. McCabe explained that JAS is a disease with an auto-inflammatory
etiology, which means the disease is “driven by dysregulation of the innate immune
system.” Pet.’s Ex. 52 at 3. While Dr. McCabe acknowledged that petitioner had a
genetic susceptibility for JAS and that infections, stress, and trauma are all known
environmental triggers associated with the onset of JAS, he opined that the HPV vaccine
is also a trigger because it provokes a strong antibody response that in turn causes the
production of pro-inflammatory cytokines. Dr. McCabe explained that pro-inflammatory
cytokines have been implicated in the etiology of autoimmune disorders like JAS and
testified that the HPV vaccine was likely to have acted as an environmental trigger for
petitioner. He further testified that he believed that a single dose of the HPV vaccine
would be sufficient to stimulate enough pro-inflammatory cytokines to cause the onset of
JAS. Dr. McCabe acknowledged that there was no direct evidence demonstrating that
4 Dr. McCabe has been a professor at the University of Rochester since 2000. Dec. 9. He also
reviews and testifies in cases involving environmental and occupational exposures for Robson
Forensic. Id.
7

Case 1:10-vv-00565-NBF Document 96 Filed 08/19/15 Page 8 of 17
petitioner had an inflammatory response to the vaccine, but testified that he would
“expect that her antibody titers in response to the HPV were increasing.” Tr. 39, 74-75.
The respondent addressed Dr. McCabe’s contentions with evidence from Dr.
Rose5 and Dr. Zwieman.6 Dr. Rose did not dispute that pro-inflammatory cytokines can
cause symptoms of JAS, but disputed that pro-inflammatory cytokines can cause the
onset of the disease itself. Put another way, Dr. Rose opined that there is no evidence
that pro-inflammatory cytokines play a role in the pathogenesis of JAS, which Dr. Rose
testified is caused by genetics and other stressors, and instead is more likely to be
involved in the symptomology of the disease. Dr. Zweiman testified that, given the
transient increase in cytokine levels produced by the vaccine, the evidence would not
support a finding that petitioner’s single dose would be sufficient to trigger JAS
symptoms.
Based on this evidence and taking into account the professional backgrounds of
the experts,7 the chief special master found that petitioner’s JAS was attributable to her
“genetic background, coupled with a family history and the presence of a known ‘trigger’
5 Dr. Rose is a board-certified pediatric rheumatologist and works at the Alfred I. duPont
Institute and at the Thomas Jefferson University’s Jefferson Medical College. Dec. 10.
6 Dr. Zweiman was board certified in internal medicine, allergy and clinical immunology, and
laboratory immunology and between 1963 and his death taught at the University of Pennsylvania
School of Medicine. Dec. 11.
7 The chief special master noted that she found Dr. Rose’s testimony more reliable and
persuasive. She explained that Dr. McCabe was “out of his depth in presenting a theory of the
cause of a medical condition, with little, if any, support in the medical and scientific literature”
whereas Dr. Rose, who diagnoses and treats JAS, was more “familiar with the etiologic factors
that are accepted as causal in the scientific and medical communities.” Dec. at 30.
8

Case 1:10-vv-00565-NBF Document 96 Filed 08/19/15 Page 9 of 17
for development of JAS,” which the chief special master identified as petitioner’s
cheerleading. Dec. 29.
Finally, the chief special master found that petitioner had also failed to satisfy the
other two Althen prongs. She noted that petitioner’s medical records merely recorded
that she had the HPV vaccine a month before she complained of her JAS symptoms
without linking the events. She further noted that she agreed with Dr. Rose that it was
not possible to determine the precise onset of petitioner’s JAS because petitioner had
initially complained of hip pain in only one hip while imaging studies showed that the
disease was present in both hips, suggesting that the disease may have existed for a
period of time without petitioner experiencing symptoms. Dec. 31.
D. The Koehn Decision
Koehn involved a claim by a 13-year-old female who developed an auto-
inflammatory disease known as systematic juvenile idiopathic arthritis (“SJIA”)
following receipt of two of three HPV vaccine doses. 773 F.3d at 1240. As in this case,
the petitioner in Koehn relied on the testimony of Dr. McCabe to support her claim that
the vaccine triggered her disease by producing cytokines. Id. at 1242. Also as in this
case, the respondent relied on the testimony of Dr. Rose to rebut Dr. McCabe’s theory.8
Id. At trial, the special master determined that the petitioner had not met her burden
under any of the Althen prongs, and specifically found against Dr. McCabe’s theory
8 Dr. Zweiman was not called as an expert in the case.
9

Case 1:10-vv-00565-NBF Document 96 Filed 08/19/15 Page 10 of 17
because it had not been peer-reviewed or published and Dr. Rose had not heard of it. Id.
at 1242-43.
In its decision, the Federal Circuit affirmed the special master, finding that
petitioner had not met Althen prong three, but stated that the special master “committed
several errors in the assessment of the first and second Althen prongs.” Id. at 1243.
Regarding prong one, the circuit criticized the special master for basing his conclusions
about the acceptance of Dr. McCabe’s theory by the scientific community on whether Dr.
Rose had heard of the theory and for finding Dr. Rose more reliable because he treats
patients. Id. at 1243-44. Regarding Dr. McCabe’s experience with patients, the circuit
stated that “[w]e see no reasonable basis for why this distinction has any meaningful
effect on the cause and effect inquiry.” Id. at 1244. Regarding Dr. McCabe’s theory
itself, the circuit stated that “[h]ad the Special Master properly evaluated the evidence,
we believe the Special Master would have likely found that Koehn met her [causation]
burden.” Id. at 1244 n.1. While the special master in that case found the Pinto article
relied on by the petitioner to be unconvincing due to Dr. Rose’s testimony that the
measurements performed in that study required a stimulus and therefore did not mirror
what might happen in the body, the circuit found that “[e]specially given the low
incidence rate of SJIA, requiring a measurement without a stimulus would have
compelled Koehn to present more than what is scientifically possible or legally
necessary.” Id. As a result, the circuit indicated that it believed that Dr. McCabe had
presented a “viable, ‘legally probable’ medical theory.” Id. (quoting Moberly v. Sec’y of
Health & Human Servs., 592 F.3d 1315, 1322 (Fed. Cir. 2010)).
10

Case 1:10-vv-00565-NBF Document 96 Filed 08/19/15 Page 11 of 17
Ultimately, the circuit agreed that Ms. Koehn had not met her burden of
establishing that the onset of symptoms had occurred within a timeframe that was
medically acceptable to infer “causation-in-fact.” Id. at 1244-45. In the opinion, the
circuit explained that Dr. McCabe had failed to explain how the timing of the SJIA onset
“aligns with the timing of a sufficient immune response in patients receiving the
vaccine,” in that Dr. McCabe agreed that the immune system produces cytokines quickly
and the petitioner’s symptoms did not appear for seven months. Id. Thus, the circuit
affirmed the special master’s decision on the ground that “Koehn did not sufficiently
establish why onset of SJIA can occur within seven months after receiving the first dose
of Gardasil, especially when cytokine release is generally a more immediate response.”
Id. at 1245.
II. STANDARD OF REVIEW
This court has jurisdiction to review the decisions of a special master in a Vaccine
Act case upon a motion from the petitioner. 42 U.S.C. § 300aa-12(e)(2). The court uses
three distinct standards of review in Vaccine Act cases: findings of fact are reviewed
under the arbitrary and capricious standard, questions of law under the not in accordance
with law standard, and discretionary rulings under the abuse of discretion standard.
Masias v. Sec’y of Health & Human Servs., 634 F.3d 1283, 1287-88 (Fed. Cir. 2011);
Munn v. Sec’y of Health & Human Servs., 970 F.2d 863, 870 n.10 (Fed. Cir. 1992); see
42 U.S.C § 300aa-12(e)(2)(B). In this connection, the court does not “reweigh the factual
evidence,” “assess whether the special master correctly evaluated the evidence,” or
“examine the probative value of the evidence or the credibility of the witnesses.” Lampe
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v. Sec’y of Health & Human Servs., 219 F.3d 1357, 1360 (Fed. Cir. 2000) (internal
quotation marks omitted) (quoting Munn, 970 F.2d at 871). If the special master “has
considered the relevant evidence of record, drawn plausible inferences and articulated a
rational basis for the decision,” then “reversible error is extremely difficult to
demonstrate.” Id. at 1360 (internal quotation marks omitted) (quoting Hines ex rel.
Sevier v. Sec’y of Health & Human Servs., 940 F.2d 1518, 1528 (Fed. Cir. 1991)).
III. DISCUSSION
A. Vaccine Act Standards
Under the Vaccine Program, there are two types of claims: claims based on
injuries listed in the Vaccine Injury Table (“Table”) and claims based on injuries not
listed in the Table, known as off-Table claims. If the petitioner presents a Table claim,
the petitioner is granted a presumption of causation if he or she shows that he or she
received a vaccine listed in the Table, that he or she suffered an injury listed in the Table,
and that the injury occurred within the prescribed time period. See Andreu v. Sec’y of
Health & Human Servs., 569 F.3d 1367, 1374 (Fed. Cir. 2009) (describing Table cases).
In an off-Table case, like the present case, a petitioner who received a vaccine listed in
the Table but suffered an injury not listed on the table does not receive a presumption of
causation, and instead must prove causation by a preponderance of the evidence. See
Moberly, 592 F.3d at 1321 (describing off-Table cases).
In order to prove causation in an off-Table case, the petitioner must show that the
injury “was caused by a vaccine” listed in the Table. 42 U.S.C. § 300aa-
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11(c)(1)(C)(ii)(I). The Federal Circuit explained the evidentiary burden placed on
petitioners to show causation-in-fact in Althen, stating that a petitioner must
show by preponderant evidence that the vaccination brought about her
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.
418 F.3d at 1278. This showing of causation requires “a reputable medical or scientific
explanation that pertains specifically to the petitioner’s case, although the explanation
need only be ‘legally probable, not medically or scientifically certain.’” Broekelschen v.
Sec’y of Health & Human Servs., 618 F.3d 1339, 1345 (Fed. Cir. 2010) (quoting
Knudsen v. Sec’y of Health & Human Servs., 35 F.3d 543, 548-49 (Fed. Cir. 1994)).9
Once the petitioner satisfies this burden under Althen, he or she is “entitled to
recover unless [the respondent] shows, also by a preponderance of evidence, that the
injury was in fact caused by factors unrelated to the vaccine.” Walther v. Sec’y of Health
& Human Servs., 485 F.3d 1146, 1151-52 (Fed. Cir. 2007) (quoting Whitecotton v. Sec’y
of Health & Human Servs., 17 F.3d 376 (Fed. Cir. 1994), rev’d on other grounds sub
nom. Shalala v. Whitecotton, 514 U.S. 268 (1995)) (citing Knudsen, 35 F.3d at 547).
The evidence presented to establish an unrelated cause of injury may also be considered
9 This determination is notably different from a medical diagnosis: “the function of a special
master is not to ‘diagnose’ vaccine-related injuries, but instead to determine ‘based on the record
evidence as a whole and the totality of the case, whether it has been shown by a preponderance
of the evidence that a vaccine caused the [petitioner’s] injury.’” Andreu, 569 F.3d at 1382
(quoting Knudsen, 35 F.3d at 549).
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in determining whether the petitioner has met the burden of establishing a prima facie
case in the first instance. Stone v. Sec’y of Health & Human Servs., 676 F.3d 1373,
1379-80 (Fed. Cir. 2012).
B. The Chief Special Master’s Conclusions Regarding Causation-In-Fact
Should Be Re-Evaluated in Light of Koehn
The primary dispute between the parties in this case concerns the first Althen
prong. Specifically, petitioner argues that she met her burden of demonstrating a legally
probable and biologically-plausible mechanism causally connecting her receipt of a
single dose of the HPV vaccine with the onset of her JAS. The government, as noted
above, argues that petitioner failed to establish such a connection by a preponderance of
the evidence as required by Althen.
According to petitioner, the expert testimony that she presented established a
legally probable theory that the HPV vaccine can be an environmental trigger that can
cause the onset of JAS in genetically-predisposed individuals, in the same manner as
other known environmental triggers such as bacterial infections or traumatic stress
injuries. Petitioner notes that the parties’ experts agreed on the genetic components of
JAS, the identified environmental triggers, the existence of other unidentified
environmental triggers, the mechanisms by which environmental triggers initiate the
disease process, and the similarity of the immune response elicited by the HPV vaccine to
the immune response to known environmental triggers. In addition, petitioner argues that
Dr. McCabe’s opinion was supported by scientific studies showing that the HPV vaccine
triggers a response that is associated with the onset of diseases like JAS. In such
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circumstances, petitioner argues that the chief special master’s failure to find a causal
connection between receipt of the HPV vaccine and the onset of JAS was arbitrary and
capricious. Regarding the second Althen prong, petitioner further argues that Dr.
McCabe was able to demonstrate through existing studies that a single dose of the HPV
vaccine would be sufficient to trigger a response capable of causing JAS symptoms.
Petitioner argues that she presented sufficient evidence to support the third Althen prong
in that her symptoms began within one month of her receiving the HPV vaccine and thus
her vaccination and the onset of symptoms were temporally-related. Finally, petitioner
argues that the discussion in Koehn regarding Dr. McCabe’s testimony in that case
demonstrates that the chief special master’s rejection of his testimony in favor of Dr.
Rose’s testimony was erroneous. According to petitioner, the Federal Circuit’s
approving statements and analysis in Koehn mean that Dr. McCabe’s theory should be
accepted in this case.
In response, the government argues that the chief special master’s decision is
rationally supported by the evidence presented and that nothing in the Koehn decision
warrants a reversal of the decision. According to the government, petitioner presented a
theory that the HPV vaccine might be a trigger for JAS symptoms but failed to present
evidence to support a finding that the HPV vaccine actually “causes” JAS as required by
the Althen test. The government relied on the testimony of its expert to draw a
distinction, which the chief special master accepted, between the vaccine triggering the
onset of symptoms in a patient with existing-but-dormant JAS and the vaccine actually
causing JAS itself. The government further argues that its experts demonstrated that
15

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there is no reliable evidence in the medical literature for petitioner’s theory that a single
dose of the HPV vaccine could trigger the onset of JAS or its symptoms. The
government contends that the chief special master properly agreed with its expert that the
study that Dr. McCabe relied upon was based on in-vitro responses and thus did not
establish what an in-vivo response would be. Thus, the government argued that the chief
special master was correct in finding that the government’s experts effectively rebutted
petitioner’s causation theory. In addition, as noted above, the government argues that the
chief special master’s rejection of petitioner’s temporal evidence is supported by the
evidence presented.
Based on the circuit’s intervening decision in Koehn, the court finds that this
matter should be remanded to the chief special master to evaluate in the first instance
whether, as the circuit suggested in Koehn, Dr. McCabe has identified a legally probable
theory of causation with regard to the HPV vaccine to satisfy the first prong of Althen in
cases involving auto-inflammatory diseases. See Graves v. Sec’y of Health and Human
Servs., 101 Fed. Cl. 310, 314 & n.2 (2011) (remanding for damages determination where
an intervening Federal Circuit decision “potentially expands the scope of recovery”
(citing Zatuchni v. Sec’y of Health & Human Servs., 516 F.3d 1312 (Fed. Cir. 2008))).
While the court recognizes that the circuit’s criticisms of the special master’s decision in
Koehn with regard to causation are dicta, the court notes that there are sufficient
similarities regarding the auto-inflammatory illnesses at issue in both cases to warrant a
review. In this connection, the court also recognizes that there are also differences
between the diseases at issue in both cases and in the dosages and the timing of
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petitioner’s reactions. The significance of these similarities and differences are matters
that are best left for the chief special master to determine in the first instance, rather than
this court.10
IV. CONCLUSION
Accordingly, for the reasons set forth above, petitioner’s motion for review is
GRANTED-IN-PART and the case is REMANDED for further proceedings in
accordance with this opinion. The chief special master shall perform the re-evaluation
within 90 days, in accordance with Vaccine Rule 28(b).
IT IS SO ORDERED.
s/Nancy B. Firestone
NANCY B. FIRESTONE
Judge
10 The court also notes that the chief special master made a finding of a more likely alternative
environmental trigger as the cause of petitioner’s JAS. This conclusion was not discussed at
length and may warrant further explanation in her new review.
17

================================================================================
DOCUMENT 4: USCOURTS-cofc-1_10-vv-00565-4
Date issued/filed: 2016-05-25
Pages: 20
Docket text: RE-DOCKETED FOR ADMINISTRATIVE PURPOSES, re: 111. Judge Vaccine Reported Opinion. Petitioner's motion for review DENIED and the special master's decision on remand is SUSTAINED. Opinion originally filed under seal on April 29, 2016. Signed by Senior Judge Nancy B. Firestone. (ypb) Service on parties made.
--------------------------------------------------------------------------------
Case 1:10-vv-00565-NBF Document 116 Filed 05/25/16 Page 1 of 20
In the United States Court of Federal Claims
No. 10-565V
(Filed: May 25, 2016)*
*Opinion originally filed under seal on April 29, 2016
)
MEGAN L. GODFREY, )
)
Petitioner, ) Vaccine Act; Motion for Review
) Following Remand, HPV Vaccine;
v. ) Gardasil; Juvenile Ankylosing
) Spondylitis; Causation in Fact
SECRETARY OF HEALTH AND )
HUMAN SERVICES, )
)
Respondent. )
)
M. Clay Ragsdale, Birmingham, AL, for petitioner. Allison L. Riley, Birmingham,
AL, of counsel.
Jennifer L. Reynaud, Torts Branch, Civil Division, United States Department of
Justice, Washington, DC, with whom were Benjamin C. Mizer, Principal Deputy
Assistant Attorney General, Rupa Bhattacharyya, Director, Vincent J. Matanoski, Deputy
Director, and Catherine E. Reeves, Assistant Director.
O P I N I O N
Firestone, Senior Judge.
Pending before the court is petitioner Megan L. Godfrey’s (“petitioner”) motion
for review of the special master’s October 27, 2015 decision on remand denying
petitioner’s claim for compensation under the National Childhood Vaccine Injury Act of
1986, 42 U.S.C. §§ 300aa-1 to -34, as amended (“the Vaccine Act”). Petitioner’s claim
was initially denied in a decision published June 11, 2014. See Godfrey v. Sec’y of
Health & Human Servs., No. 10-565V, 2014 WL 3058353 (Fed. Cl. June 11, 2014)

Case 1:10-vv-00565-NBF Document 116 Filed 05/25/16 Page 2 of 20
(“Godfrey I”). The purpose of the remand was to determine whether the United States
Court of Appeals for the Federal Circuit’s intervening decision in Koehn v. Secretary of
Health and Human Services, 773 F.3d 1239 (Fed. Cir. 2014), warranted a finding of
liability in favor of petitioner. See Godfrey v. Sec’y of Health & Human Servs., No. 10-
565V, 2015 WL 4972882 (Fed. Cl. Aug. 19, 2015) (“Godfrey II”). On October 27, 2015,
the special master, after considering Koehn, issued a decision again denying entitlement
to compensation under the Vaccine Act. See Godfrey v. Sec’y of Health & Human
Servs., No. 10-565V, 2015 WL 10710961 (Fed. Cl. Oct. 27, 2015) (“Godfrey III”).
On November 30, 2015, petitioner timely filed a motion for review of the special
master’s decision on remand. ECF No. 102. The Secretary of Health and Human
Services (“respondent”) filed a response on December 30, 2015. ECF No. 103. The
court heard oral argument on April 25, 2016.
For the reasons below, petitioner’s motion is DENIED and the special master’s
decision is SUSTAINED.
I. BACKGROUND
A. Petitioner’s Medical History
Petitioner’s undisputed medical history was described in the court’s August 19,
2015 decision and is summarized as follows. She was born on August 1, 1989 and, aside
from routine childhood illnesses, was healthy prior to the vaccination at issue. In high
school, she participated in athletics, including cheerleading. Her family history includes
Crohn’s disease and rheumatoid arthritis. Petitioner also tested positive for HLA-B27, a
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genetic marker that made her predisposed to developing juvenile ankylosing spondylitis
(“JAS”).1
On August 22, 2007, at age 18, petitioner received a single dose of the Gardasil
HPV vaccine from her pediatrician. Four months later, on December 19, 2007, petitioner
returned to her doctor complaining of sharp, intermittent pain in her left hip that had been
ongoing for the previous three months. An x-ray of her hip indicated no problems and
she did not report any recent injury. The next week, an MRI showed “[b]ilateral femoral
benign fibrous dysplasia, greater on the left side than the right, and left-sided sacroiliitis,
which the radiologist thought might have been inflammatory.” A bone scan also
indicated “increased activity at the left [sacroiliac] joint,” similar to what could be seen
“in osteomyelitis or in an inflammatory sacroiliitis.” The parties stipulated that this pain
established the onset of petitioner’s JAS. Once diagnosed with JAS, petitioner began
taking Infliximab injections, which she acknowledged were successful in terminating her
JAS symptoms. None of petitioner’s doctors expressly connected the Gardasil dose she
received with her JAS.
1 JAS is a form of spondyloarthritis which involves inflammation at sites where ligaments and
tendons attach to the bones. See Godfrey I, 2014 WL 3058353, at *11. In this regard it is
different from other conditions such as systemic juvenile idiopathic arthritis (“SJIA”) which was
at issue in Koehn and affects the whole body. Godfrey III, 2015 WL 10710961, at *10.
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B. The Chief Special Master’s Decision (Godfrey I)
Petitioner filed her petition seeking compensation under the Vaccine Act on
August 20, 2010. After a hearing, the chief special master issued a decision denying
entitlement on June 11, 2014. See Godfrey I, 2014 WL 3058353, at *1.
The primary disputed issue in this case has been whether the single dose of
Gardasil petitioner received on August 22, 2007 is causally connected to her development
of JAS. At the hearing, petitioner’s expert, Dr. Michael McCabe, Ph.D., testified that the
Gardasil vaccine triggered the development of petitioner’s JAS because studies show that
Gardasil causes a release of pro-inflammatory proteins known as cytokines and that JAS
has been shown to be triggered by environmental events that cause a sustained elevation
of pro-inflammatory cytokines in genetically predisposed individuals such as petitioner.
Thus, Dr. McCabe opined that the dose of Gardasil petitioner received acted like known
JAS triggers by causing a release of pro-inflammatory cytokines. Dr. McCabe relied on
Maxime Dougados & Dominique Baeten, Spondyloarthritis, 377 Lancet 2127 (2011)
(“Dougados,” Pet’r’s Ex. 54) for his conclusion that environmental factors which result in
a sustained elevation of pro-inflammatory cytokines play a role in the development or
onset of JAS in genetically predisposed individuals. Specifically, the Dougados article
noted that “[u]pon bacterial or mechanical stress, these pathways [stemming from HLA-
B27] can lead to the abnormal production of proinflammatory cytokines . . . .” Dougados
at 2130 (caption for figure 2).
In his testimony, Dr. McCabe conceded that “[a]bsolutely you need the sustained
elevation of the cytokines . . . in order for the disease to manifest and to continue to
4

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manifest.” Tr. 57. He went on to state, however, that the sustained cytokine response
“needn’t be . . . coming from the vaccine throughout the course of th[e] disease.” Id.
Dr. McCabe suggested that “it’s a useful analogy to say that it’s a flip that was switched,
a circuit was opened, a ball is pushed over to the apex of the hill and is going to roll down
from there.” Tr. 58. When asked what could cause petitioner’s cytokine levels to remain
elevated for four weeks, Dr. McCabe stated that “[h]er genetic background . . . causes a
trigger to manifest in her as an abnormality.” Tr. 84. Dr. McCabe also cited Morgan A.
Marks, et al., Progesterone and 17β-Estradiol Enhance Regulatory Responses To Human
Papillomavirus Type 16 Virus-Like Particles In Peripheral Blood Mononuclear Cells
From Healthy Women, 17 Clinical & Vaccine Immunology 609 (2010) (“Marks,” Pet’r’s
Ex. 87) as the best evidence that a dose of Gardasil can cause a sufficiently strong and
sustained release of pro-inflammatory cytokines to trigger the development of JAS.
Dr. McCabe acknowledged that there was no direct evidence that petitioner had an
inflammatory response to the Gardasil vaccine, but opined that he would expect a
response during the four weeks after the vaccination based on several studies. For
example, Dr. McCabe cited Ian H. Frazer, Measuring Serum Antibody to Human
Papillomavirus following Infection or Vaccination, 118 (Supp. 1) Gynecologic Oncology
S8 (2010) (“Frazer (2010),” Pet’r’s Ex. 70) for its statement, regarding immunizations in
general, that an individual’s antibody response after a single immunization “reaches a
plateau between 12 and 18 days after immunization, and then declines.” Godfrey I, 2014
WL 3058353, at *15 (citing Tr. 81-82). Dr. McCabe then explained that cytokine levels
would be increasing at the time antibody levels are declining because cytokines “are
5

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involved in bringing those antibody levels down.” Tr. 83. However, Dr. McCabe agreed
that there was no scientific evidence that a pro-inflammatory cytokine response would
continue for four weeks after receiving a single dose of Gardasil and reiterated that his
medical theory of causation did not require cytokine levels to be elevated “as elicited by
the vaccine.” Tr. 82. Dr. McCabe also cited Ian Frazer, Correlating Immunity with
Protection for HPV Infection, 11 (Supp. 2) International Journal of Infectious Diseases
(2007), S10 (2007) (“Frazer (2007)”, Pet’r’s Ex. 71);2 Ligia A. Pinto, et al., HPV-16 L1
VLP Vaccine Elicits a Broad-Spectrum of Cytokine Responses in Whole Blood, 23
Vaccine 3555 (2005) (“Pinto (2005),” Pet’r’s Ex. 73);3 Alfonso García-Piñeres, et al.,
2 The chief special master described the study in the Frazer (2007) article as:
An immunogenicity study of Gardasil show[ing] that the antibody [adaptive
immune] response of the vaccinated group, who had received the complete three
injection series, was approximately 10 to 100 times greater than the unvaccinated
control group, who had prior natural infection. Among the vaccinated group, the
[antibody or adaptive] immune response began approximately one month after the
initial dose, peaked at approximately month seven, and thereafter declined to a
plateau for two and a half years after the last dose.
Godfrey I, 2014 WL 3058353, at *10.
3 The Pinto (2005) article was the subject of the Federal Circuit’s discussion in Koehn. The
Federal Circuit described the Pinto (2005) study as follows:
[R]esearchers gave twenty female participants an HPV vaccine on the same three
dose regimen as Gardasil, and drew blood before the first injection and one month
after each of the second and third injections. The researchers either stimulated the
blood samples with varying amounts of a virus-like particle in the vaccine or
provided no stimulation at all. Cytokine levels were relatively consistent in the
vaccinated blood that received no stimulation. Cytokine levels increased,
however, for the vaccinated blood that received the virus-like particle . . . .
Koehn, 773 F.3d at 1242. However, neither Dr. McCabe nor the Federal Circuit found that the
Pinto (2005) study provided evidence of a sustained release of pro-inflammatory cytokines after
a single dose of Gardasil.
6

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Cytokine and Chemokine Profiles following Vaccination with Human Papillomavirus
Type 16 L1 Virus-Like Particles, 14 Clinical & Vaccine Immunology 984 (2007)
(“García-Piñeres,” Pet’r’s Ex. 74);4 Ligia A. Pinto, et al., Cellular Immune Responses to
Human Papillomavirus (HPV)-16 L1 in Healthy Volunteers Immunized with
Recombinant HPV-16 L1 Virus-Like Particles, 188 J. Infectious Diseases 327 (2003)
(“Pinto (2003),” Pet’r’s Ex. 75);5 Thomas G. Evans, et al., A Phase 1 Study of a
Recombinant Viruslike Particle Vaccine against Human Papillomavirus Type 11 in
Healthy Adult Volunteers, 183 J. Infectious Diseases 1485 (2001) (“Evans,” Pet’r’s
Ex. 76);6 and C. Chao, et al., Surveillance of Autoimmune Conditions following Routine
Use of Quadrivalent Human Papillomavirus Vaccine, 271 J. Internal Medicine 193
(2011) (“Chao,” Pet’r’s Ex. 80).7
4 The study described in the García-Piñeres article measured cytokine levels before receiving an
HPV vaccine and one month following the second dose of the vaccine.
5 The study described in the Pinto (2003) article measured cytokine responses at one month after
the second dose of an HPV vaccine and one month after the third dose.
6 The study described in the Evans article was cited for “changes in lymphoproliferation [an
immune response] . . . measured at six weeks.” Tr. 80.
7 The study described in the Chao article looked at the effects of Gardasil on nearly
190,000 women who received at least one dose of the vaccine. Godfrey I, 2014 WL 3058353, at
*16 (citing Tr. 65). Dr. McCabe noted that the safety review committee identified the two
months after receiving the first dose of Gardasil as a “risk period” for autoimmune conditions.
Tr. 76. However, Dr. McCabe acknowledged that the Chao study “did not reveal an increased
incidence of spondyloarthropathies like AS [ankylosing spondylitis] and JAS in the vaccinated
population.” Godfrey I, 2014 WL 3058353, at *16. Dr. McCabe “attributed the negative results
to the rarity of the disease and the study lacking the power to detect a relationship of such a rare
condition with the vaccine.” Id.
7

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Respondent’s experts, Dr. Carlos Rose, M.D., and Dr. Burton Zweiman, M.D.,
challenged Dr. McCabe’s causation theory. They agreed that certain environmental
factors that cause a sustained elevation of pro-inflammatory cytokines, such as
gastrointestinal and genitourinary bacteria and mechanical stress (specifically chronic
physical micro-trauma), can trigger JAS in genetically predisposed individuals.
However, they disagreed with Dr. McCabe’s theory that a single dose of the Gardasil
vaccine would be sufficient to trigger JAS. First, they explained that there was no
medical evidence to support a link between petitioner’s single dose of Gardasil and the
development of JAS. Second, they opined that even assuming Dr. McCabe’s theory was
possible, any release of pro-inflammatory cytokines following one dose of Gardasil
would have been too transient to have the alleged effect. Dr. Zweiman testified that
because an individual’s innate immune response does not have “immunologic memory
such as one finds in adaptive responses, . . . to get a repeat or continued elaboration of the
products of inflammatory cytokine, you have to have continued stimulation by the initial
stimulus.” Godfrey I, 2014 WL 3058353, at *20 (citing Tr. 179-80). To result in the
sustained elevated levels of pro-inflammatory cytokines required under Dr. McCabe’s
theory, “for the most part one needs to have a continued stimulation of more production
by cells,” of which there was no evidence presented. Id. (citing Tr. 202-03).
Respondent’s experts also noted that there was no evidence to suggest that
petitioner experienced a release of pro-inflammatory cytokines following her HPV
vaccination. Given petitioner’s genetics and medical history, respondent’s experts
suggested that petitioner’s development of JAS following her Gardasil vaccination was
8

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“simply coincidental” or that some other activity, such as petitioner’s cheerleading, might
have provided sustained trauma or stress and triggered her JAS.
The chief special master determined based on the evidence she received that
petitioner had failed to meet her burden of proof under the Vaccine Act. The chief
special master explained that the evidence showed that petitioner’s JAS was attributable
to her “genetic background, coupled with a family history and the presence of a known
‘trigger’ for development of JAS,” which the chief special master identified as
petitioner’s cheerleading. The chief special master noted that there was no evidence that
petitioner had experienced elevated levels of pro-inflammatory cytokines following her
vaccination, that a transient increase in cytokines cannot cause JAS, or that the elevated
levels from a single dose of Gardasil would have remained sustained for a long enough
period to trigger JAS. The chief special master also found that the link between the onset
of petitioner’s JAS and her HPV vaccination was too speculative in that petitioner’s
imaging studies showed that JAS was present in both hips, even though petitioner
complained of pain in only one hip, and thus it was uncertain how long petitioner had
JAS. The chief special master stated that the imaging suggested that petitioner’s JAS
may have existed before she received the vaccination but did not yet cause any pain. For
these principal reasons, the chief special master denied the petition.
C. This Court’s Remand Decision (Godfrey II)
On review before this court, petitioner argued that the Federal Circuit’s decision in
Koehn, 773 F.3d at 1239, which had been issued after the chief special master’s decision,
demonstrated that petitioner’s expert, Dr. McCabe, had presented a viable medical theory
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of causation and that the chief special master had erred in rejecting petitioner’s expert’s
theory in favor of respondent’s experts’ opinions. As discussed in the remand decision,
Koehn involved a claim by a 13-year-old female who developed an auto-inflammatory
disease known as systematic juvenile idiopathic arthritis (“SJIA”) following receipt of
two of three HPV vaccine doses. 773 F.3d at 1240-41. In this case, as in Koehn,
petitioner relied on the testimony of Dr. McCabe to support her claim that the vaccine
had triggered her disease by releasing pro-inflammatory cytokines. Id. at 1242. Also in
this case, as in Koehn, respondent relied on the testimony of Dr. Rose to rebut Dr.
McCabe’s theory. Id. The special master in Koehn determined that the petitioner had not
met her burden of presenting a legally probable medical theory of causation and for that
reason as well as others denied the petition. On appeal, the Federal Circuit affirmed the
special master’s rejection of Ms. Koehn’s claim but stated in dicta that the special master
had “committed several errors” in rejecting the medical theory proffered by Dr. McCabe.
Id. at 1243. Specifically, the Federal Circuit stated:
Had the Special Master properly evaluated the evidence, we believe the
Special Master would have likely found that Koehn met her burden [of
establishing a medical theory causally connecting the vaccination and the
injury]. The Pinto [(2005)] article demonstrated that the participants who
received the HPV vaccine had increased levels of the same cytokines
dysregulated in SJIA. Dr. Rose asserted that the article showed increased
levels only when the vaccinated blood received a stimulus. Koehn[’s
expert, Dr. McCabe,] explains, however, that measurement of cytokine
levels can only occur in blood samples outside the body, and the only way
to “replicate what is going on in the body” is to introduce an antigen to the
blood sample assay. A stimulus was therefore necessary to measure
cytokine levels. Especially given the low incidence rate of SJIA, requiring
a measurement without a stimulus would have compelled Koehn to present
more than what is scientifically possible or legally necessary. Thus, Koehn
likely presented a viable, “legally probable” medical theory that “there
10

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would only be an upregulation in cytokines [that are associated with SJIA]
if those cells are told to do so [by the HPV vaccine.]”
Id. at 1244 n.1 (citations omitted). Based on the Federal Circuit’s statement and
petitioner’s reliance in part on the same Pinto (2005) study in this case, this court elected
to remand the matter for the special master to determine in the first instance whether
Dr. McCabe’s medical causation theory should be reconsidered in light of Koehn.
D. The Special Master’s Decision on Remand (Godfrey III)
On remand, a new special master to whom this case had been reassigned after the
chief special master retired determined that the Federal Circuit’s footnote in Koehn
regarding Dr. McCabe’s medical theory did not require any change in the chief special
master’s causation finding in this case. In deciding that petitioner’s expert had failed to
establish causation, the special master explained that even if Dr. McCabe had, based on
the Pinto (2005) study, established a viable theory of causation in Koehn, the facts in the
present case were sufficiently different as to warrant a different outcome. First, the
special master noted that petitioner’s disease, JAS, is distinct from SJIA, the illness at
issue in Koehn. SJIA is not linked to a specific genetic marker, whereas JAS is directly
linked to the HLA-B27 gene. In addition, SJIA affects the entire body and petitioner’s
JAS was specific to her hips. Second, the special master noted that while Dr. McCabe
relied on the Pinto (2005) study to support his medical theory that pro-inflammatory
cytokines are linked to both diseases, support for the medical causation theories were not
identical. In Koehn, Dr. McCabe cited studies linking vaccines to SJIA, but, in this case,
he did not cite any studies linking vaccines to JAS. Third, the special master noted that
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Dr. McCabe testified that JAS’s manifestation was dependent on a “sustained elevation”
of cytokines but did not offer any reliable evidence indicating that a single dose of
Gardasil would cause such an elevation. At the entitlement hearing, Dr. McCabe
conceded that there was no scientific evidence to suggest that a single dose of Gardasil
could trigger elevated release of pro-inflammatory cytokines for a 1-month period, such
that it could be linked to petitioner’s development of JAS. To the contrary, evidence was
presented to show that Gardasil produces only a transient increase in cytokine levels.
Based on these distinctions, the special master determined that Dr. McCabe had not
demonstrated a legally probable medical theory connecting petitioner’s JAS with her
receiving a single dose of Gardasil. Accordingly, the special master concluded that the
Federal Circuit’s statements in Koehn did not alter the chief special master’s conclusion
that Dr. McCabe had failed to present a legally sufficient medical theory of causation in
this case.
The special master went on to examine whether, even assuming Dr. McCabe had
presented a viable medical theory of causation, petitioner could satisfy the other
requirements necessary to establish her vaccine injury claim. The special master
considered whether petitioner could show a logical sequence of cause and effect between
her vaccine and JAS. He also addressed whether she could establish a temporal
relationship between her vaccination and injury. With regard to these requirements, the
special master noted that none of petitioner’s treaters linked her vaccination with her
subsequent illness and that there was no “evidence (such as test results) that would lend
credence to Dr. McCabe’s theory by showing it ‘working’ in real time.” Godfrey III,
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2015 WL 10710961, at *14. The special master also found that Dr. McCabe did not
sufficiently explain why a one-month interval between petitioner’s Gardasil vaccination
and her first symptoms was medically acceptable. For these reasons as well, the special
master concluded that petitioner had not established causation and thus was not entitled
to compensation.
II. JURISDICTION AND LEGAL STANDARDS
To receive compensation under the Vaccine Act, a petitioner must show that she
has sustained an injury listed in the Vaccine Injury Table (“Table”), 42 U.S.C. § 300aa-
14, within the time frame prescribed or that she suffered an “off-Table” injury as a result
of receipt of a covered vaccine. See 42 U.S.C. § 300aa-11(c)(1). If a petitioner presents
a Table claim, the petitioner is granted a presumption of causation if she shows that she
suffered an injury listed in the Table and that the injury occurred within the prescribed
time period. See Andreu ex rel. Andreu v. Sec’y of Health & Human Servs., 569 F.3d
1367, 1374 (Fed. Cir. 2009). In an off-Table case, like the present case, a petitioner does
not receive a presumption of causation and instead must prove by a preponderance of the
evidence that the injury was “caused in fact” by the vaccine. See Paluck v. Sec’y of
Health & Human Servs., 786 F.3d 1373, 1379 (Fed. Cir. 2015) (citing Andreu, 569 F.3d
at 1374).
In the seminal case Althen v. Secretary of Health & Human Services, 418 F.3d
1274, 1278 (Fed. Cir. 2005), the Federal Circuit established a three-pronged test to
determine whether a petitioner in an off-Table case has met her burden. The Althen test
requires petitioners to show by preponderant evidence:
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(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.
Id. Specifically, a petitioner must offer a medical theory that answers affirmatively the
question that the vaccine at issue can cause the type of injury alleged. This showing of
causation requires “a reputable medical or scientific explanation that pertains specifically
to the petitioner’s case, although the explanation need only be ‘legally probable, not
medically or scientifically certain.’” Broekelschen v. Sec’y of Health & Human Servs.,
618 F.3d 1339, 1345 (Fed. Cir. 2010) (quoting Knudsen v. Sec’y of Health & Human
Servs., 35 F.3d 543, 548-49 (Fed. Cir. 1994)).
In addition to showing that the vaccine at issue can cause a particular injury, a
petitioner must prove by a preponderance of the evidence that the vaccine could have
actually caused the injury in the specific case. Althen, 418 F.3d at 1278. With respect to
the temporal association, a petitioner must show that the onset of symptoms also occurred
within a medically acceptable timeframe. Koehn, 773 F.3d at 1244 (citing de Bazan v.
Sec’y of Health & Human Servs., 539 F.3d 1347, 1352 (Fed. Cir. 2008)).
Once the petitioner satisfies this burden under Althen, she “is entitled to
compensation unless the government demonstrates by a preponderance of the evidence
that the injury was in fact caused by factors unrelated to the vaccine.” Paluck, 786 F.3d
at 1379 (citing 42 U.S.C. § 300aa-13(a)(1)(B)).
This court has jurisdiction to review the decisions of a special master under
42 U.S.C. § 300aa-12(e)(2). The court uses three distinct standards of review in Vaccine
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Act cases: findings of fact are reviewed under the arbitrary and capricious standard,
questions of law under the not in accordance with law standard, and discretionary rulings
under the abuse of discretion standard. See Masias v. Sec’y of Health & Human Servs.,
634 F.3d 1283, 1287-88 (Fed. Cir. 2011); Munn v. Sec’y of Health & Human Servs., 970
F.2d 863, 870 n.10 (Fed. Cir. 1992); see also 42 U.S.C § 300aa-12(e)(2)(B). In this
connection, the court does not “reweigh the factual evidence,” “assess whether the special
master correctly evaluated the evidence,” or “examine the probative value of the evidence
or the credibility of the witnesses.” Lampe v. Sec’y of Health & Human Servs., 219 F.3d
1357, 1360 (Fed. Cir. 2000) (internal quotation marks omitted) (quoting Munn, 970 F.2d
at 871). If the special master “has considered the relevant evidence of record, drawn
plausible inferences and articulated a rational basis for the decision,” then “reversible
error is extremely difficult to demonstrate.” Id. at 1360 (internal quotation marks
omitted) (quoting Hines ex rel. Sevier v. Sec’y of Health & Human Servs., 940 F.2d
1518, 1528 (Fed. Cir. 1991)).
III. DISCUSSION
At issue in this case is whether petitioner has met her burden to prove causation
under the Althen standards for her “off-Table” vaccine injury claim. As discussed above,
in Koehn, the Federal Circuit suggested that the special master in that case had erred in
rejecting Dr. McCabe’s medical theory of causation based on concerns about the same
Pinto (2005) study that Dr. McCabe relied upon in this case. The Federal Circuit
explained that it believed the Pinto (2005) study was credible and that the study
supported the conclusion that the Gardasil vaccine can cause an increased level of pro-
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inflammatory cytokines, which can be a trigger for the development of SJIA. Because
Dr. McCabe had opined in this case that pro-inflammatory cytokines were associated
with triggering JAS, the matter was remanded. On remand, the special master
determined that Koehn did not require a change from the chief special master’s initial
decision rejecting Dr. McCabe’s causation theory.
Petitioner argues that the special master’s decision on remand was arbitrary,
capricious, and not in accordance with law. In particular, petitioner argues that the
special master failed to properly apply the Federal Circuit’s rationale from Koehn.
Pet’r’s Mot. 14. Petitioner argues that the Koehn panel found, based on the results of the
Pinto (2005) study, that Gardasil likely “does, in fact, cause an increase in cytokines
sufficient to trigger an autoinflammatory condition.” Id. In effect, petitioner argues that
this conclusion alone is sufficient to establish a legally probable medical theory in her
case.
Respondent argues that there are material differences between Koehn and this
case, including the dosage of the Gardasil vaccine received by the petitioners and the
diseases at issue, and that the special master in this case was justified in rejecting
Dr. McCabe’s theory of causation. Specifically, respondent argues that under
Dr. McCabe’s theory of causation in this case, it was not enough for Dr. McCabe to opine
that petitioner’s vaccination led to a release of pro-inflammatory cytokines; he needed to
also offer evidence that a single dose of Gardasil could cause an increase in cytokines
that lasted long enough to trigger the development of JAS. In this connection, the special
master expressly found that “Dr. McCabe did not offer sufficient persuasive proof that
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such an increase [in pro-inflammatory cytokines] would be sustained enough (and over
the time that lapsed between Ms. Godfrey’s vaccination and development of hip pain
symptoms) after a single Gardasil dose to result in JAS.” Godfrey III, 2015 WL
10710961, at *11 (citation omitted).
The court reviews the special master’s decision to determine whether it is
supported and concludes for the reasons that follow that it is. At the entitlement hearing,
Dr. McCabe endeavored to link petitioner’s vaccination to her development of JAS by
relying on studies that show Gardasil can cause a release of pro-inflammatory cytokines.
Dr. McCabe acknowledged, however, that the Pinto (2005) study did not provide
evidence of what cytokine levels might have looked like during the month after a single
Gardasil dose because the individuals in the Pinto (2005) study were sampled only before
the initial dose of an HPV vaccine and 1 month after the second and third doses of the
vaccine. Tr. 63-64. Thus, the Pinto (2005) study did not address whether a single dose
of Gardasil can produce sustained pro-inflammatory cytokine levels that could trigger
JAS. Given the undisputed evidence that JAS may be triggered by environmental factors
giving rise to a sustained pro-inflammatory cytokine response, it was rational for the
special master to conclude that an adequate medical theory would require a showing that
a single dose of the Gardasil vaccine can result in a sustained pro-inflammatory cytokine
response.
In this connection, the court finds that petitioner’s reliance on the Marks study to
suggest that Dr. McCabe demonstrated that the vaccine elevates pro-inflammatory
cytokine levels for a period of time is misplaced. The Marks study measured cytokine
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levels at 72 hours after immunization with an HPV vaccine. Indeed, Dr. McCabe,
referring to the results of the Marks study at the entitlement hearing, stated that “[i]t’s not
a sustained elevation. . . . It’s being measured at 72 hours . . . .” Tr. 55.
Finally, the court finds that Dr. McCabe’s suggestion that a single dose of Gardasil
could trigger sustained, elevated levels of pro-inflammatory cytokines for an individual in
petitioner’s circumstances, because it could be viewed as the last straw or tipping point,
was not supported. When asked what could cause petitioner’s cytokine levels to remain
elevated for four weeks, Dr. McCabe stated that “[h]er genetic background . . . causes a
trigger to manifest in her as an abnormality.” Tr. 84. However, Dr. McCabe did not
provide any scientific evidence in support of this theory.
The special master also had before him the testimony of respondent’s experts,
Dr. Rose and Dr. Zweiman, who explained that even if pro-inflammatory cytokines play
a role in the development of JAS, the evidence showed that the Gardasil vaccine causes
nothing more than a transient increase in pro-inflammatory cytokines such that the
vaccine is not capable of triggering JAS. Tr. 178-80. Dr. Zweiman “rejected
Dr. McCabe’s assertions regarding the role of the vaccine in the JAS disease process,
noting that under Dr. McCabe’s theory, in order to cause JAS, cytokine production would
have to occur in a ‘prolonged, consistent fashion.’” Godfrey I, 2014 WL 3058353, at *18
(citing Tr. 200). Dr. Zweiman explained that because an individual’s innate immune
response does not have “immunologic memory such as one finds in adaptive responses,
. . . to get a repeat or continued elaboration of the products of inflammatory cytokine, you
have to have continued stimulation by the initial stimulus.” Id. at *20 (citing Tr. 179-80).
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To result in the sustained elevated levels of pro-inflammatory cytokines required under
Dr. McCabe’s theory, “for the most part one needs to have a continued stimulation of
more production by cells,” of which there was no evidence presented. Id. (citing Tr. 202-
03).
Based on the evidence presented, the court finds that the special master’s
conclusion that petitioner failed to establish a legally probable medical theory of
causation under Althen prong one must be sustained.8 The special master had sufficient
evidence before him to conclude that petitioner failed to show that a single dose of the
Gardasil vaccine could cause a sustained pro-inflammatory cytokine response of the kind
associated with environmental factors that have been shown to trigger the development of
JAS. Petitioner’s failure to establish the first Althen prong is fatal to her claim. See, e.g.,
Koehn, 773 F.3d at 1244 (finding that a petitioner’s failure to establish any of the three
Althen prongs is dispositive).9
8 Having found that the special master’s rejection of petitioner’s medical theory was not
arbitrary, capricious, or not in accordance with law, the court does not reach petitioner’s
argument that the special master erred by making a distinction between the onset of her
symptoms and the onset of her disease.
9 Even assuming that a single dose of Gardasil could cause a sustained release of pro-
inflammatory cytokines, and that reaction could lead to the development of JAS, the court finds
that the special master’s conclusions regarding petitioner’s failure to meet the other two Althen
prongs are also supported. Dr. McCabe did not provide any evidence in support of his claim that
petitioner actually experienced a sustained release of pro-inflammatory cytokines after receiving
her Gardasil vaccination. When asked for evidence that petitioner had an abnormally high level
of pro-inflammatory cytokines at any time during the month after she received her vaccine,
Dr. McCabe acknowledged that no tests had been conducted and that “there is nothing that’s
really all that convincing that she had any inflammatory response or anything going on as a
consequence of elevated, pro-inflammatory cytokines after her immunization.” Tr. 74. In
addition, Dr. McCabe could not explain why a one-month interval between petitioner’s HPV
vaccination and her first symptoms of JAS was medically acceptable. Dr. McCabe stated that
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IV. CONCLUSION
For the reasons set forth above, the court finds that special master’s decision on
remand denying entitlement was not arbitrary, capricious, or not in accordance with law.
Accordingly, petitioner’s motion for review is DENIED and the special master’s decision
on remand is SUSTAINED. The clerk is directed to enter judgment accordingly.
IT IS SO ORDERED.
s/Nancy B. Firestone
NANCY B. FIRESTONE
Senior Judge
“[i]t’s really a matter of just proximity to the trigger” and agreed that the only evidence was the
“literal temporal relationship . . . and nothing more.” Tr. 84.
20