Johnson v. Secretary of Health and Human Services

In the United States Court of Federal Claims

OFFICE OF SPECIAL MASTERS

No. 10-578V

Filed: August 18, 2016

*************************

MORGAN A. JOHNSON, * PUBLISHED

*

Petitioner, * Special Master Hamilton-Fieldman

*

v. * Gardasil; Human Papillomavirus

* (“HPV”) Vaccine; First Symptom or

SECRETARY OF HEALTH AND * Manifestation of Onset; Systemic

HUMAN SERVICES * Lupus Erythematosus (“SLE”);

* Causation-in-Fact; Dismissal.

Respondent. *

*************************

Franklin John Caldwell, Jr., Maglio, Christopher & Toale, Sarasota, FL, for Petitioner.

Lara Ann Englund, United States Department of Justice, Washington, DC, for Respondent.

DECISION 1

On August 26, 2010, Morgan Johnson (“Petitioner”) petitioned for compensation under

the National Childhood Vaccine Injury Act of 1986, 42 U.S.C. §§ 300aa-10 to -34 (2012)

(hereinafter “Vaccine Act” or “the Act”). Pet., ECF No. 1. Petitioner alleged that she developed

Systemic Lupus Erythematosus (“SLE”) as a result of the administration of Human

Papillomavirus (“HPV”) vaccinations on November 21, 2007, and March 5, and June 3, 2008.

Id. at 1.

Respondent recommended against compensation. Resp’t’s Report at 1, ECF No. 10.

1

Because this decision contains a reasoned explanation for the undersigned’s action in this case,

the undersigned intends to post this decision on the website of the United States Court of Federal

Claims, in accordance with the purposes espoused in the E-Government Act of 2002. See 44

U.S.C. § 3501 (2012). Each party has 14 days 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).

1

Generally, Respondent argued that Petitioner’s claim was “based entirely on a ‘post hoc ergo

propter hoc’ line of reasoning (i.e., her symptoms started after the vaccinations, therefore they

were caused by the vaccinations).” Id. at 8.

Petitioner filed an expert report, authored by Yehuda Shoenfeld, M.D. Pet’r’s Ex. 8, ECF

No. 29-1. Shortly thereafter, Petitioner submitted medical literature in support of Dr.

Shoenfeld’s report. See Pet’r’s Exs. 87-100. 2

Respondent countered with an expert report from Carlos Daniel Rose, M.D. Resp’t’s Ex.

A, ECF No. 34-1. Respondent likewise submitted medical literature buttressing her expert’s

report. Resp’t’s Exs. A.1-4, ECF Nos. 2-5.

Special Master Daria Zane scheduled a two-part entitlement hearing for October 29 and

December 17, 2013, in Washington, D.C. Prehearing Order at 1, ECF No. 37. On September 9,

2013, the case was reassigned to the undersigned. Notice of Reassignment at 1, ECF No. 41. The

hearing proceeded as scheduled. See Minute Entry (Oct. 29, 2013); Minute Entry (Nov. 13,

2013).

After considering the entire record, the undersigned concludes that Petitioner has failed to

prove that the Gardasil vaccine caused her injury in a manner sufficient to satisfy the legal

standard established in Althen v. Sec’y of HHS, 418 F.3d 1274, 1278 (Fed. Cir. 2005).

Accordingly, Petitioner is not entitled to compensation under the Vaccine Act.

I. FACTUAL BACKGROUND

Petitioner was born on May 22, 1991. Pet’r’s Ex. 118 at 1, ECF No. 65-1. She was a

good student, id. at 1, and an avid soccer player, participating year-round. Tr. of Proceedings

(Oct. 29, 2013) at 16, ECF No. 54 (hereinafter “Tr. A”). Petitioner even developed acne as a

result of her soccer career—she tended to wipe the sweat from her face onto her jersey. Id. at 40.

When she received an invitation to the prom in Spring 2007, she and her mother sought

treatment for the acne. Id. at 40. She was prescribed Accutane, which she took until September

of that year. Id. at 40-41. Her weight, at a June 19, 2007 appointment with Dr. Sadd, her

pediatrician, was 141.4 pounds. Pet’r’s Ex. 1 at 9, ECF No. 7-1.

On November 21, 2007, Petitioner received her first Gardasil vaccination, as well as the

Influenza and Meningococcal vaccines. Id. at 6. At that time, she weighed 143.2 pounds. Id.

2

Where the exhibits were filed via compact disc, the undersigned provides no ECF reference

number.

2

When she received her second HPV vaccination, on March 5, 2008, Petitioner weighed 144

pounds. Id. at 5. On June 3, she received her third HPV vaccination, but the physician did not

document her weight. Id. at 2.

Less than one year later, on March 18, 2009, Petitioner returned to her pediatrician,

complaining of fatigue, difficulty breathing, a racing heart, athlete’s foot, and a rash on her neck.

Id. at 4. She also weighed almost six pounds less (138.2 pounds) than she did at her last

documented visit. Id.

When she returned to Dr. Saad on April 21, her weight was down another four pounds,

at only 133.8. Id. at 6. 3 At that visit, Dr. Saad ordered a number of lab tests. Id. at 3. The

complete results are not documented in the records, but those documented show elevated SS-A

and SS-B antibodies and an elevated C3 Complement level. Id. at 17.

On April 28, petitioner visited a rheumatologist, Dr. Morris Kokhab. Pet’r’s Ex. 3 at 14,

ECF No. 7-3. She reported that she had been in good health until four months before the visit,

when she began to endure progressive fatigue and ultimately lost ten pounds. Id. About a month

before the visit, she began to suffer from joint pain, swelling, and morning stiffness. Id. She also

had a rash on her cheek, 4 and her feet showed signs of Raynaud’s.5 Id. An examination revealed

active arthritis in her PIPs 6 and confirmed the presence of Raynaud’s on her feet. Id. The labs

taken on April 21 “showed significant findings, including leukopenia at 3.8, anemia at 11.2,

elevated ESR of 30, and low C3 of 74 along with positive ANA, ds-DNA, SSA, and SSB titers.”

Id. Dr. Kokhab diagnosed Petitioner with SLE; treated her with 125 mg of SoluMedrol,

administered intramuscularly; and prescribed prednisone at a dose of 20 mg per day. Id.

3

Although “133.8” is actually in the space on the form designated “HT”, the undersigned

presumes that it refers to her weight, as 133.8 inches would be over 11 feet tall, and 133.8

centimeters would be only four feet and seven inches tall, and medical records from 2007

suggest that she was 67 inches (or five feet and seven inches) tall. See Pet’r’s Ex. 1 at 7.

4

The medical records document a “malar” rash, and malar is derived from “mala,” which means

“cheek.” Malar, Dorland’s Illustrated Medical Dictionary (32nd ed. 2012) (hereinafter

“Dorland’s”).

5

Raynaud’s (which is also known as Raynaud phenomenon or Raynaud disease) is “intermittent

bilateral ischemia of the fingers, toes, and sometimes ears and nose, with severe pallor and often

paresthesias and pain, usually brought on by cold or emotional stimuli and relieved by heat; it is

usually due to an underlying disease or anatomical abnormality.” Phenomenon, Raynaud,

Dorland’s.

6

PIPs are proximal interphalangeal joints. Joint, PIP, Dorland’s.

3

Petitioner saw Dr. Kokhab again on May 4. Id. at 12. She was “[m]arkedly better.”

Although occasionally dizzy, she had no pre-syncope or visual issues. Id. She was prescribed

Plaquenil and CellCept. Id. Dr. Kokhab ultimately referred her to an ophthalmologist. Id.

Her weight was down to 131 pounds. Id.

Petitioner returned to Dr. Kokhab on May 7. Id. at 11. Her pain was much better, but she

developed a cough on the previous night. Id. Dr. Kokhab gave her Cipro and advised that she

stop CellCept for five days. Id.

On May 8, Petitioner saw Kerry Gallagher, M.D., at the Ronald Reagan UCLA Medical

Center for a second opinion. Pet’r’s Ex. 5 at 8, ECF No. 7-5. Dr. Gallagher’s narrative explains

that Petitioner “developed fatigue, myalgias, and arthralgias, and weight loss over the previous 4

months when she began with progressive difficulty in participating in her soccer games,” as well

as joint swelling, morning stiffness, additional muscle fatigue, Raynaud’s, blurred vision, and a

cavity. Id. at 8. Petitioner also reported that she had a paternal aunt with rheumatoid arthritis.

Id. at 9. Dr. Gallagher noted that Petitioner had “a positive ANA, double-stranded DNA, low

C3, mild proteinuria, and positive Sjogren’s antibodies.” Id. at 8. A review of Petitioner’s

systems revealed alopecia, 7 dry eyes, a mild malar rash, and a history of vitiligo. 8 Id. at 9-10.

Dr. Gallagher’s examination notes state that Petitioner’s lower extremities were “dusky and

slightly cool to palpitation.” Id. In sum, Dr. Gallagher agreed with Dr. Kokhab’s evaluation:

Petitioner had lupus, should begin CellCept, and should see an ophthalmologist. Id. at 10.

On May 19, Petitioner saw Daniel Arkfeld, M.D., at the USC Keck School of Medicine

for another opinion. Pet’r’s Ex. 2 at 2-4, ECF No. 7-2. Petitioner reported that “she was in good

health until December or January when she started with fatigue, weight loss.” Id. at 2. In March

and April, her joint pain increased, but was especially noteworthy in her hands and wrists. Id.

She also had facial redness (which she thought was a butterfly rash), “very cold blue feet,” and

vitiligo. Id. Dr. Arkfeld noted her visits to Drs. Kokhab and Gallagher; Petitioner attested that

she felt better after the steroid injection, but still felt fatigued. Id. She had also been given

Plaquenil, but she developed a rash and it was discontinued. Id. On examination, Dr. Arkfeld

observed no malar rash. Id. at 3. He did observe “[q]uestionable thyromegaly,[9] but no nodules

or masses.” Id. Further examination revealed a hypopigmented area on the lower right side of

7

Alopecia refers to the “lack or loss of hair from skin areas where it normally is present.”

Alopecia, Dorland’s.

8

Vitiligo is “a chronic, usually progressive, type of hypomelanosis in which melanocytes are

destroyed, resulting in white patches on the skin that may be surrounded by a hyperpigmented

border.” Vitiligo, Dorland’s.

9

Thyromegaly is also known as “goiter.” Thyromegaly, Dorland’s.

4

her abdomen, which Petitioner called vitiligo, but which Dr. Arkfeld explained might simply be a

birth mark. Id. The notes document “significant cyanosis in both feet” and “1+ swelling in the

lower extremities.” Id. Her hand grip was “fair,” but Dr. Arkfeld detected mild weakness. Id.

In closing, Dr. Arkfeld agreed that the proper diagnosis was lupus. Id. He recommended that

Petitioner stay on prednisone until June (of 2010) and then start tapering, that she stay on

CellCept and increase her dosage up to 2000 mg, and that she see an ophthalmologist. Id. at 3-4.

Petitioner returned to Dr. Kokhab on June 9. Pet’r’s Ex. 3 at 10. She reported that while

she was feeling much better overall and her blurred vision had resolved, she still had occasional

morning stiffness for 15 minutes or less. Id.

On July 8, 2009, Petitioner saw Dr. Kokhab for a follow-up. Id. at 8. She complained of

having a cough, runny nose, fatigue and sore throat for one week, as well as joint pain and

morning stiffness. Id. Dr. Kokhab gave her Cipro and told her to stop the CellCept for five days.

Id.

Petitioner revisited Dr. Kokhab on July 28. Id. at 7. She had been off of CellCept

because of an upper respiratory infection, but restarted it two days before the appointment and

now felt less energetic. Id. Dr. Kokhab also noted that her hair loss had stabilized, and that she

had neither morning stiffness, joint pain, nor a rash. Id.

On August 17, 2009, petitioner again returned to Dr. Kokhab. Id. at 6. She reported that

she was “markedly better,” with no morning stiffness, joint pain, or rashes; however, she did

have some hair loss and sleep issues. Id.

Petitioner again saw Dr. Kokhab on September 17. Ex. 3 at 5. At that time, she noted

that her lupus symptoms had flared up and she had a urinary tract infection. Id. at 5. She was

treated with an increase in prednisone and with Cipro. Id. Although she was doing better and

denied joint problems, she felt fatigued. Id.

On November 25, Petitioner saw Dr. Kokhab for a follow-up. Id. at 4. She reported that

she had lost 13 pounds over the past 8 months and that she sometimes got a butterfly rash. Id.

She denied alopecia or joint pain. Id. Five days later, a twenty-four hour urine sample was

collected, which showed an elevated protein/creatinine ratio and total protein level. Id. at 19.

Petitioner revisited Dr. Kokhab on December 21, 2009. Ex. 3 at 3. Her weight was 128

pounds. Id. She reported that she had developed pharyngeal pain and swelling. Id. She had

been given Bactrim and it quickly resolved. Id. She was referred to Dr. Kalunian at UCSD

Medical Center for another opinion regarding treatment options. Id.

On January 14, 2010, Petitioner saw Dr. Kalunian. Pet’r’s Ex. 6 at 6, ECF No. 7-6. At

5

that time, she was taking 15 mg of prednisone (alternating with 10 mg every other day) and 2 g

of CellCept. Id. Examination was normal except for occasional purplish discoloration in her

feet. Id. Labs were taken to determine her treatment options. Id.

On February 5, Petitioner returned to Dr. Kokhab for a follow-up. Pet’r’s Ex. 3 at 2. She

reported that she had increased joint pain and fatigue and felt a “great deal of stress” because of

relationships and school work. Id. She denied rashes. Id. Her prednisone was increased to 20

mg daily. Id.

Petitioner returned to UCSD Medical Center on February 24, and saw Matthew Husa, a

resident M.D., with review by Dr. Kalunian. Pet’r’s Ex. 6 at 2. She reported for a recent two to

three week period, she experienced pain in her skin when touched, but that it was now resolved.

Id. She also denied joint pain and morning stiffness. Id. at 3. At that time, she was taking 20 mg

daily of prednisone and reported that taking less than 20 mg resulted in flares of her lupus

symptoms. Id. An examination revealed no abnormalities. Id. Her labs from January 10 had

shown mild leucopenia, mild anemia and “roughly” 300 mg of protein in her 24-hour urine test.

Id. The impression was that her symptoms seemed well-controlled on the prednisone, and the

plan was to continue her on 20 mg daily of prednisone and to repeat the lab testing. Id. at 4-5.

On June 8, 2010 Petitioner saw Dr. Jennifer Grossman for another opinion concerning the

CellCept and the need for a renal biopsy before beginning that treatment. Ex. 104 at 17-19, ECF

No. 50-4. On the new patient questionnaire, Petitioner hand-wrote that her symptoms of “rapid

loss of lots of hair” and “weight loss of 20 lbs,” had occurred “before [she was] diagnosed.” Id. at

35. Dr. Grossman described the “History of Present Illness” as one “whose symptoms began . . .

several years ago,” id. at 17, and noted that she was positive for “20-pound weight loss before she

was diagnosed with lupus and has gained some of the weight back, hair loss before she was

diagnosed which has improved,” id. at 18. Her weight at this visit was 125 pounds. Id. Dr.

Grossman did not recommend a kidney biopsy, but did think the CellCept was an appropriate

alternative for steroid sparing. Id. at 18-19. Dr. Grossman also recommended that Petitioner try

Plaquenil again, as a better alternative for steroid sparing. Id. at 19. The doctor suggested

Petitioner try brand name Plaquenil rather than generic, to see if she tolerated it better. Id.

Continued use of sunscreens was also recommended. Id.

II. APPLICABLE LEGAL STANDARD

To receive compensation under the Vaccine Act, Petitioner must prove either that she

suffered (1) a “Table Injury,” i.e., an injury falling within the Vaccine Injury Table, 10

10

The Vaccine Injury Table “lists the vaccines covered under the Act; describes each vaccine's

compensable, adverse side effects; and indicates how soon after vaccination those side effects

should first manifest themselves.” Bruesewitz v. Wyeth, LLC, 562 U.S. 223, 228 (2011).

6

corresponding to one of her vaccinations, or (2) an injury that was actually caused by a vaccine.

See 42 U.S.C. §§ 300aa-11(c)(1), 13(a)(1)(A) (2012). Petitioner must show that the vaccine was

“not only a but-for cause of the injury but also a substantial factor in bringing about the injury.”

Moberly v. Sec’y of HHS, 592 F.3d 1315, 1321-22 (Fed. Cir. 2010) (internal quotation marks

omitted).

Because Petitioner does not allege a Table injury in this case, she must show that her

injury was caused-in-fact by a covered vaccine. To do so, Petitioner must satisfy all prongs of

the test established by the Federal Circuit in Althen, which requires Petitioner to set forth: “(1) a

medical theory causally connecting the vaccination and the injury [(“Althen Prong One”)]; (2) a

logical sequence of cause and effect showing that the vaccination was the reason for the injury

[(“Althen Prong Two”)]; and (3) a showing of a proximate temporal relationship between

vaccination and injury [(“Althen Prong Three”)].” 418 F.3d at 1278.

To establish entitlement to compensation under the Program, Petitioner must establish

each of the three prongs of Althen by a preponderance of the evidence. Id. The preponderance of

the evidence standard has been interpreted to mean that Petitioner must show that the fact to be

proven is more likely than not. Moberly, 592 F.3d at 1322 n. 2.

In determining whether Petitioner is entitled to compensation, the undersigned will

consider all relevant material contained in the record. 42 U.S.C. § 300aa-13(b)(1). That material

can include circumstantial evidence. Capizzano v. Sec’y of HHS, 440 F.3d 1317, 1325 (Fed. Cir.

2006). Although Petitioner is not required to present proof of causation to the level of scientific

certainty, the undersigned is, as the finder of fact, “entitled—indeed, expected—to make

determinations as to the reliability of the evidence presented . . . and, if appropriate, as to the

credibility of the persons presenting that evidence.” Moberly v. Sec'y of HHS, 592 F.3d 1315,

1326 (Fed. Cir. 2010).

The Supreme Court has set forth a number of factors courts should consider in evaluating

the reliability of expert testimony. Daubert v. Merrell Dow Pharms., Inc., 509 U.S. 579, 592

(1993). The Federal Circuit has explained that it is appropriate for the undersigned to utilize

Daubert’s factors as a framework for evaluating the reliability of causation-in-fact theories

presented under the Vaccine Act. Terran v. Sec’y of HHS, 195 F.3d 1302, 1316 (Fed. Cir. 1999);

see also Coombs v. Sec’y of HHS, No. 08-818V, 2014 WL 1677584, at *3 (Fed. Cl. Spec. Mstr.

Apr. 8, 2014). Terran clarified that the undersigned is not required to apply all of the Daubert

factors, but is encouraged to use the Daubert framework as a tool for inquiring into the reliability

of the evidence. 195 F.3d at 1316.

“Claimants who show that a listed injury first manifested itself at the appropriate time are prima

facie entitled to compensation.” Id.

7

Accordingly, the undersigned and other special masters regularly use the following

factors for analyzing the reliability of expert testimony: “(1) whether a theory or technique can

be (and has been) tested; (2) whether the theory or technique has been subjected to peer review

and publication; (3) whether there is a known or potential rate of error and whether there are

standards for controlling the error; and, (4) whether the theory or technique enjoys general

acceptance within a relevant scientific community.” Terran, 195 F.3d at 1316 n.2 (citing

Daubert); see Snyder v. Sec’y of HHS, 88 Fed. Cl. 706, 744-45 (2009) (holding that the special

master’s “application of Daubert was in accordance with the law”).

Where opinion evidence is only connected to the data upon which it purports to rely by the

ipse dixit of the expert, that evidence may be accorded less weight. Gen. Elec. Co. v. Joiner, 522

U.S. 136, 146 (1997) (explaining that “nothing in either Daubert or the Federal Rules of

Evidence requires a district court to admit opinion evidence that is connected to existing data

only by the ipse dixit of the expert.”). The undersigned may also deem an opinion or theory

unreliable where “‘there is simply too great an analytical gap between the data and the opinion

proffered.’” Cedillo v. Sec’y of HHS, 617 F.3d 1328, 1339 (Fed. Cir. 2010) (quoting Joiner, 522

U.S. at 146); see also Caves v. Sec’y of HHS, 100 Fed. Cl. 119, 136 (2011) (holding that Special

Master did not err in deeming expert’s theory unreliable where theory and its conclusions “were

too far removed from the other evidence” in the case), aff’d sub nom., 463 F. App'x 932 (Fed.

Cir. 2012).

A. Althen Prong One

To satisfy the first prong of Althen, Petitioner must provide “a medical theory causally

connecting the vaccination and the injury.” Althen, 418 F.3d at 1278 (internal quotation marks

omitted). Petitioner’s theory must show that it is more likely than not that the vaccine she

received “can” cause the type of injury Petitioner alleges the vaccine caused. Pafford v. Sec’y of

HHS, 451 F.3d 1352, 1356 (Fed. Cir. 2006) (internal quotation marks omitted).

The medical theory set forth by Petitioner need only be “legally probable, not medically

or scientifically certain.” Knudsen v. Sec’y of HHS, 35 F.3d 543, 548-49 (Fed. Cir. 1994).

However, the theory cannot be baseless or completely speculative; it must be informed by

“sound and reliable medical or scientific explanation.” Id. at 548; see Veryzer v. Sec’y of HHS,

98 Fed. Cl. 214, 223 (2011) (noting that under 42 U.S.C.A. § 300aa-13(b)(1) and Vaccine Rule

8(b)(1), special masters must consider only evidence that is both “relevant” and “reliable”).

When Petitioner proffers a medical opinion to support the theory alleged, the basis for the

opinion and the reliability of that basis must be considered in determining how much weight to

afford the offered opinion. Broekelschen v. Sec’y of HHS, 618 F.3d 1339, 1347 (Fed. Cir. 2010);

see Perreira v. Sec’y of HHS, 33 F.3d 1375, 1377 n. 6 (Fed. Cir. 1994) (“An expert opinion is no

better than the soundness of the reasons supporting it.”).

8

The Federal Circuit has issued a number of decisions discussing what constitutes a

“reputable medical or scientific explanation” of a theory sufficient to satisfy the aforementioned

requirement. For example, a petitioner who provides a theory that the government concedes is

plausible will satisfy Althen’s first prong. Jay v. Sec’y of HHS, 998 F.2d 979, 984 (Fed. Cir.

1993). A theory that has basic indicia of reliability that is put forward by qualified experts will

also satisfy the first prong of Althen. Capizzano, 440 F.3d at 1326.

By contrast, “where basic indicia of reliability do not exist, the special master may reject

a petitioner’s medical theory.” Paluck v. Sec’y of HHS, 104 Fed. Cl. 457, 470 (2012). Thus, the

Federal Circuit affirmed a special master’s conclusion that a theory relying upon “a literature

review based on two papers from the early 1950s, which in turn considered vaccine cases

between 1929 and 1952,” was insufficient to satisfy Althen's first prong. Broekelschen, 618 F.3d

at 1350. The Federal Circuit likewise affirmed the rejection of a theory linking a pertussis

vaccine to brain damage when the theory had never been tested and was criticized by the

government's expert as biologically implausible, noting that the testimony of the petitioner’s

expert was “contradictory and confusing,” and “shockingly poor.” Moberly, 592 F.3d at 1321,

1325.

B. Althen Prong Two

While the first prong of Althen focuses on general causation, that is, whether the

administered vaccine can cause the particular injury from which the vaccinee suffers, the second

prong focuses on specific causation, that is, whether the administered vaccine actually caused the

injury. See Pafford v. Sec’y of HHS, 451 F.3d 1352, 1355-56 (Fed. Cir. 2006). To satisfy the

second prong of Althen, Petitioner must establish “a logical sequence of cause and effect showing

that the vaccination was the reason for the injury.” Althen, 418 F.3d at 1278. Petitioner may

satisfy her burden by presenting circumstantial evidence and reliable medical opinions; she is not

required to offer “epidemiologic studies, rechallenge, presence of pathological markers or genetic

disposition, or general acceptance in the scientific and medical communities” to establish a logical

sequence of cause and effect. Capizzano, 440 F.3d at 1322.

C. Althen Prong Three

To satisfy the third prong of Althen, Petitioner must produce preponderant evidence of “a

proximate temporal relationship between vaccination and injury.” Althen, 418 F.3d at 1278. This

prong helps to establish the connection between the causal theory of Prong One and the more fact-

based cause and effect arguments of Prong Two by demonstrating “that the onset of symptoms

occurred within a timeframe for which, given the medical understanding of the disorder’s

etiology, it is medically acceptable to infer causation-in-fact.” De Bazan v. Sec’y of HHS, 539

9

F.3d 1347, 1352 (Fed. Cir. 2008).

III. ANALYSIS

A. Background Information

1. Gardasil Vaccine

Gardasil is a relatively new vaccine, approved for the first time in 2006. Merck & Co.,

Inc., Gardasil Physician Prescribing Information (2011), at *1, available at

http://www.merck.com/product/usa/pi_circulars/g/gardasil/gardasil_pi.pdf. It was developed to

immunize young women (although it is also given to young men) against HPV. Id. Gardasil is a

recombinant vaccine, not a live virus vaccine. Id. That is, Gardasil “[i]s a non-infectious

recombinant quadrivalent vaccine prepared from the purified virus-like particles (VLPs) of the

major capside (L1) protein of HPV Types 6, 11, 16, and 18,” which are “produced by separate

fermentations in recombinant Saccharomyces cerevisiae and self-assembled into VLPs.” Id. at

12. There are at least 130 genetically different HPV subtypes known to date. See Margaret

Stanley, Immunobiology of HPV and HPV vaccines, 109 Gynecologic Oncology S15, at *1,

(2008). Two of them, HPV 16 and HPV 18, are known to cause cervical, esophageal, and anal

cancer, and two, HPV 6 and HPV 11, are known to cause genital warts and herpes. Id. at *1-2.

These four subtypes are incorporated into the quadrivalent Gardasil vaccine. See Prescribing

Information at 1. The Gardasil vaccine also contains an adjuvant 11 that has aluminum as a

component. Id. at 12.

2. Systemic Lupus Erythematosus

SLE is a “chronic, inflammatory, often febrile multisystemic disorder of connective

tissue that proceeds through remissions and relapses; it may be either acute or insidious in onset

and is characterized principally by involvement of the skin, . . . joints, kidneys and serosal

membranes.” Lupus, Systemic Erythematosus, Dorland’s. Although the etiology is technically

unknown, “it may be a failure of regulatory mechanisms of the autoimmune system.” Id.

B. Qualifications of the Parties’ Experts

1. Dr. Yehuda Shoenfeld

11

The aluminum adjuvant, when combined “with soluble antigen forms a precipitate,” and “slow

release of the antigen from the precipitate on infection causes prolonged, strong antibody

response.” Adjuvant, Aluminum, Dorland’s.

10

Dr. Shoenfeld is a 1972 graduate of the Hadassa Medical School at Hebrew University in

Jerusalem. Pet’r’s Ex. 9, ECF No. 29-2. He is a specialist in internal medicine, specifically

immunology and allergy, and especially autoimmunity. Transcript of Proceedings (Dec. 17,

2013) at 100, ECF No. 60 (hereinafter “Tr. B”). He served in a number of medical positions until

he was appointed Head of Department of Medicine “B” Sheba Medical Center in 1989, a position

he held until 2011, when he founded and became the Head of the the Zabludowicz Center for

Autoimmune Diseases. Pet’r’s Ex. 9. at 2. He has published well over a thousand papers, and is

an editor for a number of journals, with a research focus on autoimmune diseases. Tr. B at 100-

107. He was admitted as an expert in clinical immunology. Id. at 117.

2. Dr. Carlos Daniel Rose

Dr. Rose is a graduate of the University of Buenos Aires Medical School. Tr. B at 248.

He has been the head of the Pediatric Rheumatology Division of the Department of Pediatrics at

Thomas Jefferson University in Philadelphia since 1994. Id. at 248-49. He has a clinical and

teaching practice, and has conducted research in the areas of Lyme disease and Blau syndrome.

Id. at 249-50. He has served on many boards and commissions, and is extensively published. See

generally Resp’t’s Ex. B, ECF No. 34-6. Dr. Rose was admitted as an expert in pediatric

rheumatology. Tr. B at 251-52.

C. The Parties’ Arguments

After the hearing, both parties filed briefs summarizing their positions. See Pet’r’s Post

Hr’g Br., ECF No. 73; Resp’t’s Post Hr’g Br., ECF No. 75. Petitioner argued that she was

entitled to an award, explaining that (1) the adjuvants in the Gardasil vaccine could have caused

her injury by “mimic[king] specific sets of evolutionarily conserved molecules,” triggering an

overactive response by the immune system; (2) Petitioner’s healthy medical history prior to the

vaccine, the lack of alternative potential causes, and the temporal proximity between the vaccine

and the first symptom of SLE all suggested that the Gardasil vaccine indeed caused Petitioner to

develop SLE; and (3) the onset of the first symptom of Petitioner’s SLE was temporally

consistent with a finding that the vaccine caused her SLE. Pet’r’s Post Hr’g Br. at 10-11. To the

contrary, Respondent contended, Petitioner had not presented a prima facie case entitling her to

compensation because (1) Dr. Shoenfeld’s theory of causation is unpersuasive because it posits

that “all adjuvants are the same, that all autoimmune diseases are the same, and that any adjuvant

is capable of causing any autoimmune disease”; (2) the evidence, including that of the

development of the disease, was consistent with typical idiopathic childhood-onset SLE, none of

her treating physicians opined in favor of causation, and that potential environmental factors went

unconsidered by Dr. Shoenfeld, all rebuffed the conclusion that the Gardasil vaccine caused

Petitioner to develop SLE; and (3) the six-month period between the vaccination and the first

symptom of her SLE suggested no causal relationship between the two. Resp’t’s Post Hr’g Br. at

11

1-7.

D. The Undersigned’s Decision

After thorough consideration of the parties arguments and review of the extensive record

in this case, the undersigned concludes that Petitioner is not entitled to compensation under the

Vaccine Act. While the undersigned’s discussion focuses most extensively on Althen’s first

prong, the undersigned is careful to note that she does not believe that Petitioner has met her

burden under any of Althen’s prongs.

1. Althen Prong One

The fundamental problem with Petitioner’s theory of causation is that the theory is

overbroad, generalized, and vague, to the point that it could apply to virtually everyone in the

world who has received a vaccine containing an adjuvant and then at some time in their lives

developed an autoimmune disease. This makes the theory completely unhelpful for proving

causation of a specific injury resulting from a specific vaccine or series of vaccines within a

specific time frame.

To illustrate: Petitioner’s burden in this case was to prove by a preponderance of the

evidence that a series of three Gardasil vaccines, which contain an aluminum-based adjuvant,

can, within a time period appropriate to the theory, cause the autoimmune disease in question,

SLE. Dr. Shoenfeld’s expert opinion, however, is that all adjuvants are basically the same, that

they are designed to “increase the effect of the immune system,” and that in so doing they cause

autoimmune disease. Tr. B at 176-77. He testified that “for me, all autoimmune diseases are the

same.” Id. at 103. And, he testified that the only timing that is relevant is “that the disease came

after the vaccine and not before the vaccine.” Id. at 138-39.

In both his reports and his testimony, Dr. Shoenfeld gave numerous examples of studies

that he asserts put “a nail in the coffin of indicating that adjuvant and vaccine can cause

autoimmune disease.” Tr. B at 150; see Tr. B at 145-46 (discussing H1N1 vaccine and

narcolepsy); Pet’r’s Ex. 26 (discussing Hepatitis B vaccine and chronic fatigue syndrome); see

generally Pet’r’s Ex. 109, ECF No. 63-2 (discussing Hepatitis B and demyelinating diseases such

as GBS, transverse myelitis, and ADEM). Dr. Shoenfeld argued that these studies all

demonstrate that if an adjuvant can cause an autoimmune disease, it can cause any autoimmune

disease, 12 and likewise, if an autoimmune disease has been shown to have been caused by an

12

Notably, the only evidence Dr. Shoenfeld put forth specifically concerning Gardsail and SLE

came in the form of case reports, see Tr. B at 193-94, most of which involved patients with

preexisting SLE or other autoimmune diseases, which made their persuasiveness on causation

12

adjuvant, it can be caused by any adjuvant. And, theoretically, the development of the

autoimmune disease can happen at any time after the introduction of the adjuvant. Tr. B at 221.

As he wrote in his response to Dr. Cetaruk, “autoimmune diseases stem from a hyperactive

and deranged immune system activity. Adjuvants are stimulators of hyperactive immune

responses (whether it be Th1 or Th2). Hence immune adjuvants have all the necessary

biochemical properties to induce autoimmune diseases.” Pet’r’s Ex. 109 at 1-2 (emphasis in

original). Dr. Shoenfeld put it this way at hearing: if you have “somebody who has an hyper-

stimulated immune system and you add something else, whatever, being aluminum, being oil,

being virosome, being the new adjuvant, which will increase the immune system stimulation,

will cause the eruption eventually of an autoimmune disease in somebody who is genetically

prone to it.” Tr. B at 176-77 (emphasis added).

The undersigned simply does not find this expansive theory logically persuasive. There

is no way to measure its validity; with vaccines containing adjuvants being administered to

hundreds of millions of individuals from birth (HepB) throughout childhood and into adulthood,

and with no time limit placed on when the autoimmune reaction to those adjuvants can occur,

there is no control group, no possible manageable way to track those millions of doses and their

alleged causation of dozens, possibly a hundred or more, autoimmune diseases. By the time an

individual such as Petitioner reaches the age that she was when she developed her autoimmune

disease, she may have received multiple vaccines containing adjuvants and have been exposed to

myriad other environmental factors for which a causative connection between the factor and

autoimmunity have been shown. How, if at all, is one to determine which of those causative

factors was responsible for the development of that individual’s autoimmune disease? If this

theory is valid, is the first adjuvant-containing vaccine administered, or environmental factor

encountered, always causative? If not, why not? And if this theory is a reliable explanation for

the development of any autoimmune disease in the vaccinated population, what does that do to

the validity of the many studies, including those cited by Dr. Shoenfeld himself, that do show a

particular connection between a particular vaccine and a particular autoimmune disease? These

analytical gaps are numerous, they are large, and they are not resolved by the evidence adduced

at hearing or in the record. By attempting to explain everything autoimmune-related in adjuvant

dubious, at best, see, e.g., Pet’r’s Ex. 99 at 3. Dr. Shoenfeld admitted at hearing that no

epidemiological link between HPV and SLE has been shown to exist. Tr. B. at 191. He also

admitted that there are no published studies showing a causative link between aluminum

adjuvant and SLE, and that the review article he published in 2013 concerning the effects of

adjuvants on animal models did not include any studies showing that aluminum-based adjuvants

caused SLE in animals. Id. at 175. In fact, in a study of genetically altered SLE-prone mice

administered four adjuvants, including aluminum, only one of those adjuvants, not the

aluminum, “accelerated the onset of proteinuria,” an SLE marker symptom, in any of the mice.

See generally Pet’r’s Ex. 112, ECF No. 63-5.

13

terms, Dr. Shoenfeld has, at least to the undersigned, explained nothing. As a result, Petitioner

has not met her burden of proof under Althen’s first prong.

2. Althen Prongs Two and Three

While Petitioner’s failure to satisfy the first prong of Althen renders an analysis of the

remaining Althen prongs unnecessary, the undersigned will nevertheless proceed with a brief

analysis of those prongs. Because Althen prongs two and three have a closely overlapping

analysis, and in this case, closely overlapping factual evidence and rulings, 13 they will both be

discussed within this section.

The first major issue under Althen’s second and third prongs is that Petitioner’s depiction

of an injury that developed after the first dose of vaccine and increased in severity and number of

symptoms after each successive dose (basically a challenge/rechallenge model), see Tr. B at 153,

is inconsistent with the facts and medical records. While Petitioner’s counsel tried mightily to

construe it otherwise, the testimony of Petitioner and her parents concerning the onset of

Petitioner’s SLE symptoms showed a marked lack of recall and specificity. Neither parent had

an independent recollection of the alleged hair loss. Petitioner’s memory was also admittedly

poor, see Tr. A at 14, but to the extent she did remember, the “scary” hair loss occurred during

her senior year (2008-2009), several months after the third and final vaccination in June 2008,

Tr. A at 28-29. Both Petitioner and her mother remembered that the Raynaud’s was first

noticeable during winter church camp. Petitioner’s mother remembered that shortly after that

she took Petitioner to Dr. Saad, with what turned out to be SLE. Tr. A at 48-50. The winter

school break of 2008-2009 is the timing that fits with the medical records, which place that

symptom, along with all the others, about four months before her first visit to Dr. Saad, in March

of 2009, with what turned out to be SLE symptoms. Pet’r’s Ex. 1 at 4. The fatigue, along with

the slowing down at soccer practice and games, was noticed by the coach of Petitioner’s club

team, with whom she played when she was not playing soccer for school. Since she had no

apparent problems playing on her school team during the spring of her junior year (2008), this

again places the symptom after the last of the three HPV vaccines in June 2008. Finally, as to

the weight loss: Petitioner reached her maximum recorded weight of 144 pounds on March 5,

2008, which was the date of her second Gardasil vaccination. She still weighed 138.2 pounds

when she saw Dr. Saad on March 18, 2009, see id. at 4; it was not until over a year later, when

she saw Dr. Grossman for the first time, that she was down nearly 20 pounds, Pet’r’s Ex. 104 at

18. These records just do not support a 20 pound weight loss before diagnosis.

Taking all of the evidence together, therefore, the undersigned finds that the onset of

Petitioner’s SLE symptoms dates from approximately December of 2008. The timing of onset is

13

The Federal Circuit has held that there is no “reason why evidence used to satisfy one of the

Althen . . . prongs cannot overlap to satisfy another prong.” Capizzano, 440 F.3d at 1326.

14

therefore not compatible with Dr. Shoenfeld’s primary argument concerning causation, which

was heavily dependent on the symptoms appearing sequentially, along with the sequential

administration of the vaccines. See Tr. B at 153, 200-01.

Although Petitioner attempts to point to Dr. Shoenfeld’s argument that the timing does

not matter so long as it occurred after the vaccine, the undersigned has already dismissed that

argument under Althen prong one. Indeed, accepting this argument would force the undersigned

to render Althen’s third prong toothless, and it is therefore invalid on its face. See Hennessy v.

Sec’y of HHS, 91 Fed. Cl. 126, 142 (2010) (rejecting the petitioner’s attempt, via Dr. Shoenfeld,

“to satisfy Althen’s third prong by defining it away, positing that any time frame is appropriate”).

Finally, while it is not incumbent upon petitioners to eliminate all, or even most, potential

alternative causes for their injuries, Althen, 418 F.3d at 1281, it is not untoward to expect that

Petitioner explain an alternative cause raised by her own expert. Dr. Shoenfeld testified, both on

direct and cross examination, Tr. B at 128-29, 188-89, that “sun exposure can induce” and

“exacerbate” SLE. Tr. B at 188-89. For example, he noted, “in my country [Israel], SLE will be

much more severe in expression than in patients with SLE from Scandinavia” because of their

relative proximity to the equator. Tr. B at 129. Petitioner lived in southern California from at

least 2006-2009, Pet’r’s Ex. 118 at 1. Upland, where she lived, is only about three degrees

further north from the equator than is Jerusalem (34 degrees versus 31 degrees). Throughout

high school, until she got sick, Petitioner played soccer. She was on her high school team and a

club team; she “pretty much played year-round.” Tr. A at 16. Petitioner was in the peak age

group for SLE, Tr. B at 306-07; she was post-pubertal and subject to the effects of estrogen,

which both experts testified is related to the development of SLE, Tr. B at 103, 307-08.

According to both experts, Petitioner had a genetic predisposition to the disease. Tr. B at 180,

258. On this issue, the undersigned agrees with Dr. Rose: there is no reason to believe that a

temporally remote vaccination is more likely to have caused Petitioner’s SLE than a well-known

physical trigger (sun exposure) to which Petitioner was repeatedly exposed. Tr. B at 282-83.

For this and the reasons previously discussed, the undersigned holds that Petitioner has not met

her burden under either Althen’s second or third prongs.

IV. CONCLUSION

The undersigned sympathizes with the fact that Petitioner suffers from a painful, chronic

disease. However, because Petitioner has failed to meet her burden of proof under the three

prongs of Althen, her petition must be, and is hereby, DISMISSED. In the absence of a motion

for review filed pursuant to RCFC Appendix B, the Clerk of the Court is directed to enter

judgment herewith.14

14

Pursuant to Vaccine Rule 11(a), the parties can expedite entry of judgment by filing a notice

renouncing the right to seek review by a United States Court of Federal Claims judge.

15

/s/ Lisa D. Hamilton-Fieldman

Lisa D. Hamilton-Fieldman

Special Master

16