VICP Registry Case Source Bundle Canonical URL: https://vicp-registry.org/case/USCOURTS-cofc-1_10-vv-00489 Package ID: USCOURTS-cofc-1_10-vv-00489 Petitioner: Valeria Flores Filed: 2010-07-29 Decided: 2015-07-24 Vaccine: HPV Vaccination date: 2008-04-28 Condition: spinal cord stroke Outcome: compensated Award amount USD: 137500 AI-assisted case summary: Valeria Flores, a minor, received her first human papillomavirus (HPV) vaccination on April 28, 2008, and her second dose on June 27, 2008. The day after her second vaccination, she began experiencing left-sided weakness, severe headache, and shortness of breath, which progressed to flaccid paralysis and slurred speech. She also suffered a cardiac arrest and required ventilation. She was diagnosed with a spinal cord stroke, believed to be caused by a blood clot. Her father filed a petition for compensation under the National Vaccine Injury Compensation Program on July 29, 2010, alleging the HPV vaccine caused her injury. Valeria Flores was later substituted as petitioner upon reaching the age of majority. The respondent was the Secretary of Health and Human Services. Petitioner was represented by Clifford J. Shoemaker, and respondent was represented by Debra A. Filteau Begley. Special Master George L. Hastings initially denied the claim in a decision dated September 12, 2013, finding that the petitioner failed to prove causation-in-fact under the Althen test. The special master found that the petitioner's expert, Dr. Douglas A. Kerr, proposed a theory of causation involving genetic predisposition, immune sensitization, and inflammation or platelet aggregation, which was not supported by a preponderance of the evidence. The special master noted that the petitioner could not establish a genetic predisposition, that the blood clot likely originated in an artery rather than a vein as Dr. Kerr theorized, and that there was no evidence of inflammation or platelet aggregation. The special master also found that medical literature did not support Dr. Kerr's theory. The court, in an opinion dated March 21, 2014, by Judge Margaret M. Sweeney, reviewed the special master's decision. The court agreed that the petitioner had not met her burden of proof regarding causation, although it found that the special master had improperly required specific proof of genetic susceptibility. However, the court upheld the special master's findings that there was no evidence of inflammation or platelet aggregation, which meant the petitioner could not establish a link between the immune response and the blood clot. Therefore, the court denied the petitioner's motion for review and sustained the special master's decision. On July 24, 2015, Special Master George L. Hastings issued a decision regarding attorneys' fees and costs. Based on a stipulation between the parties, the decision awarded $137,500.00 for attorneys' fees and costs, representing all available amounts under the program, finding that the petition was brought in good faith with a reasonable basis. Theory of causation field: Petitioner Valeria Flores, age 14, received two doses of the HPV vaccine on April 28, 2008, and June 27, 2008. The day after the second dose, she developed symptoms including left-sided weakness, headache, shortness of breath, flaccid paralysis, and slurred speech, followed by cardiac arrest and requiring ventilation. She was diagnosed with a spinal cord stroke. Petitioner alleged the HPV vaccine caused the stroke. Petitioner's expert, Dr. Douglas A. Kerr, proposed a theory that the HPV vaccine caused a blood clot through immune sensitization, an exuberant immune response, and subsequent inflammation or platelet aggregation, exacerbated by a genetic predisposition to blood clotting. Respondent's experts, Drs. Peter M. Bingham and Joan Cox Gill, found this improbable, noting a lack of clinical evidence for inflammation or platelet aggregation, and suggesting an arterial rather than venous thrombosis. The Special Master denied compensation, finding petitioner failed to prove causation-in-fact under the Althen test. The Special Master found Dr. Kerr's theory unsupported by evidence regarding genetic predisposition, the origin of the clot (arterial vs. venous), and the presence of inflammation or platelet aggregation. The Court of Federal Claims affirmed, agreeing that petitioner failed to establish a logical sequence of cause and effect linking the vaccine to the injury, specifically the absence of evidence for inflammation or platelet aggregation. The court noted the special master improperly required specific proof of genetic susceptibility but found this did not change the outcome. The case was not listed on the Vaccine Injury Table. A subsequent stipulation resulted in an award of $137,500.00 for attorneys' fees and costs on July 24, 2015, based on a finding of good faith and reasonable basis for the claim. Attorneys for petitioner were Clifford J. Shoemaker; respondent was represented by Debra A. Filteau Begley. Special Master was George L. Hastings, and the reviewing judge was Margaret M. Sweeney. Public staged source text: ================================================================================ DOCUMENT 1: USCOURTS-cofc-1_10-vv-00489-cl-extra-2642515 Date issued/filed: 2013-09-12 Pages: 1 Docket text: Supplementary opinion from CourtListener cluster 2642515 -------------------------------------------------------------------------------- In the United States Court of Federal Claims OFFICE OF SPECIAL MASTERS No. 10-489V (Filed: September 12, 2013) TO BE PUBLISHED1 * * * * * * * * * * * * * * * * * * * * * * * * * * ** VALERIA FLORES, * Vaccine Act Entitlement; * Causation-in-fact; Human Petitioner, * Papilloma Virus (HPV) * Vaccine/Spinal Cord Infarction v. * * SECRETARY OF HEALTH AND * HUMAN SERVICES, * * Respondent. * * * * * * * * * * * * * * * * * * * * * * * * * * * ** Clifford Shoemaker, Vienna, Virginia, for Petitioner. Debra Begley, U.S. Department of Justice, Washington, D.C., for Respondent. DECISION HASTINGS, Special Master. This is an action in which the Petitioner, Valeria Flores, seeks an award under the National Vaccine Injury Compensation Program (hereinafter “the Program” 2), on account of a spinal cord infarction that Petitioner believes was caused by a human papilloma virus (hereinafter “HPV”) vaccination. For the reasons set forth below, I conclude that Petitioner is not entitled to an award. 1 Because I have designated this document to be published, this document will be made available to the public unless petitioner files, within fourteen days, an objection to the disclosure of any material in this decision that would constitute “medical files and similar files the disclosure of which would constitute a clearly unwarranted invasion of privacy.” See 42 U.S.C. §300aa-12(d)(4)(b). 2 The applicable statutory provisions defining the Program are found at 42 U.S.C. § 300aa-10 et seq. (2000 ed.). Hereinafter, for ease of citation, all “§” references will be to 42 U.S.C. (2000 ed.). I APPLICABLE STATUTORY SCHEME AND CASELAW Under the National Vaccine Injury Compensation Program, compensation awards are made to individuals who have suffered injuries after receiving vaccines. In general, to gain an award, a petitioner must make a number of factual demonstrations, including showings that an individual received a vaccination covered by the statute; received it in the United States; suffered a serious, long-lasting injury; and has received no previous award or settlement on account of the injury. Finally--and the key question in most cases under the Program--the petitioner must also establish a causal link between the vaccination and the injury. In some cases, the petitioner may simply demonstrate the occurrence of what has been called a “Table Injury.” That is, it may be shown that the vaccine recipient suffered an injury of the type enumerated in the “Vaccine Injury Table” corresponding to the vaccination in question, within an applicable time period following the vaccination also specified in the Table. If so, the Table Injury is presumed to have been caused by the vaccination, and the petitioner is automatically entitled to compensation, unless it is affirmatively shown that the injury was caused by some factor other than the vaccination. §300aa-13(a)(1)(A); §300aa-11(c)(1)(C)(i); §300aa-14(a); §300aa-13(a)(1)(B). In other cases, however, the vaccine recipient may have suffered an injury not of the type covered in the Vaccine Injury Table. 3 In such instances, an alternative means exists to demonstrate entitlement to a Program award. That is, the petitioner may gain an award by showing that the recipient’s injury was “caused-in-fact” by the vaccination in question. §300aa-13(a)(1)(A); §300aa-11(c)(1)(C)(ii). In such a situation, of course, the presumptions available under the Vaccine Injury Table are inoperative. The burden is on the petitioner to introduce evidence demonstrating that the vaccination actually caused the injury in question. Althen v. HHS, 418 F. 3d 1274, 1278 (Fed. Cir. 2005); Hines v. HHS, 940 F. 2d 1518, 1525 (Fed. Cir. 1991). The showing of “causation-in-fact” must satisfy the “preponderance of the evidence” standard, the same standard ordinarily used in tort litigation. §300aa-13(a)(1)(A); see also Althen, 418 F. 3d at 1278; Hines, 940 F. 2d at 1525. Under that standard, the petitioner must show that it is “more probable than not” that the vaccination was the cause of the injury. Althen, 418 F. 3d at 1279. The petitioner need not show that the vaccination was the sole cause or even the predominant cause of the injury or condition, but must demonstrate that the vaccination was at least a “substantial factor” in causing the condition, and was a “but for” cause. Shyface v. HHS, 165 F. 3d 1344, 1352 (Fed. Cir. 1999). Thus, the petitioner must supply “proof of a logical sequence of cause and effect showing that the vaccination was the reason for the injury;” the logical sequence must be supported by “reputable medical or scientific explanation, i.e., evidence in the form of scientific studies or expert medical testimony.” Althen, 418 F. 3d at 1278; Grant v. HHS, 956 F. 2d 1144, 1148 (Fed. Cir. 1992). The Althen court also provided additional discussion of the “causation-in-fact” standard, as follows: 3 No Table Injury is alleged in this case. Petitioner’s theory in this case is solely one of “actual causation.” 2 Concisely stated, Althen’s burden is to 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. If Althen satisfies this burden, she is “entitled to recover unless the [government] shows, also by a preponderance of evidence, that the injury was in fact caused by factors unrelated to the vaccine.” Althen, 418 F. 3d at 1278 (citations omitted). The Althen court noted that a petitioner need not necessarily supply evidence from medical literature supporting the petitioner’s causation contention, so long as the petitioner supplies the medical opinion of an expert. Id. at 1279-80. The court also indicated that, in finding causation, a Program factfinder may rely upon “circumstantial evidence,” which the court found to be consistent with the “system created by Congress, in which close calls regarding causation are resolved in favor of injured claimants.” Id. at 1280. Since Althen, the Federal Circuit has addressed the causation-in-fact standard in several additional rulings, which have affirmed the applicability of the Althen test, and afforded further instruction for resolving causation-in-fact issues. In Capizzano v. HHS, 440 F. 3d 1317, 1326 (Fed. Cir. 2006), the court cautioned Program factfinders against narrowly construing the second element of the Althen test, confirming that circumstantial evidence and medical opinion, sometimes in the form of notations of treating physicians in the vaccinee’s medical records, may in a particular case be sufficient to satisfy that second element of the Althen test. Both Pafford v. HHS, 451 F. 3d 1352, 1355 (Fed. Cir. 2006), and Walther v. HHS, 485 F. 3d 1146, 1150 (Fed. Cir. 2007), discussed the issue of which party bears the burden of ruling out potential non-vaccine causes. DeBazan v. HHS, 539 F. 3d 1347 (Fed. Cir. 2008), concerned an issue of what evidence the special master may consider in deciding the initial question of whether the petitioner has met her causation burden. Another important aspect of the causation-in-fact case law under the Program concerns the factors that a special master should consider in evaluating the reliability of expert testimony and other scientific evidence relating to causation issues. In Daubert v. Merrell Dow Pharmaceuticals, Inc., 509 U.S. 579 (1993), the Supreme Court listed certain factors that federal trial courts should utilize in evaluating proposed expert testimony concerning scientific issues. In Terran v. HHS, 195 F. 3d 1302, 1316 (Fed. Cir. 1999), the Federal Circuit ruled that it is appropriate for special masters to utilize Daubert’s factors as a framework for evaluating the reliability of causation-in-fact theories presented in Program cases. One of the factors listed in Daubert is whether the scientific theory “has been subjected to peer review and publication.” 509 U.S. at 593. The Court noted that while publication does not “necessarily” correlate with reliability, since in some instances new theories will not yet have been published, nevertheless “submission to the scrutiny of the scientific community is a component of ‘good science,’” so that the “fact of publication (or lack thereof) in a peer reviewed journal thus will be a relevant, though not dispositive, consideration in assessing the scientific validity” of a theory. Id. at 593-94. 3 II FACTS AND PROCEDURAL HISTORY A. Facts Valeria Flores (“Valeria” or “Petitioner”) was born on September 6, 1993, and was 14 years old at the time of the vaccination here at issue. (Petition at p. 1.) Though she had a few significant illnesses, Valeria’s medical history prior to 2008 is not relevant here. 4 At the time of her vaccination, she had experienced no recent illnesses or injuries. (Ex. 20, 5 P. 3.) On April 28, 2008, Valeria was seen for a school physical. (Ex. 7, p. 4.) During that exam, she was given her first meningococcal and HPV vaccinations. (Ex. 6, p. 1; Ex. 7, p. 6.) There are no medical records that suggest that Valeria reported any concerns following her first HPV vaccination. On June 27, 2008, Valeria received her second HPV vaccination. (Ex. 6, p. 1; Ex. 7, p. 10.) The medical records make it clear that Valeria’s symptoms began the following day, on June 28, 2008, although there is a discrepancy regarding the exact timing of symptom progression. According to the ambulance records, she awoke with left-sided weakness that progressed to shortness of breath. (Ex. 1, p. 5.) Similarly, records from the first hospital, Mt. Sinai, reflect that she awoke with a severe headache and left arm weakness. (Pet. Ex. 8, pp. 7, 28.) However, the records from Rush University Medical Center, to which she was later transferred, contain a statement from Valeria’s mother reporting that Valeria had no symptoms until 12:30 in the afternoon, when she complained of a sudden, severe headache, followed by left arm pain and weakness. (Ex. 20, p. 35.) The notes from the emergency medical technicians (“EMTs”) who arrived at Valeria’s home at 1:22 in the afternoon state that Valeria had difficulty breathing and that her symptoms had begun approximately ninety minutes earlier. (Ex. Ex. 4, p. 3.) In any event, it is clear that, at some time on June 28, Valeria experienced symptoms including left-sided weakness, headache, and shortness of breath. (Ex. 1, p. 5; Ex. 4, p. 3; Ex. 8, pp. 7, 28; Ex. 20, p. 35.) When the emergency medical service (“EMS”) arrived, Valeria developed bradycardia and suffered a cardiac arrest. (Ex. 4, p. 4.) She was intubated and responded to cardiopulmonary resuscitation and atropine. (Id.) By the time she arrived at the hospital, her blood pressure had returned to 102/74, and she was no longer asystolic. (Id.) Upon arrival in the Mt. Sinai Hospital emergency room on June 28, Valeria was awake, but unable to feel or move her extremities. (Ex. 8, p. 7.) At that emergency room, Valeria’s parents reported that she had been suffering from a severe headache and left arm weakness, followed by 4 In 1998, Valeria had a positive reaction to a tuberculin skin test and was treated with nine months of Isoniazid. (Ex. 3, p 28.) She was also followed for crystals in her urine. (Id. at pp. 8, 10.) She had measles at the age of 3. (Ex. 20, p. 3.) 5 Petitioner filed Exhibits 1 through 15 on September 17, 2010, and has since filed a number of additional consecutively-numbered exhibits. Respondent has filed Exs. A through O at various times. 4 shortness of breath. 6 (Id. at 9.) They also reported that she had received her HPV vaccination the day before. (Id.) Coagulation studies were normal, and a urinalysis showed high levels of protein. (Id. at 18, 20.) A brain CT, without contrast, was normal. (Id. at 24.) Valeria was transferred to Rush University Hospital that same day for further medical treatment. (Ex. 1, p. 5; Ex. 20, p. 3.) Upon arrival at Rush, further evaluation was conducted. In an admission note, Valeria’s mother reported that earlier that day Valeria began to complain of a headache so painful that she was in tears. (Ex. 20, p. 35.) Valeria’s mother noted that about five minutes after the headache started, Valeria began having left arm pain that developed into paralysis and loss of sensation. (Id.) By the time the EMS arrived, Valeria had developed flaccid paralysis of her upper and lower extremities and slurred speech. (Id.) An MRI showed changes in the cervical cord at C2 through C4, which was thought to possibly indicate “ischemic change . . . myelitis, or acute demyelination.” (Ex. 20, p. 1079.) A cerebral angiogram showed no evidence of aneurysms, arterial venous malformations, or arterial venus fistulae. (Id. at 813.) The potential diagnoses, as of June 29, 2008, included “ischemia/thrombotic event, myelitis, acute demyelination, vascular abnormalities, toxins (lead, heavy metals), infectious disease, and autoimmune.” (Id. at 42.) Valeria underwent an extensive workup while at Rush, in an attempt to determine the cause of her symptoms, including her paralysis. An echocardiogram did not reveal a patent foramen ovale; 7 cerebral spinal fluid cultures were negative; all autoimmune studies – rheumatoid factor, antinuclear antibodies, double-stranded DNA, Sjogren’s syndrome and SSB antibodies – were negative. (Ex. 20, pp. 883, 891, 899, 904-905, 1002.) A coagulopathy workup, including proteins C and S, Antithrombin III, and Factor V Leiden, were negative. (Id. at 884-886, 897, 949-950.) However, a MTHFR A1298C heterozygous mutation, a common genetic abnormality, was found during Valeria’s genetic work-up. (Id. at 944.) An infectious disease workout was also negative. (Id. at 980-81, 1001-08, 1031-34.) The records from Rush indicate a shift in the analysis of her condition away from possible heart-related causes, so that Valeria was then given a working diagnosis of transverse myelitis. (Ex. 20, p. 23.) On July 3, 2008, she was started on a five-day course of solumedrol, without improvement. (Ex. 20, p. 20.) She then received one dose of cyclophosphamide, and was started on a five-day course of blood plasma exchange. (Id.) She again showed no improvement. (Id. at 24.) On August 6, 2008, Valeria’s case was reviewed by two neurologists, Drs. Tilwalli and Stefofski. Dr. Tilwalli, a neurology fellow, opined that given Valeria’s quick onset, absence of inflammatory markers, and lack of response to anti-inflammatory treatment, he favored a vascular 6 It should be noted that Valeria was fluent in English and her father spoke “adequate” English at the time of the injury. The records reveal that her parents communicated with hospital staff through an interpreter. (Ex. 8, p. 5; Ex. 9, p. 1; Ex. 20, pp. 6, 26.) 7 Patent foramen ovale is a congenital condition in which there is a small opening between the chambers of the heart. 5 etiology. (Ex. 20, p. 29.) He also noted that he thought Valeria’s HPV vaccination was too close to symptom onset to induce an inflammatory response. (Id.) Similarly, a neurologist, Dr. Stefofski, opined that Valeria’s quick symptom onset “strongly favors a vascular etiology over immune mediated/inflammatory (definitely too soon for Gardasil or even for a remote preceding myelitogenic trigger).” (Id. at 488.) He also noted that due to the lack of response to corticosteroids and cyclophosphamide, he doubted an autoimmune etiology. (Id.) Valeria continued to have flaccid paralysis throughout her hospitalization. (Ex. 9, p. 1.) Ultimately, it was determined, as all the experts in this litigation agreed, that the cause for her paralysis and other symptoms was a spinal cord stroke. Due to continuous mechanical ventilation throughout her stay, Valeria understandably experienced significant anxiety. (Id. at 5.) As a result, she was started on anti-anxiety medication. (Id.) Valeria was hospitalized until August 7, 2008, when she was transferred to an inpatient rehabilitation center. 8 (Ex. 9, p. 5; Ex. 20, p. 820.) Valeria was an inpatient at the Rehabilitation Institute of Chicago from August 7, 2008, through December 16, 2008. (Ex. 11, p. 30.) During her stay, she remained ventilator- dependent, and experienced headaches, anxiety, and spasticity. (Id.) Valeria’s physical abilities did not improve during rehabilitation, and she required total assistance for mobility and all activities of daily living at the time of discharge. (Id. at 30-32.) She was also noted to have cognitive communication deficits, severe dysphagia and dysarthria, and aphonia as a result of her ventilator dependence. (Id. at 32.) During discharge from inpatient rehabilitation, Valeria returned home and was cared for by her mother and a home health nurse. (Ex. 5, p. 4.) On January 22, 2009, her family reported that the transition home had gone well, and that Valeria would soon start home-based tutoring for school. (Id.) On February 19, 2009, Valeria was evaluated at Rush Medical Center, and it was reported that she was starting to feel sensation in her extremities. (Ex. 13, p. 6.) On March 23, 2009, during a neurological evaluation, Valeria exhibited some voluntary movement in her right index finger and left thumb, and again reported a subjective increase in sensation in her extremities. (Ex. 9, p. 4.) Despite these improvements, Valeria is still dependent on a full-time ventilator. (Id.) Although Valeria is still dependent on a wheelchair and ventilator, at the time of the evidentiary hearing she was completing her senior year of high school, and was optimistic about attending college in the fall. (Tr. 5-6.) 8 During her hospitalization, Valeria developed complications, including haemophilus influenza and streptococcus pneumonia. (Ex. 20, p. 4.) She also had a persistent yeast infection, a positive klebsiella titer, and a positive enterobacter urine culture. (Id.) These conditions lengthened her hospital stay at Rush. 6 B. Procedural History The petition was filed on July 29, 2010, and the case was assigned to my docket. Petitioner submitted an expert report and medical records, as Exhibits 1-15, on September 17, 2010. Respondent filed expert reports in December 2010 and May 2011. Status conferences were held in January and June of 2011, and an evidentiary hearing was scheduled for January 31, 2012. At the evidentiary hearing, Petitioner relied on the testimony of one expert witness, while Respondent relied on two expert witnesses. At the conclusion of the hearing, Petitioner’s counsel requested that the parties file post-hearing briefs. The last of the post-hearing briefs has been filed, so that the case is ripe for a ruling concerning the issue of whether Petitioner has met her burden of demonstrating that her injury was, more probably than not, caused by her HPV vaccination. III ISSUE TO BE DECIDED In this case, Petitioner seeks a Program award, contending that she suffered a stroke that was “caused-in-fact” by her HPV vaccination received on June 27, 2008. After careful consideration, I conclude that Petitioner has failed to demonstrate vaccine causation of her injury. 9 Petitioner’s theory of the case, as asserted by her expert, Dr. Douglas Kerr, may be briefly summarized as follows. As all of the three testifying experts agree, Valeria experienced a spinal cord stroke, also known as a spinal cord “infarct” or spinal cord “infarction,” shortly after her second HPV vaccination, which she received on June 27, 2008. In a spinal cord stroke, spinal cord tissue suffers a permanent injury due to lack of oxygen. As also agreed by all the testifying experts, Valeria’s stroke was caused by a blood clot, also known as a “thrombus,” which became lodged in a spinal blood vessel, obstructing the oxygen flow and leading to the spinal cord injury. (The occurrence of a blood clot causing damage to body tissue is also described in the record of this case as a “thrombosis” or a “thromboembolic event.”) The experts in this case differ as to what caused the blood clot to form. Dr. Kerr, for reasons to be detailed below, testified that Valeria’s HPV vaccination caused the formation of the blood clot. Respondent’s two experts, Dr. Peter Bingham, and Dr. Joan Gill, on the other hand, find it improbable that Valeria’s HPV vaccination had anything to do with the formation of the blood clot. They do not claim to know what caused the clot, but note that the cause of most spinal cord strokes is unknown, and argue that there is no good evidence to support either the proposition that an HPV vaccination could cause such a blood clot in general, or that it did cause a blood clot in Valeria. 9 Petitioner has the burden of demonstrating the facts necessary for entitlement to an award by a “preponderance of the evidence.” §300aa-13(a)(1)(A). Under that standard, the existence of a fact must be shown to be “more probable than its nonexistence.” In re Winship, 397 U.S. 35 8, 371 (1970) (Harlan, J., concurring). 7 After carefully considering all of the evidence in the record, I must reject Petitioner’s claim that her stroke was caused by her HPV vaccination. There are several reasons for this ultimate conclusion, which I will discuss separately in the pages below. IV SUMMARY OF EXPERT WITNESSES’ CREDENTIALS AND OPINIONS A. Petitioner’s expert Dr. Douglas Kerr 1. Qualifications Dr. Douglas Kerr received a degree in biology from Princeton University in 1988, and graduated from Thomas Jefferson University in 1995 with a medical degree and a Ph.D. in biochemistry and molecular biology. He completed a one-year residency in the Department of Internal Medicine at the Graduate Hospital in Philadelphia in 1997, followed by a neurology residency at The Johns Hopkins Hospital from 1996 to 1999. Dr. Kerr is certified by the American Board of Psychiatry and Neurology. From 1999 until 2005, he served as an Assistant Professor at The Johns Hopkins School of Medicine in the Department of Neurology, as well as The Johns Hopkins School of Public Health in the Department of Molecular Microbiology and Immunology. Thereafter Dr. Kerr taught as an Associate Professor in both departments until 2010. He was also an Associate Professor in the Department of Cellular and Molecular Medicine from 2006 until 2010. In 1999, Dr. Kerr founded the Johns Hopkins Transverse Myelopathy Center, for which he served as the Director until 2010. Dr. Kerr became the Director for Neurodegeneration at the biotechnology company Biogen-Idec in 2010, a position that he continues to hold. He has published more than 100 professional abstracts, presentations and papers. (Ex. 17 pp. 1-21; Tr. 8-25.) 10 2. Summary of opinion of Dr. Kerr As noted above, Dr. Kerr testified that the blood clot that caused Valeria’s stroke was a result of the HPV vaccination that Valeria received the day prior to her injury. (Tr. 32.) Dr. Kerr testified that Valeria had a genetic predisposition making her susceptible to blood clotting, involving multiple genes, and that “genetic loading” conferred a risk of adverse vaccine response. (Tr. 33.) Dr. Kerr asserted that Valeria’s first HPV vaccination, which she received on April 28, 2008, sensitized Valeria’s immune system, and that the second dose, received on June 27 of that same 10 Dr. Kerr left Johns Hopkins after the institution determined that he had engaged in professional and research misconduct. (Tr. 19-20.) Dr. Kerr testified, on the other hand, that the action by Johns Hopkins was unwarranted. (Tr. 25-29.) I have reached no conclusion whatsoever about this issue, and it has played no role in my resolution of this case. I have assumed the sincerity of Dr. Kerr’s opinion, and have evaluated his testimony in light of his prestigious academic credentials. My resolution of this case is based simply on the fact that despite Dr. Kerr’s credentials, I found that the testimony of Respondent’s experts was substantially more persuasive than that of Dr. Kerr in this case. 8 year, then elicited an “exuberant” and rapid immune response. (Tr. 41-42.) Dr. Kerr testified that one of two reactions occurred, resulting in the blood clot. His first theory was that the HPV vaccination received on June 27, 2008, created inflammation due to an exuberant immune response, thereby resulting in the blood clot that caused Valeria’s spinal cord stroke. (Tr. 35-36.) Dr. Kerr’s second theory was that the same vaccination caused platelet aggregation in Valeria’s blood, which also could have resulted in the blood clot. (Tr. 36.) (In his expert report, Dr. Kerr offered a third alternative theory, that the HPV vaccination triggered an “antiphospholipid syndrome” that led to the clot. (Ex. 22, p. 4.) He withdrew that third alternative, however, during the evidentiary hearing. (Tr. 147-48.) 11) B. Respondent’s experts 1. Dr. Peter Bingham Dr. Bingham received a B.A. from Harvard College in 1981, and a medical degree from the Columbia College of Physicians & Surgeons in 1987. From 1987 through 1992 he served as a pediatric resident, and then a neurology resident, at the Children’s Hospital of Philadelphia. Dr. Bingham was also a neurology resident at the University of Pennsylvania Hospital from 1989 until 1992. He was trained in a fellowship for neuromuscular disease at the University of Pennsylvania Hospital from 1993 through 1994. Dr. Bingham has held multiple teaching positions at the University of Pennsylvania School of Medicine, first as an Instructor of Clinical Neurology from 1990 to 1994, and then as an Assistant Professor of Neurology and Pediatrics until 2000. He concurrently worked as a collaborating scientist at the Monell Chemical Senses Center in Philadelphia from 1999 through 2000. In 2000, Dr. Bingham became a Clinical Associate Professor of Neurology and Pediatrics at the University of Vermont, a position that he currently holds, in which he treats children with neurological disorders. He has published over 50 abstracts, presentations, and papers. (Ex. B, pp. 1-6; Tr. 188-93.) 2. Dr. Joan Gill Dr. Joan Gill received her B.S. from St. Norbert College in West De Pere, Wisconsin, in 1965, and her medical degree from the Medical College of Wisconsin in 1976. She was a pediatrics intern at Milwaukee Children’s Hospital in the Medical College of Wisconsin from 1976 to 1977, where she also served a pediatric residency from 1977 until 1979. Dr. Gill further 11 Concerning that third theory, Dr. Kerr wrote as follows: The term antiphospholipid syndrome describes an autoantibody-induced hypercoagulable state, whose hallmarks are recurrent thrombosis. Research shows the central role of endothelial cells, monocytes, platelets, and complement in induction of thrombosis in antiphospholipid syndrome and that vaccines may contribute to the development or activation of antiphospholipid antibodies resulting in thrombosis. * * * Thus several investigators have noted that vaccinations can trigger the generation and/or activation of antiphospholipids that interact with blood vessel inflammation and platelet aggregation to induce thrombosis. (Ex. 22, p. 4.) 9 specialized in pediatric hematology and oncology through a fellowship at the Medical College of Wisconsin and the Blood Center of Southeastern Wisconsin from 1978 to 1981. She is board-certified in both Pediatrics and Pediatric Hematology/Oncology. Dr. Gill has served in multiple faculty positions at the Medical College of Wisconsin, beginning as a Clinical Instructor of Pediatrics from 1981 to 1982. She became an Assistant Professor of Pediatrics in 1982, an Associate Professor of Pediatrics in 1988, and a Professor of Pediatrics in 1994, a position that she still holds. Additionally, Dr. Gill has served at the Medical College of Wisconsin as a Professor of Medicine since 2002, and as a Professor of Pollution Health-Epidemiology since 2009. She presently holds a position as an Investigator at the Blood Center of Southeastern Wisconsin. Her medical practice focuses on blood disorders in children, in which she commonly treats children with genetic predispositions for bleeding and clotting disorders, as well as children with immune-related blood disorders. (Tr. 124-26.) Within her field of expertise, Dr. Gill has published more than 80 professional articles, and has presented over 80 lectures. (Ex. J, pp 2-42; Tr. 123-28.) 3. Summary of opinions of Respondent’s experts Dr. Bingham agreed with Dr. Kerr’s general conclusion that Valeria suffered an infarction of her spinal cord as a result of a blood clot. (Tr. 194.) However, Dr. Bingham disagreed with Dr. Kerr’s proposed theories of vaccine-causation. Dr. Bingham testified that Valeria’s HPV vaccination did not cause a blood clot by means of inflammation, because Valeria’s clinical tests showed no evidence of inflammation. (Tr. 196, 199-200.) He further testified that there exists no established association between the HPV vaccination and spinal cord infarction, nor is that vaccine known to be a probable cause of blood clots. (Tr. 200, 216.) He opined that it is not probable that Valeria’s HPV vaccination had any causal connection to her stroke. (Tr. 195, 214, 216.) Dr. Gill testified that although Valeria suffered a spinal cord infarction, Valeria’s MTHFR gene mutation was not a contributing factor. (Tr. 138.) She also disagreed with Dr. Kerr’s conclusion that the HPV vaccine caused inflammation that resulted in a blood clot. (Tr. 138-50, 154.) Dr. Gill stated that Valeria’s lab results did not show any evidence of inflammation (Tr. 140, 142-46, 177), or platelet aggregation (Tr. 149-50). She additionally noted that a clotting response to the vaccination, produced by inflammation, would have taken at least four days after vaccination to develop, whereas Valeria suffered the onset of her stroke symptoms approximately one day post-vaccine. (Tr. 139-40, 179-80.) V DR. KERR FAILED TO DEMONSTRATE THAT A COMBINATION OF GENETIC FACTORS MADE VALERIA SUSCEPTIBLE TO BLOOD CLOTTING OR STROKES Dr. Kerr stressed that both of his causation theories are based on the assumption that Valeria must have had a “genetic predisposition” that caused her to be susceptible to such an unusual reaction to the HPV vaccine, which vaccine he acknowledged to be “very safe” in general, and which is routinely administered without any adverse consequences. (Tr. 33; Ex. 22, p. 1.) He testified that the assumption of such a genetic predisposition is “absolutely critical” to his 10 causation theories. (Tr. 33.) He explained that such a genetic predisposition would require a combination of several genes--“six or seven or maybe 10 genes.” (Tr. 33; see also Tr. 72-73.) However, Dr. Kerr acknowledged that he did not know what that combination of genes might be. (Tr. 74.) In the final analysis, I conclude that Dr. Kerr was engaging in mere speculation or guesswork in concluding that Valeria must have had such a cluster of genes. Thus, this part of his theory, which he himself claimed as “absolutely critical” to his overall theories (Tr. 33), has not been shown to be probable. In this regard, it should be noted that, as all of the testifying experts agree, Valeria does have a particular mutation in the portion of her genetic code known as “MTHFR.” (MTHFR stands for methylenetetrahydrofolate reductase--Tr. 132.) In an earlier written expert report, Dr. Kerr specifically asserted, without qualification, that Valeria’s “mutation in the MTHFR gene” gives her a “genetic predisposition to thrombosis.” (Ex. 22, p. 1.) During the evidentiary hearing, however, Dr. Kerr backed off quickly from that assertion, acknowledging that Valeria’s MTHFR mutation “alone” could not make her susceptible to blood clotting and stroke. (Tr. 74.) While asserting that Valeria must have some unknown “cluster” of genes that made her susceptible, Dr. Kerr acknowledged that her MTHFR mutation may not have been any part of that unspecified gene cluster. (Tr. 73-74.) He stated that the MTHFR mutation “may” have been “one of many factors genetically” that contributed to her alleged predisposition. (Tr. 74, lines 17-19.) 12 In contrast, the only hematologist (blood specialist) to testify, 13 Dr. Gill, testified that Valeria’s particular type of MTHFR mutation, known as the MTHFR - 1298 mutation, does not cause blood clotting. 14 (Tr. 132-38.) Dr. Gill explained that conclusion in detail, and pointed to a medical study supporting that conclusion. (Tr. 135-137; Ex. K.) Dr. Kerr, in contrast, did not point to any problems with the reasoning of Dr. Gill described in the prior paragraph. Instead, he pointed to two other medical articles to support the proposition that MTHFR mutations might cause an increased risk of clotting. (Tr. 50-51; see Exs. 27 and 45.) However, on cross examination, Dr. Kerr admitted that those two articles did not deal with the specific type of MTHFR mutation which Valeria has, the MTHFR - 1298 mutation. (Tr. 112-13.) 12 Moreover, respondent’s expert, Dr. Gill, explained that testing of Valeria did not reveal any other genetic mutations beyond her MTHFR mutation. (Tr. 149.) 13 Dr. Kerr acknowledged that if in his medical practice he had a patient with a spinal cord clot, he would consult with a hematologist or oncologist to determine the cause of the clot. (Tr. 23.) 14 In one of petitioner’s post-hearing briefs, filed on August 27, 2012, petitioner’s counsel states that Valeria’s MTHFR-1298 mutation “is associated as a risk factor for venous thrombosis--a fact acknowledged by Respondent’s expert. Tr. at 171.” (Brief at p. 3, emphasis in original.) But this grossly misrepresents what Dr. Gill said. Dr. Gill, in fact, stated clearly that while some types of MTHFR mutations might be a risk factor, the MTHFR-1298 mutation, which Valeria has, is not a risk factor for any type of blood clotting or stroke. (Tr. 136-38.) Unfortunately, this misrepresentation of an expert’s testimony reflects poorly on petitioner’s counsel. 11 Moreover, Dr. Gill explained that the mechanism by which some types of MTHFR mutations might increase the risk of clotting would be by increasing “homocysteine” levels (Tr. 132), but Valeria’s testing indicated that Valeria did not have increased homocysteine levels (Tr. 137). In sum, I find that Dr. Kerr totally failed to establish a factor what he himself called a “critical factor” in his analysis--that Valeria had some type of genetic predisposition that made her susceptible to have blood clots. In this regard, I reiterate that Dr. Kerr first asserted, without qualification (Ex. 22, p. 1), that Valeria’s MTHFR - 1298 mutation made her susceptible to blood clotting; but later, upon being contradicted by a blood specialist concerning this point, he abandoned that assertion. Instead, he could do no more than propose that Valeria might have had a cluster of several different genes that made her susceptible, but could not even propose what any of those genes might have been. In short, in my view, this “critical factor” of Dr. Kerr’s appears to be no more than sheer speculation. This speculation was also firmly rebutted by Dr. Gill’s testimony, as explained above. Accordingly, both of Dr. Kerr’s causation theories, which were both based on this flawed assumption of genetic susceptibility, have not been established as probable, for this reason alone. VI DR. KERR FAILED TO DEMONSTRATE THAT VALERIA’S STROKE WAS VENOUS RATHER THAN ARTERIAL Dr. Kerr also based his causation theories on the assertion that Valeria’s spinal cord stroke was venous (i.e., in a vein) rather than arterial (i.e., in an artery). (E.g., Tr. 238-40.) However, the evidence indicates that Valeria’s stroke was likely arterial, not venous. First, concerning this issue, I note that Dr. Kerr simply gave very little explanation concerning why he believes that Valeria’s stroke was venous rather than arterial. He failed to make a coherent argument on that issue. (See Tr. 238-40.) Dr. Gill, on the other hand, explained the difference in presentation between an arterial stroke and a venous stroke. (Tr. 129-30.) She explained that an arterial stroke would cause a sudden, dramatic onset of symptoms, while a venous stroke would not. (Id.) And Valeria’s own sudden presentation on June 28, 2008, seems to fit Dr. Gill’s description of an arterial stroke, rather than a venous stroke. Similarly, a medical article filed by respondent, the Novy article (Ex. F), supports Dr. Gill’s testimony on this point. That article studied 27 victims of arterial spinal cord strokes, all of whom suffered an acute, sudden onset of neurological symptoms, with symptoms proceeding from non-existent to very serious “usually within about 2 minutes” but always within “a few hours.” (Ex. F, p. 1115. The medical histories of those 27 arterial spinal cord stroke victims ) seem similar to that of Valeria. In contrast, the Novy article stated that in the case of a venous 12 spinal cord stroke, the victim has a “subacute progressive course” (i.e., a slower, less dramatic course) of symptoms. (Id. at p. 1119, first column.) Further, Dr. Gill explained how the results of a “D-dimer” test on Valeria make it “very, very unlikely” that Valeria’s stroke was venous. (Tr. 164.) Dr. Gill, accordingly, opined that Valeria’s stroke was likely arterial rather than venous. (Tr. 131, 170-71.) Dr. Bingham stated the same opinion. (Tr. 194.) Comparing the explanation of Dr. Gill and the Novy article described above, to the largely unexplained opinion of Dr. Kerr on this point, I find it likely that Valeria’s stroke was arterial, not venous. This is another point that militates in favor of rejecting Dr. Kerr’s causation opinion in this case, which is based upon the assumption that Valeria’s stroke was venous. VII DR. KERR FAILED TO DEMONSTRATE THAT THE HPV VACCINATION CAUSED INFLAMMATION LEADING TO VALERIA’S BLOOD CLOT A. Dr. Kerr’s “inflammation” theory in general As noted above, Dr. Kerr alternatively presented two different theories as to how Valeria’s HPV vaccination may have contributed to Valeria’s blood clot that caused her stroke. First, he theorized that the HPV vaccination created inflammation, thereby resulting in the blood clot that caused Valeria’s stroke. (Tr. 35-36.) Dr. Kerr’s second theory was that the same vaccination caused platelet aggregation, again resulting in the blood clot. (Tr. 36.) As to Dr. Kerr’s inflammation theory, his presentation failed to show that it is probable either that the HPV vaccination in general can contribute to the type of inflammation that would cause a blood clot/stroke, or that Valeria’s HPV vaccination did contribute to her blood clot by causing inflammation. In support of his theory that Valeria’s HPV vaccination contributed to her stroke by causing inflammation, Dr. Kerr asserted that the vaccination caused “massive microglial activation in Valeria’s central nervous system,” which caused the inflammation. (Tr. 242-43.) But Dr. Kerr later acknowledged, however, that he was unaware whether the HPV vaccine even contained any agents that can cause microglial activation. (Tr. 248-49.) Dr. Kerr theorized that Valeria had systemic inflammation caused by the vaccination. He opined that such systemic inflammation caused a series of symptoms, and that those symptoms were “part of a systemic inflammatory response.” (Tr. 41, lines 7-8, emphasis added.) He stated that Valeria’s arm pain was “the first manifestation of systemic inflammation” (Tr. 244, lines 3-4, emphasis added), and reiterated that she suffered from “systemic inflammation” (Tr. 246, lines 8-9, emphasis added). 13 Dr. Gill, however, provided persuasive arguments against Dr. Kerr’s inflammation theory. Dr. Gill explained that a number of different tests done on Valeria demonstrated that she did not have systemic inflammation at the time that she developed the blood clot. (Tr. 140, 142-46, 177.) Dr. Bingham also interpreted the testing of Valeria as showing no signs of inflammation. (Tr. 199-200.) Dr. Kerr also asserted that the HPV vaccine caused inflammation in Valeria’s central nervous system, but Dr. Bingham explained that testing of her spinal cord fluid did not show inflammation. (Tr. 195, 199; Ex. 20, p. 100.) Dr. Gill also testified that systemic inflammation caused by a vaccination, even by a second HPV vaccination when Valeria had previously received an initial dose of that vaccine, would take at least four days to develop, whereas Valeria’s stroke symptoms began only one day post-vaccine. (Tr. 138-40, 179-80.) Dr. Kerr argued that the one-day time period was sufficient for a second vaccination to cause very rapid inflammation, but Dr. Gill’s testimony was supported by the notes of Valeria’s actual treating physicians at the time. For example, one of Valeria’s treating neurologists, Dr. Tilwalli, expressed the opinion that due to the onset of stroke symptoms just one day after the HPV vaccination, the stroke could not have been the result of an inflammatory response to that vaccine. (Ex. 20, p. 9.) And another neurologist who treated Valeria, Dr. Stefofski, also indicated that the cause of the stroke could not have been “immune mediated inflammatory,” adding that the timing of Valeria’s stroke symptoms was “definitely too soon for Gardasil” to have been the cause. (Ex. 20, p. 488.) (Gardasil is the brand name of the HPV vaccine that Valeria received.) I found that Dr. Gill’s testimony on this point, as supported by the notations of both Dr. Tilwalli and Dr. Stefofski, was substantially more persuasive than that of Dr. Kerr. In this regard, Dr. Kerr, to be sure, did point out that any vaccination, in order to produce the immunity that is its purpose, does produce some type of inflammation in the vaccinee. (Tr. 241-42.) Dr. Kerr argued that one part of the body’s immune system, the “innate” immune system, would produce inflammation soon after vaccination (Tr. 42-43), and he seemed to suggest that such inflammation, produced by the innate immune system, resulted in Valeria’s blood clot. But Dr. Gill testified that she saw no likelihood that the innate immune system could produce localized inflammation causing a blood clot, in the absence of systemic inflammation that would have shown up on the testing of Valeria. (Tr. 140.) Dr. Gill also testified that she knew of no medical literature supporting Dr. Kerr’s opinion that the HPV vaccine could, in general, cause the type of inflammation that might cause a blood clot. (Tr. 146.) And Dr. Kerr, on cross-examination, acknowledged that he had not submitted any literature showing that HPV vaccination could cause the type of inflammation that could lead to a stroke. (Tr. 79.) B. Dr. Kerr’s reliance on medical literature concerning inflammation In support of his inflammation theory, Dr. Kerr relied upon certain medical literature. He relied upon medical articles by Petersdorf and Beeson (Ex. 52) and Ghose (Ex. 50), as well as letters to medical journals written by Perez (Ex. 29) and Finsterer (Ex. 39). (See Ex. 22, p. 2; Tr. 14 47-49.) According to Dr. Kerr, these papers “noted a link between vaccinations and the subsequent development of blood vessel inflammation and thrombosis,” thereby suggesting “that vaccines may cause immune activation which triggers thrombosis.” (Ex. 22, p. 2.) Respondent’s experts, however, argued that those four papers do not offer significant support for the general proposition that vaccines can cause the type of serious inflammation that could lead to a stroke. Significantly, as I analyze those four papers, only one of the patients described in those four papers suffered a stroke, and none of them received an HPV vaccination. Instead, a few of the described patients suffered a different condition, known as “giant cell arteritis,” after influenza vaccination. (Exs. 29, 39, 50, 52.) Giant cell arteritis, Dr. Gill explained, is a condition in which the victims suffer a certain type of inflammation of the temporal artery, involving strong evidence of “systemic immune activation.” (Tr. 153.) Thus, those articles do offer at least some support for the proposition that the influenza vaccination might lead to systemic immune activation and the type of severe inflammation involved in giant cell arteritis. Valeria, however, received the HPV vaccination, not an influenza vaccination. Moreover, there was no evidence in Valeria either of giant cell arteritis or of systemic immune activation. (See discussion at pp. 13-14, above.) Thus, for that reason alone, the four papers cited by Dr. Kerr, which describe “giant cell arteritis” after influenza vaccination, offer scant support for the very different proposition that the HPV vaccination can cause the type of inflammation that could lead to a stroke. Moreover, Dr. Gill also explained that if Valeria had experienced systemic immune activation, as is involved in giant cell arteritis, her testing results would have been quite different than they actually were, concerning several different tests. (Tr. 153-54.) Dr. Kerr did not attempt to refute that point. Accordingly, Dr. Kerr’s reliance on Exs. 52, 50, 29, and 39 again did not constitute persuasive evidence for his theory that HPV vaccination can contribute in general to the causation of strokes by causing inflammation. VIII DR. KERR FAILED TO DEMONSTRATE THAT THE HPV VACCINATION CAUSED PLATELET AGGREGATION LEADING TO VALERIA’S BLOOD CLOT As noted above, Dr. Kerr’s second theory was that the HPV vaccination caused platelet aggregation resulting in Valeria’s blood clot. (Tr. 36.) “Platelet aggregation” means that the platelets in the blood become “sticky,” and become attached to each other. (Tr. 149.) However, Dr. Gill, the only testifying hematologist (blood specialist), testified that she saw no evidence of platelet aggregation in Valeria’s medical records. (Tr. 149.) She noted that 15 persons who develop platelet aggregation 15 also develop low platelet counts (also known as thrombocytopenia), because when “platelets are clumping together, they get removed from circulation” (Tr. 149-50); Valeria’s blood testing, however, indicated a normal platelet count (Tr. 150; Ex. 8, p. 15). I found Dr. Gill’s explanation concerning this point to be persuasive, in part because of her superior credentials, as a hematologist, in this area concerning blood components; and in part because the testing results in the record support her testimony. Concerning this issue of platelet aggregation, Dr. Kerr in his expert report relied upon several medical articles. (Ex. 22, pp. 2-4.) Dr. Gill, however, persuasively explained why Dr. Kerr’s reliance in this regard was misplaced. First, Dr. Kerr relied on Ex. 40, an article about five Finnish conscripts who died after vaccinations, during the years 1948-72. (Ex. 22, p. 3; Ex. 40, p. 1414.) It is unclear why Dr. Kerr relied upon Ex. 40, however. None of the five victims received a HPV vaccination. (Tr. 82; Ex. 40, p. 1414.) The article did not reveal the cause of death of the victims--it did not say that any had suffered strokes. (Tr. 83; Ex. 40, p. 1414.) None of the victims were said to have had genetic anomalies, which Dr. Kerr said was a “critical factor” in Valeria. (Tr. 84; Ex. 40.) Most importantly, the article did not even mention platelet aggregation. For all those reasons, I cannot find that Ex. 40 offers any support to Dr. Kerr’s theory that Valeria’s HPV vaccination caused platelet aggregation leading to her blood clot. Dr. Kerr also seemed to rely, in his written expert report, on several other articles to support his platelet aggregation theory. (Ex. 22, pp. 3-4.) Some of those articles were later filed as Ex. 33, a CDC article; Ex. 24, the Baker article; 16 Ex. 37, the Rivard letter; and Ex. 47, the Granel article. 17 However, in his oral testimony on direct examination in this case, Dr. Kerr made 15 I note that in the hearing transcript, and several places the transcript states “platelet activation;” however, I believe, from the context, that the witness said “platelet aggregation.” See Tr. 151, lines 5 and 16; Tr. 152, line 23. 16 Regarding the Baker article, Dr. Kerr wrote: [I]nvestigators studied thirty-two army apprentices aged 16 and 17 years, undergoing standard immunization, and found that the heparin thrombin clotting times were significantly reduced after vaccination, indicating the development of a temporary hypercoagulable state due to platelet aggregation. This hypercoagulable state was apparent within 24 hours of the vaccination, a finding of some relevance to Ms. Flores, since her thrombosis occurred quickly after her vaccination as well. This transient hypercoagulable state was not observed in elderly individuals given vaccinations and returned to normal by 14 days after vaccination. Interestingly, the subjects of this study were 16 and 17 years old, quite close to the age of Ms. Flores when she received her Gardasil vaccine. (Ex. 22, p. 3.) 17 In the transcript, an article cited in Dr. Kerr’s report, by Kacerik, is misspelled as “Casterick.” (Tr. 101.) The article, however, was never filed into the record of this case. (Tr. 101.) 16 no reference to those articles. (See Tr. 8-55.) And most of those articles, like Ex. 40, do not even mention platelet aggregation. In contrast, Dr. Gill did comment upon two of those articles cited by Dr. Kerr--the two articles (Ex. 24 and Ex. 37) that did mention platelet aggregation. Dr. Gill argued persuasively that those articles do not support Dr. Kerr’s platelet aggregation theory in this case. (Tr. 150-53.) There is no need for me to repeat here Dr. Gill’s discussion of these articles. It is sufficient to say that Dr. Gill convincingly explained why those articles do not offer support to Dr. Kerr’s platelet aggregation theory. In contrast, Dr. Kerr in his rebuttal testimony (Tr. 239-250) made no effort to explain why Dr. Gill’s analysis of Ex. 40, Ex. 24, or Ex. 37 was flawed in any way. In short, Dr. Kerr’s presentation fell far short of demonstrating that it is probable that Valeria even suffered any platelet aggregation, much less that platelet aggregation contributed to her blood clot or stroke. IX DR. KERR’S RELIANCE UPON THE SLADE ARTICLE Dr. Kerr also seemed to rely heavily on the Slade article, which he offered to support the general principle that HPV vaccines raise the risk of stroke in a vaccinee. (See Ex. 22, pp. 4-5; Tr. 43-46.) (The Slade article is filed, in the record of this case, as both Ex. 34 and as Ex. L.) After studying that article and the experts’ discussion of it, however, I conclude that it does not offer significant support for Dr. Kerr’s general proposition that the HPV vaccine can contribute to causing strokes. The Slade article analyzed reports to the “VAERS” system concerning the HPV vaccine. VAERS, the Vaccine Adverse Event Reporting System, was created to collect data concerning incidents in which a person suffers an adverse health event soon after receiving a vaccination. (42 U.S.C. §300aa-25(b)(1).) Under the VAERS system, vaccine administrators and manufacturers are required to report any adverse health event suffered by a person soon after a vaccination, without regard to whether there is reason to believe that the vaccination caused the injury. (Id.) VAERS reports, however, can be submitted by anyone, whether a medical or health official or not. (Id.) The VAERS system, therefore, is useful chiefly as a way of sending a “signal” or “alert” to the medical community that there is a possibility that a vaccine might be causing a certain condition or disease. In other words, if a number of VAERS reports are filed describing a certain type of condition as occurring after a certain type of vaccine, the medical community might decide to take steps to investigate whether there might be a causal connection between the vaccine and the condition. (Tr. 200-02; see also Ex. O, p. 1, which states that the “primary function of VAERS is to detect early warning signals and generate hypotheses about possible new vaccine adverse events.”) 17 However, an analysis of VAERS reports by themselves is not very useful as evidence of whether a causal connection does exist. That is because, among other reasons, the VAERS system does not provide information as to the “background rate” of a certain condition in a certain population. As a hypothetical example, suppose that Condition A is known to occur in one-year-olds at a rate of about 10 cases per million one-year-olds, for unknown reasons. In that situation, if VAERS reports show a few cases of Condition A occurring in one-year-olds shortly after receiving Vaccine B, when in fact millions of one-year-olds are routinely receiving Vaccine B every year, those VAERS reports would not shed any significant light on the question of whether Vaccine B causes Condition A. If, on the other hand, the VAERS system were to receive hundreds of reports of Condition A after Vaccine B, and Vaccine B is a new type of vaccine, then the medical community would likely take that as an “alert” to set up systematic studies testing whether in fact there are proportionally more occurrences of Condition A in one-year-olds receiving Vaccine B than would be the case in one-year-olds who do not receive Vaccine B. Only such systematic studies, rigorously comparing populations who do and do not receive a certain vaccine, can yield significant evidence as to whether Condition A is associated with Vaccine B. In contrast, any analysis of VAERS reports themselves can only yield a rough “signal” as to whether systematic studies should be done. Indeed, in the Slade article itself, the authors caution that, for the reasons explained above, “VAERS data must be interpreted cautiously, and cannot generally be used to infer causal associations.” (Ex. L, pp. 756-57.) And numerous judges and special masters of this court have explained that VAERS data is of very limited utility in resolving causation issues, and cannot offer strong support to a causation conclusion. 18 With reference to the specifics of the Slade article, Dr. Kerr stated that HPV vaccines (“Gardasil”) “have been associated with disproportionately high reporting of thromboembolic events.” (Ex. 22, p. 4.) Dr. Kerr relies on this allegedly “disproportionately high” reporting of strokes after HPV vaccination in the Slade article, as evidence that the HPV vaccine can contribute, in general, to the causation of strokes. (Ex. 16, p. 5; Ex. 22, pp. 4-5; Tr. 43-45, 79-80.) 19 18 See, e.g., Analla v. HHS, 70 Fed. Cl. 552, 558 (2006) (affirming the special master’s conclusion that certain VAERS reports were not sufficient to justify a causation-in-fact finding); Ryman v. HHS, 65 Fed. Cl. 35, 40 (2005) (affirming special master’s election not to accord substantial weight to VAERS data); Capizzano v. HHS, 63 Fed. Cl. 227, 231 (2004) (affirming special master’s statement that VAERS data has limited value), vacated on other grounds, 440 F. 3d 1317 (Fed. Cir. 2006); Manville v. HHS, 63 Fed. Cl. 482, 494 (2004) (not error for the special master to discount VAERS reports); Nance v. HHS, No. 06-730V, 2010 WL 3291896 at *9 (Fed. Cl. Sp. Mstr. July 30, 2010) (indicating that reliance on VAERS data was not persuasive). 19 Dr. Kerr noted that the Slade article-- concluded that “there was disproportional reporting of syncope and venous thromboembolic events….the significance of these findings must be tempered with the limitations (possibly underreporting) of a passive reporting system.” (Ex. 22, pp. 4-5): Dr. Kerr proposed that the significance of Dr. Slade’s parenthetical is 18 However, evidence provided by the respondent persuasively indicated that the Slade article does not provide significant evidence that the HPV vaccine adds to the risk of the type of stroke that Valeria suffered. For example, Dr. Gill analyzed the Slade article, and concluded that it did not support Dr. Kerr’s analysis. (Tr. 154-157; Ex. I, pp. 2-3.) The Slade article analyzed VAERS reports filed during the first 2 ½ years during which the HPV vaccination was administered in the U.S., a period during which about 23 million doses of the HPV vaccination were distributed. (Ex. L, pp. 750-51.) Dr. Gill noted that during that period, there were 31 strokes or stroke-like events reported to VAERS after HPV vaccination. (Tr. 155; Ex. L, p. 754, third column.) However, Dr. Gill noted, none of those 31 events were similar to the stroke suffered by Valeria--that is, none were spinal cord strokes. (Tr. 155.) Further, of the victims of those 31 events, 90% had known risk factors for stroke. (Tr. 156.) That 90% figure is confirmed in the Slade article itself, which notes that “twenty-eight of the 31 cases (90%) had a known risk factor” for stroke. (Ex. L, p. 754, third column.) Also, Dr. Gill noted that in the 30 events which occurred after HPV vaccination alone (i.e., no other vaccination was administered at the same time as the HPV vaccine), the average (“mean”) time between vaccination and the event was 41.5 days. (Tr. 157; Ex. L, p. 754, third column.) This timing factor in Slade is in sharp contrast to Valeria’s stroke, the first symptoms of which occurred on the first day after her HPV vaccination. Dr. Bingham, too, discussed the Slade article (Tr. 206-209), and opined that the Slade article does not support the general theory that the HPV vaccine increases the risk of stroke (Tr. 209). Like Dr. Gill, Dr. Bingham also noted that the average time of the stroke-like events described in Slade (about 42 days) was a far cry from the one-day onset in Valeria’s case. (Tr. 208.) In addition, while all of the stroke-like events described in Slade were venous events, Valeria’s stroke was likely an arterial stroke. (See discussion at pp. 12-13 above). 20 that there may be still greater reason to accept causation than the data from a passive reporting system might suggest. (Ex. 22, p. 5.) 20 Dr. Kerr also pointed to the fact that the Slade article indicates the possibility of an increased risk of “syncope,” or fainting, after HPV vaccination. He asserted that Valeria suffered from syncope, and seemed to argue that such circumstance would add to a likelihood that HPV vaccination contributed to Valeria’s stroke. (See Ex. 22, p. 5; Tr. 45.) However, Dr. Kerr did not explain why he believes that syncope can contribute to causing a spinal cord stroke. Moreover, a close review of the Slade article indicates that none of the syncope events described in Slade seem to have been associated with a stroke. The syncope events described in Slade were mostly classified as “nonserious” events. (Ex. L, p. 753, first column.) (See Ex. N, p. 8283, noting that adolescents receiving vaccines faint fairly frequently after vaccination.) The “serious” syncope events seem to have been when a vaccinee fell after fainting, suffering a head injury as a result of the fall. (Ex. L, p. 753, first column.) Valeria, however, did not suffer from any falling event produced by fainting. To be sure, Valeria’s medical records do indicate that in the ambulance, she may have lost consciousness, which might qualify as a case of syncope. (See Tr. 55.) But Dr. Kerr did not explain how that circumstance supports a conclusion that Valeria’s stroke was caused by her HPV vaccination. 19 Accordingly, after full analysis of the Slade article, I do not find that it provides significant support to the proposition that Valeria’s HPV vaccination contributed to causing her stroke. X THE MEDICAL LITERATURE ANALYZING ADVERSE EVENTS REPORTED AFTER HPV VACCINATION ADDS REASON TO DOUBT DR. KERR’S THEORY The Vaccine Act case law makes it clear that in order to show causation under the Act’s “more probable than not” standard, a petitioner need not supply epidemiologic or other medical literature supporting causation. (See, e.g., Capizzano v. HHS, 440 F. 3d 1317, 1325 (Fed. Cl. 2006); Andreu v. HHS, 569 F. 3d 1367, 1378 (Fed. Cir. 2009).) However, when epidemiologic literature concerning the vaccine in question is placed into the record of the case, the special master may give such literature weight, as appropriate, if such literature either offers support for, or tends to contradict, the petitioner’s causation theory. (See, e.g., Taylor v. HHS, 108 Fed. Cl. 807, 819-821 (Fed. Cl. 2013) (the special master did not err in considering epidemiological evidence); Andreu v. HHS, 569 F. 3d 1367, 1379 (Fed. Cir. 2009) (a special master may assess epidemiological evidence in “reaching an informed judgment as to whether a particular vaccination likely caused a particular injury.”)) In this case, certain medical literature in the record, which analyzes reports of adverse events after HPV vaccination, adds slightly to the reasons for rejecting Dr. Kerr’s causation theory. First, as noted above, the Slade article analyzed VAERS reports filed during the 2 ½ years during which the HPV vaccination was administered in the U.S., a period during which 23 million doses of the HPV vaccine were distributed. (Ex. L, pp. 750-51.) During that period, there were 31 strokes or stroke-like events reported to VAERS after HPV vaccination. (Tr. 155; Ex. L, p. 754, third column.) However, as Dr. Gill noted, none of those 31 events were similar to the stroke suffered by Valeria--that is, none were spinal cord strokes. (Tr. 155.) In addition, while all the stroke events described in Slade were venous events, Valeria’s stroke was likely an arterial stroke. (See discussion at pp. 12-13 above.) In short, the Slade article reviewed the VAERS reports for a 2 ½ year period in which the first 23 million doses of HPV vaccines were distributed in the United States. Yet no spinal cord strokes at all were reported after HPV vaccination, nor were any arterial strokes of any kind reported (while Valeria suffered an arterial, spinal cord stroke). Thus, while VAERS reports are of very limited utility in deciding causation issues, as discussed above (pp. 17-18), in my final analysis of the Slade article, I find that the article, if anything, adds some slight weight to the case against Dr. Kerr’s causation theory, rather than in favor of his theory. The record of this case also includes other epidemiologic articles directly relating to whether the HPV vaccine is statistically associated with adverse events after vaccination. 20 For example, the Gold study, an Australian study of adverse events after HPV vaccination, was also filed. (Ex. D.) During the period covered by that study, 5.8 million doses of HPV vaccine were administered in Australia, but the study did not find any reports of strokes (thrombosis) after HPV vaccination. (Ex. D; Tr. 204.) To be sure, the Gold study, as a study of adverse event reports, seems to have the same limitations as the Slade article VAERS data discussed above. However, the study’s failure to find any strokes after 5.8 million HPV doses would seem, like the Slade article itself, to add slight additional weight to the case against Dr. Kerr’s causation theory. Also filed into the record was the Gee study. (Ex. N.) In that study, the authors compared about 600,000 U.S. females, who had received HPV vaccine at ages 9 to 26, to a comparison group of young females who had not received HPV vaccine. (Ex. N, pp. 1-2.) The study found no strokes at all among the 417,000 girls aged 9-17 who received the vaccine, and only two strokes among the 113,000 vaccinated females aged 18-26. (Id. at p. 3, Table 13.) And the two strokes among the older vaccinees were judged not to indicate a statistically significant increased risk of stroke compared to non-vaccinated individuals. (Id. at p. 4, para. 3.1.) The Gee study authors also looked at the risk for “venous thromboembolism” (“VTE”) separately from the risk of “stroke.” (Ex. N, pp. 2-5.) In this regard, as noted above (pp. 12-13), the record of this case preponderates in favor of a conclusion that Valeria herself suffered an arterial stroke, not a venous thromboembolic event. However, even if one were to assume that Valeria’s stroke was venous rather than arterial, it is noteworthy that the Gee study found no increased risk even for venous thromboembolism, among vaccinated as compared to non-vaccinated individuals. (Ex. N, p. 3, Table 3.) In short, taken together, the medical literature described in this Section X of this Decision, which analyzes reports of adverse events after HPV vaccination, adds slightly to the reasons for rejecting Dr. Kerr’s causation theory. XI THE ABSENCE OF A KNOWN CAUSE FOR VALERIA’S STROKE One striking factor about this case is that Valeria’s medical records do not identify a known cause for Valeria’s stroke, nor are respondent’s two experts able to point to a likely cause. Does this absence of a known cause offer any significant support to Dr. Kerr’s theory that Valeria’s HPV vaccination contributed to provoking the stroke? I conclude that it does not. The record of this case indicates, rather, that it is common for the cause of spinal cord strokes not to be identified. For example, the Novy article (Ex. F) discusses spinal cord strokes in general, and notes that “the pathogeneses and natural history of spontaneous * * * spinal cord infarctions remain largely unknown.” (Ex. F, p. 1113.) Moreover, that study looked at 27 particular spinal cord strokes, and in 20 of those cases, no cause (“etiology”) was identified. (Ex. F, p. 1116; Tr. 198-99.) 21 Also, Dr. Bingham confirmed that in a large percentage of spinal cord strokes, no cause is identified. (Ex. A, p. 3; Tr. 196-99.) Accordingly, the lack of an identifiable cause for Valeria’s stroke does not offer any significant support to Dr. Kerr’s speculative causation theories. XII PETITIONER’S CASE FAILS THE ALTHEN TEST As noted above, in its ruling in Althen, the U.S. Court of Appeals for the Federal Circuit discussed the Acausation-in-fact@ issue in Vaccine Act cases. The court stated as follows: Concisely stated, Althen=s burden is to 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. If Althen satisfies this burden, she is Aentitled to recover unless the [government] shows, also by a preponderance of evidence, that the injury was in fact caused by factors unrelated to the vaccine.@ Althen, 418 F.3d 1274, 1278 (Fed. Cir. 2005) (citations omitted). In the pages above, of course, I have already set forth in detail my analysis in rejecting Petitioner=s Acausation-in-fact@ theory in this case. In this part of my Decision, then, I will briefly explain how that analysis fits specifically within the three parts of the Althen test, enumerated in the first sentence of the Althen excerpt set forth above. The short answer is that I find that Petitioner=s evidence in this case clearly does not satisfy any of the three parts of the Althen test. A. Application of Althen Prongs 1 and 2 to this case One interpretative issue with the Althen test concerns the relationship between the first two elements of that test. The first two prongs of the Althen test, as noted above, are that a petitioner must provide A(1) a medical theory causally connecting the vaccination and the injury,@ and A(2) a logical sequence of cause and effect showing that the vaccination was the reason for the injury.@ Initially, it is not absolutely clear how the two prongs differ from each other. That is, on their faces, each of the two prongs seems to require a demonstration of a Acausal@ connection between Athe vaccination@ and Athe injury.@ However, a number of Program opinions have concluded that these first two elements reflect the analytical distinction that has been described as the Acan cause@ vs. Adid cause@ distinction. That is, in many Program opinions issued prior to Althen involving Acausation-in-fact@ issues, special masters or judges stated that a petitioner must demonstrate (1) that the type of vaccination in question can cause the type of injury in question, and also (2) that the particular vaccination received by the specific vaccinee did cause the vaccinee=s own injury. See, e.g., Kuperus v. HHS, 2003 WL 22912885, at *8 (Fed. Cl. Spec. Mstr. Oct. 23, 2003); Helms v. HHS, 2002 WL 31441212, at *18 n.42 (Fed. Cl. Spec. Mstr. Aug. 8, 2002). Thus, a number of judges and special masters of this court have concluded that Prong 1 of Althen is the 22 Acan cause@ requirement, and Prong 2 of Althen is the Adid cause@ requirement. See, e.g., Doe 11 v. HHS, 83 Fed. Cl. 157, 172-73 (2008); Nussman v. HHS, 83 Fed. Cl. 111, 117 (2008); Banks v. HHS, 2007 WL 2296047, at *24 (Fed. Cl. Spec. Mstr. July 20, 2007); Zeller v. HHS, 2008 WL 3845155, at *25 (Fed. Cl. Spec. Mstr. July 30, 2008). And, most importantly, the Federal Circuit itself confirmed that interpretation in Pafford, ruling explicitly that the Acan it?/did it?@ test, used by the special master in that case, was equivalent to the first two prongs of the Althen test. Pafford v. HHS, 451 F.3d at 1352, 1355-56 (Fed. Cir. 2006). Thus, interpreting the first two prongs of Althen as specified in Pafford, under Prong 1 of Althen a petitioner must demonstrate that the type of vaccination in question can cause the type of condition in question; and under Prong 2 of Althen that petitioner must then demonstrate that the particular vaccination did cause the particular condition of the vaccinee in question. A few decisions of judges and special masters have discussed issues with respect to the precise interpretation of Prongs 1 and 2 of Althen. E.g., Doe 11, 83 Fed. Cl. at 173-74; Scott v. HHS, 2006 WL 2559776, at *18 (Fed. Cl. Spec. Mstr. Aug. 21, 2006); Nussman v. HHS, 2008 WL 449656, at *12-13 (Fed. Cl. Spec. Mstr. Jan. 31, 2008), aff=d, 83 Fed. Cl. 111 (2008); Fields v. HHS, 2008 WL 2222141, at *7 n.5 (Fed. Cl. Spec. Mstr. May 14, 2008). However, it is not necessary, in this case, to delve into any such potential interpretative issues, since under any reasonable interpretation of Althen, the Petitioner=s causation evidence put forward in this case could not satisfy either of the first two prongs of the Althen test. That is, as set forth in detail above, I have concluded that Petitioner has fallen far short of demonstrating either that the HPV vaccine can contribute, in general, to the causation of spinal cord strokes, or that Valeria’s HPV vaccination of June 27, 2008, did cause Valeria’s own stroke. Thus, Petitioner=s causation arguments in this case would fail under any interpretation of Althen=s Prongs 1 and 2. Moreover, there can be no doubt whatsoever that the Althen test ultimately requires that, as an overall matter, a petitioner must demonstrate that it is Amore probable than not@ that the particular vaccine was a substantial contributing factor in causing the particular injury in question. That is clear from the statute itself, which states that the elements of a petitioner=s case must be established by a Apreponderance of the evidence.@ (' 300aa-13(a)(1)(A).) And, whatever is the precise meaning of Prongs 1 and 2 of Althen, in this case the overall evidence falls far short of demonstrating that it is Amore probable than not@ that the HPV vaccine contributed to the causation of Valeria’s stroke. B. Application of Prong 3 of the Althen test to this case Since I have concluded that Petitioner has failed to satisfy either of the first two prongs of Althen, I need not determine whether Petitioner=s case satisfies the third prong. But in the interest of completeness, I will add a brief discussion of Prong 3. To be sure, a striking aspect of this case is that Valeria suffered the first symptoms of her tragic spinal cord stroke on the next day after her HPV vaccination in question; that temporal relationship would naturally cause any lay person to consider whether a causal relationship exists. However, for the reasons detailed above, the evidence in this case failed, by a large margin, to provide any reason to believe that HPV vaccinations can cause spinal cord strokes (or any type of stroke) in general, or that Valeria’s HPV vaccination did cause her own tragic stroke. 23 Moreover, as noted above, Dr. Gill testified persuasively that systemic inflammation caused by a vaccination, even by a second HPV vaccination when Valeria had previously received the first dose of that vaccine, would take at least four days to develop, whereas Valeria’s stroke symptoms began only one day post-vaccine. (Tr. 139.) Similarly, the medical records show that one of Valeria’s treating neurologists, Dr. Tilwalli, also expressed the opinion that due to the onset of stroke symptoms just one day after the HPV vaccination, the stroke could not have been the result of an inflammatory response to that vaccine. (Ex. 20, p. 9.) And another neurologist who treated Valeria, Dr. Stefofski, likewise indicated that the cause of the stroke could not have been “immune mediated inflammatory,” adding that the timing of Valeria’s stroke symptoms was “definitely too soon for Gardasil” to have been the cause. (Ex. 20, p. 488.) (Gardasil is the brand name of the HPV vaccine that Valeria received.) Thus, while upon first impression to the layman, the occurrence of Valeria’s first stroke symptoms only one day post-vaccine might suggest a causal relationship, in fact the timing of Valeria’s symptom onset constitutes strong evidence against Dr. Kerr’s inflammation/causation theory. 21 C. This is not a close case As noted above, in Althen the Federal Circuit indicated that the Vaccine Act involves a Asystem created by Congress, in which close calls regarding causation are resolved in favor of injured claimants.@ (418 F. 3d at 1280). Accordingly, I note here that this case ultimately is not a close case. As set forth in detail in the sections above, I find that the testimony of the respondent’s experts was much more persuasive than that of Petitioner’s expert Dr. Kerr, concerning all of the issues raised by Dr. Kerr’s causation theories. Overall, I found the evidence in this case to be quite one-sided. XIII CONCLUSION The record of this case demonstrates plainly that Valeria Flores has been through a tragic and painful medical ordeal. She and her family are certainly deserving of great sympathy. Congress, however, designed the Program to compensate only the individuals whose injuries can be linked causally, either by a Table Injury presumption or causation-in-fact evidence, to a listed 21 One of Petitioner’s post-hearing briefs states that Respondent’s other expert, Dr. Bingham, “testified that the timing [of Valeria’s symptoms] appears medically appropriate.” (Br. Filed 8-27-12, p. 15.) But once again (see fn. 14 above), Petitioner’s counsel has grossly distorted the testimony of a witness. Dr. Bingham (at Tr. 232) was acknowledging only the obvious fact, which I myself noted above, that the timing of Valeria’s stroke symptoms, only one day after vaccination, is a reason a lay person might intivitively wonder if a causal connection exists (i.e., “the whole reason we’re here” (at trial)). He was certainly not conceding that the timing was “medically appropriate” for a vaccine causation finding. 24 vaccine. In this case, as described above, no such link has been demonstrated. Accordingly, I conclude that Petitioner in this case is not entitled to a Program award. 22 /s/ George L. Hastings, Jr. ____________________________________ George L. Hastings, Jr. Special Master 22 In the absence of a timely-filed motion for review of this Decision, the Clerk of the Court shall enter judgment accordingly. 25 ================================================================================ DOCUMENT 2: USCOURTS-cofc-1_10-vv-00489-0 Date issued/filed: 2014-03-21 Pages: 13 Docket text: JUDGE VACCINE REPORTED OPINION re: 43 DECISION of Special Master. Signed by Judge Margaret M. Sweeney. (kb1) -------------------------------------------------------------------------------- Case 1:10-vv-00489-MMS Document 53 Filed 03/21/14 Page 1 of 13 In the United States Court of Federal Claims No. 10-489V (Filed Under Seal: February 26, 2014) (Reissued for Publication: March 21, 2014)1 ************************************* VALERIA FLORES, * * Petitioner, * Vaccine Act; Motion for Review; HPV * Vaccine; Spinal Cord Stroke; Althen; v. * Causation-in-Fact; Burden of Proof; Genetic * Susceptibility; Medical Literature; SECRETARY OF HEALTH AND * Unknown Etiology; Logical Sequence of HUMAN SERVICES, * Cause and Effect * Respondent. * ************************************* Clifford J. Shoemaker, Vienna, VA, for petitioner. Debra A. Filteau Begley, United States Department of Justice, Washington, DC, for respondent. OPINION AND ORDER SWEENEY, Judge Petitioner seeks compensation under the National Childhood Vaccine Injury Act of 1986 (“Vaccine Act”), 42 U.S.C. §§ 300aa-1 to -34 (2006), alleging that she sustained a spinal cord stroke caused by a human papillomavirus (“HPV”) vaccination. In a September 28, 2013 decision, the special master denied petitioner’s request for compensation. Before the court is petitioner’s motion for review of the special master’s decision. For the reasons set forth below, the court denies petitioner’s motion for review and sustains the decision of the special master. 1 Vaccine Rule 18(b), contained in Appendix B of the Rules of the United States Court of Federal Claims, affords each party fourteen days in which to object to the disclosure of (1) trade secrets or commercial or financial information that is privileged or confidential or (2) medical information that would constitute “a clearly unwarranted invasion of privacy.” Neither party objected to the public disclosure of any information contained in this opinion. -1- Case 1:10-vv-00489-MMS Document 53 Filed 03/21/14 Page 2 of 13 I. BACKGROUND A. Medical History Petitioner’s medical history is not in dispute, and can be briefly summarized.2 On April 28, 2008, when she was fourteen years old, petitioner received her first HPV vaccination. She received her second HPV vaccination on June 27, 2008. The following day, she began to experience several symptoms, including left-sided weakness, severe headache, and shortness of breath. She then developed flaccid paralysis of her extremities and slurred speech. When the emergency medical service arrived at her house, petitioner developed bradycardia and suffered a cardiac arrest. She was taken to the emergency room at Mt. Sinai Hospital, and was subsequently transferred to Rush University Medical Center (“Rush”). At Rush, petitioner underwent an extensive medical workup and was given a working diagnosis of transverse myelitis. That diagnosis changed after two neurologists, Drs. Tilwalli and Stefofski, examined petitioner on August 6, 2008. As described by the special master: Dr. Tilwalli, a neurology fellow, opined that given Valeria’s quick onset, absence of inflammatory markers, and lack of response to anti-inflammatory treatment, he favored a vascular etiology. He also noted that he thought Valeria’s HPV vaccination was too close to symptom onset to induce an inflammatory response. Similarly, a neurologist, Dr. Stefofski, opined that Valeria’s quick symptom onset “strongly favors a vascular etiology over immune mediated/inflammatory (definitely too soon for Gardasil or even for a remote preceding myelitogenic trigger).” He also noted that due to the lack of response to corticosteroids and cyclophosphamide, he doubted an autoimmune etiology. Flores, 2013 WL 5587390, at *4 (citations omitted). Ultimately, it was determined that petitioner had experienced a spinal cord stroke. On August 7, 2008, petitioner was transferred from Rush to the Rehabilitation Institute of Chicago. Her physical condition did not improve; she continued to require total assistance for mobility and all activities of daily living. In addition, she had been on continuous ventilation during her stay at Rush and remained on the ventilator during her rehabilitation. Petitioner was discharged from inpatient rehabilitation on December 16, 2008. Since that time, she has shown some improvement–she has begun to feel some sensation in her extremities and exhibited voluntary movement in two fingers. However, she remains dependent on a ventilator. 2 The court derives petitioner’s undisputed medical history from the special master’s decision. See generally Flores v. Sec’y of HHS, No. 10-489V, 2013 WL 5587390, at *3-5 (Fed. Cl. Spec. Mstr. Sept. 12, 2013). -2- Case 1:10-vv-00489-MMS Document 53 Filed 03/21/14 Page 3 of 13 B. Procedural History Petitioner’s father filed a petition for compensation under the Vaccine Act on July 29, 2010, claiming that the HPV vaccine caused his daughter’s spinal cord stroke. Upon reaching the age of majority, Ms. Flores was substituted as petitioner. After the submission of medical records and expert reports, the special master convened an evidentiary hearing, during which he heard the testimony of three expert witnesses. Petitioner offered the testimony of neurologist Douglas A. Kerr, M.D., Ph.D., and respondent offered the testimony of pediatric neurologist Peter M. Bingham, M.D., and pediatric hematologist Joan Cox Gill, M.D. Posthearing briefs were filed, and the special master issued a decision on September 12, 2013. In his decision, the special master noted that all three experts agreed that petitioner had suffered a spinal cord stroke, which was caused by a blood clot that had become lodged in a spinal cord vessel, depriving petitioner’s spinal cord of oxygen and causing permanent injury. Where the experts disagreed, the special master explained, was on the cause of the blood clot. Dr. Kerr opined that the blood clot was caused by the HPV vaccine. Specifically, he asserted that petitioner had a genetic predisposition to blood clotting involving multiple genes; that petitioner’s first HPV vaccination sensitized her immune system; that the second HPV vaccination elicited an exuberant, rapid immune response; and that the immune response resulted in petitioner’s blood clot, either through inflammation or platelet aggregation. Drs. Bingham and Gill, on the other hand, found it improbable that the HPV vaccine could be connected to petitioner’s blood clot. Dr. Bingham explained that there was neither clinical evidence of inflammation, nor a noted connection between the HPV vaccine and spinal cord strokes or blood clots. Dr. Gill asserted that there was no clinical evidence of inflammation or platelet aggregation, and that a clotting response via inflammation would have taken at least four days to develop. The special master initially found that petitioner was unable to establish that she had a genetic predisposition to blood clotting. Because this genetic predisposition was a critical factor of the theory of causation advanced by Dr. Kerr, the special master concluded that petitioner could not establish that Dr. Kerr’s theory was probable. Although this conclusion, on its own, was sufficient to deny petitioner’s request for compensation under the Vaccine Act, the special master addressed other aspects of Dr. Kerr’s theory. First, he noted that Dr. Kerr’s theory was premised on petitioner’s spinal cord stroke originating from a blood clot in a vein (venous thrombosis), but that the evidence supported a finding that the blood clot originated in an artery (arterial thrombosis). Second, the special master held that petitioner failed to demonstrate that the HPV vaccine can contribute to the type of inflammation that causes blood clots and strokes or that petitioner’s second HPV vaccination did contribute to her blood clot or stroke. Similarly, the special master concluded that petitioner had not shown that she had experienced platelet aggregation or that any platelet aggregation contributed to her blood clot or stroke. In addition to addressing specific elements of Dr. Kerr’s theory of causation, the special master discussed some of the medical literature submitted by the parties. He held that the Slade -3- Case 1:10-vv-00489-MMS Document 53 Filed 03/21/14 Page 4 of 13 article, relied upon heavily by Dr. Kerr, did not offer “significant support” for the proposition that the HPV vaccine can contribute to strokes. The special master also concluded that other medical literature added “slightly” to the reasons to reject Dr. Kerr’s theories of causation. At the close of his decision, after concluding that the lack of an identifiable cause of petitioner’s spinal cord stroke did not offer “significant support” for her theory that the HPV vaccine caused the stroke, the special master analyzed petitioner’s case under the test for causation set forth in Althen v. Secretary of HHS, 418 F.3d 1274 (Fed. Cir. 2005). In Althen, the United States Court of Appeals for the Federal Circuit (“Federal Circuit”) articulated a three-part test, based on prior precedent, explaining what a petitioner must show to prove causation under the Vaccine Act: [Petitioner]’s burden is to show by preponderant evidence that the vaccination brought about [the] 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. Id. at 1278. The special master concluded that petitioner had not established either of the first two prongs of the Althen test, explaining that petitioner had not shown, more probably than not, that the HPV vaccine could contribute to spinal cord strokes or that the HPV vaccination petitioner received on June 27, 2008, did cause her stroke. The special master also noted that the timing of petitioner’s stroke was evidence that it was not caused by the HPV vaccine. Remarking that this was not a close case, the special master held that petitioner had not met her burden of proving that the HPV vaccine caused her stroke. He therefore denied petitioner’s request for compensation. Petitioner, alleging error, seeks review of the special master’s decision, which respondent opposes. The court heard argument on the parties’ competing positions on February 26, 2014.3 II. DISCUSSION The United States Court of Federal Claims has jurisdiction to review the record of the proceedings before a special master, and upon such review, may: (A) uphold the findings of fact and conclusions of law of the special master and sustain the special master’s decision, 3 During the February 26, 2014 proceedings, petitioner advanced several arguments that were not raised in her motion for review. These arguments are waived and the court will not address them. See L-3 Commc’ns EOTech, Inc. v. United States, 87 Fed. Cl. 656, 659 n.2 (2009) (“Plaintiff must not be allowed to advance new legal theories at oral argument, prejudicing defendant.”); see also SmithKline Beecham Corp. v. Apotex Corp., 439 F.3d 1312, 1319 (Fed. Cir. 2006) (“[A]rguments not raised on the opening brief are waived.”). -4- Case 1:10-vv-00489-MMS Document 53 Filed 03/21/14 Page 5 of 13 (B) set aside any findings of fact or conclusion of law of the special master found to be arbitrary, capricious, an abuse of discretion, or otherwise not in accordance with law and issue its own findings of fact and conclusions of law, or (C) remand the petition to the special master for further action in accordance with the court’s direction. 42 U.S.C. § 300aa-12(e)(2). In the instant case, petitioner enumerates, pursuant to Vaccine Rule 24, three objections to the special master’s decision. First, petitioner asserts that the special master impermissibly required her to identify the specific genes or cluster of genes that could have caused her susceptibility to blood clotting. Second, petitioner contends that the special master abused his discretion by rejecting several aspects of Dr. Kerr’s testimony regarding the logical sequence of cause and effect that connected her second HPV vaccination to her spinal cord stroke. Third, petitioner avers that the special master held her to an elevated burden of proof that was rejected in Althen and was therefore not in accordance with the law. All three objections relate to whether the special master properly held that petitioner had not established that the HPV vaccine caused her spinal cord stroke. A. Proving Causation Under the Vaccine Act Pursuant to 42 U.S.C. § 300aa-13(a)(1), the court shall award compensation if a petitioner proves, by a preponderance of evidence, all of the elements set forth in 42 U.S.C. § 300aa- 11(c)(1),4 and if there is not a preponderance of evidence that the illness is due to factors unrelated to the administration of the vaccine. A petitioner can recover in one of two ways: either by proving an injury listed on the Table or by proving causation-in-fact. See 42 U.S.C. §§ 300aa-11(c)(1)(C), -13(a)(1). Under the first method of recovery, a petitioner must demonstrate that the injury was sustained within the time frame set forth in the Table. Id. § 300aa-11(c)(1)(C)(I), -14(a). “If petitioner can make such a showing, causation is presumed and petitioner is deemed to have made out a prima facie case of entitlement to compensation under the Act.” Whitecotton v. Sec’y of HHS, 81 F.3d 1099, 1102 (Fed. Cir. 1996). To establish a prima facie case when proceeding on a causation-in-fact theory, as petitioner attempted to do in this case, a petitioner must “prove, by a preponderance of the 4 Subsection (c)(1) requires, among other things, that the following elements be satisfied: (1) that the vaccine in question is set forth in the Vaccine Injury Table (“Table”); (2) that the vaccine was received in the United States or in its trust territories; (3) that the injured person either sustained an injury as a result of the administration of a Table-designated vaccine for a period of more than six months after the administration of the vaccine, suffered illness, disability, injury, or condition from the vaccine that resulted in inpatient hospitalization and surgical intervention, or died from the administration of the vaccine; and (4) that the petitioner has not previously collected an award or settlement of a civil action for damages arising from the alleged vaccine-related injury or death. 42 U.S.C. § 300aa-11(c)(1). -5- Case 1:10-vv-00489-MMS Document 53 Filed 03/21/14 Page 6 of 13 evidence, that the vaccine was not only a but-for cause of the injury but also a substantial factor in bringing about the injury.” Shyface v. Sec’y of HHS, 165 F.3d 1344, 1352 (Fed. Cir. 1999). “[T]o show that the vaccine was a substantial factor in bringing about the injury, the petitioner must show ‘a medical theory causally connecting the vaccination and the injury.’” Id. at 1352-53 (quoting Grant v. Sec’y of HHS, 956 F.2d 1144, 1148 (Fed. Cir. 1992) (per curiam)). In other words, “[t]here must be a ‘logical sequence of cause and effect showing that the vaccination was the reason for the injury,’” id. at 1353 (quoting Grant, 956 F.2d at 1148), and “[t]his ‘logical sequence of cause and effect’ must be supported by a sound and reliable medical or scientific explanation,” Knudsen v. Sec’y of HHS, 35 F.3d 543, 548 (Fed. Cir. 1994) (citing Daubert v. Merrell Dow Pharms., Inc., 509 U.S. 579 (1993); Jay v. Sec’y of HHS, 998 F.2d 979, 984 (Fed. Cir. 1993)); see also 42 U.S.C. § 300aa-13(a)(1) (“The special master or court may not make such a finding based on the claims of a petitioner alone, unsubstantiated by medical records or by medical opinion.”). However, medical or scientific certainty is not required. Knudsen, 35 F.3d at 548-49; Bunting v. Sec’y of HHS, 931 F.2d 867, 873 (Fed. Cir. 1991). As noted above, the Federal Circuit, in Althen, distilled this prior precedent into a three- part test, holding that to prove causation-in-fact, a petitioner must 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.” 418 F.3d at 1278. All three prongs “must cumulatively show that the vaccination was a ‘but-for’ cause of the harm, rather than just an insubstantial contributor in, or one among several possible causes of, the harm.” Pafford v. Sec’y of HHS, 451 F.3d 1352, 1355 (Fed. Cir. 2006). Once a petitioner has established a prima facie case, the burden shifts to the respondent to show, by a preponderance of the evidence, that the injury was caused by a factor unrelated to the vaccine. 42 U.S.C. § 300aa-13(a)(1)(B); Shalala v. Whitecotton, 514 U.S. 268, 270-71 (1995); de Bazan v. Sec’y of HHS, 539 F.3d 1347, 1352 (Fed. Cir. 2008). However, if a petitioner fails to establish a prima facie case, the burden does not shift. Bradley v. Sec’y of HHS, 991 F.2d 1570, 1575 (Fed. Cir. 1993). Regardless of whether the burden ever shifts to the respondent, the special master may consider the evidence presented by the respondent in determining whether the petitioner has established a prima facie case. See Stone v. Sec’y of HHS, 676 F.3d 1373, 1379 (Fed. Cir. 2012) (“[E]vidence of other possible sources of injury can be relevant not only to the ‘factors unrelated’ defense, but also to whether a prima facie showing has been made that the vaccine was a substantial factor in causing the injury in question.”); de Bazan, 539 F.3d at 1353 (“The government, like any defendant, is permitted to offer evidence to demonstrate the inadequacy of the petitioner’s evidence on a requisite element of the petitioner’s case-in-chief.”). B. Allegations That Portions of the Special Master’s Decision Were Not in Accordance With the Law Within her enumerated objections to the special master’s decision, petitioner contends that several of the special master’s conclusions were not in accordance with the law. -6- Case 1:10-vv-00489-MMS Document 53 Filed 03/21/14 Page 7 of 13 Specifically, she argues that the special master, in various portions of his decision, required her to provide “objective confirmation in the medical community” linking her second HPV vaccination to her spinal cord stroke, impermissibly elevating her burden beyond what is permitted by the Vaccine Act. Mot. 16. 1. Genetic Susceptibility Petitioner first asserts that the special master improperly elevated her burden of proof by requiring her to identify the specific genes or cluster of genes that made her susceptible to a vaccine injury. In his decision, the special master noted that Dr. Kerr’s theory of causation depended on petitioner being genetically susceptible to blood clotting, and that Dr. Kerr testified that such a genetic predisposition would involve a combination of several genes. However, Dr. Kerr was unable to identify what genes or gene combination would be involved. In addition, Dr. Kerr acknowledged that a gene mutation discovered during petitioner’s workup at Rush–a MTHFRA1298C heterozygous mutation–could not, by itself, cause susceptibility to blood clotting or stroke, and that the MTHFR gene might not have been part of the gene cluster at all. Indeed, remarked the special master, Dr. Gill, a hematologist, explained that petitioner’s MTHFR gene mutation does not cause blood clotting, and that there was no clinical evidence of petitioner having other MTHFR gene mutations that might increase the risk of blood clots. Based on all of this testimony, the special master concluded that Dr. Kerr’s assertion that petitioner must have had a cluster of genes causing a predisposition to blood clotting was no more than mere speculation, and was therefore insufficient to meet petitioner’s burden of establishing a probable theory of causation. A close examination of the special master’s analysis reveals that he did require petitioner to offer proof of the specific genes or gene cluster that contributed to petitioner’s predisposition to blood clotting. See, e.g., Flores, 2013 WL 5587390, at *8 (“Dr. Kerr acknowledged that he did not know what that combination of genes might be. In the final analysis, I conclude that Dr. Kerr was engaging in mere speculation or guesswork in concluding that Valeria must have had such a cluster of genes. Thus, this part of his theory . . . has not been shown to be probable.” (citation omitted)), *9 (“I find that Dr. Kerr totally failed to establish . . . that Valeria had some type of genetic predisposition that made her susceptible to have blood clots. . . . [H]e could do no more than propose that Valeria might have had a cluster of several different genes that made her susceptible, but could not even propose what any of those genes might have been.”). The special master was incorrect to do so. Under the second prong of the Althen test, petitioner must show a logical sequence of cause and effect connecting her second HPV vaccination to her spinal cord stroke. In making this showing, she cannot be required to prove “the presence of . . . genetic disposition” because such a requirement is “inconsistent with allowing ‘the use of circumstantial evidence envisioned by the preponderance standard’” and therefore “impermissibly raises [her] burden under the Vaccine Act . . . .” Capizzano v. Sec’y of HHS, 440 F.3d 1317, 1325 (Fed. Cir. 2006) (quoting Althen, 418 F.3d at 1280). Thus, while direct evidence of genetic susceptibility is probative, in -7- Case 1:10-vv-00489-MMS Document 53 Filed 03/21/14 Page 8 of 13 the absence of such direct evidence, petitioner was entitled to demonstrate genetic susceptibility through medical opinion. Id. at 1326. Therefore, requiring petitioner to identify the specific genes or gene cluster that contributed to her purported blood clotting predisposition is contrary to law. Nevertheless, this error is not dispositive. As the court explains later in this decision, because the special master correctly concluded that petitioner failed to establish other aspects of the causation theory advanced by Dr. Kerr, she cannot demonstrate entitlement to compensation under the Vaccine Act. 2. Medical Literature Another portion of the special master’s decision that was contrary to law, asserts petitioner, is the special master’s review of and reliance on medical literature. Specifically, she contends that although the special master stated that he was not requiring her to submit medical literature, he improperly used the submitted medical literature showing that there was no association between the HPV vaccine and her injury to “bolster the weight of evidence” against her. Mot. 15. According to petitioner, this practice was rejected by the Federal Circuit in Althen and Capizzano. Upon reviewing the special master’s decision, however, the court discerns no error. In Althen and Capizzano, the Federal Circuit merely held that a special master could not require a petitioner to submit medical literature to prove causation. Capizzano, 440 F.3d at 1324; Althen, 418 F.3d at 1280. In neither case did the Federal Circuit preclude, much less discuss, a special master’s review and use of medical literature submitted by the parties on their own volition. In fact, in Andreu v. Secretary of HHS, the Federal Circuit remarked: Although Althen and Capizzano make clear that a claimant need not produce medical literature or epidemiological evidence to establish causation under the Vaccine Act, where such evidence is submitted, the special master can consider it in reaching an informed judgment as to whether a particular vaccination likely caused a particular injury. Althen makes clear that a claimant’s theory of causation must be supported by a “reputable medical or scientific explanation.” The assessment of whether a proffered theory of causation is “reputable” can involve assessment of the relevant scientific data. 569 F.3d 1367, 1379-80 (Fed. Cir. 2009) (citations omitted). In his decision, the special master thoroughly evaluated the Slade article, which was submitted by both parties in support of their respective positions, and concluded that it did not provide “significant support for Dr. Kerr’s general proposition that the HPV vaccine [could] contribute to causing strokes.” Flores, 2013 WL 5587390, at *13-15. The special master then addressed other medical literature in the record–specifically the Gold and Gee articles–and determined that it “add[ed] slightly to the reasons for rejecting Dr. Kerr’s causation theory.” Id. at *16. There is no indication that the special master required petitioner to provide medical literature supporting Dr. Kerr’s causation theory; indeed, the special master clearly recognized that medical literature or epidemiological -8- Case 1:10-vv-00489-MMS Document 53 Filed 03/21/14 Page 9 of 13 evidence was not required to prove causation. Thus, under binding Federal Circuit precedent, it was not legally improper for the special master to consider the articles submitted by the parties and determine whether they supported or detracted from the theory of causation advanced by Dr. Kerr. 3. Unknown Etiology of Petitioner’s Injury The third portion of the special master’s decision challenged by petitioner as contrary to law is the special master’s discussion of the lack of evidence supporting an alternative cause for her injury. Petitioner contends that this lack of evidence is only relevant to respondent’s burden of establishing an alternative cause, and not to Dr. Kerr’s theory of causation. Petitioner is mistaken. As noted above, a special master may consider the existence of alternative causes of injury in determining whether the petitioner has established a prima facie case of causation. See Stone, 676 F.3d at 1379; de Bazan, 539 F.3d at 1353. Here, the special master noted that neither the medical records, nor respondent’s experts, identified a known cause of petitioner’s spinal cord stroke. He therefore inquired whether the lack of evidence of a known cause supported Dr. Kerr’s theory that petitioner’s second HPV vaccination caused her stroke. Upon reviewing the evidence in the record, the special master concluded that because it was “common for the cause of spinal cord strokes not to be identified,” the fact that the cause of petitioner’s stroke was not identified did not make Dr. Kerr’s theory more tenable. Flores, 2013 WL 5587390, at *17. As the unambiguous Federal Circuit precedent makes clear, the special master did not err in considering evidence related to an alternative cause in determining whether petitioner had met her burden of proof of causation. C. Allegations That the Special Master Abused His Discretion In addition to arguing that parts of the special master’s decision were contrary to law, petitioner contends that the special master abused his discretion in rejecting Dr. Kerr’s testimony regarding certain elements of the logical sequence of cause and effect that allegedly connected her second HPV vaccination to her spinal cord stroke; namely, the origin of her blood clot and the existence of inflammation and platelet aggregation. An abuse of discretion occurs when a “decision is based on clearly erroneous findings of fact, is based on erroneous interpretations of the law, or is clearly unreasonable, arbitrary or fanciful.” Cybor Corp. v. FAS Techs., Inc., 138 F.3d 1448, 1460 (Fed. Cir. 1998) (en banc); accord Hendler v. United States, 952 F.2d 1364, 1380 (Fed. Cir. 1991) (“An abuse of discretion may be found when (1) the court’s decision is clearly unreasonable, arbitrary, or fanciful; (2) the decision is based on an erroneous conclusion of the law; (3) the court’s findings are clearly erroneous; or (4) the record contains no evidence upon which the court rationally could have based its decision.”), quoted in Murphy v. Sec’y of HHS, 30 Fed. Cl. 60, 61 (1993). It is well settled that under this standard, the court accords -9- Case 1:10-vv-00489-MMS Document 53 Filed 03/21/14 Page 10 of 13 deference to the special master’s factual findings and fact-based conclusions.5 It is not the court’s role to reweigh the evidence. See Hodges v. Sec’y of HHS, 9 F.3d 958, 961 (Fed. Cir. 1993) (“[O]n review, the Court of Federal Claims is not to second guess the Special Master[’]s fact-intensive conclusions; the standard of review is uniquely deferential for what is essentially a judicial process. . . . That level of deference is especially apt in a case in which the medical evidence of causation is in dispute.”). Despite this unambiguous standard, a review of petitioner’s contentions reveals that this is precisely what petitioner is asking the court to do–reweigh the evidence. 1. The Origin of Petitioner’s Blood Clot Petitioner first contends that the special master abused his discretion by rejecting Dr. Kerr’s testimony that her spinal cord stroke originated from a venous thrombosis in favor of Dr. Gill’s testimony that her stroke originated from an arterial thrombosis. In support of this contention, petitioner notes that Dr. Kerr has more experience than Dr. Gill with spinal cord strokes and avers that Dr. Gill relied on the results of a test–the D-dimer test–that do not support her position. Accordingly, petitioner argues, the special master’s conclusion that Dr. Gill was more persuasive on the origin of the blood clot was improper. While petitioner’s first point–that Dr. Kerr was more experienced than Dr. Gill regarding spinal cord strokes–may be true, it is only one aspect of what the special master could have considered in analyzing the origins of petitioner’s blood clot. Indeed, the special master’s decision reflects that he considered the testimony of all three experts regarding the bases for their respective positions, as well as a medical article that supported Dr. Gill’s position. That the special master assigned different weights to this evidence than the weights preferred by petitioner is not an abuse of discretion. Petitioner’s second point concerns the results of three D-dimer tests she underwent at Rush on July 5 and 6, 2008. According to the undisputed testimony of Dr. Gill, the D-dimer test shows whether there is ongoing coagulation, and a negative result suggests that a venous thrombosis is highly unlikely. The reference range for petitioner’s D-dimer tests was “0.00 - 0.60 ug/mL,” and appended to the results of each test was the following comment: “D-Dimer results of less than 0.5 ug/mL have been shown to contribute to the exclusion of venous 5 There is abundant precedent from the Federal Circuit to this effect. See, e.g., Whitecotton, 81 F.3d at 1108 (“Congress desired the special masters to have very wide discretion with respect to the evidence they would consider and the weight to be assigned that evidence.”); Munn v. Sec’y of HHS, 970 F.2d 863, 871 (Fed. Cir. 1992) (emphasizing that “the probative value of the evidence” and “the credibility of the witnesses” were within the special master’s purview as fact finder); Hines v. Sec’y of HHS, 940 F.2d 1518, 1527 (Fed. Cir. 1991) (“[A]rguments as to the weighing of evidence, particularly where, as here, witness credibility is involved, do not demonstrate reversible error.”). -10- Case 1:10-vv-00489-MMS Document 53 Filed 03/21/14 Page 11 of 13 thromboembolism with a negative predictive value of approximately 98% when results are used as part of the total clinical evaluation of the patient.” Pet’r’s Ex. 20 at 928-32. The results of petitioner’s three D-dimer tests were 0.51 ug/mL, 0.46 ug/mL, and 0.49 ug/mL. Id. Dr. Gill testified that these test results made it “very unlikely” that petitioner suffered from a venous thrombosis. Tr. 164. Petitioner advances two arguments related to the D-dimer test results: (1) Dr. Gill’s testimony was contradicted by the comment in the test results, and (2) Dr. Gill acknowledged that petitioner was taking medication that could lower the test results. Petitioner’s first argument suffers from an error in logic. Petitioner contends that the 0.51 ug/mL test result contradicts Dr. Gill’s testimony because it does not meet the “less than 0.5 ug/mL” threshold described in the test result comment.6 However, the fact that test results that are less than 0.5 ug/mL may help exclude the existence of a venous thrombosis with 98% certainty does not mean that test results that are greater than 0.5 ug/mL reflect the existence of a venous thrombosis. Rather, the more logical conclusion is that a test result that is greater than 0.5 ug/mL, but still within the reference range, may help exclude the existence of a venous thrombosis, but with less than 98% certainty. This interpretation is supported by Dr. Gill’s characterization of petitioner’s D-dimer test results as “negative,” id., and “within the normal range,” id. at 182-84. Thus, the comment in the D- dimer test results does not contradict Dr. Gill’s testimony as petitioner contends. Petitioner’s second argument fares no better. While Dr. Gill acknowledged that one of petitioner’s medications could lower the D-dimer test results, she did not retract her conclusion that the test results made a venous thrombosis unlikely. As a result, the record contains evidence that supports the special master’s reliance on Dr. Gill’s analysis of the D-dimer test results. Petitioner therefore has not demonstrated that the special master’s acceptance of Dr. Gill’s testimony was an abuse of discretion. Instead, all that she has established is that she would weigh the evidence regarding the effect of petitioner’s medication on the D-dimer test results differently. In sum, the special master’s conclusion that Dr. Gill was more persuasive than Dr. Kerr regarding the origin of petitioner’s blood clot was not improper. 2. Inflammation and Platelet Aggregation In addition to arguing that the special master should not have rejected Dr. Kerr’s testimony that she experienced a venous thrombosis, petitioner contends that the special master abused his discretion in rejecting Dr. Kerr’s testimony regarding how the immune response triggered by her second HPV vaccination led to a blood clot, and instead accepting the testimony of Dr. Gill. 6 Petitioner does not address the other two D-dimer test results in her motion for review. -11- Case 1:10-vv-00489-MMS Document 53 Filed 03/21/14 Page 12 of 13 Dr. Kerr proposed two mechanisms that might link petitioner’s immune response to her blood clot: inflammation and platelet aggregation. With respect to inflammation, petitioner asserts that Dr. Kerr’s theory relied upon the presence of localized inflammation, i.e., inflammation in her central nervous system, and that Dr. Gill rejected Dr. Kerr’s theory because (1) there was no evidence of systemic inflammation in her test results and (2) her spinal cord stroke occurred too soon after her second HPV vaccination. Petitioner contends that the special master’s acceptance of Dr. Gill’s testimony over the testimony of Dr. Kerr was improper because Dr. Gill was looking for systemic inflammation based on an incorrect diagnosis of her neurological injury, and because the timing of her stroke was appropriate because her immune system was primed by her first HPV vaccination. She further contends, with respect to platelet aggregation, that the special master improperly required her to prove a specific biological mechanism of injury.7 Ultimately, Dr. Gill’s characterization of petitioner’s injury and the possible priming effect of petitioner’s first HPV vaccination were not material to the special master’s decision to reject Dr. Kerr’s testimony. Not only did Dr. Gill and Dr. Bingham testify that none of petitioner’s test results reflected systemic inflammation, Dr. Bingham further testified that the results of tests of petitioner’s spinal cord fluid did not show inflammation, i.e., there was no evidence of localized inflammation. Moreover, Dr. Gill testified that there was no evidence of platelet aggregation in petitioner’s test results. The special master was therefore entitled to conclude that if the logical sequence of cause and effect posited by Dr. Kerr included the existence of inflammation or platelet aggregation, but there was no evidence of inflammation or platelet aggregation in any of petitioner’s test results, then petitioner could not establish an essential element of causation linking her second HPV vaccination to her spinal cord stroke. The court’s conclusion finds ample support in Federal Circuit precedent. See, e.g., Moberly v. Sec’y of HHS, 592 F.3d 1315, 1324 (Fed. Cir. 2010) (noting that “the special master is entitled to require some indicia of reliability to support the assertion of the expert witness” and holding that the special master did not err in rejecting the petitioner’s theory of causation when petitioner’s expert could not identify any evidence that the mechanism underlying his theory was at work in the petitioner’s case); see also Capizzano, 440 F.3d at 1327 (“A claimant could satisfy the first and third prongs [of the Althen test] without satisfying the second prong when medical records and medical opinion do not suggest that the vaccine caused the injury . . . .”). The Federal Circuit’s decision in Stone is particularly instructive. In that case, the injured children suffered from Severe Myoclonic Epilepsy of Infancy, a seizure disorder. Stone, 676 F.3d at 1374. The theory of causation proposed by the petitioners’ expert was that the vaccine at issue caused a fever, triggering initial febrile seizures, which caused lasting brain injury, leading to the seizure disorder. Id. at 1376, 1384. The special master concluded that there was no evidence that the children suffered brain damage as a result of the initial seizures. Id. at 1384. In rejecting the petitioners’ argument that the special master improperly required them to prove a biological 7 Petitioner did not raise this argument with respect to Dr. Kerr’s proposed mechanism of inflammation. -12- Case 1:10-vv-00489-MMS Document 53 Filed 03/21/14 Page 13 of 13 mechanism of causation, the Federal Circuit remarked: “[T]he special master did not insist on evidence of the biological mechanism by which the brain damage was caused. He merely sought evidence of the existence of brain damage–a key component of [the expert’s] theory–and [the expert] was unable to provide any.” Id. at 1385. Noting that the special master concluded that the expert’s “inference of brain damage, in the face of clinical records showing no brain damage, was unpersuasive and . . . therefore insufficient to carry the petitioners’ burden on causation,” the Federal Circuit explained that the special master had “denied compensation not because the parties failed to show how the vaccines caused brain damage, but because they failed to show that the vaccines caused any brain damage.” Id. at 1384. Similarly here, the special master denied petitioner compensation because she failed to show that her second HPV vaccination actually did lead to a blood clot, either through inflammation or platelet aggregation. This was not an abuse of discretion. D. Application of the Althen Test The theory of causation advanced by Dr. Kerr was that petitioner had a genetic predisposition to blood clotting involving multiple genes; that petitioner’s first HPV vaccination sensitized her immune system; that the second HPV vaccination elicited an exuberant, rapid immune response; that the immune response resulted in the blood clot, either through the creation of inflammation or platelet aggregation; and that the blood clot caused petitioner’s spinal cord stroke. To establish the second prong of the Althen test–a logical sequence of cause and effect connecting the vaccine to the injury–petitioner was required to demonstrate each link in this causative chain by a preponderance of the evidence. 42 U.S.C. § 300aa-13(a)(1). The court concluded that the special master improperly required petitioner to provide specific proof of genetic susceptibility to blood clotting. However, the special master’s rejection of Dr. Kerr’s testimony regarding inflammation and platelet aggregation, which the court concluded was not an abuse of discretion, leads the court to find that petitioner was unable to establish another link in the causative chain–the link between the immune response triggered by her second HPV vaccination and her blood clot. Thus, the special master’s determination that petitioner was not entitled to compensation under the Vaccine Act because she did not establish that the HPV vaccine caused her spinal cord stroke must be upheld. III. CONCLUSION For the reasons stated above, the court DENIES petitioner’s motion for review and SUSTAINS the decision of the special master. The clerk is directed to enter judgment accordingly. IT IS SO ORDERED. s/ Margaret M. Sweeney MARGARET M. SWEENEY Judge -13- ================================================================================ DOCUMENT 3: USCOURTS-cofc-1_10-vv-00489-1 Date issued/filed: 2015-07-24 Pages: 2 Docket text: PUBLIC DECISION (Originally filed: 070215) regarding 64 DECISION Fees Stipulation/Proffer Signed by Special Master George L. Hastings. (jtl) Copy to parties. -------------------------------------------------------------------------------- Case 1:10-vv-00489-MMS Document 65 Filed 07/24/15 Page 1 of 2 In the United States Court of Federal Claims OFFICE OF SPECIAL MASTERS No. 10-489V (Not to be published) * * * * * * * * * * * * * * * * * * * * * * * * * * VALERIA FLORES, * * Petitioner, * * Filed: July 2, 2015 v. * * Decision on Attorneys’ SECRETARY OF HEALTH AND * Fees and Costs HUMAN SERVICES * * Respondent. * * * * * * * * * * * * * * * * * * * * * * * * * * * DECISION (ATTORNEYS’ FEES AND COSTS) In this case under the National Vaccine Injury Compensation Program,1 I issued a decision on September 12, 2013. On July 30, 2015, the parties filed a stipulation concerning attorneys’ fees and costs in this matter. The parties’ stipulation requests a total payment of $137,500.00, representing all attorney’s fees and costs available under 42 U.S.C. § 300aa-15(e). In accordance with General Order #9, the stipulation includes a statement that Petitioner incurred no reimbursable costs in pursuit of his claim. I find that this petition was brought in good faith and that there existed a reasonable basis for the claim. Therefore, an award for fees and costs is appropriate, pursuant to 42 U.S.C. § 300aa-15(b) and (e)(1). Further, the proposed amount seems reasonable and appropriate. Accordingly, I hereby award the total $137,500.00 as a lump sum in the form of a check payable jointly to Petitioner and Petitioner’s counsel, Clifford Shoemaker. 1 The applicable statutory provisions defining the program are found at 42 U.S.C. § 300aa-10 et seq. (2012). Case 1:10-vv-00489-MMS Document 65 Filed 07/24/15 Page 2 of 2 In the absence of a timely-filed motion for review filed pursuant to Appendix B of the Rules of the U.S. Court of Federal Claims, the clerk of the court shall enter judgment in accordance herewith.2 IT IS SO ORDERED /s/ George L. Hastings, Jr. George L. Hastings, Jr. Special Master 2 Pursuant to Vaccine Rule 11(a), the parties may expedite entry of judgment by filing a joint notice renouncing the right to seek review.