BRIAN H. CORCORAN, Special Master.
On June 28, 2010, Shea Sullivan filed this action seeking compensation under the National Vaccine Injury Compensation Program (the "Vaccine Program"),
The record in this case consists of Ms. Sullivan's medical records, a daily self-health log she prepared, affidavits from her as well as her mother and father, the testimony of two experts, and medical or scientific literature submitted by the parties in support of their respective positions. I have reviewed the entire record as required by the Vaccine Act. In this ruling I address the sufficiency of Petitioner's evidence in support of an award of compensation.
Petitioner was nearly sixteen years old at the time she received her first Gardasil
On August 10, 2007, Ms. Sullivan's mother contacted Valerie Kozak, M.D. (Petitioner's primary care physician) at Pediatric and Adult Medicine to report that Petitioner appeared to be suffering from heart palpitations. Pet'r's. Ex. 5 at 55. Ms. Sullivan was apparently seen again on August 29, 2007, when she received her second Gardasil vaccination. Pet'r's Ex. 3 at 3. There are no subsequent records of any medical visits between August 27, 2007, and the time Petitioner received her third Gardasil vaccination on January 4, 2008. Pet'r's Ex. 5 at 56.
On February 11, 2008, Ms. Sullivan's mother called Dr. Kozak, this time to report that Petitioner was suffering from a sore throat, headache, and abdominal pain, and Dr. Kozak prescribed an antibiotic. Pet'r's Ex. 5 at 56. Ms. Sullivan was not seen again by a physician until April 18, 2008 (fifteen weeks after receiving her third Gardasil vaccination), when she reported experiencing left knee pain over the prior one to two weeks. Id. at 57. In the relevant medical history, it was noted that Petitioner ran track at school. Id. On examination, Ms. Sullivan's left knee proved to be tender medially and in the patella (knee cap) region, but she had full range of motion and the knee was otherwise stable, so she was merely referred to orthopedics for an evaluation (although the medical records do not indicate whether she followed through with the evaluation). Id.
Months later, Ms. Sullivan went back to Dr. Kozak for a follow-up visit in October of 2008 regarding the knee pain that she had been experiencing as well as swelling in her hands, feet, and forearms. Pet'r's Ex. 5 at 56. The possibility of arthritis as an explanation for Petitioner's symptoms is recorded in the medical history from this visit. Id. Laboratory studies showed normal comprehensive metabolic panel ("CMP"), complete blood count ("CBC"), and urinalysis results. Id. at 58-63. An antinuclear antibody ("ANA") screen, double-stranded DNA, smooth muscle antibody, C3 complement, cardiolipin antibodies, thyroid function, and direct antiglobulin tests were also negative for abnormalities. Id.
Ms. Sullivan subsequently saw Eric Wei En Lee, M.D. at Orange Orthopedic Medical Group in Orange, California on October 21, 2008, for an orthopedic evaluation. Pet'r's Ex. 7 at 6-8. As the treatment records from that visit indicate, Petitioner reported that her onset of symptoms had occurred in April 2008 "while running track." Id. at 6. She also related to Dr. Lee that she had experienced another episode of pain while running on the beach during the same period, and characterized the pain as constant and severe. Id. She specifically reported "objective instability, mechanical popping clicking, weakness, and decreased range of motion." Id. A physical examination performed on Petitioner revealed "peripheral joint stiffness." Id. at 7. An examination of her knee in particular revealed no erythema, swelling, drainage, or sign of infection; other aspects of her exam also had normal results, although there was a 1+ effusion and abnormalities with the patellar exam. Id. Dr. Lee diagnosed Ms. Sullivan with a patellofemoral chondromalacia (damage to the patella) and malalignment, as well as mild flexible pes planus (flat feet). Id.
Ms. Sullivan underwent an MRI of her knee on October 22, 2008, which showed intact menisci, tendons, and ligaments. Pet'r's Ex. 7 at 10. A moderate amount of joint effusion was observed (although its etiology was unclear). Id. She returned to Dr. Lee's clinic for follow-up on October 29, 2008, at which time (taking into account the MRI) she was again diagnosed with left knee patellofemoral chondromalacia, leading Dr. Lee to recommend physical therapy. Id. at 11, 12.
On November 3, 2008, Ms. Sullivan presented to Scott Graham, M.D. at South County Orthopedic Specialists in Laguna Woods, California for a second opinion regarding her left knee pain. Pet'r's Ex. 8 at 6-7. She again reported that her pain had existed since April of 2008 after "running on the beach," and although she could not remember if there had been a specific injury, she did recall having pain and swelling the next day. Id. The medical records from that visit note that Petitioner's family history was significant for arthritis, diabetes, cancer, and stroke. Id. at 6. A physical examination showed left knee swelling and tenderness, without warmth, but Petitioner nevertheless demonstrated a full range of motion and no hip irritability. Id. Dr. Graham reviewed the imaging studies and agreed that they were normal except for the presence of effusion. Id. He diagnosed Ms. Sullivan with a possible occult medial meniscal tear, and gave her a cortisone injection. Id. at 7. There was no mention of vaccination in Petitioner's treatment records from this visit, nor was Gardasil, or any other vaccine, identified as a possible cause of Ms. Sullivan's injuries.
Petitioner had a follow-up visit with Dr. Graham on December 1, 2008. Pet'r's Ex. 8 at 11. Because she continued to report knee pain despite the cortisone injection she had received in November, surgical intervention was recommended. Id. Ms. Sullivan subsequently underwent arthroscopic knee surgery performed by Dr. Graham on December 16, 2008. Id. at 12-13. Her post-operative diagnoses were: (1) medial compartmental synovitis scar tissue, (2) lateral tibial plateau grade III chondral fissure, and (3) suprapatellar plica; follow-up physical therapy was recommended. Id. at 21-24. Ms. Sullivan underwent physical therapy treatments at Knight Physical Therapy in Anaheim, California, but not consistently, and she did not complete all of her sessions. See Pet'r's Ex. 9 at 2-9. At a session on February 2, 2009, she was noted to be doing well overall, although her knee was more swollen than usual due to standing for an extended period of time at a recent concert, and she was urged to keep up with her therapy. Id. at 11.
On February 11, 2009, Ms. Sullivan was seen by Dr. Graham for a post-surgery follow-up. Pet'r's Ex. 8 at 26. Petitioner now reported that although her knee pain had improved, she was experiencing pain in multiple joints. Id. She thereafter went back to Dr. Kozak on April 6, 2009 (a year after she claims to have first experienced knee pain) with complaints of joint pain in her arms and hands, as well as a new kind of knee pain different from what she had previously experienced. Pet'r's Ex. 5 at 63. It was now noted (for the first time in the medical records) that Ms. Sullivan "associates [her symptoms] with HPV vaccine." Id. The contemporaneous medical records specifically note that Petitioner had looked up information regarding the connection between the Gardasil vaccination and rheumatoid arthritis ("RA") on the internet and reported having found five cases associated with a class action lawsuit regarding the vaccine. Id.
Ms. Sullivan returned to Dr. Kozak on July 13, 2009. Pet'r's Ex. 5 at 64. By this time, Petitioner reported that she had been diagnosed with "inflammatory" arthritis "per rheumatology" (id.), presumably referring to the assessment of Thomas R. Powell, M.D., a rheumatologist in Orange, California, who saw Petitioner that same month. See generally Pet'r's Ex. 10. She later saw Dr. Kozak again in August, at which time she repeated her concern that the Gardasil vaccine was the cause of her arthritic condition. Pet'r's Ex. 5 at 65. As a written phone record from August 3, 2009, indicates, Dr. Kozak informed Ms. Sullivan's mother that there were no scientific articles linking the Gardasil vaccine to arthritis. Id. Laboratory work performed by Dr. Powell showed that Ms. Sullivan's cyclic citrullinated peptide antibody ("CCP") (the presence of which is strongly associated with RA) was elevated, while serum protein electrophoresis, rheumatoid factor ("RF"), ANA, CBC, and CMP results were normal. Pet'r's Ex. 10 at 3-9.
On September 9, 2009, Petitioner was seen by William Shiel, M.D., FACP, FACR, at Mission Internal Medicine Group, Inc. in Mission Viejo, California for a rheumatologic evaluation. Pet'r's Ex. 11 at 1-3. A physical examination was significant for hyperhydrosis of the feet, swollen proximal interphalangeal ("PIP") joints with decreased flexion, swollen wrists, trace swelling of the knees with decreased flexion to 120 degrees, and tender metatarsophalangeal ("MTP") joints. Id. at 2-3. Ms. Sullivan's erythrocyte sedimentation rate (a test used to measure the degree of inflammation present) was slightly elevated at thirty-two. Id. 5-7. RF and ANA tests were negative, while her anti-CCP antibody was strongly positive. Id. Petitioner was diagnosed with symmetric polyarthritis, based on such test results and the generally-observed loss of range of motion of the wrists and PIP joints. Id. at 4. Dr. Shiel ultimately felt that Ms. Sullivan's symptoms were very suggestive of RA, and recommended a number of medications to treat her symptoms. Id.
At a follow-up visit with Dr. Shiel on September 25, 2009, Ms. Sullivan complained of "[p]ain all over the joints for [two] years" and was started on medication to treat her symptoms. Pet'r's Ex. 11 at 10. Imaging studies included a normal bilateral wrist x-ray series, hand x-rays that showed mild periarticular osteopenia, and foot x-rays that showed periarticular osteopenia. Id. at 11-14. Petitioner was thereafter formally diagnosed by Dr. Kozak as suffering from Juvenile Rheumatoid Arthritis ("JRA").
1. Dr. Richard Roseff — Petitioner's expert, Richard Roseff, M.D., graduated from Boston University School of Medicine in 1980 (after completing his undergraduate degree at Amherst College). Tr. at 5; ECF No. 12-1 at 3. Dr. Roseff went on to complete his residency at Boston Medical Center, followed by a two-year fellowship in rheumatology at Massachusetts General Hospital. Tr. at 5. Dr. Roseff is board certified in internal medicine and rheumatology but not in pediatric rheumatology. Id. at 6, 43. He is currently a member of the American College of Rheumatology, and he has a rheumatology sub-specialty private practice in Connecticut. Id. at 7. Dr. Roseff has lectured on RA, but he has not published any articles on this topic. Id. Dr. Roseff is also not an immunologist, epidemiologist, or toxicologist, and he has no personal expertise in the subject of vaccine causation. Id. at 80, 136-38.
Dr. Roseff's opinion is based on his review of Petitioner's medical records, affidavits (from Petitioner as well as her parents), and medical or scientific literature (including articles on vaccine-induced autoimmune illness as well as articles on the latency period
Dr. Roseff's opinion began with testimony about RA, which he characterized as an "inflammatory polyarthritis of unclear etiology." Pet'r's Expert Report dated Feb. 2, 2011 at 3 [hereinafter "Roseff Report"]; see also Tr. at 10. As Dr. Roseff explained, RA has several patterns of onset, but classically results in a symmetric (meaning bilateral) inflammation of joints associated with stiffness and pain that, if left untreated or treated inadequately, can result in disability and even mortality. Tr. at 10. The majority of individuals who develop RA fall into the same demographic as Petitioner (i.e., young adult females), although Dr. Roseff later clarified that he believed Ms. Sullivan fell on the younger end of that spectrum. Id. at 10-11.
Dr. Roseff acknowledged that certain hereditary and environmental factors may place an individual at higher risk for developing RA (Tr. at 2), and that Ms. Sullivan's illness could have been caused by such non-vaccine related factors. Addendum to Pet'r's Expert Report, dated Feb. 9, 2011 (ECF No. 12-3) at 2 [hereinafter "Roseff Amended Report"]. However, Dr. Roseff opined that it was unlikely that Petitioner's RA could be attributed to this type of random occurrence. Tr. at 17. He initially reached this conclusion after reading various reports from the Gardasil Vaccine Adverse Event Reporting ("VAERS") database concerning the experiences of other individuals who developed RA after receiving the Gardasil vaccine — suggesting to him a correlation between the two. Id. at 18. He later admitted, however, that the VAERS database is a passive reporting system permitting anyone to report an adverse event, regardless of whether a medical professional has concluded that the adverse event can be linked to vaccination. Id. at 46.
As additional support for his causation opinion, Dr. Roseff pointed to findings from clinical studies included in the Gardasil vaccine package insert, which indicated that of the 9,412 individuals receiving placebo, two developed RA, while of 10,706 individuals who had received Gardasil, six developed this condition. Roseff Report at 3. Dr. Roseff characterized such numbers as a "disturbing trend," while admitting that they were nevertheless small and not otherwise corroborated by any statistical evidence from any specific scientific or medical studies regarding the Gardasil vaccine (or even the HPV vaccine more generally). Id. at 3, 8.
Dr. Roseff opined that because various viral antigens have been implicated in the development of RA, "[b]y extension, it is reasonable to suppose that immunizations can also be potential environmental triggers for RA development." Roseff Report at 3. As evidence of this concept, Dr. Roseff asserted that "[i]t had been known for years that exposure to the rubella vaccine represents a causal link to a chronic arthritis resembling RA in a small percentage of patients." Id. (emphasis added). Dr. Roseff also cited an article
For the precise mechanism by which the Gardasil vaccine could result in the development of RA, Dr. Roseff proposed molecular mimicry. Tr. at 76. Under Dr. Roseff's theory, (a) components of the Gardasil vaccine present to the body an antigen,
Dr. Roseff also proposed an alternative mechanism for how the Gardasil vaccine could produce an autoimmune response leading to the development of RA. He testified that aluminum contained in the Gardasil vaccine
One factual issue that Dr. Roseff's opinion attempted to address was the lengthy time gap between when Ms. Sullivan received the three separate Gardasil vaccines (between June 27, 2007, and January 4, 2008) and when her symptoms actually began. (As noted below, after an onset hearing held by the prior special master presiding over this case, a fact ruling was issued determining that onset of Ms. Sullivan's illness occurred sometime in "late March or early April 2008, in the few weeks prior to April 18, 2008." See Sullivan v. Sec'y of Health & Human Servs., No. 10-398V, 2013 WL 4011056, at *16 (Fed. Cl. Spec. Mstr. June 30, 2013) [hereinafter "Ruling Regarding Finding of Fact"]). Dr. Roseff acknowledged that the first time Petitioner sought care for her knee problem was on April 18, 2008, at which time she reported experiencing knee problems for only a week or two. Tr. at 44-45.
Dr. Roseff admitted that he could not distinguish which of three Gardasil vaccinations that Petitioner received was the primary cause of her RA, but argued that the build-up of all three vaccinations in her system could have been the instigating factor. Tr. at 69. However, he acknowledged that he could identify no particular study to support the conclusion that the series of Gardasil vaccines that Petitioner received could have had such a "cumulative effect." Id. at 85. Dr. Roseff also acknowledged that if the first vaccine that Ms. Sullivan received in June 2007 represented the beginning of this proposed build-up, the timeframe between her initial vaccination and onset of her alleged injury in April 2008 was greater than two months (Id. at 54), but he maintained that even the ten months between the first vaccination to onset would not be so long as to exonerate the Gardasil vaccination as having caused Ms. Sullivan's illness. Id. at 73.
To support his opinion regarding the lengthy temporal gap between vaccination and onset in this case, Dr. Roseff attempted to analogize Ms. Sullivan's circumstances to studies of other diseases featuring long latency periods, such as Lyme arthritis. Tr. at 23.
Dr. Roseff went on to discuss another article addressing a case study that considered from a retrospective standpoint the records of ten lupus patients to evaluate the length of time in which each individual developed lupus after receipt of the Hepatitis B vaccine. See N. Agmon-Levin, Y. Zafrir, Z. Paz, T. Shilton, G. Zandman-Goddard & Y. Shoenfeld, Ten Cases of Systemic Lupus Erythematosus Related to Hepatitis B Vaccine, 18 Lupus 1192, 1194-96 (2009) (ECF No. 39-4) (Pet'r's Ex. 32) [hereinafter "Agmon-Levin"]. The researchers found that there was variable timing for onset of disease following vaccination, ranging from a few days to as long as a year, with an average time of onset around two months post-vaccination. Id. at 1193; Tr. at 27. Dr. Roseff opined that based on such results, Ms. Sullivan's initial development of knee symptoms about two months after exposure to her last Gardasil vaccine was a reasonable timeframe. Tr. at 28.
In addition, Dr. Roseff also cited an article evaluating a rise in an autoimmune form of diabetes (Type 1, insulin dependent diabetes mellitus ("IDDM")) in children in Finland following the introduction of the Hemophilus influenza B vaccine, finding an increase in the diagnosis clustering in a period starting at about the thirty-eighth month mark from the date of vaccination and lasting approximately six months. Tr. at 32; see John Barthelow Classen & David C. Classen, Clustering of Cases of Insulin Dependent Diabetes (IDDM) Occurring Three Years After Hemophilus Influenza B (HiB) Immunization Support Causal Relationship Between Immunization and IDDM, 35 Autoimmunity 247, 250-52 (2002) (ECF No. 59-2) (Pet'r's Ex. 30) [hereinafter "Classen"]. He also referred to a prospective cohort study which attempted to evaluate the possibility of an autoimmune response following annual influenza ("flu") vaccination in healthy adults by looking at the change in antibodies post-vaccination, using blood samples taken prior to vaccination and then at one month and six months post-vaccination. Tr. at 29-30; see N. Toplak, T. Kveder, A. Trampus-Bakija, V. Subelj, S. Cucnik, & T. Avcin, Autoimmune Response Following Annual Influenza Vaccination in 92 Apparently Healthy Adults, 8 Autoimmunity Reviews 134, 137-38 (2008) (ECF No. 59-1) (Pet'r's Ex. 29) [hereinafter "Toplak"]. While the flu vaccination generally did not alter the percentage of healthy adults with positive autoantibodies, the Toplak researchers found that six months post-vaccination, approximately thirteen percent of patients either had higher titers of antibodies or developed new antibodies. Tr. at 30; Toplak at 2. Dr. Roseff focused on the presence of antibodies and postulated that six months post-exposure to a vaccination could actually be too soon to look for manifestations of clinical disease. Tr. at 30.
Dr. Roseff admitted that none of these studies involved the HPV vaccine generally (or the Gardasil vaccine more specifically), but justified his reliance on such studies in the absence of relevant, non-industry-funded, independent studies addressing the specific issue of RA following vaccination with Gardasil. Tr. at 33-34. Dr. Roseff also acknowledged that he knew of no persuasive epidemiologic or biologic evidence directly supporting his theory, but nevertheless opined "that it may just be too early to establish a statistical link." Roseff Report at 3. He maintained overall that there is "a strong possibility, knowing what we know about immunizations, and Gardasil specifically, that" the vaccinations that Ms. Sullivan received caused her RA. Id.; Tr. at 17.
In distinguishing reliable from unreliable studies, Dr. Roseff expressed the general opinion that studies sponsored by the pharmaceutical industry are inherently suspect due to bias. Tr. at 67 (referencing articles that he had read regarding bias in studies sponsored by the pharmaceutical industry); see also Joel Lexchin, Lisa A. Bero, Benjamin Djulbegovic & Otavio Clark, Pharmaceutical Industry Sponsorship and Research Outcome and Quality: Systematic Review, 326 BMJ 1167 (2003) (ECF No. 30) (Pet'r's Ex. 33) [hereinafter "Lexchin"]. He specifically questioned the scientific methodology of certain such studies. See, e.g., Tr. at 68. Thus, he opined that early studies sponsored by Merck, which did not observe harmful effects associated with the Gardasil vaccination, were tainted — both generally by Merck's involvement, as well as more specifically by the failure to use what he referred to as a "true placebo" group. Id. at 73. He testified that there were six initial studies conducted by Merck that purported to compare individuals who received the Gardasil vaccination to a placebo group, but only one study used a saline placebo (which Dr. Roseff deemed as the most scientifically reliable control) while most of the others used an aluminum-containing placebo (which he viewed as not a true placebo). Id. at 25. Dr. Roseff thus expressed the opinion that this group of studies was ultimately not reliable. Id. at 73.
2. Dr. Carlos Rosé — Respondent's expert, Daniel Carlos Rosé, M.D., graduated in 1977 from the University of Buenos Aires School of Medicine in Argentina, completing his residency in internal medicine at the University's hospital. Tr. at 87; Resp't's Ex. B. He then went on to an adult rheumatology fellowship in the National Institute of Rehabilitation; Department of Medicine, Rheumatology Division, Buenos Aires. Tr. at 87. In 1987, Dr. Rosé finished a pediatric residency at Thomas Jefferson University in Philadelphia, Pennsylvania, which was followed by a fellowship in pediatric rheumatology at Children's Hospital of Philadelphia. Id. Dr. Rosé is board-certified in pediatrics as well as pediatric and adult rheumatology. Id. He is currently a Professor of Pediatrics at Thomas Jefferson University where he teaches pediatric rheumatology to medical students, residents, adult fellows, and pediatric fellows, and he also lectures and publishes papers on the topic of RA. Id. at 89. He is a reviewer for several journals and on the editorial board for Rheumatology International. Id. at 89-90. He also serves on various Data Safety Monitoring Committees — also known as Data Safety Monitoring Boards (which are committees of independent experts responsible for monitoring patient safety and treatment efficacy data during ongoing clinical trials).
Dr. Rosé has been treating rheumatology patients for over thirty years. Tr. at 88. Since 1989 he has practiced at the duPont Hospital for Children in Wilmington, Delaware, where he is currently the Head of Pediatric Rheumatology with supervisory responsibility over four pediatric rheumatologists. Tr. at 86-88. As part of his rheumatology practice, Dr. Rosé sees patients at least twice a week, ranging from infants to young adults. Id. at 88. Dr. Rosé diagnoses both RA and JRA because he sees patients up to eighteen years of age, and the relevant diagnostic criteria require a diagnosis of RA (rather than JRA) if onset occurred after the patient was sixteen years of age.
Relying on his experience treating patients with rheumatologic disease, Dr. Rosé formulated his opinion in this case after reviewing Petitioner's medical records, affidavits from Petitioner as well as her parents, and pertinent medical or scientific literature. Resp't's Expert Opinion Report dated Mar. 9, 2011 (ECF No. 19-1) [hereinafter "Rosé Report"] at 1; Resp't's Expert Opinion Supplementary Report dated Apr. 30, 2011 (ECF No. 19-1) [hereinafter "Rosé Supplementary Report"]; Tr. at 91-92. Based on this review, Dr. Rosé formed an opinion that it is more likely than not that the series of Gardasil vaccinations that Ms. Sullivan received were unrelated to the onset and development of her RA. Tr. at 92, 94.
Dr. Rosé began by providing an overview of arthritis generally, and RA more specifically. Dr. Rosé explained that RA is a disease of unknown etiology, with one hundred percent of cases being idiopathic. Tr. at 95. He indicated that RA is a uniform disease (although many rheumatologists distinguish between individuals with RA who are seronegative versus those who are seropositive).
Dr. Rosé opined that there is no scientific or medical support for an association between the Gardasil vaccination and rheumatic disease. Rosé Report at 5-6. He indicated that although several human infections have arthritis as part of their clinical presentation or are associated with the development of a rheumatoid-like disease, there are no known viral causes of RA. Tr. at 96. Moreover, the wild-type human papillomavirus is not a known cause of acute or chronic arthritis in humans — making it even less likely in his estimation that the Gardasil vaccine could be so associated. Rosé Report at 5-6; Tr. at 98. Although he acknowledged that the Gardasil vaccine contains viral particles from multiple strains of HPV rather than a single strain from the wild type infection, he maintained his view that it was unlikely that the Gardasil vaccine can cause arthritic conditions. Tr. at 99.
Dr. Rosé further testified that his view was supported by scientific and medical literature (or at least the absence of negating literature). Dr. Rosé opined that he could not find a single case of RA established to have been caused by the Gardasil vaccination. Tr. at 98-99. Moreover, he expressed the view that if such an association existed, he would expect to have seen it in his clinical practice, but never has. Id. at 98. Indeed, clinical trial data collected to date (from a safety database built with data from spontaneous reporting by those patients who participated in clinical trials and their treating physicians) on the development of autoimmune disease following receipt of a different formulation of the HPV vaccination
Dr. Rosé went on to attempt to rebut Dr. Roseff's proposed mechanism by which RA could result after receipt of Gardasil. Although he agreed with Dr. Roseff's general characterization of the concept of molecular mimicry, he opined that there was no evidence that this mechanism is implicated in the development of RA; in fact, he indicated that it has not even been discussed in serious scientific or medical literature as a potential mechanism for the development of RA in at least the last ten years, even though it was previously considered, a fact he attributed mainly to an evolving understanding of RA. Tr. at 104-05. He also emphasized that (as Dr. Roseff acknowledged in his expert report) the relationship between the development of anti-CCP antibodies associated with RA and their reactivity with host tissues is unclear (thus underscoring that the biological mechanism by which RA develops is not fully understood). Rosé Report at 4; Roseff Report at 3.
Dr. Rosé specifically took issue with the assumption that the existence of some homology between peptide chains in human tissue and the components of vaccines logically leads to the conclusion that an autoimmune process will occur. Rosé Report at 4-5; Tr. at 106-07. Dr. Rosé indicated that short peptide homology, referenced in the Kanduc article relied upon by Dr. Roseff in formulating his opinion, "is at most a hypothesis generation step towards a theory of molecular mimicry." Rosé Report at 4. Moreover, he noted that because there are only a limited number of amino acids in nature that can be assembled in a limited number of ways to make proteins, it is not uncommon to find five amino acids that are homologous merely by chance. Tr. at 107. Dr. Rosé further testified that the Kanduc article made what he termed "extremely far-fetched statements" regarding potential side effects associated with receipt of the HPV vaccine, including setting forth (based on peptide homology) "a whole list of diseases that bear limited relationship with immune responses," yet even the authors had not suggested or concluded that receipt of the HPV vaccine would result in the development of RA. Id.
Dr. Rosé also questioned the logic of Dr. Roseff's opinion that the series of Gardasil vaccines that Ms. Sullivan received could have cumulatively resulted in the onset and development of her RA. Tr. at 108. Dr. Rosé noted that the vaccine contains only microdoses of aluminum insufficient in volume to have a negative effect in the body, while the protein components of the vaccine would themselves not accumulate in similar fashion (if at all). Id. at 108-09. Alternatively, Dr. Rosé asserted, if Dr. Roseff meant to argue that "more challenge"
Dr. Rosé then pointed out what he saw as deficiencies in Dr. Roseff's explanations for the lapse of time between Petitioner's receipt of the Gardasil vaccinations and her development of RA. Tr. at 97-98. As a general matter, Dr. Rosé acknowledged that there could be a variable period of time between a viral or bacterial infection (such as Lyme disease) and the development of some arthritic conditions. Id. But he contested Dr. Roseff's assertion that such conditions were analogous to RA.
The parties debated the evidentiary significance of an epidemiological study cited by Respondent in rebuttal of Petitioner's claim. C. Chao, et al., Surveillance of Autoimmune Conditions Following Routine Use of Quadrivalent Human Papillomavirus Vaccine, 271 J. Intern. Med. 193 (2012) (ECF No. 49-4) (Resp't's Ex. F) [hereinafter "Chao Study"]. This peer-reviewed observational study
While acknowledging that he did not have any special expertise in identifying conflicts of interest in scientific studies (Tr. at 62, 84-85),
In response, Dr. Rosé argued that the factors cited in the article referenced by Dr. Roseff — inappropriate comparator to the product being investigated and publication bias — were not applicable to the Chao Study. For instance, he argued that the requirement that Merck publish the Chao Study's findings regardless of outcome lent credibility to its results. Tr. at 110-13, 117. Dr. Rosé also disputed the validity of Dr. Roseff's concerns regarding the study's control group. He noted that it would likely have been approved by the Food and Drug Administration ("FDA") in advance, and in fact appeared to him (from his own review of the Chao Study) that the control group had been carefully selected. Id. at 113-14. Further, Dr. Rosé contested Dr. Roseff's argument that the only possible persuasive study regarding the safety of the Gardasil vaccine (in terms of autoimmune side effects, such as RA) would be a prospective, placebo-controlled study using saline for the control group. Id. at 114. Because autoimmune diseases occur so infrequently, such a study would require depriving thousands of control group participants of a vaccine that has been demonstrated to be beneficial — an outcome Dr. Rosé deemed unethical. Id.
Ms. Sullivan submitted four affidavits regarding the onset of her symptoms, including two from herself. See Pet'r's Exs. 1, 21. One of Petitioner's own affidavits indicated that prior to receipt of the Gardasil vaccinations she was "a healthy and active teenager," but after receiving the vaccinations she "began to experience chronic joint pain, joint inflammation, severe systemic body pain, problems concentrating, memory difficulties, headaches, and changes in [her] personality and temperament." Id. at 1. Petitioner's affidavits were supplemented by a daily self-health log (essentially a journal) in which she documented her daily symptoms beginning in January of 2010. Id. at 4-52 (Pet'r's Ex. A). Petitioner also submitted affidavits from her parents, Sandy and Dennis Sullivan, which included information regarding their understanding of the onset of her symptoms. Pet'r's Exs. 23, 24.
Both sides also offered substantial scientific and medical literature. Ms. Sullivan submitted eleven articles relied upon by Dr. Roseff in formulating an opinion in this case. Respondent cites certain literature submitted by Petitioner, as well as eleven additional articles, relied upon by her expert in formulating his opinion or rebutting Petitioner's expert.
Ms. Sullivan filed her Petition on June 28, 2010. Pet. at 1. In it, she specifically alleged that she suffers from chronic fatigue, severe joint and body pain, joint inflammation, cognitive impairment, headaches, numbness and tingling in her extremities, and irregular or heavy menstrual cycles which were all caused in fact by the HPV vaccine. Id. at 3-4. Since the filing of the Petition, Ms. Sullivan has alleged more specifically (and offered testimony during the hearing to this end) that her vaccination caused her to develop RA. See, e.g., Pet'r's Pre-Hr'g Filing (ECF No. 54); Tr. at 17.
On September 27, 2010, Respondent filed her Rule 4(c) report denying that Ms. Sullivan was entitled to compensation. ECF No. 7. In the ensuing twelve months, Petitioner filed medical records and both sides submitted expert reports. Thereafter, in September of 2011, the special master previously responsible for this matter scheduled a hearing for January 24, 2012, to resolve factual issues regarding the onset of Petitioner's condition. ECF No. 26.
The onset fact hearing was held as scheduled, with both sides filing pre- and post-hearing memoranda. That hearing included testimony from Petitioner plus her mother and father. See Ruling Regarding Finding of Fact at 7. After completion of the hearing and the passage of additional time, the special master issued a Ruling Regarding Finding of Fact on June 30, 2013, determining as follows:
Ruling Regarding Finding of Fact at 19.
In light of the results of this ruling, the parties were directed to file supplemental expert reports incorporating the Court's factual determinations and evaluating to what extent, if any, their experts' conclusions were altered as a result. ECF No. 45. Those supplemental reports were submitted in the fall of 2013. The report submitted by Dr. Roseff indicated that the timing outlined in the Ruling Regarding Finding of Fact did not change his opinion regarding the role that Gardasil played in Ms. Sullivan's ultimate development of rheumatic disease (indicating that there are "precedents in the rheumatic diseases, or in the literature, that support a delay of several months (as opposed to weeks) between exposure to an offending antigen, and onset of disease"). Supplemental Expert Report by Dr. Roseff dated Sept. 16, 2013 (ECF No. 48-1) (Pet'r's Ex. 28) at 1.
In January of 2014, I was assigned to this matter, and I scheduled an evidentiary hearing for July 10, 2014. ECF No. 53. The parties made additional pre-hearing filings and then participated in the hearing as scheduled, concluding the proceeding in a single day, and filing no post-trial briefs. The matter is now ripe for resolution.
To receive compensation under the Vaccine Program, a petitioner must prove either: (1) that she suffered a "Table Injury" — i.e., an injury falling within the Vaccine Injury Table — corresponding to one of the vaccinations in question, or (2) that her illness was actually caused by a vaccine (a category of claim often generically referred to as a "non-Table Injury"). See §§ 300aa-13(a)(1)(A),11(c)(1); § 300aa-14(a), as amended by 42 C.F.R. § 100.3; § 300aa-11(c)(1)(C)(ii)(I); see also Moberly v. Sec'y of Health & Human Servs., 592 F.3d 1315, 1321 (Fed. Cir. 2010); Capizzano v. Sec'y of Health & Human Servs., 440 F.3d 1317, 1320 (Fed. Cir. 2006).
Petitioners bear the burden of demonstrating actual causation by preponderant evidence. Cedillo v. Sec'y of Health & Human Servs., 592 F.3d 1315, 1321 (Fed. Cir. 2010); § 300aa-13(a)(1). To do so, 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." Althen v. Sec'y of Health & Human Servs., 418 F.3d 1274, 1278 (Fed. Cir. 2005). The preponderance standard requires a petitioner to demonstrate that it is "more likely than not" that the vaccine at issue caused her injury. Moberly, 592 F.3d at 1322 n.2. Proof of medical certainty is not required. Bunting v. Sec'y of Health & Human Servs., 931 F.2d 867, 873 (Fed. Cir. 1991). In particular, a petitioner must demonstrate that the vaccine was "not only [the] but-for cause of the injury but also a substantial factor in bringing about the injury." Moberly, 592 F.3d at 1321 (quoting Shyface v. Sec'y of Health & Human Servs., 165 F.3d 1344, 1352-53 (Fed. Cir. 1999)); Pafford v. Sec'y of Health & Human Servs., 451 F.3d 1352, 1355 (Fed. Cir. 2006). To determine if the petitioner has carried her burden, I must assess "the record as a whole" and may not make an entitlement decision in her favor based solely on her own claims "unsubstantiated by medical records or by medical opinion." § 300aa-13(a)(1).
Each of the Althen prongs requires a different showing (although the preponderant evidence standard applies to each). Under Althen prong one, petitioners must provide a "reputable medical theory," demonstrating that the vaccine received can cause the type of injury alleged. Pafford, 451 F.3d at 1355-56 (citations omitted). To satisfy this prong, petitioner's theory must be based on a "sound and reliable medical or scientific explanation." Knudsen v. Sec'y of Health & Human Servs., 35 F.3d 543, 548 (Fed. Cir. 1994). Such a theory must only be "legally probable, not medically or scientifically certain." Knudsen, 35 F.3d at 549.
Petitioners may satisfy the first Althen prong without resort to medical literature, epidemiological studies, demonstration of a specific mechanism, or a generally accepted medical theory. Andreu v. Sec'y of Health & Human Servs., 569 F.3d 1367, 1378-79 (Fed. Cir. 2009) (citing Capizzano, 440 F.3d at 1325-26). Special masters, despite their expertise, are not empowered by statute to conclusively resolve what are essentially thorny scientific and medical questions, and thus scientific evidence offered to establish Althen prong one is viewed "not through the lens of the laboratorian, but instead from the vantage point of the Vaccine Act's preponderant evidence standard." Andreu, 569 F.3d at 1380; W.C. v. Sec'y of Health & Human Servs., 704 F.3d 1352, 1356 (Fed. Cir. 2013) (a petitioner "must do more than demonstrate a `plausible' or `possible' causal link between the vaccination and the injury; he must prove his case by a preponderance of evidence") (citations omitted).
Often, however, establishing a sound and reliable medical theory requires that the parties present expert testimony in support of their claims. Lampe v. Sec'y of Health & Human Servs., 219 F.3d 1357, 1361 (Fed. Cir. 2000). Vaccine Program expert testimony is usually evaluated according to the factors for analyzing scientific reliability set forth in Daubert v. Merrell Dow Pharm., Inc., 509 U.S. 579, 594-96 (1993). Cedillo, 617 F.3d at 1339 (citing Terran v. Sec'y of Health & Human Servs., 195 F.3d 1302, 1316 (Fed. Cir. 1999)). "The Daubert factors for analyzing the reliability of testimony are: (1) whether a theory or technique can be (and has been) tested; (2) whether the theory or technique has been subjected to peer review and publication; (3) whether there is a known or potential rate of error and whether there are standards for controlling the error; and (4) whether the theory or technique enjoys general acceptance within a relevant scientific community." Terran, 195 F.3d at 1316 n.2 (citing Daubert, 509 U.S. at 592-95).
In other federal judicial fora (such as the district courts), the Daubert factors are employed by judges (in the performance of their evidentiary gatekeeper roles) to exclude evidence that is unreliable and/or could confuse a jury. In Vaccine Program cases, by contrast, these factors are used in the weighing of the reliability of scientific evidence proffered. Davis v. Sec'y of Health & Human Servs., 94 Fed. Cl. 53, 66-67 (2010) ("uniquely in this Circuit, the Daubert factors have been employed also as an acceptable evidentiary-gauging tool with respect to persuasiveness of expert testimony already admitted"). The flexible use of the Daubert factors to determine the persuasiveness of expert testimony has routinely been upheld. See, e.g., Snyder v. Sec'y of Health & Human Servs., 88 Fed. Cl. 706, 742-45 (2009). In this matter (as in numerous other Vaccine Program cases), Daubert has not been employed at the threshold, to determine what evidence should be admitted, but instead is employed to determine whether expert testimony offered is reliable and/or persuasive.
Where both sides offer expert testimony, a special master's decision may be "based on the credibility of the experts and the relative persuasiveness of their competing theories." Broekelschen v. Sec'y of Health & Human Servs., 618 F.3d 1339, 1347 (Fed. Cir. 2010) (citing Lampe, 219 F.3d at 1362). However, nothing requires the acceptance of an expert's conclusion "connected to existing data only by the ipse dixit of the expert," especially if "there is simply too great an analytical gap between the data and the opinion proffered." Snyder, 88 Fed. Cl. at 743 (quoting Gen. Elec. Co. v. Joiner, 522 U.S. 146 (1997)). Weighing the relative persuasiveness of competing expert testimony, based on a particular expert's credibility, is part of the overall reliability analysis to which special masters must subject expert testimony in Vaccine Program cases. Moberly, 592 F.3d at 1325-26 ("[a]ssessments as to the reliability of expert testimony often turn on credibility determinations"); see also Porter v. Sec'y of Health & Human Servs., 663 F.3d 1242, 1250 (Fed. Cir. 2011) ("this court has unambiguously explained that special masters are expected to consider the credibility of expert witnesses in evaluating petitions for compensation under the Vaccine Act").
The second Althen prong requires proof of a logical sequence of cause and effect, usually supported by facts derived from a petitioner's medical records. Althen, 418 F.3d at 1278; Andreu, 569 F.3d at 1375-77; Capizzano, 440 F.3d at 1326; Grant v. Sec'y of Health & Human Servs., 956 F.2d 1144, 1148 (Fed. Cir. 1992). In this regard, the opinions and views of the injured party's treating physicians are entitled to some weight. Andreu, 569 F.3d at 1367; Capizzano, 440 F.3d at 1326 ("medical records and medical opinion testimony are favored in vaccine cases, as treating physicians are likely to be in the best position to determine whether a `logical sequence of cause and effect show[s] that the vaccination was the reason for the injury'") (quoting Althen, 418 F.3d at 1280). Medical records are generally viewed as trustworthy evidence, since they are created contemporaneously with the treatment of the patient. Cucuras v. Sec'y of Health & Human Servs., 993 F.2d 1525, 1528 (Fed. Cir. 1993).
However, medical records setting forth a treating physician's views do not per se bind the special master to adopt the conclusions of such an individual, even if they must be considered and carefully evaluated. § 300aa-13(b)(1) (providing that "[a]ny such diagnosis, conclusion, judgment, test result, report, or summary shall not be binding on the special master or court"); Snyder, 88 Fed. Cl. at 746 n.67 ("there is nothing . . . that mandates that the testimony of a treating physician is sacrosanct— that it must be accepted in its entirety and cannot be rebutted"). Rather, as with expert testimony offered to establish a theory of causation, the opinions or diagnoses of treating physicians are only as trustworthy as the reasonableness of their suppositions or bases. The views of treating physicians should also be weighed against other, contrary evidence also present in the record — including conflicting opinions among such individuals. Hibbard v. Sec'y of Health & Human Servs., 100 Fed. Cl. 742, 749 (2011) (not arbitrary or capricious for special master to weigh competing treating physicians' conclusions against each other), aff'd, 698 F.3d 1355 (Fed. Cir. 2012); Caves v. Sec'y of Dep't of Health & Human Servs., 100 Fed. Cl. 119, 136 (2011), aff'd, 463 F. App'x 932 (Fed. Cir. 2012); Veryzer v. Sec'y of Health & Human Servs., No. 06-522V, 2011 WL 1935813, at *17 (Fed. Cl. Spec. Mstr. Apr. 29, 2011).
The third Althen prong requires establishing a "proximate temporal relationship" between the vaccination and the injury alleged. Althen, 418 F.3d at 1281. That term has been equated to the phrase "medically-acceptable temporal relationship." Id. A petitioner must offer "preponderant proof that the onset of symptoms occurred within a timeframe which, given the medical understanding of the disorder's etiology, it is medically acceptable to infer causation." Bazan v. Sec'y of Health & Human Servs., 539 F.3d 1347, 1352 (Fed. Cir. 2008). The explanation for what is a medically acceptable timeframe must also coincide with the theory of how the relevant vaccine can cause an injury (Althen prong one's requirement). Id. at 1352; Shapiro v. Sec'y of Health & Human Servs., 101 Fed. Cl. 532, 542 (2011), recons. denied after remand, 105 Fed. Cl. 353 (2012), aff'd mem., 2013 WL 1896173 (Fed. Cir. 2013); Koehn v. Sec'y of Health & Human Servs., No. 11-355V, 2013 WL 3214877 (Fed. Cl. Spec. Mstr. May 30, 2013), mot. for review denied (Fed. Cl. Dec. 3, 2013), aff'd, 773 F.3d 1239 (Fed. Cir. 2014).
I find, based on the existing record and testimony at hearing, that Ms. Sullivan has not met her burden of proof with respect to any of the Althen prongs.
At the outset, I note that Dr. Roseff's testimony on the "can cause" Althen prong one required him to go beyond his immediate professional expertise in the field of rheumatology. By his own admission, Dr. Roseff is not an immunologist, and has no demonstrated experience evaluating the effects of any vaccines in causing injury, in his own medical practice or elsewhere.
I have heard and considered Dr. Roseff's testimony despite the above. However, I may take into account an expert's overall competence in the field upon which he testifies as part of my weighing of the evidence. See, e.g., Walton v. Sec'y of Health & Human Servs., No. 04-503V, 2007 WL 1467307, at *17-18 (Fed. Cl. Spec. Mstr. Apr. 30, 2007) (otolaryngologist not well suited to testify about disciplines other than her own specialty). Dr. Roseff's lack of expertise on the topic of the capacity of vaccines such as Gardasil to cause injury leads me to give his testimony less weight than I might give the testimony of an expert with greater demonstrated experience in the subject matter. See, e.g., King v. Sec'y of Health & Human Servs., No. 03-584V, 2010 WL 892296, at *78-79 (Fed. Cl. Spec. Mstr. Mar. 12, 2010) (petitioner's expert far less qualified to offer opinion on general causation issues pertaining to autism than specific issues pertaining to the petitioner's actual medical history, given the nature of the expert's qualifications).
Putting that aside, I find that the substance of Dr. Roseff's opinion was unpersuasive and not supported by reliable evidence. He referenced no studies in which the Gardasil vaccine, any other HPV vaccination, or even a single strain of HPV wild virus, has caused RA (or any disease comparable to RA). Instead, he attempted to develop his theory by way of analogy to studies involving arthritic conditions arising after exposure to different viruses (such as the rubella virus or human parvovirus), or studies (like Toplak) observing autoimmune responses after vaccination. See supra Section IB1 (outlining Dr. Roseff's testimony). In effect, Dr. Roseff argues, (a) other viruses can produce arthritic conditions, and (b) vaccines can cause autoimmunity, therefore (c) it is reasonable to conclude by means of extrapolation from such evidence that the Gardasil vaccine could cause RA.
Although there is logic to such reasoning, I do not find that the evidence upon which it is based is sufficiently reliable to bulwark Petitioner's causation theory with the needed evidentiary ballast. As another special master noted in considering the Althen prong one analysis, "[t]he weight to be given an expert's opinion is based in part on the size of the gap between the science and the opinion proffered." Isaac v. Sec'y of Health & Human Servs., No. 08-601V, 2012 WL 3609993, at *17 (Fed. Cl. Spec. Mstr. July 30, 2012), mot. for review den'd, 108 Fed. Cl. 743 (2013), aff'd, 540 Fed. App'x 999 (Fed. Cir. 2013) (citing Cedillo, 617 at 1339). Here, that gap is too great. The fit between the literature Dr. Roseff cites and the theory he proposes is poor, based on inapposite comparisons involving different vaccines and different illnesses or untestable premises. Dr. Roseff assumes, without demonstrating, that other viruses that have been scientifically observed to produce arthritic conditions are comparable not only to the HPV wild virus but to the Gardasil vaccine itself (which contains four HPV strains). He also conclusorily reasons that a generalized reaction to one kind of vaccine is comparable to the type of reaction that one would expect to see from an entirely different vaccine. And in some cases, (specifically, with regard to the Classen article purporting to identify a causal link between other vaccines and IDDM), he relies on literature directly relating to theories that have been routinely rejected when offered to establish causation involving the tested vaccine. See, e.g., Meyers v. Sec'y of Health & Human Servs., No. 04-1771V, 2006 WL 1593947, at *5 (Fed. Cl. Spec. Mstr. May 22, 2006) ("[t]his court has previously considered and discredited the theories advanced by Dr. Classen") (discussing Baker v. Sec'y of Health & Human Servs., No. 99-653V, 2003 WL 22416622, at *33 (Fed. Cl. Spec. Mstr. May 22, 2006)).
Ms. Sullivan's overall theory regarding how the Gardasil vaccination could cause RA fails to hold up when analyzed under the Daubert framework used to evaluate the reliability of expert testimony in Vaccine Program cases. It has not been tested, subjected to peer review, or shown to be generally accepted in the relevant medical community. Terran, 195 F.3d at 1316 n.2 (citing Daubert, 509 U.S. at 592-95). While some of the individual pieces of literature cited by Petitioner may meet those criteria, that does not mean that Petitioner's overall theory (in support of which they are cited) is similarly reliable. In addition, (as noted above) nothing about Petitioner's theory is derived from Dr. Roseff's personal expertise, further diminishing its reliability (since he is the theory's author). And in many instances Dr. Roseff (who appeared to me an honest witness) undercut his opinion with admissions that Ms. Sullivan's illness may just as likely be of unknown origin. See, e.g., Roseff Report at 3 (indicating that "we cannot exclude the possibility that her development of disease was a random event," and admitting that "how [molecular mimicry] could result in our patient's CCP positivity is unclear").
The same considerations apply to Dr. Roseff's proposed molecular mimicry mechanism. A petitioner may successfully establish causation without proving the mechanism of injury. Knudsen, 35 F.3d at 548-49 (citations omitted). And there are Vaccine Program decisions in which molecular mimicry has been found to be a scientifically acceptable explanation sufficient to meet the preponderant, "more likely than not" evidentiary standard. See, e.g., Tompkins v. Sec'y of Health & Human Servs., No. 10-261V, 2013 WL 3498652, at *22 (Fed. Cl. Spec. Mstr. June 21, 2013) (in the specific context of establishing causation of Guillain-Barré syndrome after vaccination, "[t]he molecular mimicry theory is the one most widely accepted for the agents most frequently accepted as causal"), mot. for review denied, 117 Fed. Cl. 713 (2014); but see Wirt v. Sec'y of Health & Human Servs., No. 11-118V, 2014 WL 1911421, at *9-10 (Fed. Cl. Spec. Mstr. Apr. 18, 2014) (petitioner failed to satisfy Althen prong one in case in which expert proposed molecular mimicry as a mechanism by which the HPV vaccine could cause RA).
A petitioner cannot, however, simply intone the phrase "molecular mimicry" and thereby be deemed to have satisfied her Althen prong one burden. Hennessey v. Sec'y of Health & Human Servs., 91 Fed. Cl. 126, 134-35 (2010) (noting expert's overly broad application of the molecular mimicry theory made it meaningless). Here, and for the same reasons stated above, Petitioner has not sufficiently connected this aspect of her causation theory to the Gardasil vaccine or her RA to be legally persuasive,
Petitioner offers a few alternative mechanisms, but they are incompletely sketched out at best. Dr. Roseff proposed that aluminum contained in the Gardasil vaccine (as an adjuvant) could be responsible for stimulating an individual's immune system in a destructive manner (and he ties this argument in with his criticisms of a Merck study that used a placebo containing aluminum). See, e.g., Tr. at 25. Yet he admitted that this theory was highly speculative and based on very little scientific literature, if any. Id. at 60. Indeed, it appears from my review of the record that the only piece of filed literature even mentioning aluminum as a vaccine adjuvant, and the potentially negative impact it could have in causing a reactive disease or condition, is the Judicial Watch article — an advocacy piece with little scientific reliability, and which is conclusory in making this assertion as well. Joiner, 522 U.S. at 146 ("[t]rained experts commonly extrapolate from existing data[,] but nothing in either Daubert or the Federal Rules of Evidence requires a district court to admit opinion evidence that is connected to existing data only by the ipse dixit of the expert.").
Overall, Dr. Roseff has (by his own admission) done no more than opine that it is intellectually conceivable that administration of the Gardasil vaccine could result in the onset and development of RA. But this is insufficient to meet Petitioner's burden of proof, which (while not requiring scientific certainty) does obligate Petitioner to provide a "legally probable" explanation. Moberly, 592 F.3d at 1322 (quoting Knudsen, 35 F.3d at 548-49). Dr. Roseff's opinion, and the evidence offered in support of it, do not rise to that level of preponderant proof. See also Wirt, 2014 WL 1911421, at *9 (determining that "[t]here are simply too many unknowns, too many gaps in the analytical process of the theory, [] to conclude that Petitioner has proven a medical theory causally connecting the [HPV] vaccination and the injury [RA].") (citation omitted).
Also relevant to my analysis is the fact that Respondent offered credible and persuasive epidemiologic evidence — the Chao Study — undermining Petitioner's theory. Unquestionably, a petitioner need not offer epidemiologic proof to establish a reasonable and scientifically-reliable theory under Althen prong one. Capizzano, 440 F.3d at 1325. However, I may properly weigh such evidence against Petitioner's proof in evaluating whether she has carried her overall burden as to this first Althen prong. Koehn, 2013 WL 3214877, at *25 ("[t]he Federal Circuit has endorsed consideration of epidemiological studies as one factor in the special master's analysis");
The Chao Study is directly relevant to Ms. Sullivan's claim, and is persuasive evidence contradicting her causation theory. The same study has been determined in other Vaccine Program cases (in which it was invoked by Respondent) to be a valid epidemiologic study. See, e.g., C.K., 113 Fed. Cl. at 770; Godfrey v. Sec'y of Health & Human Servs., No. 10-565V, 2014 WL 3058353, at *17 (Fed. Cl. Spec. Mstr. June 11, 2014); Harris v. Sec'y of Health & Human Servs., No. 10-322V, 2014 WL 3159377, at *13-14 (Fed. Cl. Spec. Mstr. June 10, 2014), mot. for review denied, __ Fed. Cl. __ (Sept. 23, 2014). Although the Chao Study is not proof positive (from a legal standpoint) that Gardasil does not "cause" RA (and indeed as a special master I am not empowered to make such a scientific determination), the Chao Study undermines Petitioner's case that "more likely than not" the vaccine could have that effect.
Ms. Sullivan endeavored to call into question the study's credibility by impugning its source. The argument that a given study's authorship might impinge on the reliability of its findings is reasonable. See, e.g., Harris, 2014 WL 3159377, at *13 ("the source for Dr. Chao's funding opens a potential (if ultimately unresolvable) argument that her conclusions are not valid"). But the Supreme Court in Daubert, as well as the cases following it, has provided analytical tools for evaluating the existence of alleged errors in a study's methodology or analysis that, if present, would illustrate bias better than the unsubstantiated argument that an interested sponsor automatically casts doubt on the honesty of the study's findings. Daubert, 509 U.S. at 592-95.
Therefore, in order to put flesh on the bones of her argument that the Chao Study was biased, Petitioner needed to point out specific elements of the study demonstrating its unreliability. She failed to do so. The Chao Study simply looked at what actually happened to a large group of individuals who received the Gardasil vaccine versus those who did not, performing some subsequent statistical analyses to evaluate the significance of the incidence of autoimmune diseases after vaccination. An argument could be made that a larger sample size was needed to produce more reliable results, but Petitioner does not make that assertion. Hart v. Sec'y of Dep't of Health & Human Servs., 60 Fed. Cl. 598, 608 (2004) (quoting In re Norplant Contraceptive Prods. Liab. Litig., 215 F.Supp.2d 795, 830 (E.D. Tex. 2002)) ("epidemiological data that is not statistically significant cannot provide a scientific basis for an opinion of causation"). And the low incidence rate ratio for vaccinated individuals who subsequently developed RA (0.71) supports (at least from a statistical standpoint) the Chao Study's conclusion that Gardasil is highly unlikely to cause RA. See Daubert, 43 F.3d at 1321 (citing DeLuca v. Merrell Dow Pharm., Inc., 911 F.2d 941, 958 (3rd Cir. 1990)) ("[f]or an epidemiological study to show causation under a preponderance standard, `the relative risk of . . . [the defect or injury] arising from the epidemiological data . . . will, at a minimum, have to exceed `2'").
Those criticisms of the Chao Study Dr. Roseff did raise, such as the adequacy of its methodological control group, were not backed up by reliable evidence. Dr. Roseff's complaint that a truly independent study of vaccine safety would have created a blinded control group to receive a "true placebo" (saline) amounts to the assertion that only a randomized control study is trustworthy, as opposed to the observational study set forth in the Chao Study. It may be true that a more scientifically certain (and therefore persuasive) study is conceivable, and it is also the case that observational studies have their own inherent flaws. Dwyer v. Sec'y of Health & Human Servs., No. 03-1202V, 2010 WL 892250, at *64 (Fed. Cl. Spec. Mstr. Mar. 12, 2010) ("[e]very observational epidemiological study has some weaknesses because such studies examine the world as it is"). But (operating from the well-worn maxim that "the perfect is the enemy of the good")
The only other proof that Ms. Sullivan offers to support her causation theories are VAERS reports and data from the Gardasil package insert — none of which are particularly persuasive evidence. Because of their passive nature and unverified claims, VAERS reports are too anecdotal and unscientific to have much probative value in establishing a causation theory.
There is a notable lack of record support for the second Althen prong — that the Gardasil vaccine "did" cause Ms. Sullivan's injuries. Petitioner's contemporaneous medical records provide no evidence — such as a treating physician's statement, or a test result — supporting the view that the Gardasil series she had received was connected to her RA. There is only the fact that Ms. Sullivan received her last dose of the vaccine in January 2008, and then began to complain of knee-related pain no earlier than late March to early April of 2008 (as the Ruling Regarding Finding of Fact establishes).
During the hearing, both experts acknowledged this lack of record support linking Ms. Sullivan's vaccination to her RA. Aside from a single rheumatologist (who appears to have been merely recounting Mr. Sullivan's view that her RA was connected to the Gardasil vaccine), none of Petitioner's treating physicians ever identified Gardasil as a possible cause of her injury. Tr. at 74-75, 138. Dr. Rosé indicated that (based on his own ample experience diagnosing RA) he did not himself see anything in her treatment record that would support such a connection. Id. at 138. Dr. Roseff's expertise in rheumatology would have made him well-qualified to point out contrary evidence from the record (such as a test result that suggested a connection between the Gardasil vaccine and the development of Ms. Sullivan's symptoms, even if overlooked by a treating physician), but he admitted he could identify no such evidence either. Id. at 75. Petitioner has thus failed to offer preponderant evidence in support of the second Althen prong.
As I explained above, Ms. Sullivan did not provide a reliable theory for how the Gardasil vaccine could cause RA. Accordingly, she cannot satisfy the third Althen prong either, since the adequacy of the proposed timeframe in which the Gardasil vaccine could have caused the Petitioner's injury must relate to the medical theory for how this would occur in the first place. Bazan, 539 F.3d at 1352; Shapiro, 101 Fed. Cl. at 542. But even if I had found that Petitioner had provided preponderant evidence in satisfaction of Althen prong one, I would still find that this third prong has not been similarly satisfied.
Petitioner inconsistently argued what was a medically acceptable timeframe for onset in this case — sometimes appearing to measure onset from the last in the series of three Gardasil vaccinations she received, while other times suggesting that the series in total had a "cumulative effect,"
Measuring from the last Gardasil vaccination Ms. Sullivan received (January 4, 2008), the onset of her RA symptoms (beginning "somewhere between March and April 2008," as determined at the onset fact hearing) occurred ten to twelve weeks thereafter. Dr. Rosé proposed, however, that a reasonable timeframe in which any vaccine might conceivably cause some kind of arthritic condition would be no more than two to four weeks.
Ms. Sullivan attempted to substantiate three months as medically acceptable, pointing to literature showing purportedly analogous diseases that can be latent for that same period or longer. For instance, Dr. Roseff analogized RA to an inflammatory arthritic condition caused by Lyme disease (an insect-borne bacterial infection). Before being first recognized as a separate entity, Lyme arthritis was initially confused with early RA, so facially this comparison is not inapt. See Allen C. Steere & Lisa, Glickstein, Elucidation of Lyme Arthritis, 4 Nature Reviews Immunology 143 (2004) (Pet'r's Ex. 31 at 2). But Dr. Rosé persuasively argued that the timeframe for the development of Lyme arthritis was more logically attributed to persistence of inflammation (despite the otherwise successful treatment of the initial infection) rather than latent onset.
The same is true for the other purportedly analogous cases (as referenced in the Toplak or Agmon-Levin articles) involving latency periods cited by Dr. Roseff. The main common ground those articles generally have with present circumstances is the fact that they display a delayed autoimmune response following receipt of a vaccine. Otherwise, they all involve different vaccines and different diseases, and thus cannot be assumed to be scientifically comparable to a sufficient degree to support the theory that Ms. Sullivan could have experienced delayed onset of RA-related symptoms months after any of the series of Gardasil vaccines that she received. Indeed, these pieces of literature themselves are far more limited in the scope of their conclusions (as Dr. Roseff himself specifically admitted with respect to the Toplak article (see, e.g., Tr. at 47-48)). The Toplak article concludes with the specific observation that the flu vaccine did not "increase the percentage of positive autoantibodies in the general healthy adult population," even if some autoantibody increases were seen at certain temporal points after vaccine administration — increases having "no clear clinical significance." Toplak at 138; Tr. at 30.
Petitioner was also unable to establish preponderant evidence that the series of three Gardasil vaccinations she received could produce in concert the onset of her RA symptoms in the early spring of 2008. In an attempt to do so, she proposed (through Dr. Roseff's testimony) something along the lines of a "cumulative effect" or challenge-rechallenge theory — that Ms. Sullivan's successive vaccinations (whether due to build-up of aluminum in Ms. Sullivan's body, or simply from her system being primed immunologically) culminated in her initial knee symptoms and ultimate development of RA. But this theory was thinly substantiated and inadequately explained. The record shows absolutely no evidence that Ms. Sullivan experienced any reaction after receipt of the prior two Gardasil vaccines, as Dr. Rosé noted would be expected to have occurred if her immune system was being challenged after each successive vaccination. Tr. at 109; see also Hall v. Sec'y of Health & Human Servs., No. 02-1052V, 2007 WL 3120284, at *7 (Fed. Cl. Sept. 12, 2007) (a petitioner who suffered from a shoulder injury was entitled to compensation based on a challenge-rechallenge theory when petitioner received two doses of the hepatitis B vaccine and after each dose, she experienced problems in her shoulder within two weeks of the vaccination; the amount of time between the first vaccination and the start of her problems was more than the amount of time between the second vaccination and the start of problems; and the reaction to the second vaccination was also more severe). And as discussed above, Dr. Roseff himself did little more than speculate that it was possible that the Gardasil series Ms. Sullivan received could have built up in her body in some manner to result in her initial symptoms, supporting this speculation with unscientific literature like the Judicial Watch article rather than reliable scientific or medical proof. Petitioner thus did not establish that it was more likely than not that the total series of Gardasil vaccinations could cumulatively produce her initial symptoms two to three months after receipt of the final vaccination.
I have great sympathy for the suffering Ms. Sullivan experienced after receiving the Gardasil vaccinations. However, based on the records filed and testimony at hearing, I cannot conclude that she is entitled to an award of compensation in this case. The Vaccine Act permits me to award compensation only if a Petitioner alleging a "non-Table Injury" can show by medical records or competent medical opinion that the injury was more likely than not vaccine-caused. Here, there is insufficient evidence to support an award of compensation, leaving me no choice but to hereby
In the absence of a timely-filed motion for review (see Appendix B to the Rules of the Court), the Clerk shall enter judgment in accord with this decision.
Tompkins v. Sec'y of Health and Human Servs., No. 10-261V, 2013 WL 3498652, at *16 (Fed. Cl. Spec. Mstr. June 21, 2013), review denied sub nom., Tompkins v. United States, 117 Fed. Cl. 713 (2014).
However, neither party asked me to reconsider the Ruling Regarding Finding of Fact prior to the entitlement hearing in this case, nor did Petitioner attempt to argue that newly-discovered or additional proof relevant to onset favored a different outcome. Moreover, Dr. Roseff submitted a supplemental opinion in which he applied the findings from the Ruling Regarding Finding of Fact but still determined that his original opinion was valid. Supplemental Expert Report by Dr. Roseff dated Sept. 16, 2013 (ECF No. 48-1) (Pet'r's Ex. 28) at 1. Given the above (plus the fact that the Ruling Regarding Finding of Fact is comprehensive and was the result of a proceeding in which both sides had full opportunities to present evidence), in the exercise of my discretion I find that it is appropriate to adopt the Ruling Regarding Finding of Fact herein. See Pacific Gas & Elec. Co. v. United States, 114 Fed. Cl. 146, 149 (2013) (when a successor judge is transferred a case in which a prior order has been rendered, the successor judge "should not overrule the earlier judge's order or judgment merely because the later judge might have decided matters differently," but should exercise his discretion in determining if circumstances warrant reopening the previously-determined issue) (quoting United States v. O'Keefe, 128 F.3d 885, 891 (5th Cir. 1997)).
