LISA HAMILTON-FIELDMAN, Special Master.
Petitioners, Shon Sumner
The undersigned now finds that Petitioners have failed to prove, by a preponderance of the evidence, that S.E.B.'s injuries resulted from the administration of the MMR vaccine to Ms. Sumner during pregnancy. The Clerk's Office is ordered to enter judgment in favor of Respondent unless a motion for review is filed.
Ms. Sumner delivered her first child on December 7, 1995, via cesarean section. Pet. Ex. 5 at 65. The child, S.E.B.'s older sibling, was born full-term, and no congenital abnormalities were noted. See Ex. 5 at 65.
S.E.B. appears to have been conceived in early 1996; Ms. Sumner's last known menstrual period is alternatively dated February 15
Ms. Sumner's first prenatal visit took place on August 19, 1996, approximately 27 weeks into her pregnancy. Pet. Ex. 3 at 57-59. Ultrasounds performed on August 28, 1996 and November 6, 1996 were unremarkable. Pet. Ex. 5 at 22-23.
S.E.B. was born on November 21, 1996, at Taylor Regional Hospital in Hawkinsville, Georgia, at approximately 40 weeks gestation. Pet. Ex. 2 at 8, 41; see also Pet. Ex. 6 at 4 (noting that S.E.B.'s gestational age at birth was "approximately 38 weeks"). Delivered by repeat cesarean due to cephalopelvic
While at CCMC, S.E.B. received a hearing screening, a computerized tomography ("CT") scan, and a cranial ultrasound. Pet. Ex. 6 at 4-5, 25-27. She was discharged with a diagnosis of hydrocephalus ex vacuo
On December 9, 1996, S.E.B. was evaluated by her pediatrician, Dr. Johnny Peeples, at Eastman Pediatric Clinic ("Eastman"). Pet. Ex. 10 at 38. No abnormalities were noted, though Dr. Peeples observed that S.E.B. had a slightly large and elongated head. Id. When S.E.B. saw Dr. Peeples again on January 29, 1997, Dr. Peeples again noted no abnormalities except that S.E.B. had a slightly bulging fontanel. Id. at 36.
In approximately mid-March 1997, S.E.B. began having "episodes of jerking and clonic movements three times a day, followed by being tired and sleepy." Pet. Ex. 8 at 125. At a visit with Dr. Peeples on April 10, 1997, Ms. Sumner reported that she "noticed some spells when [S.E.B.] turns off to the side for about a second at a time for about 15 times in a row," and that she was concerned that S.E.B. was having seizures. Pet. Ex. 10 at 36. Dr. Peeples noted that she "has an appointment with Dr. Smithson with in [sic] the next week," and "[w]e will probably get an EEG." Id.
In early May of 1997, S.E.B. began to have episodes of "severe and prolonged jerks" with "eyes shifting back and forth lasting for 5-10 minutes." Pet. Ex. 8 at 125. Ms. Sumner brought S.E.B. to the Medical College of Georgia ("MCG") on May 12, 1997, where she reported that S.E.B.'s seizures had become more severe and prolonged "three to four days" prior. Id. at 125-26. S.E.B. was admitted "for hydrocephalus and to rule out tumor." Id.
On May 12, 1997, while at MCG, S.E.B. underwent a magnetic resonance imaging ("MRI") without contrast, a CT, and an electroencephalogram ("EEG") of her brain, which showed agenesis or partial agenesis of the corpus callosum,
After discharge, S.E.B. continued to treat at MCG. On July 1, 1997, neurosurgeon Anne Marie Flannery noted that there had been "[n]o seizures since discharge on 5/12/97." Pet. Ex. 8 at 50-51. Pediatric ophthalmologist Steven Brooks noted upon examination that, although "[t]he anterior segment of each eye was normal[,] . . . the funduscopic examination did show characteristic fundus lesions of Aicardi's [sic] syndrome. Specifically, there were numerous `punched-out' lacuner-type [sic] lesions throughout both fundae." Id. at 45. Dr. Brooks noted that his "colleague, Dr. Dennis Marcus, whom [sic] specializes in retina, also had a look at the left fundus but felt that the pigmentation overlying the nerve was . . . consistent with the Aicardi's [sic] syndrome." Id.
As of October 7, 1997, MCG neurologist James Carroll noted that S.E.B. had AS and that she continued to have "about 10 sets of spasm-like episodes per day." Pet. Ex. 8 at 38-39. On December 3, 1997, MCG pediatric neurologist Patricia Hartlage noted that S.E.B. had "responded somewhat to ACTH [Adrenocorticotropic hormone], although she still had as many as ten mild clusters a day until recently." Pet Ex. 8 at 36. During another visit with S.E.B. on October 6, 1998, when S.E.B. was almost two years old, Dr. Hartlage noted that S.E.B. "ha[d] a history of AICARDI syndrome and infantile spasms. She is cruising but is not walking independently. Her verbal development is a little more advanced than her gross motor skills, with perhaps 10 words, a good listening vocabulary, good social interaction, and a sense of humor." Pet. Ex. 8 at 35 ("Aicardi" capitalized in original).
On December 11, 1998, S.E.B. was re-admitted to MCG for placement of a Ventriculoperitoneal shunt, in order to relieve intraventricular pressure. Pet. Ex. 8 at 74-91. Post-surgery, S.E.B. was noted to be "more alert" and "more verbal." Id. at 25. On January 12, 1999 and August 24, 1999, S.E.B. was again noted to have been "doing well." Id. at 8-9, 19-21.
On January 10, 2001, S.E.B. was seen at Eastman for a fever. Pet. Ex. 10 at 26. Records indicate that "she was recently seen at the ER for a breakthrough seizure." Id. The assessment at Eastman was acute viral syndrome and AS with seizure disorder. Id. On August 15, 2002, S.E.B. was taken by ambulance to Dodge County Hospital in Eastman, Georgia because she was having seizures. Pet. Ex. 11 at 78. Her treating physician prescribed an increase in Phenobarbital. Id. at 75.
On April 22, 2004, S.E.B. was seen at Houston Neurology in Warner Robins, Georgia. Pet. Ex. 10 at 79. Notes from the exam indicate that S.E.B. had been fairly stable since her last visit. Id. S.E.B. had been taking 120 mg of Phenobarbital a day and 500 mg of Lamictal twice a day. Id. S.E.B.'s condition further stabilized, and at a follow-up appointment on July 29, 2004, she was having only two or three brief seizures a week. Pet. Ex. 10 at 78. Her treating neurologist, Abdul Qadir, recommended decreasing her Phenobarbital to 105mg a day in divided dosages. Id.
S.E.B. returned to Houston Neurology again on February 3, 2005. Pet. Ex. 10 at 77. Her mother complained that she had periods of "behavioral outbursts" and questioned whether her shunt was working properly. Id. During the exam, S.E.B. was uncooperative and had poor eye contact. Id. A CT scan was recommended, and her prescribed Phenobarbital dosage was decreased due to infrequent seizures (occurring only once every two weeks). Id. The CT scan results from March 7, 2005 showed hydrocephalus ("more pronounced on the left side") and indicated that the shunt tube may not be working. Pet. Ex. 10 at 45.
S.E.B. was seen at the Children's Neurology Center of Macon on April 6, 2006. Pet. Ex. 10 at 71. Her EEG results from January 2006 were described as "profoundly abnormal" and she was noted to be symptomatic of secondary generalized epilepsy syndrome. Id. Other medical impressions were AS, West's Syndrome, Mental Retardation, Cerebral Palsy, and possible Lennox-Gastaut Syndrome.
On April 30, 2008, S.E.B. was noted to be stable and her medication was "tolerated well." Pet. Ex. 10 at 66. The working impression of S.E.B.'s condition was "Lennox-Gastaut Syndrome with a history of pharmacoresistant epilepsy." Id. at 67. S.E.B. returned to the Children's Neurology Center on September 30, 2008, where notes indicate that she had "a remarkable reduction in the frequency of breakthrough seizures" on the medication Topamax.
On February 15, 2010, an EEG resulted in "findings consistent with a diffuse underlying disturbance of neuronal function with superimposed interictal features of a secondary generalized epilepsy such as that can be seen in Lennox-Gastaut syndrome." Pet. Ex. 9 at 17.
S.E.B. was seen at East Texas Medical Center in Tyler, Texas on June 21, 2012. Pet. Ex. 15 at 9. The physician's assessment was that S.E.B.'s diagnoses included AS and chronic seizure disorder (now only on one medication). Id. The physician also noted that S.E.B. was having an increasing amount of interaction with family members and more difficulty with discipline. Id. At her follow-up visit on August 16, 2012, she was reportedly still having seizures, as well as daily partial spells. Pet. Ex. 15 at 10. She was also having grand mal seizures during her menstrual period. Id. Notes indicate that an increase in her anticonvulsant medication, Banzel, to three a day, appeared to decrease the number of generalized seizures. Id.
The most recent medical record available is from a May 13, 2013 neurological follow-up. Pet. Ex. 15 at 13-14. At that time, S.E.B. she was noted to have mental retardation, AS, and frequent seizures. Id. Her medications included Depo-Provera and Banzel. Id.
The procedural history of this case is straightforward but protracted. Petitioners filed this vaccine petition on S.E.B.'s behalf on November 19, 1999, and the case was initially assigned to Special Master George Hastings. Medical records, including Exhibits 1 through 8, were filed between December 22, 1999 and March 21, 2000.
On April 18, 2000, Respondent filed a Rule 4 Report recommending against compensation in this case because, Respondent argued, Petitioners had not established by a preponderance of the evidence that S.E.B. suffered a vaccine-related injury. Resp. Report at 1-2. Respondent also took the position that, under 42 U.S.C. § 300aa-11(c)(1)(A), S.E.B. had not "received" a vaccine set forth in the Vaccine Injury Table, because the vaccine had been administered to her pregnant mother. Id. at 5. Respondent subsequently moved for dismissal of the petition under § 300aa-11(c)(1)(A). See Motion to Dismiss, July 13, 2000.
On February 8, 2001, Special Master Hastings ruled that Petitioners' stated legal theory was "untenable," see Burch v. Sec'y of Health & Human Servs., 99-946V, 2001 WL 180129 (Fed. Cl. Spec. Mstr. Feb. 8, 2001), but subsequently held the case "in abeyance for an indefinite period, in light of currently ongoing efforts to amend the Vaccine Act, amendments which might affect petitioner's burden in this proceeding." Order, March 29, 2001.
Six years later, Special Master Hastings issued an order directing Petitioners to file a status report indicating whether they desired to continue with the proceedings that were held in abeyance or whether another course of action was favored. Order, May 14, 2007. Petitioners requested and were given an opportunity to re-brief the issue of whether S.E.B. is eligible for a Program award based on the immunization administered to her mother while pregnant. Status Report, June 27, 2007; Order, July 16, 2007. Petitioners filed their brief on October 22, 2008, Respondent filed her brief on December 22, 2008, and Petitioners filed a Reply on February 24, 2009.
On April 9, 2010, Special Master Hastings concluded, in light of intervening United States Supreme Court opinions, that Petitioners would qualify for a Program award if they could prove, as a factual matter, that S.E.B.'s injuries were caused by the MMR vaccine. Burch v. Sec'y of Health & Human Servs., 99-946V, 2010 WL 1676767, at *2-3 (Fed. Cl. Spec. Mstr. Apr. 9, 2010). In other words, although Master Hastings held as a legal matter that S.E.B. could "receive" the vaccine as a result of the administration of the vaccine to Shon while she was pregnant with S.E.B., he did not to rule on the factual matter of whether such receipt actually occurred. See generally id. at *7-8. Rather, Special Master Hastings held, "[i]n light of my legal ruling above, the petitioners should determine whether they can obtain an expert report opining (1) that the vaccine likely proceeded through [Ms. Sumner]'s system into the system of the in utero [S.E.B.], and (2) that the vaccine likely caused injury to [S.E.B.]." Id. at *13 (emphasis in original). Petitioners were to file an expert report in compliance with Special Master Hastings' Order "as soon as possible;" in the event that "no such report [was] filed in 60 days, the petitioners . . . [were to file] status reports at 60-day intervals . . . until such an expert report is filed." Id. at *10.
Between June 8, 2010 and October 7, 2011, Petitioners filed nine status reports.
Special Master Hastings subsequently directed Petitioners to file status reports every 30 days until an expert report had been filed. Order, December 14, 2011, at 1. After Petitioners had filed four more status reports,
Petitioners ultimately filed their first expert report, authored by Dr. Joseph Bellanti, on October 9, 2012. See Pet. Ex. 12. Petitioners later filed two supplemental expert reports, also authored by Dr. Bellanti, on September 10, 2013 and November 8, 2013.
An entitlement hearing was held in Washington, D.C., on November 22, 2013. Both parties' experts testified. Although the parties ultimately agreed that S.E.B.'s signs and symptoms are consistent with Aicardi syndrome, they disagreed as to the etiology of S.E.B.'s Aicardi syndrome. Tr. at 28, 64-65. Dr. Bellanti took the position that a partial rubella infection can cause an injury with the same signs and symptoms as Aicardi syndrome and that, in this instance, the rubella vaccine caused such an infection in S.E.B.'s pregnant mother, that the infection crossed the placenta, and that it infected in utero S.E.B. Tr. at 20-23, 65. Dr. Raymond agreed that Aicardi syndrome is the correct diagnosis for S.E.B., but argued that congenital rubella syndrome ("CRS")
After the hearing, Petitioners and Respondent filed several additional articles, some of which had been discussed at the hearing. See Pet. Exs. 34, 35, 36; Resp. Exs. D, E. One of the articles filed after the hearing was Petitioners' Exhibit 35, the translation of Petitioners' Exhibit 28, which the undersigned had admitted at hearing over Respondent's objection. See infra note 30; tr. at 24-32. Respondent filed a second supplemental expert report, authored by Dr. Raymond, in response to the new medical literature that had been filed. See Resp. Ex. F. This matter is now ripe for a ruling.
To receive compensation under the Vaccine Act, Petitioners must demonstrate either that: (1) S.E.B suffered a "Table injury" by receiving a covered vaccine and subsequently developing a listed injury within the time frame prescribed by the Vaccine Injury Table set forth at 42 U.S.C. § 300aa-14, as amended by 42 C.F.R. § 100.3; or (2) S.E.B. suffered an "off-Table Injury," one not listed on the Table as a result of her receipt of a covered vaccine. See 42 U.S.C. §§ 300aa-11(c)(1)(C)(ii)(I); Moberly v. Sec'y of Health & Human Servs., 592 F.3d 1315, 1321-22 (Fed. Cir. 2010); Capizzano v. Sec'y of Health & Human Servs., 440 F.3d 1317, 1320 (Fed. Cir. 2006).
Because Petitioners do not allege a Table injury in this case, they must prove that S.E.B.'s injury was caused-in-fact by a covered vaccine. To establish causation-in-fact, Petitioners must demonstrate by a preponderance of the evidence that the vaccine was the cause of the injury. § 300aa-13(a)(1)(A). Petitioners are required to prove 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 1321-22 (quoting Shyface v. Sec'y of Health & Human Servs., 165 F.3d 1344, 1352-53 (Fed. Cir. 1999)).
In Althen v. Secretary of the Department of Health and Human Services, the Federal Circuit set forth a three-pronged test used to determine whether a petitioner has established a causal link between a vaccine and the claimed injury. 418 F.3d 1274, 1279 (Fed. Cir. 2005). The Althen test requires the petitioners to set forth: "(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. To establish entitlement to compensation under the Program, a petitioner is required to establish each of the three prongs of Althen by a preponderance of the evidence. Id.
Under the first prong of Althen, Petitioners must offer a scientific or medical theory that explains how the relevant vaccine could have caused S.E.B.'s alleged injury. Andreu v. Sec'y of Health & Human Servs., 569 F.3d 1367, 1375 (Fed. Cir. 2009); Pafford v. Sec'y of Health & Human Servs., 451 F.3d 1352, 1355-56 (Fed. Cir. 2006). Petitioners' theory of causation must be informed by a "sound and reliable medical or scientific explanation." Knudsen v. Sec'y of Health & Human Servs., 35 F.3d 543, 548 (Fed. Cir. 1994) (citing Grant v. Sec'y of Health & Human Servs., 956 F.2d 1144, 1148 (Fed. Cir. 1992)); see also Veryzer v. Sec'y of Health & Human Servs., 98 Fed. Cl. 214, 222-24 (2011) (noting that special masters are bound by both § 300aa-13(b)(1) and Vaccine Rule 8(b)(1) to consider only evidence that is both "relevant and reliable").
Vaccine Rule 8(b)(1) provides, in part, that the special master "must consider all relevant and reliable evidence governed by principles of fundamental fairness to both parties." Id. Emphasis added. The seminal case on what constitutes reliable evidence in the scientific context is Daubert v. Merrell Dow Pharmaceutical, Inc., 509 U.S. 579 (1993). In Daubert, the Court held that "in order to qualify as `scientific knowledge,' an inference or assertion must be derived by the scientific method. Proposed testimony must be supported by appropriate validation—i.e., `good grounds,' based on what is known." Id. at 590. The application of Daubert principles in Program cases has been approved repeatedly by the Federal Circuit. See, e.g., Cedillo v. Sec'y of Health & Human Servs., 617 F.3d 1328, 1338-39 (Fed. Cir. 2010) ("We have previously held that Special Masters may look to the Daubert standards in evaluating expert testimony.") (footnote omitted); Terran v. Sec'y of Health & Human Servs., 195 F.3d 1302, 1316 (Fed. Cir. 1999) (holding that it is appropriate for Special Masters to utilize Daubert as a framework for evaluating reliability of causation-in-fact theories presented in Program cases).
Daubert makes clear that no single factor or even group of factors constitutes a litmus test for the reliability of scientific evidence. Daubert, 509 U.S. at 594-95. See also Kumho Tire Co. v. Carmichael, 526 U.S. 137, 151 (1999) (the Daubert "list of factors was meant to be helpful, not definitive."). That does not mean, however, that scientific evidence should be admitted and evaluated in legal proceedings without regard to its reliability. Rather, the factors considered when evaluating reliability are intended to be flexible and to fit the particular case and kind of evidence involved. See Daubert, 509 U.S. at 594-95 (1993) (holding that "[t]he inquiry envisioned . . . [is] a flexible one. Its overarching subject is the scientific validity and thus the evidentiary relevance and reliability — of the principles that underlie a proposed submission. The focus, of course, must be solely on principles and methodology, not on the conclusions that they generate.")
If a petitioner relies on a medical opinion to support her theory, Special Masters must consider the basis for the opinion, and the reliability of that basis, in determining how much weight to afford the proffered opinion. See Broekelschen v. Sec'y of Health & Human Servs., 618 F.3d 1339, 1347 (Fed. Cir. 2010) ("The special master's decision often times is based on the credibility of the experts and the relative persuasiveness of their competing theories.") (citing Lampe v. Sec'y of Health & Human Servs., 219 F.3d 1357, 1361 (Fed. Cir. 2000)). When evaluating the reliability of an expert's opinion, special masters must ascertain whether the information upon which the expert is relying is accurate, because inaccuracies in the expert's factual assumptions compromise the reliability of the view offered. See Perreira v. Sec'y of Health & Human Servs., 33 F.3d 1375, 1376-77 (Fed. Cir. 1994) (an expert opinion is no better than the soundness of the reasons supporting it). The persuasiveness of the expert's testimony must be evaluated, and the testimony of one side's expert may be rejected when there is a reasonable basis for doing so. Burns v. Sec'y of Health & Human Servs., 3 F.3d 415, 417 (Fed. Cir. 1993).
In addition to showing that the vaccine at issue can cause a particular injury, a petitioner must also prove that the vaccine actually did cause the alleged injury in a particular case. Althen, 418 F.3d at 1279; see also Pafford v. Sec'y of Health & Human Servs., No. 01-165V, 2004 WL 1717359 at *4 (Fed. Cl. Spec. Mstr. July 16, 2004). 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. See, e.g., Andreu v. Sec'y of Health & Human Servs., 569 F.3d 1367, 1375-77 (Fed. Cir. 2009); Capizzano v. Sec'y of Health & Human Servs., 440 F.3d 1317, 1326 (Fed. Cir. 2006); Grant v. Sec'y of Health & Human Servs., 956 F.2d 1144, 1148 (Fed. Cir. 1992). "Petitioner must show that the vaccine was the `but for' cause of the harm . . . or in other words, that the vaccine was the `reason for the injury.'" Pafford v. Sec'y of Health & Human Servs., 451 F.3d 1352, 1356 (Fed. Cir. 2006) (internal citation omitted). A petitioner does not meet this obligation by showing a temporal association between the vaccination and the injury; the petitioner must explain how and why the injury occurred. Id.
A petitioner need not make a specific type of evidentiary showing, i.e., the petitioner is not required to offer "epidemiologic studies, rechallenge, the presence of pathological markers or genetic predisposition, or general acceptance in the scientific or medical communities to establish a logical sequence of cause and effect." Cappizano, 440 F.3d at 1325. Instead, a petitioner may satisfy her burden by presenting circumstantial evidence and reliable medical opinions. See id. at 1325-26.
The third Althen prong requires a petitioner to establish a "proximate temporal relationship" between the vaccination and the injury alleged. Althen, 418 F.3d at 1278-81. This term has been equated to the phrase "medically-acceptable temporal relationship." Id. at 1281. The petitioner must present "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-in-fact." de Bazan v. Sec'y of Health & Human Servs., 539 F.3d 1347, 1352 (Fed. Cir. 2008).
A petitioner's Althen Prong 3 theory must coincide with her theory as to how the relevant vaccine can cause the alleged injury under Prong 1. de Bazan, 539 F.3d at 1354. A Special Master cannot infer causation from temporal proximity alone. In fact, where a petitioner's expert views the temporal relationship as the "key" indicator of causation, the claim must fail. See Thibaudeau v. Sec'y of Health & Human Servs., 24 Cl. Ct. 400, 403-04 (Fed. Cl. Oct. 23, 1991); see generally Grant v. Sec'y of Health & Human Servs., 956 F.2d 1144, 1148 (Fed. Cir. 1992); Hasler v. United States, 718 F.2d 202, 205 (6th Cir. 1983).
Dr. Joseph Bellanti attended medical school at The University of Buffalo School of Medicine in 1958 and completed his residency in pediatrics at the Children's Hospital of Buffalo in 1961. Pet. Ex. 13 at 3. He was board-certified in pediatrics and by the conjoint board of Allergy and Immunology in 1964 and 1974, respectively. Pet. Ex. 13 at 4; tr. at 11. At the time of the entitlement hearing, Dr. Bellanti was a professor of pediatrics, microbiology, and immunology, and the Director of the International Center for Interdisciplinary Studies of Immunology at the Georgetown University School of Medicine, where he had joined the faculty in 1963. Pet. Ex. 13 at 1, 3; tr. at 10.
Dr. Bellanti testified that he has published over 400 peer-reviewed articles and over 20 books or book chapters, including a textbook in immunology (the fourth edition of which was published in 2012). Tr. at 10; Pet. Ex 13 at 12-41. He has been the president of several scientific organizations, including the Society for Pediatric Research, the American Association of Clinical Immunologists, and the American College of Allergy and Immunology. Tr. at 11; Pet. Ex. 13 at 5-7. He has served as editor-in-chief of several journals related to the study of pediatrics and immunology. Pet. Ex. 13 at 6; tr. at 11.
Dr. Bellanti also testified that he has a variety of experience specifically relevant to the issues in this case. He received post-doctoral training in developmental immunology at the University of Florida, where he studied the immune responses of young infants. Pet. Ex. 13 at 3; tr. at 10-12. He and his colleagues were "among the first to show the predominance of the IgM response in either infection or immunization in the newborn and in the fetus." Tr. at 11-12. While a research virologist at the Walter Reed Army Institute of Research between 1962 and 1964, he studied a group of infants infected with CRS and isolated the rubella virus for the first time from several bodily organs. Pet. Ex. 13 at 3; tr. at 12. Dr. Bellanti and his fellow researchers "were the first to describe the IgM as the predominant antibody following intrauterine infection." Tr. at 12; Pet. Ex. 17.
Based on the above qualifications, the undersigned admitted Dr. Bellanti as an expert in pediatrics, infectious diseases, immunology, and vaccines. Tr. at 12-13, 16.
Dr. Bellanti testified that he was "familiar with" the field of genetics, having done post-doctoral training and taken courses in the area. Tr. at 49. He also testified that he regularly diagnosed genetic conditions. Tr. at 50. However, Dr. Bellanti testified, he does not consider himself an expert in genetics. Id.
Dr. Gerald Raymond attended medical school at the University of Connecticut before completing two years of pediatric residency at Johns Hopkins Hospital and four years of additional residency training in neurology, with special qualifications in child neurology, at Massachusetts General Hospital and abroad. Resp. Ex. B at 1; tr. at 106. After his residency training, Dr. Raymond did fellowships in developmental neuropathology and in genetics and teratology. Resp. Ex. B at 1; tr. at 107. At the time of the entitlement hearing, Dr. Raymond was a neurology professor at the University of Minnesota and the Director of Pediatric Neurology at the University of Minnesota Medical Center. Resp. Ex. B at 1; tr. at 107. He is board-certified in neurology, with special qualifications in child neurology, and in clinical genetics. Tr. at 108.
Dr. Raymond has "a standard pediatric neurology outpatient practice" in which he regularly diagnoses and treats patients with genetic and neurological disorders. Tr. at 108. He also sees patients "who have and who we evaluate for teratogenic effects."
The undersigned admitted Dr. Raymond as an expert in pediatrics, neurology, and genetics. Tr. at 110.
Dr. Bellanti's theory, as expressed at the hearing,
Generally speaking, Dr. Bellanti defined CRS as
Tr. at 20-21. Unlike "classic" CRS (which enters the upper respiratory tract, replicates, and enters the bloodstream), CRS acquired by injection "goes directly into the tissues of the blood." Tr. at 85-86. Once in Ms. Sumner's bloodstream, Dr. Bellanti argued, the rubella virus — which, in a vaccine, is in its attenuated form
In an exhibit that was discussed during the hearing and filed post-hearing, Petitioners provided a case report of a "fatal case of the encephalitis associated with measles-rubella (MR) vaccine." Pet. Ex. 34 at 1.
Once the reversion had taken place in Ms. Sumner's body, Dr. Bellanti testified, the virulent (also known as "wild-type"
Id. "[T]he amount of virus. . . . [is] determined by the amount of viral replication in the placenta and in the baby;" only cases of full-blown infection will have the classic findings of "high IgM, the thymus, the eyes, the heart and so forth." Tr. at 86-87. The "damage [to the fetus] . . . is largely dependent upon the severity of the infection and also the stages of fetal development during which the fetus is infected." Tr. at 34, 45.
Moreover, Dr. Bellanti testified, a CRS infection can be variable both in terms of severity and in terms of clinical expression. Tr. at 22. Although the "classical presentation" of CRS involves "microcephaly, cataracts, heart disease, jaundice," "there are variations of it that can occur with one or two or three symptoms. All signs and symptoms don't have to be present." Id. A rubella infection can affect "any of the organs or tissues of the fetus." Tr. at 33; see also Pet. Ex. 33
The fact that Ms. Summer had been immunized with an MMR vaccine 18 years prior, see Pet. Ex. 1 at 2, would not have precluded the alleged pathogenesis, because of "the waning of immunity following immunization." Tr. at 45-46, 90-92.
According to Dr. Bellanti, a "hallmark of intrauterine or neonatal infection" is "a very prominent" immunoglobulin M ("IgM") in the bloodwork of a newborn. Tr. at 53. The degree of elevation in IgM "depends upon the degree of viral involvement, whether the immune system is infected and so forth. So, not all babies with — with congenital rubella syndrome have an elevated IgM." Tr. at 56. In a sample taken from S.E.B.'s cord blood, "the [total] IgM reported was 8, and the normal range is 5 to 25." Tr. at 54. Dr. Bellanti testified that the absence of IgM elevation doesn't exclude the possibility of a partial rubella infection. Tr. at 56. He also testified that a test for specific rubella IgM antibody, the results of which would have permitted a conclusive diagnosis of rubella infection, was not performed on S.E.B. Tr. at 98-100.
Petitioners provided one article describing a case study of a newborn who displayed symptoms consistent with Aicardi syndrome, and for whom, according to the author, "a serologic diagnosis of [CRS] was made." Pet. Ex. 35 at 1.
Dr. Bellanti explained that, despite its name, CRS is "not really a syndrome;" it is a disease. Tr. at 20-21. "The basic difference [between a "disease" and a "syndrome"] is [that] a disease is an entity with signs and symptoms where we know what the etiology is. We know the cause. A syndrome is a group of signs and symptoms where we don't know. There may be many causes." Tr. at 23. When the entity "CRS" was named, prior to 1964, researchers believed that the signs and symptoms were associated with a virus, but they did not know. Tr. at 23-24. The cause of CRS is now generally understood to be a full-blown rubella infection.
Petitioners ultimately conceded that S.E.B.'s signs and symptoms are consistent with Aicardi syndrome,
Dr. Bellanti also conceded that the eye features and agenesis of the corpus callosum — both of which are present in S.E.B. — are almost always present in Aicardi, and are rarely, if ever, present in CRS. Tr. at 96. In addition, Dr. Bellanti agreed that the hallmarks of CRS — including cataracts, heart disease, hearing loss, and thrombocytopenic purpura — are not present in S.E.B.'s case, but he explained this in part by noting that CRS can infect any tissue in the body. Tr. at 21-22, 60-61. The fact that the rubella virus was introduced directly to Ms. Sumner's bloodstream, as opposed to through the respiratory tract, avoided some of Ms. Sumner's immunological system, and thereby "avoid[ed] some of the defense of the mother's immunological system and her ability to stop it going into the fetus through the placenta." Tr. at 44-45.
Dr. Bellanti agreed that it is rare for an attenuated virus to revert to a virulent virus — also known as a "wild" virus — but that it has happened before. Tr. at 34, 40-41, 96. He admitted that he has never encountered a case of a "vaccine virus, such as the type received by [Ms. Sumner], result[ing] in congenital rubella syndrome." Tr. at 62. According to the MMR vaccine package insert, of 700 pregnant women surveyed who received the rubella vaccine during pregnancy, none of the newborns had abnormalities consistent with CRS. Pet. Ex. 32 at 6; tr. at 62-64. According to the Centers for Disease Control and Prevention (CDC) Guidelines for Vaccinating Pregnant Women, of 226 pregnant women who received the MMR vaccine between 1971 and 1989, there were no reported cases of CRS. Pet. Ex. 25
Dr. Bellanti explained that S.E.B.'s case is an extremely rare event, and that neither of the above surveys has studied large enough populations of pregnant women to be probative. Tr. 63-64. For ethical reasons, a larger study would be impossible, however. Id.
Dr. Raymond agreed with Dr. Bellanti that "there is a theoretical risk to the fetus from vaccination of the mother during pregnancy with MMR," and that the MMR vaccine is contraindicated in pregnant women. Pet. Ex. 25 at 4; tr. at 103, 136-37. However, Dr. Raymond stated that there exists no epidemiologic evidence of a case of CRS "secondary to a pregnant individual receiving the MMR vaccine." Tr. at 112. Dr. Raymond agreed that the fact that the vaccine was administered to Ms. Sumner, rather than to S.E.B., has no bearing on whether it would regress to a wild virus. Tr. at 155. Dr. Raymond also agreed that it was possible, though rare, for a virus to convert to its virulent form. Tr. at 146-49. For instance, subacute sclerosing panencephalitis ("SSPE"), which is "an example of a case where the measles virus converts and then becomes virulent," occurs in about one in a million doses of the measles vaccine. Id. Dr. Raymond conceded that "a relatively minor [infection] in the mother . . . [could] still be a significant infection in the fetus." Tr. at 156. Depending on when the infection's viral load is spiking, a rubella infection may affect fetal development at different times of gestation. Tr. at 137-38.
Dr. Raymond testified that S.E.B. was tested for a broad IgM panel, but that a test specifically for IgM to rubella was not done; therefore, the blood testing results neither support nor refute Dr. Bellanti's theory. Tr. at 144. Similarly, although an IgG test was positive for rubella, this merely reflected that Ms. Sumner was immune, potentially as a result of her earlier MMR vaccination, and passed this immunity on to her child; it does not reflect that the child was infected with rubella in utero. Tr. at 145.
Dr. Raymond did not agree, however, that a rubella infection was the likely cause of S.E.B.'s injuries. Tr. at 113-14. Notwithstanding his testimony regarding the effects on a fetus of mild infections in the mother, Dr. Raymond opined that, specifically in the context of an attenuated rubella strain, "[i]f there was conversion to wildtype rubella, the mother should have been ill even if it was only a mild infection." Resp. Ex. F at 1.
Based on what is generally understood about the etiology of Aicardi syndrome, Dr. Raymond disagreed that infections are likely to play a role in causing it. There exists no epidemiologic evidence of a single case of CRS "secondary to a pregnant individual receiving the MMR vaccine." Tr. at 112. Aicardi syndrome is presumed to be caused by a dominant de novo mutation in an X-linked gene, and it generally occurs only in females (though it has been reported in rare instances in males with an extra X chromosome). Tr. at 113-15; Resp. Ex. A-1 at 3.
Dr. Raymond opined that, for the most part, the signs and symptoms that define each syndrome do not overlap. Aicardi syndrome is characterized by either partial or complete absence of the corpus callosum, distinctive lesions or "lacunae" of the retina of the eye, heterotopia,
In identifying the recommended surveillance standards for rubella and CRS, the World Health Organization ("WHO") recommends that serologic screening — that is, a blood test for rubella-specific IgM — be conducted in any case involving two primary symptoms or one primary symptom and one secondary symptom. Resp. Ex. E;
Dr. Raymond explained that the signs and symptoms attributable to rubella infections and to Aicardi are different in kind because their etiologies are different. In general, Aicardi is a patchy abnormality consistent with X chromosome inactivation, see tr. at 113-14, and CRS, which is the result of an in utero infection that affects cell proliferation, produces a more diffuse abnormality. Tr. at 126-27. Rubella infections, in other words, reduce "the number of cells available," which explains the etiology of symptoms such as microcephaly and salt and pepper retinopathy. Tr. at 160. See also Pet. Ex. 22 at 584. Aicardi, in contrast, turns on inappropriate genes, resulting in the formation of a brain and/or a retina which, essentially, have holes in them. Tr. at 160. Accordingly, Dr. Raymond's opined, a child who had a rubella infection in utero "should . . . manifest congenital rubella syndrome and not an unrelated pattern of malformation." Resp. Ex. F at 1.
In response to Orquin, Dr. Raymond argued that the authors had failed to substantiate their claim that they had obtained serologic evidence of CRS in the studied newborn. Resp. Ex. F. Additionally, Dr. Raymond argued, the newborn's symptoms did not meet the WHO criteria for CRS. Id.; see also Resp. Ex. E.
At the entitlement hearing, Dr. Bellanti conceded that his pre-hearing reports included some missteps, including asserting in his First Report that S.E.B.'s Aicardi syndrome was caused by the mumps component of the vaccine, tr. at 19, and confusing Aicardi syndrome with Aicardi-Goutières syndrome (AGS) in his First Supplemental Report. Tr. at 66-69; see infra Section (D)(a)(1)(iii). Petitioners affirmed at hearing that Petitioners' causation theory was focused solely on the rubella component of the vaccine, tr. at 52, that Aicardi syndrome, not Aicardi-Goutières syndrome, is the injury at issue in this case, tr. at 66-69, and that S.E.B.'s symptoms are consistent with the characteristics of Aicardi syndrome. Tr. at 28.
Mindful of the mandate that special masters "shall consider the entire record," 42 U.S.C. §300aa-13(b)(1); see also Hines ex rel. Sevier v. Sec'y of the Dep't of Health & Human Servs., 940 F.2d 1518, 1528 (Fed. Cir. 1991), the undersigned has considered the experts' prehearing reports and exhibits both because they still provide relevant substantive information and because they are relevant to an assessment of the experts' credibility and the reliability of their overall scientific methodology. See Porter v. Sec'y of Health & Human Servs., 663 F.3d 1242, 1250-51 (Fed. Cir. 2010) citing Moberly, 592 F.3d 1315, 1326 (holding that special masters are expected to consider the credibility of expert witnesses in evaluating petitions for compensation under the Vaccine Act). That discussion follows in Section (D)(a)(1).
However, because Dr. Bellanti articulated a new theory of causation at the entitlement hearing, the undersigned has determined that it is appropriate to apply the Althen analysis primarily to Dr. Bellanti's hearing testimony as the most recent and complete iteration of Petitioners' theory of the case. That discussion is the focus of Section (D)(a)(2).
In the present case, the reliability issues with Dr. Bellanti's reports and testimony are so myriad and pervasive that they cast doubt upon the reliability of his opinions. A detailed discussion of several of the more problematic issues follows.
It is a basic tenet of due process and fundamental fairness that all parties to a proceeding should have an opportunity to review and evaluate all of the evidence upon which the decision in that proceeding may be based. In the vaccine context, where discovery is limited, see generally Vaccine Rule 7, this principle has been given effect in a number of ways, including full disclosure of medical records, early disclosure of expert opinions and the basis therefor, and post-hearing briefing where necessary. The findings of a special master will be overturned if they appear to be based on information the parties did not have an opportunity to address at hearing or in briefing. Davis v. Sec'y of Health & Human Servs., 94 Fed. Cl. 53, 65-66 (2010); Kirkpatrick v. Sec'y of Health & Human Servs., No. 90-877V, 1991 WL 242997, at *3 (Fed. Cl. Spec. Mstr. 1991). Advance notice of evidence and theories is particularly important in a highly scientific or technical context such as the Vaccine Program, where an adequate response to new information may require additional scientific research and evaluation.
This type of notice issue was particularly problematic in this case, as will be discussed in detail below.
The undersigned understands that circumstances arise in vaccine cases that make the late filing of expert reports or exhibits necessary: The petitioner's diagnosis is in dispute, or her medical condition changes; the science in the field is changing rapidly, and new studies are being filed; petititioners have difficulties obtaining an expert. But no such circumstances applied in this case. S.E.B.'s Aicardi diagnosis had been consistent in the medical notes of treating physicians since she was an infant, and while there was a delay of almost two years while Petitioners obtained updated medical records, neither expert used those records in any substantive way in formulating his opinions. The questions of whether the vaccine could cross the placenta and cause injury, and whether the attenuated vaccine virus could revert to virulence, had been pending in the case from its filing, and at a minimum since Special Master Hastings' ruling on the vaccinee issue in 2010. And yet, Horstmann, published in 1969, Petitioners' intended answer to those questions, was not filed until November 20, 2013, two days before hearing. See Pet. Ex. 33. Orquin was published in 1981, and most of the literature upon which Petitioners relied had been published decades before the case went to hearing. See Pet. Ex. 28, 35. Dr. Bellanti filed his First Report in 2012, and yet he was still formulating his theory concerning "partial" infection and "full-blown" versus "not full-blown" CRS as he was testifying at hearing.
There are no extenuating circumstances in this case, no reason for these late filings. The prejudice, the damage to the proceedings, to Respondent's ability to understand the literature and the theories and respond to them cogently, is obvious. Evidence submitted this late in proceedings, in the absence of extenuating circumstances, raises issues under the fundamental fairness provision of Vaccine Rule 8.
In his Second Supplemental Report, Dr. Bellanti quoted Orquin as saying:
Pet. Ex. 28 at 4. However, this is not actually a quote from the article itself. It is a two-sentence English-language summary of the article, the source of which is uncertain. The actual article is in French; it was attached to Dr. Bellanti's Second Supplemental Report and relied on at hearing without translation. Dr. Bellanti's Second Supplemental Report was filed November 8, 2013, fourteen days before hearing. In preparing for the hearing, it simply did not occur to the undersigned that experienced counsel and an experienced expert witness would rely on an untranslated article at hearing. Petitioners had not attempted to get a translation by the date of hearing, however, instead asserting that "Dr. Bellanti, I think, understands French fairly well and can probably interpret fairly well what is said there," Tr. at 24, to which Respondent, obviously, objected under Vaccine Rule 8.
This would have been a reliability issue even if Orquin was peripheral to Petitioners' claims, but it was not. Orquin, along with Gualberto (which was not submitted until the day of hearing), was the basis of Petitioners' argument that one of the etiologies of the constellation of symptoms that constitute Aicardi syndrome is congenital rubella infection. Tr. at 65-66; see also Pet. Ex. 34, 35. In addition, "what the serologic basis was for that [Orquin] diagnosis of congenital rubella," was also crucial. Tr. at 25, 81-84.
Orquin was published in 1981; the Aicardi diagnosis and whether it was caused by the MMR vaccine has been the issue since the petition was filed. There was no reason a translation could not have been available at, and before, hearing. The fact that it was not undermined the reliability of this specific argument, and further undermined the undersigned's confidence in Dr. Bellanti's expert opinion as a whole.
This significant reliability issue is exemplified by Petitioners use of Horstmann. See Pet. Ex. 33. This article was submitted for publication on August 15, 1969, and was published in the October 1969 volume of the Yale Journal of Biology and Medicine. Id. Petitioners cited it in response to Special Master Hastings' 2010 question concerning "whether the vaccine likely proceeded through Mrs. [Sumner]'s system into the system of an in utero S.E.B." Pet. Ex. 27 at 1; 2010 Ruling at 13. It was the only evidence submitted by Petitioners on the issue of whether the vaccine could have crossed the placenta. In addition, along with a single case report about vaccine reversion in an adult that was submitted on the day of hearing,
Horstmann was cited by Petitioners for this assertion: "Because all rubella vaccines contain live virus, they are contraindicated in pregnancy. This is particularly true since there is now evidence from trials in women scheduled for therapeutic abortion that the attenuated virus can infect the placenta, and probably the fetus." Pet. Ex. 33 at 9 (emphasis in original). The article documenting that "evidence from trials" was published in August 1969; it was filed as Respondent's Exhibit D. It included this summary:
Resp. Ex. D at 4. These quotes point out the perils of relying on literature that is almost 45 years old. The first live attenuated vaccine, HPV-77, had been developed in 1966, only three years before these articles were published. Lee at 4. The HPV-77 DE-5 underlying the Horstmann article "became the first rubella vaccine licensed for use in the United States" in 1969. Id. However, "[s]oon afterward, other live attenuated RV vaccines became available, and one of these, the RA 27/3 strain, became the mainstay of vaccination programs in most developed countries." Id. The medical technology upon which the Petitioners' cited research relied was in its nacency; its efficacy and safety had 25 years to improve before the MMR vaccine was administered to Shon Sumner/S.E.B. in 1996. Pet. Ex. 1 at 1. Lee, published in 2000, concluded "[s]ince vaccination does not result in congenital abnormalities when inadvertently given in early pregnancy, comparisons of vaccine strains with wild-type strains may reveal important motifs associated with teratogenicity." Pet. Ex. 22 at 15. This conclusion is contrary to the conclusion concerning the teratogenicity of the vaccine reached by Horstmann quoted above. See Pet. Ex. 33.
The other literature upon which Dr. Bellanti relied was similarly dated: for example, Orquin was published in 1981. As Dr. Raymond noted at hearing, this article "is over 30 years old, and the field of study of Aicardi syndrome has moved way beyond that." Tr. at 130; see also Pet. Ex. 35. Dr. Bellanti's reliance on this extremely outdated literature is another strike against the reliability of his scientific methodology.
Petitioners filed Dr. Bellanti's First Expert Report on October 9, 2012. See Pet. Ex. 12. In that report, Dr. Bellanti recognized the correct Aicardi syndrome, and that S.E.B. had been diagnosed with Aicardi. See generally Pet. Ex. 12. At page 7 of his First Expert Report, after the first reference to Aicardi syndrome set forth in his summary of S.E.B.'s medical records, Dr. Bellanti dropped this footnote: "Aicardi syndrome is a rare genetic malformation syndrome characterized by the partial or complete absence of a key structure in the brain called the corpus callosum, the presence of retinal abnormalities, and seizures in the form of infantile spasms." Pet. Ex. 12 at 7, n.5. His medical records summary then continues with a detailed discussion of the medical conditions from which S.E.B. suffers which supported her many treating physicians' diagnoses of Aicardi. See generally Pet. Ex. 12.
Dr. Bellanti's First Report concludes: "Clinical notes on 7/3/97 indicate that [S.E.B.] was an 8-month-old youngster with a diagnosis of Aicardi's [sic] syndrome, developmental delays and seizures. . . .These genetic malformations are direct results of the vaccination that Shon [Sumner] had on March 25, 1996." Pet. Ex. 12 at 26.
By the time of his First Supplemental Report, Dr. Bellanti had purportedly "undertaken a detailed review of the medical literature on Aicardi syndrome." Pet. Ex. 16 at 1. In reality, however, he had merely attached a number of articles about AGS, a condition linked to Aicardi syndrome only by the fact that they were both first discovered and written about by the same doctor, Dr. Jean Aicardi. Pet. Ex. 18-21, 23. In his First Supplemental Report, Dr. Bellanti erroneously described Aicardi as being "characterized by acquired microcephaly, cerebral calcifications, leukodystrophy, poor feeding, jitteriness, cerebral atrophy, problems with white matter, and chilblains-like (scaly or necrotic) skin lesions, usually on the fingers, toes and ears." Pet. Ex. 16 at 1. Clearly this is not the same condition described in his First Report, the condition from which S.E.B. clearly suffers, and which Dr. Bellanti agreed she had. And yet, Dr. Bellanti's First Supplemental Report concludes: "In conclusion, as described in my previous opinion, I believe that it is highly unlikely that [S.E.B.] has Aicardi syndrome, and [S.E.B.]'s current medical conditions of developmental delay, seizures, and ophthalmological damage are to a reasonable degree of medical and scientific certainty more likely than not caused or contributed to by the MMR vaccine administered to her mother in utero [sic] at 28 days gestation." Pet. Ex. 16 at 2.
Another example of Dr. Bellanti's failure to reread his own report and the medical records can be found in his treatment of page 45 of Petitioners' Exhibit 8. In support of his first Report, Dr. Bellanti engaged in a thorough review of S.E.B.'s medical records, and 25 of the report's 26 pages concern an extensive summary of those records. Included in that summary is this lengthy excerpt from Exhibit 8 at 45:
First Report at 8-9 (emphasis added). The entire purpose of this letter was for Dr. Brooks to confirm that he and his colleague, Dr. Marcus, both ophthalmologists and faculty members at Medical College at Georgia, had examined S.E.B., and that the lacunar lesions and hyperpigmentation in her eyes were indeed consistent with a diagnosis of Aicardi syndrome, and Dr. Bellanti recognized that purpose in his First Report. Pet. Ex. 12. But in his First Supplemental Report, Dr. Bellanti discusses only the highlighted sentence concerning "slightly enlarged head circumference" as support for his conclusion that S.E.B. does not have Aicardi syndrome. Pet. Ex. 16 at 2.
Dr. Bellanti opens his First Supplemental Report by saying "[t]his letter is to update my expert opinion in the [S.E.B.] case. . .The following are my rebuttal arguments to those made by Dr. Raymond that [S.E.B.]'s medical conditions are the result of Aicardi syndrome." But at a minimum, the contradictory conclusions noted above demonstrate that Dr. Bellanti did not even review his own first report before preparing his second. Pet. Ex. 16. Nor did Dr. Bellanti read any of the literature cited by Dr. Raymond in support of Respondent's first report. Had Dr. Bellanti made even a cursory review of his own first report and Sutton, attached to Dr. Raymond's report, he would have recognized the distinction between AS and AGS, before leading the parties on a wild goose chase after the wrong syndrome. It is a basic tenet of scientific research that one reviews one's own work before supplementing it, and Dr. Bellanti's failure to do so further calls into question the reliability of his scientific methodology, the substance of which is the subject of the remainder of this decision.
For the reasons that follow, the undersigned finds that Petitioners have failed to articulate a persuasive, reliable theory by which a partial congenital rubella infection could result in an injury that produces signs and symptoms consistent with Aicardi syndrome.
It is unclear to the undersigned whether Dr. Bellanti's theory is that the infection caused the alleged injury by causing a genetic mutation or whether, alternatively, the infection caused the injury by inflicting teratologic damage on the developing fetus. See tr. at 45. One interpretation of Petitioners' argument is that environmental factors — i.e., a partial congenital rubella infection from a reverted rubella vaccine that crossed the placenta — caused one of S.E.B.'s X chromosomes to mutate. See tr. at 65 (Dr. Bellanti testifying that "[w]e don't know the genetic basis of Aicardi, but we know that there are probably many causes of that or could be, and one of the causes is congenital rubella syndrome").
Another interpretation of Petitioners' argument is that the rubella virus, having reverted and crossed the placenta, caused teratological damage to the developing fetus, causing injuries that later manifested as Aicardi. See tr. at 73-74 (Dr. Bellanti noting that, "[o]nce you have congenital rubella syndrome as the cause, then, by definition, it's no longer Aicardi because it's no longer a genetic condition").
Petitioners provided no scientific basis for the first interpretation of their theory, and in light of their statements in support of the second interpretation, it is not clear to the undersigned that this was actually a theory they were advancing. However, in an abundance of caution, the undersigned has analyzed that theory in light of the record before her.
In response to that interpretation, Dr. Raymond agreed that the gene that causes Aicardi syndrome has not yet been identified. Resp. Ex. A-1 at 3. Dr. Raymond argued, however, and Petitioners do not dispute, that there is no known case of a gene mutation resulting from a teratologic agent. See Resp. Ex. F at 1-2. He also asserted that "as a teratogenic effect, rubella should be rubella should be rubella. . . . It should result in features consistent with congenital rubella syndrome" rather than by causing the damage characteristic of a genetic mutation, or by causing the mutation itself. Tr. at 149. In addition, Respondent's primary Aicardi reference, the Sutton article, states that "[a]t least six pairs of twins who are discordant for Aicardi syndrome are known, five of whom are confirmed dizygotic, excluding the possibility that the etiology is a prenatal toxin or other disruptive event." Resp. Ex. A-1 at 3. As acknowledged by both experts, although the affected gene itself has not been identified, the majority of cases of Aicardi syndrome occur in the absence of a rubella infection. Tr. at 65-67, 96.
Ultimately, in the absence of any evidence that an infection can cause genetic damage, and in light Dr. Raymond's qualifications in teratology and genetics, see generally Resp. Ex B; tr. at 108-10, the undersigned declines to find that Petitioners have provided a "sound and reliable scientific explanation" for the theory that a partial congenital rubella infection from a reverted rubella vaccine that crossed the placenta caused one of S.E.B.'s X chromosomes to mutate. See Knudsen v. Sec'y of Health & Human Servs., 35 F.3d 543, 548 (Fed. Cir. 1994).
The second interpretation of Petitioners' theory, that the partial rubella infection resulting from the reverted attenuated vaccine virus can cause teratological damage to a fetus that mimics the damage characteristic of Aicardi, was the argument they more rigorously advanced at hearing. Dr. Bellanti argued that "[r]ubella in fetal tissues has a propensity to persist throughout pregnancy;" its clinical expression depends on "the amount of viral replication, the stage at which [the] virus is entered, and . . . the degree of virulence of the infecting virus," and the partial rubella infection may have affected "any of the organs or tissues of the fetus." Tr. at 33, 88.
The undersigned finds, based on the reliable scientific evidence presented, that the signs and symptoms associated with Aicardi essentially do not overlap with the signs and symptoms associated with CRS. See tr. at 96, 120-21 (noting that the eye features and agenesis of the corpus callosum, which are hallmarks of Aicardi syndrome, are rarely, if ever, noted in CRS; the signs and symptoms associated with each syndrome are very dissimilar); see also Willis at 4 ("The `salt and pepper' pigmented fundus often seen with congenital syphilis or rubella is distinctly unlike the fundus in the Aicardi syndrome;" "[a]genesis of the corpus callosum, another feature of the Aicardi syndrome, is not found in the infections, except in one doubtful case of congenital rubella.") Moreover, Petitioners have not explained why it is reasonable to believe that a "partial" congenital rubella infection, or a congenital rubella infection acquired from a reverted vaccine that crossed the placenta, or a congenital rubella infection acquired via the bloodstream rather than via the respiratory tract, can cause signs and symptoms that are strikingly dissimilar from those associated with a "full-blown" congenital rubella infection.
The undersigned finds particularly compelling Dr. Raymond's argument that the signs and symptoms associated with Aicardi are qualitatively different from the types of damage caused by rubella infections; that they are different in kind. Tr. at 114-18. Aicardi, which results from X chromosome inactivation, is a patchy abnormality; CRS, which results from an in utero infection that affects cell proliferation, produces a more diffuse abnormality. Tr. at 113-14, 126-27. The undersigned finds that, whether a rubella infection is "full-blown" or "partial," the resulting abnormalities are likely to be diffuse (consistent with abnormal cell proliferation) rather than patchy (consistent with X chromosome inactivation). See, e.g., tr. at 93-96, 120 (Dr. Raymond's discussions of the pigmented fundus that is characteristic of congenital rubella and the lacunar deformation of the eye that is associated with Aicardi).
The undersigned is also perplexed as to how a syndrome that bears not a single symptom characteristic of a congenital rubella infection nor has any serological marker that could confirm congenital rubella infection could nevertheless allegedly be caused by a congenital rubella infection. All of the literature submitted by both experts concerning congenital rubella anticipates being able to confirm the congenital rubella infection diagnosis through symptoms, see, e.g., Willis at 4 ("certain associated abnormalities would make a diagnosis of congenital infection more likely than the Aicardi syndrome"), serology, see Pet. Ex. 17 at 2-3, or both. Lee at 572; Resp. Ex. E at 1-2. None of the submitted literature supports Petitioners' argument that no symptoms plus no serology can still equal congenital rubella infection, even a "partial" one.
Although facially supportive of Petitioners' theory, the Gualberto and Orquin case studies do not constitute reliable evidence that a congenital rubella infection can cause injuries consistent with Aicardi syndrome. As noted by Dr. Raymond, the child referenced in Orquin did not meet the WHO criteria for CRS, and her CRS diagnosis was never serologically confirmed. See Resp. Ex. F at 1. Gualberto — which is the only article cited by Petitioners that concerns the reversion theory — discusses a patient with fulminant encephalitis. Resp. Ex. F at 1. Encephalitis is a known complication of rubella infection; if the vaccine virus did revert to wild-type virus in this single patient, the reverted virus caused damage consistent with what the wild-type virus would cause. Id.; tr. at 155-56. Gualberto does not support Petitioners' argument that a reverted virus can cause injuries completely uncharacteristic of the injuries associated with the wild-type virus.
For the reasons stated above, the undersigned finds that Petitioners have failed to provide preponderant evidence in support of a reliable theory of causation pursuant to Althen Prong One.
Assuming, arguendo, that a partial congenital rubella infection can cause the injury that manifested in S.E.B. as Aicardi, Petitioners' claim also fails on Althen's second prong. Petitioners' theory hinges upon a series of extremely unlikely events, all of which are required to have happened in succession in order for the vaccine to have caused S.E.B.'s injuries. Tr. at 34-35, 40-48. After vaccination, the attenuated virus would have had to revert to virulence in the absence of any documented symptoms in Ms. Sumner. Tr. at 34-37; 40-45. The virus would then have had to cross the placenta. Tr. at 45. Having crossed the placenta, the virulent virus would have had to cause a partial infection in the fetus, and the viral load would have had to spike throughout gestation, mutating S.E.B.'s X chromosome and/or otherwise causing her injuries. See tr. at 137-38.
The undersigned notes that there has been no serologic confirmation that S.E.B. ever had a rubella infection. Tr. 98-100. As has been generally acknowledged, two serological measurements — IgG and IgM — are the classic criteria for diagnosis of CRS. See Resp Ex. E at 2. In both his 1965 article Congenital Rubella
The undersigned also finds that none of the classic clinical symptoms of CRS are evident in S.E.B. The classic clinical symptoms supporting a diagnosis of CRS are "congenital heart disease, cataracts, heptosplenomegaly, and thrombocytopenic purpura;" deafness is the most common. Pet. Ex. 17 at 1. See also Ex. E; tr. at 61, 118-19. S.E.B. has none of these symptoms. Tr. at 60-61. Nor did S.E.B. exhibit even any of the minor diagnostic characteristics of CRS, save mental retardation, which is a symptom attributable to so many disorders that it cannot be considered to be diagnostic in the absence of other diagnostic criteria. Tr. at 151-52; see generally Pet. Ex. E.
The undersigned understands that Petitioners' theory posits that S.E.B. suffered only from a partial rubella infection, and that such infections can exist without any outward manifestations or confirmatory serological results. Tr. at 86-87. But neither Petitioners nor Dr. Bellanti have submitted any medical literature, or any other documentation, regarding the existence of a phenomenon that he refers to as "a partial infection." 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 v. Sec'y of Health & Human Servs., 88 Fed. Cl. 706, 743 (Fed. Cl. 2009) (emphasis in original) (quoting Gen. Elec. Co. v. Joiner, 522 U.S. 136, 137 (1997)). See also Moberly v. Sec'y of Health & Human Servs., 592 F.3d 1315, 1324 (Fed. Cir. 2010) ("[T]he special master is entitled to require some indicia of reliability to support the assertion of the expert witness.")
Accordingly, the undersigned finds that Petitioners have failed to provide preponderant evidence of a logical sequence of cause and effect under Althen Prong Two.
The facts of this case complicate the process of assessing whether Petitioners have made an adequate showing of a proximate temporal relationship between vaccination and injury. Althen, 418 F.3d at 1279. It is not disputed that Ms. Sumner received the vaccination when she was between four and eight weeks pregnant, and that S.E.B. was born with her injuries. See Resp. Ex. A at 1; Pet. Ex. 12 at 3. It is also not disputed that the formation of the corpus callosum occurs at 14 to 18 weeks gestation. Tr. at 124.
The undersigned finds that agenesis of the corpus callosum and heterotopias, both of which are major characteristics of Aicardi syndrome and both of which are evident in S.E.B., are critical to the temporal component of Althen. See Sutton at 1-2; tr. at 116-17. The timeframe in which these brain structures manifest in a developing fetus has been definitively established: "[t]he development of the corpus callosum occurs between 14-18 weeks gestation and disorders of neuronal migration that result in formation of the heterotopias occur at 20-23 weeks gestation." Resp. Ex. A at 4; tr. 124. Thus, formation of the relevant structures of S.E.B.'s brain did not occur until at least six weeks after administration of the vaccine.
The undersigned acknowledges Petitioners' arguments that "[r]ubella in fetal tissues has a propensity to persist throughout pregnancy," and that the viral load can "spike" at different times after vaccine administration. Tr. 88, 137-38. The undersigned notes, however, that according to Petitioners' own medical literature, even an acknowledged rubella infection is unlikely to cause defects after the first trimester: while "the fetus can still be infected [with rubella] after the first trimester," there are unlikely to be any congenital defects after 18-20 weeks gestation. Lee at 584. Moreover, as Dr. Raymond argued, in S.E.B.'s case a rubella infection in the fetus would have affected fetal development throughout the first trimester, causing "much wider and different abnormalities to the brain" than those S.E.B. sustained. Tr. at 126.
The undersigned concludes that Petitioners have failed to prove, by a preponderance of the evidence, that there is a proximate temporal relationship between the administration of the MMR vaccine and the injuries that manifested as Aicardi syndrome in S.E.B.
The undersigned has no doubt that S.E.B. is now a profoundly challenged young woman with significant ongoing needs. However, those compelling circumstances standing alone cannot be the basis of a vaccine award. The undersigned finds that Petitioners have failed to put forward a reliable theory of vaccine causation and have not established with reliable evidence that S.E.B. has congenital rubella syndrome or Aicardi syndrome caused by the rubella component of the MMR vaccine.
The only reliable evidence offered in the case proves that Petitioner Shon Sumner received an MMR vaccine; that the vaccine was passed through to the in utero S.E.B. in the form of immunity (elevated IgG for rubella); and that S.E.B. was born with a genetic malformation whose symptoms are known as Aicardi syndrome. There is no other reliable evidence tying the one to the other. The Petition must therefore be, and is,
In the absence of a motion for review filed pursuant to RCFC Appendix B, the clerk of the court
