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In the United States Court of Federal Claims
No. 03-654V
Filed: July 24, 2009
ROLF and ANGELA
HAZLEHURST, parents of
WILLIAM YATES
HAZLEHURST,
Petitioners,
v.
SECRETARY, DEPARTMENT
OF HEALTH & HUMAN
SERVICES,
Respondent.
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Vaccine Act—Omnibus Autism
Proceeding: In a proceeding to
determine the relationship, if any,
between the measles, mumps, and
rubella vaccine and the development of
regressive autism, the special master
did not err in relying on evidence
generated in another litigation and
offered on the eve of hearing, failing to
consider evidence that would not have
altered her conclusion, or declining to
rule whether regressive autism is a
distinct phenotype from classic autism.
Curtis R. Webb, Twin Falls, ID, attorney of record for petitioners.
Linda S. Renzi and Lynn E. Ricciardella, with whom were Assistant Attorney
General Tony West, Director Timothy P. Garren, Acting Deputy Director
Catharine E. Reeves, and Assistant Director Gabrielle M. Fielding, Torts Branch,
Civil Division, U.S. Department of Justice, Washington, DC, for respondent.
OPINION
WIESE, Judge.
Petitioners, Rolf and Angela Hazlehurst, seek review of a decision entered by
the special master on February 12, 2009, denying their son, William Yates
Hazlehurst, compensation under the National Childhood Vaccine Injury Act of 1986
(“the Vaccine Act”), 42 U.S.C. §§ 300aa-1 to -34 (2006), for a neurological injury,
identified as regressive autism, allegedly caused by the administration of the measles,
mumps, and rubella (“MMR”) vaccine. Petitioners contend that the special master
improperly based her decision on evidence that should have been excluded,
disregarded other evidence that should have been considered, and declined to decide
an issue of fact necessary for a reasonable resolution of their claim. The matter has
A description of the procedural history of the omnibus proceeding,
1
including the creation of the Petitioners’ Steering Committee, can be found in
Hazlehurst v. Secretary, Dep’t of Health & Human Servs., No. 03-654V, 2009 WL
332306, at *1–3 (Fed. Cl. Feb. 12, 2009). Although petitioners in the instant suit
agreed to have their claim serve as a test case, petitioners’ counsel was not a member
of the Petitioners’ Steering Committee.
Hearings were conducted in Hazlehurst and Snyder on October 15–18,
2
2007, and November 5–9, 2007, respectively. As the special master explained in her
decision, the parties in each of the test cases presented general causation evidence
(continued…)
2
been briefed by the parties and the court heard oral argument on June 11, 2009. For
the reasons set forth below, petitioners’ motion for review is denied.
BACKGROUND
This case is the second of three test cases heard by the Office of Special
Masters as part of the Omnibus Autism Proceeding (“the omnibus proceeding”), a
global effort to determine the relationship, if any, between the MMR vaccine,
vaccines containing thimerosal, and autism (or autism spectrum disorders). In order
1
to address the approximately 5,000 autism claims pending before the court, a panel
of attorneys representing the various petitioners, referred to as the Petitioners’
Steering Committee (“the steering committee”), identified three general theories of
causation: (1) that vaccines containing thimerosal, when combined with the MMR
vaccine, can cause autism; (2) that vaccines containing thimerosal alone can cause
autism; and (3) that the MMR vaccine alone can cause autism. The steering
committee then selected three test cases that fell within the same general causation
theory, namely that vaccines containing thimerosal acting in combination with the
MMR vaccine can cause or contribute to the development of autism. These test
cases—Cedillo v. Secretary, Dep’t of Health & Human Servs., No. 98-916V,
Hazlehurst v. Secretary, Dep’t of Health & Human Servs., No. 03-654V (the instant
case), and Snyder v. Secretary, Dep’t of Health & Human Servs., No. 01-
162V—were in turn assigned to three different special masters for resolution.
A hearing was held in the first case, Cedillo, in June 2007. At the hearing,
petitioners presented testimony from six expert witnesses, including experts in
toxicology, immunology, molecular biology, virology, neurology, and
gastroenterology. Respondent countered with evidence from nine expert witnesses,
in the subject areas addressed by petitioners as well as pediatric psychiatry and
epidemiology. By agreement of the parties, the record in the present case includes
all of the general causation evidence admitted in the Cedillo and Snyder hearings.2
(…continued)
2
(related to whether vaccines containing thimerosal in combination with the MMR
vaccine could cause autism) and specific causation evidence (regarding whether the
administered vaccines had caused the autistic condition of the child whose particular
case was being heard). Hazlehurst, 2009 WL 332306, at *3.
Petitioners define regressive autism as a condition characterized by the loss
3
of previously acquired skills rather than by the failure to develop certain skills in the
first instance. Whether regressive autism is a distinct category from classic autism
is the subject of debate, however, and is the focus of Section III of the discussion
below.
3
The petition in the instant case was filed on March 26, 2003. According to
the record, William Yates Hazlehurst was born on February 11, 2000. During the
first year of his life, Yates received the standard childhood vaccinations, including
up to 11 vaccines possibly containing thimerosal. On February 8, 2001, three days
before his first birthday, Yates additionally received the MMR vaccine.
While the record indicates that Yates developed normally prior to receiving
the MMR vaccine, in the month following the vaccination, Yates became, in the
words of his family, “wild,” “very hyperactive,” and “out of control.” By the summer
of 2001, Yates had lost all meaningful speech and had developed an obsession with
letters and numbers. Also during this period, Yates began to experience chronic
diarrhea and abdominal pain.
Yates’s developmental and gastrointestinal issues led petitioners to seek out
a number of treatments over the next several years. In July 2002, after a series of
evaluations for developmental and speech delays, Yates was diagnosed as
demonstrating a significant number of behaviors consistent with autism. Two
months later, in September 2002, Yates began treatment with Dr. Jean-Ronel
Corbier, a pediatric neurologist, for that condition. Over the next several months,
Yates additionally underwent an immunological evaluation and a colonoscopy. The
results of both tests were normal.
In June 2007, petitioners filed an amended petition with this court alleging
that Yates’s MMR vaccination, or a combination of the MMR vaccination and the
vaccines containing thimerosal that Yates had received during his first 12 months,
caused him to develop regressive autism. The special master summarized
3
petitioners’ theory as follows:
[P]etitioners assert that the measles component of the MMR vaccine
causes an immune dysfunction that impairs the vaccinee’s ability to
clear the measles virus. Unable to properly clear the measles virus
Dr. Corbier additionally noted that the presence of immunologic problems
4
in such children strengthens the case for MMR-vaccine causation but is not an
essential part of the clinical profile. Hazlehurst Tr. at 314A.
In their post-hearing brief, petitioners explained that although their claim
5
(continued…)
4
from the body, the vaccinee experiences measles virus persistence
which leads to chronic inflammation in the gastrointestinal system
and, in turn, chronic inflammation in the brain. Petitioners argue that
the inflammation in the brain causes neurological damage that
manifests as autism.
Hazlehurst v. Secretary, Dep’t of Health & Human Servs., No. 03-654V, 2009 WL
332306, at *86 (Fed. Cl. Feb. 12, 2009).
The special master convened a hearing in this case in October 2007. As noted
above, both parties relied in part on the general causation evidence presented in the
Cedillo hearing. In addition, petitioners offered the case-specific testimony of Dr.
Corbier, Yates’s pediatric neurologist, and respondent offered the testimony of Dr.
Thomas T. MacDonald (a gastrointestinal immunologist), Dr. Christine McCusker
(a pediatric immunologist), and Dr. Robert S. Rust (a pediatric neurologist).
During the hearing, Dr. Corbier testified that differences in the timing of the
first appearance of the symptoms associated with autism suggest that there are
differences in the underlying causes of autism. The earlier the onset of the
symptoms, Dr. Corbier opined, the more likely that the cause of the autism is genetic,
prenatal, or metabolic. In the case of regressive autism, however, Dr. Corbier
testified that the causal factors are “very likely [to be] genetic influences and external
environmental factors.” Hazlehurst Tr. at 270A.
Dr. Corbier went on to note that studies have implicated the MMR vaccine
as an environmental factor that can contribute to the development of regressive
autism in children who fit within a particular clinical profile. That profile, according
to Dr. Corbier, consists of children who developed normally before receiving the
MMR vaccination, displayed symptoms of regressive autism within one to nine
months following the receipt of the MMR vaccine, and experienced gastrointestinal
problems. Consistent with this profile, Dr. Corbier observed that Yates had
4
developed normally before his MMR vaccination, regressed within several months
after the receipt of the MMR vaccine, and suffered from lymphonodular hyperplasia
colitis (inflamation of the gut). Hazlehurst Tr. at 302A. Dr. Corbier therefore
concluded that Yates’s receipt of the MMR vaccine played a significant role in the
development of Yates’s regressive autism. Hazlehurst Tr. at 302A–303.
5
(…continued)
5
had originally been designated by the steering committee as a test case for Theory I—
identifying the combination of the MMR vaccine and vaccines containing thimerosal
as a cause of autism—it became clear at the hearing that a much stronger case could
be made linking Yates’s condition solely to the MMR vaccine. Petitioners thus
focused exclusively on MMR causation in making their case. As a result, the special
master limited her specific causation discussion to the causal connection, if any,
between the MMR vaccine and the development of Yates’s regressive autism. In
order fully to address the steering committee’s general causation theory, however, the
special master nevertheless analyzed the evidence relating to the potential
contribution of thimerosal as a cause of autism spectrum disorders.
As evidence that the measles virus can persist in the biological material of
6
autistic children, petitioners relied primarily on the following articles: H.
Kawashima, et al., Detection and Sequencing of Measles Virus From Peripheral
Mononuclear Cells From Patients With Inflammatory Bowel Disease and Autism,
Dig. Dis. Sci. 45(4): 723–29 (Apr. 2000) (co-authored by Dr. Wakefield); V.
Uhlmann, et al., Potential Viral Pathogenic Mechanism for New Variant
Inflammatory Bowel Disease, Mol. Pathol. 55(2): 84–90 (Apr. 2002) (co-authored
by Drs. Wakefield, O’Leary, and Sheils); and C.M. Martin, et al., Detection of
Measles Virus in Children With Ileo-Colonic Lymphoid Nodular Hyperplasia,
Enterocolitis and Developmental Disorder, Mol. Psychiatry 7 Suppl. 2: S47–48
(2002) (co-authored by Drs. Uhlmann, O’Leary, and Sheils). In addition, petitioners
cited the preliminary results of the Walker group purporting to find the existence of
the measles virus in the bowel biopsies of autistic children. S.J. Walker, et al.,
Persistent Ileal Measles Virus in a Large Cohort of Regressive Autistic Children
With Ileocolitis and Lymphonodular Hyperplasia: Revisitation of an Earlier Study,
poster presentation at the International Meeting For Autism Researchers (IMFAR),
University of California, Davis (June 2006).
5
Central to Dr. Corbier’s theory were several studies purporting to find the
presence of the measles virus in the biological material of autistic children who had
received the MMR vaccine. These studies came from primarily two sources: the
work of Dr. Andrew Wakefield of the Royal Free Hospital in London, England, and
his colleagues Drs. John O’Leary and Orla Sheils at the Unigenetics laboratory in
Dublin, Ireland; and the research of Dr. Stephen Walker and his colleagues at Wake
Forest University School of Medicine in Winston-Salem, North Carolina (“the
Walker group”). According to the special master, Dr. Wakefield was the principle
6
proponent of the hypothesis that the receipt of the MMR vaccine results in the
development of autism spectrum disorders and gastrointestinal problems in certain
children. Dr. Wakefield’s work, the special master explained, helped to precipitate
litigation in the United Kingdom examining the causal connection, if any, between
the MMR vaccine and autism (“the UK litigation”). In order to support the UK
PCR testing is a standard technique for detecting and identifying particular
7
gene sequences in tissue samples by exponentially replicating strands of DNA.
Hazlehurst, 2009 WL 332306, at *95.
The methods used by Unigenetics formed the basis for the research in the
8
2002 Uhlmann article, one of the articles on which petitioners primarily relied.
Cedillo Tr. at 1938A. In addition, Unigenetics tested tissue and cerebrospinal fluid
samples from—and purported to detect the presence of the measles virus in—the
vaccinees in the other two test cases, Michelle Cedillo and Colten Snyder. Yates, by
contrast, underwent no such testing.
Dr. Wakefield published an article in 1993 positing a causal connection
9
between the measles virus and infarctions of small blood vessels in the gut wall
leading to Crohn’s disease. A.J. Wakefield, et al., Evidence of Persistent Measles
Infection in Crohn’s Disease, J. Med. Virol. 39(4): 345–53 (Apr. 1993). The special
master noted that in response to the public “furor” created by the 1993 Wakefield
article, the Medical Research Council of the United Kingdom reviewed Dr.
Wakefield’s work and concluded that Dr. Wakefield had performed his experiments
with reagents that were not specific for the measles virus and without important
controls that the manufacturer of the testing equipment recommended. Hazlehurst,
2009 WL 332306, at *87. The special master additionally observed that following
a series of methodologically sound studies conducted in the late 1990s, the scientific
community ultimately dismissed Dr. Wakefield’s hypothesis as having little scientific
merit. Id.
Dr. Wakefield published two additional articles in 1998 and 2000, the first
advancing the hypothesis that the MMR vaccine leads to the development of autism
spectrum disorders with gastrointestinal manifestations and the second reporting the
finding of enterocolitis in children with developmental disorders. A.J. Wakefield,
et al., Ileal-Lymphoid-Nodular Hyperplasia, Non-Specific Colitis, and Pervasive
Developmental Disorder in Children, Lancet 351(9103): 637–41 (Feb. 1998); A.J.
Wakefield, et al., Enterocolitis in Children With Developmental Disorders, Am. J.
(continued…)
6
litigation, Drs. O’Leary and Sheils of Trinity College in Dublin formed the
Unigenetics laboratory, a non-accredited, for-profit institution that used a technique
called PCR (polymerase chain reaction) to test for the presence of the measles virus
in biopsied tissue. The positive findings reported by the Unigenetics laboratory
7 8
were later the focus of the Walker group, whose preliminary testing purported to
replicate Unigenetics’ results.
The special master observed, however, that Dr. Wakefield’s work has been
widely discredited by the scientific community, and that the testing conducted at
9
(…continued)
9
Gastroenterology 95(9): 2285–95 (2000). Both articles were the subject of extensive
criticism, however, and the special master ultimately found them to be “scientifically
unreliable.” Hazlehurst, 2009 WL 332306, at *90. In addition, the special master
observed that ten of Dr. Wakefield’s 12 co-authors on the 1998 article later retracted
the study’s conclusion that a potential causal link exists between the MMR vaccine
and autism. Id. at *90–92.
7
both the Unigenetics and Wake Forest laboratories contained procedural flaws that
compromised their reliability. The special master thus found that the studies on
which Dr. Corbier relied were “scientifically flawed or unreliable” and that Dr.
Corbier’s opinion regarding that aspect of petitioners’ causation theory (positing the
existence of persisting measles virus in the gut tissue of autistic children) “could not
be credited as sound or reliable.” Hazlehurst, 2009 WL 332306, at *13. The special
master accordingly concluded that petitioners’ theory of causation was “premised
upon a series of biological implausabilities” and was “at variance with the known
science.” Id. at *148–49.
Following the issuance of the special master’s decision denying
compensation, petitioners now ask the court to address three issues on appeal.
Specifically, petitioners object to: (1) the special master’s consideration of evidence
discrediting Unigenetics, the laboratory that detected the measles virus in the tissue
of autistic children; (2) the special master’s failure to consider evidence
demonstrating the reliability of results obtained by the Walker group, also purporting
to find the presence of the measles virus in the tissue of autistic children; and (3) the
special master’s failure to decide whether regressive autism is a distinct phenotype
from classic autism. We address these issues in turn below.
DISCUSSION
When deciding a motion for review of a special master’s decision under the
Vaccine Act, the court may:
(A) uphold the findings of fact and conclusions of law of the
special master and sustain the special master’s decision,
(B) set aside any findings of fact or conclusion of law of the
special master found to be arbitrary, capricious, an abuse of
discretion, or otherwise not in accordance with law and issue its own
findings of fact and conclusions of law, or
(C) remand the petition to the special master for further action
Even if petitioners are successful in making a prima facie case for
10
causation, the special master may nevertheless deny compensation where the
respondent has shown by a preponderance of the evidence that the injury is due to
(continued…)
8
in accordance with the court’s direction.
42 U.S.C. § 300aa-12(e)(2). The Federal Circuit has interpreted 42 U.S.C. § 300aa-
12(e)(2)(B) as setting forth three distinct standards of review: (1) the special master’s
findings of fact are to be reviewed under the arbitrary and capricious standard; (2) the
special master’s discretionary rulings are to be reviewed under the abuse of discretion
standard; and (3) the special master’s legal conclusions are to be reviewed de novo
under the not in accordance with law standard. Turner v. Secretary, Dep’t of Health
& Human Servs., 268 F.3d 1334, 1337 (Fed. Cir. 2001). Reversible error is
extremely difficult to establish, however, so long as the special master has
“considered the relevant evidence in the record as a whole, drawn plausible
inferences from that evidence, and articulated a basis for [the] decision which is
rational.” Hines v. Secretary, Dep’t of Health & Human Servs., 940 F.2d 1518, 1527
(Fed. Cir. 1991).
There are two methods for establishing entitlement to compensation under the
Vaccine Act. If the vaccinee suffered one of the injuries identified in the Vaccine
Injury Table within the prescribed time period (42 U.S.C. § 300aa-14(a) (initial
Table) and 42 C.F.R. § 100.3 (updated Table)), a petitioner may assert what is
commonly referred to as a “Table injury,” with a rebuttable presumption that the
injury was caused by the vaccine. 42 U.S.C. § 300aa-11(c)(1)(C)(i); Pafford v.
Secretary, Dep’t of Health & Human Servs., 451 F.3d 1352, 1355 (Fed. Cir. 2006).
If the vaccinee suffered an injury not identified in the Vaccine Injury Table, however
(as in the present case), no such presumption exists and a petitioner must show that
the vaccine “caused” or “significantly aggravated” the injury in question (commonly
referred to as a causation-in-fact claim). 42 U.S.C. § 300aa-11(c)(1)(C)(ii)(I);
Pafford, 451 F.3d at 1355.
In order to demonstrate that Yates’s injury was caused in fact by the
challenged vaccine, petitioners must prove their claim by a preponderance of the
evidence, a standard that is satisfied by showing that it is “more probable than not”
that the vaccine at issue caused the vaccinee’s injury. Althen v. Secretary, Dep’t of
Health & Human Servs., 418 F.3d 1274, 1279 (Fed. Cir. 2005). To make a prima
facie case for causation under Althen, petitioners 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.” Id.
at 1278. Although petitioners are not required to present “epidemiologic studies,
10
(…continued)
10
factors unrelated to the administration of the vaccine. Walther v. Secretary, Dep’t
of Health & Human Servs., 485 F.3d 1146, 1150 (Fed. Cir. 2007).
Citing the testimony of several expert witnesses (among them Dr. Diane
11
Griffin—an acknowledged authority on measles), the special master observed that
the vaccine-strain measles virus, in contrast to the wild-type measles virus, is much
less virulent, has been specifically designed not to replicate well in the human body,
and does not exhibit the most significant complications associated with the wild-type
measles virus. Hazlehurst, 2009 WL 332306, at *149–50. The special master
additionally noted that in the “rare circumstance” that the wild-type measles virus
persists in the body and causes disease, the resulting injuries are distinguishable from
the impairments associated with autism and include neurological deterioration that
results in death. Id. at *149.
9
[evidence of] rechallenge, the presence of pathologic markers or genetic disposition,
or general acceptance in the scientific or medical communities,” to establish
causation, Capizzano v. Secretary, Dep’t of Health & Human Servs., 440 F.3d 1317,
1325 (Fed. Cir. 2006), they must nevertheless provide a “reputable medical or
scientific explanation” for their claim, Althen, 418 F.3d at 1278. The determination
of whether a proffered theory of causation is “reputable” may “involve an assessment
of the relevant scientific data.” Andreu v. Secretary, Dep’t of Health & Human
Servs., No. 2008-5184, 2009 WL 1688231, at *9 (Fed. Cir. June 18, 2009). “Medical
literature and epidemiological evidence must be viewed, however, not through the
lens of the laboratorian, but instead from the vantage point of the Vaccine Act’s
preponderant evidence standard.” Id.
In the instant suit, petitioners assert that the measles component of the MMR
vaccine can cause an immune dysfunction in certain children that impedes their
systems from clearing the measles virus. According to this hypothesis, the persisting
measles virus leads to chronic inflammation in both the gastrointestinal system and
the brain. The inflammation in the brain, petitioners maintain, causes neurological
damage that manifests as autism.
In analyzing petitioners’ medical theory under the Althen standard, the special
master identified two cardinal flaws in petitioners’ case. First, the special master
explained that petitioners’ experts based their opinions on the characteristics of the
“wild-type” measles virus rather than on the characteristics of vaccine-strain measles,
despite the fact that the measles vaccine is distinguishable from the wild-type
measles virus in several key respects. Second, the special master observed that
11
petitioners’ experts further based their opinions on studies (detecting the presence of
the measles virus in the gut tissue of autistic children) that the special master found
to be unreliable. As a result of these deficiencies, the special master held that
The special master additionally held that petitioners had failed to establish
12
a temporal association under the third prong of Althen because the vaccine-strain
measles virus does not replicate well in the human body and the only evidence
petitioners offered for measles persistence—the Uhlmann article—was discredited.
Id. at *150.
10
petitioners had failed to satisfy the first two prongs of the Althen standard because
their medical theory was premised upon a series of biological implausibilities and the
presented evidence did not support a logical sequence of cause and effect between
the vaccine and the injury. Hazlehurst, 2009 WL 332306, at *149–50.12
In reaching her conclusion, the special master described the finding of
persistent measles virus in the gut tissue of autistic children as the “linchpin” of
petitioners’ theory. Id. at *171. The special master went on to describe that
proposition, however, as “glaringly unreliable” based on her assessment that the
studies on which petitioners’ experts based their conclusions were “critically flawed
and scientifically untenable.” Id. In particular, the special master devoted extensive
discussion to an analysis of the testing methods of the Unigenetics laboratory,
explaining that petitioners’ reliance on those test results, coupled with respondent’s
criticism of them, made it necessary for her to analyze Unigenetics’ practices “with
more scrutiny than generally occurs in vaccine proceedings.” Id. at *126. It is this
scrutiny that serves as the first ground for petitioners’ appeal.
I. The Special Master’s Reliance on Evidence That
Should Not Have Been Considered
The special master based her assessment regarding the reliability of the
testing conducted at Unigenetics in part on the testimony of Dr. Stephen A. Bustin,
a molecular biologist who appeared as an expert witness both for the vaccine
manufacturers in the UK litigation and for respondent in the omnibus proceeding.
As part of the UK litigation, Dr. Bustin was charged with evaluating the 2002
Uhlmann article and examining the testing methods used by the Unigenetics
laboratory. Dr. Bustin later testified that he spent 1,500 hours analyzing data from
the laboratory, including two site visits, and billed approximately $400,000 for his
efforts.
Based on his analysis of Unigenetics’procedures, equipment, and laboratory
notebooks, Dr. Bustin concluded that the Unigenetics researchers had failed to follow
the laboratory’s own standard operating procedures, failed to adhere to certain
standard laboratory practices, and failed to comply with the standards set forth by the
manufacturer of the testing equipment, all of which diminished the reliability of the
test results purporting to show the presence of the measles virus in the gut tissue of
autistic children. Dr. Bustin speculated that the Unigenetics researchers had detected
Prior to their admission in the Cedillo case, Dr. Bustin’s reports, like all
13
of the exhibits in the UK litigation, had been under seal by the British court. Dr.
Bustin additionally had been the subject of a court order prohibiting him from
testifying about Unigenetics’ procedures, equipment, and laboratory notebooks in any
other case. Both Dr. Bustin’s reports and his testimony were made available,
however, following the respondent’s successful application to the British court.
The special master explained that the steering committee had informed the
14
special masters hearing the three test cases of its decision not to seek the release of
additional documents from the British court because its efforts to do so likely would
have been unsuccessful given the steering committee’s inability to get the requisite
consent from the experts whose reports they sought. Hazlehurst, 2009 WL 332258,
at *8.
11
DNA contamination rather than the measles virus in the biopsied tissue.
Dr. Bustin was subsequently identified as an expert in the Cedillo case in late
May/early June 2007 in support of a motion in limine by the respondent unrelated to
the testimony presently at issue. On June 7, 2007, two business days before the
commencement of the hearing in Cedillo, the respondent sought to introduce two
expert reports by Dr. Bustin obtained from the UK litigation (Cedillo Resp. Exs. WW
and XX), along with Dr. Bustin’s testimony regarding his evaluation of Unigenetics’
procedures, equipment, and laboratory notebooks. The petitioners objected to the
last-minute filings and disclosure, but the exhibits were nevertheless provisionally
admitted into evidence on June 8, 2007. (The presiding special master deferred
ruling on whether he would rely on the reports, but allowed either party to question
Dr. Bustin.) By order dated June 11, 2007, however, the special masters assigned
to the three test cases advised that they would “favorably consider joining in a request
for release of relevant reports” if the steering committee filed a formal application
with the British court.13
Dr. Bustin was the subject of a similar challenge in the present case. In a
motion filed on September 4, 2007, petitioners objected to the admission of Dr.
Bustin’s reports regarding Unigenetics under the theory that consideration of that
evidence in the absence of the other expert reports prepared in the UK litigation
would be prejudicial. In addressing petitioners’ motion, the special master noted that
petitioners had been afforded a “generous” period of time to obtain the release of
additional expert reports from the British court but had declined to do so. Hazlehurst
v. Secretary, Dep’t of Health & Human Servs., No. 03-654V, 2009 WL 332258, at
*8 (Fed. Cl. Feb. 12, 2009). Observing that both parties had been given “an
14
opportunity, procedurally, to obtain and to present relevant information for
consideration in deciding this case,” the special master concluded that petitioners
were indeed prepared to address the reliability of the Unigenetics results, and thus,
Petitioners challenge only that portion of Dr. Bustin’s analysis pertaining
15
to his review of the Unigenetics laboratory: Cedillo Resp. Ex. WW, “Summary
Report on Real-Time RT-PCR Assays Carried Out by Unigenetics, Ltd.,” (Nov. 10,
2004) (prepared in the course of the UK litigation); Cedillo Resp. Ex. XX, “Report
on MMR/MR Vaccine Allegations,” (June 30, 2003) (also prepared in the course of
the UK litigation); Cedillo Resp. Ex. 13, “PCR and Reliability of the Unigenetics
Laboratory,” (PowerPoint presentation introduced at the Cedillo hearing); and
Cedillo Tr. at 1962A– 2069.
The Vaccine Rules were amended on July 13, 2009, renumbering Vaccine
16
Rule 8(c), to which the parties refer, as Vaccine Rule 8(b)(1).
12
more than a year and a half after the hearing in Cedillo, denied petitioners’ motion
to strike the testimony of Dr. Bustin. Id. at *8–9.
Petitioners now argue, however, that the special master’s consideration of Dr.
Bustin’s testimony and reports was fundamentally unfair and was inconsistent with
the purpose and nature of the Vaccine Program in violation of both the Vaccine Rules
and the relevant case law. Specifically, petitioners maintain that the special
15
master’s reliance on Dr. Bustin’s analysis violated the Vaccine Rules’ requirement
that the consideration of evidence in the Vaccine Program be “governed by principles
of fundamental fairness to both parties.” Vaccine Rule 8(b)(1). The admission of
16
Dr. Bustin’s testimony and reports was fundamentally unfair, petitioners argue,
because the material was submitted a mere two working days before the beginning
of the Cedillo hearing, severely impairing the ability of the Cedillos’ attorney to
mount an effective cross-examination of Dr. Bustin or to prepare an adequate
response to his analysis. Further compounding this inequity, in petitioners’ view, is
the fact that petitioners could not have countered Dr. Bustin’s analysis without
spending large sums of money, something they were unable—and should not in the
spirit of the Vaccine Program have been required—to do. Finally, petitioners
maintain that even if they had received adequate notice of Dr. Bustin’s analysis and
had sufficient funds to address it, they nevertheless would have been unable to
counter Dr. Bustin’s testimony because the Unigenetics laboratory no longer exists
and Unigenetics’ equipment and laboratory notebooks are no longer available for
review. Such prejudice, petitioners maintain, can only be remedied by excluding Dr.
Bustin’s testimony and reports.
In addition, petitioners contend that the admission of Dr. Bustin’s testimony
and reports converted the proceeding into “full blown tort litigation,” thereby
contravening Congress’s intention that individuals injured by vaccines receive
compensation “quickly, easily, and with certainty and generosity.” Knudsen v.
Secretary, Dep’t of Health & Human Servs., 35 F.3d 543, 549 (Fed. Cir. 1994)
(quoting H.R. Rep. No. 99-908, at 3 (1986), as reprinted in 1986 U.S.C.C.A.N.
13
6344). Petitioners assert that admitting evidence inconsistent with the purpose and
nature of the Vaccine Program is an error of law and thus urge the court to review the
special master’s reliance on such evidence de novo under the not in accordance with
law standard.
In respondent’s view, petitioners cannot contend that Unigenetics’ testing is
critical to their case and yet object when respondent offers evidence to challenge its
reliability. Respondent argues that Dr. Bustin’s reports are reliable evidence that is
directly applicable to the issues in this litigation and are thus vital to assessing the
correctness of petitioners’ theory of causation. In addition, respondent maintains that
the subject of Dr. Bustin’s reports should have come as no surprise to petitioners
because several of petitioners’ expert witnesses had direct knowledge of the problems
with Unigenetics’ testing methods identified by Dr. Bustin. Indeed, respondent
points out that four of petitioners’ experts in the omnibus proceeding also served as
expert witnesses in the UK litigation, and petitioners’ expert Dr. Ronald Kennedy
specifically testified about the Unigenetics laboratory during the Cedillo hearing.
Finally, respondent endorses the special master’s conclusion set forth in her denial
of petitioners’ motion to strike: “[F]airness to the parties has been achieved by
affording both parties an opportunity, procedurally, to obtain and to present relevant
information for consideration in deciding this case.” Hazlehurst, 2009 WL 332258,
at *8.
Vaccine Rule 8(b)(1) indeed requires that proceedings within the Vaccine
Program be conducted in a manner that is fundamentally fair. And petitioners are
correct that the program does not anticipate or encourage complex litigation. See
Andreu, 2009 WL 1688231, at *4 (recognizing that Congress, in enacting the
Vaccine Act, was “acutely aware that the traditional tort system had proven
ineffective in providing redress for vaccine-injured individuals ‘because it resulted
in lengthy delays, high transaction costs, and sometimes no recovery,’” quoting
Lowry v. Secretary, Dep’t of Health & Human Servs., 189 F.3d 1378, 1381 (Fed. Cir.
1999)). We do not believe, however, that the special master violated either principle
in the instant case.
It is evident, as an initial matter, that petitioners were given adequate time to
address Dr. Bustin’s analysis. Although petitioners were notified of the submission
of Dr. Bustin’s reports a mere two business days before the Cedillo hearing, the
special masters nevertheless made every effort to accommodate petitioners and
remedy any element of surprise by leaving the record open for more than a year
following the Cedillo hearing to allow petitioners to recall witnesses (including Dr.
Bustin) or to provide additional evidence. The special masters additionally offered
to lend their names to a request for relevant reports filed in the UK litigation.
Hazlehurst, 2009 WL 332306, at *93. Given these circumstances, we are unable to
conclude that petitioners were unfairly prejudiced as a result of the timing of the
Indeed, given the fact that respondent neither commissioned nor paid for
17
the reports, it is difficult to distinguish them conceptually from any information
existing in the public domain.
14
submission of Dr. Bustin’s reports.
Nor do we believe that the special master’s consideration of Dr. Bustin’s
analysis transformed the proceeding into complex tort litigation. Although Dr.
Bustin’s reports were created in connection with the UK litigation and funded by the
vaccine manufacturers, the relevant consideration is not the cost of Dr. Bustin’s
reports but rather their purpose: to rebut critical evidence introduced by petitioners.17
Petitioners themselves acknowledge that Unigenetics’ results are central to their
claim. Dr. Bustin’s testimony speaks directly to whether that evidence has any merit.
The proposition that “fundamental fairness” requires the special master to ignore
evidence so crucial to the case—in effect to contend that respondent has no right to
mount a defense—is untenable. Indeed, a special master’s refusal to consider such
“highly relevant and probative evidence” has been found to be an abuse of discretion.
DeFazio v. Secretary, Dep’t of Health & Human Servs., 40 Fed. Cl. 462, 467 n.5
(1998).
As the special master correctly noted in her decision, petitioners had no
obligation to submit medical studies in support of their claim. But once petitioners
had done so, the special master was duty-bound to assess the reliability of those
studies. Hazlehurst, 2009 WL 332306, at *17 (citing Daubert v. Merrell Dow
Pharmaceuticals, Inc., 509 U.S. 579, 590 (1993)); see also Campbell ex rel. Campbell
v. Secretary, Dep’t of Health & Human Servs., 69 Fed. Cl. 775, 781 (2006)
(interpreting the relevant case law as requiring a special master “to rely on reliable
medical or scientific evidence not only in finding causation, but also the lack
thereof”).
The only difficulty we have then with Dr. Bustin’s analysis is that it
essentially goes unanswered in petitioners’ case. Despite the special masters’ best
efforts to accommodate petitioners, the unfortunate fact remains that Dr. Bustin’s
testimony and reports reflect 1,500 hours of critical evaluation that petitioners have
no way to replicate. While petitioners’ experts Dr. Karin Hepner (a molecular
biologist) and Dr. Ronald Kennedy (a professor and the chair of the Department of
Microbiology and Immunology at Texas Tech University Health Sciences Center)
each filed supplemental reports addressing Dr. Bustin’s analysis and the validity of
Unigenetics’ testing, Cedillo Pet. Exs. 120 and 121, neither expert had the
opportunity to review the primary materials on which Dr. Bustin based his
conclusions. The closest either expert actually came to the Unigenetics laboratory,
in fact, was Dr. Kennedy’s participation in a meeting in which he and several
Dr. Kennedy described the meeting with Dr. Sheils as follows:
18
[O]ver four-and-a-half to five hours, [Dr. Sheils] was asked a number
of questions relative to the technology, the standard operating
procedures, the immunohistochemistry that was shown, how she
detected what were her primers, what were the sensitivity, how was
isolation done, what were controls, what were positive controls, how
did she know that this was not contamination, what was the samples.
She was essentially taken apart by, I would say, three or four
extremely good microbiologists.
Cedillo Tr. at 811A.
15
colleagues questioned Dr. Sheils about Unigenetics’ research practices. We do not,
18
however, consider Dr. Kennedy’s testimony a legitimate counterweight to Dr.
Bustin’s testimony regarding Unigenetics’ procedures because the former spent a
mere five hours interviewing Dr. Sheils while the latter spent 1,500 hours with full
access to Unigenetics’ facilities and records. Their experiences are simply not
comparable.
Dr. Kennedy’s supplemental report illustrates the significance of this
imbalance. Addressing Dr. Bustin’s criticism of the Unigenetics laboratory, Dr.
Kennedy opined as follows:
What becomes clear in a review of [Dr. Bustin’s] testimony and his
PowerPoint presentation is that while he readily identifies problems,
he omits any explanatory references which would place the issue into
context. By selectively highlighting only a few pages which he
claims supports his criticism that the [Unigenetics] laboratory was
less than diligent, it is unknown whether these laboratory notebooks
also contain information which demonstrates that the laboratory took
the appropriate action to resolve unexpected issues. The lack of
access to the laboratory notebooks will, of course, affect my
comments.
Cedillo Pet. Ex. 121 at 2. Addressing Dr. Bustin’s specific criticisms of the
contamination issue, Dr. Kennedy additionally observed as follows:
It is easy to rectify contamination of negative controls and does not
invalidate positive results by any laboratory that is competent in PCR
technologies. While Dr. Bustin identified the contamination problem,
he attempted to use this one page to imply that contamination issues
were never resolved, yet his PowerPoint presentation did not include
During oral argument, petitioners’ counsel raised the issue whether his
19
clients should be bound by procedural decisions made by the steering committee or
by the counsel in Cedillo (i.e., the decision not to seek expert reports from the British
court). Petitioners themselves, however, could have sought evidence filed in the UK
litigation, particularly when it became clear at the Cedillo hearing that the reliability
of the Unigenetics results would be an issue in dispute.
16
any further support that contamination was an unremedied problem
in the [Unigenetics] laboratory. He did not include any additional
pages from the laboratory notebooks that indicate contamination
issues were pervasive and unresolved. Since contamination is an ever
present problem in laboratories, an isolated day of problems should
not be used to impugn a reputation developed over a life time of
achievement.
Cedillo Pet. Ex. 121 at 3 (citation omitted). Dr. Kennedy offered similar
observations regarding Dr. Bustin’s other criticisms, describing many of them as
irrelevant or unverifiable without having access to the laboratory notebooks upon
which Dr. Bustin relied. As Dr. Kennedy noted, “an isolated page from a laboratory
notebook does not provide any context for the conditions associated with [a]
particular experiment.” Cedillo Pet. Ex. 121 at 3.
Given that the special master’s critique of Unigenetics’ practices reflects a
greater level of scrutiny than generally occurs in vaccine proceedings, Hazlehurst,
2009 WL 332306, at *126, we find this disparity of access to Unigenetics’ facilities
and laboratory notebooks troubling. Few institutions, we suspect, can entirely
withstand the level of scrutiny provided by Dr. Bustin, particularly without
explicative or rehabilitative testimony. And we acknowledge, as Dr. Kennedy
charges, that Dr. Bustin’s criticisms may be taken out of context.
But while we are sympathetic to petitioners’ concerns on this score, it would
be an extraordinary remedy to exclude such relevant and probative evidence. The
only solution, we believe, is the one the special master employed: mitigating any
potential prejudice by affording petitioners the opportunity to seek relevant reports
from the UK litigation and to recall Dr. Bustin for further questioning. The fact that
petitioners did neither considerably weakens their position. See Snyder v. Secretary,
Dep’t of Health & Human Servs., No. 01-162V, 2009 WL 332044, at *27 (Fed. Cl.
Feb. 12, 2009) (holding that petitioners waived any argument regarding the reports
filed in the UK litigation because of their failure to seek their release).
19
Most significant for the purposes of our analysis, however, is the fact that we
believe that the special master would have reached the same conclusion regarding
Unigenetics even in the absence of Dr. Bustin’s analysis. As the special master
In particular, the special master identified the testimony of respondent’s
20
experts Dr. Brian J. Ward (an infectious disease specialist), Dr. Diane Griffin (an
immunologist), and Dr. Bertus Rima (a virologist) as “the most persuasive on the
subject of vaccine-strain measles virus persistence,” Hazlehurst, 2009 WL 332306,
at *7, and relied upon the testimony of those same experts in her discussion of the
Unigenetics laboratory, id. at *128–32.
Specifically, the Walker group contended that they (1) detected measles
21
virus genomic material in the gut tissue of children with regressive autism using the
PCR technology employed by Unigenetics, and (2) confirmed that the product
identified as measles virus genomic material through PCR testing was in fact measles
virus genomic material by matching its genetic sequence to that of the measles virus.
17
explained in her decision, she did not “rely solely on [Dr. Bustin’s] testimony in
evaluating the reliability of the test results obtained by Unigenetics,” but also based
her conclusions on “the testimony of other witnesses and the filed scientific literature
addressing Unigenetics’ testing techniques.” Hazlehurst, 2009 WL 332306, at *93.20
Notably, the flaws identified by the special master in the challenged articles
would have been evident even without the scrutiny given by Dr. Bustin to the
Unigenetics laboratory. First, the “reported positive findings of measles virus have
not been replicated by laboratories independent of [Unigenetics],” thereby
“diminish[ing] the confidence of the scientific community in the validity of the
reported findings.” Id. at *124. Second, “the published articles on which petitioners
rely do not include sufficient laboratory data to evaluate the conducted testing
procedures and the validity of the test results,” thereby “impair[ing] the scientific
community’s ability to scrutinize the reported findings for methodological errors.”
Id. Thus, even if we were to consider the admission of Dr. Bustin’s testimony unfair
to petitioners, the special master’s consideration of that evidence would rise at most
to the level of harmless error. Hines, 940 F.2d at 1526 (holding that it was harmless
error for the special master to rely on a medical textbook, even if unfair to the
petitioner, because “the special master’s decision was based on a number of factors
and [petitioner had] not shown that reliance on the . . . textbook was likely critical to
the result”).
II. The Special Master’s Disregard of Relevant Evidence
In addition to the Unigenetics studies, petitioners also relied on the
preliminary, unpublished findings of the Walker group reporting the existence of the
measles virus in the bowel biopsies of children with regressive autism. Petitioners
21
argue that these findings not only offer independent support for their causation theory
regarding measles persistence, but also provide clear evidence that the challenged
Sequencing is the process of confirming that the product obtained through
22
PCR testing contains the proper nucleotide composition for the targeted product
(here, the measles virus). “Sequencing is the only way to be certain that the
amplified material is the targeted material.” Hazlehurst, 2009 WL 332306, at *119.
M.A. Afzal, et al., Absence of Delectable Measles Virus Genome
23
Sequence in Blood of Autistic Children Who Have Had Their MMR Vaccination
During the Routine Childhood Immunization Schedule of UK, J. Med. Virol. 78(5):
623–30 (May 2006); Y. D’Souza, et al., No Evidence of Persisting Measles Virus in
Peripheral Blood Mononuclear Cells From Children With Autism Spectrum
Disorder, www.pediatrics.org/cgi/doi/10.1542/peds.2006-1242.
A primer is a “short piece of DNA or RNA [that is] complementary to a
24
given DNA sequence and acts as the point from which replication proceeds during
the process of polymerase chain reaction.” Hazlehurst, 2009 WL 332306, at *112
(quoting Dorland’s Illustrated Medical Dictionary 764, 1506 (30th ed. 2003)).
Such an accomplishment is significant, Dr. Hepner explained, because a
25
(continued…)
18
Unigenetics testing was reliable. Petitioners contend, however, that the special
master failed to take into account evidence that the Walker group had verified their
PCR testing through genetic sequencing, thereby violating 42 U.S.C. § 300aa-
22
13(b)(1)’s requirement that the special master consider all relevant evidence.
Petitioners maintain that had such evidence been weighed properly, it would have
confirmed the correctness of Dr. Corbier’s hypothesis linking Yates’s regressive
autism to the MMR vaccine. Petitioners thus argue that the special master’s finding
that the Unigenetics and Walker group results were unreliable was arbitrary and
capricious.
Petitioners’ expert Dr. Hepner indeed cited her own work with the Walker
group as evidence of the reliability and reproducability of the Uhlmann article’s
results. Cedillo Pet. Ex. 120 at 1. According to Dr. Hepner, although other
studies—most notably by researchers M.A. Afzal and Yasmin D’Souza —had
23
attempted to replicate the Uhlmann results, the Walker group investigators were the
first to do so successfully, in part because of their use of gut tissue. (Dr. Hepner
explained that the Afzal and D’Souza studies, by contrast, each used other biological
material. Cedillo Tr. at 629A, 631.) Dr. Hepner testified that the Walker group’s
results, though preliminary, were nevertheless a “technical accomplishment,” because
they demonstrated that the primer sets used in the Uhlmann article successfully
24
amplified the measles virus and that vaccine-strain measles virus could indeed be
found in the tissue of autistic children who suffer from gastrointestinal problems.
Cedillo Tr. at 682; Cedillo Pet. Ex. 120 at 3. Dr Hepner additionally noted—both
25
(…continued)
25
chief criticism of the Uhlmann article is that its results could not be replicated and
the Walker group had thus taken the first step in doing so. Cedillo Pet. Ex. 63 at 5.
In her initial expert report filed on May 25, 2007, Dr. Hepner advised that
26
the Walker group had confirmed “[v]accine strain specificity . . . in a percentage of
[their] samples using nucleotide sequencing.” Cedillo Pet. Ex. 63 at 5. In her
supplemental report filed on October 22, 2007, Dr. Hepner further advised as
follows:
Dr. S. Walker has confirmed that various primer sets used in the
Uhlmann study successfully amplify [measles virus] and his PCR
results were further verified using nucleotide sequencing analysis.
. . . The conclusion drawn is simply this: Using the Uhlmann assay
conditions, a product corresponding to the target gene is amplified
and verified in a manner considered to be the most rigorous by all
standards. If [a measles virus] target sequence is amplified and
verified by sequencing using the Uhlmann primer sets, it is
necessarily true that these Uhlmann primer sets are capable of
amplifying the predicted [measles virus] target.
Cedillo Pet. Ex. 120 at 1–2. In addition, Dr. Hepner’s testimony contains several
references to the Walker group’s sequencing of their results. See, e.g., Cedillo Tr.
at 662A, 667. Finally, the abstract itself noted that 14 of the 82 patients who had
tested positive for the presence of measles virus had their results “verified by DNA
sequence.” Cedillo Pet. Ex. 120, Tab C at 1.
As the special master explained in her decision, proper PCR testing
27
requires the use of four controls—positive, negative, experimental, and control
samples—to be run every time an experiment is conducted. The special master
described the necessity for positive and negative controls as follows:
A positive control is a sample that contains the measles virus. The
(continued…)
19
in her testimony and in her two expert reports—that the Walker group’s results had
been “verified using nucleotide sequencing analysis” which is universally recognized
as the most rigorous of scientific standards in genetic testing.
26
Respondent points out, however, that genetic sequencing is only one aspect
of proper PCR technique and argues that the use of sequencing does not overcome
the other shortcomings of the Walker group’s study, most significantly the absence
of proper controls. Accordingly, respondent contends that the Walker group’s
27
(…continued)
27
sample must be positive every time the experiment is run. If the
positive control is negative, there is a flaw in the experimental design,
and no information can be obtained. A negative control . . . is a
sample in which measles virus is not present. The sample must be
negative every time the experiment is run. If the negative control is
positive, there is either a flaw in the experimental design (such as a
primer that is not sufficiently specific to the desired target) or cross-
contamination between the negative control and the measles virus.
The negative samples within the experiment function as a control for
contamination. . . . [W]hen the controls do not function true to
designation, confidence in the results obtained from the experiments
diminishes.
Hazlehurst, 2009 WL 332306, at *120 (citations omitted). The special master
additionally described the need for experimental and control samples as follows:
The second level of control includes experimental subjects
and the normal controls. . . . By design, the control group has to be
similar to the experimental group but has to differ by the variable of
interest.
In running an experiment, the investigator must run all four
controls (the positive, negative, experimental and control samples) at
the same time. The controls must be run every time an experiment is
conducted. That is standard laboratory practice.
Id. (citations omitted).
A blinded experiment is one in which the researcher does not know
28
whether he is working with a positive control, a negative control, or the sample in
question so as to avoid introducing the researcher’s subjectivity into the analysis.
Respondent, we believe, overreads Dr. Hepner’s testimony on these points.
29
(continued…)
20
results are not reliable because there is no internal consistency in the study and the
positive findings could very likely be due to contamination. Respondent additionally
notes that Dr. Hepner herself acknowledged that the preliminary data from the study
was “not useful at this time” (Cedillo Tr. at 682), declined to draw any conclusions
about the biological significance of the Walker group’s findings (Cedillo Tr. at 682),
and identified what respondent describes as several significant drawbacks to the
study, including that the experiments had not been “blinded” and had lacked
28
negative controls (Cedillo Tr. at 658, 681). Respondent thus argues that the special
29
(…continued)
29
Dr. Hepner explained that the Walker group’s data was “not useful at this time”
because the results for the experimental group (i.e., children with autism) had not
been compared to a control group (i.e., children without autism), so no biological
conclusions could be drawn regarding the connection between the measles virus and
autism. Cedillo Tr. at 657–58. Dr. Hepner repeatedly maintained, however, that the
Walker group results were relevant to the omnibus proceeding because they showed
primer-set specificity, thereby helping to validate the Uhlmann article’s results
detecting measles persistence in the gut tissue of autistic children. Cedillo Tr. at 682.
Similarly, while Dr. Hepner acknowledged that the Walker study was not blinded,
she testified that “there would be no point in being blinded because there [were] only
experimental samples.” Cedillo Tr. at 681. Finally, Dr. Hepner explained that while
the Walker group had not yet found control samples they deemed suitable (i.e.,
developmentally normal children with gastrointestinal issues), they had nevertheless
run no-template controls in every experiment to ensure against contamination.
Cedillo Tr. at 658, 662A.
21
master correctly determined that the Walker group’s preliminary, unpublished, and
unconfirmed findings do not support the validity of the Unigenetics test results.
Although the special master recognized sequencing as the “gold standard” for
determining the reliability of PCR testing, Hazlehurst, 2009 WL 332306, at *116, she
made no mention of the Walker group’s sequencing in her decision. The special
master relied instead on the testimony of Dr. Bustin, who explained that in the
absence of both positive and negative controls, he could not have “any confidence”
in the test results presented by the Walker group. Cedillo Tr. at 1959A. The special
master thus dismissed the Walker group’s findings as preliminary and concluded that
she could not “place much weight” on such findings because “test results without the
use of these controls during PCR experiments may not be reliable.” Hazlehurst, 2009
WL 332306, at *125.
There is evidence in the record, however, that Dr. Bustin was not aware that
the Walker group had sequenced their results. Seemingly without regard to this fact,
Dr. Bustin expressed concern about several unidentified bands in the Walker group’s
poster presentation, explaining that he could not rule out the possibility of
contamination in the absence of negative controls. Cedillo Tr. at 1959A. Dr. Bustin
went on to testify that in order to address the possibility of contamination, a
researcher must “do additional techniques to confirm the identity of that band,”
noting that the “best way” to confirm that the band is the target “is sequencing, is
getting a DNA sequence.” Cedillo Tr. at 1942A.
Dr. Bustin unfortunately was never cross-examined on this point so we have
no way of knowing what conclusions he would have drawn from the Walker group’s
We are unable to assess with any confidence either the legitimacy of Dr.
30
Bustin’s criticism of the Walker group’s procedures or the correctness of petitioners’
response to that criticism. Dr. Bustin testified that he had no faith in the results of
the Walker group’s study because of the absence of negative controls. Cedillo Tr. at
1959A. Petitioners’ counsel contended at oral argument, however, that despite Dr.
Bustin’s criticism, the Walker group in fact used negative internal controls in their
experiments and Dr. Hepner testified that a no-template control, designed to
“function[] as a control for contamination,” was run with every sample. Cedillo Tr.
at 658, 662. The record unfortunately provides no way to reconcile these statements.
Similarly, it is unclear from the testimony whether the use of sequencing—a
process designed to ensure the integrity of the targeted material—would nevertheless
have made up for the absence of a negative control—a device designed to ensure
primer specificity and to guard against contamination. As Dr. Hepner testified, “if
we sequence through the vaccine strain nucletide[,] that will distinguish it from any
kind of potential contamination source.” Cedillo Tr. at 667. Petitioners’ failure to
cross-examine Dr. Bustin on this point, however, essentially means his testimony
went unchallenged.
Indeed, respondent notes that the results of the Walker group’s
31
investigation still have not been published.
22
sequencing of their results. Even if we were to assume, however, that the special
30
master overlooked this evidence, we are unable to conclude that such an omission
rises to the level of reversible error. On balance, we do not believe the fact that the
Walker group sequenced a portion—albeit not all—of their results carries enough
weight to overcome the special master’s conclusion that the Walker group’s results
were preliminary, unpublished, and not entitled to substantial weight. As petitioners’
experts acknowledged, poster presentations are not subject to peer review and as a
result do not receive the scrutiny of the scientific community that confers an element
of reliability on published test results. Indeed, respondent’s expert Dr. Brian Ward
31
testified that based on his own experience, such abstracts often turn out to be wrong.
Cedillo Tr. at 1865. We are therefore unwilling to disturb the special master’s
finding on this point. See Cox v. Secretary, Dep’t of Health & Human Servs.,
30 Fed. Cl. 136, 144 (1993) (describing as “harmless error” the special master’s
decision to strike an expert report because the report would not have changed the
outcome of the case).
III. The Special Master’s Failure to Decide a Critical Issue
Having found no evidence to conclude that childhood vaccines lead to the
development of autism, the special master declined to reach the issue of whether
The special master defined phenotype as “the entire physical, biochemical,
32
and physiological makeup of an individual as determined both genetically and
environmentally, as opposed to genotype [(meaning the “genetic constitution” of the
individual)].” Hazlehurst, 2009 WL 332306, at *24 (quoting Dorland’s at 1421).
The special master went on to explain:
Inherent in the definition of a “phenotype” is the combined effect of
genetic and environmental influences on an individual. Underlying
petitioners’ argument that regressive autism is a distinct phenotype is
their theory that this type of autism is caused, in part, by
environmental factors that include childhood vaccines.
Id.
23
regressive autism is a distinct phenotype with different causes than classic autism.32
As the special master observed:
[T]he evidence presented and considered in this litigation does not
support a finding, under the applicable preponderance of the evidence
legal standard, that postnatal exposure to the vaccines of interest leads
to the development of autism of any type. Unpersuaded that
childhood vaccines lead to the development of autism, the
undersigned need not decide whether the evidence supports a finding
that regressive autism is a separate phenotype.
Hazlehurst, 2009 WL 332306, at *24.
Petitioners maintain, however, that the resolution of this issue is critical to
their medical theory causally linking Yates’s MMR vaccination to his regressive
autism. Petitioners argue that in the absence of such a determination, the special
master could not have made a rational assessment regarding the neuroanatomy of
autism, Dr. Corbier’s credibility, or the appropriate weight to be given Dr. Corbier’s
testimony. Petitioners thus urge the court to set the special master’s decision aside
on the ground that it is arbitrary and capricious.
In support of this point, petitioners note that approximately 80 percent of
individuals with autism suffer from classic autism. Petitioners observe, however,
that the majority of the evidence considered by the special master concerning the
neuroanatomy of autism—particularly the testimony of respondent’s expert Dr. Rust
and the articles on which he relied—fail to distinguish between classic autism and
regressive autism. Petitioners thus posit that this evidence may apply only to persons
with classic autism and not to individuals with regressive autism. According to
petitioners, the special master therefore could not have assessed the relevance of such
The Federal Circuit reached a similar conclusion in Andreu, a decision
33
issued one week after the oral argument in this case. Andreu, 2009 WL 1688231.
In Andreu, the court found that the special master had erred by failing to give
sufficient weight to the testimony of a treating physician. Id. at *5. (Like Dr.
Corbier, Yates’s treating neurologist, the treating physician in Andreu concluded that
a link existed between the vaccine and the asserted injury because no other causes
were found and a close temporal relationship existed between the vaccination and the
onset of the injury. See Hazlehurst Tr. at 299; Andreu, 2009 WL 1688231, at *6.)
Although the Andreu holding would appear to strengthen petitioners’ case,
the decision is distinguishable in at least one key respect: while the respondent in
Andreu acknowledged that the petitioner had presented a biologically plausible
medical theory (i.e., satisfying the first prong of the Althen standard), respondent in
the instant case has made no such concession. Indeed, respondent’s expert Dr.
MacDonald, when asked about the plausibility of petitioners’ medical theory,
testified that it was “fantastic, improbable and . . . most importantly not based on any
data.” Hazlehurst Tr. at 643A . Similarly, Dr. Griffin, when asked whether measles
virus in the gut tissue could move through the blood into the brain as petitioners
theorized, responded: “I just don’t see why that would be happening.” Cedillo Tr. at
2782A.
24
evidence without first determining whether regressive and classic autism have the
same causes.
Nor, in petitioners’ view, could the special master have rationally assessed
Dr. Corbier’s credibility or the appropriate weight to be given his testimony without
first determining whether regressive autism is a separate phenotype from classic
autism and correspondingly whether Yates’s regression after receiving the MMR
vaccination implicated environmental causes. Petitioners explain that if regressive
autism is a separate phenotype with environmental causes, Dr. Corbier correctly
characterized the fact that Yates regressed about a month after receiving the MMR
vaccine as having “paramount” importance and the special master accordingly should
have given his testimony considerably more weight. As petitioners observe, “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.’” Capizzano, 440 F.3d at 1326 (quoting Althen, 418 F.3d at 1280).
33
According to respondent, petitioners’ contention that regressive autism is
distinct from classic autism necessarily depends upon a finding that regressive autism
has a distinct cause from classic autism. The problem with petitioners’ argument, in
respondent’s view, is that it is circular: petitioners offered no credible evidence,
either through their own expert witnesses or on cross-examination of Dr. Rust, to
limit the applicability of Dr. Rust’s testimony to classic autism and offered no
Dr. Rust testified that classic and regressive autism were “not entirely
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distinct from each other,” but are “distinguished from one another very reliably by
the fact that children [with regressive autism] are not so severely impaired as those
children [with] classic autism.” Hazlehurst Tr. at 543A–44A.
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reliable evidence of distinct causes of regressive autism. Respondent thus contends
that petitioners fault the special master for failing to draw a distinction about the
neuroanatomy of regressive autism that the scientific community has not recognized
and petitioners have not proved. Finally, respondent asserts that whether regressive
autism is a separate phenotype has no bearing on Dr. Corbier’s credibility or on the
weight to be given his testimony. In respondent’s view, the special master gave Dr.
Corbier’s opinion little weight because she had concluded that the evidence
underlying it was unreliable.
The special master addressed this issue as follows:
Petitioners argue that because the body of epidemiological evidence
to date has focused on autism in general and not on the regressive
form of autism in particular, the conclusions of the discussed and
cited studies have limited relevance to petitioners’ [omnibus
proceeding] claims.
The undersigned finds petitioners’ contention unavailing. . . .
[M]ultiple epidemiological studies of different populations by
different researchers using different study designs have failed to show
an association between the MMR vaccine, thimerosal-containing
vaccines, the onset of autism, and the development of gastrointestinal
symptoms. That the collective body of epidemiological evidence has
consistently failed to show any association makes petitioners’ claims
of a causal relationship less likely. Moreover, even if many of the
conducted studies were not designed to examine whether an
association exists between regressive autism and the vaccines of
interest in this litigation, at least two of the conducted studies
specifically looked for an association between the MMR vaccine and
the development of regressive autism and found none.
Hazlehurst, 2009 WL 332306, at *39.
Contrary to petitioners’ assertion, Dr. Rust in fact distinguished between
classic and regressive autism, but did not attribute the significance to this
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distinction that petitioners urge. Asked about Dr. Corbier’s theory regarding the
effect of environmental factors on the development of regressive autism, Dr. Rust
testified that “the emerging view of autism as I’ve described is the working out of a
genetic development of brain that doesn’t develop properly, and the degree of that
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abnormality helps to differentiate the time of the onset of subtypes of autistic
disorders.” Hazlehurst Tr. at 527A–28A. Further, when asked directly if there are
different genetic or environmental factors involved in the causation of classic versus
regressive autism, Dr. Rust responded that he did not “think that environmental
factors are involved at all in any way.” Hazlehurst Tr. at 550A.
Given the above, we can find no fault with the special master’s declining to
draw a distinction between classic and regressive autism that the scientific
community itself has not identified and for which petitioners have offered no proof.
The special master found that petitioners had failed to offer persuasive evidence that
the MMR vaccine causes any type of autism and therefore did not need to determine
whether regressive autism has a different cause than classic autism. That conclusion,
we believe, was entirely proper.
CONCLUSION
In hearing this appeal, the court is not without sympathy for Yates, the
Hazlehursts, and the other children and families dealing with autism and autism
spectrum disorders. And this court, like the special master, acknowledges both the
burdens many of these families have faced and the tremendous love and support they
have shown their children. The facts, however, do not support petitioners’ appeal
and we have no choice but to deny their motion. Accordingly, for the reasons set
forth above, the special master’s decision of February 12, 2009, is AFFIRMED.
s/John P. Wiese
John P. Wiese
Judge