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En el Tribunal dels Estats Units de Reclamacions Federals
N º 03-654V
Classificat: 24 juliol 2009
Rolf i ANGELA
Hazlehurst, els pares de
Guillermo Iots
Hazlehurst,
Els peticionaris,
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Secretari del Departament
DE SALUT I HUMANS
SERVEIS,
Demandat.
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Vacuna contra la Llei Òmnibus- Autisme
Procediment: En un procediment per
determinar la relació, si s'escau,
entre el xarampió, les galteres i la
vacuna contra la rubèola i el desenvolupament de
autisme regressiu, l'Auxiliar Judicial
no va incórrer en error en basar-se en dades
generats en altres litigis i
ofert en la vigília de l'audiència, si no a la
considerar l'evidència que no tindria
va alterar la seva conclusió, o negar-se a
pronunciar-se sobre l'autisme regressiu és un
fenotip diferent de l'autisme clàssic.
Curtis R. Webb, Twin Falls, ID, advocat del cas dels peticionaris.
Linda S. Renzi i Lynn E. Ricciardella, amb els quals eren de Justícia Auxiliar
Tony West, director Timothy P. Garren, Director Adjunt Interí
Catalina I. Reeves, i el subdirector de Gabrielle M. Fielding, greuges Branch,
De la Divisió Civil, Departament de Justícia dels EUA, Washington, DC, per al demandat.
OPINIÓ
Wiese, jutge.
Els peticionaris, Rolf i Hazlehurst Angela, sol · licitar la revisió d'una decisió formulada per
l'Auxiliar Judicial el 12 de febrer de 2009, la negació del seu fill, William Iots
Hazlehurst, indemnització en virtut de la Llei de lesions infantils Nacional de Vacunació de 1986
("La vacuna contra la Llei"), 42 USC § § 300aa-1 a -34 (2006), per una lesió neurològica,
identificat com l'autisme regressiu, suposadament causats per l'administració de la vacuna de xarampió,
les galteres i la rubèola ("MMR") de la vacuna. Els peticionaris sostenen que el mestre especial
indegudament fonamentar la seva decisió en proves que haurien d'haver estat exclosos,
cas omís d'altres proves que haurien d'haver estat considerats, i es va negar a decidir
una qüestió de fet necessària per a una resolució raonable de la seva reclamació. L'assumpte té
Una descripció dels antecedents processals del procediment general,
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incloent la creació del Comitè de Direcció dels peticionaris, es pot trobar a
Hazlehurst contra el Secretari, Dep de Salut i Serveis Humans Servs., N º 03-654V, 2009 WL
332306, a * 1-3 (Fed. Cl 12 febrer 2009). Malgrat els peticionaris en la demanda instantània
va accedir a que la seva sol · licitud de servir com un cas de prova, l'advocat dels peticionaris no era membre
del Comitè de Direcció dels peticionaris.
Les audiències es van dur a terme en Hazlehurst i Snyder l'octubre 15-18,
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2007, i 5 a 9 nov, 2007, respectivament. A mesura que el mestre especial explica en el seu
decisió, les parts en cada un dels casos de prova presentat evidència general de la causalitat
(Continuarà ...)
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estat informat per les parts i el tribunal va escoltar els informes orals el 11 de juny de 2009. Per
les raons exposades a continuació, el moviment dels peticionaris per a revisar-se li nega.
ANTECEDENTS
Aquest cas és el segon dels tres casos de prova escoltats per l'Oficina d'Educació Especial
Mestres com a part del procediment de Omnibus Autisme ("el procediment general"), una
esforç global per determinar la relació, si n'hi ha, entre la vacuna triple vírica,
les vacunes que contenen Timerosal i l'autisme (o trastorns de l'espectre autista). En ordre
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per fer front als aproximadament 5.000 reclamacions autisme pendent davant del tribunal, un panell
dels advocats que representen als diversos peticionaris, coneguts com dels peticionaris
Comitè Directiu ("el comitè de direcció"), va identificar tres teories generals de la
la relació de causalitat: (1) que les vacunes que contenen Timerosal, quan es combina amb la vacuna MMR
vacuna, pot provocar l'autisme, (2) que les vacunes que contenen Timerosal si sol pot causar
l'autisme, i (3) que la vacuna MMR per si sol pot causar autisme. La direcció
comitè de continuació, seleccioneu tres casos de prova que van caure dins de la general de la causalitat mateixa
teoria, a saber, que les vacunes que contenen Timerosal actuació en combinació amb el
La vacuna MMR pot causar o contribuir al desenvolupament de l'autisme. Aquestes proves
casos-Cedillo contra el secretari, Dep de Salut i Serveis Humans Servs., N º 98-916V,
Hazlehurst contra el Secretari, Dep de Salut i Serveis Humans Servs., N º 03-654V (en l'instant
cas), i Snyder contra el Secretari, Dep de Servs Salut i Serveis Humans, N º 01. -
162V-al seu torn van ser assignats a tres diferents mestres especials per a la seva resolució.
Es va celebrar una audiència en el primer cas, Cedillo, el juny de 2007. En l'audiència,
peticionaris van presentar el testimoni de sis testimonis experts, inclosos experts en
toxicologia, immunologia, biologia molecular, virologia, neurologia i
gastroenterologia. Demandat respondre amb l'evidència de nou perits,
en les àrees temàtiques abordades pels peticionaris, així com de psiquiatria pediàtrica i
l'epidemiologia. Per acord de les parts, el registre en el present cas inclou
tota l'evidència general de la causalitat admès al Cedillo i hearings.2 Snyder
(... Continuació)
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(Relacionat amb si les vacunes que contenen Timerosal en combinació amb el MMR
vacuna podria causar autisme) i l'evidència la relació causal específica (respecte a si el
vacunes administrades havia causat la condició del nen autista, l'especial
cas estava sent escoltat). Hazlehurst, 2009 WL 332306, a * 3.
Els peticionaris definir l'autisme regressiu com una condició caracteritzada per la pèrdua
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de les prèviament adquirides habilitats en lloc de per la manca de desenvolupament de certes habilitats en l'
primera instància. Tant autisme regressiu és una categoria diferent de autisme clàssic
és objecte de debat, però, i és el focus de la secció III de la discussió
a continuació.
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La petició en aquest cas va ser presentada el 26 de març de 2003. D'acord amb
el registre, William Iots Hazlehurst néixer l'11 de febrer de 2000. Durant el
primer any de la seva vida, Yates va rebre les vacunes infantils habituals, incloses
fins a 11 vacunes que contenen Timerosal, possiblement. El 8 de febrer de 2001, tres dies
abans del seu primer aniversari, Iots, a més, va rebre la vacuna MMR.
Mentre que l'expedient indica que Iots es van desenvolupar amb normalitat abans de rebre
la vacuna triple vírica, en el mes següent a la vacunació, Iots es va convertir, en el
paraules de la seva família, "salvatges", "molt hiperactiu", i "fora de control." Per a l'estiu
de 2001, Iots havia perdut tot el discurs significatiu i havia desenvolupat una obsessió amb la
lletres i números. També durant aquest període, Iots va començar a experimentar crònica
diarrea i dolor abdominal.
Qüestions de desenvolupament i gastrointestinals Iots va portar peticionaris a cercar
una sèrie de tractaments durant els pròxims anys. El juliol de 2002, després d'una sèrie de
avaluacions de retards en el desenvolupament i la parla, Iots va ser diagnosticat com
demostrant un gran nombre de comportaments compatibles amb l'autisme. Dues
mesos més tard, el setembre de 2002, Iots va començar el tractament amb el Dr Jean-Ronel
Corbier, un neuròleg pediàtric, per aquesta condició. Durant els propers mesos,
Iots, a més, es va sotmetre a una avaluació immunològica i la colonoscòpia. La
resultats d'ambdues proves van ser normals.
El juny de 2007, els peticionaris van presentar una petició esmenada amb aquest tribunal al · legant
que la vacunació de Iots MMR, o una combinació de la vacunació MMR i el
les vacunes que contenen Timerosal que Iots havia rebut durant els seus primers 12 mesos,
el va portar a desenvolupar autisme regressiu. El mestre especial de resum
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La teoria dels peticionaris de la següent manera:
[P] etitioners afirmar que el component de xarampió de la vacuna triple vírica
causa una disfunció immunològica que afecta la capacitat de la persona vacunada a
eliminar el virus del xarampió. No es pot eliminar adequadament el virus del xarampió
El Dr Corbier ha assenyalat a més que la presència de problemes immunològics
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en aquests nens enforteix el cas de la causalitat-la vacuna MMR, però no és un
part essencial del perfil clínic. Hazlehurst Tr. a la 314A.
En el seu missatge a l'audiència, els peticionaris va explicar que malgrat la seva reclamació
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(Continuarà ...)
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des del cos, el vacunat experimenta persistència del virus del xarampió
el que condueix a la inflamació crònica en el sistema gastrointestinal
i, al seu torn, la inflamació crònica al cervell. Els peticionaris argumenten que
la inflamació al cervell causa un dany neurològic que
es manifesta com l'autisme.
Hazlehurst contra el Secretari, Dep de Salut i Serveis Humans Servs., N º 03-654V, 2009 WL
332306, a * 86 (Fed. Cl 12 febrer 2009).
El mestre especial convocar a una audiència en aquest cas, l'octubre de 2007. Com s'ha assenyalat
anterior, ambdues parts es va basar en part en les proves causalitat general presentada al
Cedillo audiència. A més, els peticionaris van oferir el testimoni d'un cas específic de la Dra
Corbier, neuròleg pediàtric de Iots, i la part demandada va oferir el testimoni del Dr
Thomas T. MacDonald (un immunòleg gastrointestinal), la Dra Christine McCusker
(Un immunòleg pediàtric), i el Dr Robert S. Rust (un neuròleg pediatre).
Durant l'audiència, el Dr Corbier va declarar que les diferències en el moment de la
primera aparició dels símptomes associats amb l'autisme suggereixen que hi ha
diferències en les causes subjacents de l'autisme. L'anterior a l'inici del
símptomes, el Dr Corbier opinar, és més probable que la causa de l'autisme és genètic,
prenatal, o metabòlic. En el cas d'autisme regressiu, però, el Dr Corbier
declarar que els factors causals són "molt probable [que] les influències genètiques i externes
factors ambientals ". Hazlehurst Tr. a la 270A.
El Dr Corbier continuar assenyalant que els estudis han implicat a la vacuna triple vírica
com un factor ambiental que pot contribuir al desenvolupament de regressiu
l'autisme en els nens que encaixen en un perfil clínic en particular. Aquest perfil, d'acord
el Dr Corbier, es compon dels nens que es van desenvolupar normalment abans de rebre el
MMR vacunació, van mostrar símptomes d'autisme regressiu dins de 1-9
mesos següents a la recepció de la vacuna triple vírica, i amb experiència gastrointestinals
problemes. D'acord amb aquest perfil, el Dr Corbier observar que Iots havia
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es van desenvolupar amb normalitat abans que la seva vacuna MMR, una regressió en diversos mesos
després de la recepció de la vacuna triple vírica, i patia de hiperplàsia linfonodular
colitis (inflamació de l'intestí). Hazlehurst Tr. a la 302A. Per tant, el Dr Corbier
va arribar a la conclusió que la recepció de Iots de la vacuna MMR juga un paper important en la
desenvolupament d'autisme regressiu de Iots. Hazlehurst Tr. en 302A-303.
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(... Continuació)
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originalment havia estat designat pel comitè de direcció com un cas de prova per la Teoria de la I-
la identificació de la combinació de la vacuna MMR i les vacunes que contenen Timerosal
com una causa de l'autisme-es va posar de manifest a l'audiència que un cas molt més fort possible
es va fer la vinculació condició de Iots únicament a la vacuna triple vírica. Els peticionaris per tant
centrat exclusivament en la relació de causalitat MMR en la presa del seu cas. Com a resultat, l'especial
mestre limita la seva discussió causalitat específica per a la connexió causal, si n'hi ha,
entre la vacuna SPR i el desenvolupament d'autisme regressiu de Iots. En
per a la plena per fer front a la teoria general de la causalitat del comitè de direcció, però, el
mestre especial, però va analitzar les proves relacionades amb el potencial
contribució de Timerosal com a causa de trastorns de l'espectre autista.
Com evidència que el virus del xarampió pot persistir en el material biològic de
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els nens autistes, els peticionaris es basaven principalment en els següents articles: H.
Kawashima, et al., Detecció i seqüenciació dels virus del xarampió a Perifèric
Les cèl · lules mononuclears de pacients amb malaltia inflamatòria intestinal i l'autisme,
Dig. Dis. Ciència. 45 (4): 723-29 (abril 2000) (co-escrit pel Dr Wakefield); V.
Uhlmann, et al., Mecanisme potencial patogen viral per a la nova variant
Malaltia inflamatòria intestinal, Mol. Pathol. 55 (2): 84-90 (abril 2002) (coautor
pels Drs. Wakefield, O'Leary, i Sheils), i CM Martin et al, Detecció de.
Virus del xarampió en infants amb ili-colònica hiperplàsia nodular limfoide,
Trastorn d'enterocolitis i del Desenvolupament, Mol. Psiquiatria 7 Supl. 2: S47-48
(2002) (co-escrit pels Drs. Uhlmann, O'Leary i Sheils). A més, els peticionaris
va citar els resultats preliminars del grup de Walker que pretenia constatar l'existència de
el virus del xarampió en les biòpsies intestinals dels nens autistes. SJ Walker et al.,
La persistència del virus del xarampió ileal en una gran cohort de nens autistes regressius
Amb ileocolitis i linfonodular Hiperplàsia: revisitació d'un estudi anterior,
cartell de presentació a la Reunió Internacional d'Investigadors per al Autisme (IMFAR),
Universitat de Califòrnia a Davis (juny de 2006).
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Central a la teoria del Dr Corbier de diversos estudis que pretenen trobar el
presència del virus del xarampió en el material biològic dels nens autistes que tenien
van rebre la vacuna triple vírica. Aquests estudis procedeixen de dues fonts principalment: la
treball del Dr Andrew Wakefield del Royal Free Hospital a Londres, Anglaterra, i
seus col · legues els Drs. John O'Leary i Orla Sheils al laboratori de Unigenetics
Dublín, Irlanda, i la investigació del Dr Stephen Walker i els seus companys de la Wake
Forest University School of Medicine a Winston-Salem, Carolina del Nord ("el
Walker grup "). D'acord amb el mestre especial, el Dr Wakefield va ser el principi
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defensor de la hipòtesi que la recepció dels resultats de la vacuna triple vírica en el
desenvolupament dels trastorns de l'espectre de l'autisme i els problemes gastrointestinals en alguns
nens. El treball del Dr Wakefield, l'Auxiliar Judicial va explicar, va ajudar a precipitar
els litigis en el Regne Unit d'examinar la relació de causalitat, si s'escau, entre
la vacuna triple vírica i l'autisme ("el litigi Regne Unit"). Per tal de donar suport al Regne Unit
Les proves de PCR és una tècnica estàndard per a la detecció i identificació especial
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seqüències de gens en mostres de teixit de forma exponencial replicar brins d'ADN.
Hazlehurst, 2009 WL 332306, a * 95.
Els mètodes utilitzats per Unigenetics va formar la base de la recerca en el
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2002 Uhlmann article, un dels articles en què es va basar principalment peticionaris.
Cedillo Tr. a la 1938. A més, Unigenetics provat fluid cerebroespinal i teixit
Les mostres de-i pretesos per detectar la presència del virus del xarampió en el
vacunats en els casos de prova dos, Michelle Cedillo i Snyder Colten. Iots, per
Per contra, no va patir aquesta prova.
El Dr Wakefield publicar un article el 1993, postulant una relació de causalitat
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entre el virus del xarampió i d'infarts de petits vasos sanguinis a la paret de l'intestí
que condueix a la malaltia de Crohn. AJ Wakefield i col., Evidència de xarampió persistents
La infecció en la malaltia de Crohn, J. Med. Virol. 39 (4): 345-53 (abril 1993). L'especial
mestra va assenyalar que en resposta a l'opinió pública "furor" creat pel Wakefield 1993
article, el Consell d'Investigació Mèdica del Regne Unit va revisar el Dr
El treball de Wakefield i va arribar a la conclusió que el Dr Wakefield havia dut a terme els seus experiments
amb reactius que no eren específics per al virus del xarampió i sense important
controls que el fabricant de l'equip de proves recomanades. Hazlehurst,
2009 WL 332306, a * 87. El mestre especial, a més, va observar que, després
una sèrie d'estudis metodològicament sòlids dut a terme a finals de 1990, la comunitat científica
la comunitat en última instància, desestimar la hipòtesi del Dr Wakefield és que té poc científica
mereixen. Identificació.
El Dr Wakefield publicar dos articles addicionals el 1998 i 2000, la primera
avançar la hipòtesi que la vacuna MMR provoca el desenvolupament de l'autisme
trastorns de l'espectre amb manifestacions gastrointestinals i en el segon les
la recerca de la enterocolitis en els nens amb trastorns del desenvolupament. AJ Wakefield,
et al., ileal-limfoide-nodular hiperplàsia, colitis no específica, i generalitzat
Trastorn del Desenvolupament en la infància, The Lancet 351 (9103): 637-41 (febrer 1998), AJ
Wakefield, et al., Enterocolitis en nens amb trastorns del desenvolupament, Am J.
(Continuarà ...)
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litigis, els Drs. O'Leary i Sheils del Trinity College a Dublín, va formar el
Unigenetics laboratori, una institució no acreditada, amb fins de lucre que utilitza una tècnica de
anomenat PCR (reacció en cadena de la polimerasa) per detectar la presència del virus del xarampió
en el teixit de la biòpsia. Els resultats positius informats pel laboratori Unigenetics
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van ser més tard, l'enfocament del grup Walker, el preliminar proves pretenia
replicar els resultats dels Unigenetics.
El mestre Especial observar, però, el treball que el Dr Wakefield ha estat
àmpliament desacreditat per la comunitat científica, i que les proves realitzades en
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(... Continuació)
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Gastroenterology 95 (9): 2285-95 (2000). Tots dos articles van ser objecte d'àmplia
la crítica, però, i en última instància, l'Auxiliar Judicial trobar que eren "científicament
poc fiable ". Hazlehurst, 2009 WL 332306, a * 90. A més, el mestre especial
observar que deu dels 12 el Dr Wakefield els co-autors en l'article de 1998 més tard es va retractar
l'estudi de la conclusió que una relació causal potencial entre la vacuna triple vírica
i l'autisme. Identificació. * En el 90-92.
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tant en el Unigenetics i laboratoris de Wake Forest contenia defectes de procediment que
compromès la seva fiabilitat. El mestre especial en aquest sentit que els estudis sobre
que el Dr Corbier es va basar eren "científicament errònia o poc fiable" i que el Dr
Corbier opinió respecte a aquest aspecte de la teoria de la causalitat dels peticionaris (plantejant la
l'existència del virus del xarampió que persisteix en el teixit intestinal dels nens autistes) "no es va poder
ser acreditat com el so o fiable ". Hazlehurst, 2009 WL 332306, a * 13. L'especial
mestre en conseqüència va arribar a la conclusió que la teoria dels peticionaris de la causalitat "va ser la premissa
en una sèrie de implausabilities biològics "i que estava" en desacord amb la coneguda
la ciència. "Id * En el 148-49.
Després de la publicació de la decisió del mestre especial de negar
la compensació, els peticionaris ia demanar a la cort per fer front a tres temes en l'apel · lació.
Específicament, els peticionaris objectar: ​​(1) el mestre especial d'examen de les proves
Unigenetics descrèdit, el laboratori que va detectar el virus del xarampió en el teixit
dels nens autistes, (2) el fracàs del mestre especial per examinar les proves
demostrant la fiabilitat dels resultats obtinguts pel grup Walker, també pretén
per trobar la presència del virus del xarampió en el teixit dels nens autistes, i el (3)
mestre especial de la manca de decidir si l'autisme regressiu és un fenotip diferent
l'autisme clàssic. Abordem aquests temes, al seu torn a continuació.
DISCUSSIÓ
En decidir un recurs de revisió de la decisió d'un mestre especial en el marc del
Vacuna contra la Llei, el tribunal pot:
(A) mantenir les conclusions de fet i conclusions de dret de la
mestre especial i mantenir la decisió del mestre especial, la
(B) deixar de banda totes les conclusions de fet o de la conclusió de la llei de la
mestre especial que es troba per ser arbitrària, capritxosa, un abús de
discreció, o d'altre tipus que no estigui conforme amb la llei i emetre la seva pròpia
les conclusions de fet i conclusions de dret, o
(C) tornar la denúncia al mestre especial d'adoptar noves mesures
Fins i tot si els peticionaris tenen èxit en la fabricació d'un cas prima facie per
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la relació de causalitat, però, l'Auxiliar Judicial pot negar la compensació quan la
demandat ha demostrat per la preponderància de l'evidència que la lesió es deu a
(Continuarà ...)
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d'acord amb la direcció de la cort.
42 USC § 300aa-12 (i) (2). El Circuit Federal ha interpretat 42 USC § 300aa-
12 (e) (2) (B), que estableix tres nivells diferents de revisió: (1) l'especial de mestratge
les conclusions de fet han de ser analitzades en virtut de la norma arbitrària i capritxosa, (2) de la
decisions discrecionals mestres especials són per a ser examinat sota l'abús de discreció
norma, i (3) les conclusions jurídiques del mestre especial de s'han de revisar de novo
en què no estigui conforme amb la norma la llei. Turner contra el Secretari, Dep de Salut
I Servs Humans., 268 F.3d 1334, 1337 (Fed. Cir. 2001). L'error és reversible
extremadament difícil establir, però, sempre que el mestre té especial
"Considera les proves pertinents en el registre com un tot, dibuixat possible
inferències a partir d'aquesta evidència, i articula una base per [la] decisió que és
racional ". Hines contra el Secretari, Dep de Salut i Serveis Humans Servs., 940 F. 2d 1518, 1527
(Fed. Cir. 1991).
Hi ha dos mètodes per establir el dret a indemnització d'acord amb el
Vacuna contra la Llei Si la persona vacunada va patir una de les lesions identificades en la vacuna
Lesions taula dins el termini establert (42 USC § 300aa-14 (a) (inicial
Taula) i 42 CFR § 100.3 (Taula actualitzada)), el peticionari pot fer valer el que és
comunament es coneix com una "lesió de taula," amb una presumpció refutable que la
lesió va ser causada per la vacuna. 42 USC § 300aa-11 (c) (1) (C) (i); Pafford v
Secretari, Dep de Salut i Serveis Humans Servs., 451 F. 3d 1352, 1355 (Fed. Cir. 2006).
Si la persona vacunada va patir una lesió no identificada a la taula de Lesions de Vacunes, però,
(Com en el cas que ens ocupa), no existeix aquesta presumpció, i el peticionari ha de demostrar que
la vacuna contra la "causa" o "significativament greu" la lesió en qüestió (normalment
a què es refereix com un reclam relació de causalitat en el fet). 42 USC § 300aa-11 (c) (1) (C) (ii) (I);
Pafford, 451 F.3d el 1355.
Per tal de demostrar que el dany Iots va ser causada pel fet
desafiar la vacuna, els sol · licitants han de demostrar la seva reclamació per la preponderància de la
proves, una norma que està satisfet en mostrar que és "més probable que no"
que la vacuna en qüestió causat un perjudici del vacunat. Althen contra el Secretari, Dep de
Salut i Serveis Humans Servs., 418 F.3d 1274, 1279 (Fed. Cir. 2005). Per realitzar una vista
cas prima la relació de causalitat en Althen, els sol · licitants hauran de presentar: "(1) una teoria mèdica
causalment la connexió de la vacunació i la lesió, (2) una seqüència lògica de causa
i l'efecte que mostra que la vacunació va ser la raó de la lesió, i un (3)
mostra d'una relació de proximitat temporal entre la vacunació i les lesions. "Id
el 1278. Encara que els peticionaris no estan obligats a presentar "els estudis epidemiològics,
10
(... Continuació)
10
factors no relacionats amb l'administració de la vacuna. Walther contra el Secretari, Dep't
de Salut i Serveis Humans Servs., 485 F.3d 1146, 1150 (Fed Cir. 2007).
Citant el testimoni de diversos testimonis experts (entre ells la Dra Diane
11
Griffin, una autoritat reconeguda sobre el xarampió), el mestre especial observar que
el virus de la vacuna contra el xarampió-deformació, en contrast amb el virus de tipus salvatge del xarampió, és molt
menys virulent, ha estat específicament dissenyat per a no replicar bé en el cos humà,
i no presenta les complicacions més importants associades amb el tipus salvatge
virus del xarampió. Hazlehurst, 2009 WL 332306, a * 149-50. El mestre especial
ha assenyalat a més que en la "circumstància excepcional" que la de tipus salvatge del virus del xarampió
persisteix en la malaltia dels cossos i les causes, les lesions resultants es distingeixen de
els impediments associats amb l'autisme i inclouen el deteriorament neurològic que
resulta en la mort. Identificació. al * 149.
9
[Proves de] la reexposició, la presència de marcadors patològics o predisposició genètica,
o l'acceptació general a la comunitat científica o mèdica ", per establir
la relació de causalitat, Capizzano contra el Secretari, Dep de Salut i Serveis Humans Servs., 440 F. 3d 1317,
1325 (Fed Cir. 2006), però, ha de proporcionar un metge "de bona reputació o
explicació científica "per al seu reclamació, Althen, 418 F.3d el 1278. La determinació
de si una teoria de la causalitat oferta és "respectable" pot "incloure una avaluació
de les dades científiques pertinents ". Andreu contra el Secretari, Dep de Salut i Serveis Humans
Servs., N ° 2008-5184, 2009 WL 1.688.231, a * 9 (Fed. Cir. 18 de juny 2009). "Metge
la literatura i l'evidència epidemiològica ha de ser vist, però, no a través de la
lent de la tècnic de laboratori, sinó que des del punt de vista de la Llei de Vacunes
criteri d'evidència preponderant ". Id
En la demanda instantània, els peticionaris afirmen que el xarampió, els components de la triple vírica
vacuna pot causar una disfunció immune en certs nens que els impedeix
sistemes de neteja de virus del xarampió. Segons aquesta hipòtesi, la persistència
virus del xarampió condueix a la inflamació crònica tant en el sistema gastrointestinal i
el cervell. La inflamació al cervell, els peticionaris sostenen, causes neurològiques
danys que es manifesta com l'autisme.
En l'anàlisi de la teoria dels peticionaris mèdica sota la norma Althen-, l'especial
mestre identificat dues deficiències cardinals en el cas dels peticionaris. En primer lloc, el mestre especial
Ha explicat que els experts dels peticionaris van basar les seves impressions de les característiques de la
"Tipus salvatge" del virus del xarampió en lloc de en les característiques del cep vacunal contra el xarampió,
malgrat el fet que la vacuna contra el xarampió és distingible de la de tipus salvatge
virus del xarampió en diversos aspectes clau. En segon lloc, el mestre especial observar que
11
experts dels peticionaris més basat les seves opinions en els estudis (la detecció de la presència de
el virus del xarampió en el teixit intestinal dels nens autistes) que el mestre especial que es troba
ser poc fiables. Com a resultat d'aquestes deficiències, l'Auxiliar Judicial va sostenir que
El mestre especial, a més, va sostenir que els peticionaris no havien establert
12
una associació temporal amb el tercer nivell de Althen-pel fet que la vacuna contra la soca-
virus del xarampió no es replica bé en el cos humà i l'única evidència
peticionaris que s'ofereixen per al xarampió, la persistència de l'article-es Uhlmann desacreditat.
Identificació. al * 150.
10
peticionaris no havia fet els dos primers dents de la norma, perquè Althen
seva teoria mèdica es basava en una sèrie de inverosimilitudes biològics i el
les proves presentades no va recolzar una seqüència lògica de causa i efecte entre
la vacuna i la lesió. Hazlehurst, 2009 WL 332306, a * 149-50.12
En arribar a la seva conclusió, el mestre especial que descriu la troballa de
contra el xarampió la persistència del virus en el teixit intestinal dels nens autistes com "pedra angular" de la
La teoria dels peticionaris. Identificació. al * 171. El mestre especial va passar a descriure que
proposició, però, com "notòriament poc fiables" sobre la base de la seva avaluació que el
estudis en els quals els experts dels peticionaris van basar les seves conclusions eren "seriosament defectuosos
i científicament insostenible. "Id En particular, el mestre especial dedicat una àmplia
la discussió a una anàlisi dels mètodes d'assaig del laboratori Unigenetics,
explicant que la dependència dels peticionaris en els resultats de la prova, juntament amb el demandat
la crítica d'ells, han fet necessari per al seu per analitzar les pràctiques dels Unigenetics "amb
un major control del que generalment passa en els procediments de la vacuna ". Id al * 126. És aquesta
escrutini que serveix com el primer motiu d'apel · lació dels peticionaris.
I. El Mestre Especial de confiança en l'evidència que
No hauria d'haver estat considerat
El mestre especial sobre la base de la seva avaluació pel que fa a la fiabilitat de la
les proves realitzades en el Unigenetics en part en el testimoni del Dr Stephen A. Bustin,
un biòleg molecular que va aparèixer com un testimoni expert, tant per a la vacuna
fabricants al Regne Unit i els litigis de part demandada en el procediment general.
Com a part del litigi Regne Unit, el Dr Bustin va ser encarregat d'avaluar la 2002
Uhlmann article i l'examen dels mètodes d'assaig utilitzats pels Unigenetics
laboratori. El Dr Bustin va declarar més tard que ell va passar 1.500 hores analitzant les dades de
el laboratori, incloent dues visites de camp, i se li facturarà uns 400.000 dòlars per la seva
esforços.
Basat en la seva anàlisi de Unigenetics'procedures, equips i laboratoris
quaderns, el Dr Bustin va arribar a la conclusió que els investigadors Unigenetics no havia seguit
del laboratori propis procediments operatius estàndard, no s'adhereixen a certa
pràctiques de laboratori estàndard, i no va complir amb les normes establertes pel
fabricant de l'equip de prova, la qual cosa disminueix la fiabilitat del
resultats de les proves que pretenen demostrar la presència del virus del xarampió en el teixit intestinal de
els nens autistes. El Dr Bustin especulat que els investigadors havien detectat Unigenetics
Abans de la seva admissió en el cas de Cedillo, el Dr Bustin els informes, com tots els
13
dels objectes exposats en el litigi Regne Unit, havia estat sota el segell de la cort britànica. El Dr
Bustin, a més, havia estat objecte d'una ordre judicial que li prohibia
testimoni sobre els procediments de Unigenetics, equips, i els quaderns de laboratori en qualsevol
altre cas. Tant el Dr Bustin d'informes i el seu testimoni es van posar a disposició,
No obstant això, després de l'aplicació amb èxit del demandat a la cort britànica.
El mestre especial va explicar que el comitè directiu havia informat a la
14
mestres especials dels tres casos de prova de la seva decisió de no buscar l'alliberament de
documents addicionals de la cort britànica, ja que els seus esforços per fer era probable que el
no han tingut èxit donada la incapacitat del comitè de direcció per obtenir la necessària
el consentiment dels experts els informes que buscaven. Hazlehurst, 2009 WL 332258,
al * 8.
11
Contaminació en lloc d'ADN del virus del xarampió en el teixit de la biòpsia.
El Dr Bustin es va identificar posteriorment com un expert en el cas de Cedillo a finals de
De maig / principis de juny de 2007 en suport d'una moció in limine pel demandat no tenen relació amb
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 HR Rep. No. 99-908, at 3 (1986), as reprinted in 1986 USCCAN
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 US 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 (ie, 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. La
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.
MA 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 USC § 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 MA 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, eg, 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. La
(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 (ie, children with autism) had not
been compared to a control group (ie, 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 (ie,
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 (ie, 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
34
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.
25
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
34
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
26
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