Holt v. Secretary of Health and Human Services

In the United States Court of Federal Claims

OFFICE OF SPECIAL MASTERS

No. 05-0136V

Filed: June 24, 2015

For Publication

********************************

LAURA HOLT, parent of *

A.H.T., a minor, * Autism; Entitlement;

* Mitochondrial

Petitioner, * Disorder;

* Hepatitis B Vaccine;

v. * Encephalopathy;

* Colic; Gastrointestinal

SECRETARY OF THE DEPARTMENT * Problems; Diagnosis;

OF HEALTH AND HUMAN SERVICES, * Timing; Lack of Logical

* Connection

Respondent. *

*

********************************

Andrew D. Downing, Van Cott & Talamante, PLLC, Phoenix, AZ for petitioner.

Alexis B. Babcock, U.S. Dept. of Justice, Washington, DC, for respondent.

DECISION1

Vowell, Chief Special Master:

On January 21, 2005, Laura Holt [“Ms. Holt” or “petitioner”] filed a “short-form”

petition seeking compensation under the National Vaccine Injury Compensation

Program, 42 U.S.C. §300aa-10, et seq.2 [“Vaccine Act” or “Program”] on behalf of her

1 The E-Government Act of 2002, Pub. L. No. 107-347, 116 Stat. 2899, 2913 (Dec. 17, 2002), requires

that this decision be publicly available. In accordance with Vaccine Rule 18(b), petitioner has 14 days to

identify and move to redact medical or other information, the disclosure of which would constitute an

unwarranted invasion of privacy. If, upon review, I agree that the identified material fits within this

definition, I will redact such material from public access.

2The National Vaccine Injury Compensation Program [“Vaccine Program”] is set forth in Part 2 of the

National Childhood Vaccine Injury Act of 1986, Pub. L. No. 99-660, 100 Stat. 3755, codified as amended,

42 U.S.C. § 300aa-10 et seq. (2006). All citations in this decision to individual sections of the Vaccine Act

are to 42 U.S.C. § 300aa.

daughter, A.H.T. Such petitions, authorized by Autism General Order #1,3 alleged in a

summarized fashion that the vaccinee has a disorder on the autism spectrum.4

However, petitioner now appears to be repudiating ASD as the claimed injury,

while nevertheless asserting that the neurological symptoms relied on for the ASD

3 By electing to file a Short-Form Autism Petition for Vaccine Compensation, petitioner alleged that:

As a direct result of one or more vaccinations covered under the National Vaccine Injury

Compensation Program, the vaccinee in question has developed a neurodevelopmental

disorder, consisting of an Autism Spectrum Disorder or a similar disorder. This disorder

was caused by a measles-mumps-rubella (MMR) vaccination; by the “thimerosal”

ingredient in certain Diphtheria-Tetanus-Pertussis (DTP), Diphtheria-Tetanus-acellular

Pertussis (DTaP), hepatitis B, and Hemophilus Influenza Type B (Hib) vaccinations; or by

some combination of the two.

Autism General Order #1, 2002 WL 31696785 (Fed. Cl. Spec. Mstr. July 3, 2002), Exhibit A, Master

Autism Petition for Vaccine Compensation at 2. In filing a short-form petition, petitioner joined the

Omnibus Autism Program [“OAP”]. A more detailed discussion of the OAP and the effects of joining it can

be found in the OAP test case decisions. See, e.g., Dwyer v. Sec’y, HHS, No. 03-1202V, 2010 WL

892250, at *3 (Fed. Cl. Spec. Mstr. Mar. 12, 2010).

4I use the abbreviation “ASD” to refer to the broad category of autism spectrum disorders. These

disorders were defined for petitioner by Dr. (Ph.D.) Laurie Grimes, a clinical psychologist who evaluated

A.H.T. in 2004. Her report, which was provided to Ms. Holt (see Petitioner’s Exhibit [“Pet. Ex.”] 17, pp.

154-55), stated:

Autism, also referred to as pervasive developmental disorder (PDD) or autism spectrum

disorder (ASD), is a term for a spectrum of handicaps in which there are impairments in

social communication. The level and nature of impairment varies from child to child so

that no two people with autism have the same blend of communication challenges.

Social communication includes behaviors such as facial expression, emotional gesture,

melody (prosody) of speech, and knowledge of social rules (pragmatics) of

communication that are used in human interaction to convey cognitive and emotional

information. Social communication skills develop early in life and are a primary mode for

learning about the environment through non-verbal means. Autism is sometimes

associated with a lack of language skills, odd and stereotyped behaviors, profound

inability at social interaction, and/or mental retardation. While such children may have

varying degrees of some of these problems, others have normal intelligence and

language and only mild deficits in social interaction skills. What is shared by all people

with autism are handicaps in dealing with other people due to their inability to use and

understand common verbal, gestural, and expressive communication. Current research

uses four domains to evaluate social communication: affective reciprocity (one's ability

to send and receive social signals to others using facial expression, tone of voice, and

social and emotional gestures), emotional joint attention (one's efforts to share

interests with others – show things, talk reciprocally, smile socially, direct others’ attention

to objects of interest, show affection), verbal joint attention (one's ability to be verbal

social[ly], to use give-and-take conversation, to show interest in others), and theory of

mind (in young children seen as social imagination; one's ability to converse

appropriately; one's ability to infer another's intentions).

Id., pp. 144-45 (emphasis original).

2

diagnosis constitute at least part of the compensable injury.5 An amended petition,

which does not use the terms “ASD” or “autism,” was filed on September 22, 2011.6

This petition alleges that, as the result of a hepatitis B vaccination received on April 4,

2002, A.H.T. experienced a variety of symptoms affecting her feeding, sleeping,

temperament, and gastrointestinal function. Petition at 1. However, petitioner does not

appear to be claiming that these particular symptoms are the injury for which she seeks

compensation. Rather, she contends that this vaccination “significantly aggravated an

underlying mitochondrial disorder,”7 presumably with the manifestations being the

symptoms exhibited following the vaccination, and causing “the resulting

encephalopathic event.” Petition, ¶¶ 15-16. The reference to an “encephalopathic

event” is ambiguous, in that it could refer to symptoms after the vaccination or the

behavioral symptoms that resulted in her sensory integration disorder diagnosis many

months after the vaccination, and other diagnoses, including ASD, over the ensuing

years.8

5 Ms. Holt claimed not to understand the term “autism spectrum disorder” during her testimony.

Transcript [“Tr.”] at 73. However, throughout A.H.T.’s medical records, Ms. Holt and A.H.T.’s physicians

used the terms “autism,” “pervasive developmental disorder,” and “PDD-NOS.” See, e.g., Pet. Exs. 47, p.

2052 (intake form for Dr. Andrew Levinson, dated May 23, 2010, with petitioner indicating that A.H.T. had

been diagnosed with autism and pervasive developmental delay-not otherwise specified and that she was

seeking biomedical treatment for that condition); 17, p. 145 (notation in report provided to A.H.T.’s

parents that one test had shown her to be at “moderate risk for autism spectrum disorder”). Moreover,

Ms. Holt frequently reported that her maternal uncle had autism, a disorder on the autism spectrum,

reflecting her understanding of the condition and term. See, e.g., Pet. Exs. 39, p. 1826; 41, p. 1832.

Other health care providers used the term “autism spectrum” in A.H.T.’s medical records. See, e.g., Pet.

Exs. 30, p. 1231 (noting that delayed sleep was seen in “individuals on the autism spectrum”); 44, p. 1878

(letter indicating A.H.T. had an original diagnosis “on the autism spectrum”). The pages of each exhibit

were not individually numbered, resulting in the large page numbers for later-filed exhibits.

6Hereinafter, unless the context clearly indicates otherwise, any references to “petition” are to this

amended petition.

7 A mitochondrial disorder is one affecting the function of the mitochondria—organelles contained in

varying numbers in virtually every cell of the body. Tr. at 424-25. The mitochondria use oxygen and food

to produce adenosine triphosphate [“ATP”], the primary source of energy for all bodily functions, through

a process labeled “the respiratory chain” or “electron transport chain” [“ETC”]. Tr. at 300, 424-25.

Problems with energy production in the ETC can occur as the result of genetic defects in either the

mitochondria’s own DNA [“mtDNA”] or in the DNA found in the nucleus of cells themselves [“nuclear DNA”

or “nDNA”]. Tr. at 430. The sole function of the mtDNA is to make proteins that are components of the

ETC. Tr. at 433. When a DNA defect results in clinical symptoms, a person is said to have a “primary”

mitochondrial disease or defect. Other bodily processes including metabolic disorders, hypoxia, and

some drugs may also affect the ETC, causing diminished ETC function, producing “secondary

mitochondrial dysfunction.” Tr. at 398, 428-29. In the absence of an identified genetic defect or the

presence of clusters of symptoms fitting a known mitochondrial syndrome, diagnosing a mitochondrial

disorder is difficult. See generally, Pet. Ex. 79 (expert report of Dr. Frances Kendall); Respondent’s

Exhibit [“Res. Ex.”] G (expert report of Dr. Shawn McCandless). Doctor Kendall’s report indicated that the

“vast majority of pediatric mitochondrial disease” involves nDNA, with about 10% related to defects in

mtDNA. Pet. Ex. 79 at 2494.

8 The filed medical records do not establish when and how A.H.T. was first diagnosed with an ASD. At

the hearing, petitioner used several pages of an intake form dated August 12, 2005, that she completed

for Dr. Phillip DeMio. See Petitioner’s Trial Exhibit [“Pet. Tr. Ex”] 1. This document contains petitioner’s

assertion that A.H.T. was diagnosed with pervasive developmental delay in September 2004 by Dr.

3

The amended petition in this case and petitioner’s apparent disavowal of an ASD

diagnosis appear to be part of the trend by some former OAP petitioners to re-

characterize their children’s diagnoses as something other than ASD, in an attempt to

render irrelevant the impressive body of evidence produced in the OAP test cases

establishing that vaccines are exceedingly unlikely to be responsible for ASD.9 The

filing (or amendment) of claims for compensation based on the particular theory

advanced in this case—that a vaccine significantly aggravated an underlying

mitochondrial disorder, causing manifestation of ASD or a similar neurological

disorder—stems from another, and widely-publicized, vaccine injury case. In that case,

discussed more extensively in n.76 and in Section IV, Part B(1)(a) below, a child with a

mitochondrial disorder and autistic symptoms received compensation based on her

presentation with severe neurological symptoms within the Table injury10 period for the

vaccines that she received.

Vinjay Puri. Doctor Puri, a pediatric neurologist, evaluated A.H.T. on September 16, 2004. The records

from this visit do not reflect a pervasive developmental disorder or delay diagnosis. Rather, he diagnosed

a sensory integration disorder, night terrors, and a mild language loss or regression. Pet. Ex. 31, p. 1265.

The intake form also reflects that someone in the Jefferson County Public School system diagnosed

A.H.T. with autism in February 2005. Pet. Tr. Ex. 1, p. 1. The records reflecting this diagnosis were not

filed and thus it is unclear what diagnostic testing, if any, led to the school district’s conclusions. I note

that in October 2004, Dr. Grimes, a clinical psychologist, administered standard diagnostic tests for ASD.

She concluded that A.H.T. “has demonstrated behaviors that were suggestive of ASD, though [the test

results] do not support that diagnosis at this time.” Pet. Ex. 17, p. 146. This is the only mention of

diagnostic testing for ASD in the record. However, ASD, autism, and PDD-NOS (pervasive

developmental disorder-not otherwise specified) diagnoses appear throughout A.H.T.’s medical records

after 2005. See, e.g., Pet. Exs. 16, pp. 133, 142; 19, p. 214; 27, pp. 629-30; 31, pp. 1245-46; 38, p.

1689; 51, pp. 2188-89. I also note that in Jan. 2005, just days after filing the short-form petition in this

case and thereby joining the OAP, petitioner and Mr. Tipton revoked permission for Dr. Grimes to disclose

A.H.T.‘s negative test results for autism to the school system. Pet. Ex. 17, pp. 161-62. Three months

later, they wrote Dr. Grimes, requesting that she “correct” her October 2004 evaluation. Id., pp. 157-58.

In doing so, they pointed out the presence of “very abnormal autistic-like behaviors” in A.H.T. Id., p. 158.

Both of respondent’s experts were unwilling to opine that A.H.T. had ASD, in view of the lack of

diagnostic testing, but noted the presence of symptoms commonly seen in children with ASD. Tr. at 537,

545, 560-61.

9 Since January 2007, I have been one of the small group of special masters assigned primarily to the

“autism docket.” I presided over two of the six OAP test case hearings and issued decisions in each.

These lengthy decisions were necessitated by one of the purposes for the omnibus proceeding—to

create a body of evidence that could be relied upon to resolve the remaining OAP cases like this one—as

well as to evaluate the causation theories presented in the context of the individual test cases. After

appellate review of the test case decisions was completed, I oversaw the effort to resolve the remaining

open OAP cases. The majority of these cases were dismissed based on petitioners’ motions. However,

some petitioners elected to proceed with their cases, either on a new theory of causation or based on

injuries other than ASD. Most of the OAP petitioners who have continued to press claims for vaccine

compensation have presented variations on the theory presented here—that vaccines “significantly

aggravated an underlying mitochondrial disorder, resulting in autism-like symptoms.”

10A “Table” injury is an injury listed on the Vaccine Injury Table, 42 C.F.R. § 100.3, corresponding to the

vaccine received within the time frame specified.

4

Prior to the hearing, petitioner filed a joint submission of the parties, listing the

jurisdictional and factual issues upon which they agreed. The parties indicated that

“[t]he issue to be decided is whether the vaccinations [A.H.T. received] (either alone or

in combination) caused-in-fact her subsequently diagnosed developmental,

neurological, or mitochondrial issues.” Joint Submissions at ¶ 7. This joint submission

clarifies the injuries for which compensation is sought.

Regardless of how A.H.T.’s condition is characterized, petitioner has the burden

to demonstrate by preponderant evidence that a vaccine actually caused or significantly

aggravated A.H.T.’s condition.11 For the reasons set forth below, I find that petitioner

has failed to do so and thus is not entitled to compensation.

I. Procedural History.

After the short-form petition was filed, A.H.T.’s case, like most other OAP cases,

remained on hold until litigation in the test cases was completed.12 After the resolution

of the test cases in 2010, the special masters began the process of determining how the

11 Because the Vaccine Injury Table, 42 C.F.R. § 100.3, lists no injuries for the hepatitis B vaccine (the

only vaccine A.H.T. ever received), petitioner cannot avail herself of any presumption in favor of

causation. Her burden of proof is the traditional tort burden: she must produce preponderant evidence

that a vaccine caused or significantly aggravated A.H.T.’s condition. 42 U.S.C. § 300aa-13(a)(1)(A);

Moberly v. Sec’y, HHS, 592 F.3d 1315, 1322 (Fed. Cir. 2010) (citing de Bazan, 539 F.3d 1347, 1351

(Fed. Cir. 2008); Pafford v. Sec’y, HHS, 451 F.3d 1352, 1355 (Fed. Cir. 2006); Capizzano v. Sec’y, HHS,

440 F.3d 1317, 1320 (Fed. Cir. 2006); Althen v. Sec’y, HHS, 418 F.3d 1274, 1278 (Fed. Cir. 2005)).

Loving v. Sec’y, HHS, 86 Fed. Cl. 135, 144 (2009), established a methodology for evaluating a significant

aggravation claim. The first three steps require the fact-finder to: (1) determine the vaccinee’s condition

prior to administration of the vaccine; (2) determine the vaccinee’s current condition or condition following

the vaccine; and (3) decide whether the vaccinee’s condition was significantly worsened after the

vaccination. The remaining three steps involve the application of Althen in a significant aggravation

context, and require the petitioner to produce preponderant evidence of (4) a medical theory causally

connecting the significantly worsened condition to the vaccine; (5) a logical sequence of cause and effect

demonstrating that the vaccine was the reason for the significant aggravation; and (6) a proximate

temporal relationship between the vaccine and the significant aggravation. This methodology has been

cited with approval by the Federal Circuit. W.C. v. Sec’y, HHS, 704 F.3d 1352, 1357 (Fed. Cir. 2013).

12The Petitioners’ Steering Committee [“PSC”], an organization formed by attorneys representing

petitioners in the OAP, litigated six test cases presenting two different theories on the causation of ASD.

Decisions in each of the three test cases pertaining to the PSC’s first theory rejected the petitioners’

causation theories. Cedillo v. Sec’y, HHS, No. 98-916V, 2009 WL 331968 (Fed. Cl. Spec. Mstr. Feb. 12,

2009), aff’d, 89 Fed. Cl. 158 (2009), aff’d, 617 F.3d 1328 (Fed. Cir. 2010); Hazlehurst v. Sec’y, HHS, No.

03-654V, 2009 WL 332306 (Fed. Cl. Spec. Mstr. Feb. 12, 2009), aff’d, 88 Fed. Cl. 473 (2009), aff’d, 604

F.3d 1343 (Fed. Cir. 2010); Snyder v. Sec’y, HHS, No. 01-162V, 2009 WL 332044 (Fed. Cl. Spec. Mstr.

Feb. 12, 2009), aff’d, 88 Fed. Cl. 706 (2009). Petitioners in Snyder did not appeal the decision of the U.S.

Court of Federal Claims. Decisions in each of the three “test cases” pertaining to the PSC’s second

theory also rejected the petitioners’ causation theories, and petitioners in each of the three cases chose

not to appeal. Dwyer, 2010 WL 892250; King v. Sec’y, HHS, No. 03-584V, 2010 WL 892296 (Fed. Cl.

Spec. Mstr. Mar. 12, 2010); Mead v. Sec’y, HHS, No. 03-215V, 2010 WL 892248 (Fed. Cl. Spec. Mstr.

Mar. 12, 2010). The petitioners in each of the three Theory 2 cases did not seek review of the special

masters’ decisions.

5

approximately 4,800 remaining OAP claims would be resolved by ordering each

claimant to indicate if he or she wished to proceed or exit the Vaccine Program.

On March 15, 2011, petitioner filed a motion to substitute Mr. Downing as her

attorney of record. I granted the motion and, interpreting it as evincing petitioner’s intent

to proceed with her claim, I ordered her to file an amended petition that asserted the

specific basis for her causation claim. Order, issued Apr. 4, 2011. Petitioner complied

on September 22, 2011, filing several statements or declarations and some medical

records and other evidence along with the petition. See Pet. Exs. 1-6. Over the next

six months, petitioner filed additional medical records, statements and affidavits, 13 and

some medical literature.14 Petitioner filed a statement containing an opinion on

causation and the curriculum vitae [“CV”] of Dr. Levinson on February 29, 2012 and a

similar opinion and CV from Dr. Phillip C. DeMio on March 12, 2012.15 See Pet. Exs.

59-60; 62-63. She filed the expert report and CV of Dr. Fran D. Kendall on May 15,

2012. See Pet. Exs. 79-80.

In July 2012, respondent filed her Rule 4(c) report; and the expert reports and

accompanying medical literature from Drs. Max Wiznitzer and Shawn McCandless. See

Respondent’s Rule 4(c) report; Respondent’s Exhibits [“Res. Exs.”] A-Q. After

consultation with the parties, I scheduled an entitlement hearing in Washington, D.C.

from February 13-15, 2013. Order, issued Aug. 16, 2012; Pre-Hearing Order, issued

Aug. 31, 2012.

Four physicians, Drs. DeMio, Kendall, McCandless, and Wiznitzer, testified in

person. Petitioner, Garrick Tipton (A.H.T’s father), and Mrs. Christy Holt [“Christy Holt”]

(A.H.T.’s aunt) also testified in person. I heard telephonic testimony from Mrs. Mary Jo

Holt Dunn (A.H.T.’s maternal grandmother), and Ms. Amy Hunter, the doula who

assisted with A.H.T.’s birth.16

Based on testimony at the hearing about the availability of video evidence

supporting petitioner’s case (see Tr. at 116, 121), I ordered petitioner to file video

records of A.H.T. from birth to three years of age. Three DVDs were filed on April 4,

2013 as Pet. Tr. Ex. 3.17 Post hearing briefs were received from petitioner on May 9,

2013, and from respondent on June 17, 2013. On September 3, 2013, I also filed a

medical journal article, N. Wolf & J. Smeitink, Mitochondrial disorders: a proposal for

13 See Pet. Exs. 73-78.

14 See Pet. Exs. 67-71.

15The filed documents are titled “statements” rather than expert reports, although they do contain

opinions on vaccine causation.

16Petitioner intended to call Dr. Levinson to testify telephonically, but efforts to reach him were not

successful. See Tr. at 284, 290.

17Subsequent references to the videos will identify them as Video 1, Video 2, and Video 3. Pertinent

provisions will be identified by the date of the recording and elapsed time from the start of the video.

6

consensus diagnostic criteria in infants and children, Neurol. 59(9): 1402-05 (2002)

[cited hereinafter as “Wolf & Smeitink, Court Exhibit [“Court Ex.”] I, and provided the

parties and their experts an opportunity to comment on the exhibit. See ECF # 90; Pet.

Resp. to Court’s Order and Ex., filed on September 30, 2013; Res. Ex. S. This article

sets forth the diagnostic criteria ostensibly used by the physician who diagnosed A.H.T.

with a mitochondrial disorder.

II. Summarized Medical History.

A.H.T. was born in 2002, following a normal pregnancy. Tr. at 11-12; Joint

Submissions at ¶ 2, filed on January 22, 2013. She was delivered at home, with the

assistance of a midwife, Juliet Dietsch, and doula, Amy Edwards Hunter. See

Petitioner’s Exhibits [“Pet. Exs”] 77, 82 (statements of Amy Edwards Hunter18 and Juliet

Dietsch). A.H.T. had Apgar scores of 7 and 9.19 Id. Both Ms. Dietsch and Ms. Hunter

said that A.H.T. was healthy, alert, and nursing well shortly after birth. Id.

At her initial visit to her pediatrician, Dr. Rhonda Buttleman, A.H.T. was alert and

her physical examination was normal. Pet. Ex. 58, p. 2330.20 A.H.T.’s parents

indicated that she was nursing every few hours and was voiding and stooling frequently.

Id.; Tr. at 109-10 (testimony of Mr. Tipton). Ms. Holt testified that A.H.T. was sleeping

18-20 hours per day and that she had gained 10 ounces since birth. Tr. at 16-17; see

also Pet. Ex. 58, pp. 2313 (birth weight), 2330 (weight at five days of age).

The only two vaccinations A.H.T. ever received (two hepatitis B vaccinations)

were administered before she was six weeks old. She received the first at this initial

pediatric visit. Pet. Ex. 58, pp. 2313, 2326, 2330. The documentary evidence and

testimony establish that, within days after the first vaccination, A.H.T. developed

problems with constipation and that she cried more often and more robustly than many

infants. Tr. at 22-23, 56 (Ms. Holt); 129-30 (Mr. Tipton); Pet. Exs. 52, p. 2234; 34, p.

1287. Her sleeping patterns changed and Ms. Holt testified about problems with

breastfeeding. See, e.g., Tr. at 20-22, 24, 29, 32, 56, 91-92. These issues are

discussed in more detail in Section V, Part B(4), below.

Mr. Tipton did not remember any specific reactions to the second vaccination.

He testified that A.H.T. “continued to worsen as time went on,” but stopped short of

18 Petitioner filed two statements from Ms. Hunter. The first statement was labeled “Statement of Amy

Edwards” and filed on September 22, 2011 as Pet. Ex. 3. The second statement was labeled “Statement

of Amy Edwards Hunter” and filed on April 16, 2012 as Pet. Ex. 77. The substance of the two statements

is the same.

19 The Apgar score is a numerical assessment of a newborn’s condition (with lower numbers indicating

problems), usually taken at one minute and five minutes after birth. The score is derived from the infant’s

heart rate, respiration, muscle tone, reflex irritability, and color, with from zero to two points awarded in

each of the five categories. See DORLAND’S ILLUSTRATED MEDICAL DICTIONARY (32d ed. 2012)

[“DORLAND’S’”] AT 1682; NELSON TEXTBOOK OF PEDIATRICS (19th ed. 2011) [“NELSON’S ”] at 536-37.

20 Doctor Buttleman’s records were also filed as Pet. Ex. 4.

7

saying that she regressed or lost skills. Tr. at 131, 133. Ms. Holt also testified that

A.H.T. got worse, but more as a progression of the symptoms she was already

experiencing.21 Tr. at 37, 63. However, prior to their testimony, A.H.T.’s parents told

Dr. John D. Shoffner, the physician who diagnosed her with a probable mitochondrial

disorder, that there were no adverse reactions to the second hepatitis B vaccination.22

Pet. Ex. 61, p. 2343.

Over time, some of the problems that first manifested in the days and weeks after

A.H.T’s initial vaccination varied in intensity. The medical records and the testimony of

her parents and other family members about the persistence and intensity of these

problems were often in conflict with other evidence. What seems clear from the record

as a whole is that A.H.T. was a difficult infant and toddler. Behavioral problems

continued as she grew older, and by the time she was six years old, they accounted for

most of the health care visits and support services rendered. See generally, Pet. Exs.

16 (2008 therapy records of Dr. (Ph.D.) Julie Murray, a treating psychologist); 51 (2009

neuropsychological evaluation by Dr. (Ph.D.) Andrew Jones, clinical psychologist); 38

and 54 (2009-12 records from an agency providing behavior analysis and support

services); 7, p. 51 (2010 letter from psychiatrist Dr. Arehanna Barry).23

Notwithstanding any temperament, sleep, feeding, and gastrointestinal issues,

A.H.T. appeared to be developing normally for her first 15-17 months of life. See

generally, Pet. Exs. 52, 58. She gained weight appropriately. See Pet. Ex. 58, p. 2314

(growth chart). She interacted with parents at home and caregivers at her pediatric

21 When pressed for a specific symptom that worsened after the second vaccination, Ms. Holt testified

that A.H.T.’s bowel movements became either rock hard, or loose and foul-smelling, and that nursing got

worse. Tr. at 37. Although she did not attach a specific time frame to onset of loose stools, there is no

corroborating, and much contradictory, evidence for any assertion that A.H.T. experienced loose stools in

close temporal proximity to the second vaccination. Both the contemporaneous medical records and

histories Ms. Holt provided later reflect that A.H.T. suffered from constipation throughout much of her first

year of life. See, e.g., Pet. Exs. 34, p. 1287; 28, p. 1088. The first complaint of loose stools or diarrhea

does not appear until January 10, 2003, when A.H.T., then nine months old, experienced a bout of

enteritis. Pet. Ex. 52, 2233. Thereafter, reports of both diarrhea and constipation were common,

although the diarrhea was generally noted in conjunction with an illness or in response to one of the many

medical interventions she received. See, e.g., Pet. Exs. 52, p. 2230, 23, p. 239 (reporting diarrhea after

treatment with a chelating agent), p. 259 (diarrhea in conjunction with illness (the abbreviation “N/V/D”

representing nausea, vomiting, and diarrhea)); 46, p. 2037 (reporting chronic problems with alternating

constipation and diarrhea at a January 2005 evaluation); 38, p. 1690 (indicating a drug A.H.T. took

caused diarrhea); 19, p. 214 (reporting that dairy products caused diarrhea).

22Petitioner’s Tr. Ex. 1, the intake form for Dr. DeMio (dated August 12, 2005), reflects the two

vaccinations, followed by a comment that she had such severe reactions to these two vaccinations that

no other vaccines had been administered. Id., p. 3.

23 This letter merely reflects A.H.T.’s diagnoses; therapy records from Dr. Barry were not provided,

although there is evidence that she ordered laboratory testing and an electrocardiogram. See Pet. Ex.

37, pp. 1324-26. Medical records contain conflicting references regarding whether A.H.T. was receiving

ongoing psychiatric treatment. See, e.g., Pet. Ex. 7, pp. 54, 67 (Medicaid form from 2010 (dated on p.

67), reflecting continuing treatment by Dr. Berry); 30, p. 1230 (initial note from sleep clinic during same

period in 2010 reflecting that A.H.T. had seen a psychiatrist but that she was no longer doing so).

8

visits. Videos of her taken at one to nine months of age show an alert and interactive

infant engaged with toys, household items, and her parents. See generally Videos 1

and 2.24 At her regular pediatric visits, she was observed to be developing at a pace

appropriate for her age and meeting developmental milestones,25 although she may not

have begun walking until 14-15 months of age, a little later than average. See, e.g., Pet

Exs. 31, p. 1262 (reporting she began walking at 15 months); 46, p. 2037 (reporting that

she began walking at 14 months); but see Pet Ex. 52, p. 2229 (15 month well-child visit

with notation that A.H.T. had been walking for 2 months).

Neither her first pediatrician, Dr. Rhonda Buttleman, who saw her from five days

to about nine months of age, nor the family practice physician, Dr. Richard Hefner,26

who was her primary care provider thereafter, recorded any concerns about her

development during this period. See generally Pet. Exs. 52, 58. Doctor Hefner, who

saw A.H.T. for the first time when she was about five months old for a second opinion

on her gastrointestinal problems, observed her while she was crying. He diagnosed her

with colic. Pet. Ex. 52, p. 2234. Nevertheless, he referred her to a pediatric

gastroenterologist, Dr. Stephen, who diagnosed mild constipation and mild

gastroesophageal reflux when A.H.T. was six months old. Pet. Ex. 34, p. 1287.

24Video 1, from 46:51 (recorded May 18, 2002) through 3:23:22 (recorded October 31, 2002); Video 2,

Set 1, from 00:01 (recorded November 23, 2002) through 15:46 (recorded January 3, 2003).

25 The medical records contain notes and marks on developmental checklists reflecting A.H.T.’s

development. At about five weeks of age, A.H.T. was “alert” and her general appearance was “AFA,” an

acronym for “appropriate for age.” Pet. Ex. 58, p. 2326. She was holding her head up, startling with loud

sounds, grasping fingers, and making noises. Id., p. 2327. At her two month checkup, A.H.T. was

smiling, cooing, holding her head up, focusing on people, and holding a rattle. Pet. Ex. 58, p. 2325. At

her four month well-child visit, she was described as alert, and she was rolling over, holding her head up,

reaching for toys, playing with her hands, looking at a mobile, vocalizing with her parents, and laughing

and smiling. Pet. Ex. 58, p. 2323. Doctor Thomas Stephen, a pediatric gastroenterologist, described her

as a “well developed, well-appearing young infant, happy, in no distress” when she was six months old.

Pet. Ex. 34, p. 1287. At her six month well-child visit, she was sitting with help with no head lag, rolling

over, moving toys from hand to hand, reaching for toys, bearing some weight, laughing and babbling,

turning to sounds, and making sounds. Pet. Ex. 58, p. 2320. At nine months of age, A.H.T. was pulling

up on furniture, sitting by herself, crawling, banging toys, playing patty-cake and peek-a-boo,

understanding words such as “no, no” and “bye-bye,” starting to feed herself, and having stranger anxiety.

Id., p. 2316. She did not yet utter one or two meaningful syllables, and did not respond to her name. Id.

However, according to Dr. Hefner’s assessment, she met all developmental milestones at one year of

age, including the use of some words. Pet. Ex. 52, p. 2232. He also found that she met all

developmental milestones at 15 months of age: she could stand alone, imitate scribbling, play patty cake,

say “mama” or “dada”, and take lids off containers. Id., p. 2229. Doctor Wiznitzer testified that A.H.T.’s

development was normal through 15 months of age. Tr. at 639-42; see also Res. Ex. A at 7.

26Doctor Hefner’s specialty does not appear in his records, but is referred to in the records of clinical

psychologist Dr. Laurie Grimes, who noted that Dr. Hefner was a family practice specialist. Pet. Ex. 17,

pp. 166, 168.

9

Aside from a one-page document from Dr. James O’Dell, a naturopath who saw

A.H.T. in July 2002,27 there were no records from other health care providers covering

A.H.T.’s first 17 months of life.28

Developmental problems were first noted in September 2003 at A.H.T.’s 18

month well-child visit, when Dr. Hefner observed that A.H.T. was not using two-word

phrases, indicating a possible language delay. Pet. Ex. 52, p. 2226. In a history taken

in May 2004, Ms. Holt reported that her concern about A.H.T.’s speech arose at about

18 months of age as well.29 Pet. Ex. 55, p. 2255. Doctor Hefner elected to take a “wait

and see” approach, but by A.H.T.’s next well-child visit six months later when A.H.T.

was about two years of age,30 the delay was still evident. Although the records of this

visit do not reflect it (see Pet. Ex. 52, p. 2226), Dr. Hefner apparently referred A.H.T. for

an evaluation by the state’s early intervention program (see id., p. 2225 (records from

next visit to Dr. Hefner in August 2004, with the chief complaint listed as “here to

discuss therapy recommended [at] 2 yr well baby”)).

The remaining medical treatment and therapy records are extensive, and except

when relevant to one of the issues in controversy, are not set forth in detail in this

decision. In summary, A.H.T. was seen by many different health care providers, in

addition to her primary care provider, Dr. Hefner. These caregivers fall into four

27See Pet. Ex. 73; see also http://drjamesodell.com/index.php/about for information regarding Dr. O’Dell’s

qualifications and practice. Ms. Holt’s journal entries (Pet. Ex. 6, pp. 44-45) also reflect this visit. A

naturopathic doctor is one who subscribes to “a drugless system of health care, making use of a wide

variety of therapies, including hydrotherapy, heat, massage, and herbal medicine.” DORLAND’S at 1233.

28 According to a March 14, 2012 statement, Dr. Sean Brady (a chiropractor who had previously treated

Ms. Holt) began treating A.H.T. on June 13, 2002. Pet. Ex. 66 at 2366. Inexplicably, there are no records

for such treatment before June 9, 2004, and although Dr. Brady indicated that he had billing and medical

coding records establishing the dates of initial and subsequent treatment, the billing and coding records

were not filed. His records of A.H.T.’s treatment from June 2004 onward were filed as Pet. Ex. 48.

Doctor Brady did not opine on causation in this March 2012 statement; he merely stated that he recalled

clearly Ms. Holt’s statements that A.H.T.’s problems began shortly after the vaccination that she received

at five days of age. Pet. Ex. 66 at 2366-67. Given the lack of contemporaneous records of treatment, I

attach little weight to a statement made nearly 10 years after the events in question, particularly as the

statement was made after Dr. Brady read Ms. Holt’s own affidavit. See id. at 2367. There is a journal

entry reflecting a consultation with a Dr. Zieve (Pet. Ex. 6, pp. 40-41) from mid-May 2002, but Ms. Holt

testified that this was a telephonic consultation. Tr. at 62.

29 In a developmental chronology prepared for A.H.T.’s first appointment with Dr. Kartzinel in June 2007,

Ms. Holt reported that she first noticed developmental problems at about 18 months of age. Pet. Ex. 24,

p. 464. In a much later history (provided in May 2010), Ms. Holt reported that her concerns about delayed

development first arose at around 12 months of age. Pet. Ex. 47, p. 2052 (email intake form completed

for Dr. Levinson). She also reported that speech problems were first noted at 18 months of age to Dr.

Cecil in December 2011. Pet. Ex. 56, p. 2287. However, she testified that the report from May 2004

about her concerns first arising at 18 months of age was not correct. Tr. at 70.

30 The filed medical records show no health care provider visits between 18-24 months of age. This six-

month gap appears to be the longest period A.H.T. went without seeing a health care provider, although it

is possible that she saw Dr. Brady during this period. See n.28, supra.

10

categories: therapists addressing specific areas of developmental delay or behavior

concerns; several different types of mental health specialists; at least five alternative or

complementary medicine providers; and specialists who assessed or treated her for

gastrointestinal, urinary, and sleep disorders. Other than Dr. Hefner and Dr. Puri and

his associates, none of the health care providers treated A.H.T. over a long period of

time.

Aside from the primary care records, the records from the early intervention

program provide the evidence prepared closest in time to the events after A.H.T.’s initial

hepatitis B vaccination. Through the early intervention program, A.H.T. received

Applied Behavioral Analysis [“ABA”] therapy31 (which appears to have been termed

developmental intervention [“DI”] services),32 speech and language therapy [“ST”],33 and

occupational therapy [“OT”].34 Each of these records supplies some insights into the

nature and severity of A.H.T.’s developmental delays and behavioral symptoms at

around the time delays became apparent.

31ABA therapy consists of the “application of learning theory based on operant conditioning” and “is the

only intervention recommended by the Surgeon General” for ASD. Dwyer, 2010 WL 892250, at 272,

n.650.

32 No therapy records specifically identified as ABA therapy were filed as a part of the early intervention

records, but there are references indicating that A.H.T. received ABA therapy. See, e.g., Pet. Exs. 31, p.

1257 (July 2005 note by Dr. Puri that A.H.T. was “making good progress on ABA therapy”); 24, p. 466

(June 2007 note that she was receiving four to five hours of ABA therapy). The developmental

intervention services she received through Carriage House were likely the ABA therapy referred to in

these records. See, e.g., Pet. Ex. 39, p. 1818 (progress summary in December 2004 for developmental

intervention services rendered since June 2004). Pet. Ex. 25 contains some ABA-type worksheets, but

no actual therapy records.

33See generally Pet. Ex. 18. The initial assessment and testing for speech and language services took

place on May 19, 2004. Pet. Ex. 39, pp. 1822-23. A.H.T., then 26 months old, had the language

comprehension skills of a 9-12 month old, and the expressive language skills of a 6-9 month old, with

scattered skills in both categories up to the 15 month level. Id., p. 1823. However, the developmental

assessment performed two weeks earlier had placed her receptive and expressive language skills in the

12-14 month range. Id., p. 1827.

34 See generally Pets. Ex. 28 and 55. A thorough but concise summary of A.H.T.’s medical history and

level of functioning appears in the September 2004 OT assessment. Pet. Ex. 28, pp. 1088-91. The

evaluator assessed A.H.T.’s fine and gross motor skills at the 17-18 month level. Id., p. 1090. She was

28 months old at that point. In addition to OT, A.H.T. attended a two-week sensory learning center

program at the Therapy Learning Center in Ohio in November 2005, for which no records are available.

Pet. Ex. 49, p. 2178 (letter dated Jan 11, 2012, explaining the lack of records and providing the writer’s

recollection of A.H.T.’s issues). This treatment did not appear to be helpful, as Ms. Holt cancelled a

December 2004 OT appointment explaining that A.H.T. had “regressed” since returning from the sensory

learning program. Pet. Ex. 28, pp. 1083, 1094. Subsequent occupational therapy records do not appear

to be complete, and many of those filed are handwritten and difficult to read, but it appears she received

some OT services from Cardinal Hill in 2005-07 and through the school system in 2007-08. See, e.g.,

Pet. Exs. 27, pp. 630, 705; 16, p. 142. Intensive OT began again in March 2010 and continued into 2011.

See generally Pet. Ex. 27. According to testimony at the hearing, A.H.T. was discharged from OT in 2011

at around the time she began treatment for a mitochondrial disorder. Tr. at 117.

11

She received ST with the early intervention program until she was discharged in

March 2005, because early intervention services terminated at three years of age. Pet.

Ex. 18, p. 184. She continued to receive ST services, according to her primary care

records (see Pet. Ex. 52, p. 2219 (well-child visit at four years of age reflecting

improvements with speech therapy)). There are some speech therapy records from

Cardinal Hill in 2011. See, e.g., Pet. Ex. 27, pp. 606-23. According to testimony at the

hearing, A.H.T. was still receiving ST services. Tr. at 117; See also Pet. Ex. 27, p. 614

(last ST record filed).

A.H.T. began receiving physical therapy [“PT”] services in March 2007, at the

recommendation of Dr. Puri. Pet. Ex. 37, p. 1495. She was discharged from PT in

February 2008, based on her improved functioning. Pet. Ex. 33, pp. 1285-86. She was

re-evaluated in 2009 and received services again until February 2010.35 Pet. Ex. 37,

pp. 1356, 1362-63.

Beginning in late 2010, the primary therapy for addressing A.H.T.’s continuing

behavior problems was behavioral analysis and ancillary support services from

Community Ties and Homeplace Support Services. These problems included defiance,

temper tantrums or meltdowns, verbal aggression, and physical aggression towards

property, pets, and people. Services continued at least into early 2012. See generally

Pet. Exs. 38, 57.36 These very detailed records of A.H.T.’s behavior overlap with the

diagnosis and initiation of treatment for a probable mitochondrial disorder and, thus,

provide insights into the efficacy of such treatment. She also saw her pediatric

neurologist occasionally in 2011 (after more than a year’s break in treatment). See Pet.

Ex. 31, pp. 1234-41 (2011 records), pp.1243-45 (prior visit in August 2009). The

records from Dr. Puri and his associates also overlap with the period when she was

diagnosed and treated for a mitochondrial dysfunction or disorder.

A.H.T.’s treatment by alternative or complementary medical providers began as

early as July 2004 when she saw Anne Linden Steele.37 Another treatment facility, the

35For a brief period beginning in early March 2011, A.H.T. again received PT, but this was due to injuries

sustained in an automobile accident. Services were discontinued in April 2011 because she no longer

seemed to be in pain. See Pet. Ex. 43, pp. 1869-74 (noting inconsistent reports of pain and not enough

objective findings to “legitimate” neck and back pain).

36The records from these two agencies are in the same format, likely reflecting a name change in the

agency rather than two different service providers.

37Ms. Steele’s records do not reflect her specialty, but her website (http://www.annelindensteele.com/)

does (last visited Oct. 23, 2014). Ms. Holt’s journal contains recommendations for treatment by a cranial-

sacral therapist (Pet. Ex. 6, p. 45), and a reference to having tried this therapy appears in the treatment

history provided at the Carriage House (early intervention) intake interview. See Pet. Ex. 39, p. 1826.

There was no evidence discussing what this therapy involved or what specific problems it was intended to

address.

12

Biohealth Centers, was consulted in late 2004 to obtain orders for testing by Great

Plains Laboratory.38 Pet. Ex. 76.

The unidentified health care provider who saw A.H.T. at Integrative Health

Specialists from March-June 2005 assessed her with “candida” (yeast overgrowth),

vitamin and mineral deficiency, and “metal toxicity.”39 A.H.T. was prescribed nystatin

(an antifungal agent) and probiotics. She was also chelated with DMSA during this

period,40 but she developed increased behavior problems during chelation. Pet. Ex. 19,

pp. 213-15. Diagnoses included sensory integration disorder, PDD, central nervous

system dysfunction, delays in fine motor skills, and expressive and receptive language

disorder. Id. at 214.

A.H.T. saw three Defeat Autism Now! [“DAN!”]41 physicians: Dr. DeMio (from

September 2005-November 2008),42 Dr. Kartzinel (from June-October 2007),43 and Dr.

Levinson (beginning in May 2010).44 These physicians, along with the provider from

38Testing by Great Plains laboratory is common in OAP cases. Great Plains laboratories test blood, urine,

and stool for many different minerals, parasites, and nutritional markers. See Pet. Ex. 76, pp. 2462-84

(A.H.T.’s test results).

39 It is unclear from these records which “toxic” metals were of concern.

40 See Snyder, 2009 WL 332044, at *67 n.192. Chelation is the use of chemicals to break the bond

formed between some heavy metals and body tissue. Chelation therapy has been approved to reduce

lead levels in children and for cases of mercury poisoning. Its use in treating children with ASD remains

highly controversial, as there are no controlled studies testing its efficacy and there are significant risks

associated with the treatment. DMSA (dimercaptosuccinic acid) is a water-soluble and relatively non-

toxic chelating agent. Dwyer, 2010 WL 892250, at 103, n.428. DMPS (2, 3–dimercaptopropane–1–

sulfonate).is another chelating agent that A.H.T. received. See Snyder, 2009 WL 332044, at *177, n.506

(internal citations omitted); see, e.g., Pet. Ex. 23, p. 236 (A.H.T.’s treatment with DMPS by Dr. DeMio).

41 DAN! physicians subscribe to “biomedical” treatment protocols developed by the Autism Research

Institute. These treatments may include chelation and other therapies not vetted as efficacious by

controlled clinical studies. Dwyer, 2010 WL 892250, at *20, *178. See also Pet. Ex. 60 at 2340 (Dr.

Levinson’s CV, listing several lectures on “biomedical” approaches to autism treatment he delivered at

Autism Research Institute meetings). Both Drs. Wiznitzer and McCandless characterized Dr. DeMio, Dr.

Kartzinel, and Dr. Levinson as “alternative” or “complementary” health care providers. See Res. Exs. A at

4; G at 1. In his testimony, Dr. DeMio discussed DAN!, the Autism Research Institute, its annual

conferences, and biomedical treatment and training. Tr. at 265-67, 269. According to Dr. DeMio, the

biomedical view of autism considers ASD to be a metabolic, gastrointestinal, immune, and nutritional

disorder often caused by environmental toxins, including vaccines and mercury. Tr. at 233.

42Although the last record from Dr. DeMio in Pet. Ex. 23 is dated November 18, 2008 (id., p. 290; Tr. at

247-48 ),Dr. DeMio began treating her again in August 2012 (see Pet. Ex. 87; Tr. at 247-48).

43Ms. Holt identified Dr. Kartzinel as a “DAN” doctor when providing an updated client history to Easter

Seals in 2007. Pet. Ex. 27, pp. 629-30. According to Dr. Kartzinel’s records, he renewed a prescription

for Singulair for A.H.T. in February 2008, but the last treatment record is dated October 29, 2007. Pet.

Ex. 24, p. 452.

44

According to Ms. Holt, she consulted Dr. Levinson because she wanted to return to the DAN! treatment

methods. Pet. Ex. 47, p. 2055.

13

Integrative Health Specialists, recommended or administered a variety of alternative

treatments including chelation, hyperbaric oxygen therapy [“HBOT”], secretin

infusions,45 intravenous immunoglobulin [“IVIG”],46 vitamin and mineral supplements,

antifungal and antiviral medications, folinate or folinic acid, methyl B-12, and Actos,47

among many others. See generally Pet. Exs. 19, 23, 24, 47. In addition to occasional

in-person consultations, most consultations with Drs. DeMio, Kartzinel, and Levinson

were by telephone or email. Id.; see also Tr. at 242-44 (testimony by Dr. DeMio

acknowledging that many of the medical consultations regarding A.H.T. were

telephonic). A DNA test ordered by Dr. Levinson revealed a single MTHFR mutation

(A1298C).48 A.H.T. stopped seeing Dr. Levinson in 2011 (see Pet. Ex. 47, p. 2058

(most recent treatment)), as Ms. Holt was “uncomfortable with his office policies.” Tr. at

77-78.

45In controlled studies, secretin was found less effective than a placebo in treating ASD and

gastrointestinal symptoms in those with ASD. See Snyder, 2009 WL 332044, at *175.

46IVIG infusions are used to treat individuals with immune system deficiencies or dysfunction. “IVIG”

stands for intravenous immunoglobulin. Neil M. Davis, MEDICAL ABBREVIATIONS, 15th Edition, at 178

(2011). There is no objective evidence that A.H.T. has an immune system problem. Immunoglobulin

testing performed by Great Plains laboratory in 2004 showed her IgA level to be mildly elevated and her

IgM to be slightly low, but Dr. Puri, who reviewed and commented on these results, did not indicate that

the results were of any concern. Pet. Ex. 31, p. 1259. Immunoglobulin testing by Baptist Hospital in 2007

showed results within the reference ranges. Pet. Ex. 15, p. 126. Nevertheless, in 2012 Dr.DeMio began

IVIG therapy. Tr. at 220; Pet. Ex. 87, pp. 2558-59.

47Actos (Pioglitazone Hydrochloride) is used in the treatment of type 2 diabetes, acting to decrease

insulin resistance. See PHYSICIANS’ DESK REFERENCE [“PDR”] (66th ed. 2012), at 2805. There are

no tests or diagnostic records showing that A.H.T. had type 2 (or any other type of) diabetes.

48 MTHFR stands for methylenetetrahydrofolate reductase, which is a protein involved in getting rid of

homocysteine. According to Dr. McCandless, A.H.T.’s MTHFR test result is unimportant. A couple of

common polymorphisms had been identified in this MTHFR gene that were once thought to increase the

risk of having elevated homocysteine, a risk factor for blood clots. When testing based on this hypothesis

began, a lot of people with the altered genes were found, but no increased risk for blood clots or other

problems. It has nothing to do with the folate deficiency later found in A.H.T.’s cerebrospinal fluid. Tr. at

602. A polymorphism is a DNA change, but not one that is disease causing or with functional

implications. A common polymorphism is one found in more than 1% of the population. Tr. at 600-02.

14

In addition to treatment by the DAN! physicians, A.H.T. saw a developmental

pediatrician, several pediatric neurologists,49 several child psychologists,50 and a

psychiatrist.

A comprehensive neurodevelopmental evaluation was performed in early 2005 at

the Weisskopf Child Evaluation Center [“Weisskopf Center”], a part of the University of

Louisville School of Medicine Department of Pediatrics. Pet. Ex. 46. Doctor Gail

Williams, a developmental pediatrician, diagnosed A.H.T. with a regulatory disorder51

and with central nervous system dysfunction, as “manifested by toe walking and

decreased muscle tone.” Pet. Ex. 46, pp. 2038, 2041, 2045. Like Dr. Grimes, she

concluded that A.H.T. did not meet the diagnostic criteria for autism, based on her

“better developed social skills” and “clear evidence of joint attention.” Id., pp. 2038,

2041.

49She saw the first pediatric neurologist, Dr. James McKiernan, in August 2004 to determine if she had

been experiencing seizures. He concluded that it was “unlikely” she was having seizures. Pet. Ex. 40, p.

1831. She initially saw Dr. Puri, the pediatric neurologist who treated her for the longest period of time, in

September 2004, also for possible seizures. He ordered several diagnostic tests for seizures and

metabolic disorders. Pet. Ex. 31, p. 1265 (tests ordered). A.H.T. continued to see Dr. Puri, at least into

2011. Testing, including an EEG and MRI, failed to find any evidence of a seizure disorder. See Pet. Ex.

31, pp. 1273, 1275. Much later, some of the “seizure-like” spells were identified as self-stimulatory

behavior. See Pet. Ex. 16, pp. 136-37. One of Dr. Puri’s associates, Dr. A.C. Anikumar, saw A.H.T. in

July 2007 regarding possible seizures or a movement disorder, but concluded that the movements were

most probably behaviorally related and non-epileptic in nature. Pet. Ex. 31, p. 1249. However, Dr.

DeMio’s records contain several references to A.H.T. experiencing “extrapyramidal” signs or effects which

could possibly be related to seizures (involuntary movements) (abbreviated “EX SXS” on several

records), based on viewing videos of A.H.T. in 2006. See, e.g., Pet. Ex. 23, pp. 245, 247-48, 250.

A.H.T.’s neurologist apparently viewed the same video records and told A.H.T.’s parents that the videos

showed normal child behavior. See id., p. 245.

50These included Dr. (Ph.D.) Grimes, the clinical psychologist who concluded in 2004 that A.H.T. did not

meet the criteria for an ASD diagnosis (Pet. Ex. 17, p. 146); Dr. (Ph.D.) Julie Murray, who saw A.H.T. or

her parents for nine sessions between July and October 2008 for symptoms of anxiety, obsessiveness,

impulsivity, and poor concentration, and for assistance in managing temper tantrums and symptoms of

anxiety. Pet. Ex. 16, pp. 133 (initial assessment) and 134-41; Dr. (Ph.D.) Andrew Jones, a clinical and

forensic psychologist who administered a battery of tests and, in spite of some concerns about their

validity (see Pet. Ex. 51, p. 2195 (expressing concern about “multiple elevated T scores… which were

greater than anticipated”), diagnosed her with a bipolar disorder with depressed mood (id., p. 2210)). She

also saw Dr. Michael Cecil, a clinical neuropsychologist, in late 2011. He conducted many tests and

made recommendations as to educational accommodations and the need for ongoing OT and ST. Pet.

Ex. 56, pp. 2286-89.

51I was unable to find a clear definition for regulatory disorder, as the diagnosis does not appear in

standard medical references such as DORLAND’S or NELSON’S or in either the 4th or 5th editions of the

DIAGNOSTIC AND STATISTICAL MANUAL OF MENTAL DISORDERS. According to an article posted on the

National Institutes of Health website (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2765395/),

“Regulatory Disorders of Sensory Processing (RDSP) constitute a specific diagnostic category in the

Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood

(DC: 0-3R). . . .Children with regulation disorders exhibit specific symptom constellations in sensory,

motor and behavioral domains.” Tr. at 686-87. Doctor Wiznitzer testified that the regulatory disorder

diagnosed by Dr. Williams explained A.H.T.’s behavior problems. Tr. at 687-88.

15

By 2007, Dr. Puri’s practice seemed to have accepted a pervasive

developmental disorder diagnosis, although it is unclear whether this was based on the

history of the diagnosis provided by Ms. Holt or on an independent assessment of

A.H.T.’s functioning. See Pet. Ex. 31, pp. 1246 (noting a previous diagnosis of “sensory

integration disorder/PDD” in the history section of the office notes in 2007), 1249

(recording diagnoses of pervasive developmental disorder, sensory integration disorder,

autistic disorder, and behavioral disorder later in 2007).

In February 2009, when A.H.T. was almost seven years old, Dr. Jones diagnosed

her with a bipolar disorder and depression and, according to Dr. Puri, he referred A.H.T.

to Dr. Barry. Pet. Exs. 31, p. 1243; 51, p. 2207. In August 2009, Dr. Puri recorded

diagnoses of PDD-NOS, bipolar affective disorder, learning disability, central auditory

processing disorder, and insomnia. Doctor Puri seemed particularly concerned about

A.H.T.’s sleeping difficulty, since lack of sleep “can be a problem in some

temperamental children like her.” Pet. Ex. 31, p. 1245.

A.H.T. also received care and treatment for several medical issues not directly

related to her behavior problems. She had an endoscopy and colonoscopy in the spring

of 2007. Pet. Ex. 12, p. 102. She also saw a pediatric urologist in 2008 for frequent

urinary tract infections [“UTI”]. Pet. Ex. 14, p. 116.52 She saw a pediatric cardiologist,

Dr. Roddy McDowell, in 2009, based on a reportedly abnormal electrocardiogram. After

additional testing, he concluded that A.H.T.’s heart was structurally normal, in spite of

an “innocent heart murmur.” Pet. Ex. 13, pp. 105-06. She saw Dr. McDowell one more

time in July 2010 when he made a similar assessment. Id., p. 103.

Beginning in June 2010, A.H.T. was evaluated and treated at the Behavioral

Sleep Medicine Clinic, a part of the University of Louisville’s Pediatric Sleep Medicine

Center, where she saw Dr. (Ph.D.) Sarah Honaker, a clinical psychologist, and Dr.

Vincent McCarthy. The records from this clinic reflect a significant behavioral

component to A.H.T.’s widely varying sleep hours, and a great degree of difficulty in

getting A.H.T.’s parents to document sleeping patterns and to implement the

recommended changes.53 Ms. Holt sought physiological explanations for A.H.T.’s sleep

difficulties, but laboratory testing did not find any physiological problems, according to

52She had previously been seen by or consulted with Dr. Kartzinel and Dr. Hefner, her primary care

provider, for such infections. See Pet. Exs. 24, p. 452 (telephonic consultation in October 2007 with Dr.

Kartzinel referencing five or six prior UTIs); 52, p. 2216 (sick child visit in February 2008 with Dr. Hefner

for a UTI, mentioning one prior UTI in 2005).

53See Pet. Ex. 30, pp. 1231 (reporting A.H.T. was awake for 26 hours, slept for 6 hours and then awake

for another 22 hours; parents unable to keep sleep log); 1228-29 (parents resistant to melatonin use in

spite of assurances that it was unrelated to prior nightmares); 1225 (parents inconsistent in sitting with

her until she falls asleep and are not sure of times of sleep onset); 1223 (therapist reporting that there

were two major barriers to success of therapy, in that parents had great difficulty in waking A.H.T. at the

scheduled time and A.H.T. resisted going to bed, and therapist was unsure how well parents enforced

bedtime).

16

the therapist.54 Id., p. 1224. A.H.T.’s sleep improved markedly during the therapy. Id.,

p. 1217.

The sleep center observations by Dr. (Ph.D.) Honaker regarding parental

inconsistency in setting and enforcing bedtimes and in seeking physiological

explanations for A.H.T.’s sleeping difficulties were mirrored by the behavior analysis

specialists who saw her from October 2010 through at least January 2012. After

several months of observation of A.H.T. and her caregivers, these analysts developed a

plan to change targeted behaviors, which scripted certain daily activities and

implemented a “token economy” reward system in which completion of tasks was

rewarded by tokens which A.H.T. could redeem weekly for preferred activities or

objects. See Pet. Ex. 38, pp. 1690-98. The records reflect numerous concerns by the

analysts about A.H.T.’s parents’ poor compliance with the behavior modification

program.55 Over time, both parental compliance and A.H.T.’s behavior improved,

although there were peaks and valleys. See Pet. Exs 38, pp. 1750-58; 57, pp. 2309-10.

The medical and therapy records relevant to the factual conflicts and other issues

in this case are discussed in more detail below.

III. Expert Qualifications.

Five physicians offered opinions on vaccine causation and other matters in

dispute. Three of the experts (Drs. Kendall, McCandless, and Wiznitzer) were well-

qualified to offer expert opinions; the other two (Drs. Levinson and DeMio) had

experience in treating children with autism and children with mitochondrial disorders, but

are best characterized as alternative or complementary medical providers who lacked

the academic background, research qualifications, or specialized training important in

my assessments of the bases for and reliability of the opinions they offered.56 They

treated A.H.T. for periods of time far removed from the manifestation of the symptoms

after her initial vaccination or the onset of her autistic-like behaviors. I have carefully

considered their records as treating physicians and their opinions on causation in light

54 Toward the end of the sleep therapy treatment, Dr. Vincent observed that A.H.T had “not been

optimally medicated for those diagnoses [referring to issues other than sleep-related] that are medical.”

Pet. Ex. 30, p. 1221. He also stated: “It is difficult for me to tell whether some of her activities are just

totally behavioral in nature or whether there is actually an underlying medical/psychiatric diagnosis.” Id.,

p. 1222.

55 See, e.g., Pet Ex. 38, pp. 1773 (parents have not yet implemented task analysis and token economy,

resulting in minimal progress in behavioral changes), 1774 (parents have not yet used reinforcement for

motivation), 1784 (parents had not taken data requested by behavior analyst and claimed that A.H.T.’s

sleep disorder prevented them from implementing most procedures outlined in the behavior plan), 1778

(mom’s report that playtime was contingent upon completing home school was contrary to observations of

behavioral analyst and parents were inconsistent with keeping data); 1781 (parents not providing tokens

at the time of task performance and reinforcing A.H.T.’s escape from and avoidance of tasks), 1793

(parents not recording data).

56According to Dr. McCandless, most of what Dr. Levinson said about mitochondrial function was simply

wrong (see Res. Ex. G at 3; Tr. at 588-89) and Dr. Kendall did not appear to place any reliance on Dr.

Levinson’s opinion, as it was not mentioned at all in her testimony.

17

of Federal Circuit precedent on the value of treating physicians’ opinions. See

Capizzano, 440 F.3d at 1326 (commenting that 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.’”) (internal citations omitted). See also

Moberly, 592 F.3d at 1325 (“Weighing the persuasiveness of particular evidence often

requires a finder of fact to assess the reliability of testimony, including expert testimony,

and we have made clear that the special masters have that responsibility in Vaccine Act

cases.”) (citing Terran v. Sec’y, HHS, 195 F.3d 1302, 1316 (Fed. Cir. 1999)); Cedillo,

617 F.3d at 1339 (“[a] court may conclude that there is simply too great an analytical

gap between the data and the opinion proffered”) (quoting Gen. Elec. Co. v. Joiner, 522

U.S. 136, 146 (1997) (additional internal citations omitted); Lalonde v. Sec’y, HHS, 746

F.3d 1334, 1337-38 (Fed. Cir. 2014) (“In Vaccine Act cases, petitioners must proffer

trustworthy testimony from experts who can find support for their theories in medical

literature in order to show causation under the preponderance of the evidence

standard.”); Snyder v. Sec’y, HHS, 88 Fed. Cl. 706, 745 n.67 (2009) (emphasizing that

a statement of a treating physician is not “sacrosanct” and can be rebutted).

The Federal Circuit has upheld the special masters’ use of Daubert and

summarized the four Daubert factors as “(1) general acceptance in the scientific

community, (2) whether the theory has been subjected to peer review and publication,

(3) whether the theory can and has been tested, and (4) whether the known potential

rate of error is acceptable.” Cedillo, 617 F.3d at 1339 (citing Daubert v. Merrell Dow

Pharms., Inc., 509 U.S. 579, 593–94 (1993)); see also Andreu v. Sec’y, HHS, 569 F.3d

1367, 1379 (Fed. Cir. 2009). The Federal Circuit also approved the use of the Daubert

factors in evaluating an expert’s “reliability” as well as their “methodology.” Cedillo, 617

F.3d at 1339.

In this case, Drs. Levinson and DeMio’s status as treating physicians adds little

to the reliability of their causation opinions, which largely consisted of conclusory

statements. With regard to the logical connection between vaccination and injury, these

particular treating physicians are no more percipient as witnesses about what actually

transpired after the vaccinations than any other physician who testified in this case.

Moreover, nothing in Capizzano requires special masters to give weight to the opinions

of treating doctors who espouse “junk science,” and who treat children based on

unproven hypotheses, with drugs with no known efficacy against the medical conditions

presented,57 and without test results to warrant the speculative diagnoses proffered.58

57In ordering tests, Dr. DeMio recorded a number of diagnoses, including static encephalopathy,

metabolic derangement, metabolic error, glycemic disorder, autoimmune disease, and hypothyroidism.

See, e.g., Pet. Ex. 37, pp. 1533-35, 1577, 1591, 1665. Other than static encephalopathy, these were all

new diagnoses unsupported by the medical testing ordered.

58Doctor DeMio ordered many standard laboratory tests on a monthly basis between February 2006 and

June 2007, in spite of repeated results within reference ranges. See generally Pet. Exs. 23; pp. 293-370;

37, pp. 1534-1665; 42, pp.1836-67. He also ordered tests that were less routine. He had a standing

order for a comprehensive metabolic panel and complete blood count [“CBC”] with differential and

platelets, on a monthly basis. Pet. Ex. 37, p. 1533. Other tests ordered included plasma amino acids,

red blood cell elements, urine toxic metals, various virus antibodies, stool parasites and bacteria, thyroid,

18

See Capizzano, 440 F.3d at 1325-27. See also Dwyer, 2010 WL 892250, at *116, 141

(criticizing the practitioners and researchers who convinced parents of the efficacy of

various specious treatment methods for their children with ASD). Both Drs. DeMio and

Levinson prescribed treatments of dubious efficacy, ordered tests with results that

conflicted with their hypotheses, and made diagnoses unsupported by the evidence. I

have not entirely rejected their observations about A.H.T., but I cannot credit their

statements about the connection between A.H.T.’s vaccination and her subsequent

medical and behavioral problems.

However, I have fully credited the records of the treating physicians, Drs.

Buttleman and Hefner, who saw A.H.T. during her first year of life and who treated her

for irritability and constipation, and diagnosed colic.

The four physicians who testified at the hearing offered opinions regarding

symptoms A.H.T. allegedly displayed after the vaccinations and whether these were

symptoms that suggested a mitochondrial regression had occurred. Although they were

not percipient witnesses, their testimony about the likelihood of the events described is

a factor in the factual findings set forth in Section V, Part C, below. The primary

contributions of the experts were in explaining mitochondrial disorders, the distinction

between primary mitochondrial disorders and secondary mitochondrial dysfunction, and

explaining the evidence and conflicting opinions surrounding A.H.T.’s diagnosis and

vaccine causation.

The witnesses’ training and experience that bear on their qualifications to testify

as experts and on the weight I accorded their testimony are set forth below, along with

some observations and impressions regarding their testimony.

A. Petitioner’s Experts.

All three of petitioner’s experts opined that the hepatitis B vaccination was

responsible for the symptoms A.H.T. displayed after vaccination. All three stated that

myelin antibodies, and fecal metals, among many others. Most results were entirely within reference

ranges, but occasionally, a few individual results would be slightly high or low. See, e.g., Pet. Ex. 23, pp.

364 (all red blood cell elements within reference range, except selenium), 356 (urine toxic metals all

within reference range), 345 (CBC and metabolic panel with nearly all results within reference ranges),

320 (comprehensive metabolic panel with results all within reference ranges); 24, pp. 378-79 (viral panel,

stool culture, and thyroid testing all within reference ranges). Most of these laboratory reports were from

Doctors’ Data, a laboratory seen with some frequency in records from OAP cases, and one with some

difficulties with licensing agencies. See Dwyer, 2010 WL 892250, at *182 n.687. Although Dr. DeMio

testified that he saw a lot of immune and metabolic issues in A.H.T. on testing (Tr. at 211-12), he did not

point to specific tests that demonstrated those problems. He testified that she had “issues eventually with

organisms like yeast and viruses.” and had “accumulated a lot of metal toxins.” Id. Like Dr. DeMio, Dr.

Levinson ordered many laboratory tests (see Pet. Ex. 47, pp. 2059-2107, 2129-43). With the exception of

some elevated white blood cell counts and a positive streptococcus antibody test, all the results on the

traditional laboratory tests were within the reference ranges, including the comprehensive metabolic

panel. Id., pp. 2140-43. Testing by Geneva Diagnostics encompassed a toxic element clearance profile,

completed on June 17, 2010 (Pet. Ex. 47, pp. 2134-39), and a nutritional evaluation completed on June

28, 2010, assessing oxidative stress, organic acids, amino acids, essential fatty acids, and toxic and

nutrient elements (Pet. Ex. 47, pp. 2059-86).

19

A.H.T. had a mitochondrial disorder or dysfunction which was aggravated by her

hepatitis B vaccination, but their theories about how the vaccination did so varied

considerably. Their backgrounds and qualifications were likewise quite divergent as

well.

1. Doctor Levinson.

Doctor Levinson graduated from the University of Miami School of Medicine, and

completed a residency in psychiatry. Pet. Ex. 60 at 2339. He did not list any

publications on his CV, although the CV included a reference to his dissertation on the

use of valerian root as a sleep aid. According to his CV, he has lectured on the

“biomedical” treatment of autism and gastrointestinal issues in autistic patients, as well

as on “detoxification” and dietary interventions. He has also appeared in several

television programs on subjects as diverse as reversing aging, autism, and heavy metal

poisoning. Id. at 2340-41. According to his February 2012 statement, he regularly

treated patients “with mitochondrial disease, metabolic disorders, and immune-system

related conditions” and “frequently lecture[d] on mitochondrial disorder[s]and the

potential for environmental and biological triggers of this condition.”59 Pet. Ex. 59 at

2336.

From the filed records, it is difficult to determine what diagnoses informed his

treatment of A.H.T., as his records from 2010 and 2011 do not reflect a diagnosis. He

referred A.H.T. to Dr. Shoffner for mitochondrial disorder testing about a year after Ms.

Holt completed his intake form. In his February 2012 statement, Dr. Levinson

mentioned his treatment of A.H.T. for a mitochondrial disorder and her improvement on

such treatment, but he did not indicate the nature of the treatment, when it began, or

what constituted improvement or how it differed from the treatment he provided prior to

her diagnosis. See Pet. Ex. 59 at 2336-37.

His February 2012 statement was conclusory in nature. He did not explain his

reasoning or point to anything that supported the opinions he expressed regarding

diagnosis and causation. These were serious deficiencies, given his lack of any training

in immunology, oxidative stress, or mitochondrial disorders, matters about which he

opined.

2. Doctor DeMio.

59Doctor McCandless expressed skepticism about Dr. Levinson’s qualifications to lecture about

mitochondrial disorders, pointing out three specific statements in Dr. Levinson’s causation opinion “that

demonstrate a lack of understanding of mitochondrial biology and physiology.” Res. Ex. G at 3. He

added in testimony that these three statements were not supported by solid, underlying research. Tr. at

588. He explained that most people who treat children with mitochondrial diseases “often see some

deterioration associated with viral illnesses and fever,” but to opine why this happens or to attribute it

happening to a vaccination in a five-day old was simply speculation. Tr. at 589.

20

Doctor DeMio testified as both treating physician and expert, although precisely

what qualified him as an expert in either mitochondrial disorders or the causes of autism

spectrum disorders remains elusive. He graduated from medical school at Case

Western Reserve University. Pet. Ex. 63, p. 2358. He is board certified in emergency

medicine. Tr. at 226. He has no formal specialized training in metabolic diseases or in

any of the several areas (pediatrics, immunology, neurology, or gastroenterology), in

which he proffered opinions. Tr. at 227-28. His only publications involved chapters on

arthritis, gout, inflammation, and nutrition in an integrative medicine textbook. Pet. Ex.

63, p. 2360.

He did partial residencies in pathology and internal medicine, followed by a three-

year residency in emergency medicine, all in the Cleveland, OH area. Tr. at 183-84. As

a part of his emergency medicine residency, he received some pediatric training. Tr. at

226-27; Pet. Ex. 63, p. 2359. After completing his residency in 1989, he worked briefly

in Massachusetts, before returning to Cleveland’s Mount Sinai hospital as a part-time

faculty member. He also worked at emergency medicine departments in two other

hospitals and in their residency training programs. Tr. at 185-86. None of his

appointments during this period were full-time faculty or clinical positions at any one

institution. Tr. at 186-87. He also maintained a private medical practice in which he

offered nutritional treatments as an alternative to drugs. Tr. at 188.

At the time of his testimony, he held no faculty appointments, although he had

privileges at several hospitals. Tr. at 228. He currently treats patients with immune

dysfunction, metabolic disorders, mitochondrial disorders, developmental problems,

behavior and mood issues, and cognitive dysfunction diagnosed “by other people who

basically aren’t doing much, if any, medical treatment for them.” Tr. at 188-89, 230.

The majority of his patients are children with developmental disabilities, including ASD,

obsessive compulsive disorder [“OCD”], attention deficit hyperactivity disorder,

dyspraxia, apraxia, mitochondrial dysfunction, and mitochondrial disease. Mitochondrial

dysfunction patients comprised from a quarter to a third of his patients over the last nine

years. Tr. at 194-95. His clinical practice is a “cash office,” which does not directly bill

medical insurers for the care rendered. Tr. at 229-30.

He serves as the Chief Medical Officer of the U.S. Autism and Asperger’s

Association (Tr. at 190) and has assisted the Autism Research Institute with their “think

tanks” and meetings (Tr. at 191). He is the founder and executive director of the

American Medical Autism Board, which he described as “the board certified by medical

doctors who do the kind of treatment that several of us out there are doing” (Tr. at 192),

presumably referring to biomedical approaches to the treatment of autism. He

acknowledged that this board is not recognized by the American Board of Medical

Specialties. Tr. at 231.

Much of Dr. DeMio’s testimony involved broad, general statements, even when

he was discussing his own treatment of A.H.T. In describing that treatment, he used

medical terminology vaguely and indiscriminately. For example, he testified regarding

21

his treatment of A.H.T. that: “then there’s methylation[60] and some other metabolic

support that we did. Methylation’s one of the metabolic things that we do, and so we

added in a lot of those treatments.” Tr. at 213. He “found [A.H.T.] to have accumulated

a lot of metal toxins,” but did not indicate which metals were toxic or how he knew that

they were at toxic levels.61 Id. The tests initially performed for various metals were all

within the reference ranges. See, e.g., Pet. Ex. 23, pp. 328, 350, 356. One later urine

test, which was performed after chelation began, showed one slightly elevated result for

tin, but no results were significantly above the reference ranges.62 Id., p. 348. Although

he testified that he found many immune and metabolic issues as the result of the testing

he ordered for A.H.T. (Tr. at 211-12), he did not point to any specific tests that

demonstrated these issues. He found her gastrointestinal system was not “to the

balance that we want and we also found issues eventually with organisms like yeast

and viruses” either based on tests or “clinically,” but once again, he did not point to

specific tests. Tr. at 213.

He was equally vague about how A.H.T. responded to his “biomedical”

treatments. He testified that:

She definitively had responses, and a lot of them were very good, and

then she ended up getting some upheavals I call them. Many people call

them side effects, things that showed she was able to respond to those. . .

.Some of them for a few months would really help her a lot to kind of

impress the speech therapist that she was able to learn better. . . a lot of

[her symptoms of OCD, cognitive function, and focus] got better, and

some of them either got worse or she shifted over to some other things, so

she had had hallucinations or some very intense preoccupations.

Tr. at 214.

To summarize, I did not find his testimony reliable in general or useful in

resolving either the factual disputes or causation questions. Although Dr. DeMio had

60 “Methylation” is defined chemically as the addition of methyl groups to a substance. DORLAND’S at

1152. I doubt that this was what Dr. DeMio meant. It is likely that he was referring to the methyl B 12

(methylcobalamin) treatments he ordered during his early treatment of A.H.T. Testing by Geneva

Diagnostics encompassed a toxic element clearance profile, completed on June 17, 2010 (Pet. Ex. 47,

pp. 2134-39), and a nutritional evaluation completed on June 28, 2010, assessing oxidative stress,

organic acids, amino acids, essential fatty acids, and toxic and nutrient elements (Pet. Ex. 47, pp. 2059-

86). I note that problems in methylation of DNA and methylcobalamin treatments were discussed in the

Theory 2 test case decisions (see. e.g., Dwyer, 2010 WL 892250, at *140-42) as a part of the oxidative

stress aspects of the mercury causation theory, a theory rejected in each of the Theory 2 OAP test cases.

61On cross-examination, Dr. DeMio acknowledged that a section of his website discussed his belief that

one of the major causes of the “autism epidemic” is mercury and aluminum in vaccines. Tr. at 232-33.

62As chelation is performed to remove metals such as lead and mercury from the body, increases in

urinary levels of metals susceptible to chelation is expected. This does not mean that toxic levels were

present in the body prior to chelation. Snyder, 2009 WL 332044, at *176-78; Pet. Ex. 23, p. 348.

22

treated A.H.T.,63 I gave little weight to his testimony about the events after the

vaccination as the testimony was based primarily on what was reported to him by

A.H.T.’s parents, years after the events in question. As for his opinions regarding their

credibility and ability as historians (see Tr. at 203), I had the opportunity to assess these

matters for myself. Unlike Dr. DeMio, I carefully reviewed every medical record filed

and noted that Ms. Holt’s recitations of A.H.T.’s medical history varied over time, and

some of the matters she reported were inexplicably absent from the contemporaneous

records.64 See, e.g., n.30, supra. On at least one occasion, Mr. Tipton’s reports

seemed calculated to mislead health care providers about A.H.T.’s medical history. See

Pet. Ex. 43, p. 1876 (screening form signed by Mr. Tipton in which he falsely reported

that A.H.T. had received the chickenpox vaccine and was up to date on immunizations).

63 Doctor DeMio began treating A.H.T. about three years after the events in question.

64For example, after reviewing the early pediatric records during cross-examination, Dr. Kendall

acknowledged that the normal growth and development described in the primary care records through

nine months of age were inconsistent with the testimony of A.H.T.’s family members. Tr. at 388-89.

23

3. Doctor Kendall.

Doctor Kendall, a biochemical geneticist and mitochondrial disease specialist,

obtained her medical degree from the New Jersey Medical School. Tr. at 291; Pet. Ex.

80 at 2504.65 She completed a residency in pediatrics, followed by a fellowship in

genetics and metabolism at Boston Children’s Hospital and Harvard Medical School,

and then a research fellowship in genetics and metabolism at Tufts. Tr. at 291-92; Pet.

Ex. 80 at 2504. Both fellowships involved an active clinical practice in patients with

suspected or known genetic and metabolic disorders. The research fellowship involved

work in a mitochondrial research laboratory as well. Tr. at 292. After her fellowship,

she began a mitochondrial disorders program at Boston’s Children’s Hospital which

focused on the diagnosis, care, and management of mitochondrial disease patients. Tr.

at 295. She has been treating patients with mitochondrial disorders for 22 years and is

board certified in biochemical genetics. Tr. at 293, 298. Although Dr. Kendall trained as

a pediatrician and had been board certified in pediatrics at one time, her certification

was not current, and she did not see pediatric patients for treatment other than that

related to mitochondrial disease. Tr. at 298-300, 332-33.

She has held academic appointments at both Harvard Medical School and

Emory Medical School as a geneticist in the pediatrics department. Tr. at 293-94.

She currently teaches and lectures at symposiums, at Emory University Nursing School,

and annually at the United Mitochondrial Disease Foundation’s symposium. She has a

hospital appointment at Children’s Healthcare of Atlanta as a clinical geneticist. Tr. at

295. However, her primary work is in an outpatient setting, in her role as President,

Virtual Medical Practice, where she manages patients with a known diagnosis,

evaluates patients for mitochondrial disease, and provides second opinion consultations

throughout the world as the “virtual” part of the practice. Pet. Ex. 80 at 2505; Tr. at 295,

298-99. She also evaluates patients being considered for enrollment in clinical trials.

Tr. at 299.

Doctor Kendall’s CV listed three research interests: inborn errors of metabolism;

the pathophysiology of multisystem problems in disorders of mitochondrial energy

production; and the efficacy of clinical treatment in disorders of mitochondrial energy

production. Pet. Ex. 80 at 2505. There were eight journal articles listed as “Original

Reports” on her CV, Pet. Ex. 80, but only one of them explicitly involved mitochondrial

disorders. Id., p. 2509. However, she testified that her most recent publication (which

did not appear on Pet. Ex. 80, her CV) was a review article on mitochondrial disease

and diagnostics. Tr. at 296-97. The CV also listed “Reviews,” which appeared to

include book chapters and journal articles, including one on testing in mitochondrial

disorders and one entitled “Bridging the Gap between ASD and Mitochondrial Disease.”

65Doctor Kendall testified that this CV was out of date and indicated that she would provide a copy of the

new one. Tr. at 297. An updated CV was never filed.

24

Pet. Ex. 80, at 2509.66 She did not indicate that she was a peer reviewer or editor for

any professional publications.

Unlike Dr. DeMio, Dr. Kendall possessed the requisite qualifications to opine

about mitochondrial disorders. The reliability and credibility problems posed by Dr.

Kendall’s testimony did not concern her qualifications to opine about mitochondrial

disorders, but rather her lack of familiarity with the medical records regarding A.H.T.’s

growth, development, and treatment during the relevant periods, and her evasiveness in

answering my questions as well as those from opposing counsel.

Her lack of familiarity about the medical records was somewhat unusual for an

expert witness testifying in the Vaccine Program. She was unsure what diagnostic

criteria Dr. Shoffner used (Tr. at 324-25), although it was clearly identified in the

diagnostic report. Pet. Ex. 61, pp. 2349-50. She was unable to recall when A.H.T.

manifested some of the symptoms upon which the diagnosis was based. See Tr. at

310. When asked if she had reviewed A.H.T.’s medical records from her first year of

life, Doctor Kendall replied that she was “assuming” that she did. Tr. at 339. She could

not recall if fever was mentioned in the medical records as a symptom occurring after

A.H.T.’s vaccination. Tr. at 341-42. She could not recall when A.H.T. was diagnosed

with hypotonia. Tr. at 344. She could not recall when A.H.T. started having autistic-like

behaviors. Tr. at 345. She could not recall when A.H.T. began displaying symptoms of

dysautonomia (temperature instability),67 nor did she recall how often this symptom

occurred. Tr. at 345-46. She believed that the medical records reflected A.H.T.

suffered from fatigue, but could not identify a particular time frame when fatigue was

reported as a problem. Tr. at 348. She testified that the medical records described

A.H.T. as lethargic after her vaccination (Tr. at 339-40), but that description does not

appear in any contemporaneous record. After reviewing the early pediatric records

during cross-examination, Dr. Kendall acknowledged that the normal growth and

development described in the primary care records through nine months of age were

inconsistent with the testimony of A.H.T.’s family members. Tr. at 388-89. Her lack of

preparation for testimony was disappointing.

Additionally, Dr. Kendall avoided giving straight answers to straightforward

questions. When asked whether a neonate with primary mitochondrial disease would

likely have normal growth and weight gain, she replied, “[t]hey can.” When pressed to

indicate if such growth and weight gain would be expected, she responded “it depends

on the patient.” She was similarly evasive in answering questions regarding motor and

intellectual development in a neonate with a primary mitochondrial disease, responding

again, “it depends on what their clinical presentations are.” Tr. at 348. These

tautological answers were not informative about what is generally or typically seen in

66The CV listed “abstracts” separately. Pet. Ex. 80 at 2510. In general, they appeared to be the

abstracts of the journal publications listed earlier.

67Doctor Kendall‘s report indicated that dysautonomia, including temperature instability, was a possible

symptom of mitochondrial disease. Pet. Ex. 79 at 2500; see also Tr. at 308-09.

25

such patients. This evasiveness, coupled with the lack of support for some aspects of

her opinion, caused me to question whether her testimony was entirely reliable.

Her testimony provided details on her theory of vaccine causation that her expert

report lacked. The portion of her report addressing causation (Pet. Ex. 79 at 2496-97)

was very short, only about two paragraphs long, and was based on two cited journal

articles, one of which was largely a case report, discussing autistic regression in

children with diagnosed mitochondrial disorders. As Dr. Kendall admitted on cross

examination, A.H.T. did not experience autistic regression in the classic sense of losing

“speech and those type of things,” and she agreed that there were many differences

between the children described in the studies and A.H.T.’s presentation. Tr. at 356;

357-58.

When asked about support for specific aspects of her theory of causation, she

avoided a direct answer, as exemplified by the following exchange:

Q: What other literature are you relying on for your theory?

A: As I indicated, some of the other articles that talk about temperature.

Q: Can you be more specific?

A. They are noted in some of the other articles.

Q: Nothing was filed with your report, so I’m just - -

A: No, I understand. I’m just mentioning it based on the questions that you’re

posing, and it’s coming up, so that’s what I’m saying.

Q: But you did not submit anything to support your theory, is that correct?

A. I did not submit those articles, no.

Tr. at 358. She clarified that not all the articles she cited in her report were actually filed

as evidence. Tr. at 360. The failure of petitioner to file supportive evidence for her

opinions, particularly after Dr. McCandless challenged her reliance on other literature

she claimed was supportive of her opinions (see Res. Ex. G at 4), was troubling.

B. Respondent’s Experts.

With regard to A.H.T.’s symptoms after vaccination and the likelihood that they

occurred as described by the witnesses, I accorded greater weight to the testimony of

respondent’s two experts. Both were currently board certified in pediatrics, displayed

familiarity with the contemporaneous records, gave careful attention to the testimony of

A.H.T.’s parents and fact witnesses, and provided reasons for their conclusions. Both

Drs. Wiznitzer68 and McCandless were far better prepared to discuss A.H.T.’s medical

68 During his testimony, Dr. Wiznitzer indicated that he did not have Dr. Hefner’s records at the time he

wrote his expert report (Res. Ex. A), thus explaining why his comments in that report about A.H.T.’s

development ended at nine months of age, when she stopped seeing Dr. Buttleman. Res. Ex. A at 7; Tr.

at 670. Also, on cross-examination, petitioner’s counsel noted that Dr. Wiznitzer’s report referred to

A.H.T.’s birth as occurring in a hospital. See Tr. at 691-92. I note that the filed medical records do not

include any records regarding A.H.T.’s home birth; Dr. Buttleman’s records do not mention where A.H.T.

was born; and Dr. Puri, A.H.T.’s pediatric neurologist, referred obliquely to a hospital birth. See generally

Pet. Exs. 58 (Dr. Buttleman’s records); 31, p. 1262 (recording “vaginal delivery and was home with the

26

records than Dr. Kendall. With regard to neurological issues, including

encephalopathies in general, I found Dr. Wiznitzer to be the most qualified and reliable

witness. Although he displayed the unfortunate tendency of sparring with opposing

counsel, particularly with respect to hypothetical questions, his responsiveness to my

questions distinguished him from Dr. Kendall. Of the two mitochondrial disease experts,

Dr. McCandless was the better witness, and his opinions were better supported than

hers. His explanations were clear and he genuinely tried to answer questions, rather

than to dodge them.

1. Doctor McCandless.

Doctor McCandless holds three board certifications: pediatrics, clinical genetics,

and clinical biochemical genetics. After completing medical school and a residency in

pediatrics, he practiced pediatric medicine for five years. He then completed a clinical

genetics residency at Case Western Reserve University in Cleveland, Ohio. Tr. at 414.

This was followed by a faculty position in clinical genetics at the University of North

Carolina. He later returned to Cleveland for a fellowship in clinical biochemical

genetics. Tr. at 413-14.

In his current positions at Rainbow Babies and Children’s Hospital and Case

Medical Center, he evaluates and cares for patients who have, or are suspected to

have, biochemical genetic disorders. Tr. at 414. He is also involved in outpatient care

for the same disorders. He is the medical director of a Prader-Willi syndrome clinic and

of the Center for Human Genetics. He diagnoses and treats children and adults with

mitochondrial disorders. He has been caring for such patients for the last 17 years. Tr.

at 414-16.

Doctor McCandless holds a faculty appointment at the Case Western Reserve

School of Medicine, where he teaches genetics to medical students and graduate

students, and serves as the director of the residency training program in medical

genetics. Since 1996, his teaching has focused primarily on inborn errors of

metabolism, some general genetics, and mitochondrial diseases as a part of the

biochemical genetics program. He is a member of several professional societies,

including the American Academy of Pediatrics, is a fellow of the American College of

Medical Genetics, and a member of the board of directors for the Society for Inherited

Metabolic Disorders. Tr. at 416-17. He lectures about mitochondrial disorders at the

medical school, and developed the program on mitochondrial disorders for a national

meeting of the American College of Medical Genetics and the Society for Inherited

Metabolic Disorders joint session.

His research has focused primarily on fatty acid oxidation disorders, with fewer

publications in the area of respiratory chain disorders. Tr. at 418. He is the principal

site investigator for a multicenter clinical trial of coenzyme Q-10 therapy for children with

mother in a few days). I thus do not consider this incorrect statement regarding A.H.T.’s birth location as

a dereliction on Dr. Wiznitzer’s part.

27

mitochondrial disorders. His research laboratory uses mouse models to try to

understand how mitochondrial dysfunction leads to symptoms and how to better treat

those symptoms. He is involved in several clinical trials related to the treatment of urea

cycle disorders and drug trials to treat phenylketonuria and other lysomal storage

diseases. Tr. at 419.

Doctor McCandless has testified as an expert witness twice for plaintiffs and

once for a defendant in courts other than the Vaccine Program. This was his first

appearance as a witness in a Vaccine Act case. Tr. at 421-22.

Although not lengthy, his opinion (Res. Ex. G) was well-written and well-

reasoned. The primary discrepancy in his opinion—stating that Dr. Shoffner diagnosed

a possible, rather than a probable, mitochondrial disorder—is not inaccurate, just

incomplete. Because Dr. Shoffner’s records regarding A.H.T. were filed as a part of

three different exhibits (Pet. Exs. 26, 47, and 61) and Dr. Shoffner apparently changed

his diagnosis between August 1 and August 10, 2011, without any reference to the

earlier diagnosis, much less an explanation for the change, Dr. McCandless apparently

missed the later diagnosis of a probable mitochondrial disorder. I find this oversight

understandable, particularly as there was no additional testing conducted by Dr.

Shoffner between the two visits that would account for the change in diagnostic

category.

2. Doctor Wiznitzer.

After graduating from medical school, Dr. Wiznitzer completed a three year

residency in pediatrics at what is now Cincinnati Children’s Hospital, followed by a year-

long fellowship in developmental pediatrics at the Cincinnati Center for Developmental

Disorders. Tr. at 619. He then completed a three year fellowship in child neurology at

the University of Pennsylvania and an additional two year fellowship at the National

Institutes of Health on disorders of higher cortical function in children. Tr. at 619-20. He

is board certified in pediatrics, neurology (with special qualifications in child neurology),

and neurodevelopmental disabilities. Tr. at 620.

At the time of the hearing, he was an associate professor of pediatrics,

neurology, and international health at Case Western Reserve University School of

Medicine, and teaches at the nursing and medical schools. Tr. at 620-21. His primary

clinical appointment is as a child neurologist at Rainbow Babies and Children’s hospital.

His clinical responsibilities there include services at the inpatient unit, outpatient clinical

practice, the epilepsy service and teaching residents. His responsibilities also include

administration of research grants, including one involving autism treatments. Tr. at 621.

He is a member of and holds positions in several relevant professional

organizations, including teaching and course development as a fellow of the American

Academy of Neurology [“AAN”], where he has presented courses or lectures on ADHD,

autism, and pediatric behavioral neurology. He is part of an AAN task force charged

with developing a position paper on interventions in autism. Tr. at 621-22. He is a

28

member of the executive committee of the American Academy of Pediatrics [“AAP”] and

serves as that organization’s liaison to the executive committee of the Council on

Children with Disabilities. He is a member of the autism subcommittee of the AAP and

a member of various AAP working groups, including one on neuromotor examinations in

children. Tr. at 622. He chairs a task force dealing with dyspraxia, a developmental

coordination disorder. Tr. at 646. He is also a member of the Child Neurology Society

and the International Society for Autism Research. Tr. at 622-23.

Doctor Wiznitzer is a member of the editorial boards of two professional journals.

He is a peer reviewer on a regular basis for medical journals dealing with pediatrics,

neurology, and other specialties. Tr. at 623. As a member of the Brighton

Collaboration, an international organization dealing with vaccine safety, he has helped

to develop definitions for various conditions to help in standardizing studies into adverse

events after vaccination. Tr. at 623. He also develops questions for various medical

certification examinations. Tr. at 624.

He has diagnosed and treated children with ASD and other developmental

disabilities for about 25 years. He has conducted research into and has numerous peer

reviewed publications, including journal articles, book chapters, and abstracts, on the

topics of autism (including co-morbid conditions such as tuberous sclerosis), ADHD,

and other developmental disabilities. Tr. at 624-25. He treats children with

mitochondrial dysfunction and disorders in his clinical practice. He refers children with

suspected mitochondrial disorders to the genetics department and the mitochondrial

team for testing and diagnosis. Tr. at 625.

In addition to his clinical, teaching, writing, and research responsibilities, Dr.

Wiznitzer devotes about four to five hours per week to litigative consultations. Although

he primarily reviews cases for respondent in the Vaccine Program, he has

recommended compensation in some of those cases, and has supported claims of his

own patients for compensation. Tr. at 625-26. He has testified frequently on behalf of

respondent in the Vaccine Program. Doctor Wiznitzer was offered as an expert in

pediatric neurology and developmental disabilities, without objection. Tr. at 626-27.

IV. The Causation Theories Presented.

A. Mitochondrial Disorder, Disease, and Dysfunction.

Neither party filed much background information about mitochondrial disorders in

general. The comprehensive literature review filed by petitioner, D. Rossignol & R.

Frye, Mitochondrial dysfunction in autism spectrum disorders: a systematic review and

meta-analysis, MOLEC. PSYCHIATRY, 17: 290-314 (2010), Pet. Ex. 71 [hereinafter

“Rossignol & Frye, Pet. Ex. 71”], did not discuss the wide variety of mitochondrial

disorders, focusing more on the co-morbidities in mitochondrial dysfunction,

mitochondrial disease, and ASD, and the relative rates of various clinical findings.

Some of the various clinical phenotypes, such as Alper and Leigh syndromes, were

mentioned in C. Verity, et al., The clinical presentation of mitochondrial diseases in

29

children with progressive intellectual and neurological deterioration: a national,

prospective, population-based study, DEV. MED. & CHILD NEUROL., 52: 434-40 (2010).69

As this study focused on patients with progressive disease, it did not provide information

on the wide variety of other mitochondrial disorders.

Mitochondrial disease can present in a wide variety of ways, according to Dr.

McCandless. Tr. at 435. He added that “it has been said that mitochondrial dysfunction

can cause almost any symptom in any part of the body at almost any time, which to a

certain extent is true.” Id. However, “mitochondrial diseases tend to present in some

very characteristic ways [which are] usually related to the tissue that’s most involved,

and those are the tissues that use the most energy.” Id. Doctor Kendall explained that

“there are subtypes of mitochondrial disease that are clearly defined [that] are

descriptive of a group of clinical features that are seen over and over again and often in

constellation with a specific gene defect or a specific biochemical feature,” but that most

patients do not fall into a “well-categorized subtype.” Tr. at 349. She testified that

A.H.T. does not fit into one of these subtypes. Tr. at 349-50.

Initially, petitioner claimed that A.H.T. has a mitochondrial disorder, one which

was “significantly aggravated” by A.H.T.’s initial hepatitis B vaccination. Petition, ¶¶15-

16. This claim appears to have been modified by petitioner’s post-hearing brief.

Drawing from the headings in the brief, petitioner claims that A.H.T. has mitochondrial

dysfunction (Petitioner’s Post-Hearing Brief [“Pet. Br.”] at 1-3), which was vaccine

induced (id. at 3-10), entitling her to compensation (id. at 10-13). Likewise, Dr.

Kendall’s expert report claimed that A.H.T. has a mitochondrial disorder, but in

questioning Dr. Kendall, petitioner’s counsel primarily asked about “mitochondrial

dysfunction.” For example, Dr. Kendall testified that A.H.T. had probable mitochondrial

dysfunction (Tr. at 328-29), but her report referred to “clinical features and biochemical

and enzymatic data in support of a mitochondrial disorder.” (Pet. Ex. 79 at 2497)

(emphasis added).

The terms used to characterize A.H.T.’s condition varied throughout the post

hearing brief, suggesting that petitioner thinks the terms mitochondrial disorder and

dysfunction are interchangeable.70 They are not. The distinction is significant, in that

while respondent conceded that A.H.T. has laboratory evidence of some moderate

mitochondrial dysfunction, respondent contends that such dysfunction is not responsible

for A.H.T.’s clinical symptoms, and that it is unlikely A.H.T. has a mitochondrial disorder

69Hereinafter cited as “Verity, Res. Ex. K” or as the “PIND study” (Progressive Intellectual and

Neurological Deterioration). Witnesses referred to this study either as “Verity” or “PIND.”

70 Petitioner’s post hearing brief uses the terms mitochondrial “dysfunction” and “disorder”

interchangeably throughout. See, e.g., header using “Mitochondrial Dysfunction” at 1; “mitochondrial

disorder” at 1; citations to testimony about “mitochondrial dysfunction” at 2-3; citations to articles

discussing mitochondrial disease at 3. I note that even Dr. DeMio agreed that the terms “mitochondrial

disease” and “mitochondrial dysfunction” have different meanings. Tr. at 262-63.

30

or disease.71 Tr. at 471-501, 565-66; Respondent’s Post-Hearing Brief [“Res. Br.”] at

18-19. Id.

The most helpful information concerning the distinction between mitochondrial

disorders and mitochondrial dysfunction came from Dr. McCandless. He defined

primary mitochondrial disease as “a set of clinical abnormalities that directly result from

mitochondrial dysfunction.” Res. Ex. G at 2. In primary mitochondrial disease, there is

evidence that the mitochondria do not function normally and there is a measurable

clinical effect of the dysfunction. Tr. at 423, 564-66.

In testimony, Dr. Kendall defined a primary mitochondrial disorder as one “in

which there is an alteration in a gene that alters a protein that is directly involved in

energy production.” Tr. at 396-97. In essence, she asserted that a defect in either

mtDNA or nDNA is necessary to have a primary mitochondrial disorder or disease. Tr.

at 397-98. Doctor McCandless agreed that the defect had to be one that “leads to a

protein in the mitochondria that’s not doing its job properly and that leads to the

dysfunction,” but he did not require that the defect be genetic. Tr. at 428. In a primary

mitochondrial disorder, “the basic underlying problem is the mitochondrial structure or

function is wrong from the beginning,” leading to symptoms of mitochondrial disease.

Tr. at 429.

According to Dr. McCandless, secondary mitochondrial defects exist when some

other process causes dysfunction of the mitochondria, leading to symptoms. Tr. at 429.

When dysfunction of the mitochondria is observed in a laboratory setting, there must be

some evidence that the dysfunction also causes an identifiable clinical finding or

symptom before the patient can be characterized as having a mitochondrial disease or

disorder. Res. Ex. G at 2; Tr. at 428. In testimony, he clarified that one can infer from

in vitro (laboratory) testing of tissue to what may happen in vivo, but there still must be

some evidence of dysfunction in the body. This evidence may be test results or some

clinical symptomology. He pointed to hypoxia or rotenone (a fish poison) as examples

of an outside agent that could produce mitochondrial dysfunction. Tr. at 428-29.

Most of the few studies filed in this case focused on individuals with diagnosed

mitochondrial disorders, rather than individuals with some evidence of mitochondrial

dysfunction. Thus, the applicability of these studies to someone with mitochondrial

dysfunction, rather than a mitochondrial disorder, is questionable. Additionally, although

A.H.T. has been diagnosed with a probable mitochondrial disorder, the evidence

supporting that diagnosis rests on the presence of certain symptoms, about which there

are significant factual disputes. This may explain petitioner’s shift in focus from

mitochondrial disorder to mitochondrial dysfunction in petitioner’s post hearing brief.

And, as it is more difficult to establish how a vaccine can trigger a genetic condition

71 The parties’ witnesses agreed that the terms “mitochondrial disorder” and “mitochondrial disease” were

interchangeable. Tr. 264 (DeMio); 428 (McCandless). Doctor McCandless also testified that it is very

important to clarify what people mean when they use the terms “disease,” “disorder,” and “dysfunction” in

discussing mitochondrial problems. Tr. at 426-27.

31

present since birth, the focus on dysfunction rather than disorder eases, to some extent,

petitioner’s burden to prove that a vaccination can, more likely than not, be responsible

for A.H.T.’s symptomology.

B. The Theories.

The causation theory identified in the amended petition—that mitochondrial

disease can be aggravated by an outside event—builds on an observed characteristic

of mitochondrial disorders that is not particularly controversial, even if it has not been

well studied or documented. That is, the condition of individuals with mitochondrial

disorders often worsens over time. This may occur gradually, or there may be abrupt

regressions or decompensations that result in illness and/or the inability to perform

motor or cognitive tasks once mastered. Pet. Ex. 79 at 2494; Res. Ex. A at 8; Res. Ex.

G at 2; Tr. at 444-46, 588.

These regressions may occur without any apparent cause or may be temporally

related to events such as viral or febrile illness, anesthesia, dehydration, surgery, and

the use of some drugs, such as HIV medications and statins. Pet. Ex. 79 at 2494; Res.

Ex. G at 4; Tr. at 392-93, 398, 572, 588-89, 608-09. Some of those who experience

decompensation or regression return to baseline, some plateau, and in many, the loss

of skills signals a downward spiral in the progression of mitochondrial disease.

Unfortunately, many mitochondrial diseases are relentlessly progressive and ultimately

fatal. Res. Ex. G at 2-3; see also Verity, Res. Ex. K at 435, 439 (noting that mortality

rates of children with mitochondrial disease enrolled in this study were high, with 40 of

the 112 children enrolled in the study beginning in1997 having died by 2008).

In certain types of mitochondrial or metabolic disorders, there is a measurable

physiological response that causes the decompensation. In individuals with urea cycle

disorders, an illness (or dehydration due to an illness) may produce an excess of

ammonia in the body, termed “hyperammonemia,” resulting in a metabolic

decompensation. See J. Kingsley, et al., Immunizations for Patients with Metabolic

Disorders, PEDIATRICS, 118(2): e460-70 (2006), filed as Pet. Ex. 70, at e464

(hyperammonemiac states are produced by breakdown of muscle tissue during periods

of anorexia, such as may be seen in ill children) [hereinafter “Kingsley, Pet. Ex. 70]; T.

Morgan, et al., Vaccines are not Associated with Metabolic Events in Children with Urea

Cycle Disorders, PEDIATRICS 127: e1147-53 (2011) [hereinafter “Morgan, Res. Ex. I” or

the “Morgan study”] at e1148 (“children with [urea cycle disorders] are at high risk of

devastating metabolic decompensation in the setting of acute childhood illnesses”).

See also Tr. at 502-03 (Dr. McCandless discussing vaccinations in children with urea

cycle disorders and the Morgan study).

Decompensation or regression occurs in other types of mitochondrial or

metabolic disorders as well as in urea cycle disorders. A correlation has been drawn

between metabolic stressors, such as illnesses and surgery, and periods of regression

in these patients, based on a temporal relationship between such stressors and a

regression or decline in health. This relationship has not been well documented, but it

32

appears to be generally accepted as a causal one. Res. Ex. G at 4; Tr. at 502-03.

Fever, in particular, has been recognized as a stressor that can possibly aggravate a

mitochondrial disorder, although fever in the absence of an illness has not been

systematically studied. Tr. at 352, 392, 572; Pet. Ex. 61, pp. 2347-48. Several of the

filed medical journal articles discussed the connection between fever, febrile illness, and

decompensation. However, Dr. McCandless testified that it was the underlying illness,

and not merely the febrile response to it, that was responsible for the deterioration. Tr.

at 512-13, 572-73.

The lack of both specificity and strength in the association between illness and

decompensation or regression has contributed to the uncertainty about the causal

mechanism—that is, what is it about a fever or illness that causes the loss of skills? Not

all individuals with mitochondrial disorders experience periods of decompensation with

such stresses, and many experience such periods of decompensation even in the

absence of metabolic stress.72 The same patient may experience an illness and lose

skills, but handle the next several illnesses without any apparent regression. Tr. at 445-

46, 590-91. The nature of the underlying mitochondrial disorder, the specific

manifestation in a particular individual, the type of illness, and the nature of the

regression are all factors affecting the response of a patient with a mitochondrial

disorder to an illness. Whether the regression persists is also quite variable among and

within the various types of mitochondrial disorders.73

Both Drs. Kendall and McCandless testified about some of the theories regarding

the causal mechanism for decompensation or loss of skills. Tr. at 352-53, 444-45.

Petitioner’s theory that a vaccine can cause onset of a dormant or underlying

mitochondrial disease or cause long-lasting mitochondrial dysfunction was presented

primarily by Dr. Kendall. This theory extends what is generally accepted about

mitochondrial disorders in three specific ways. First, petitioner contends that an

external event can trigger onset of a mitochondrial disorder that would otherwise have

remained dormant, not simply cause regressions or loss of skills in individuals with a

diagnosed or, at least suspected, mitochondrial disorder. Second, petitioner claims that

a vaccine, not just an illness, can exacerbate, aggravate, or trigger this onset or cause

mitochondrial dysfunction. Third, petitioner claims that this aggravation can cause the

manifestation of symptoms, not only shortly after vaccination, but new symptoms

72 To illustrate the frequency of illness or regression, Dr. McCandless testified that observations over a

period of several years of 100 hypothetical children with confirmed mitochondrial disease would show that

somewhere between 40-60% of them would get sicker and stay sick longer than their siblings without

mitochondrial disease when confronted with a cold or influenza, and that they would return to baseline

more slowly than their siblings. Of those who got sicker, less than ten would have a severe or significant

deterioration. Some of these might not return to baseline. However, not all illnesses would produce this

effect of being sicker for longer, even in the small percentage of children who experienced a severe

deterioration with illness. Tr. at 590-93. The response to illness may be cyclic, occurring several times in

one year, and then not occurring at all in subsequent years. Tr. at 593-94.

73For example, Dr. Kendall testified that, in individuals who present with a mitochondrial encephalopathy,

some improve, 20-30% experience severe progressive deterioration, and the remainder are stable with

periodic ups and downs. Tr. at 338.

33

manifesting many months later. Petitioner attributed A.H.T.’s post vaccination irritability

and constipation to aggravation of her mitochondrial disorder or causation of

mitochondrial dysfunction, signaling some form of brain injury, and also contended that

the behavioral symptoms and developmental delays that manifested more than 15

months later were likewise the result of this injury.

The medical witnesses petitioner presented did not agree on the specific nature

and mechanism of the damage. During the hearing and in her post hearing brief,

petitioner advanced Dr. DeMio’s theory that ongoing “brain inflammation” was

responsible for A.H.T.’s symptoms. The “brain inflammation” theory ostensibly

incorporated most of Dr. Kendall’s theory that a vaccination can trigger an underlying

mitochondrial disorder, producing a loss of skills. However, Dr. DeMio also claimed that

the initial insult of the hepatitis B vaccine produced inflammation in A.H.T.’s brain and

this inflammation was responsible for A.H.T.’s early and later symptoms. Yet a third

theory was proposed by Dr. Levinson—that A.H.T.’s symptoms were the result of

oxidative stress as the result of the interaction of her underlying mitochondrial disorder

and the immunological stress of the hepatitis B vaccine. This theory was not explicitly

argued in the post hearing brief, but petitioner quoted a portion of Dr. Levinson’s

statement regarding this position in her post hearing brief. Pet. Br. at 10. Each of these

theories, along with some of the evidence provided by respondent, is discussed in more

detail below.

1. Doctor Kendall’s Theory.

Doctor Kendall’s expert report provided few details on her theory of causation.

The portion of Pet. Ex. 79 that addressed causation was very short, only two

paragraphs long. Id. at 2497. She referenced two medical journal articles as the

support for her assertions.74 When examined carefully, neither article provided

substantial support and one contradicted her assertion that vaccines alone could cause

or trigger a decompensation in a patient with a mitochondrial disorder.

Her testimony provided some of the details that her expert report lacked. She

testified that A.H.T. had an underlying mitochondrial disorder, that the hepatitis B

vaccination was “an immunological trigger” for her fever (Tr. at 352), which stressed her

system, “outstrip[ped] the body’s ability to develop energy for functionality” and primarily

led to damage to her central nervous system. (Tr. at 353).

In terms of timing, she pointed to symptoms that developed between hours to

days after the vaccination. Tr. at 353-54. Her theory accounting for the observed

74Petitioner’s Ex. 69, which was also filed as Res. Ex. P, is primarily a case report. J. Poling, et al.,

Developmental Regression and Mitochondrial Dysfunction in a Child with Autism, J. CHILD NEUROL., 21(2):

170-72 (2008) [hereinafter “Poling, Pet. Ex. 69”]. Doctor Shoffner, the physician who diagnosed A.H.T.

with a probable mitochondrial disorder, was one of the co-authors of this case report. The second journal

article was filed as Pet. Ex. 68 and Res. Ex. Q: J. Shoffner, et al., Fever Plus Mitochondrial Disease

Could be Risk Factors for Autistic Regression, J. CHILD NEUROL., 25 (4): 429:34 (2010) [hereinafter

“Shoffner, Pet. Ex. 68”].

34

temporal link between illnesses and deterioration or regression in mitochondrial disease

was based on the increased energy demands that such illnesses or stressors place on

the body and the inability of impaired or defective mitochondria to meet those increased

energy demands. Brain and muscle tissue require high levels of energy, and when

illness increases the demands, the supply available to brain and muscle is reduced,

resulting in lost motor and cognitive skills, among other symptoms. Tr. at 301, 303-04,

352.

This theory could account for the observation in Wolf and Smeitink, Court Ex. I,

at 1402, that the presenting symptom in children with mitochondrial disorders is often

neuromuscular in nature. However, it does not account for deterioration observed

without an identifiable triggering event.

The specific mechanism of an energy deficit to account for clinical deterioration is

less well accepted than the fact that regressions do occur. See Res. Ex. G at 4 (Dr.

McCandless stating that the “strength and mechanism of any such association are not

at all clear”); Tr. at 556-57 (discussing Dr. Kendall’s theory, another theory, and his

opinion that both might contribute to diminished energy production in the mitochondria,

along with other factors as yet unknown). Nevertheless, in this decision, I will assume,

arguendo, that Dr. Kendall’s increased energy demand mechanism is correct. The

difficulty comes in finding evidence, other than her very cursory opinion and testimony

(Dr. Kendall’s direct examination, including establishing her qualifications to opine,

encompassed only about 40 pages of testimony), to support the other contested

aspects of her opinion.

a. Can a Dormant Mitochondrial Disorder Be Triggered by an External

Event?

Doctor Kendall was unequivocal in stating that a vaccination does not cause

alteration in a “genetic blueprint” or alter “the functionality of . . . protein structure.” Tr.

at 334. She testified that an individual can “harbor either DNA changes or the

propensity for these diseases and not exhibit them from the time of birth, for example.”

Tr. at 303. Although she did not explicitly testify that an external trigger is required for

an underlying mitochondrial disorder to manifest, she appeared reasonably certain that

A.H.T.’s disorder was so triggered. Tr. at 352-54.

Other than Dr. Kendall’s opinion, there is little evidence in this record to suggest

that a metabolic stressor can trigger a dormant or unrecognized mitochondrial disorder.

The anecdotal evidence linking stress to a regression is based on what mitochondrial

disease specialists have seen in their own patients (see, e.g., Tr. at 557), necessarily

implying that the mitochondrial disorder was already diagnosed or strongly suspected

(see also Verity, Res. Ex. K, at 436 (reporting that 33 of the 112 participants diagnosed

with mitochondrial disease had experienced an exacerbation of their condition “in

association with fever or minor illness”)). Doctor McCandless testified that he could not

recall any patient who was normal and then experienced a sudden decompensation

(“crash and burn”) due to illness. Tr. at 608-09.

35

Relying on the anecdotal experience of one of her patients and Pet. Exs. 68-69,

Dr. Kendall claimed that an event such as an illness could trigger a previously

unrecognized mitochondrial disorder. She described an asymptomatic teenager who

developed symptoms of a mitochondrial disorder (progressive muscular manifestations)

after a severe case of influenza. Later, genetic testing disclosed a previously

unsuspected mtDNA deletion syndrome. Tr. at 302-03. However, mitochondrial

disorders can manifest at virtually any point in life, as Dr. Kendall acknowledged (see

Tr. at 302-03), and thus this temporal relationship could be due to coincidence alone.

The Poling case report, filed as Pet. Ex. 69, was weak support for an external

event acting as the trigger for a mitochondrial disorder. Doctor Poling, the lead author

of Pet. Ex. 69, wrote the report about the experience of his infant daughter.75 The child

reportedly experienced symptoms of a developmental regression within 48 hours of a

DTaP vaccination and more symptoms within five to 15 days of a measles vaccination

administered at 19 months of age. Poling, Pet. Ex. 69, at 2 (factual presentation). The

onset of neurological symptoms was within the periods for a DTaP Table

encephalopathy (72 hours) and a measles Table encephalopathy (five to 15 days). See

42 C.F.R. § 100.3(a)(II)(B) and (a)(III)(B)(2011) (Vaccine Injury Table identifying

encephalopathy as an associated injury for DTaP and measles vaccines and setting

forth the time periods required). The child was eventually diagnosed with both autism

and a mitochondrial disorder. Poling, Pet. Ex. 69, at 3.

Even though the Poling claim was compensated, a published decision in the

case indicates that compensation was based on the presence of a Table injury, in which

entitlement to compensation is legally presumed. Poling v. Sec'y, HHS, No. 02–1466V,

2011 WL 678559, at *1 (Fed. Cl. Spec. Mstr. Jan. 28, 2011) (fees and costs decision,

noting that the case was compensated as a Table injury). Such a decision cannot be

precedential under any circumstances, as decisions issued by special masters and

judges of the Court of Federal Claims constitute persuasive, but not binding, authority.

(Hanlon v. Sec’y, HHS, 40 Fed. Cl. 625, 630 (1998)), and certainly not in a case

75 The familial relationship was not disclosed by Dr. Poling in the case report. Disclosure of possible

conflicts of interest is expected when submitting a medical journal article for publication. Conflicts of

interest are a matter to be considered when applying Daubert. In its opinion on remand in Daubert, the

Ninth Circuit considered whether the matters an expert proposed to testify about flowed from research

conducted independently of involvement in the litigation in question, noting that this factor provides

objective proof that the research was conducted for scientific purposes. Daubert v. Merrell Dow

Pharmaceuticals, 43 F.3d 1311, 1317 (9th Cir. 1995); see also Exxon Shipping Co. v. Baker, 128 S. Ct.

2605, 2626 n.17 (2008) (declining to consider research funded in part by a party to the litigation). The

familial connection, and the fact that a vaccine injury claim for the child’s injuries was compensated, were

mentioned in a commentary on the Verity study, Res. Ex. K. See M. Sharrard, Clinical presentation of

mitochondrial diseases in children with progressive intellectual and neurological deterioration, DEV. MED.

& CHILD NEUROL., 52: 407-08 (2010) [hereinafter “Sharrard, Res. Ex. J”]. Sharrard stated that the child in

this case report was described by her father as having “developed autistic features after vaccination and

a subsequent febrile illness, and was later found to have a mitochondrial disorder.” Id. at 407. Sharrard

also indicated that the vaccine injury claim was successful. Id. I also note that Drs. Rossignol and Frye

disclosed their potential conflict of interest in the article filed as Pet. Ex. 71.

36

involving a different vaccine (one without any associated Table injury), a different

clinical presentation, and different timing.76

As Dr. McCandless observed, information acquired through experience in which

a causal connection between two events is inferred can be misinterpreted as proof of

that causal connection. Tr. at 593. See Paluck v. Sec'y, HHS, 104 Fed. Cl. 457, 475

(2012) (noting that although “case reports ‘do not purport to establish causation

definitively, and this deficiency does indeed reduce their evidentiary value’…. ‘case

reports can by their nature only present indicia of causation does not deprive them of all

evidentiary weight.’” (quoting Campbell v. Sec'y, HHS, 97 Fed. Cl. 650, 668 (2011));

Bast v. Sec'y, HHS, No. 01–565V, 2012 WL 6858040, at *24, *28 (Fed. Cl. Spec. Mstr.

Dec. 20, 2012), motion for rev. denied, 117 Fed. Cl. 104 (2014) (discussing the limited

value of case reports); The REFERENCE MANUAL ON SCIENTIFIC EVIDENCE, Federal

Judicial Center, 2011(3d ed.) at 724 (noting that in determining medical causation, case

reports “are at the bottom of the evidence hierarchy,” largely because they lack controls

and thus do not provide the level of information or detail found in epidemiologic studies;

nevertheless, they “may be the first signals of adverse events or associations that are

later confirmed with larger or controlled epidemiological studies.)” Id. at 475. “[S]ome

courts have suggested that attempts to infer causation from anecdotal reports are

inadmissible as unsound methodology under Daubert.” Id. at 217 n.14 (citing McClain

76 In the recent Federal Circuit decision in a mitochondrial disorder case, Paluck v.Sec’y, HHS, No. 2014–

5080, 2015 WL 2403354, at *8-9 (Fed. Cir. May 20, 2015), the panel relied to some degree on the Poling

case study in reversing the special master’s decision denying compensation. The panel also found that

the special master and respondent had conceded the plausibility of the petitioner’s causation theory in

Paluck. The Poling case settlement itself cannot be viewed as a concession that vaccines can trigger or

aggravate mitochondrial disorders. Because the Vaccine Injury Table represents a blend of science and

policy (Shyface v. Sec’y, HHS, 165 F.3d 1344, 1352-53. (Fed. Cir. 1999) (quoting legislative history

acknowledging that the Table may provide compensation to some whose injuries are not vaccine-

caused); Shifflett v. Sec’y, HHS, 30 Fed. Cl. 341, 345 (1994) (observing that Congress designed the

Vaccine Injury Table to be “overinclusive.”); a settlement of a Table injury case cannot be viewed as a

concession of Prong 1 of Althen in every case involving the same vaccine and injury. Rather, the Table

makes actual causation irrelevant when an injury meets all the Table criteria. Quinn v. Sec’y, HHS, No.

90-0884V, 1992 WL 183197, at *6-7 (Fed. Cl. Spec. Mstr. July 15, 1992) (when the Table injury criteria

for encephalopathy are met, the fact that the vaccine in question has never been shown to cause the

injury resulting in the encephalopathy is irrelevant). And, even if a case meets the Table injury criteria,

respondent may still defend on the basis of a factor unrelated, but only if the “factor unrelated” is not an

idiopathic or unknown cause. § 13(a)(2)(A); Snyder v. Sec’y, HHS, 553 Fed.Appx. 994, 999-1000 (Fed.

Cir. 2014) (presumption of causation in a Table encephalopathy case rebutted by a factor unrelated—

evidence of genetic disorder known to cause seizure disorders). Moreover, a concession by respondent

in one case does not constitute a concession in another, as science and medicine are not immutable, and

evidence filed in one case may not be filed in another case. For example, a concession that the measles

vaccine can cause an encephalopathy occurring within five to 15 days of a vaccination is not a

concession that it can do so at times shorter or longer. Shyface, 165 F.3d at 1351 (quoting the

legislative history of the Vaccine Act asserting that a similarity to conditions or time periods in the Table

would not be sufficient to demonstrate vaccine causation). Here, respondent’s expert conceded that

regression or decompensation had been observed to occur in conjunction with febrile or viral illness in

those with mitochondrial or metabolic disorders. He did not concede that such events occurred in

conjunction with a vaccination or that such illnesses could trigger or aggravate an underlying

mitochondrial disorder or dysfunction.

37

v. Metabolife Int’l, Inc., 401 F.3d 1233, 1244 (1th Cir. 2005) (additional internal citations

omitted).

Another study reported the “onset of clinical symptoms [seizures in both] was

temporally associated with vaccination” in two of the 112 children in the study, which

looked at children with severe progressive neurological impairments. Verity, Res. Ex. K

(the PIND study) at 436. The authors noted that there was some evidence of a fever in

one child and the other was febrile on admission and had evidence of a Norwalk viral

infection at the time of onset. Id. at 436. However, the authors drew no conclusions

regarding any role of vaccination, illness, or fever in the activation or triggering of the

disorders.

No other evidence that illness could trigger a dormant mitochondrial disorder

appears in this record.77

b. Vaccination or Vaccination with Fever as a Triggering or Aggravating

Event.

Assuming arguendo that a dormant mitochondrial disorder can be triggered,

activated, or exacerbated by illness, can a vaccine, with or without fever, perform the

same function as an illness?

Doctor Kendall’s opinion that a vaccination alone can exacerbate or trigger

mitochondrial disease (see Tr. at 342-43 (testifying that when she was a biochemical

geneticist in training, the fact that immunizations can cause “metabolic

decompensations” was “pounded into us”)) represents a significant extension from what

is generally accepted about the causes of such decompensations.78 Doctor

McCandless agreed that sometimes in training, students are told that they should be

careful about giving vaccines to those with mitochondrial disorders, but added that there

was no evidence to support that caution, and that “we’re probably doing a disservice to

our trainees by saying that.” Tr. at 502. He noted that those with urea cycle disorders

are prone to metabolic decompensations, and the only study to look at the relationship

between vaccinations and decompensations in those with urea cycle disorders found no

77 Doctor McCandless testified that “[i]n the laboratory, there’s all kinds of things you can do to samples to

make the mitochondrial function abnormal.” Tr. at 567-68. However, the context of this testimony

indicates that he was not referring to the trigger or activation of a primary mitochondrial disorder, but

rather an external factor affecting the functioning of the mitochondria, causing a secondary mitochondrial

problem. He explained that muscle biopsies performed on children with neurological injuries such as

cerebral palsy often disclose “subtle abnormalities of mitochondrial dysfunction that in the final

interpretation we don’t believe are the primary cause of their neurological disease . . . and so we believe

that that is because there’s some secondary effect on the mitochondrial function.” Tr. at 569-69.

78 Triggering a decompensation or regression in a previously asymptomatic individual is not necessarily

the same as causing or triggering the loss of skills in a person in whom a mitochondrial disorder has

already manifested.

38

evidence of any causal relationship.79 He testified that he was unaware “of any

evidence that would support a vaccine directly causing a decompensation and

deterioration in an underlying mitochondrial disorder,” although he would not say it was

impossible. Tr. at 505.

With the exception of a brief statement about the Poling case by the CDC

director (who plays no role in Vaccine Act proceedings and whose specialty as a

physician was not identified) filed as Pet. Ex. 83, there was no other evidence in this

record that a vaccination alone, unaccompanied by a fever, could trigger the onset of

clinical symptoms of a mitochondrial disorder.80

According to Dr. McCandless, there is no evidence that a mitochondrial disease

or a metabolic illness can be triggered or exacerbated by the hepatitis B vaccine. Tr. at

501-02. He indicated that the possibility that one could be was a topic of discussion,

referring to the Shoffner and Poling articles (Pet. Exs. 68 and 69), but that “it’s not

because those of us who actually do it are that worried about [it].” Tr. at 502.

Vaccination accompanied by a fever, as opposed to vaccination alone, seemed

to play a more central role in Dr. Kendall’s causation theory, because, as she testified,

there was more support for fever causing such regressions and there was support in in

vitro studies81 for increased temperature adversely affecting mitochondrial function. Tr.

at 303-04. The presence of fever helped explain why the theory of increased energy

demands would apply to A.H.T.’s case and why the hepatitis B vaccination was the

triggering event for her subsequent symptoms. See Tr. at 335 (testifying that the

vaccination caused fever); 342, 352 (fever is a stressor in metabolic disorders); 343,

352 (unfiled in vitro studies associating heat with diminished energy production in

mitochondria); 352-53 (damage as a result of the lack of energy producing central

nervous system symptoms within hours to days).

Although this chain of events fits Dr. Kendall’s theory about the role of increased

energy demands, there was little evidence to support her assertion that vaccination

alone could activate or worsen a mitochondrial disorder. At best, there were articles

mentioning the possibility that vaccines could exacerbate disorders involving inborn

79 Doctor McCandless referenced the Morgan study, Res. Ex. I, for this point. Tr. at 503. He

acknowledged on cross examination that this was a small study, like the others filed in this case, and

characterized it as a pilot study, not a definitive one. Tr. at 516-17. He disagreed with petitioner’s

counsel that the study showed a disproportionate number of adverse events (hyperammonemic episodes)

after hepatitis B vaccinations than other vaccinations. Tr. at 518-22. He supported the conclusion of the

study’s authors that additional research on vaccine safety in children with a variety of inborn errors of

metabolism should be performed. Tr. at 521-22.

80 Petitioner’s post hearing brief began with a quote from the former Director of the Centers for Disease

Control and Prevention, Dr. Julie Gerberding, filed as Pet. Ex. 83, commenting on the Poling case. Pet.

Br. at 1. The commentary was prefaced by Dr. Gerberding’s statement “I don’t have all the facts because

I still haven’t been able to review the case files myself.” Pet. Ex. 83 at 2519.

81 None of these studies were filed. Tr. at 343.

39

errors of metabolism.82 The one study filed that actually examined the role of

vaccination in metabolic decompensations contradicted her position that vaccines

caused decompensations.83

Even the support for vaccination accompanied by a fever as an aggravating

event was scant. The Poling case report noted the presence of a fever. And, as the

title of the Shoffner case study suggested, fever was a prominent factor in the causation

analysis postulated by Dr. Shoffner. Doctor Kendall identified both of these articles as

supportive of her opinion that the hepatitis B vaccine was responsible for A.H.T.’s

condition. See Pet. Ex. 79 at 2497 (citing to the Shoffner and Poling articles in stating

that A.H.T.’s “exposure to the [h]epatitis B vaccination aggravated a pre-existing

condition with subsequent onset of clinical symptoms and regression” and noting that

this process was “documented and reported by several groups, noting a precedent for

this association”). I note the overlap of Dr. Shoffner as an author of both of the articles

Dr. Kendall cited in support of her opinion, suggesting that the “several groups” cited

were actually part of the same group.

The Shoffner article, Pet. Ex. 68, was not supportive of Dr. Kendall’s opinion that

a vaccine alone could trigger onset of a mitochondrial disorder. This very small study

looked retrospectively at 28 patients with co-morbid diagnoses of autism and

mitochondrial disease. Pet. Ex. 68 at 429. About 61% (17 of 28) of the children studied

were said to have experienced an “autistic regression” (“defined as the loss of

developmental skills that included speech, receptive skills, eye contact, and social

interests in individuals”)—a higher percentage of regression than commonly reported in

those with ASD. Id. at 430. The authors also reported that 12 of the 17 children

experienced an autistic regression within two weeks of a febrile episode. Id.

Vaccination, without any associated fever, was not associated with regression. Id. at

431.

82See, e.g., Kinsley, Pet. Ex. 70. The authors conducted a literature review to find recommendations for

or against vaccination of children with specific types of inborn errors of metabolism. In most disorders,

the full schedule of vaccinations was recommended, albeit with the caution to closely monitor for fever in

some. See id., Tables 1-4. Live viral vaccines were the only contraindicated vaccines and then only in

those children with severe combined immunodeficiency disorders. Id., Table 1.

83 Morgan, Res. Ex. I, was a retrospective investigation to determine if children with urea cycle disorders

had an increased risk of hyperammonemic episodes after vaccination. Patients with such disorders

“typically experience recurrent hyperammonemic episodes (HAEs) during periods of excessive protein

intake or catabolic stress. Id. at e1148. Petitioner quoted another sentence from this description of the

rationale behind the study in her post hearing brief at 3: “Immunizations may mimic infections, causing

similar, typically milder inflammatory and metabolic responses.” Morgan, Res. Ex. I at e1148. However,

this was a statement of the hypothesis being tested in the study, not the conclusions drawn from the

evidence found. The authors found no evidence to support the hypothesis that childhood vaccine

exposure triggers HAEs in children with [urea cycle disorders].” Id. at e1151. Hepatitis B was among the

vaccines administered to the study population. Id. at e1149. The authors concluded that these results

likely had reassuring implications for other medically vulnerable children, but recommended additional

research focusing on vaccine safety with other inborn errors of metabolism, including mitochondrial

disorders. Id. at e1152.

40

Doctor McCandless characterized the Shoffner study authors as saying that

vaccines can cause inflammation, which in turn can cause autistic regression. Tr. at

503-04. He thought this hypothesis merited additional study, but that the Shoffner and

Poling papers Dr. Kendall relied upon did not “really prove what they claim or purport to

be proving. And, if you read them carefully, they’re not really claiming [a causal

association].” Tr. at 504.

Aside from Dr. McCandless’ criticisms, I note that the Shoffner study relied upon

a very small sample, making it difficult to assign it much weight.84 Additionally, the lack

84 In recent Vaccine Act cases, Federal Circuit judges have expressed concern about special masters’

reliance on small studies involving rare events, perhaps because the studies may not be sufficiently

powered to detect the events being studied. Paluck, 2015 WL 2403354, at *8-9 (finding that the special

master erred in determining a period of onset for symptoms of neurodegeneration using only articles and

a case study containing very few participants, but relying on the Poling and Shoffner studies as evidence

supporting Althen’s first prong); Koehn v. Sec’y, HHS, 773 F.3d 1239, 1243 (Fed. Cir. 2014) (questioning

the special master’s reliance on a study insufficiently powered “to produce statistically significant results”).

The “power” of a study to detect events is one factor in determining how much weight to give such

studies. Reference Manual on Scientific Evidence, Federal Judicial Center, 2011(3d ed.) at 218-19. The

concern about small studies expressed by the Circuit judges is one shared by special masters. However,

in the traditional toxic tort case, plaintiffs rarely prevail without epidemiological evidence showing a

relative risk (odds ratio) of 2 or greater, both to establish general causation (the “can it cause?” query)

and that the toxic substance is more likely than not the responsible agent in the case at bar (the “did it

cause?” query) by preponderant evidence. Id. at 217 n.14 (citing McClain v. Metabolife Int’l, Inc., 401

F.3d 1233, 1244 (11th Cir. 2005) (additional internal citations omitted)). Toxic tort cases are very similar

to Vaccine Act cases in the scientific subject matter, the lack of definitive proof of a substance’s effects on

the human body, and in the application of the preponderant evidence standard. Unlike toxic tort litigation,

a study involving an odds ratio of 2 or greater is rarely, if ever, seen in contested Vaccine Act causation in

fact cases. Respondent routinely concedes causation or settles at close to full value in cases where the

epidemiology is far less definitive. Cases involving influenza vaccine and Guillain Barré syndrome do not

have epidemiology showing a relative risk greater than 2, but the vast majority of such cases are settled.

See, e.g., Jones v. Sec’y, HHS, No. 14-1007V, 2015 WL 2359064, at *1 (Fed. Cl. Spec. Mstr. Apr. 23,

2013) (typical of settlements routinely seen in influenza-Guillain Barré cases). Respondent has agreed to

settle cases where the available proof of vaccine causation is even lower. See, e.g., Tompkins v. Sec’y,

HHS, No. 10-261V, 2013 WL 3498652, at *2 (Fed. Cl. Spec. Mstr. June 21, 2013), motion for rev. denied,

117 Fed. Cl. 713 (2014) (recounting the procedural history of the execution of a settlement agreement in

the case (rendered void by the death of the vaccinee from unrelated causes)). Tompkins later proceeded

to hearing on petitioner’s causation in fact claim, and in the subsequent decision, I ruled that petitioner

had failed to produce preponderant evidence, based in part on the epidemiological evidence regarding

both influenza and tetanus vaccines and the lack of a causal association of the tetanus vaccine with

Guillain Barré syndrome.

In a Program where Daubert is not used to exclude evidence or experts, causation of rare

conditions is often alleged, and there is little evidence on general and specific causation other than

opinions. Special masters often discuss the evidence filed and relied upon by a party as a part of their

statutory mandate to consider the record as a whole. They may accept less definitive epidemiology as

some support for a causation opinion, but rarely does a special master rely upon epidemiology alone.

Evidence from small studies may be the only evidence available to support or undercut an opinion on

causation. When there is no support for a causation theory other than the expert’s own ipse dixit, a judge

in another court may refuse to admit the testimony (Joiner, 522 U.S. at 146) (citing Daubert, 509 U.S. at

589), but a special master is not similarly constrained by the federal rules of evidence. In the OAP test

cases, the special masters heard evidence from the petitioners on theories that other state and federal

courts refused to admit, based on Daubert and Frye v. United States, 293 F. 1013 (D.C. Cir. 1923). See

Blackwell v. Wyeth, 971 A.2d 235 (2009); Doe v. Ortho-Clinical Diagnostics, Inc. 440 F. Supp. 2d 465

41

of explanation of the methodology used makes reliance on the study problematic. The

Shoffner paper did not clearly indicate when mitochondrial disease was diagnosed in

the patients; thus, it is impossible to determine if the autistic regression occurred prior to

or after the onset of mitochondrial disorder symptoms or diagnosis. See Tr. at 598 (Dr.

McCandless commenting that the article did not explain how or when the mitochondrial

disorder diagnosis was made). The Shoffner study did not reflect whether the

regression was reported contemporaneously, was pulled from later histories in the

participants’ medical records, or was elicited from interviews of the study participants’

parents.85 It appears from comments about the group with fever that either a records

review or some form of interview was conducted.86 Shoffner, Pet. Ex. 68, at 431.

The authors of the Shoffner study acknowledged some limitations themselves.

They “did not investigate changes that could be important in the induction of regression

such as dehydration, hypoglycemia, decreases in substrate ability to oxidative

phosphorylation, and other metabolic abnormalities such as fatty acid oxidation

(M.D. N.C. 2006); Redfoot v. B.F. Ascher & Co., No. C 05-2045 PJH, 2007 WL 1593239 (N.D. Cal. June

1, 2007).

I emphasize that I am not requiring epidemiological evidence in this (or any other) case, but I

must consider the epidemiological evidence the parties filed as part of the statutory requirement to

consider the evidence as a whole. When two well-qualified experts testify contradictory to one another on

vaccine causation, support (or lack thereof) in the scientific literature is one factor identified in Daubert

itself as a matter to consider in deciding if the expert testimony is reliable. Daubert, 509 U.S. at 596; see

also Caves v. Sec’y, HHS, 100 Fed. Cl. 119, 133-34 (2011) (an expert may testify without medical

literature support the opinion, but such experts are rarely persuasive)

85In the OAP test cases, considerable doubt about the validity of later-reported regressions was noted,

particularly in view of the widespread information about the purported link between MMR vaccines and

onset of autistic symptoms or loss of skills. Dwyer, 2010 WL 892250, at *36, n.163, *169; Snyder, 2009

WL 332044, at *44, *137. In my own experience as a special master, with close to 1700 autism cases on

my docket, I have read medical records of many children who reportedly experienced an autistic

regression at a particular time, usually proximate to a vaccination, as reported in a later history, the

petition, or affidavits. When the contemporaneous medical records and histories more proximate to the

events in question were examined, the regression, if any, did not occur as reported in the vast majority of

cases. Conflation of events to place their occurrence close in time to a possible cause has been quite

common in the OAP cases, although, with rare exceptions, it does not appear that the conflation was

deliberate. See Hodges v. Sec’y, HHS, 9 F.3d 958, 961 (Fed. Cir. 1993) (noting that Congress

contemplated the special masters would use their accumulated expertise in the field of vaccine injuries to

judge the merits of individual claims). Using parental recall to establish that a regression occurred

instead of contemporaneous medical records reporting such a regression is a significant flaw in the

methodology. Based on the information provided in the Shoffner paper, Pet. Ex. 68, it is impossible to

determine what the authors relied on to determine that a regression had occurred in close temporal

proximity to a febrile episode.

86 The reference to the degree of fever includes the qualifier “as reported by parents,” which could mean

interviews as a part of the study, a review of contemporaneous records, or a review of later histories in

the medical records. However, the authors also commented that the “precise fever duration was difficult

to ascertain because patients were usually managed in the home.” Shoffner, Pet. Ex. 68, at 431. This

comment suggests that the presence or absence of fever around the time of regression was based on

parental recall.

42

dysfunction.” Shoffner, Pet. Ex. 68 at 432. The authors also commented: “In our

patients with mitochondrial disease and autism spectrum disorders, the vaccines did not

appear related to the neurological regression.” Id. Thus, this article is a thin reed upon

which to hang Dr. Kendall’s opinions that vaccines, with or without fever, can trigger

onset of a mitochondrial disorder or cause mitochondrial dysfunction.

c. Logical Connection and Timing.

Moving from theory to the logical connection between vaccination and onset of

A.H.T.’s symptoms, Dr. Kendall testified that A.H.T.’s irritability and inconsolability were

evidence that she experienced “some encephalopathy, some altered neurological

change” after the vaccination Tr. at 329-30, 334-35. She did not explain how this

encephalopathy could be followed by apparently normal growth and development, with

onset of behavioral symptoms many months later. On cross examination, she

acknowledged that irritability and inconsolability were non-specific symptoms that could

be caused by factors other than an encephalopathic event. Tr. at 336. In response to

my questions, she agreed that they might represent symptoms of colic, rather than an

encephalopathy reflecting some brain injury. Tr. at 383.

Her conclusion that the vaccination triggered or otherwise activated A.H.T.’s

underlying mitochondrial disorder appeared to focus on the lack of any other

explanation for her symptoms. When asked if A.H.T.’s “reaction to the [h]epatitis B

vaccination was the triggering event for this child that caused her to become

symptomatic,” she testified that “certainly there does not seem to be any other

mechanism in place, and what I mean by that is there’s no other documented illness,

there’s no other documented trigger, and there certainly seems to be no period of

normalcy, as was kind of explained in detail by a lot of the questions posed to [A.H.T.’s]

parents and other witnesses. So, yes, it appears that that was an aggravating event for

her.” Tr. at 330-31. The lack of any other cause and a presence of a temporal

connection are not sufficient to establish that the vaccine was responsible, either

separately or together. See Lalonde, 746 F.3d at 1341 (“a temporal correlation alone is

not enough to demonstrate causation”) (citing Moberly, 592 F.3d at 1323); Hibbard v.

Sec’y, HHS, 698 F.3d 1355, 1366 (Fed. Cir 2012) (rejecting the assertion that lack of

any other identified cause can demonstrate vaccine causation, even when the vaccine

in question has been associated with the injury claimed and the temporal relationship is

appropriate).

Although Dr. Kendall did not specifically testify that the autistic-like symptoms

and developmental delays that A.H.T. demonstrated 15-17 months after vaccination

were also caused by activation of the underlying mitochondrial disorder, the last two

paragraphs of her expert report so indicate. Pet. Ex. 79 at 2497; see also Tr. at 329-30.

Because these symptoms occurred so long after the vaccination, they must derive from

an injury that occurred shortly after the vaccination in order to find the vaccination

responsible, based on her “hours to days” testimony on timing. Whether this is the

result of the “activation” or triggering of the mitochondrial disorder or of some damage

43

(see Tr. at 330) caused by the initial activation was not set forth clearly in testimony or

expert report.

Appropriate timing, like the rest of Dr. Kendall’s causation theory, is based on the

Poling and Shoffner articles. However, there are many significant differences between

the facts of A.H.T.’s case (even accepting the facts relied upon by petitioner and Dr.

Kendall) and those of the Poling child and the children discussed in the Shoffner article.

Not only were there differences in the timing of onset (A.H.T.’s autistic-like symptoms

occurred long after the vaccination) and the strength of the mitochondrial diagnosis,

both articles discussed “autistic regression,” and Dr. Kendall agreed that A.H.T. did not

experience an autistic regression at any point. Tr. at 350-55; see also Res. Ex. G at 2

(Dr. McCandless discussing Dr. Kendall’s reliance on these two journal articles and

noting that the medical records show no deterioration in A.H.T.’s neurological status,

loss of developmental milestones, or any plateau in A.H.T.’s neurological development).

2. Brain Inflammation Theory.

Petitioner’s reliance on the brain inflammation theory discussed by Dr. DeMio did

not become clear until late in the hearing. During his cross-examination of Dr.

Wiznitzer, Mr. Downing attempted to clarify petitioner’s causation theory. He initially

indicated that the hepatitis B vaccine produced systemic inflammation, based on the

presence of the fever. Tr. at 678-81. In response to a clarifying question by Dr.

Wiznitzer, Mr. Downing indicated that brain inflammation was a necessary part of the

theory. Tr. at 682. It does not appear that brain inflammation was part of Dr. Kendall’s

theory (or a part of the medical literature upon which Dr. Kendall’s theory was based).

The term “brain inflammation” was never used by Dr. Kendall in her testimony. The

closest she came to talking about inflammation of any kind was in response to a

question:

Q: Dr. Kendall, is it biologically possible for an immunological or

inflammatory trigger to aggravate an underlying latent mitochondrial issue

to the point where the individual becomes symptomatic?

A: Yes.

Tr. at 303. However, the causal mechanism she identified as causing the injury was not

inflammation itself; it was inability of the defective mitochondria to cope with increased

stress, causing some unspecified form of damage. Tr. at 352-53. Some of the

stressors that she identified as possible triggers of a mitochondrial regression, which

included surgery and certain drugs, would be unlikely causes of brain inflammation.

The ‘brain inflammation” theory has its roots in the testimony of Dr. DeMio, but it

was not explicitly raised in his February 2012 statement. In that statement, he

commented that he had treated A.H.T. for numerous medical problems, “including those

of the central nervous system, metabolism, the immune system, and the gastrointestinal

system.” Instead of the term “brain inflammation,” he opined more generally that she

had “brain damage.” Pet. Ex. 62 at 2356. However he did not offer any theory as to

44

how the brain damage occurred. He merely described the temporal relationship as “an

appropriate time course.” Id. at 2357. In view of the alleged regression when A.H.T.

was one week old and onset of ASD-type symptoms at around 18 months of age, some

further explication of the lengthy temporal relationship was necessary.

Doctor DeMio’s statement paid lip service to the mitochondrial disorder diagnosis

by attributing improvement in the many problems he identified (“abnormally low ability to

do intellectual tasks, . . .abnormal thinking . . .cannot function normally in settings with

family and peers, . . .abnormal gait, . . .abnormal play and social interactions, . .

.abnormal obsessions, . . . abnormal oppositionality”) to the “mitochondrial treatment”

she received. Pet. Ex. 62 at 2356-57 (setting out four bullet points, each concluding

that some aspect of A.H.T.’s medical issues had improved with mitochondrial

treatment). However, his earlier opinions and treatment of A.H.T. had focused on the

inflammation caused by toxins and presumed immune issues that are central to a

biomedical approach to treating autism symptoms,87 and mitochondrial treatments such

as those A.H.T. received would not likely improve either inflammation or immune

system problems. Indeed, as the two mitochondrial specialists acknowledged, the

available treatment for mitochondrial disorders does not improve symptoms of those

disorders in most cases. Tr. at 375-77, 460-61; see also

This text is long and has been trimmed here. Open the source document for the complete record.