Anderson v. Secretary of Health and Human Services

Case 1:02-vv-01314-UNJ Document 106 Filed 11/01/16 Page 1 of 41

In the United States Court of Federal Claims

OFFICE OF SPECIAL MASTERS

No. 02-1314V

(To be Published)

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

BRUCE ANDERSON and *

DONNA ANDERSON, * Special Master Corcoran

as parents and natural guardians of *

R.A., a minor, * Filed: November 1, 2016

*

Petitioners, * Entitlement Decision; Measles,

v. * Mumps, and Rubella (“MMR”);

* Autism Spectrum Disorder (“ASD”);

SECRETARY OF HEALTH * Mitochondrial Disease

AND HUMAN SERVICES, *

*

Respondent. *

*

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

Ronald Homer, Conway, Homer & Chin-Caplan, P.C., Boston, MA, for petitioners.

Jason Bougere, U.S. Department of Justice, Washington, DC, for respondent.

DECISION1

On October 1, 2002, Bruce and Donna Anderson filed a petition on behalf of their

child, R.A., seeking compensation under the National Vaccine Injury Compensation

Program (the “Vaccine Program”).2 The Andersons sought to establish that the measles,

mumps, and rubella (“MMR”) vaccine that R.A. received on December 13, 1999,

exacerbated an underlying mitochondrial disorder, in turn causing him to experience a

1

Because this decision contains a reasoned explanation for my action in this case, it will be posted on the

United States Court of Federal Claims’ website, in accordance with the E-Government Act of 2002, 44

U.S.C. § 3501 (2012). As provided by Vaccine Rule 18(b), each party has 14 days within which to request

redaction “of any information furnished by that party: (1) that is a trade secret or commercial or financial in

substance and is privileged or confidential; or (2) that includes medical files or similar files, the disclosure

of which would constitute a clearly unwarranted invasion of privacy.” Vaccine Rule 18(b). Otherwise, the

entire decision will be available to the public.

2

The Vaccine Program comprises Part 2 of the National Childhood Vaccine Injury Act of 1986, Pub. L. No.

99-660, 100 Stat. 3758, codified as amended, 42 U.S.C. §§ 300aa-10 through 34 (2012) (“Vaccine Act” or

“the Act”). Individual section references hereafter will be to § 300aa of the Act.

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developmental regression ultimately manifesting as an Autism Spectrum Disorder

(“ASD”).

A hearing was held on December 8-9, 2015, and in the months following the parties

submitted post-hearing briefs. Having completed my review of the evidentiary record and

the parties’ filings, I hereby DENY Petitioners’ request for compensation, for the reasons

stated below.

I. FACTUAL BACKGROUND

The record in this case consists of the following: R.A.’s medical records; an

affidavit from R.A.’s father (co-petitioner Bruce Anderson), as well as his live testimony;

the written reports and testimony of two experts (one for each side); and medical or

scientific literature submitted by the parties in support of their respective positions. I have

reviewed the entire record as required by the Vaccine Act. Section 13(a)(1).3

A. R.A.’s Early Medical History

R.A. was born on December 10, 1998, following a normal pregnancy and delivery

by caesarean section, and shortly thereafter was assessed as a well-child at an early

pediatric visit approximately two weeks later. Pet’rs’ Ex. 2 at 10, 15; Ex. 5 at 77. In the

following months, R.A.’s pediatrician, Laura Beverly, M.D., at Children’s Medical Group,

P.A., was consulted regarding various parental concerns, including bacterial and viral

infections. See, e.g., Pet’rs’ Ex. 5 at 73-74 (R.A. seen for yeast infection); id. at 72 (seen

for cold symptoms and a rash); id. at 67-68 (mother reported R.A. vomiting with fever). In

the first year of his life, R.A. received several routine childhood immunizations, in

accordance with the vaccination schedule set forth by his doctor.4

3

The medical records in this case are voluminous, and include many records pertaining to R.A.’s post-

vaccination treatment that bear only tangentially on the issues to be resolved in this entitlement proceeding,

since they do not relate to the causal effect of the relevant vaccines. Accordingly, I do not discuss all such

medical records in detail, but instead focus on what both sides have identified as the most significant

records relevant to the causation issues presented herein. See Paterek v. Sec’y of Health & Human Servs.,

527 Fed. App’x 875, 884 (Fed. Cir. 2013). The same goes for the extensive medical literature submitted by

both sides; I have reviewed all such literature filed in preparing my decision, even if each individual piece

of literature is not specifically discussed in this decision. Moriarty v. Sec’y of Health & Human Servs., No.

15-5072V, 2016 WL 1358616, at *5 (Fed. Cir. Apr. 6, 2016) (“[w]e generally presume that a special master

considered the relevant record evidence even though he does not explicitly reference such evidence in his

decision”) (citation omitted). A meaningful discussion of all of the literature offered in this case would double

or triple the size of this decision, without providing any further illumination as to the reasoning behind it.

4

Thus, on January 13, 1999, R.A. received his first Hepatitis B (“Hep. B”) vaccination. Pet’rs’ Ex. 5 at 7. On

February 15, 1999, R.A. received several additional vaccines, including: a second Hep. B vaccination; the

2

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On February 15, 1999, R.A. had a two-month well-child visit where he was reported

to smile, lift his head, and was noted as being active, alert, and healthy. Pet’rs’ Ex. 5 at

73-74. R.A. again saw his pediatrician in March 1999 after his mother reported thrush,

cold symptoms for nine days, and a rash on his face. Id. at 72-74. R.A. was diagnosed

with a viral infection. Id. at 72. By his next well-child visit on April 5, 1999, however, he

was reported as healthy. Id. at 71.

R.A. next saw his pediatrician for his six-month well-child visit on June 2, 1999,

where he was reported as playful and healthy. Pet’rs’ Ex. 5 at 70. Two months later, in

August 1999, R.A. was reported as having a fever and vomiting, but no diarrhea. Id. at

67. R.A. was taken to the hospital for gastroenteritis on August 11, 1999. Id. at 68.

However, at his next well-child visit on September 9, 1999, R.A. was again characterized

as healthy and active. Id. at 67.

B. December 13, 1999 Vaccination and Purported Reaction

R.A. returned to the pediatrician for his one-year well-child visit on December 13,

1999. Pet’rs’ Ex. 5 at 66; Tr. at 12. At this time, R.A. received his first MMR and Varicella

vaccinations. Pet’rs’ Ex. 5 at 7. Records from the visit indicated that R.A. continued to be

characterized as healthy and normal in development. Id. at 66. Six days later, on

December 19, 1999, R.A.’s mother telephoned the pediatrician reporting that R.A. had

been running a high fever (103.3 degrees on the prior day) and was slightly congested,

but otherwise generally happy. Id. at 63. R.A. was therefore brought back to his

pediatrician the next day, December 20, 1999, and the Andersons reported that R.A. had

been suffering from a runny nose for several days, followed by a high fever for only the

past day. R.A.’s temperature at that time was 101.6 degrees, but the examination notes

state that R.A. was otherwise alert and awake with clear rhinorrhea and nasal congestion.

Id. R.A. was diagnosed with “viral syndrome/viral URI [upper respiratory infection.].” Id.

There is no mention made of a relationship between R.A.’s viral episode and a vaccine

as of this pediatric visit.

That evening (the seventh day after R.A. received the MMR vaccine), R.A.’s fever

spiked to over 105 degrees, according to Mr. Anderson’s trial testimony. Tr. at 13. After

combination vaccine DTP-Hib, which includes vaccinations for diphtheria, tetanus, pertussis (“DTP”), and

Haemophilus influenza type b (“Hib”); and an oral polio vaccine. Id. Then, on April 5, 1999 R.A. received a

second DTP-Hib vaccine and a second oral polio vaccine. Id. On June 2, 1999, R.A. received three more

vaccinations: a third DTP vaccine, a third Hib vaccine, and a third oral polio vaccine. Id. On September 9,

1999, R.A. received his third Hep. B vaccination. The record sets forth no particular instance after any of

these vaccinations when R.A. experienced a notable reaction.

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contacting the pediatrician again, the Andersons were instructed to take R.A. to the

emergency room, and they did so. Id. at 13-15. R.A.’s temperature at that time was

officially recorded to be 105.1 degrees, and the emergency treaters took blood cultures

and started him on an antibiotic, but he was not admitted overnight and went home. Pet’rs’

Ex. 19 at 2, 5-6; Tr. at 13. The Andersons brought R.A. back to the pediatrician the next

day, on December 21, 1999, and although he was still running a fairly high fever (102.2

degrees), he was nevertheless described as awake and alert with clear rhinorrhea. Pet’rs’

Ex. 5 at 64. The pediatrician opined that R.A.’s illness was “probably viral,” but

recommended continuing antibiotics pending the result of the blood cultures. Id.

R.A.’s fever thereafter persisted for roughly two days, abating around December

22, 1999. Tr. at 15. That day, in a telephone call with the pediatrician, R.A.’s mother

reported that he had slept all afternoon, was eating and drinking well, and doing “much

better.” Pet’rs’ Ex. 5 at 63.

C. R.A.’s Health History in Early 2000

The contemporaneous records do not document any subsequent progressive

worsening of R.A.’s overall health in the six months immediately following his December

1999 vaccinations, nor do they set forth treater concerns about any related symptoms.

However, R.A. was taken back to the pediatrician several times in the ensuing period,

and it is the Petitioners’ allegation that these subsequent visits were precipitated by a

reaction to the MMR vaccination.

Thus, in January 2000, R.A. was seen by his pediatrician three times. First, on

January 20, 2000, R.A. was reported to have had a cold for two days with pink, swollen

eyes, and was diagnosed with conjunctivitis. Pet’rs’ Ex. 5 at 62. Next, on January 28,

2000, R.A. was diagnosed with exudative tonsillitis after presenting with a fever, and

being reported as clinging, fussy, with a decreased appetite and bright red and white

tonsils. Id. at 61. Later, on January 30, 2000, R.A. was taken back to the pediatrician due

to discovery of a red area at the base of his penis, and was diagnosed with a probable

penile adhesion due to pulling. Id. at 60. None of the records from these visits, however,

link any of the diagnosed conditions or illnesses with the MMR vaccine, and the records

filed do not link them as part of a progressive set of related symptoms.

There are no medical records reporting any illnesses for R.A. in February 2000.

On March 3, 2000, R.A. was taken to the pediatrician with a fever and a sore throat, and

diagnosed with pharyngitis and viral-like rash. Pet’rs’ Ex. 5 at 59. Later that same month,

on March 22, 2000, R.A. again saw the pediatrician for his fifteen-month well-child visit.

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Id. at 58. At this time, however, R.A. was reported as being healthy, developing and

walking well for the past two months, and saying about five words. Id. at 58.

Six weeks later, in May 2000, R.A. went to his pediatrician following a visit to the

emergency room due to a fever and lethargy. Pet’rs’ Ex. 5 at 57. At the follow-up visit on

May 30, 2000, R.A. was still running a fever, and was reported to be suffering from

diarrhea for two days. Id. R.A. was taken to the pediatrician on two more occasions that

same month, either because of recurring diarrhea or pharyngitis. Id. at 55-56; Pet’rs’ Ex.

41 at 1.5

D. Concerns about R.A.’s Development

The first medical records hinting at possible developmental concerns for R.A. are

not found until June 2000. At that time, R.A. was taken to the pediatrician for an 18-month

well-child checkup. Pet’rs’ Ex. 5 at 53-54. In addition to consideration of R.A.’s diarrhea

from the prior month (Id. at 55; Pet’rs’ Ex. 41 at 3), the records from this checkup mention

R.A.’s developmental status. Thus, R.A.’s pediatrician observed his word usage, noting

that R.A. was able to say “hi,” “bye,” and “dada.” Id. R.A. would also come when called,

would look up if asked “where is the moon,” would say “moo” if asked what a cow said,

and had a “good response to no.” Id. Overall, R.A. was deemed a healthy eighteen month-

old, normal in development. Id. at 53. However, two concerns are noted in these records

as well, without characterizing their significance: R.A. did not “really follow commands,”

and he would not point out pictures in books. Id.; Pet’rs’ Ex. 41 at 4. Accordingly, although

the records from this pediatric visit are the first in which any concerns about R.A.’s

development are noted, they are inconclusive in their characterization of that

development.

There is thereafter a multi-month gap in the medical history, with no evidence of

any subsequent doctor’s visits until September 11, 2000, when R.A. underwent his 21-

month well-child visit. The records from that visit described R.A. as a healthy 21-month

old that could sing the vowels, understood “no” and slept well. However, R.A.’s doctor

reiterated prior concerns about R.A.’s following of commands and interactivity first noted

in June, and stated she had “some developmental concerns.” Pet’rs’ Ex. 5 at 52-53. R.A.’s

pediatrician therefore recommended a speech and hearing evaluation. Id. at 51. By his

two-year well-child visit on December 6, 2000, R.A.’s developmental delays had become

more pronounced and self-evident. Id. at 50. Thus, R.A.’s pediatrician reported that R.A.

5

The pediatric records are primarily handwritten and some portions of difficult to read. Petitioners provided

transcribed portions of the pediatric record as Pet’rs’ Ex. 41, but the transcriptions did not include R.A.’s

visit of May 30, 2000.

5

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did not have 20 words despite progress in other areas. Id. at 50. He was recommended

for further evaluation, including genetics testing. Id. However, his health was otherwise

deemed good, and throughout the entirety of 2000, R.A. continued to receive scheduled

vaccinations. Id. at 7.

E. Efforts to Treat R.A.’s Developmental Problems

Once R.A.’s developmental problems were clearly evident, the Andersons began

a comprehensive effort to discern their cause and treat them effectively, seeking input

from a variety of medical specialists including pediatric, neurocognitive, dietary, and

genetic specialists. In the course of their efforts, R.A. underwent numerous behavioral,

genetic, and biological evaluations.6

On January 11, 2001, R.A. was evaluated by Laura Bailet, Ph.D., a neurocognitive

specialist at the Nemours Children’s Clinic in Jacksonville, Florida. Pet’rs’ Ex. 3 at 5-7.

During the initial evaluation, R.A.’s parents provided a history of R.A.’s development,

informing Dr. Bailet that R.A. was generally very healthy, with no significant illnesses,

accidents, or hospitalizations to date. Id. at 5. They also reported that R.A.’s motor

coordination was fair, but characterized his language skills as poor. Specifically, the

Petitioners reported that he had spoken his first words prior to turning one, but since that

time showed very slow language progression. They also noted that, while R.A. could say

a few understandable words, he primarily babbled, pointed, or reached for what he

wanted. Id. at 6. Based upon the recited history, Dr. Bailet recorded that “no history of

frank language regression was reported.” Id. After a second evaluation on January 25,

2001, Dr. Bailet concluded R.A. showed developmental delays and several mild

behavioral characteristics that could be associated with autism. Id. at 30.

R.A. was next evaluated by Daniel Shanks, M.D., a pediatric neurologist, on

January 31, 2001. Pet’rs’ Ex. 3 at 17. Dr. Shanks’s notes record the Andersons informing

him that they had harbored “concerns all along in regard to [R.A.’s] language

development,” but otherwise recounted “no evidence of developmental regression,” as

opposed to a more general failure to progress developmentally. Id. Dr. Shanks also

reported that “[w]ith motor development, [R.A.] has had no significant difficulty other than

being a little bit clumsy but is very loose-jointed.” Id. Dr. Shanks diagnosed R.A. with static

encephalopathy with a communication disorder spectrum, and stated it would be

6

In addition to seeking advice from medical professionals, the Andersons also initiated their own research

into possible causes of R.A.’s developmental delays starting around the winter of 2001. Tr. at 37-38. This

included researching alternative diets such as those set forth in the cookbook Special Diets for Special Kids

by Karyn Seroussi and Lisa Lewis. Tr. at 37-38. The Andersons also conducted their own review of medical

literature on pervasive developmental disorder and autistic spectrum disorder. Tr. at 41; Pet’rs’ Ex. 3 at 38.

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reasonable to consider genetic testing. Id. at 19. Dr. Shanks also noted that R.A.’s “very

limber” joints may have been inherited from his mother’s side of the family, while his “low

tone and ligamentous laxity” could be unrelated. Id. at 18.

R.A. received a genetic evaluation from Pamela Arn, M.D., on February 5, 2001.

Pet’rs’ Ex. 3 at 22-24. The genetic testing revealed normal chromosomes. Id. at 38-39.

However, the records from this evaluation elaborate on the nature and timing of R.A.’s

developmental problems. Dr. Arn’s history noted that R.A.’s mother first became

concerned about R.A.’s development when he was 15 months old (or in March 2000 –

months before the first record evidence of developmental concerns), at which time she

began to observe delays in his verbal and interactive skills. Id. at 22. Dr. Arn also stated

that R.A. showed no other problems with other physical systems. Id. at 23. R.A. was

reported as being a picky eater, but would generally eat foods from all food groups without

difficulty, and he had no current food intolerance. Id. He had not had any seizures or any

neurologic episodes suspicious for seizures. Id. R.A.’s motor milestones were overall

deemed normal, with only his verbal skills characterized as delayed. Id.

R.A. was then evaluated two months later, on April 12, 2001, by Donald George,

M.D., a gastroenterologist at Nemours Children’s Clinic. Pet’rs’ Ex. 3 at 41-43. The

Andersons contacted Dr. George for information and advice relating to dietary control of

behavior. Id. at 41. Dr. George’s report of the visit notes that the Andersons first became

concerned about R.A.’s developmental progress in the fall of 2000 (when R.A. would have

been 20-21 months old). Id. at 41. After conducting their own research, the Andersons

had become interested in the possibility that R.A.’s behavior reflected autistic tendencies,

and began to pursue diet restrictions and other treatments recommended by some of the

independent specialists they had contacted. Id. at 41. Thus, Dr. George reported, R.A.

had been taking a wide variety of supplements, including dimethyl glycine, glutamine,

acidophilus, fluoride, diflucan, and a variety of proprietary vitamins. Id. at 42.

R.A. was next evaluated by Dr. Karoly Horvath, M.D., a pediatric

gastroenterologist, on June 7, 2001. Pet’rs’ Ex. 6. Dr. Horvath performed endoscopies,

biopsies, and microbiologic analysis of body fluid cultures. Id. at 23-35. Dr. Horvath found

no significant abnormalities or pathology from these evaluative tests, however. Id. R.A.

was later seen again by Dr. Bailet on November 12, 2001, when R.A. was 25 months old.

Pet’rs’ Ex. 3 at 61-65. Dr. Bailet concluded that R.A. was currently functioning at an 18-

month level overall in language skills, and scored as moderate-to-severely autistic on the

autism rating scale. Id. at 64.

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Beginning in 2001, R.A. started receiving treatment from Dan Rossignol, M.D. and

Jeffrey Bradstreet, M.D.,7 two doctors associated with the “Defeat Autism Now” (“DAN!”)

project.8 Among the treatments prescribed to R.A. by Drs. Rossignol and Bradstreet were

intravenous infusions of Intravenous Immunoglobulin (“IVIG”), Vitamin C, Secretin,

Solumedrol, and glutathione. Pet’rs’ Ex. 13 at 353. In a justification of these treatments

from a record dated February 6, 2008, Dr. Bradstreet stated that “[R.A.] suffered

neurological, gastrointestinal, and immune system injuries and dysfunction as a result of

vaccines, including but not limited to persistent measles virus infection, post measles

encephalitis, chronic diarrhea, and inflammatory bowel disease (IBD) from his Measles

Mumps Rubella (MMR) vaccination at 12 months of age.” Id. at 876. Notably, this is the

first medical record in which any treater not only connects R.A.’s autism diagnosis to the

MMR vaccine, but places the onset of his developmental symptoms at the time of

vaccination.

7

Dr. Bradstreet was a practicing physician who specialized in children with autism spectrum disorder and

attention deficit hyperactivity disorder, and who espoused the belief that there is a causal link between

autism and the MMR vaccine (particularly due to what he alleged to be toxic amounts of mercury contained

within the vaccine). See, e.g., Hearing before the Committee on Government Reform, June 19, 2002, Serial

No. 107-121, available at https://www.gpo.gov/fdsys/pkg/CHRG-107hhrg82358/html/CHRG-

107hhrg82358.htm (site last visited on October 31, 2016). But treatments promoted by Dr. Bradstreet have

not been proven effective, and even termed dangerous. Trine Tsouderos and Patricia Callahan, Risky

alternative therapies for autism have little basis in science, Chicago Tribune, Nov. 22, 2009 (treatments

such as chelation therapy and hyperbaric chamber therapy sessions are unproven and potentially

dangerous). Dr. Bradstreet committed suicide on June 19, 2015, shortly after his clinic was raided by state

and federal authorities. Michael E. Miller, Anti-Vaccine Doctor behind ‘Dangerous’ Autism Therapy Found

Dead. Family cries foul, Washington Post, June 29, 2015, available at

https://www.washingtonpost.com/news/morning-mix/wp/2015/06/29/anti-vaccine-doctor-behind-

dangerous-autism-therapy-found-dead-family-cries-foul/ (site last visited October 31, 2016).

8

DAN! was composed of doctors and medical professionals who believed, among other things, that autism

could be caused by vaccines. See Dwyer v. Sec’y of Health & Human Servs., No. 03-1202V, 2010 WL

892250, at *165 (Fed. Cl. Spec. Mstr. Mar. 12, 2010). The Autism Research Institute (“ARI”), which was

founded by Bernard Rimland, MD in 1967, created the DAN! Protocol in 1995. Moving Forward: The

Expanding Mission of ARI, Autism Research Institute, http://www.autism.com/expanding_2014 (last visited

October 31, 2016). “DAN! Doctors [were] trained in an approach to autism treatment that begins with the

idea that autism is a biomedical disorder caused by a combination of lowered immune response, external

toxins from vaccines and other sources, and problems caused by certain foods.” DAN! PROTOCOL, Autism

Services and Resources Connecticut, http://www.autismconnecticut.org/dan-protocol (last visited Aug. 5,

2016). Accordingly, DAN! “doctors may recommend treatments including nutritional supplements, special

diets, testing for hidden food allergies, treatment of intestinal yeast or bacterial overgrowth, and

detoxification of heavy metals.” Id.

ARI discontinued the DAN! Protocol in 2011, however, noting that individuals included on the list of

providers were merely doctors who attended training seminars, and there was therefore no way to assure

that such practitioners were providing high quality services. Lisa Jo Rudy, What Was the DAN! (Defeat

Autism Now) Protocol?, Very Well (updated Dec. 30, 2015), https://www.verywell.com/dan-defeat-autism-

now-is-no-more-3971489 (last visited Oct. 31, 2016).

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R.A. was also evaluated for possible seizure disorder in May 2002 following a

reported history of 15 seconds of eyes rolling up and absence. Pet’rs’ Ex. 13 at 702. An

EEG was recorded, which indicated multiple episodes of 3-cycle spikes and waves lasting

less than 1.5 seconds. R.A. was subsequently diagnosed with absence seizures.9 Id.

In 2003, R.A. began receiving care at Progressive Pediatrics, where he received

intramuscular immunoglobulin (“IMIG”) regularly from October 2003 until January 2005.

Pet’rs’ Ex. 4 at 4-35. R.A. also received treatments in a hyperbaric chamber three times

each week during the summer of 2005.10 Id. at 38. R.A. continued to receive care at

Progressive Pediatrics for both sick visits and well-child visits until at least 2010. Id. at 68.

During that time, a diagnosis of “active autism” was consistently noted.11

F. Consideration of Mitochondrial Disorder as Basis for R.A.’s

Condition

Starting in 2001, R.A. was periodically tested for various markers of metabolic

abnormalities, including ammonia, lactic acid, and liver enzymes aspartate transaminase

(“AST”) and alanine transaminase (“ALT”). See Pet’rs’ Ex. 13 at 22-268. Dr. Bradstreet

deemed some results as significant, including evidence of a low free and total carnitine12,

9

Absence seizures or absence epilepsy is characterized by staring spells that can last 1-10 seconds.

http://www.mayoclinic.org/diseases-conditions/petit-mal-seizure/basics/definition/con-20021252 (last

visited Oct. 31, 2016). Absence seizures generally do not elicit the same behavior as grand mal seizures

where the subject falls to the ground, but instead was described by Dr. Cohen, respondent’s expert, as if

“[t]heir circuit-breakers have been resent.” Tr. at 222.

10

Hyperbaric oxygen therapy (which is used to treat a variety of conditions) involves breathing pure oxygen

in a pressurized room or body-sized tube. Tests and Procedures: Hyperbaric Oxygen Therapy, Mayo Clinic

(Nov. 25, 2014), http://www.mayoclinic.org/tests-procedures/hyperbaric-oxygen-therapy/basics/risks/prc-

20019167?B p=1 (last visited Oct. 31, 2016). When an individual is placed in a hyperbaric oxygen therapy

chamber, air pressure is increased to three times higher than normal, permitting the lungs to gather more

oxygen than would be possible at normal air pressure. Id. The individual’s blood then carries this oxygen

throughout the body, which purportedly helps fight infection and promotes healing. Id. However, medical

science has not confirmed that hyperbaric oxygen therapy is an effective autism treatment. Id. Moreover,

although hyperbaric oxygen therapy is generally a safe procedure, it does involve risks, including the

possibility of lung collapse, middle ear injuries, and seizures. Id.

11

Throughout this period, R.A. was receiving a significant number of medications and supplements. As of

July 21, 2008, they included Gamunex immunoglobulin (IVIG), SecreFlo Secretin, Gluthathione and

Cysteine, Zyrtec, Spironolactone, Methyl-B12, Digest Right 1, Nordic Natural Cod Liver Oil, Probiotic

Pearls, Ther-Biotic Complete, Nordic Natural ProEPA, Calcium and magnesium tablets, Child Essence

multi-vitamin, FolaPro, L-Carnitine, Coenzyme Q10, Ester-C, Taurine, Zinc, NasalCrom, and Ayr Saline.

Pet’rs’ Ex. 13 at 461-62.

12

Carnitine is a substance necessary for the digestion of fatty acids. Testing for “free” carnitine tests how

much usable carnitine a subject has and compares it with the total amount in the subject’s body.

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increased lactate13 and increased ammonia14. Pet’rs’ Ex. 13 at 460. However, test results

suggesting the existence of abnormal biochemical markers were inconsistent with other

tests indicating that R.A.’s free and total carnitine, lactate, and ammonia were not, in fact,

elevated. See Pet’rs’ Ex. 13 at 961 (indicating normal free and total carnitine on February

5, 2001), Ex. 13 at 24, 53, 60, 83 (showing normal levels of lactic acid on July 23, 2008;

January 23, 2009; June 1, 2009; and October 1, 2010), and Ex. 13 at 24, 51, 59, 130,

143, 146, 156, 171, 185 (showing normal ammonia on January 20, 2005; August 17,

2005; April 12, 2006; April 28, 2006; June 14, 2006; February 2, 2007; January 23, 2009;

July 27, 2009; and October 1, 2010).

In 2008 – significantly, more than seven years after R.A. had received the MMR

vaccine – R.A. was referred to John Shoffner, M.D., a specialist in mitochondrial

disorders, for an evaluation to determine whether R.A.’s developmental limitations were

attributable to a defect in cellular energetics or another class of metabolic disease. Pet’rs’

Ex. 10 at 15. Dr. Shoffner evaluated R.A. on July 22, 2008 at Medical Neurogenetics in

Atlanta, GA, and conducted a series of tests including muscle biopsies and metabolic

studies, in additional to reviewing R.A.’s medical history. Pet’rs’ Ex. 10 at 15; Pet’rs’ Ex.

9 at 42. The muscle biopsies were performed at the Pediatric Center at Atlanta Outpatient

Surgery Center (see Pet’rs’ Ex. 10 at 26), while the metabolic studies involved samples

taken from R.A. on July 23, 2008 and then analyzed at Medical Neurogenetics, LLC, also

in Atlanta, Georgia. See Pet’rs’ Ex. 9 at 1.

After reviewing the lab results, Dr. Shoffner diagnosed R.A. with a mitochondrial

disease and renal tube dysfunction. Pet’rs’ Ex. 9 at 42. But his diagnosis relied heavily on

what had been recounted to Dr. Shoffner about the timing of R.A.’s developmental

difficulties. Thus, Dr. Shoffner reported (without corroboration from the medical record)

that R.A. had been developing normally until his MMR vaccination at 12 months of age.

Pet’rs’ Ex. 9 at 42; Ex. 10 at 15. Following that, he continued, R.A. developed a high fever,

https://www.urmc.rochester.edu/encyclopedia/content.aspx?contenttypeid=167&contentid=carnitine_total

_free (last visited October 31, 2016). R.A. exhibited low levels of free and total carnitine in samples taken

on April 29, 2008. Pet’rs’ Ex. 13 at 112.

13

Increased lactate was shown in samples taken on April 29, 2008 and June 27, 2008. Pet’rs’ Ex. 13 at

100, 101.

14

Increased ammonia was reflected in several samples, including those taken on December 10, 2001;

January 20, 2005; April 27 2007; April 29, 2008; June 27, 2008; December 22, 2008; and June 1, 2009.

Pet’rs’ Ex. 13 at 52, 64, 99, 111, 126, 184, and 268. Ammonia levels can be significant because they can

act as indirect biochemical markers of mitochondrial dysfunction. See, e.g., D. Rossignol et al.,

Mitochondrial Dysfunction in Autism Spectrum Disorders: A Systematic Review and Meta-Analysis, Mol.

Psych. 17, 290-314 at 292 (2012). Further, according to Petitioners’ expert Dr. Huq, higher levels of

ammonia over a long period of time can also damage the brain. Tr. at 117-18.

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although he acknowledged that it was not associated with any immediately evident

neurological changes. Pet’rs’ Ex. 10 at 15. He then recounted that R.A. had received

another vaccine at 16-17 months of age associated with a fever, and that shortly

thereafter, at 17-18 months of age, experienced a regression of skills including a loss of

speech, motor skills, cognitive ability, and receptive/expressive speech. Pet’rs’ Ex. 10 at

15, Ex. 9 at 42. As already noted, however, no evidence of a second fever, or a

skills/language regression, is found in the medical records already discussed (although

there is evidence of a number of URI-related fevers from the winter and early spring of

2000).

Besides R.A.’s recounted medical history, Dr. Shoffner’s diagnosis relied on

extensive evaluations of various metabolic marker test results, including free and total

carnitine levels, lactose levels, and the concentration of amino acids in R.A.’s cerebral

spinal fluid, blood plasma, and urine. Pet’rs’ Ex. 9 at 4, 5, 25, 31. Dr. Shoffner’s testing

indicated that carnitine levels were normal. Pet’rs’ Ex. 9 at 1. R.A.’s lactate levels as

measured in his cerebral spinal fluid (“CSF”) were also within normal ranges, but slightly

elevated in his plasma. Id. at 5, 26; Tr. at 133-34. R.A.’s amino acid levels showed a

normal profile as measured in his CSF and plasma (Pet’rs’ Ex. 9 at 4, 5, 25, 42), but R.A.’s

urine showed elevations of multiple amino acids, including taurine, glutamine and

cysteine. Ex. 9 at 31. Based on the increased urine amino acids, Dr. Shoffner concluded

that R.A. had a proximal renal tubule defect causing a generalized aminoaciduria15. Pet’rs’

Ex. 9 at 31, 41-42. Dr. Shoffner specifically discounted the possibility that the elevated

levels of amino acids were related to supplements he was taking at the time. Id. at 42.16

Dr. Shoffner also conducted a biopsy of R.A.’s skeletal muscles in order to perform

enzymology tests. In particular, Dr. Shoffner conducted a variety of assays to determine

the activity of various mitochondrial enzymes, referred to as Complexes I through IV, by

testing the functioning of mitochondria found in biopsied muscle tissue samples. Pet’rs’

Ex. 9 at 24; see also Id. at 49 (additional background information regarding mitochondrial

15

Aminoaciduria is an excess of amino acids in the urine. This can be caused by a general excessive level

of a given amino acid in the blood or defective transport mechanisms for amino acids in the renal tubules

of the kidneys. Dorland’s Illustrated Medical Dictionary 61 (32nd ed. 2012) (hereinafter “Dorland’s”).

16

Dr. Cohen testified during the hearing of this matter that R.A.’s elevated amino acids could be attributable

to the supplements he was prescribed - and specifically supplements purportedly not reflected in Dr.

Shoffner’s report, such as taurine or 3-methyl glycine. In fact, however, Dr. Shoffner’s report recognized

that R.A. had been prescribed 975 mg of taurine. See Pet’rs’ Ex. 10 at 17.

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function)17. Only one of the two assays conducted evaluating Complex I activity, however,

suggested reduced enzyme activity. Id. Rather, the Complex I assay results overall fell

within the normal range to a 95 percent confidence interval. Pet’rs’ Ex. 9 at 24. Of the two

assays evaluating Complex IV, only one indicated reduced activity. Id. The study also

showed a reduction in citrate synthase - an important marker enzyme in the mitochondria

that provides a proxy measurement of mitochondrial content in the muscle.18

Dr. Shoffner examined R.A.’s muscle fibers, conducting a physical examination of

them under a microscope, a histochemistry analysis, and an immunochemistry analysis.

Pet’rs’ Ex. 9 at 9, 41. Dr. Shoffner observed a moderate size variation due to atrophy of

one type of muscle fiber, Type II, and increased myofiber lipids. Id. at 9. The histochemical

and immunochemical analyses were unremarkable, however. Id. at 9, 41.

Following the evaluation of R.A.’s laboratory tests and muscle biopsies, Dr.

Shoffner diagnosed R.A. with a “probable oxidative phosphorylation disease,” Complex I

defect, and ASD with proximal renal tubule defect. Pet’rs’ Ex. 9 at 42. Based on the

recommendations of Drs. Bradstreet and Shoffner, R.A.’s supplements were changed to

include substances more targeted to affect mitochondrial function, such as carnitine and

ribose. Tr. at 64-65; Pet’rs’ Ex. 13 at 443.

Dr. Frances Kendall, a clinical biochemical geneticist, also evaluated R.A. and

performed genetic testing on December 30, 2013. Pet’rs’ Ex. 26 at 12. The history section

from the records of this evaluation noted that R.A.’s early development was normal, but

that Petitioners had observed R.A. begin to withdraw socially and lose skills immediately

following his receipt of the MMR vaccine and febrile illness (contrary to the medical

records discussed above, which do not document even incipient concerns about R.A.’s

speech until he was 19 months old). Pet’rs’ Ex. 26 at 1. Dr. Kendall determined that there

were two mutations present in R.A. which have been linked to intellectual disability,

neurodevelopmental disorders, and autism. Id. at 10. However, Dr. Kendall

acknowledged that these variants were of uncertain significance, stating “it is purely

speculative as to whether or not they are causative for [R.A.]”. Pet’rs’ Ex. 26 at 10.

17

Complex I is a term describing a group of proteins in the mitochondria that are integral to the production

of cellular energy. Typically, five protein complexes (referred to as Complex I – V) work in sequence in the

mitochondria to produce cellular energy. See Pet’rs’ Ex. 9 at 48-49.

18

Citrate synthase is an enzyme in mitochondria. Salvatore DiMauro and Eric Schon, Mitochondrial

Respiratory-Chain Diseases, N. England J. Med., 348 (26) at 2657 (2003); Dorland’s at 455. It is used as

a marker enzyme to increase the diagnostic reliability of mitochondrial testing. See Bruce Cohen,

Neuromuscular and Systemic Presentations in Adults: Diagnoses Beyond MERRF and MELAS,

Neurotherapeutics (10) 227-42 at 239.

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After the evaluation by Dr. Shoffner, R.A. experienced improvements in his energy

to the point where he could maintain significant physical activity for 3-6 hours a day. Tr.

at 66-67. Today, R.A. has made advances in his physical and mental development. R.A.

is participating in basketball and enrolled in a high school for high-functioning children.

However, R.A. still goes to speech therapy, and his level of abstract thinking is not as

advanced as others his own age. Tr. at 72-74.

II. TESTIMONY PRESENTED AT HEARING

A. Mr. Anderson

Mr. Anderson provided fact testimony regarding the circumstances of R.A.’s

alleged vaccine reaction and subsequent condition, along with information about R.A.’s

treatment over the past several years.

Prior to R.A.’s 12-month well-child visit on December 13, 1999 at which he

received the MMR vaccine, R.A. appeared to Mr. Anderson to be developing normally -

pointing and gesturing at objects, making eye contact, and vocalizing basic words like

“mama” or “dada.” Tr. at 10-12. Mr. Anderson testified, however, that within a few days of

receiving the MMR vaccination, R.A. became lethargic and had a low-grade fever,

eventually spiking (in several days) to over 105 degrees. Id. at 13. After contacting R.A.’s

pediatrician’s office, the Andersons took R.A. to the emergency room. Id. at 13-15. R.A.’s

fever persisted for roughly two days, and, according to Mr. Anderson, abated around

December 22, 1999. Id. at 15.

Immediately following R.A.’s fever and emergency room visit, Mr. Anderson

observed R.A. to be “low-energy,” “fussy and tired,” and not interested in the toys he

received for Christmas. Tr. at 18-19. Mr. Anderson also stated that R.A. was not

interacting well with family members. Specifically, R.A. was not as engaging in terms of

eye contact, did not want to be hugged or held, and “there was not the quantity and quality

of smiles and laughs that we saw before.” Tr. at 19.

Between January and June of 2000, Mr. Anderson recalled a gradual but

progressively worse change in R.A.’s behavior and development.19 Tr. at 23-26. R.A.

began to avoid eye contact, did not want to be held, and lost interest in books and

gesturing for things he desired. Id. at 24. Mr. Anderson also testified that R.A.’s babbling

19

Mr. Anderson specifically testified that he noticed a change in R.A.’s behavior starting around January

2000, but also admitted that his schedule was extremely busy, and therefore his opportunities to observe

closely changes in R.A. were more limited throughout the early part of that year. Tr. at 9-10.

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gradually started “sounding less like he was trying to speak and becoming more, like,

tantrums or meltdowns or just screaming.” Id. R.A.’s diet became significantly more

limited in this period, a change coinciding with the development of chronic diarrhea

starting around the end of May 2000 and lasting for several years. Id. at 29-31.

Although Mr. Anderson sought to place the onset of R.A.’s developmental

problems in the days and weeks after receipt of the MMR vaccine in December 1999, he

admitted that neither he nor his wife ever raised any concerns with R.A.’s pediatrician in

this time period (consistent with the actual records as discussed above). Tr. at 27-28. Mr.

Anderson attempted to explain this omission by asserting that he and his wife felt that

R.A. would just get better as soon as they could devote more time to him, and therefore

did not see the need to raise the issue with an existing treater. Id. at 28.

At the same time that R.A. was purportedly observed displaying early

developmental problems, Mr. Anderson testified, he was also seen to be in declining

health in other respects. Thus, Mr. Anderson stated that he and his wife had to take R.A.

to the pediatrician regularly for treatment of various ailments, including low-grade fever,

runny nose, and congestion, compared to the time before R.A. received the MMR

vaccination. Tr. at 27.

Following R.A.’s diagnoses of autism, the Andersons began educating themselves

on the disorder by conducting research on the internet, reading books, and attending

educational conferences aimed at parents of autistic children. The first time Mr. Anderson

was introduced to the concept that the MMR vaccine may have contributed to R.A.’s

autism was based on his own research, either upon reading a book by Karyn Seroussi in

early 2001, or after attending a DAN! Conference in April of 2001. Tr. at 84-86. After the

DAN! Conference, Mr. Anderson had several exchanges with R.A.’s pediatrician, in which

he disputed her assertions about the comparative safety of vaccines. Id. at 87.

By the end of 2000, the Andersons had begun a comprehensive treatment program

for R.A., including speech and occupational therapy. Tr. at 36. The Andersons also

pursued various therapies on their own based on their personal autism treatment

research (and concordant views about it). For example, the Andersons decided to remove

gluten and casein from R.A.’s diet in early 2001. Id. at 37-39. They also began

administering various medications and supplements, such as cod liver oil, probiotics, and

colostrum for his diarrhea. Id. at 45.

Mr. Anderson asserted his overall belief that the care and treatment R.A. had

received had resulted in slow and gradual improvement in his development and overall

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health. Tr. at 38-41, 46-47. Mr. Anderson also asserted that R.A.’s therapists and

pediatrician had themselves observed these improvements. Id. at 38-40, 46-47, 66-68.

B. Petitioners’ Expert - Dr. Ahm Mahbubul Huq

Ahm Mahbubul Huq, MBBS, Ph.D., offered two expert reports plus testimony at

the entitlement hearing in support of Petitioners’ claim. See generally Pet’rs’ Ex. 27,

Medical Expert Report of Ahm Mahbubul Huq, MBBS, Ph.D., dated September 21, 2014

(the “Huq Rpt.”); Pet’rs’ Ex. 29, Supplemental Medical Expert Report of Ahm Mahbubul

Huq, MBBS, Ph.D., dated May 11, 2015 (the “Huq Supp. Rpt.”); Tr. at 90-205. Overall,

Dr. Huq theorized that R.A.’s MMR vaccination led to a febrile illness and significantly

aggravated R.A.’s alleged underlying mitochondrial dysfunction (which predisposed R.A.

to further deficits in cellular energy metabolism), resulting in an encephalopathy with

features of autism spectrum disorder. Huq Rpt.at 6.20

Dr. Huq is a board-certified neurologist with a special qualification in child

neurology and clinical genetics. Tr. at 92, Pet’rs’ Ex. 28. Dr. Huq graduated from Dhaka

Medical College in Bangladesh, and went on to study in Japan, focusing on a number of

areas including pyruvate metabolism disorder, pyruvate dehydrogenase deficiency, stem

cell transplantation, and dopamine metabolism. Tr. at 91, Pet’rs’ Ex. 28. Following that,

Dr. Huq completed a residency in neurology and genetics, and several years in clinical

and medical genetics. Id. After training in genetics, Dr. Huq completed a child neurology

program, and is currently a professor of pediatrics and neurology at Wayne State

University. He has also conducted research as a faculty member, mostly in the area of

autism and the genetics of autism. Tr. at 92. In addition, Dr. Huq has published roughly

40 articles on the topics of “inborn errors of metabolism, pyruvate dehydrogenase

deficiency and mostly clinical work in vitamin D receptor metabolism,” as well as

hematopoietic stem cell transplantation, autism, and other clinical observations. Id. at 93.

Dr. Huq’s opinion centered on the question of whether R.A. suffers from an

underlying mitochondrial disorder21 – a question he answered in the affirmative. He began

20

As discussed in greater detail below, although Dr. Huq’s reports initially characterized R.A.’s

developmental problems as manifesting as a regression in previously acquired skills, he clarified at hearing

that in fact the medical record evidence did not support the conclusion that R.A. ever regressed at all. Tr.

at 177-85. He therefore backed away from his prior embrace of the term “regression,” characterizing R.A.’s

reaction as a failure of development. Id. at 185-86.

21

Notably, and by Dr. Huq’s admission, the vast majority of Dr. Huq’s patients (based on those seen on a

yearly basis) do not have mitochondrial disorders (Tr. at 190) – thus reducing somewhat his expertise in

diagnosing the condition (although he also has experience with metabolic disorders more generally).

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by explaining his understanding of mitochondrial diseases and disorders generally.

Monogenic mitochondrial disease, he proposed, is caused by a recognized single gene

mutation, resulting in a defined diagnosis such as Leigh Disease.22 Tr. at 103. By contrast,

mitochondrial dysfunction occurs when an as-yet-unidentified genetic susceptibility

(which in Dr. Huq’s opinion likely underlies the dysfunction) interacts with environmental

stressors, such as inflammation, cytokine activation, or some sort of immune activation.

Id at 104-06. In this case, Dr. Huq proposed, R.A. did not suffer from a recognized

mitochondrial disease, but instead a less severe form of mitochondrial dysfunction that

was still significant enough to precipitate his subsequent developmental problems. Id. at

95.

Dr. Huq’s conclusion that R.A. has underlying mitochondrial dysfunction was

based not on a defined set of clinical criteria23, but instead on a number of overlapping

factors, including R.A.’s clinical history and treater opinions, which were in turn the

product of extensive lab work and related testing and which Dr. Huq deemed relevant.

Dr. Huq specifically pointed to the following aspects of R.A.’s clinical history as supportive

of his determination: (1) dysfunction of the central nervous system, (2) gastrointestinal

system (diarrhea) problems, (3) musculoskeletal system issues (hyperextensibility), and

(4) liver dysfunction (as evidenced by elevated liver enzymes). Tr. at 112-13, 126-31.

Dr. Huq cited different components of the record to substantiate each of these

clinical factors. With respect to the first three, he primarily relied on a mix of anecdotal

evidence and parent testimony. Thus, Dr. Huq’s determination that R.A. suffered from

severe gastrointestinal problems was derived less from an individual treater diagnosis or

evidence of a severe problem resulting in medical intervention, than from the Andersons’

individual reports that R.A.’s diarrhea was out of the ordinary and their documented efforts

to have it treated by his pediatricians. See Tr. at 41-42; Huq Rpt. at 2; Pet’rs’ Exs. 6 at 27

and 8 at 1. He similarly concluded that R.A.’s purported hyperextensibility was clinically

significant, although he referenced no treater determination reaching that conclusion, or

22

As explained by respondent’s expert, Dr. Cohen, Leigh Disease is a progressive neurometabolic disorder

generally manifesting in infants that are born healthy but thereafter show severe, progressive deterioration

in neurological function following a fever or viral illness, ultimately resulting in death. See Tr. at 215.

23

Because of the overlapping factors involved in diagnosing mitochondrial dysfunction, Dr. Huq testified,

he does not rely on fixed criteria, such as what is referred to as the “Walker” or “Modified Walker” Criteria.

Tr. at 170-71. These criteria are diagnostic guidelines, based upon published medical literature, for

evaluating whether a child suffers from some kind of mitochondrial disease through application of a point

system for various symptoms or test results observed in the diagnosed patient. Id. at 272-73; see also

Ulrich A. Walker et al., Respiratory Chain Encephalomyopathies: A Diagnostic Classification, Eur. Neurol.

36:260-67 (1996).

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medical record in which such a condition was acknowledged or underscored as

particularly debilitating.24 As evidence of nervous system dysfunctionality, Dr. Huq

pointed (reflexively) to R.A.’s autism diagnosis. Tr. at 112, Huq Supp. Rpt. at 1. He also

noted that R.A. had been diagnosed with absence seizures, another central nervous

system problem likely related to mitochondrial dysfunction. Tr. at 112, Huq Supp. Rpt. at

1.

Dr. Huq also considered what he referred to as “bioclinical abnormalities,” or

indirect markers of mitochondrial dysfunction. Tr. 95, 113. These “abnormalities” were

first described in tests conducted over a large period of time in R.A.’s life, from 2001

through 2010, many of which were primarily performed by Dr. Shoffner, and which

included metabolic evaluations of R.A.’s liver enzymes, ammonia levels, lactic acid levels,

and carnitine. See generally Pet’rs’ Ex. 13 at 22-26, 134, and 961. Notably, these tests

were not performed around the time when R.A. was allegedly experiencing the vaccine-

induced onset of developmental problems, but instead years later – and after R.A. had

been diagnosed with autism. Tr. at 95, Pet’rs’ Ex. 9.25 The biochemical abnormalities Dr.

Huq cited as relevant included mildly elevated lactate levels (Tr. at 134), low free and total

carnitine levels (Tr. at 113), multiple amino acids in the urine (Tr. at 113-14), and elevated

liver enzymes (Tr. at 125-29). Dr. Huq also cited to evidence of elevated ammonia levels

that fluctuated with normal values over a period of three years as indicative of

mitochondrial dysfunction. Tr. at 117-18.

However, Dr. Huq’s conclusions were based on results that varied widely

throughout the history of R.A.’s clinical testing. Dr. Huq addressed the inconsistency of

such results, explaining that some of the abnormal results were not replicated in later

tests. Tr. at 114 (stating “ideally you want [abnormal test results] to be repeated many,

many times…. Often, I have patient[s] where I have molecularly proven mitochondrial

disorder, and I will get abnormality in one visit, and I will not get abnormality in other

visit.”). However, he downplayed the significance of the conflicting results, emphasizing

that the body’s compensatory mechanisms adjust and equilibrate enzyme pathways to

normalize values regardless. Tr. at 113-16.

24

Thus, as noted above, during a January 2001 pediatric visit R.A.’s purported “loose joints” were briefly

mentioned but not identified as having any negative effects on his overall health. Pet’rs’ Ex. 3 at 17, 18.

25

The fact that all biomarker tests were performed so long after the alleged onset of R.A.’s developmental

problems was not deemed by Dr. Huq as diminishing the value of the testing. In his view, later-acquired

laboratory results could still reflect an individual’s physiological status during an earlier period of life,

because when a biomarker is consistently abnormal over a period of time it is reasonable to assume that

the source of dysfunction originates within the individual’s body, rather than as the product of a transient

external factor. Tr. at 200-01.

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Dr. Huq also did not deny the inconclusive or negative quality of some of the other

testing performed on R.A. relevant to the mitochondrial disorder diagnosis. Thus, he

acknowledged that there was no evidence of any genetic cause for R.A.’s purported

mitochondrial dysfunction. Tr. at 205. He agreed as well that while the muscle fiber

abnormalities revealed in Dr. Shoffner’s testing could be evidence of mitochondrial

dysfunction, they could also simply be evidence of a nascent susceptibility to dysfunction,

making it difficult to place too much confidence in this category of testing. Id. at 136.

Moving on from testimony about R.A.’s purported underlying mitochondrial

dysfunction, Dr. Huq opined on the impact the MMR vaccine could have on a similarly-

situated child. As Dr. Huq testified, R.A.’s developmental injury began with administration

of the MMR vaccine, which induced a response that initiated a cascade of events, leading

to inflammation, exacerbated by immune dysfunction (as well as mitochondrial

dysfunction), and culminating in R.A.’s subsequent development of mild autism. Tr. at

140, 163. Specifically, Dr. Huq explained how mitochondrial dysfunction could be

triggered or worsened by a variety of external environmental stressors, such as

inflammation or immune activation, that could in turn produce reactive oxygen species.

Id. at 102. When such external environmental stressors interacted with mitochondria

susceptible to damage due to underlying genetic mutation (as was alleged to have been

the case here), the external stressors could trigger a condition resembling, if in milder

form, a more well-observed monogenic mitochondrial disease or disorder. Id. at 99-103.

In this case, Dr. Huq maintained, the febrile illness R.A. experienced after the MMR

vaccine was the initial triggering external factor. Fever caused the production of

inflammatory cytokines that produce reactive oxygen species. Tr. at 142. The reactive

oxygen species, in turn, could lead to further production of free radicals, and further impair

mitochondrial and immune function. Id. at 142, 175. In addition, Dr. Huq claimed that the

MMR vaccine was itself immune-suppressive. The result, according to Dr. Huq, was a

cyclical process impairing mitochondrial function and overall immune function, and

ceasing only when vulnerable cells were eliminated or when the body’s compensatory

mechanisms equilibrated the body. Id. at 140-42.

Despite putting forward this theory, however, Dr. Huq struggled to identify evidence

from the record substantiating it. Thus, he pointed to little from R.A.’s medical history

evidencing the inflammatory/immunologic cascade he proposed had been triggered by

the MMR vaccine – whether a contemporaneous treater diagnosis or testing that would

18

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corroborate his theory.26 Instead, he primarily relied on the fact that, in the six months

after the December 1999 vaccination, R.A. had been taken to the pediatrician multiple

times for URIs or other viral illnesses, citing this pattern as proof of an ongoing linked

process (a determination that R.A.’s own treaters did not themselves make at the time).

Tr. at 95.

Importantly, Dr. Huq conceded that the nature of R.A.’s injury was not as his report

had suggested. Thus, as he agreed on cross-examination, the contemporaneous medical

records from six days, eight days, six months, and even nine months after R.A.’s

vaccination did not in fact suggest that R.A. had experienced a regression in prior-

acquired skills or language, and that he was unaware of evidence to the contrary. Tr. at

177-85, Pet’rs’ Ex. 3 at 6. He therefore admitted that “my use of the term ‘regression’ [in

the expert report] was not – was not probably appropriate.” Tr. at 185.

To support the theory of the triggering impact of a vaccine on a child with

preexisting mitochondrial dysfunction, Dr. Huq relied heavily on three studies: Jon S.

Poling, et al., Developmental Regression and Mitochondrial Dysfunction in a Child with

Autism, J. Child Neurol. 21(2) 170-72 (2006), filed as Pet’rs’ Ex. 27 Tab N (“Poling”); John

Shoffner et al., Fever Plus Mitochondrial Disease Could Be Risk Factors for Autistic

Regression, J. Child Neurol., 25:429-34 (2010), filed as Pet’rs’ Ex. 27 Tab P; (“Shoffner”);

and Weissman, et al., Mitochondrial Disease in Autism Spectrum Disorder Patients: A

Cohort Analysis, PLoS ONE 3(11): e3815 (2008),27 filed as Pet’rs’ Ex. 27 Tab T

(“Weissman”). Huq Rpt. at 3, Tr. at 189-90.

Dr. Huq referenced the Poling case involving a 19-month-old child who, “Within 48

hours of vaccination [] was inconsolable, crying, irritable, lethargic, and refused to walk,”

and who could not walk up stairs at all four days later. Poling at 171. Dr. Huq testified that

there was a striking similarity between the time course of the abnormality described in

Poling and R.A. Tr. at 144. However, the distinctions between Poling and R.A.’s

26

The decisions of this tribunal undermine the component of Dr. Huq’s opinion connecting R.A.’s repeated

URIs and related health problems to the alleged immunologic process that led to his autism. Thus, Dr.

Huq’s suggestion at hearing that the MMR vaccine has immunosuppressive qualities (Tr. at 141-42) was

facially not well founded (at least in instances where autism is the alleged injury). That theory was

thoroughly evaluated, and discredited, in prior decisions in cases alleging that a vaccine produced autism.

See Snyder v. Sec’y of Dept. of Health and Human Services, No. 01-162V, 2009 WL 332044, at *102-04

(Fed. Cl. Spec. Mstr. Feb. 12, 2009), aff’d, 88 Fed. Cl. 706 (2009) (evidence demonstrating that measles

vaccines are routinely given to children with challenged or compromised immune systems, without harmful

effects, undercuts the theory that the vaccine virus is immunosuppressive or leads to viral persistence).

27

Weissman (which the hearing transcript erroneously refers to as “Weizman” (Tr. at 193) was submitted

twice in this case – first as Petitioners’ Exhibit 27, Tab T, and then as Exhibit 29, Tab P. Hereinafter I shall

cite only to the Exhibit 27 copy.

19

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circumstances were more evident – for, as Dr. Huq conceded at trial, not only did R.A.

not experience any developmental regression, but his developmental delays were evident

only months after the vaccination as opposed to days, and the severity of his delays or

motor difficulties was not comparable either. Id. at 144, 191-192.

Shoffner (authored by the same Dr. Shoffner who treated R.A. in 2008) involved a

retrospective chart review of 28 individuals diagnosed with both mitochondrial disease

and ASD. Nearly a third of the studied individuals (17 of 28) experienced developmental

regression, and nearly 71 percent of that subset regressed after fever (although the

precise extent and duration of fever for each subject were unknown, as the study relied

wholly on parental reports of fever rather than clinically-confirmed data, making that

variable unreliable scientifically). Further, the clinical situation described in Shoffner

involved regression within a two-week window following a vaccination. Dr. Huq proposed

that there was a “similar mechanism or similar pathophysiology” in this case, rendering

Shoffner relevant. Tr. at 146. Like Poling, however, Shoffner dealt with regression rather

than the mere development of autism manifesting as delayed development. Further,

Shoffner itself undermined the weight Dr. Huq placed upon it, since its authors explicitly

recognized that their study found no relationship between vaccination and the observed

regression. Shoffner at 432 (“the vaccines did not appear related to the neurologic

regression”).

Dr. Huq further relied on Weissman as providing an analog to R.A.’s own

experience. Huq Rpt. at 6. Weissman was a retrospective review of the medical histories

of 25 ASD-diagnosed patients who also had identifiable mitochondrial disease or

dysfunction, and argued that “defective mitochondrial oxidative phosphorylation is an

additional pathogenetic basis for a subset of individuals with autism.” Weissman at 5. But

this article, like Poling and Shoffner, mainly involved individuals who had unquestionably

experienced some form of developmental regression or markedly delayed early motor

milestones. Weissman at 3. Further, as Dr. Huq admitted, of the 25 individuals studied,

only one had suffered neurodevelopmental deterioration following vaccination – the child

described in Poling. Tr. at 194.

In addition to offering scientific literature intended to directly support Petitioners’

theory, Dr. Huq offered a variety of other literature intended to “fill in the blanks” – in

particular, by suggesting a broader relationship between mitochondrial disorders and

autism, independent of whether a vaccine could trigger a reaction in a child with

preexisting mitochondrial dysfunction. In particular, he referenced several pieces of

literature involving brain tissue studies in which associations between those regions of

the brain responsible for behaviors affected by autism and mitochondrial dysfunction were

20

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examined. See generally A. Anitha, et al., Brain Region-Specific Altered Expression and

Association of Mitochondria-Related Genes in Autism, Molecular Autism, 3:12, 1-12

(2012), filed as Pet’rs’ Ex. 44 (“Anitha”); Abha Chauhan, et al., Brain Region-Specific

Deficit in Mitochondrial Electron Transport Chain Complexes in Children with Autism, J.

Neurochem., 117:209-20 (2011), filed as Pet’rs’ Ex. 45 (“Chauhan”); and Guomei Tang,

et al., Mitochondrial Abnormalities in Temporal Lobe of Autistic Brain, Neurobiology of

Disease 54:349-61 (2013), filed as Pet’rs’ Ex. 46 (“Tang”).

Anitha explored gene expression and genetic association of specific genes related

to mitochondrial functions by testing postmortem brain tissue samples taken from eight

autistic patients, and showed altered gene expression in the examined brain regions.

Anitha at 1; Tr. at 147. As Dr. Huq explained, Anitha showed abnormalities of

mitochondrial gene expression and abnormal activity in those brain regions associated

with social communication and language function – the same regions from which the

pattern of language dysfunction exhibited by R.A. would also be expected to arise. Tr. at

147-49. However (and as Dr. Cohen later emphasized), the tissue samples studied in

Anitha may have been compromised, yielding questionable results. Tr. at 375-78. More

significantly, the genes which showed altered expressions in Anitha were not indicated

(based upon testing performed in December 30, 2013 by Dr. Kendall) as altered in R.A.

Compare Pet’rs’ Ex. 25 (reporting R.A. exhibited genetic variants only in the BRWD3 gene

and the AUTS2 gene) with Anitha at 5 (genes with altered expression in studied

postmortem brain tissue samples did not include either the BRWD3 or the AUTS2 gene).

Chauhan examined levels of mitochondrial proteins in postmortem frozen brain

tissue samples from brain regions of subjects with autism, finding that abnormalities in

mitochondria leading to oxidative stress and abnormal energy metabolism may play some

role in autism’s general etiology. Chauhan at 209, 217. Dr. Huq testified that Chauhan,

like Anitha, showed mitochondrial dysfunction in the frontal lobe, cerebellum, and

temporal lobe, and the presence of reactive oxygen species that could encourage

additional dysfunction in children with autism. Tr. at 150. Chauhan, however, suffered

from some of the same sample source deficiencies that characterized Anitha.28 Tang

examined mitochondrial proteins in frozen brain tissue samples taken from autistic

28

Thus, as Dr. Cohen later argued in his testimony, the tissue samples studied in Chauhan (like those in

Anitha) may have been compromised, given that the subjects from which the samples were derived had

died from seizure or drowning. Tr. at 375-78; see also Chauhan at Table S1 available at

www.ncbi.nlm.nih.gov/pmc/articles/PMC4839269/bin/NIHMS593243-supplement-supplemental_info.pdf

(last visited October 31, 2016). This is because, as Dr. Cohen explained, mitochondria rapidly degrade

after brain tissue reaches room temperature, which would inevitably occur since the tissues were derived

from deceased individuals.

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subjects, and reported mitochondrial defects within the temporal cortex of autistic subjects

compared to controls. Tang at 356. Dr. Huq characterized the defects discussed in Tang

as a complex dysfunction that he “would expect from a gene-environment interaction or

external stressors.” Tr. at 151.

C. Respondent’s Expert—Bruce Cohen, M.D.

Dr. Cohen submitted an expert report and testified at hearing. Tr. at 206-403; Ex.

A, Expert Report of Bruce H. Cohen, M.D., dated February 5, 2015 (the “Cohen Rpt.”) Dr.

Cohen’s testimony attempted to directly rebut Petitioners' assertion that R.A. suffered

from a mitochondrial disease or disorder of some kind related to his alleged post-

vaccination developmental regression.

Dr. Cohen graduated from Albert Einstein College of Medicine of Yeshiva

University in 1982 (after completing his undergraduate degree at Washington University

in St. Louis). Cohen Rpt. at 1. He went on to complete a pediatric residency at Children's

Hospital of Philadelphia, followed by a pediatric neurology residency at the Neurological

Institute of New York and Babies Hospital of Columbia Presbyterian Medical Center, and

a pediatric neuro-oncology fellowship at the Children's Hospital of Philadelphia. Id. Dr.

Cohen is board-certified in neurology, with special competence in child neurology, and

has in the past been board-certified in pediatrics. Ex. B at 2.He is currently the Director

of Neurology at the Children's Hospital Medical Center of Akron, and a Professor of

Pediatrics at Northeast Ohio Medical University, where he teaches general pediatric

neurology to medical students, residents, and fellows. Resp't's Ex. B at 2; Tr. at 207-08.

Dr. Cohen has demonstrated experience in studying mitochondrial diseases and

related metabolic disorders. He has also taught courses specifically on mitochondrial

disease in symposia. Resp't's Ex. B at 5. He is a reviewer for several journals, and serves

on the editorial board for the Mitochondrion and the Pediatric Neurology Journal. Id. at 3.

He also serves on various review committees, including the Neurofibromatosis

Consortium. Id. In addition, Dr. Cohen has written extensively on issues of mitochondrial

diseases, authoring or co-authoring nearly 25 peer-reviewed articles on the topic. Id. at

35-40. Dr. Cohen has served in many different capacities for the United Mitochondrial

Disease Foundation since 1999 and served on many different committees involving the

topic of mitochondrial disease. Id. at 3-4.

Dr. Cohen’s expertise on the topic of mitochondrial diseases and disorders

includes treatment of patients with the condition for the past 22 years. Tr. at 208. Roughly

75 percent of Dr. Cohen’s clinical practice concerns mitochondrial patients, amounting to

22

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thousands of patients over the past 15 years. Id. at 208-09. He routinely diagnoses

mitochondrial diseases or dysfunction in his patients, estimating that in the past 22 years

he has seen several thousand patients in which the disease was suspected, or actually

diagnosed. Id. Although Dr. Cohen does not diagnose ASDs, some of his patients have

autism as well as suspected mitochondrial diseases. Id. at 209-10.

Dr. Cohen formulated his opinion after reviewing R.A.’s medical records and

objective data plus the expert reports and journal articles filed. Cohen Rpt. at 8. Based

on this review, Dr. Cohen disagreed with Dr. Huq’s conclusions, and opined instead that

there is no credible evidence that R.A. has a mitochondrial illness, or that any vaccination

R.A. received in any way contributed to his autism or other medical conditions. Cohen

Rpt. at 10; Tr. at 213.

Dr. Cohen began by providing background on the difference between

mitochondrial disorder and dysfunction, defining those terms to mean primary and

secondary mitochondrial diseases, respectively. Tr. at 217. Primary mitochondrial

disease results from pathogenic mutations in genes that regulate mitochondrial function.

Id. at 217. Patients with a primary mitochondrial disease affecting Complex I function are

devastatingly ill, with symptoms including loss of vision, dystonia, severe encephalopathy

classified as Leigh or Leigh-like disorders, and death. Id. at 215-16. In contrast, secondary

mitochondrial disease refers to impairments to mitochondrial function that do not result

from pathogenic gene mutations. Id. Secondary mitochondrial disease may be triggered

by environmental stimuli, such as chemotherapy or poisons. Id. 218, 271-72, 399-400.

Dr. Cohen’s opinion that R.A. does not have mitochondrial disease or dysfunction

was derived from review of R.A.’s medical history, contrasting what he saw in it to

assumptions Dr. Shoffner had made about that history when he treated R.A. in 2008.29

First, Dr. Cohen emphasized, it was readily evident to him that R.A. was not suffering

from a primary mitochondrial disease. He described the clinical presentation of

mitochondrial disease, which would include dementia, strokes, ataxia, abnormal MRI

scans, cardiomyopathy, myopathy, cirrhosis, loss of night and color vision, hearing loss,

and other progressive symptoms – none of which were present for R.A. Tr. at 244-47.

Genetic testing performed on R.A. was largely inconclusive as well, showing the presence

of some mutations but nothing that would establish a known form of primary mitochondrial

disease. Id. at 239.

29

In discussing the clinical guidelines used to diagnose a mitochondrial disease or dysfunction, Dr. Cohen

testified that (like Dr. Huq), he does not always use the Walker criteria to diagnose mitochondrial disease,

and instead prefers genetic testing as the most reliable indicator that disease is present. Tr. at 238-39, 285.

23

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Second, Dr. Cohen noted that there was insufficient record evidence that R.A.

even suffered from a lesser, secondary mitochondrial disease. In this case, Petitioners

allege a neurologic injury as the prompt for R.A.’s developmental problems, and therefore

damage to R.A.’s brain tissue should have been evident on MRI scans. Tr. at 319-20.

Here, however, not only did R.A. not exhibit common neurological symptoms, but his MRI

scan was normal. Id. at 246. In addition, while mitochondrial disease can lead to

multisystem involvement (as Dr. Huq had suggested was evident in R.A.’s case), the

clinical presentation for R.A. did not support the conclusion that multisystem failure was

present. See Cohen Rpt. at 9. Thus, Dr. Cohen took issue with Dr. Huq’s reliance on

evidence of R.A. suffering from chronic diarrhea as proof of a gastrointestinal failure

evidencing a mitochondrial disorder. In Dr. Cohen’s view, patients suffering from even

secondary mitochondrial disease would experience something more demonstrably

severe, such as horrible constipation, rather than what R.A. is reported to have suffered.

Id. at 244-45.30

Dr. Cohen also questioned the strength of Petitioners’ assertions that R.A.’s

purported absence seizures evidenced a central nervous system manifestation of an

underlying mitochondrial disorder. The EEG from the medical records showed a three

second episode of a three-per-second spike and wave. However, as Dr. Cohen testified,

absence seizures can occur in generally healthy children, and are typically diagnosed

only after an EEG shows more than one episode of spike and wave, and usually lasting

more than three seconds. Id. at 221-22. Further, if absence seizures were a concern,

additional EEGs would have been sought for R.A. but this did not occur. Id. at 223. Dr.

Cohen therefore discounted the accuracy of Dr. Huq’s conclusion that R.A. had ever

suffered from absence seizures at all.

Dr. Cohen next noted inaccuracies in Dr. Shoffner’s factual assumptions about

R.A.’s medical history. Dr. Shoffner’s assessment was based in part on the proposition

that R.A. had experienced a regression in his development. A regression of skills at 17-

18 months of age, according to Dr. Shoffner, is a clinical indicator of mitochondrial

dysfunction. Id. at 220; Pet’rs’ Ex. 9 at 42. However, R.A. never in fact showed signs of

regression – something, as noted above, that Dr. Huq conceded. Id. at 220.

Similarly, Dr. Shoffner had assumed that R.A.’s onset of his developmental

problems was contemporaneous with the fever he had experienced in the six days

following his receipt of the MMR vaccine (which presumably caused the fever). Tr. at 220.

30

Dr. Cohen also proposed, as an alternative explanation, that R.A.’s chronic diarrhea could have been the

result of R.A.’s treatments, like IVIG. Tr. at 244.

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Such an assumption was consistent with Dr. Shoffner’s proposals about the relationship

between fever and developmental regression. Shoffner at 430 (“[a] relationship between

fever and autistic regression is defined as regression beginning within 2 weeks of a febrile

episode without the suggestion of infectious meningitis or encephalitis”). Yet in this case,

as the medical records revealed,31 R.A.’s developmental problems had manifested no

earlier than five to six months after the MMR vaccination - not within the two-week window

that Dr. Shoffner’s own article said would be expected if fever had been the triggering

factor. Id. at 220-21. Dr. Cohen also opined that the febrile illness R.A. exhibited was

most likely caused by a rhinovirus rather than the MMR vaccine, given what the medical

records showed. Id. at 363.

Dr. Cohen went on to review Dr. Shoffner’s medical evaluation of R.A., and in

particular the testing that Dr. Huq relied on as supporting evidence of a probable Complex

I mitochondrial defect. Pet’rs’ Ex. 10 at 27-30; Tr. at 224-44. Dr. Cohen opined that the

metabolic, biochemical, and genetic laboratory test results generated in R.A.’s case did

not support a diagnoses of mitochondrial disorder. He specifically considered each

relevant testing component in reaching this conclusion.

First, Dr. Cohen challenged Dr. Shoffner’s conclusions that testing revealed R.A.

had an elevated lactic acid level sufficient to establish the existence of secondary

mitochondrial disease. As Dr. Cohen explained, lactic acid readings alone are insufficient

for a mitochondrial dysfunction diagnosis, because elevated levels can occur in otherwise

healthy individuals simply when a patient struggles during the sampling procedures. Tr.

at 227. This is particularly true with autistic children, where “it’s hard to get a normal blood

lactate because, in fact, there is often a struggle, and there is certainly the use of a

tourniquet.” Id.; Cohen Rpt. at 9. For an elevated lactate reading to be meaningful, Dr.

Cohen maintained, it must be correlated with a concomitant amino acid draw showing

elevated alanine. Id. at 225, 227. But in R.A.’s case, alanine levels tested as normal.

Lactate levels can also fluctuate widely in different clinical settings, and can actually drop

when certain patients clinically worsen, further reducing their value as a diagnostic tool.

Id. at 338-39. Overall, Dr. Cohen stated, lactate readings were being viewed as less and

less helpful to experts in the field of mitochondrial disease study, given all the limitations

of such testing. Tr. at 227, 338-39.

Dr. Cohen next discussed the amino acid test results from R.A.’s urine samples

that had led Dr. Shoffner to conclude that R.A. possibly had proximal renal tubular

31

Of course, Petitioners contend that R.A. manifested developmental problems far closer to the time of his

vaccination. However, and as I discuss in greater detail below, such contentions are not corroborated by

the contemporaneous fact record, and I therefore give them less evidentiary weight.

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acidosis. In Dr. Cohen’s view, some of the nutritional or vitamin supplements R.A. was

taking at the time, which included amino acid supplements of taurine, 3-methyl glycine,

and cysteine, could artificially elevate amino acid levels. Tr. at 228.32 Moreover, the

normal levels of amino acids found in R.A.’s cerebral spinal fluid suggested instead that

his amino acids were not high, but that his kidneys were instead appropriately flushing

excess amino acids introduced into R.A.’s body by the variety of supplements he was

then taking (which explained the urine testing results). Id. at 228-29. Thus, Dr. Shoffner

placed too much reliance on the urine test results, while ignoring contrary but relevant

results that did not corroborate the conclusion that R.A. suffered from renal tubular

acidosis. Id.

Dr. Cohen further opined that R.A.’s muscle biopsy results were similarly

unsupportive of Dr. Shoffner’s diagnostic conclusions. In reviewing the relevant testing,

Dr. Cohen acknowledged that R.A.’s muscle histology as reviewed under the light

microscope was abnormal, but otherwise not indicative of a mitochondrial dysfunction. Tr.

at 229-30, Cohen Rpt. at 9. Further, the immunohistochemistry tests did not show any

features of mitochondrial illness, specifically ragged red or blue fibers, COX negative

fibers, or excessive staining on whole and panel stains. Id. at 230-32.

Dr. Cohen next discussed Dr. Shoffner’s enzymology testing. Such tests isolated

mitochondria from R.A., and then evaluated each of four protein complexes that typically

work in conjunction to produce energy in heathy cells. Tr. at 233. Dr. Shoffner had relied

on R.A.’s phosphorylation enzymology results to conclude that he suffered from a

Complex I defect. See Pet’rs’ Ex. 9 at 42. But Dr. Cohen proposed that the testing was

too incomplete to support that conclusion. Dr. Shoffner had conducted two separate tests

for Complex I and Complex IV, but only one of each returned abnormal results. Id. at 393-

94, Pet’rs’ Ex. 9 at 24. Thus, Dr. Cohen questioned whether the abnormal results were

truly reliable.

More significantly, in Dr. Cohen’s view, Dr. Shoffner had failed to standardize the

results against a marker enzyme called citrate synthase – an essential step, in Dr.

32

As noted previously, at hearing Dr. Cohen proposed that Dr. Shoffner had failed to take into account the

role of these supplements in skewing the amino acid level test results of R.A.’s urine. Tr. at 228, 345, see

also Pet’rs’ Ex. 10 at 16-17. In fact, the medical record indicates that Dr. Shoffner recognized that R.A. was

at the time taking 975 mg of taurine. See Pet’rs’ Ex. 10 at 17. It does not, however, similarly reveal that Dr.

Shoffner took account of the possibility that other supplements (like 3-methyl glycine or cysteine) could

have affected R.A.’s amino acid counts. Overall, I find that the record is too ambiguous on this point to

determine that the amino acid test results alone are incorrect, or should be discounted along the lines

proposed by Dr. Cohen. At the same time, however, given the weight of the other test results, I do not find

the positive amino acid test results to be particularly probative in support of Petitioners’ contention that Dr.

Shoffner’s diagnosis is trustworthy from an evidentiary standpoint.

26

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Cohen’s opinion, when evaluating a muscle enzymology result. Id. at 235-37, Cohen Rpt.

at 10. As Dr. Cohen explained, citrate synthase is an important marker enzyme in the

mitochondria that provides a proxy measurement of mitochondrial content in the muscle,

and thus helps confirm the success rate of the extraction process when testing. Cohen

Rpt. at 11. Citrate synthase levels are therefore used to standardize mitochondrial

enzyme values, “[b]ecause if the citrate synthase is low, your other enzymes are going to

be low as well.” Tr. at 234. Dr. Cohen performed that standardization himself in preparing

his expert opinion, relying on recognized diagnostic criteria for evaluation of mitochondrial

disease as well as the citrate synthase levels measured by Dr. Shoffner at the time. Id. at

233-35. In so doing, Dr. Cohen found that R.A.’s enzyme function was either normal or

only slightly above normal. Id.; Cohen Rpt. at 9-10. According to Dr. Cohen, the remaining

enzymology results were normal, and therefore there was “just zero evidence … that this

child ha[d] a Complex I defect.” Tr. at 235.

Dr. Cohen also reviewed the testing of R.A.’s ammonia levels, which Dr. Huq had

deemed significant because high levels of ammonia can be a biomarker of mitochondrial

dysfunction. Tr. at 117-18. In Dr. Cohen’s view, the ammonia testing results were too

fluctuating to support a diagnosis of mitochondrial disease, or were otherwise too close

to the normal range to be alarming. Tr. at 240-42. Rather, Dr. Cohen attributed R.A.’s

slightly elevated ammonia to the amino acid supplements he was taking. Id. at 241. Dr.

Cohen did, however, acknowledge the presence of ammonia level test results for R.A. at

various times that did support Petitioners’ argument. Id. at 342.

Dr. Cohen took a similar view of the liver enzyme levels observed in Dr. Shoffner’s

testing – in particular, AST and ALT. As Dr. Cohen explained, chronically elevated liver

enzymes can be an indication of specific mitochondrial disease, such as Alpers disease.

Tr. at 242-43. R.A.’s liver enzymes, however, exhibited periodic rises, but then returned

to normal, which would not occur in individuals with primary or secondary mitochondrial

disease. Id. at 243. And certain drugs and supplements R.A. was ingesting were known

to elevate ALT levels, including Solu Cortef, Solu Medrol, and IVIG. Id. at 241-42, 342-

43.

Dr. Cohen also discussed some of the broader aspects of Dr. Huq’s causation

theory. In particular, he disputed the significance of R.A.’s post-vaccination illnesses from

the winter and spring of 2000 as evidencing multisystem inflammation – according to Dr.

Huq, proof of the interaction of his alleged secondary mitochondrial disease and his

immune system. To Dr. Cohen, nothing in R.A.’s medical record corroborated this view.

Tr. at 249-50. Rather, the infections and pediatric illnesses R.A. had experienced in this

time period were not unusual for an otherwise healthy child of the same age. Id. at 251,

27

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369-70. Indeed, individuals with demonstrated inborn metabolic errors, or even primary

mitochondrial disease, do not typically exhibit significant sequela from vaccinations,

further reducing the significance of R.A.’s purported progressive susceptibility to infection.

Id. at 252.

Finally, Dr. Cohen questioned Dr. Huq’s proposal (based on Anitha and similar

studies examining post-mortem brain tissue of autistic individuals) that autism could be

causally associated with mitochondrial disease or dysfunction. Tr. at 147-51. In Dr.

Cohen’s view, such papers were fundamentally flawed because the marker molecules

they tested for, which revealed Complex I and Complex IV activity, would disappear

rapidly after brain tissue reaches room temperature (which would inevitably occur since

the tissues were derived from deceased individuals), rendering their conclusions

unreliable. Tr. at 375-78. Further, while the articles indicated there was a change in the

mitochondria in the subjects’ brains, Dr. Cohen testified there is no real understanding of

why this occurs, rending the studies of little probative value and “not relevant to [R.A.].”

Id. at 377-78.

III. APPLICABLE LEGAL STANDARDS

A. Evidentiary Burden in Vaccine Program Cases

To receive compensation in the Vaccine Program, a petitioner must prove either:

(1) that he suffered a “Table Injury” - i.e., an injury falling within the Vaccine Injury Table

- corresponding to one of the vaccinations in question within a statutorily prescribed

period of time or, in the alternative, (2) that his illnesses were actually caused by a vaccine

(a “Non–Table Injury”). See Sections 13(a)(1)(A), 11(c)(1), and 14(a), as amended by 42

C.F.R. § 100.3; § 11(c)(1)(C)(ii)(I); see also Moberly v. Sec'y of Health & Human Servs.,

592 F.3d 1315, 1321 (Fed. Cir. 2010); Capizzano v. Sec'y of Health & Human Servs., 440

F.3d 1317, 1320 (Fed. Cir. 2006). Petitioners are not asserting a Table claim in this case.

For both Table and Non–Table claims, Vaccine Program petitioners bear a

“preponderance of the evidence” burden of proof. Section 13(1)(a). That is, a petitioner

must offer evidence that leads the “trier of fact to believe that the existence of a fact is

more probable than its nonexistence before [he] may find in favor of the party who has

the burden to persuade the judge of the fact's existence.” Moberly, 592 F.3d at 1322 n.2;

see also Snowbank Enter. v. United States, 6 Cl. Ct. 476, 486 (1984) (mere conjecture

or speculation is insufficient under a preponderance standard). Proof of medical certainty

is not required. Bunting v. Sec'y of Health & Human Servs., 931 F.2d 867, 873 (Fed. Cir.

1991). In particular, a petitioner must demonstrate that the vaccine was “not only [the]

but-for cause of the injury but also a substantial factor in bringing about the injury.”

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Moberly, 592 F.3d at 1321 (quoting Shyface v. Sec'y of Health & Human Servs., 165 F.3d

1344, 1352–53 (Fed. Cir. 1999)); Pafford v. Sec'y of Health & Human Servs., 451 F.3d

1352, 1355 (Fed. Cir. 2006). A petitioner may not receive a Vaccine Program award

based solely on his assertions; rather, the petition must be supported by either medical

records or by the opinion of a competent physician. Section 13(a)(1).

In attempting to establish entitlement to a Vaccine Program award of

compensation for a causation-in-fact claim, a petitioner must satisfy all three of the

elements established by the Federal Circuit in Althen v. Sec’y of Health & Human Servs.,

418 F.3d 1274, 1278 (Fed. Cir. 2005): “(1) a medical theory causally connecting the

vaccination and the injury; (2) a logical sequence of cause and effect showing that the

vaccination was the reason for the injury; and (3) a showing of a proximate temporal

relationship between vaccination and injury.”

Each of the Althen prongs requires a different showing. Under Althen prong one,

petitioners must provide a “reputable medical theory,” demonstrating that the vaccine

received can cause the type of injury alleged. Pafford, 451 F.3d at 1355–56 (citations

omitted). To satisfy this prong, petitioner's theory must be based on a “sound and reliable

medical or scientific explanation.” Knudsen v. Sec'y of Health & Human Servs., 35 F.3d

543, 548 (Fed. Cir. 1994). Such a theory must only be “legally probable, not medically or

scientifically certain.” Id. at 549.

Petitioners may satisfy the first Althen prong without resort to medical literature,

epidemiological studies, demonstration of a specific mechanism, or a generally accepted

medical theory. Andreu v. Sec'y of Health & Human Servs., 569 F.3d 1367, 1378–79

(Fed. Cir. 2009) (citing Capizzano, 440 F.3d at 1325–26). Special masters, despite their

expertise, are not empowered by statute to conclusively resolve what are essentially

thorny scientific and medical questions, and thus scientific evidence offered to establish

Althen prong one is viewed “not through the lens of the laboratorian, but instead from the

vantage point of the Vaccine Act's preponderant evidence standard.” Id. at 1380.

Accordingly, special masters must take care not to increase the burden placed on

petitioners in offering a scientific theory linking vaccine to injury. Contreras v. Sec'y of

Health & Human Servs., 121 Fed. Cl. 230, 245 (2015) (“[p]lausibility ... in many cases

may be enough to satisfy Althen prong one” (emphasis in original)). But this does not

negate or reduce a petitioner's ultimate burden to establish his entitlement to damages

by preponderant evidence. W.C. v. Sec'y of Health & Human Servs., 704 F.3d 1352, 1356

(Fed. Cir. 2013) (citations omitted).

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The second Althen prong requires proof of a logical sequence of cause and effect,

usually supported by facts derived from a petitioner's medical records. Althen, 418 F.3d

at 1278; Andreu, 569 F.3d at 1375–77; Capizzano, 440 F.3d at 1326; Grant v. Sec'y of

Health & Human Servs., 956 F.2d 1144, 1148 (Fed. Cir. 1992). In establishing that a

vaccine “did cause” injury, the opinions and views of the injured party's treating physicians

are entitled to some weight. Andreu, 569 F.3d at 1367; Capizzano, 440 F.3d at 1326

(“medical records and medical opinion testimony are favored in vaccine cases, as treating

physicians are likely to be in the best position to determine whether a ‘logical sequence

of cause and effect show[s] that the vaccination was the reason for the injury’ ”) (quoting

Althen, 418 F.3d at 1280). Medical records are generally viewed as particularly

trustworthy evidence, since they are created contemporaneously with the treatment of the

patient. Cucuras v. Sec'y of Health & Human Servs., 993 F.2d 1525, 1528 (Fed. Cir.

1993).

However, medical records and/or statements of a treating physician's views do not

per se bind the special master to adopt the conclusions of such an individual, even if they

must be considered and carefully evaluated. Section 13(b)(1) (providing that “[a]ny such

diagnosis, conclusion, judgment, test result, report, or summary shall not be binding on

the special master or court”); Snyder v. Sec'y of Health & Human Servs., 88 Fed. Cl. 706,

746 n.67 (2009) (“there is nothing ... that mandates that the testimony of a treating

physician is sacrosanct—that it must be accepted in its entirety and cannot be rebutted”).

As with expert testimony offered to establish a theory of causation, the opinions or

diagnoses of treating physicians are only as trustworthy as the reasonableness of their

suppositions or bases. The views of treating physicians should also be weighed against

other, contrary evidence also present in the record—including conflicting opinions among

such individuals. Hibbard v. Sec'y of Health & Human Servs., 100 Fed. Cl. 742, 749

(2011) (not arbitrary or capricious for special master to weigh competing treating

physicians' conclusions against each other), aff'd, 698 F.3d 1355 (Fed. Cir. 2012); Caves

v. Sec'y of Health & Human Servs., 100 Fed. Cl. 119, 136 (2011), aff'd, 463 Fed. App’x

932 (Fed. Cir. 2012); Veryzer v. Sec'y of Health & Human Servs., No. 06–522V, 2011 WL

1935813, at *17 (Fed. Cl. Spec. Mstr. Apr. 29, 2011), mot. for review den'd, 100 Fed. Cl.

344, 356 (2011), aff'd without opinion, 475 Fed. App’x 765 (Fed. Cir. 2012).

The third Althen prong requires establishing a “proximate temporal relationship”

between the vaccination and the injury alleged. Althen, 418 F.3d at 1281. That term has

been equated to the phrase “medically-acceptable temporal relationship.” Id. A petitioner

must offer “preponderant proof that the onset of symptoms occurred within a timeframe

which, given the medical understanding of the disorder's etiology, it is medically

acceptable to infer causation.” Bazan v. Sec'y of Health & Human Servs., 539 F.3d 1347,

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1352 (Fed. Cir. 2008). The explanation for what is a medically acceptable timeframe must

also coincide with the theory of how the relevant vaccine can cause an injury (Althen

prong one's requirement). Id. at 1352; Shapiro v. Sec'y of Health & Human Servs., 101

Fed. Cl. 532, 542 (2011), recons. den'd after remand, 105 Fed. Cl. 353 (2012), aff'd mem.,

2013 WL 1896173 (Fed. Cir. 2013); Koehn v. Sec'y of Health & Human Servs., No. 11–

355V, 2013 WL 3214877 (Fed. Cl. Spec. Mstr. May 30, 2013), mot. for review den'd (Fed.

Cl. Dec. 3, 2013), aff'd, 773 F.3d 1239 (Fed. Cir. 2014).

B. Law Governing Analysis of Fact Testimony

The process for making determinations in Vaccine Program cases regarding

factual issues begins with consideration of the medical records. Section 11(c)(2). The

special master is required to consider “all [ ] relevant medical and scientific evidence

contained in the record,” including “any diagnosis, conclusion, medical judgment, or

autopsy or coroner's report which is contained in the record regarding the nature,

causation, and aggravation of the petitioner's illness, disability, injury, condition, or death,”

as well as “the results of any diagnostic or evaluative test which are contained in the

record and the summaries and conclusions.” Section 13(b)(1)(A). The special master is

then required to weigh the evidence presented, including contemporaneous medical

records and testimony. See Burns v. Sec'y of Health & Human Servs., 3 F.3d 415, 417

(Fed. Cir. 1993) (it is within the special master's discretion to determine whether to afford

greater weight to contemporaneous medical records than to other evidence, such as oral

testimony surrounding the events in question that was given at a later date, provided that

such a determination is evidenced by a rational determination).

Medical records that are created contemporaneously with the events they describe

are presumed to be accurate and “complete” (i.e., presenting all relevant information on

a patient's health problems). Cucuras, 993 F.2d at 1528; Doe v. Sec'y of Health & Human

Servs., 95 Fed. Cl. 598, 608 (2010) (“[g]iven the inconsistencies between petitioner's

testimony and his contemporaneous medical records, the special master's decision to

rely on petitioner's medical records was rational and consistent with applicable law”), aff'd,

Rickett v. Sec'y of Health & Human Servs., 468 Fed. App’x 952 (Fed. Cir. 2011) (non-

precedential opinion). This presumption is based on the linked propositions that (i) sick

people visit medical professionals; (ii) sick people honestly report their health problems

to those professionals; and (iii) medical professionals record what they are told or observe

when examining their patients in as accurate a manner as possible, so that they are aware

of enough relevant facts to make appropriate treatment decisions. Sanchez v. Sec'y of

Health & Human Servs., No. 11–685V, 2013 WL 1880825, at *2 (Fed. Cl. Spec. Mstr.

Apr. 10, 2013); Cucuras v. Sec'y of Health & Human Servs., 26 Cl. Ct. 537, 543 (1992),

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aff'd, 993 F.2d 1525 (Fed. Cir. 1993) (“[i]t strains reason to conclude that petitioners would

fail to accurately report the onset of their daughter's symptoms. It is equally unlikely that

pediatric neurologists, who are trained in taking medical histories concerning the onset of

neurologically significant symptoms, would consistently but erroneously report the onset

of seizures a week after they in fact occurred”).

Accordingly, if the medical records are clear, consistent, and complete, then they

should be afforded substantial weight. Lowrie v. Sec'y of Health & Human Servs., No. 03–

1585V, 2005 WL 6117475, at *20 (Fed. Cl. Spec. Mstr. Dec. 12, 2005). Indeed,

contemporaneously medical records are generally found to be deserving of greater

evidentiary weight than oral testimony—especially where such testimony conflicts with

the record evidence. Cucuras, 993 F.2d at 1528; see also Murphy v. Sec'y of Health &

Human Servs., 23 Cl. Ct. 726, 733 (1991), aff'd, 968 F.2d 1226 (Fed. Cir.), cert. den'd,

Murphy v. Sullivan, 506 U.S. 974 (1992) (citing United States v. United States Gypsum

Co., 333 U.S. 364, 396 (1947) (“[i]t has generally been held that oral testimony which is

in conflict with contemporaneous documents is entitled to little evidentiary weight.”)).

However, there are situations in which compelling oral testimony may be more

persuasive than written records, such as where records are deemed to be incomplete or

inaccurate. Campbell v. Sec'y of Health & Human Servs., 69 Fed. Cl. 775, 779 (2006)

(“like any norm based upon common sense and experience, this rule should not be

treated as an absolute and must yield where the factual predicates for its application are

weak or lacking”); Lowrie, 2005 WL 6117475, at *19 (“[w]ritten records which are,

themselves, inconsistent, should be accorded less deference than those which are

internally consistent”) (quoting Murphy, 23 Cl. Ct. at 733). Ultimately, a determination

regarding a witness's credibility is often needed when determining the weight that such

testimony should be afforded. Andreu, 569 F.3d at 1379; Bradley v. Sec'y of Health &

Human Servs., 991 F.2d 1570, 1575 (Fed. Cir. 1993).

When witness testimony is offered to overcome the presumption of accuracy

afforded to contemporaneous medical records, such testimony must be “consistent, clear,

cogent, and compelling.” Sanchez, 2013 WL 1880825, at *3 (citing Blutstein v. Sec'y of

Health & Human Servs., No. 90–2808V, 1998 WL 408611, at *5 (Fed. Cl. Spec. Mstr.

June 30, 1998)). In determining the accuracy and completeness of medical records, the

Court of Federal Claims has listed four possible explanations for inconsistencies between

contemporaneously created medical records and later testimony: (1) a person’s failure to

recount to the medical professional everything that happened during the relevant time

period; (2) the medical professional's failure to document everything reported to her or

him; (3) a person's faulty recollection of the events when presenting testimony; or (4) a

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person's purposeful recounting of symptoms that did not exist. La Londe v. Sec'y Health

& Human Servs., 110 Fed. Cl. 184, 203–04 (2013), aff'd, 746 F.3d 1334 (Fed. Cir. 2014).

In making a determination regarding whether to afford greater weight to

contemporaneous medical records or other evidence, such as testimony at hearing, there

must be evidence that this decision was the result of a rational determination. Burns, 3

F.3d at 417.

C. Analysis of Expert Testimony

Establishing a sound and reliable medical theory often requires a petitioner to

present expert testimony in support of his claim. Lampe v. Sec'y of Health & Human

Servs., 219 F.3d 1357, 1361 (Fed. Cir. 2000). Vaccine Program expert testimony is

usually evaluated according to the factors for analyzing scientific reliability set forth in

Daubert v. Merrell Dow Pharm., Inc., 509 U.S. 579, 594–96 (1993). See Cedillo v. Sec'y

of Health & Human Servs., 617 F.3d 1328, 1339 (Fed. Cir. 2010) (citing Terran v. Sec'y

of Health & Human Servs., 195 F.3d 1302, 1316 (Fed. Cir. 1999)). “The Daubert factors

for analyzing the reliability of testimony are: (1) whether a theory or technique can be (and

has been) tested; (2) whether the theory or technique has been subjected to peer review

and publication; (3) whether there is a known or potential rate of error and whether there

are standards for controlling the error; and (4) whether the theory or technique enjoys

general acceptance within a relevant scientific community.” Terran, 195 F.3d at 1316 n.2

(citing Daubert, 509 U.S. at 592–95).

The Daubert factors play a slightly different role in Vaccine Program cases than

they do when applied in other federal judicial fora (such as the district courts). Daubert

factors are usually employed by judges (in the performance of their evidentiary

gatekeeper roles) to exclude evidence that is unreliable and/or could confuse a jury. In

Vaccine Program cases, by contrast, these factors are used in the weighing of the

reliability of scientific evidence proffered. Davis v. Sec'y of Health & Human Servs., 94

Fed. Cl. 53, 66–67 (2010) (“uniquely in this Circuit, the Daubert factors have been

employed also as an acceptable evidentiary-gauging tool with respect to persuasiveness

of expert testimony already admitted”). The flexible use of the Daubert factors to evaluate

the persuasiveness of expert testimony has routinely been upheld. See, e.g., Snyder, 88

Fed. Cl. at 742–45. In this matter (as in numerous other Vaccine Program cases), Daubert

has not been employed at the threshold, to determine what evidence should be admitted,

but instead to determine whether expert testimony offered is reliable and/or persuasive.

Respondent frequently offers one or more experts of her own in order to rebut a

petitioner's case. Where both sides offer expert testimony, a special master's decision

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may be “based on the credibility of the experts and the relative persuasiveness of their

competing theories.” Broekelschen v. Sec'y of Health & Human Servs., 618 F.3d 1339,

1347 (Fed. Cir. 2010) (citing Lampe, 219 F.3d at 1362). However, nothing requires the

acceptance of an expert's conclusion “connected to existing data only by the ipse dixit of

the expert,” especially if “there is simply too great an analytical gap between the data and

the opinion proffered.” Snyder, 88 Fed. Cl. at 743 (quoting Gen. Elec. Co. v. Joiner, 522

U.S. 146 (1997)); see also Isaac v. Sec'y of Health & Human Servs., No. 08–601V, 2012

WL 3609993, at *17 (Fed. Cl. Spec. Mstr. July 30, 2012), mot. for review den'd, 108 Fed.

Cl. 743 (2013), aff'd, 540 Fed. App’x 999 (Fed. Cir. 2013) (citing Cedillo, 617 F.3d at

1339). Weighing the relative persuasiveness of competing expert testimony, based on a

particular expert's credibility, is part of the overall reliability analysis to which special

masters must subject expert testimony in Vaccine Program cases. Moberly, 592 F.3d at

1325–26 (“[a]ssessments as to the reliability of expert testimony often turn on credibility

determinations”); see also Porter v. Sec'y of Health & Human Servs., 663 F.3d 1242,

1250 (Fed. Cir. 2011) (“this court has unambiguously explained that special masters are

expected to consider the credibility of expert witnesses in evaluating petitions for

compensation under the Vaccine Act”).

In determining whether a particular expert's testimony was reliable or credible, a

special master may consider whether the expert is offering an opinion that exceeds the

expert's training or competence. Walton v. Sec'y of Health & Human Servs., No. 04–503V,

2007 WL 1467307, at *17–18 (Fed. Cl. Spec. Mstr. Apr. 30, 2007) (otolaryngologist not

well suited to testify about disciplines other than her own specialty). While (in keeping

with the liberality with which evidence offered in Vaccine Program cases is treated) all

testimony of the experts offered at the entitlement hearing was heard and considered, a

special master may properly evaluate, and give appropriate weight to, whether certain

testimony is beyond a particular expert's purview. See e.g., King v. Sec'y of Health &

Human Servs., No. 03–584V, 2010 WL 892296, at *78–79 (Fed. Cl. Spec. Mstr. Mar. 12,

2010) (petitioner's expert far less qualified to offer opinion on general causation issues

pertaining to autism than specific issues pertaining to the petitioner's actual medical

history, given the nature of the expert's qualifications).

D. Mitochondrial Disease and Dysfunction

As my recitation above of the testimony by the experts at hearing reveals, the

function of mitochondria in the human body is highly pertinent to Petitioners’ case (and

particularly their causation theory). The mitochondria are cellular organelles that are

present in the body’s cells and are primarily responsible for creating energy. Dorland’s

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Illustrated Medical Dictionary 61 (32nd ed. 2012); Tr. at 98. Mitochondrial dysfunction,

according to Dr. Huq, is a loosely used term for conditions that result from mitochondria

not properly functioning. Tr. at 104. Mitochondrial disease can manifest with a multitude

of symptoms, including dysfunction of the central nervous system, gastrointestinal

system, and musculoskeletal system. Tr. at 112. Mitochondrial disease can also manifest

through altered biochemical and clinical abnormalities, such as elevated levels of certain

amino acids and biomarkers like lactic acid. Tr. at 111. But it can be difficult to diagnose

mitochondrial disease given the variety of possible symptoms and the lack of a reliable

and agreed-upon diagnostic biomarker. Id. at 102-03; 114; 214-18.

Although there is a distinction between primary mitochondrial disease and

secondary, the parties largely do not dispute that only the secondary form (in which

mitochondrial dysfunction is the product of some kind of environmental, external stimuli,

rather than directly the result of an underlying genetic mutation) is applicable to R.A.’s

claim. Tr. at 101-03, 169, 217-18.

ANALYSIS

I. R.A. Does Not Suffer from Mitochondrial Dysfunction

The central deficiency in Petitioners’ case is their inability to establish by

preponderant evidence that R.A. actually had some form of secondary mitochondrial

disease. The medical record does not support that conclusion, and the treater opinion

and testing results relied upon for the diagnosis are either based on demonstrably

incorrect assumptions or inconclusive evidence. Because Petitioners’ claim is dependent

on this finding, the entirety of their causation theory cannot stand.

An important point right off the bat is not disputed: R.A. did not suffer from a primary

mitochondrial disease. As a result, Petitioners concede that the kind of obvious symptoms

associated with the more well-recognized forms of mitochondrial disease are absent,

leading them to propose that a variety of lesser evidence in the medical record supports

their theory. Petitioners rely heavily on R.A.’s immediate post-vaccination illness and

medical history in the subsequent months.

That evidence, however, is at best inconclusive, and otherwise provides weak

support for evidence of mitochondrial dysfunction. There is no testing from the period in

which R.A. would have been experiencing a vaccine reaction that would confirm he

possessed any mitochondrial dysfunction. R.A.’s frequent trips to the pediatrician in the

first half of 2000 are more suggestive of the variable health of an infant than that of a child

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experiencing progressive symptoms inexorably leading to a cessation of language or

motor development. No contemporaneous treaters thought otherwise; none proposed

that the URIs or other symptoms for which R.A.’s parents sought treatment were evidence

of a greater medical issue. Moreover, Dr. Huq’s attempts to characterize certain of R.A.’s

symptoms – for example, his diarrhea – as components of some multisystemic failure

reflecting mitochondrial dysfunction are unpersuasive, inflating a less severe

gastrointestinal problem that was more likely as not attributable to other factors into an

alarming warning sign. The same is true of Dr. Huq’s claims that R.A.’s autism33 or

purported seizure disorder (the latter being especially unsupported by the record)

evidence central nervous system failure.

In addition, the conclusion that R.A. did have some kind of mild secondary

mitochondrial disease is largely the product of Dr. Shoffner’s treatment in 2008. Putting

aside the fact that he treated him long after the vaccination, the test results that Dr.

Shoffner relied upon in part for his conclusion are not robust or trustworthy enough to find

it “more likely than not” that R.A. possessed mitochondrial dysfunction. Thus, as Dr.

Cohen persuasively established, the lactic acid test results were untrustworthy, and would

under more generally accepted diagnostic approaches today be deemed of far less utility

in evaluating the presence of mitochondrial dysfunction. Tr. at 227. More significantly, the

enzymology testing failed to appropriately standardize results by using the marker

enzyme citrate synthase, and positive results were otherwise inconsistent or not

replicated. Tr. at 235-37, 393-94; Cohen Rpt. At 10; Pet’rs’ Ex. 9 at 24. Otherwise, it is

evident that Dr. Shoffner accepted recitations about R.A.’s medical history – in particular,

the fact that he had experienced regression – as accurate, applying his own theories as

a result about the interaction of fever and regression that are not relevant herein. Pet’rs’

Ex. 9 at 42; Pet’rs’ Ex. 10 at 15; Tr. at 185, 191-92.

I acknowledge the fact that Dr. Shoffner was one of R.A.’s treaters. But that does

not mean that his opinion automatically is entitled to the level of deference and evidentiary

weight given to contemporaneous treater records in many Program cases – especially

when, as here, he reached his conclusions long after the immediately relevant time

period. Nuttall v. Sec’y of Health & Human Servs., 122 Fed. Cl. 821, 832 (2015) (“[t]he

reasoning underlying the finding that opinions of treating physicians should be given

33

It is especially unpersuasive when Program petitioners seeking to prove a child suffering from a

mitochondrial disorder was rendered autistic after vaccination point to the autism as proof of causation R.V.

v. Sec'y of Health & Human Servs., No. 08-504V, 2016 WL 3882519, at *34 n. 80 (Fed. Cl. Spec. Mstr.

Feb. 19, 2016), mot. for review den’d, 127 Fed. Cl. 136 (2016). This kind of circular logic underscores the

weakness of Petitioners’ overall claim.

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particular weight does not apply when . . . the treating physician only saw the patient after

the injury and based his opinion on the same evidence as relied upon by the retained

experts”). Overall, the testing results he obtained were too erratic, with some supporting

Petitioners’ argument while others did not. And in this case, there is not a rigid set of

criteria that call for one diagnostic conclusion depending on how those tests bear out. Dr.

Huq himself embraced a more expansive, totality-of-the-circumstances form of

diagnosing a secondary mitochondrial disease. Tr. at 104-05. Accepting that approach, I

cannot find that the overall picture of R.A.’s condition suggests it more likely than not that

he suffered from some kind of secondary mitochondrial dysfunction.

In finding as I do, I am giving Dr. Cohen’s testimony more weight than Dr. Huq’s,

and crediting his interpretation of the record over Petitioners’ expert’s testimony. But I am

appropriately tasked with weighing expert testimony, which includes assessing the

relative competencies of competing experts on a given subject matter. Porter, 663 F.3d

at 1250; Moberly, 592 F.3d at 1325–26. Both experts were qualified to offer the opinions

they did, but Dr. Cohen is the far more experienced medical practitioner when it comes

to the subject of mitochondrial diseases and disorders, with more demonstrable expertise

studying, diagnosing, and treating the condition. Although not all of Dr. Cohen’s

assertions were equally convincing, overall he persuasively established that, based on

his own professional experience, R.A.’s history is not that of a child suffering from any

form of mitochondrial disease.

II. Petitioners Have Not Satisfied the Althen Prongs

Because Petitioners cannot establish the keystone of their argument (as their

theory relies on a finding that R.A. had an underlying mitochondrial condition that was

negatively affected by the MMR vaccine), their case cannot succeed, and technically I

need not evaluate the Althen factors. Lasnetski v. Sec'y of Health & Human Servs., No.

14-580V, 2016 WL 5851889, at *21 (Fed. Cl. Sept. 9, 2016). But, in an abundance of

caution, I will briefly review each of those factors, in order to demonstrate that the

weaknesses of Petitioners’ case extended beyond the diagnostic issue presented above.

A. Althen First Prong – A Reliable Causation Theory

Petitioners have failed to offer a reliable scientific theory linking the MMR vaccine

to autism. Much of the scientific basis for their theory assumes vaccine-induced

developmental regression, which it is conceded R.A. did not experience. Accordingly,

articles like Shoffner linking fever to regression do not aid their argument. More generally,

however, Petitioners have offered little persuasive or reliable support for the proposition

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that the MMR vaccine could initiate the “inflammatory cascade” they posit eventually, and

over many months’ time, result in autism. Indeed, they even rely on discredited concepts,

such as the MMR vaccine’s alleged immuno-suppressive capacity, to pad out the theory.

See, Snyder v. Sec’y of Dept. of Health and Human Servs., No. 01-162, 2009 WL 332044,

at *102-4 (Fed. Cl. Spec. Mstr. Feb. 12, 2009), aff’d, 88 Fed. Cl. 706 (2009) (evidence

demonstrating that measles vaccines are routinely given to children with challenged or

compromised immune systems, without harmful effects, undercuts the theory that the

vaccine virus is immunosuppressive or leads to viral persistence).

The component of Petitioners’ theory relating to the connection between

mitochondrial disease and autism was similarly unreliable. Fundamentally, the literature

offered by Dr. Huq does not posit a causal reaction between one and the other, except in

cases involving clear primary mitochondrial disease, which R.A. unquestionably did not

have. Some of the studies Petitioners offered (in particular, the post-mortem brain tissue

studies like Anitha) observe an association between genes related to mitochondrial

performance and the areas of the brain linked to functions associated with autism. While

these studies individually may not be unreliable34, they would have to be joined by

substantially more corroboration, in the form of additional studies involving live

individuals, before they could credibly link autism with a secondary mitochondrial disease

sufficient to constitute a reliable theory for purposes of Vaccine Act causation. See, e.g.,

Holt v. Sec'y of Dep't of Health & Human Servs., No. 05-0136V, 2015 WL 4381588, at

*30 (Fed. Cl. June 24, 2015) (explaining that 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).

More broadly, however, the theory that a vaccine (in particular, the MMR vaccine)

could cause autism is one that has been consistently unsuccessful in the Program’s

history – at least since the time of the Omnibus Autism Proceedings and subsequent

decisions.35 Indeed, as Special Master Hastings noted in the recent Hardy decision, to

34

In addition, some of that same literature may be flawed, as Dr. Cohen pointed out, because it involved

the testing for energy-producing organelles found in dead brain tissue. Tr. at 375-78.

35

The theories were first advanced in proceedings related to the Omnibus Autism Proceeding (“OAP”),

where thousands of petitioners’ claims that certain vaccines caused autism were joined for purposes of

efficient resolution. A “Petitioners’ Steering Committee” was formed by many attorneys who represent

Vaccine Program petitioners, with about 180 attorneys participating. This group chose “test” cases to

represent the entire docket, with the understanding that the outcomes in these cases would be applied to

cases with similar facts alleging similar theories.

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date every post-OAP non-Table claim36 seeking compensation for autism injuries

purportedly related to a vaccine that has been tried has failed. See, e.g., Hardy v. Sec’y

of Health & Human Servs., No. 08-108V, 2015 WL 7732603, at *4-5 (Fed. Cl. Spec. Mstr.

Nov. 3, 2015) (referencing eleven autism claims unsuccessfully tried, plus six that were

rejected (over the petitioners’ objections) without trial). The same result has occurred in

those cases where petitioners claim a child’s underlying metabolic disorder (most

commonly a mitochondrial disease of some kind) was exacerbated by a vaccine, resulting

in a developmental regression or autism itself. See, e.g., Hardy, 2015 WL 7732603, at *4-

5 (petitioners failed to demonstrate that DTaP vaccine caused or significantly aggravated

underlying mitochondrial disease resulting in ASD); R.V. v. Sec'y of Health & Human

Servs., No. 08-504V, 2016 WL 3882519, at *42 (Fed. Cl. Spec. Mstr. Feb. 19, 2016), mot.

The Petitioners’ Steering Committee chose six test cases to present two different theories regarding

autism causation. The first theory alleged that the measles portion of the MMR vaccine precipitated autism,

or, in the alternative, that MMR plus thimerosal-containing vaccines caused autism, while the second theory

alleged that the mercury contained in thimerosal-containing vaccines could affect an infant’s brain, leading

to autism.

The first theory was rejected in three test case decisions, all of which were subsequently affirmed. See

generally Cedillo v. Sec’y of Health & Human Servs., No. 98-916V, 2009 WL 331968 (Fed. Cl. Spec. Mstr.

Feb. 12, 2009), mot. for review den’d, 89 Fed. Cl. 158 (2009), aff’d, 617 F.3d 1328 (Fed. Cir. 2010);

Hazlehurst v. Sec’y of Health & Human Servs., No. 03-654V, 2009 WL 332306 (Fed. Cl. Spec. Mstr. Feb.

12, 2009), mot. for review den’d, 88 Fed. Cl. 473 (2009), aff’d, 605 F.3d 1343 (Fed. Cir. 2010); Snyder v.

Sec’y of Health & Human Servs., No. 01-162V, 2009 WL 332044 (Fed. Cl. Spec. Mstr. Feb. 12, 2009), aff’d,

88 Fed. Cl. 706 (2009).

The second theory was similarly rejected. Dwyer v. Sec’y of Health & Human Servs., No. 03-1202V, 2010

WL 892250 (Fed. Cl. Spec. Mstr. Mar. 12, 2010); King v. Sec’y of Health & Human Servs., No. 03-584V,

2010 WL 892296 (Fed. Cl. Spec. Mstr. Mar. 12, 2010); Mead v. Sec’y of Health & Human Servs., No. 03-

215V, 2010 WL 892248 (Fed. Cl. Spec. Mstr. Mar. 12, 2010).

Ultimately a total of 11 lengthy decisions by special masters, the judges of the U.S. Court of Federal

Claims, and the panels of the U.S. Court of Appeals for the Federal Circuit, unanimously rejected the

petitioners’ claims. These decisions found no persuasive evidence that the MMR vaccine or thimerosal-

containing vaccines caused autism. The OAP proceedings concluded in 2010.

36

In a single instance, petitioners (the parents of a vaccinated child) successfully established a Table injury

– an encephalopathy – after vaccination that resulted in an autistic-like developmental regression. See,

e.g., Wright v. Sec’y of Health & Human Servs., No. 12-423V, 2015 WL 6665600 (Fed. Cl. Spec. Mstr. Sept.

21, 2015). In Wright, the petitioners met the Table criteria for an “acute encephalopathy” following

vaccination by establishing by preponderant evidence that the vaccinated child experienced a seizure

followed by loss of consciousness shortly after receipt of pertussis-containing vaccine; the severe reaction

lasted for more than 24 hours, with resulting demonstrable significant changes in behavior. But the special

master responsible for that decision (former Chief Special Master Vowell) explicitly noted in her decision

that petitioners would not have been able to establish entitlement under their non-Table claim, because

their expert presented a causation opinion that she found “absurd and biologically impossible.” Wright, 2015

WL 6665600, at *2.

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for review den’d, 127 Fed. Cl. 136 (2016) (holding the factual record does not support

petitioners’ contention that petitioner suffered from a mitochondrial disease or that the flu

vaccine had a causal connection to the development of ASD); Miller v. Sec’y of Health &

Human Servs., No. 02-235V, 2015 WL 5456093 (Fed. Cl. Spec. Mstr. Aug. 18, 2015)

(petitioners failed to demonstrate that several childhood vaccines caused encephalopathy

or aggravated underlying mitochondrial disease/dysfunction); Lehner v. Sec’y of Health

& Human Servs., No. 08-554V, 2015 WL 5443461 (Fed. Cl. Spec. Mstr. July 22, 2015)

(petitioners failed to demonstrate that flu vaccine resulted in autoimmune

encephalitis).The theory presented in this case was not sufficiently novel or compelling to

alter this trend.

B. Althen Second Prong – Sequence of Cause and Effect

The record does not allow the conclusion that R.A. experienced any reaction to the

MMR vaccine. Unquestionably he experienced a high fever within a week of the

vaccination that was sufficiently alarming for his parents to seek emergency care, but it

was diagnosed as viral and then resolved. Pet’rs’ Ex. 5 at 64. There were no trailing or

progressively concerning symptoms thereafter in the next two to three months, and his

illnesses in the first half of 2000 were not shown to be linked or associated with a pattern

different from what a healthy infant free of developmental problems might also

experience. R.A. suffered no demonstrated neurologic injury that could be linked to his

subsequent autism diagnosis. R.A.’s autism did not fully manifest for months after, without

any evidence of a physiologic process by which it was going to occur. To the extent the

Petitioners have attempted to establish onset in late December 1999, their allegations are

contradicted by the contemporaneous medical records, which identify nothing about

developmental problems for R.A. prior to June of 2000 – six months after vaccination.

I also greatly discount Dr. Shoffner’s diagnosis that R.A. did have some form of

mitochondrial disease. Not only did he evaluate R.A. nearly eight years after vaccination,

but the record reveals that he relied on incorrect facts about R.A.’s history,

mischaracterizing the evolution of R.A.’s developmental problem as a regression when

there is (as Dr. Huq agreed) no such evidence in the record. The test results Dr. Shoffner

relied upon were overall inconclusive and had too much variability to conclude that R.A.

suffered from a true metabolic disorder causally related to the MMR vaccine. There is no

corroborative diagnosis from any other treaters other than Dr. Huq, whose opinion (based

upon the same evidence) was effectively rebutted by Dr. Cohen. The evidence suggests

it is more likely than not that R.A.’s autism was idiopathic in origin, rather than caused by

the MMR vaccine.

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C. Althen Third Prong – a Medically Acceptable Timeframe

Viewed loosely, the facts of this case would fit the timeframe that Petitioners urge

flows from their theory. Thus, R.A.’s purported inflammatory cascade was triggered within

a week of vaccination, and then his symptoms slowly agglomerated (as evidenced by his

intermittent infections) until his developmental issues were facially apparent six or more

months later. But looked at more carefully, the proposed timeframe does not work, and

ultimately reflects the temporal reasoning rejected by controlling precedent. LaLonde v.

Sec’y of Health & Human Servs., 746 F.3d 1334, 1341 (Fed. Cir. 2014) (holding that “the

basis for Ms. LaLonde’s petition reduces to a temporal relationship between the

administration of the DTaP vaccine and M.L.’s focal brain injuries. As we have stated

before, a temporal correlation alone is not enough to demonstrate causation.”); Althen,

418 F.3d at 1278 (petitioners must show a proximate temporal relationship between

vaccination and injury). For even if it is assumed that the MMR could trigger a neurologic

injury leading to developmental problems of any kind within a few days to a week after a

vaccine was administered, Petitioners’ theory does not explain why it would subsequently

be expected to take four to six months or more before the developmental side of the injury

– the primary injury complained of here – to manifest, without any other obvious

physiologic signs. No literature or reliable scientific support was offered to explain why it

took so long without any demonstrable change in R.A., and the record itself also provides

no illumination of this point.

CONCLUSION

The Andersons plainly love their son, and Mr. Anderson’s dedication in attempting

to grasp and understand R.A.’s condition was clear to me from his heartfelt testimony,

which brought to life R.A. as a person. But the factual record simply does not support

Petitioners’ contention that the MMR vaccine had any connection to R.A.’s ASD

diagnosis, nor have the Petitioners established that the vaccine could result in

developmental problems in the manner proposed by their theory. The evidence offered,

plus the record, is not nearly enough to satisfy the Act’s otherwise-lenient preponderance

evidentiary standard. This is not a close case. Petitioners have not established

entitlement to a damages award.37

IT IS SO ORDERED.

/s/ Brian H. Corcoran

Brian H. Corcoran

Special Master

37

Pursuant to Vaccine Rule 11(a), the parties may expedite entry of judgment by filing a joint notice

renouncing their right to seek review.

41