McCollum v. Secretary of Health and Human Services

In the United States Court of Federal Claims

OFFICE OF SPECIAL MASTERS

No. 14-790V

(to be published)

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

MICHAEL McCOLLUM, *

*

* Filed: September 15, 2017

Petitioner, *

*

v. * Entitlement;

* Influenza (“Flu”) vaccine;

* Narcolepsy; Cataplexy;

SECRETARY OF HEALTH AND * Preponderance Standard;

HUMAN SERVICES, * Althen Prong One; Relevance

* of Epidemiologic Evidence

Respondent. *

*

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

Richard Gage, Richard Gage P.C., Cheyenne, WY, for Petitioner.

Alexis B. Babcock, U.S. Dep’t of Justice, Washington, DC, for Respondent.

DECISION DENYING ENTITLEMENT1

On August 29, 2014, Michael McCollum filed a petition seeking compensation under the

National Vaccine Injury Compensation Program (the “Vaccine Program”)2, alleging that he

developed narcolepsy with cataplexy due to his receipt of the influenza (“flu”) vaccine in the fall

of 2011. Petition (“Pet.”) (ECF No. 1) at 1.

1

This decision 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). This means the ruling will be available to anyone with access to

the internet. As provided by 42 U.S.C § 300aa-12(d)(4)(B), however, the parties may object to the decision’s inclusion

of certain kinds of confidential information. To do so, Vaccine Rule 18(b) permits each party fourteen (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. Id.

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 at 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 (but will omit that statutory prefix).

An entitlement hearing was held in this matter on April 4, 2017, in Washington, D.C. After

considering the record as a whole, and for the reasons explained below, I find that Petitioner is not

entitled to compensation, primarily due to his inability to establish a reliable causation theory.

I. Factual Background

A. Pre-Vaccination Medical History

Mr. McCollum’s medical records are significant for several pre-existing health conditions,

including obstructive sleep apnea (“OSA”),3 smoking, attention deficit/hyperactivity disorder

(“ADD”), obesity (having a body mass index score above 35), type II diabetes, severe

hypertension4, and chronic back problems. Ex. 1 at 4-5, 22-24; Ex. 2 at 4-5, 10, 25.5 He was 51

years old at the time of his vaccination and subsequent sleep-related symptoms.

Throughout the records obtained from Petitioner’s primary care physician, Dr. Joseph C.

Petrini, there are several documented incidents of general sleep-related issues that predate the

alleged flu vaccination. Ex. 1 at 4-5, 64-68. Those incidents vary in description and occur

sporadically from October 2009 to July 2011. Id. at 64-68. Most were referred to in general terms,

however - “sleep problems,” “sleep disturbance,” “sleepiness,” “difficulty sleeping,” and “still too

fatigued to work.” Id. at 64-68.

Mr. McCollum also experienced other health issues prior to vaccination that echo the

symptoms complained of in this case. A year prior to the vaccination at issue, for example,

Petitioner was hospitalized on July 10, 2010, at Salinas Valley Memorial Healthcare System

(“Salinas Memorial”) in Salinas, CA, for “an altered level of consciousness with difficulty

expressing himself and bilateral shaking of his arms.” Ex. 1 at 22. His blood pressure when he

arrived at the emergency department was low (82/52), which eventually improved but remained

low (108/66). Id. These symptoms lasted several hours before he was admitted at the hospital. Id.

at 23. At this time, Mr. McCollum specifically reported that he fell asleep while riding in a car and

had “developed speech disturbance” earlier in the day. Ex. 2 at 31. Consulting neurologist, Dr.

3

OSA consists of periods in which one stops breathing during sleep. Dorland’s Illustrated Medical Dictionary 117

(32d ed. 2012) (hereinafter “Dorland’s”). Risk factors include obesity (a body mass index above 35), being male,

hypertension, snoring, and daytime sleepiness. Transcript (“Tr.”) at 144.

4

Hypertension is otherwise known as high blood pressure. Dorland’s at 896.

5

Narcolepsy was also listed in an undated portion of the medical history section of the notes of Petitioner’s primary

care physician, Dr. Petrini. Ex. 1 at 5. This record is preceded by a page dated October 27, 2009 – suggesting that Mr.

McCollum had been diagnosed prior to his vaccination with the condition - but that record is immediately followed

by another record that indicates Petitioner was being treated at Stanford, which did not occur until 2012. Ex. 1 at 4-6.

It is also unclear if the narcolepsy-referencing record was written by Dr. Petrini, or if it was Mr. McCollum describing

his own medical history. Because of these factors, I cannot afford significant weight to this stray reference to

narcolepsy possibly pre-dating Petitioner’s vaccination.

2

Gerald Wahl, recommended an electroencephalogram (“EEG”) and an echocardiogram;6 both of

which showed normal results. Ex. 1 at 23. Dr. Wahl concluded that Petitioner’s clinical

presentation was indicative of a transient ischemic attack7 (“TIA”), but that the TIA could not

account for the shaking of his arms. Ex. 2 at 32. Petitioner recovered at the hospital and was

discharged on July 12, 2010. Ex. 1 at 22. On a follow-up visit, Dr. Petrini ultimately proposed that

Petitioner’s hypertension medications were a likely cause of his symptoms, stating “I feel that the

patient’s altered level of consciousness and hypotension was due to taking his antihypertensive

medications as prescribed. They will be reduced.” Id. at 23. The record does not reveal a similar

occurrence until after Mr. McCollum received the flu vaccine over a year later.

B. Circumstances Relating to Mr. McCollum’s 2011 Vaccination

Petitioner lacks direct proof establishing that he received the flu vaccine in October 2011

as alleged, but instead has sought to prove this via circumstantial evidence. Accordingly, certain

facts involving third parties to this claim bear on resolution of that issue.

Linda McCollum, Petitioner’s wife, was admitted to the Salinas Memorial emergency room

on September 24, 2011, after experiencing a “near syncopal episode” likely due to hypotension.8

Ex. 12 at 4-10. Upon discharge later that day, Mrs. McCollum received the flu vaccine, and was

advised that the entire family should follow suit. See Affidavit of Linda McCollum, filed as Ex.

34 at 1; Transcript (“Tr.”) at 7. Mrs. McCollum asserts that she specifically told Petitioner he also

needed to receive the flu vaccination, which he claims to have accomplished a few weeks later.

Tr. at 7-8.

Mr. McCollum has contended specifically that he received a flu vaccine from a Walgreens

pharmacy near his home around October 5, 2011. See Affidavit of Michael McCollum, filed as

Ex. 35. The Walgreens Company could not produce records regarding Petitioner’s vaccination,

however. Id. at 1-2. At best, Walgreens has confirmed that the H1N1 vaccine was being

administered at its store locations across the U.S. in the fall of 2011, and that the cost for the

vaccine was $31.99 for patients who were not insured. Ex. 38 at 1. Petitioner filed bank records

for the relevant months in an attempt to show that he used a bank debit card at Walgreens numerous

times in September or October of 2011. The bank records revealed that the only purchase dated

6

An EEG is a test that detects electrical activity in your brain. Dorland’s at 600. An echocardiogram uses sound waves

to create an image of the subject’s heart. Dorland’s at 589.

7

A TIA is caused by a clot blocking blood from reaching the brain. It is similar to a stroke, but much shorter in

duration. See Dorland’s at 1927, 1953, 961.

8

A syncopal episode is a loss of consciousness due to “generalized cerebral ischemia.” Hypotension is otherwise

known as low blood pressure. Dorland’s at 1818, 906.

3

after Mrs. McCollum’s hospitalization that matched or surpassed the cost of a flu vaccine in 2011

occurred on October 18, 2011.9 Ex. 36 at 5.

C. Post-Vaccination Medical History

Although the records from the months immediately after Mr. McCollum received the flu

vaccine do not reference any possible early signs of narcolepsy, Petitioner contends that he was in

fact beginning to experience such symptoms.10 Mr. McCollum recalled at trial his first symptoms

of narcolepsy beginning around December 2011, when he “would just drop [into sleep] like a

stone.” Tr. at 49. He remembered really noticing the symptoms shortly before he saw Dr. Petrini

in January 2012, when he hallucinated while driving on the freeway. Id. at 64. During this time,

he would sit in front of the television and would suddenly wake up and realize he had dropped the

cup that was in his hand. Id. at 49. Mrs. McCollum specifically recalled that Petitioner’s first

incidence of cataplexy11 was when they were watching football in late January. Id. at 18-19. She

stated that Petitioner felt the cataplexy when he became animated by telling jokes, playing with

his granddaughter, or when receiving praise. Id. 18-20.

On January 29, 2012 (three months after the alleged vaccination), Mr. McCollum reported

to the Community Hospital of the Monterey Peninsula emergency room complaining about

weakness in his left leg, tingling on the left side of his face, lightheadedness, and dizziness. Ex. 1

at 51. The attending physician, Dr. Samuel Melton, gave Petitioner a neurologic examination and

a TIA workup, but both were normal. Id. Dr. Melton concluded that Petitioner’s sedative

medications, Soma and Norco, which had previously been prescribed for Petitioner’s back pain,

had likely contributed to his symptoms. Id. Petitioner went to see Dr. Petrini again on January 30,

2012, at which time Dr. Petrini noted that the cause of Petitioner’s recent symptoms could be

neurological. To that end, Dr. Petrini referred Petitioner to a neurologist, Dr. Wayne Shen. Ex. 1

at 69.

Petitioner visited Dr. Shen on February 7, 2012. Ex. 3 at 1. Mr. McCollum now reported

(consistent with his trial testimony) that he had started to experience double vision, hallucinations,

the sudden onset of sleep on long drives, weakness and numbness in his leg, and that he would get

“a weird feeling on his face” when he laughed. Id. Petitioner also complained of constant

sleepiness, increased sleeping generally, and sleep paralysis. Id. Mr. McCollum recalled that the

9

These bank records did not itemize goods bought, but instead only denoted the total amount purchased -- $55.97.

See generally Ex. 36.

10

For example, on November 16, 2011, Mr. McCollum visited Dr. Petrini complaining about a productive cough, and

was diagnosed with bronchitis. Ex. 1 at 69.

11

Cataplexy is a condition characterized by abrupt attacks of muscle weakness or hypotonia brought on by emotional

stimuli (e.g. mirth, fear, surprise), and is often found in association with narcolepsy. Dorland’s at 303.

4

symptoms started a week before his visit to Dr. Shen, although his wife relayed to Dr. Shen that

she had noticed the symptoms weeks prior to the visit. Id.

In response, Dr. Shen proposed several differential diagnoses including narcolepsy, and

ordered a Multiple Sleep Latency Test (“MSLT”) to evaluate narcolepsy’s likelihood. Id. at 3-4.

Dr. Shen’s notes from his examination of Mr. McCollum indicate the following:

This is a very complicated patient with reports of hypersomnolence during the day and

night with some symptoms of sleep paralysis and sensation of muscle weakness and

laughing that raises the possibility of Narcolepsy. Other consideration is toxic

encephalopathy from his medications with sedation but he has been on this regimen long

term without these symptoms in the past. He has ADD which might cause difficulty with

attention but the history does not suggest that his symptoms are due to distraction. He could

also suffer daytime sleepiness from Obstructive Sleep Apnea Syndrome with the obesity

and snoring but he reportedly already had a negative sleep study.12 With the movements

during dream sleep noted by the spouse we cannot rule out a REM state sleep disorder. Ex.

3 at 3.

D. Confirmation of Narcolepsy Diagnosis and Subsequent Treatment

By mid-February, about two months after his initial symptoms began, Petitioner started to

experience cataplexy more often. He distinguished the symptoms from narcolepsy symptoms

because with cataplexy he would drop straight to the ground, which frightened him before he knew

what it was. Tr. at 50-51.

On March 1, 2012, Mr. McCollum returned to Dr. Shen reporting worsening symptoms

that included “[s]leep dreaming and waking up.” Ex. 3 at 5. During such an episode, Petitioner

stated he “awoke from sleep and thought that he was carrying a leather pouch and wanted to give

it to [his] son.” Id. Dr. Shen also shared the results of the MSLT, which indicated sleep onset

latency of five minutes, confirming for Dr. Shen the appropriateness of a diagnosis of narcolepsy

along with “near cataplexy.”13 Id. at 6. At the same time, the other diagnostic tests returned

negative results, helping Dr. Shen eliminate other potential causes such as a cord compression or

abnormality. However, in an effort to further corroborate his diagnosis, Dr. Shen referred

Petitioner to a neurologist/sleep specialist, Dr. June Seliber-Klein, at the June Klein Practice in

Monterey, California, for additional evaluation. Id. at 5-7, Ex. 8 at 1.

12

The records for this sleep study were never filed nor was there any other mention of such a sleep study being

performed.

13

Dr. Shen amended Mr. McCollum’s diagnosis to formally include cataplexy on March 29, 2012. Ex. 3 at 10.

5

Petitioner saw Dr. Klein on April 16, 2012. See generally Ex. 8. As the notes from this visit

indicate, because Mr. McCollum had by this time received from Dr. Shen a narcolepsy diagnosis

that had some reliable clinical support, Dr. Klein felt it unnecessary to perform a second MSLT,

even though the test had not generated evidence of sleep onset REM (“SOREM”) - typically the

hallmark diagnostic criteria of narcolepsy. Ex. 8 at 2; Tr. at 140. She further indicated that she

wanted to rule out OSA because Mr. McCollum possessed the necessary risk factors. Ex. 8 at 2.

Mr. McCollum, however, did not follow-up with Dr. Klein and the records from the visit are

limited. Ex. 8 at 2. On April 30, 2012, Petitioner followed up with Dr. Shen reporting that his

cataplexy was better, although he still experienced daily cataplectic attacks. Ex. 3 at 12. Dr. Shen

referred him to a sleep clinic at the Stanford Sleep Medicine Center (“Stanford Clinic”) in

Redwood City, California. Id. at 13.

On June 20, 2012, Mr. McCollum visited the Stanford Clinic and was seen by Drs. Vikas

Jain and Emmanuel Mignot.14 Ex. 6 at 33. They conducted a diagnostic polysomnogram,15 and

after reviewing its results diagnosed Petitioner with “hypersomnia with sleep apnea

(unspecified)”— a condition characterized by excessive day-time sleepiness but distinct from

narcolepsy, as it is caused by the relaxation of muscles in the throat, which makes it difficult to

breathe, leading a person’s brain to wake them from nocturnal sleep. Id at 31; Obstructive sleep

apnea: Symptoms and causes, Mayo Clinic, http://www.mayoclinic.org/diseases-

conditions/obstructive-sleep-apnea/symptoms-causes/dxc-20205871 (last visited June 26, 2017).

Although there is not extensive explanation of the doctors’ evaluation of Mr. McCollum’s

condition, there is an indication at his first visit to Stanford of treater awareness of his prior MSLT

and the flu shot. As Dr. Jain stated:

“[Mr. McCollum] presents today for evaluation for narcolepsy/cataplexy…He only had

an MSLT performed without PSG performed the night before. He was found to have a

short sleep latency which raised concern for hypersomnia. He received the H1N1

vaccination in 2010. He also received flu shot this past year [2011] in September.” Id. at 3.

The Stanford Sleep Clinic doctors took a blood sample from Petitioner in order to test for

the presence of the gene that predisposes individuals to narcolepsy16—although it is also fairly

14

Dr. Mignot is a recognized expert in the field of narcolepsy, and has published several research papers on the topic

as well as running the Stanford Sleep Clinic. Dr. Mignot has also been recognized as an expert on the subject in the

Program. See, e.g., D’Tiole v. Sec’y of Health & Human Servs., No. 15-085, 2016 WL 7664475 (Fed. Cl. Spec. Mstr.

Nov. 28, 2016) (denying entitlement on other grounds), mot. for review den’d, 2017 WL 2729570 (Fed. Cl. Mar. 2,

2017), appeal docketed, No. 2017-1982 (Fed. Cir. May 4, 2017); Garrison v. Sec’y of Health & Human Servs., No.

14-762V, 2015 WL 7424016 (Fed. Cl. Spec. Mstr. Oct. 29, 2015).

15

A polysomnogram is the recording of multiple physiological variables during sleep. Dorland’s at 1494.

16

Human Leucocyte Antigen (HLA)-DQB1*06:02 is a genetic marker present in 12-38 percent of the general

population. See Ex. 13 at 6. Narcoleptic patients with low hypocretin almost all express the genetic marker. Id.

6

common in the general population without narcolepsy— and found that Mr. McCollum possessed

the gene. They did not, however, perform a spinal tap to look for the presence of hypocretin in his

cerebral spinal fluid, a finding that constitutes strong diagnostic evidence of narcolepsy. Ex. 6 at

37; Tr. at 140, 154. Nevertheless, on July 13, 2012, the Stanford doctors revised Mr. McCollum’s

diagnosis to include narcolepsy and cataplexy after Petitioner took part in a sleep study at the

Stanford Clinic, during which time he exhibited hypoventilation, low oxygen saturations, and

OSA. Ex. 6 at 52-57.

Mr. McCollum visited the Stanford Clinic on numerous occasions between August 2012

and April 2013. He also took part in additional research conducted through the sleep clinic at

Stanford. Ex. 5 at 7-10, 14-17, 30-34, 42-48; see also De la Herran-Arita et al., CD4+T cell

Autoimmunity to Hypocretin/Orexin and Cross Reactivity to a 2009 H1N1 Influenza A Epitope in

Narcolepsy, Science Transitional Med 5, 216ra176 (2014) (Retracted), filed as Ex. 19.17 Despite

the heavy medication he received to counteract his symptoms, Petitioner still reported “rather

significant cataplexy.” Ex. 5 at 7. Dr. Chad Ruoff suggested that Mr. McCollum might also have

narcoleptic REM sleep behavior disorder (“RBD”). Id. at 9-10. Subsequently, Mr. McCollum

reported that he had not experienced sleep paralysis in months, had decreased his napping to three

times a week, and was able to drive for over two hours, although he continued to report cataplectic

attacks and hallucinations. Id. at 25, 31. Petitioner’s medication was eventually increased. Id. at

31, 34, 42-48. Mr. McCollum was finally able to return to work on May 10, 2013. Ex. 4 at 15.

On September 10, 2013, Mr. McCollum returned to the Stanford Clinic to ask for

paperwork necessary to reinstate his driver’s license. Ex. 5 at 55. Dr. Ruoff noted that Mr.

McCollum had improved significantly. Id. In an e-mail message exchange between Petitioner and

Dr. Ruoff in September 2013, Dr. Ruoff confirmed that Mr. McCollum possessed the HLA-

DQB1*06:02 gene that may have predisposed him to narcolepsy. Id. at 65. Dr. Ruoff also stated

“[q]uestionable reported history transient ischemic attacks - I do not know the details but could

imagine a cataplectic attack being interpreted as a “TIA,” although he acknowledged as well that

he had not reviewed the prior records and was therefore speculating. Id. at 60.

II. Fact Witness Testimony

Petitioner presented three witness affidavits - two from Mrs. McCollum and one from

himself. Exs. 34-35, 37. In addition, Mr. and Mrs. McCollum both testified at the hearing. Tr. at

4-73.

The McCollums’s testimony focused on the attempt to establish that Mr. McCollum did in

fact receive the flu vaccine in the fall of 2011. Neither of them could recall the specific day that

17

This article was ultimately retracted, because its results could not be replicated. D’Tiole, 2016 WL 7664475, at *12

n.17.

7

Petitioner received the vaccine, but they both testified that the vaccination occurred at their local

Walgreens shortly after Mrs. McCollum’s hospitalization in late September 2011. Tr. at 7, 41-42.

Although Petitioner could not remember in which arm he received the vaccine, he specifically

recalled that it was an injection administered in his arm, noting the big knot he got in his arm

following vaccination. Id. at 8, 42, 61. The McCollums also verified that due to the proximity of

the Walgreens to their home, they—more frequently Mr. McCollum—dropped by the location

quite often, making it difficult to pinpoint in their billing records which charge could have been

the vaccination. Id. at 29.

Mr. and Mrs. McCollum addressed in their testimony the issue of Petitioner’s documented

sleep problems predating the fall 2011 vaccination. Both admitted that they could not completely

explain such prior sleep issues. Tr. at 10, 44. However, the McCollums did propose that Mr.

McCollum’s earlier two back surgeries had made it uncomfortable for him to sleep. Id. They also

suggested that Petitioner had sleep apnea at the time but it was undiagnosed. Id.

Both Mr. and Mrs. McCollum also noted in their testimony that during Mr. McCollum’s

treatment at the Stanford sleep clinic, his physicians requested (contrary to the theory proposed

herein relating the vaccine to the claimed illness) that he receive an additional flu shot, and that

he did so in October 2012, although (like the vaccination at issue in this case) there is no formal

record of it. Tr. at 56-57. Mr. McCollum recalled that Mrs. McCollum was hesitant for Petitioner

to receive the vaccine, but he was convinced to go ahead with vaccination because he wanted to

help others with the condition by assisting the clinic in evaluating whether the vaccine was in fact

related. Id. at 56. Petitioner stated that this vaccine was received at a local CVS, not at the Stanford

Clinic. Tr. at 39. He and Mrs. McCollum also reported that his vivid dreams became more severe

for about a week after receipt of his second flu shot, but did not otherwise report any other related

symptoms stemming from the second vaccination. Tr. at 22-23.

III. Expert Testimony

One expert witness was presented by each party. Petitioner offered Dr. Marcel Kinsbourne,

a neurologist. Respondent presented Dr. Maryanne Deak, whose specialty is sleep disorders. The

opinions and testimony of the relevant experts are set forth below.

A. Dr. Marcel Kinsbourne

Dr. Kinsbourne testified at hearing, and offered two expert reports opining that the flu

vaccine caused Petitioner to develop narcolepsy and cataplexy. Tr. at 74-128; Expert Report, filed

on Sept. 15, 2015 as Ex. 13 (ECF No. 21) (“Kinsbourne First Rep.”); Supplemental Expert Report,

filed on Feb. 22, 2017, as Ex.41 (ECF No. 40) (Kinsbourne Second Rep.”).

8

As his CV indicates, Dr. Kinsbourne is board certified in pediatrics. See Dr. Kinsbourne

Curriculum Vitae, filed on Sep. 15, 2015 as Ex. 14 (ECF No. 21) (“Kinsbourne CV”), at 1. He

received his medical degree in England, and he has been licensed to practice medicine in North

Carolina since 1967. Id. From 1967 to 1974, Dr. Kinsbourne served as an associate professor in

pediatrics and neurology and a senior research associate at Duke University Medical Center before

holding a series of academic positions, including professorships in pediatrics, neurology, and

psychology. Id. at 2. His clinical experience includes serving as a senior staff physician in Ontario

from 1974-1980, and a clinical associate in neurology at Massachusetts General Hospital from

1981-1991, although (as noted in other cases) many years have passed since he regularly saw

patients. Pope v. Sec’y of Health & Human Servs., No. 14-078V, 2017 WL 2460503, at *8 (Fed.

Cl. Spec. Mstr. May 1, 2017). He does not have any specific expertise in narcolepsy, nor has he

studied or researched the immunologic issues raised by theories claiming vaccine causation

(although his general neurologic expertise made him competent to discuss such matters).

Dr. Kinsbourne proposed that by way of the mechanism of molecular mimicry, the H1N1-

containing flu vaccine that Petitioner received in October 2011, was the cause of his narcolepsy

and cataplexy. See Kinsbourne First Rep. at 10. As Dr. Kinsbourne explained, narcolepsy is a

condition characterized by a “disturbance of the wake/sleep cycle such that the sleep aspect of the

wake/sleep cycle is exaggerated.” Tr. at 76, 80. Narcolepsy is very often associated with a

deficiency of hypocretin, a neuropeptide found in the brain that helps regulates sleep. Id. at 80.

Hypocretin is secreted throughout the day and when it is signaled by another neuron in the brain,

it is projected to other areas of the brain and activates those areas, which has the effect of

stimulating neurotransmitters that control the activation level in the brain sufficient to maintain a

person’s wakeful state. Id. In patients with narcolepsy, by contrast, the receptors responsible for

the release of the hypocretin are blocked or destroyed. Id. at 79. Today, narcolepsy is understood

to be an autoimmune condition, based on its association with an immune system marker— human

leukocyte antigen—as well as the fact that certain autoantibodies are believed likely to cause the

hypocretin receptor interference that results in the condition’s sleep-related clinical symptoms. Id.

at 78.

In support of his statements about how narcolepsy is believed to occur, Dr. Kinsbourne

referenced animal studies. See, e.g., Ying Li, et al., Hypocretin/Orexin Excites Hypocretin Neurons

via a Local Glutamate Neuron - A Potential Mechanism for Orchestrating the Hypothalamic

Arousal System, 36 Neuron 1169, 1169-81 (2002), filed as Ex. 43 (ECF No. 43-2); Ming-Fing Wu,

et al., Role of the Hypocretin (orexin) Receptor 2 (Hcrt-r2) in the Regulation of Hypocretin Level

and Cataplexy, 31 J. Neuroscience 6305, 6305-10 (2011), filed as Ex. 44 (ECF No. 43-3); Akihiro

Yamanaka, et al., Orexin Directly Excites Orexin Neurons Through Orexin 2 Receptors, 30 J.

Neuroscience 12642, 12642-52 (2010) filed as Ex. 45 (ECF No. 43-4). These studies focused on

the idea of positive feedback within hypocretin neurons, ultimately showing that hypocretin

neurons produce “hypocretin which then stimulates the neuron’s own hypocretin receptor further

9

to activate the neuron.” Tr. at 83. But if the hypocretin receptor is blocked from sending feedback,

then less hypocretin will be produced because the neuron is dramatically less activated. Id. Dr.

Kinsbourne opined that if that positive feedback theory is accurate, it explains why hypocretin

levels fade away in patients with narcolepsy – some biologic process blocks the receptors. Id. at

84.

With that context in mind, Dr. Kinsbourne opined specifically how the flu vaccine could

have a causal relationship to narcolepsy, by relying on epidemiologic evidence involving a

different form of flu vaccine. Pandemrix is an inactivated, adjuvanted monovalent H1N1 flu

vaccine18 administered in Europe and associated with a high rate of narcolepsy in a number of

countries, such as Finland. See Elizabeth Miller et al., Risk of Narcolepsy in Children and Young

People Receiving AS03 Adjuvanted Pandemic A/H1N1 Influenza Vaccine: Retrospective Analysis,

Brit. Med. J. 346, 794 (2014), filed as Ex. 29 (ECF No. 23); Jacques Montplaisir, et al., Risk of

Narcolepsy Associated with Inactivated Adjuvanted (AS03) A/H1N1 (2009) Pandemic Influenza

Vaccine in Quebec, 9 PLOS One, no. 9, 2014, at 1-9, filed as Ex. 30 (ECF No. 23); D. O’Flanagan,

et al., Investigation of an Association Between the Onset of Narcolepsy with Pandemic Influenza

Vaccine, Ireland April 2009-2010, 19 Euro Surveillance 5, 5-15 (2014), filed as Ex. 32 (ECF No.

23) (“O’Flanagan”); Markku Partinen, et al., Increased Incidence and Clinical Picture of

Childhood Narcolepsy Following the 2009 H1N1 Pandemic Vaccination Campaign in Finland, 7

PLOS One, no. 3, 2012, at 1-8 (“Partinen”).19

Recent research in the United States has attempted to determine what lies beneath the

generally observed association between Pandemrix and narcolepsy. Dr. Kinsbourne relied

specifically upon a series of related articles: S. Sohail Ahmed, et al., Narcolepsy, 2009 A(H1N1)

Pandemic Influenza, and Pandemic Influenza Vaccinations: What is Known and Unknown About

the Neurological Disorder, the Role for Autoimmunity, and Vaccine Adjuvants, 50 J.

Autoimmunity 1, 7 (2014), filed as Ex. 40 (ECF No. 39) (“Ahmed I”), and S. Sohail Ahmed, et

al., Antibodies to Influenza Nucleoprotein Cross-React with Human Hypocretin Receptor 2, 7 Sci.

Translational Med. 294 (2015) , filed as Ex. 15 (ECF No. 22) (“Ahmed II”).

Researchers had initially opined that an adjuvant Pandemrix contained, as opposed to the

inactivated H1N1 virus itself, was responsible for the high association with narcolepsy. Ahmed I,

however, observed that “no similar association has been reported to date with the [similarly-

adjuvanted] pandemic vaccine made using the Canadian inactivation/purification protocol

[Arepanix],” and widely administered in Canada, suggesting that the adjuvant itself may not have

18

A vaccine is rendered inactive through the process of destroying the biological activity of the virus in the vaccine,

by the action of heat or other physical or chemical means. Dorland’s at 925. In a vaccine, the adjuvant serves to

increase the adaptive immune response created by the antigen—in this case the antigen for the flu. Tr. at 86.

19

Petitioner’s expert, Dr. Kinsbourne, referenced the Partinen article in his first expert report; however, the article

was never filed. The article is now filed as Court’s Exhibit 1.

10

played a causal role. See Ahmed I at 8. Rather, the Ahmed I authors proposed that autoantibodies

generated in response to a cross reaction with the H1N1 components (via a molecular mimicry

process) contained in Pandemrix likely blocked hypocretin receptors sufficient to trigger

narcolepsy in those individuals susceptible to it (mainly because they possess the genetic haplotype

HLA-DQB1*0602). Kinsbourne First Rep. at 7; Ahmed I at 8.

There still remained the question of what specific aspect or feature of the H1N1

components in the flu vaccines studied could be implicated in the autoimmune process that resulted

in blocking of the hypocretin receptors. Ahmed II’s authors began to suspect that that the

nucleoprotein (“NP”) antibody content of the H1N1-based flu vaccines was a more likely causal

factor for narcolepsy than the adjuvant. Ahmed II at 1-2. To evaluate why different forms of the

same adjuvanted flu vaccine could have different associations with narcolepsy, they measured the

amounts of NP in different versions, finding in fact that Pandemrix was high in NP due to the

process used to inactivate its H1N1 viral components – while other versions had less NP. Id. at 4.

Thus, any vaccine containing similar H1N1 viral strain components could have the same effect,

depending on the NP amounts contained therein. Kinsbourne First Rep. at 7-8.

There is an immediate facial limitation, however, to the application of such literature to

this case. Pandemrix is not a form of the flu vaccine administered in the U.S. Tr. at 86; see also

Narcolepsy Following Pandemrix Influenza Vaccination in Europe, CDC,

https://www.cdc.gov/vaccinesafety/concerns/history/narcolepsy-flu.html (last visited September

5, 2017). It is also undisputed in this case that Petitioner did not receive Pandemrix. Indeed, if he

had, his claim would have been promptly dismissed, since the 2009 monovalent H1N1 vaccine is

not a covered Program vaccine. Morris Sabin v. Sec’y of Health & Human Servs., No. 13-624V,

2014 WL 2979385, at *2 (Fed. Cl. Spec. Mstr. Feb. 7, 2014) (citations omitted).

In order to apply the Pandemrix-associated findings to the likely form of the vaccine

administered herein, Dr. Kinsbourne made several contentions. First, he noted literature

associating the wild H1N1 virus with narcolepsy. Kinsbourne Rep. at 4; Fang Han, et al.,

Narcolepsy Onset is Seasonal and Increased Following the 2009 H1N1 Pandemic in China, 70

Am. Neurological Ass’n 410, 410-17 (2011), filed as Ex. 22 (ECF No. 22) (“Han”). Han was a

retrospective study of narcolepsy onset in patients diagnosed in Beijing, China from 1998-2010.

Han at 1. Han purported to show that the occurrence of narcolepsy onset was seasonal, based upon

a reported increase in the condition’s onset following the 2009 H1N1 winter influenza pandemic.

Accordingly, the wild H1N1 influenza virus itself, along with other upper airway infections, was

highly correlated to narcolepsy. Han at 1. However, Han’s authors acknowledged that the sample

of patients in the study was not representative of China as a whole. Id. at 7. The Ahmed articles

also conceded that Han’s findings were far from definitive in establishing a wild virus-narcolepsy

link. See, e.g., Ahmed II at 6 (observing that “studies outside China have not reported an increase

11

in narcolepsy cases in unvaccinated subjects,” and proposing that the high residential density of

Beijing might simply have made the studied residents more susceptible to flu infection).

Second, Dr. Kinsbourne pointed to certain findings in the literature on Pandemrix and NP

levels that pertained to other forms of the vaccine akin to what has been administered in the United

States. A chart presented in Ahmed II compared the levels of NP in different flu vaccines, including

some actually administered in the United States, such as Fluvirin and Fluzone. Ahmed II at 8,

Table 2; Kinsbourne Second Rep. at 5; Tr. at 123-26. The NP levels for certain non-Pandemrix

forms of the trivalent flu vaccine that are administered in the U.S. were in fact comparable to

Pandemrix. Id. Dr. Kinsbourne allowed for the fact that “it makes sense that Pandemrix had the

strongest effect because it had the most nucleoprotein in it,” thereby making the risk of narcolepsy

lower for different forms – but (as the Ahmed II Chart established) that did not mean the other

forms could not also have the same cross-reactive impact, given their similar NP levels. Tr. at 102.

Dr. Kinsbourne also addressed in his opinion an observational epidemiologic study20 filed

by both sides that undermines the proposed connection between non-Pandemrix forms of the

vaccine and narcolepsy. See Jonathan Duffy et al., Narcolepsy and Influenza A (H1N1) Pandemic

2009 Vaccination in the United States, 83 Neurology 1823, 1823-30 (2014), filed as Ex. 20 (ECF

No. 22) (“Duffy”). Duffy’s authors studied the association between narcolepsy and the

unadjuvanted version of the H1N1 vaccine utilized in the United States, retrospectively surveying

650,995 individuals vaccinated with an H1N1 strain flu vaccine in 2009, but failed to find an

increase in narcolepsy. Id. at 1823. Of these patients, zero developed symptoms during the 180

days following receipt, despite an expected incidence of 6.52. Id. In the 2010-11 seasonal flu

vaccine study, 870,530 individuals received some form of the vaccine, but only two had onset of

narcolepsy symptoms during the defined time period, compared to 8.83 expected. Id. at 1827. The

Duffy authors hypothesized that the H1N1 antigens in these versions of the vaccine were

themselves not sufficient to increase narcolepsy incidence. Id. Dr. Kinsbourne argued, however,

that Duffy’s reliability was limited by the fact that it was not a controlled study, and that its authors

admitted that because of the inherent limits to the study, its conclusions “must be interpreted with

caution.” Id. at 1828; Kinsbourne First Rep. at 5; Tr. at 116.

In his testimony, Dr. Kinsbourne was also asked to address Mr. McCollum’s prior TIA

diagnoses, along with his pre-vaccine history of sleepiness. Dr. Kinsbourne characterized such

instances as distinguishable from Petitioner’s post-vaccination symptoms, attributing some to a

20

Dr. Kinsbourne’s report flatly denies the existence of any “published formal epidemiological study of the association

of H1N1 vaccines and narcolepsy.” First Kinsbourne Rep. at 4. He nevertheless discussed Duffy at trial and in his

report, but denied that it constituted epidemiologic evidence, characterizing it instead as either an “ecological study”

or merely an “observational” but “uncontrolled” study that was therefore inherently less reliable. Kinsbourne First

Rep. at 4; Tr. at 116. But (as discussed in greater detail below) Dr. Kinsbourne’s attempts to make category distinctions

between Duffy and a “true” epidemiologic study were not persuasive.

12

failure to get enough sleep rather than as evidence of narcolepsy, which he proposed would more

likely present as sleeping too much or being unable to resist day sleep urges. Tr. at 110. He

acknowledged that one of Mr. McCollum’s Stanford doctors, Dr. Ruoff, had speculated that the

incidents of TIA could have reflected undiagnosed cataplexy, but expressed adamant

disagreement, arguing that the TIA incident had lasted far too long to be so considered. Id. at 112.

TIA, he maintained, is a mini stroke and would therefore only effect one side of the body, where

a cataplectic attack affects a person’s entire body. Id.

Dr. Kinsbourne finally addressed appropriate timelines for the onset of narcolepsy. He

recognized that “typical” onset is difficult to determine because narcolepsy’s symptoms can go

undiagnosed for a long period, or be confused with other conditions. Nonetheless, based on a chart

in O’Flanagan setting forth time periods between vaccination with Pandemrix and discovery of

narcolepsy, Dr. Kinsbourne opined that he would expect onset to occur between six weeks and six

months after vaccination. Kinsbourne First Rep. at 9-10, O’Flanagan at 6, Table 3. O’Flanagan

listed the percentage of 32 patients who developed narcolepsy after vaccination, starting at 4.6

percent at 0-6 days and ending at 100 percent after 12 months had passed since vaccination. Id. As

a result, Dr. Kinsbourne felt that Petitioner’s development of narcolepsy in two to three months

after vaccination was temporally appropriate, especially in light of its “subtle” and

“underdiagnosed” character. Kinsbourne First Rep. at 10.

B. Dr. Maryanne Deak

Dr. Deak testified at hearing, and offered one expert report. Ex. A, dated June 13, 2016

(ECF No. 32) (“Deak Expert Rep.”); Tr. at 128-57. She opined not only that the evidence linking

the flu vaccine to narcolepsy was weak, but also that Mr. McCollum’s symptoms had not been

shown to fit the proper clinical criteria for a narcolepsy diagnosis, and that his prior symptoms

ruled out vaccine causation in any event.

Dr. Deak is a board-certified neurologist and sleep specialist currently employed at eviCore

healthcare, where she works on guideline development and clinical case review for sleep medicine

or neurology cases. See generally Ex. B (ECF No. 32) (“Deak CV”); Tr. at 130-32. She graduated

from Georgetown University School of Medicine in 2004 after completing her bachelor’s degree

there in 2000. Deak CV at 1. Dr. Deak completed residencies in neurology at New York University

and University of Massachusetts. Id. She then served as a clinical and research fellow in sleep

medicine at Brigham and Women’s Hospital at Harvard Medical School before becoming an

instructor there in the Division of Sleep Medicine in the Department of Internal Medicine. Id. As

part of this work, she worked in the sleep clinic, which meant that she saw a fairly large patient

population all with sleep related issues. Tr. at 133. She stated that she had often seen patients being

evaluated for narcolepsy, although many were ultimately diagnosed with a different sleep disorder.

Id. Dr. Deak has also helped develop a stimulant medicine for patients with narcolepsy and central

13

hypersomnia. Id. at 8. Her CV also indicates that she has written or coauthored several peer

reviewed articles and book chapters in the area of sleep disorders. Id. at 8-10.

The initial focus of Dr. Deak’s testimony and expert report was the overall propriety of Mr.

McCollum’s narcolepsy diagnosis. In her view, Petitioner’s clinical symptoms and test results did

not meet the objective criteria for diagnosis for narcolepsy established by the American Academy

of Sleep Medicine—an organization in which Dr. Deak previously served as a committee member.

Tr. at 140-41. Although Mr. McCollum underwent an MSLT sleep study when he was first

diagnosed by Dr. Shen, Dr. Deak did not consider the study to have been performed under the

proper conditions to reliably diagnose narcolepsy because Mr. McCollum had not tracked his sleep

patterns in advance of the test, an overnight polysomnography was not performed the night before

the MSLT, nor did the study consider the medications he had been taking at the time. Id. at 142-

43. She therefore felt that the Stanford sleep specialists may have over-relied on the MSLT results

without double-checking. Id. at 154-55. However, literature Dr. Deak filed suggests that the MSLT

testing might not be all that conclusive for older individuals believed to possibly suffer from

narcolepsy like Mr. McCollum. See Christian Guilleminault, et al., Narcolepsy: Diagnosis and

Management, in Principles and Practice of Sleep Medicine 957-67 (5th ed. 2011), filed as Ex. C

(ECF No. 32) (“Guilleminault”) at 960 (MSLT too stringent to apply to older patients).

Dr. Deak further maintained that Mr. McCollum possessed several co-morbidities that

could have contributed to some form of sleep disorder. Deak Expert Rep. at 4. For example, she

suggested that Mr. McCollum might suffer from daytime sleepiness due to his use of sedating

medications, and because of his apnea-related trouble breathing while he slept. Tr. at 144. And she

noted the absence of any lab results confirming that Mr. McCollum possessed the lesser levels of

hypocretin in his CSF associated with narcolepsy (a well-known strong link with the condition),

although such testing appears never to have been performed on Mr. McCollum in the first place.

Id. at 154; Guilleminault at 960.

Dr. Deak addressed the difficulty of determining the onset of narcolepsy due to its insidious

nature – a fact that in her view undercut the conclusion that Mr. McCollum’s symptoms likely

post-dated his vaccination. Deak Expert Rep. at 5. As she noted, narcolepsy can go undiagnosed

for as long as decades, especially when it is not also seen in the presence of cataplexy. Id. The

diagnostic criteria she filed as part of her medical literature, however, limited that time frame,

stating “[c]ataplexy most often occurs within one year of onset but in rare cases, may precede the

onset of sleepiness or commence up to 40 years later.” See American Academy of Sleep Medicine,

International Classification of Sleep Disorders 12 (3d ed. 2014), filed as Ex. D (ECF No. 32)

(“AASM”).

Finally, Dr. Deak discussed the pathogenesis of narcolepsy in connection with vaccines.

While she recognized that Pandemrix has been associated with higher incidence of narcolepsy

abroad, she rejected the idea that vaccines in the United States, made without adjuvants, could be

14

equally associated with narcolepsy due to the lack of confirming research in the area. Tr. at 145-

46.

Dr. Deak’s report relied on some literature evaluating the relative role of the H1N1

components in a flu vaccine versus the adjuvant in triggering narcolepsy. In particular, her report

cited a review article authored in part by one of the individuals most associated with first observing

the relationship between Pandemrix and narcolepsy. See Markku Partinen, et al., Narcolepsy as an

Autoimmune Disease: the Role of H1N1 Infection and Vaccination, 13 Lancet Neurol. 600, 600-

13 (2014), filed as Ex. G (ECF No. 32-7) (“Partinen II”). Partinen II embraces the consensus in

the medical and scientific community that narcolepsy is autoimmune in nature, and that “an H1N1

virus-derived antigen might be the trigger” for the condition. Partinen II at 600, 605-06. But (even

while underscoring the reliable evidence linking Pandemrix to narcolepsy), Partinen II also notes

that it could not be concluded that adjuvants contained in Pandemrix and similar H1N1 flu vaccines

played no contributory role, and therefore the two factors (NP content plus adjuvant) might have

a “dual effect.” Id. at 608; see also Outi Vaarala, et al., Antigenic Differences Between AS03

Adjuvanted Influenza A (h1n1) Pandemic Vaccines: Implications for Pandemrix-Associated

Narcolepsy Risk, 9 PLOS, no. 10, 2014, at 20, filed as Ex. I (ECF No. 32) (“[t]he role of [the

adjuvant] may have been indispensable as a booster of the immune response triggering

narcolepsy”). Partinen II’s authors proposed that this relationship should be further investigated,

“because no reports exist of narcolepsy in association with other non-adjuvanted H1N1 virus-

containing vaccines” – thus suggesting that it could not be assumed that the NPs derived from the

H1N1 components of the vaccine were alone enough to cause narcolepsy, even if they were a more

significant factor than the adjuvant. Id. (emphasis added).

IV. Procedural History

Mr. McCollum filed his Petition on August 29, 2014. ECF No. 1. Petitioner thereafter

began to file medical records, although the glaring lack of documented proof of vaccination – a

central matter in any Vaccine Program case - became apparent soon after the case was filed.

Despite this, Respondent filed his Rule 4(c) Report on April 20, 2015. ECF No. 13. Throughout

the remainder of 2015, Petitioner continued filing medical records and the first expert report from

Dr. Kinsbourne, while also attempting to gather evidence of proof of vaccination from Walgreens

and through the affidavits of Mr. and Mrs. McCollum.

Those efforts produced some results, including a letter from Walgreens stating the type of

flu vaccine offered during the relevant time period, plus its cost and formulation for the 2011

season. See e.g., Exs. 38-39. However, by December 2016, Petitioner was still unable to provide

direct proof of vaccination. After a status conference, I scheduled the case for hearing in April

2017, noting that it would provide the parties the opportunity at trial to address the proof of

15

vaccination question along with the greater issue of entitlement. The hearing was held as scheduled

on April 4, 2017, and this case in now ripe for a decision.

V. Applicable Legal Standards

A. Petitioner’s Overall 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).21

In this case, Petitioner does not assert a Table claim.

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.”

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

Non-Table 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 (Fed. Cir. 2005): “(1) a

medical theory causally connecting the vaccination and the injury; (2) a logical sequence of cause

21

Decisions of special masters (some of which I reference in this ruling) constitute persuasive but not binding

authority. Hanlon v. Sec’y of Health & Human Servs., 40 Fed. Cl. 625, 630 (1998). By contrast, Federal Circuit rulings

concerning legal issues are binding on special masters. Guillory v. Sec’y of Health & Human Servs., 59 Fed. Cl. 121,

124 (2003), aff’d 104 F. App’x 712 (Fed. Cir. 2004); see also Spooner v. Sec’y of Health & Human Servs., No. 13-

159V, 2014 WL 504728, at *7 n.12 (Fed. Cl. Spec. Mstr. Jan. 16, 2014).

16

and effect showing that the vaccination was the reason for the injury; and (3) a showing of

proximate temporal relationship between vaccination and injury.” Althen, 418 F.3d at 1278.

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, a

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)), vacated on other grounds, 844 F.3d

1363 (Fed. Cir. 2017). But this does not negate or reduce a petitioner’s ultimate burden to establish

his overall 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).22

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).

22

Although decisions like Contreras suggest that the burden of proof required to satisfy the first Althen prong is less

than the other two, there is ample contrary authority for the more straightforward proposition that the first Althen

prong (as a component of the overall test) simply requires application of a preponderance evidentiary standard when

evaluating if a reliable and plausible causation theory has been established. Broekelschen v. Sec’y of Health & Human

Servs., 618 F.3d 1339, 1350 (Fed. Cir. 2010).

17

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 Dept. 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.” de Bazan

v. Sec’y of Health & Human Servs., 539 F.3d 1347, 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 Evidence

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

18

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 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/70 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 F. 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), aff’d, 993

F.2d at 1525 (Fed. Cir. 1993) (“[i]t strains reason to conclude that petitioners would fail to

accurately report the onset of their daughter’s symptoms.”).

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, contemporaneous 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 per curiam,

968 F.2d 1226 (Fed. Cir. 1992), 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

19

those which are internally consistent”) (quoting Murphy, 23 Cl. Ct. at 733)). Ultimately, a

determination regarding a witness’s credibility is 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 person’s purposeful recounting of symptoms that did not exist. La Londe v.

Sec’y of 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 for a (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

20

& 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 and reliability 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 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 91997)); 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”).

D. Consideration of Medical Literature

Both parties filed medical and scientific literature in this case, but not all such items factor

into the outcome of this decision. While I have reviewed all of the medical literature submitted in

this case, I discuss only those articles that are most relevant to my determination and/or are central

to this Decision – just as I have not exhaustively discussed every individual medical record filed.

Moriarty v. Sec’y of Health & Human Servs., No. 2015-5072, 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); see also Paterek v. Sec’y of Health & Human Servs., 527 F. App’x 875, 884 (Fed. Cir.

2013) (“[f]inding certain information not relevant does not lead to – and likely undermines – the

conclusion that it was not considered”).

21

ANALYSIS

A. Althen Prong One

I have recently had the occasion to consider the scientific reliability and evidentiary

persuasiveness of the theory that flu vaccines administered in the U.S. and containing the H1N1

influenza strain can provoke an autoimmune process that (via molecular mimicry) results in

blockage of the hypocretin receptors in the brain responsible for sleep regulation, thereby

producing narcolepsy. See, e.g., D’Toile v. Sec’y of Health & Human Servs., No. 15-085, 2016

WL 7664475 (Fed. Cl. Spec. Mstr. Nov. 28, 2016) (denying entitlement), mot. for review den’d,

2017 WL 2729570 (Fed. Cl. Mar. 2, 2017), appeal docketed, No. 17-1982 (Fed. Cir. May 4, 2017).

I denied entitlement in D’Toile because I determined that the version of the flu vaccine at

issue – Flumist, a nasally-administered live attenuated influenza vaccine – could not (based upon

the evidence presented) be reliably shown to cause narcolepsy as opposed to other, more well-

studied forms such as Pandemrix. Not only was Flumist manufactured differently (and therefore

contained fewer of the NPs proposed by some of the reliable literature to be the trigger for the

autoimmune process leading to narcolepsy), but the expert testimony and literature offered in that

case acknowledged (directly and indirectly) that the theory could not be reliably extended to cover

the relevant form of the vaccine for other reasons. D’Tiole, 2016 WL 7664475, at *20-28.

As I recognized in D’Toile, the general theory that certain formulations of H1N1-

containing flu vaccines can cause narcolepsy due to their NP content has several reliable

components.23 For example, the proposition that narcolepsy is an immune-mediated condition is

fairly well-established. Tr. at 78, 139. In addition, as Dr. Kinsbourne opined, the decrease in, or

complete disappearance of, hypocretin caused by autoantibodies produced via the mechanism of

molecular mimicry likely results in a disruption in a person’s wake cycle leading to narcolepsy.

These deficiencies in the hypocretin-mediated neurotransmission process have been studied and

persuasively linked to narcolepsy. Ahmed II at 2. And there is extensive literature associating

narcolepsy with Pandemrix, and persuasive studies suggesting that the NP content of Pandemrix-

like versions of the flu vaccine may be an important causal factor (although such studies do not

23

Petitioner’s pretrial brief maintains that “the fact that the H1N1 influenza vaccine can cause narcolepsy in a

susceptible individual (Althen Step I) cannot seriously be disputed” (perhaps intending to suggest that any failure by

the Petitioner to offer adequate evidence in support of causation herein is attributable to the obviousness of the

question). Pre-Hearing Statement, dated February 23, 2017 (ECF No. 41) at 1 (emphasis in original). But this vastly

overstates what the reliable scientific evidence offered in this case establishes. Such literature limits the “can cause”

association upon which Petitioner relies to a form of the flu vaccine that has never been administered in the U.S. and

is not involved in this case. And it is not a defense to the failure to offer sufficient evidence in support of a causal

theory at the appropriate time to argue that the question presented was so obviously in one’s favor that there was no

need to even try. Program claimants may not reserve their real evidentiary “fire power” for only after their initial

showing has been found inadequate.

22

completely rule out the previous conventional wisdom in the scientific community that the

adjuvants also play a contributory role in encouraging an autoimmune process).

But can science regarding a different form of flu vaccine be applied to the version Mr.

McCollum allegedly received, allowing the determination that the latter could cause narcolepsy?

I conclude that Petitioner has not so established.

Based upon unrebutted evidence, Petitioner most likely received an H1N1-containing

inactive, unadjuvanted version of the flu vaccine, as that was the predominant form being

administered in the fall of 2011. See Exs. 38-39. Petitioner offered no direct evidence, however,

suggesting that such a version has been tested in connection with narcolepsy to the degree his other

evidence associates narcolepsy with the Pandemrix version. Instead, Petitioner sought to leverage

what is known about Pandemrix to the facts of this case.

To do so, he relies on two points. First, Petitioner notes that H1N1 flu vaccines

administered in the U.S. in the relevant time period contained levels of NP almost comparable to

that of Pandemrix, allowing for the conclusion that the vaccine he received could have the same

cross-reactive capacity. Tr. at 96; Ahmed II at 8. This argument in turn relies on the concept that

it is the NP levels that trigger narcolepsy. Ahmed II provides somewhat reliable support for this

contention. Indeed, studies of similar adjuvanted H1N1 vaccines less associated with narcolepsy

than Pandemrix, such as Arepanix, corroborate the importance of the manner in which the H1N1

components were inactivated as determinant of NP levels.24

As I noted in D’Toile, however, there are limits to the conclusiveness of the Ahmed II

findings about NP content. Not only are its own experiments insufficiently powered enough in

terms of numeric sample to be fully reliable in establishing causation, but Ahmed II’s authors

admit that the interplay between NP content and genetic susceptibility impact whether any form

of an H1N1 vaccine can be associated with the condition. D’Toile, 2016 WL 7664475, at *21, 23

n.22; Ahmed II at 10. More importantly, as discussed above, while Ahmed II shifts the focus on

the likely primary cause of narcolepsy away from the adjuvants contained in the Pandemrix-like

vaccines, it does not wholly eliminate the adjuvant as possibly playing an important role (thus

reducing the applicability of its findings to the proposed causal effects of unadjuvanted vaccines).

Partinen II at 608.

Second, Petitioner proposed that there was reliable evidence suggesting that the wild H1N1

virus can cause narcolepsy, offering two articles discussing that link. See, e.g., Han I; Fang Han,

et al., Genome-Wide Analysis of Narcolepsy in China Implicates Novel Immune Loci and Reveals

24

See T. Harris et al., Did Narcolepsy Occur Following Administration of AS03 Adjuvanted Pandemic Vaccine in

Ontario, Canada? A Review of Post-Marketing Safety Surveillance Data, 19 Euro Surveillance 1, 1-5 (2014), filed as

Ex. 23 (ECF No. 22).

23

Change in Association Prior to Versus after the 2009 H1N1 Influenza Pandemic, 9 PLOS

Genetics, no. 10, 2013, filed as Ex. 21 (ECF No. 22). While Respondent did not rebut the findings

in these items of literature, I note (as I also observed in D’Toile) that such studies have been

inconsistent in their findings, and even (as the Ahmed authors agree) that circumstances unique to

the relevant countries may play more of a role in the findings than the virus itself. Ahmed, et al.,

Mechanistic Insights into Influenza Vaccine-Associated Narcolepsy, in Human Vaccines and

Immunotherapies 12 (2016).25 The findings in Han and similar articles may also only establish that

the development of narcolepsy requires a confluence of factors (an H1N1 vaccine containing an

adjuvant, coupled with an ongoing pandemic involving the wild virus) – strengthening the

conclusion that the capacity of the vaccine’s NP content to spark narcolepsy still requires other

boosting factors if it is to occur.

All of the above must be evaluated in a context in which Duffy, the sole relevant

epidemiologic evidence regarding the impact of the version of the H1N1 flu vaccine administered

in the U.S., contradicts Petitioner’s contentions about a causal link. Petitioners are of course not

obligated to offer epidemiologic evidence supporting their causation theory, and cannot be

required by special masters to produce it. 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). Thus, the fact that Mr.

McCollum could offer no such evidence establishing an association between unadjuvanted

versions of the H1N1 vaccine and narcolepsy does not mean he could not still prevail. But both

sides filed Duffy, and it is reasonable to consider whether it negatively impacts Petitioner’s

evidentiary showing. Taylor v. Sec’y of Health & Human Servs., 108 Fed. Cl. 807, 819–21 (Fed.

Cl. 2013) (special master did not err in considering epidemiological evidence); Andreu, 569 F.3d

at 1379 (a special master may assess epidemiological evidence in “reaching an informed judgment

as to whether a particular vaccination likely caused a particular injury.”).26

In a recent decision, Crutchfield v. Sec’y of Health & Human Servs., No. 09-0039V, 2014

WL 1665227 (Fed. Cl. Spec. Mstr. Apr. 7, 2014), former Special Master Hastings provided a

cogent explanation of the evidentiary purpose served by reliable epidemiologic evidence, and the

proper manner in which it is to be evaluated under the Vaccine Program’s lenient evidentiary

standards. The petitioner in Crutchfield sought to establish that the measles-mumps-rubella

(“MMR”) vaccine caused her to develop Type I diabetes. To rebut that contention, Respondent’s

experts relied in part on epidemiologic studies that demonstrated no association between the two.

Crutchfield, 2014 WL 1665227, at *13. Special Master Hastings (observing the fact that Program

25

This piece of medical literature was referenced in Dr. Kinsbourne’s supplemental report (Ex. 41) but was not filed

as an exhibit in the case.

26

I also note that the Petitioner has offered several items of epidemiologic evidence involving Pandemrix intended to

support his theory, offering studies that persuasively linked it to narcolepsy. See, e.g., Exs. 29-30, O’Flanagan.

Arguments that epidemiologic evidence cannot in fairness be marshalled against a Program petitioner lose much of

their limited effectiveness when the claimant relies on evidence of the same category.

24

case law permits consideration of epidemiologic evidence even though it simultaneously does not

mandate that claimants offer it in their prima facie case) evaluated it and found it tended to negate

Petitioner’s claim. Id. at *13-15.

The Petitioner’s expert in Crutchfield attempted to distinguish the epidemiologic studies

offered by Respondent by arguing that the very rarity of a vaccine-caused injury rendered such

studies incapable of detecting the possibility of the injury (except where the study was large

enough to be considered adequately powered in a statistical sense). Crutchfield, 2014 WL

1665227, at *15. This argument arises from the oft-cited proposition (noted above) that

epidemiologic evidence need not be offered by petitioners at all – and Special Master Hastings

credited its logic. Yet he rejected it nonetheless:

It is, in fact, always true that epidemiologic studies can never prove definitively that

Factor A never causes Condition B. Even when large studies fail to identify an association

between Factor A and Condition B, it is always theoretically possible that Factor A

causes Condition B in a very small number of cases, an effect too rare for the study to

detect. But it is not the Respondent’s burden in this case to prove that it is impossible

that [the relevant vaccine] can cause [the alleged injury]. It is, rather, the Petitioner’s

burden to [show the vaccine can cause the injury] . . . And, therefore, the epidemiologic

studies cited in this case . . . clearly do not help Petitioner carry her burden.

Id. at *15 (emphasis in original). Special Master Hastings’s reasoning in Crutchfield is highly

persuasive and I shall apply it to this case weighing Duffy.

Duffy involved forms of the flu vaccine that are administered in the U.S. (unadjuvanted

H1N1 flu vaccines), yet observed no increase in the occurrence of narcolepsy after receipt by

thousands of individuals. I have previously found Duffy to be a reliable and persuasive piece of

evidence. See D’Toile, 2016 WL 7664475, at *22-23. It is true that Duffy studied versions of the

H1N1 vaccine produced in different years than the precisely relevant year herein, but because

Petitioner’s theory focuses on antigens contained in the H1N1 strain as the primary cause of the

hypocretin receptor blockage resulting in narcolepsy, I do not find such distinctions reduce its

evidentiary value. Duffy stands as the only evidence directly relevant to the propensity of the

version of the H1N1 flu vaccine administered in the U.S. to cause narcolepsy – but does not support

Petitioner’s theory at all.

Dr. Kinsbourne attempted to belittle Duffy as not a “true” epidemiologic study, but was

unpersuasive in so doing (putting aside the fact that opining on the trustworthiness of this kind of

evidence is somewhat outside of his primary area of expertise). Contrary to Dr. Kinsbourne’s

suggestion, an observational study like Duffy is not distinguishable from an epidemiologic study,

but is instead a kind of epidemiologic study. Michael D. Green et al., Reference Guide on

25

Epidemiology, in Reference Manual on Sci. Evidence 549, 555-56 (3d ed. 2011) (hereinafter

“Green”) (in an observational epidemiologic study, researchers analyze groups of individuals who

were exposed to a test agent, comparing them with groups not so exposed).27 He also attacked

Duffy as lacking the greater trustworthiness of a controlled experiment or case-controlled

observational study, which would more precisely establish, or rebut, an association between

vaccine and illness. I acknowledge the validity of Petitioner’s general objections that such a study

has limitations. Dwyer v. Sec’y of Health & Human Servs., No. 03-1202V, 2010 WL 892250, at

*64 (Fed. Cl. Spec. Mstr. Mar. 12, 2010) (“[e]very observational epidemiological study has some

weaknesses because such studies examine the world as it is”). But Duffy still stands as reasonable

evidence that calls into doubt Petitioner’s theory – and it is not enough to respond by arguing (as

Dr. Kinsbourne proposed) that the rare nature of a vaccine injury renders all epidemiologic

evidence effectively useless. Kinsbourne First Rep. at 8; Crutchfield, 2014 WL 1665227, at *15.

Weighing all of the above together, I find that Petitioner has not offered preponderant

reliable medical and scientific evidence sufficient to satisfy the first Althen prong. The concept

that an adjuvanted version of the H1N1 vaccine comparable to Pandemrix could cause narcolepsy

finds support in the Ahmed articles plus other literature offered by Dr. Kinsbourne. If Pandemrix

were the version of the vaccine at issue, none of the foregoing analysis would be necessary. But

the contention that the NP content of an unadjuvanted H1N1 vaccine administered in the U.S. is

enough by itself to cause narcolepsy is far weaker, and rebutted by reliable and relevant

epidemiologic evidence.

Petitioner’s theory remains intriguing despite my determination. It may not be long before

reliable evidence sufficient to establish the causal propensity of the relevant version of the flu

vaccine administered in the U.S. will exist to fill in the evidentiary holes. But special masters have

frequently observed that an evidentiary gap in a causal theory can be fatal to the overall claim –

even if it is foreseeable that the gap may be filled sometime in the future. Isaac v. Sec’y of Health

& Human Servs., No. 08-601V, 2012 WL 3609993, at *18 (Fed. Cl. Spec. Mstr. July 30, 2012),

mot. for review denied, 108 Fed. Cl. 743 (2013), aff’d, 540 F. App’x 999 (Fed. Cir. 2013) (“[i]n

most cases, there are no definitive answers to the question of vaccine causation. The answers will

come in the future, as medical science progresses”); Browning v. Sec’y of Health & Human Servs.,

No. 02-929V, 2010 WL 3943556, at *3 n.8 (Fed. Cl. Spec. Mstr. Sept. 27, 2010)(“[s]pecial masters

cannot delay indefinitely making decisions in vaccine cases to find out what the future holds”). I

thus do not find the first Althen prong has been satisfied.

27

Dr. Kinsbourne similarly erred in classifying Duffy as an “ecological” study. First Kinsbourne Rep. at 4. An

ecological study is a kind of observational study in which broader data about a group as a whole is gathered, instead

of individualized data. Green at 561. Duffy, by contrast, is properly considered a “cohort” observational study, in

which a group classified based on exposure to the “agent of interest” (here, the flu vaccine) is “constructed

retrospectively” and “followed over historical time toward the present” in order to observe the proportion of

individuals who develop the relevant disease in comparison to individuals not exposed to the agent in question. Id. at

557. Indeed, Duffy itself acknowledges its cohort observational design. Duffy at 1824.

26

B. Althen Prong Two

Before addressing Petitioner’s overall “did cause” showing, I will consider two fact issues

raised in the case, both of which I resolve in his favor.

1. Petitioner Likely Received the Flu Vaccine in October 2011 - The most

immediate factual obstacle facing Petitioner in this case was the lack of documented proof of

vaccination. A Vaccine Act petitioner must, as a threshold matter in advancing a claim for

damages, establish by a preponderance of the evidence receipt of “a vaccine set forth in the

Vaccine Injury Table.” § 300aa–11(c)(1)(A). The preponderance of the evidence standard means

that an allegation is established to be “more likely than not.” Moberly v. Sec’y of Health & Human

Servs., 592 F.3d 1315, 1322 n.2 (Fed. Cir. 2010).

Although contemporaneous documentation of vaccination from a healthcare provider is the

best evidence that a vaccination occurred, it is not absolutely required in all cases. Centmehaiey v.

Sec’y of Health & Human Servs., 32 Fed. Cl. 612, 621 (1995) (“[t]he lack of contemporaneous

documentary proof of a vaccination . . . does not necessarily bar recovery”). Indeed, as Vaccine

Rule 2 states, “[i]f the required medical records are not submitted, the petitioner must include an

affidavit detailing the efforts made to obtain such records and the reasons for their unavailability.”

Vaccine Rule 2(c)(2)(B)(i). Furthermore, if a petitioner’s claim is “based in any part on the

observations or testimony of any person, the petitioner should include the substance of each person's

proposed testimony in a detailed affidavit(s) supporting all elements of the allegations made in the

petition.” Vaccine Rule 2(c)(2)(B)(ii).

Special masters have found that vaccine administration occurred even in the absence of

direct documentation. In such cases, preponderant evidence was provided in the form of other

medical records and/or witness testimony. For example, corroborative, though backward-looking,

medical notations have been found to tip the evidentiary scale in favor of vaccine receipt. Lamberti

v. Sec’y of Health & Human Servs., No. 99–507V, 2007 WL 1772058, at *7 (Fed. Cl. Spec. Mstr.

May 31, 2007) (finding multiple medical record references to vaccine receipt constituted adequate

evidence of administration); Groht v. Sec’y of Health & Human Servs., No. 00–287V, 2006 WL

3342222, at *2 (Fed. Cl. Spec. Mstr. Oct. 30, 2006) (finding a treating physician's note—“4/30/97—

Hep B. inj. # 1 (not given here) (pt. wanted this to be charted)”—to be sufficient proof of

vaccination); Wonish v. Sec'y of Health & Human Servs., No. 90–667V, 1991 WL 83959, at *4 (Cl.

Ct. Spec. Mstr. May 6, 1991) (finding parental testimony “corroborated strongly by medical records

[referring] back to the [vaccination]” to be sufficient to establish vaccine administration).

In addition to corroborative medical records, witness testimony can also help establish a

sufficient basis for a finding that a vaccine was administered as alleged. Alger v. Sec’y of Health &

27

Human Servs., No. 89–31V, 1990 WL 293408, at *2, 7 (Fed. Cl. Spec. Mstr. Mar. 14, 1990) (oral

testimony from a parent and the doctor who administered the vaccine was “more than adequate to

support a finding that the vaccine was administered”). The Court of Federal Claims has recognized

that special masters may base a finding of vaccination on lay testimony. Epstein v. Sec'y of Health

& Human Servs., 35 Fed. Cl. 467, 478 (Fed. Cl. 1996); see also Brown v. Sec'y of Health & Human

Servs., 18 Cl. Ct. 834, 839–40 (1989) (proof of vaccination in the absence of contemporaneous

medical records established via testimony of petitioner’s parent, her personal calendar, and

evidence of a charge for the vaccine on the physician's billing statement), rev’d on other grounds,

920 F.2d 918 (Fed. Cir. 1990).

In the present case, Petitioner has marshaled enough circumstantial evidence for me to

find that he more likely than not received an unadjuvanted trivalent H1N1 flu vaccine

(administered by injection rather than in intranasal fashion like Flumist) in October 2011.

Although Mr. McCollum was not able to produce documentary proof from Walgreens providing

direct evidence of his vaccination, he did establish that he made a purchase at Walgreens for the

appropriate amount and during the relevant time period. Ex. 36 at 5. Walgreens also confirmed the

types of flu vaccines being administered at the time (which included the H1N1 version) and their

general costs. Ex. 7. In addition, Petitioner established a specific reason to obtain the flu vaccine

—his wife’s hospitalization. Tr. at 41-42. I also credit his testimony recalling the administration

of the vaccine, as well as his wife’s recollection of the circumstances in which she encouraged him

to obtain it. Tr. at 7.

Based on Petitioner’s bank statements, the only charge from Walgreens that could have

included the vaccine is one from October 18, 2011, and I will therefore adopt that as the date of

vaccination in this case.

2. Petitioner’s Prior Symptoms Are Likely Unrelated to his Narcolepsy -

Fundamentally, a Vaccine Act claim must establish that the injury in question did not precede the

relevant vaccine’s administration. See, e.g., Shalala v. Whitecotton, 514 U.S. 268, 273-74 (1995).

Thus, onset of an injury must be shown to have occurred after the date of vaccination (for, except

where a significant aggravation claim is pled, only under those circumstances can the vaccine

possibly be said to have caused the alleged injury).

As Respondent argued, the medical record revealed several instances suggesting that Mr.

McCollum had a pre-vaccination history of sleepiness or sleep disturbances. See, e.g., Ex. 1 at 4-

5, 64-68. Arguably, these instances establish that his narcolepsy (only diagnosed in 2012) predated

vaccination. Given the literature discussing the fact that formal diagnosis of narcolepsy often

comes long after symptoms first began, this interpretation of the medical record is entirely

plausible.

28

Nevertheless, I find that the evidence offered by Petitioner is sufficient to conclude that his

symptoms prior to vaccination were either related to his back problems or undiagnosed OSA – and

therefore not evidence of pre-vaccination onset. While it is now understood that Petitioner has

OSA, he had many, if not all of the risk factors for OSA before vaccination—excess weight,

hypertension, nasal congestion, smoking, male gender, family history of OSA, etc. Obstructive

Sleep Apnea: Symptoms and Causes, Mayo Clinic, http://www.mayoclinic.org/diseases-

conditions/obstructive-sleep-apnea/symptoms-causes/dxc-20205871 (last visited June 26, 2017).

OSA can lead to daytime fatigue and sleepiness, which are very similar to what Mr. McCollum

reported experiencing, but the causal mechanisms for OSA are unrelated to those of narcolepsy.

Rather than being a result of depletion of hypocretin in the brain, OSA occurs when the muscles

of the throat relax too much and do not allow for a normal breathing rhythm. Id.

Other prior instances of sleep-related problems are also distinguishable. Thus, the instance

in 2010 when Mr. McCollum reported “an altered level of consciousness with difficulty expressing

himself and bilateral shaking of his arms” and was briefly hospitalized appeared to provide

evidence of a day sleepiness/altered consciousness occurrence that looks more like a narcolepsy

symptom than his OSA symptoms, although it was at the time diagnosed as TIA. Ex. 2 at 32.

However, the instance was interpreted by Dr. Petrini to be the result of a change in hypertension

medication, resulting in low blood pressure. Ex. 1 at 23. Once the medication balances were

altered, Petitioner did not again experience anything similar until the late fall of 2011 (after he had

received the flu vaccine). Dr. Ruoff’s speculation, as set forth in the medical records, that

Petitioner’s TIA might have actually been a misdiagnosed instance of cataplexy is self-limited by

his admission that he pondered this possibility without the benefit of review of the actual record.

Respondent otherwise did not establish strong grounds that would permit me to conclude that these

occurrences, despite the degree to which they suggest narcolepsy, were in fact evidence of it.

Petitioner’s overall medical picture makes it difficult to assign significance to these prior

sleep-related incidents. Petitioner has suffered from a variety of interrelated illnesses and medical

problems, making it difficult to tell where one ends and the next begins. But given the ambiguity

of the evidence purportedly showing related sleep problems, I cannot conclude that Mr.

McCollum’s narcolepsy more likely than not predated his receipt of the flu vaccine.

3. Conclusions with Respect to Second Althen Prong – Despite my

determinations above, I find that preponderant evidence does not support the conclusion that the

flu vaccine more likely than not caused Mr. McCollum’s narcolepsy. Admittedly, the evidence

largely supports the diagnosis, and Dr. Deak’s efforts to rebut it were not persuasive.28 Petitioner

28

Dr. Deak argued that narcolepsy was an incorrect diagnosis, but undercut that opinion with admissions at trial that

the diagnosis actually had medical plausibility. Tr. at 151. Moreover, her opinion must be weighed against the equally-

qualified sleep specialist treaters at Stanford who opined as to Petitioner’s condition. Indeed, Mr. McCollum took part

in a research sleep study at Stanford that published results indicating that the doctors had confirmed that Mr.

McCollum had met the diagnostic criteria for narcolepsy. In addition, Dr. Shen’s notes from his evaluation of Mr.

29

has also proposed a logical sequential explanation consistent with his causation theory – although

he has not established (beyond evidence of the genetic haplotype associated with narcolepsy) that

Mr. McCollum possessed biomarkers for the condition, such as low hypocretin, and largely relies

on the existence of post-vaccination symptoms rather than offering other circumstantial

evidence.29 But Petitioner’s failure to establish a persuasive causal theory ultimately dooms his

Althen two showing. Because the unadjuvanted H1N1 vaccine Mr. McCollum likely received has

not been shown to cause narcolepsy, it does not matter how consistent Petitioner’s arguments are

with the causation theory proposed but rejected.

C. Althen Prong Three

As Petitioner has argued, the nature of narcolepsy as a condition makes it difficult to

establish a clear timeframe in which it would develop after the autoimmune process leading to it

(whatever its cause) began, thus allowing for a wide range of ostensibly medically appropriate

onset timeframes. Tr. at 109. Here, and based upon my determination that Mr. McCollum received

the vaccine on October 19, 2011, approximately four to six weeks passed before his first symptoms

manifested. Petitioner primarily relied on O’Flanagan to conclude that this was a medically

acceptable timeframe – although that article unquestionably did not involve the relevant

formulation of the vaccine, and had other weaknesses that make it difficult to give it the weight

urged by Petitioner.30 Respondent’s expert, however, devoted more energy to attempting to rebut

the first two prongs, thus largely not contesting this showing.31

McCollum indicate that he performed a thorough review of Mr. McCollum’s symptoms and eliminated other potential

causes before diagnosing Petitioner with narcolepsy. Ex. 3 at 3. Similarly, Dr. Klein indicated that she recognized that

the MSLT needed be repeated but did not do so because of Mr. McCollum’s convincing clinical presentation of

narcolepsy. Ex. 8 at 2. Due to such evidence, I do not find that Respondent persuasively established that the narcolepsy

diagnosis was in error.

29

I also note the testimony of the McCollums that Petitioner received a second flu vaccine sometime during his

treatment at the Stanford Sleep Clinic as somewhat suggestive of the uncertainty surrounding the link between

vaccination and his condition (since it is not likely his treaters would have been cavalier about exacerbating his

condition had they been certain of a causal connection), although this evidence on this matter is fairly vague in the

record.

30

O’Flanagan’s limitations go beyond the fact that, like most of Petitioner’s scientific or medical proof, it involved

Pandemrix. It (like the criticized Duffy study) was a retrospective cohort study – again underscoring the extent to

which Petitioner and his experts were inconsistent in their views as to the reliability of such epidemiologic evidence,

embracing it when invoked in favor of the claim, while criticizing it where it assisted Respondent. O’Flanagan at 1.

In addition, O’Flanagan involved a sample of only 32 individuals diagnosed with narcolepsy, and relied on an

individual’s first contact with a treater as the best evidence of onset given the difficulties in diagnosing the condition

– something that Program case law rejects as proper evidence of onset. Id. at 3-4. Moreover, of that sample only three

individuals were adults like Mr. McCollum; O’Flanagan’s authors were forthright in admitting how little could be

reliably concluded based on so few observed cases. Id. at 7, 10.

31

Dr. Deak endeavored to rebut the very possibility that the vaccine could cause narcolepsy, rather than attacking the

timeframe in which it might be expected to do so. She only briefly discussed onset of narcolepsy, which she allowed

could fall within an extremely broad timeframe, extending from one to 15 years. Tr. at 142.

30

Nevertheless, the deficiencies in Petitioner’s causation theory make it impossible for him

to establish that onset of his narcolepsy was temporally reasonable. It therefore does not matter

that onset of Mr. McCollum’s narcolepsy post-dated his vaccination by a month or two consistent

with ranges proposed for Pandemrix in a single piece of literature. Caves v. Sec’y of Health &

Human Servs., No. 07-443V, 2010 WL 5557542, at *22 (Fed. Cl. Spec. Mstr. Nov. 29, 2010) (a

finding of an appropriate temporal relationship is insufficient to show causation-in-fact, as the

other two prongs must also be met). Absent more compelling proof that the version of the H1N1

vaccine in question administered in the U.S. can cause narcolepsy, I cannot conclude that the

proposed timeframe herein has preponderant support.

Indeed – even if Petitioner had more successfully established the first prong, the

amorphous, somewhat open-ended nature of the proposed timeframe for the onset of narcolepsy

would make it difficult to conclude (based on present science) that the timeframe in question is

medically acceptable. This Court has in the past noted that arguments about the acceptability of

widely varied time periods between receipt of a vaccination and onset of an autoimmune illness or

condition run the risk of rendering “Althen’s first and third prongs essentially meaningless.”

Hennessey v. Sec’y of Dep't of Health & Human Servs., 91 Fed. Cl. 126, 135 (2010) (rejecting

argument of claimant’s expert that an almost unlimited time period was possible for onset of

autoimmune-induced diabetes). O’Flanagan itself observed “onset” (defined therein as treater

contact – not first symptom, as is mandated by relevant case law) of anywhere from a few days to

an entire year. O’Flanagan at 6, Table 3. Such a wide range is very difficult to square with the

Program’s requirements of establishing a proximate, medically acceptable timeframe as a matter

of law.

CONCLUSION

This case presented numerous reasonably-disputed questions regarding onset, proof of

vaccination, and prior evidence of similar symptoms. While I have found that Petitioner was

successful in establishing some of these matters in his favor, he could not provide preponderant

evidence on a key component of his claim, for the evidence supporting the proposed causal theory

with respect to the version of the flu vaccine in question was too thin: there simply is not enough

reliable scientific evidence at this point in time to conclude that the unadjuvanted version of the

flu vaccine administered in the United States is associated with narcolepsy. Accordingly, Petitioner

is not entitled to compensation under the Vaccine Program.

In the absence of a timely-filed motion for review (see Appendix B to the Rules of the

Court), the Clerk shall enter judgment in accord with this decision.32

32

Pursuant to Vaccine Rule 11(a), the parties may expedite entry of judgment by filing a joint notice renouncing their

right to seek review.

31

IT IS SO ORDERED.

/s/ Brian H. Corcoran

Brian H. Corcoran

Special Master

32