Case: 22-1960 Document: 46 Page: 1 Filed: 12/13/2023

United States Court of Appeals for the Federal Circuit ______________________

DONALD WINKLER, Petitioner-Appellant

v.

SECRETARY OF HEALTH AND HUMAN SERVICES, Respondent-Appellee ______________________

2022-1960 ______________________

Appeal from the United States Court of Federal Claims in No. 1:18-vv-00203-CNL, Judge Carolyn N. Lerner. ______________________

Decided: December 13, 2023 ______________________

MICHAEL P. MILMOE, Law Offices of Leah V. Durant, PLLC, Washington, DC, argued for petitioner-appellant. Also represented by GLENN ALEXANDER MACLEOD.

NINA REN, Vaccine/Torts Branch, Civil Division, United States Department of Justice, Washington, DC, ar- gued for respondent-appellee. Also represented by BRIAN M. BOYNTON, C. SALVATORE D’ALESSIO, GABRIELLE M. FIELDING, HEATHER LYNN PEARLMAN, RYAN D. PYLES. ______________________

Before LOURIE, MAYER, and STARK, Circuit Judges. Case: 22-1960 Document: 46 Page: 2 Filed: 12/13/2023

2 WINKLER v. HHS

Opinion for the court filed by Circuit Judge LOURIE. Dissenting opinion filed by Circuit Judge MAYER. LOURIE, Circuit Judge. Donald Winkler appeals from a decision of the United States Court of Federal Claims sustaining a Special Mas- ter’s denial of compensation under the National Vaccine In- jury Compensation Program, pursuant to the National Childhood Vaccine Injury Act of 1986, 42 U.S.C. §§ 300aa- 1 to -34, for the development of Guillain-Barré Syndrome (“GBS”) following a Tdap vaccination. Winkler v. Sec’y of Health & Hum. Servs., No. 18-203V, 2022 WL 1528779 (Fed. Cl. May 13, 2022); Winkler v. Sec’y of Health & Hum. Servs., No. 18-203V, 2021 WL 6276203 (Fed. Cl. Spec. Mstr. Dec. 10, 2021) (“Special Master Decision”). For the following reasons, we affirm. BACKGROUND In 2017, Winkler stepped on rusted metal. Concerned about contracting tetanus, he received a Tdap vaccination on April 26, 2017. Special Master Decision at *3. Two days later, he visited a physician complaining of itchy, tingling legs. Id. The physician administered a Prevnar vaccine and assessed Winkler as having, among other things, day- time somnolence, varicose veins, and proteinuria. Id. The physician concluded that the itchiness was perhaps related to the varicose veins. Id. Winkler returned to his physician five days later on May 3, 2017, complaining of fatigue, mus- cle aches, headaches, diarrhea, and feeling feverish. Id. The physician assessed him as having gastroenteritis, an inflammation of the stomach and intestinal linings. Id. Evidence in the record supports the general contention that gastroenteritis may be caused by a bacterial infection. In particular, the bacterium Campylobacter jejuni is known as an infectious agent that may cause gastroenteri- tis. Special Master Decision at *2. However, the physician treating Winkler did not order a laboratory test to confirm Case: 22-1960 Document: 46 Page: 3 Filed: 12/13/2023

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whether or not Winkler’s gastroenteritis was the result of such an infection. Known causes of gastroenteritis other than bacterial infections include food poisoning, viral infec- tions, and consumption of irritating food or drink. Id. at *3 n.7. Rarely, a gastrointestinal infection, including those caused by C. jejuni, may subsequently trigger GBS, a type of acute monophasic peripheral neuropathy that often pre- sents with rapidly progressive, ascending motor neuron pa- ralysis. Id. at *2, *23. On May 11, 2017, fifteen days after his Tdap vaccina- tion and eight days after his gastroenteritis diagnosis, Win- kler went to an emergency room complaining of diffuse weakness and calf pain. Special Master Decision at *3. His attending doctors suspected GBS. Id. at *3−5. A lumbar puncture performed the following day confirmed that diag- nosis. Id. In 2018, Winkler filed a petition for relief in the Court of Federal Claims’ Office of Special Masters asserting that he should be compensated under the National Vaccine In- jury Compensation Program for GBS allegedly resulting from the Tdap vaccination. On December 10, 2021, the Special Master issued a decision denying the requested re- lief. See Special Master Decision at *26. Winkler filed a timely Motion for Review in the Court of Federal Claims, which affirmed the Special Master’s decision. He then timely appealed to this court. We have jurisdiction pursu- ant to 42 U.S.C. § 300aa-12(f). DISCUSSION We review the Court of Federal Claims’ review of the Special Master’s decision without deference. Hines ex rel. Sevier v. Sec’y of Health & Hum. Servs., 940 F.2d 1518, 1523−24 (Fed. Cir. 1991). We examine the Special Master’s legal determinations under a “not in accordance with the law” standard and factual determinations under an “arbi- trary and capricious” standard. Munn v. Sec’y of Dep’t of Case: 22-1960 Document: 46 Page: 4 Filed: 12/13/2023

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Health & Hum. Servs., 970 F.2d 863, 870 n.10 (Fed. Cir. 1992). The parties agree that GBS is not listed in the Vaccine Injury Table as a covered condition for Tdap vaccines. Pet. Br. at 6; Resp. Br. at 1; Special Master Decision at *22. Winkler’s GBS thus constitutes an off-Table injury, for which he had the burden to prove was actually caused by the Tdap vaccination. 42 U.S.C. §§ 300aa-13(a)(1), −11(c)(1)(C)(ii)(I). A showing of causation-in-fact is evalu- ated using the three-prong test set forth in Althen v. Secre- tary of Health and Human Services requiring that the petitioner show: (1) a medical theory causally connecting the vaccina- tion and the injury; (2) a logical sequence of cause and effect showing that the vaccination was the reason for the injury; and (3) . . . a proximate temporal relationship between vac- cination and injury. 418 F.3d 1274, 1278 (Fed. Cir. 2005). The evidence set forth for those prongs “must cumulatively show that the vaccination was a ‘but-for’ cause of the harm, rather than just an insubstantial contributor in, or one among several possible causes of, the harm.” Pafford v. Sec’y of Health & Hum. Servs., 451 F.3d 1352, 1355 (Fed. Cir. 2006). In evaluating Winkler’s claim for relief, the Special Master made separate holdings for each Althen prong. First, she assumed that Winkler had established the first prong, without fully evaluating whether he had in fact done so. Special Master Decision at *23. She then held that he had not established the second prong but had established the third. Id. at *23−26. She subsequently denied relief because of a failure to show, by preponderant evidence, that the Tdap vaccine was the reason for Winkler’s GBS. Id. at *26. Case: 22-1960 Document: 46 Page: 5 Filed: 12/13/2023

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In reaching her conclusion on the second Althen prong, the Special Master thoroughly reviewed evidence relating to Winkler’s May 3, 2017 visit to his physician during which he was diagnosed with gastroenteritis. See Special Master Decision at *23−25. Although the physician did not probe further to determine whether or not the gastroenter- itis was due to a gastrointestinal infection, expert testi- mony submitted on behalf of the government supported a conclusion that Winkler likely suffered from such an infec- tion. Id. at *24. In particular, a medical expert testifying on behalf of the government reviewed Winkler’s complaints of “fatigue, bloody stools, chills, and feeling feverish” and found that that particular constellation of symptoms was consistent with a C. jejuni infection. Id. at *20, *24. The Special Master thus considered two potential triggers of the GBS: the Tdap vaccine and the diarrheal illness that was consistent with a C. jejuni infection. Winkler argues on appeal that the Special Master erred by requiring him to disprove that he suffered from a C. jejuni infection. Pet. Br. at 6. However, Winkler mis- characterizes the burden that he was required to meet. In asserting an off-Table injury, Winkler needed to show, by preponderant evidence, that his Tdap vaccination was a substantial factor in causing his GBS. He did not need to show that he did not suffer from a gastrointestinal infec- tion, or that said gastrointestinal infection did not contrib- ute to his GBS. Nor did he have to show that the Tdap vaccination was the only cause of his GBS. The Special Master made that clear, explaining that “petitioner is not required to eliminate other potential causes in order to be entitled to compensation.” Special Master Decision at *25 (citing Walther v. Sec’y of Health & Hum. Servs., 485 F.3d 1146, 1149−52 (Fed. Cir. 2007)). Here, the Special Master did not conclude that Winkler was not entitled to relief be- cause he did not disprove evidence of an infection. Rather, the Special Master held that Winkler was not entitled to relief because he did not establish a prima facie case of Case: 22-1960 Document: 46 Page: 6 Filed: 12/13/2023

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causation of his GBS by the Tdap vaccine. As explained in Doe v. Secretary of Health and Human Services, a “peti- tioner’s failure to meet his burden of proof as to the cause of an injury or condition is different from a requirement that he affirmatively disprove an alternative cause.” 601 F.3d 1349, 1356−58 (Fed. Cir. 2010) (discussing 42 U.S.C. § 300aa-13(a)(1)). Winkler further argues that the Special Master erred in failing to make a factual finding as to whether or not he actually suffered from a C. jejuni infection. Pet. Br. at 6. He also contends that, without said factual finding, it was error for the Special Master to consider “irrelevant evi- dence” of a C. jejuni infection. Id. We disagree. As set forth in Stone v. Secretary of Health and Human Services, “evidence of other possible sources of injury can be relevant . . . to whether a prima facie showing has been made that the vaccine was a substantial factor in causing the injury in question.” 676 F.3d 1373, 1379 (Fed. Cir. 2012) (emphasis added). There is no dispute that Winkler’s diarrheal illness was a possible source of injury. Indeed, an expert testifying on Winkler’s behalf acknowledged that “it is not possible to distinguish whether . . . the diarrheal illness alone was responsible for [the] GBS.” Special Mas- ter Decision at *24. Nor is there a dispute that the diar- rheal illness could have been due to a C. jejuni infection and that such an infection could have caused Winkler’s GBS. Id. at *10, *12−13. Especially given that lack of dis- pute regarding C. jejuni as a possible source of injury, eval- uating the strength of Winkler’s prima facie case did not require an explicit finding that Winkler actually suffered from a C. jejuni infection. The Special Master was free to consider evidence relating to whether or not Winkler suf- fered from a C. jejuni infection, as well as the likelihood that said infection triggered Winkler’s GBS. Such contem- plation of a potential causative agent when evaluating whether or not a petitioner has established a prima facie case is in accordance with the law. Case: 22-1960 Document: 46 Page: 7 Filed: 12/13/2023

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To the extent that Winkler challenges the way in which the Special Master weighed evidence relating to C. jejuni infections in the absence of an express finding that he suf- fered from one, we find no abuse of discretion. “We do not reweigh the factual evidence, assess whether the special master correctly evaluated the evidence, or examine the probative value of the evidence or the credibility of the wit- nesses—these are all matters within the purview of the fact finder.” Porter v. Sec’y of Health & Hum. Servs., 663 F.3d 1242, 1249 (Fed. Cir. 2011) (citing Broekelschen v. Sec’y of Health & Hum. Servs., 618 F.3d 1339, 1349 (Fed. Cir. 2010)). As explained in Hodges v. Secretary of Health and Human Services, “[t]hat level of deference is especially apt in a case in which the medical evidence of causation is in dispute.” 9 F.3d 958, 961 (Fed. Cir. 1993). That makes re- versible error and abuses of discretion “extremely difficult to demonstrate” when, as is the case here, the Special Mas- ter “considered the relevant evidence of record, dr[ew] plausible inferences and articulated a rational basis for the decision.” Hines, 940 F.2d at 1528. Using that discretion, the Special Master found that Winkler “failed to provide preponderant evidence of a logical sequence of cause and effect required under Althen Prong Two.” Special Master Decision at *25. We see no abuse of discretion in the Spe- cial Master’s evaluation of the evidence that would man- date overturning her holding. Ultimately, while, based on the record before us, the Special Master could have gone either way, it was not ar- bitrary or capricious for her to conclude that Winkler did not prove his case. And the failure to prove an alternate cause does not obviate the need for proof of causation by the vaccine. CONCLUSION We have considered Winkler’s remaining arguments and do not find them persuasive. For the foregoing rea- sons, we affirm the Special Master’s holding that Winkler Case: 22-1960 Document: 46 Page: 8 Filed: 12/13/2023

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failed to prove causation of GBS by the Tdap vaccine by preponderant evidence. AFFIRMED Case: 22-1960 Document: 46 Page: 9 Filed: 12/13/2023

United States Court of Appeals for the Federal Circuit ______________________

DONALD WINKLER, Petitioner-Appellant

v.

SECRETARY OF HEALTH AND HUMAN SERVICES, Respondent-Appellee ______________________

2022-1960 ______________________

Appeal from the United States Court of Federal Claims in No. 1:18-vv-00203-CNL, Judge Carolyn N. Lerner. ______________________

MAYER, Circuit Judge, dissenting. The special master here improperly required the peti- tioner, Donald Winkler, to eliminate other potential causes of his Guillain-Barré syndrome (“GBS”) and permitted the government to defeat his claim without producing any credible evidence that he was afflicted with a Campylobac- ter jejuni (“C. jejuni”) infection or that it, rather than vac- cination, triggered his GBS. See J.A. 30–34. Under the special master’s reasoning, the government can defeat a claim for compensation under the National Childhood Vac- cine Injury Act of 1986, Pub. L. No. 99-660, 100 Stat. 3755, codified as amended, 42 U.S.C. §§ 300aa-10 to -34 (“Vaccine Act”), simply by speculating—rather than establishing— that an agent other than vaccination caused a petitioner’s Case: 22-1960 Document: 46 Page: 10 Filed: 12/13/2023

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illness. Such an approach will make it nearly impossible for claimants—even those who, like Winkler, can provide cogent medical evidence linking their vaccination to their injury—to prevail in off-Table claims for compensation. The special master’s approach has no place in the pro- claimant compensation system designed by Congress, a system where awards are to “be made to vaccine-injured persons quickly, easily, and with certainty and generosity,” H.R. Rep. No. 99–908, 99th Cong., 2d Sess. 3 (1986), re- printed in 1986 U.S.C.C.A.N. 6344, 6344, where a link be- tween vaccination and an injury can be found “in a field bereft of complete and direct proof of how vaccines affect the human body,” Althen v. Sec’y of HHS, 418 F.3d 1274, 1280 (Fed. Cir. 2005), and where “close calls regarding cau- sation [must be] resolved in favor of injured claimants,” id. I therefore respectfully dissent. I. The special master’s initial order, issued pursuant to Vaccine Rule 5, was correct. See J.A. 103–04. She deter- mined that because Winkler’s expert, John R. Rinker, M.D., a neurologist with subspecialty training in neuro-im- munology, J.A. 63, had done “a good job explaining” why Winkler could meet all three prongs for vaccine causation set out in Althen, 1 she “would not be opposed to finding” that Winkler satisfied his burden to demonstrate that the tetanus-diphtheria-acellular-pertussis (“Tdap”) vaccine he

1 In an off-Table case, the petitioner must show by preponderant evidence that the vaccination caused his in- jury by providing: “(1) a medical theory causally connecting the vaccination and the injury; (2) a logical sequence of cause and effect showing that the vaccination was the rea- son for the injury; and (3) a showing of a proximate tem- poral relationship between vaccination and injury.” Althen, 418 F.3d at 1278. Case: 22-1960 Document: 46 Page: 11 Filed: 12/13/2023

WINKLER v. HHS 3

received on April 26, 2017, led to the development of his GBS. J.A. 103. The special master further stated that while the government alleged that a C. jejuni infection, ra- ther than vaccination, caused Winkler’s GBS, it could “have difficulty proving the [gastrointestinal] infection was more likely than not the cause of [Winkler’s] GBS.” J.A. 104. Citing to precedent from this court, the special master emphasized that because there were at least two potential independent causes of Winkler’s GBS, it was the govern- ment’s burden to demonstrate that it was a C. jejuni infec- tion, rather than vaccination, which caused Winkler’s condition. J.A. 104 (citing Walther v. Sec’y of HHS, 485 F.3d 1146, 1151 (Fed. Cir. 2007)). Inexplicably, however, when the special master issued her final decision, she reversed course, absolving the gov- ernment of any duty to establish either that Winkler had been afflicted with a C. jejuni infection or that it was the likely trigger for his GBS. See J.A. 32–33. Indeed, the spe- cial master denied Winkler’s claim without making a find- ing that he ever experienced a C. jejuni infection. See J.A. 32–33. Nor could she have made such a finding on the rec- ord presented. In support of its assertion that it was a C. jejuni infec- tion that led to Winkler’s GBS, the government relied heav- ily on the testimony of its expert, Vinay Chaudhry, M.D. Chaudhry’s testimony, however, rested upon conjecture stacked upon speculation after speculation and was there- fore wholly inadequate to derail Winkler’s strong prima fa- cie case of causation. As a preliminary matter, none of Winkler’s laboratory tests showed any indicia of a C. jejuni infection, J.A. 32, 43, 105, and there was no evidence that any physician who treated him for his non-specific diarrheal illness considered it to have been caused by such an infection, J.A. 4–5. The record shows, moreover, that the overwhelming majority of diarrheal illnesses are not the result of a C. jejuni infection. Case: 22-1960 Document: 46 Page: 12 Filed: 12/13/2023

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As the special master acknowledged, “[c]auses of gastroen- teritis include food poisoning, viral infections, and con- sumption of irritating food or drink.” J.A. 5 n.7. Notably, Rinker pointed to medical literature showing that while “[e]stimates for annual incidence of diarrheal illnesses in the United States range from 179 million to 350 million,” the Centers for Disease Control and Prevention (“CDC”) es- timates that only “approximately 1.5 million instances of gastroenteritis are caused by Campylobacter each year (in- cluding unconfirmed cases).” J.A. 105 (citations omitted). This means that Campylobacter accounts for less than 1% of all cases of gastroenteritis in the United States. 2 J.A. 105. By contrast, “among gastroenteritis cases in which the pathogen was identified, norovirus is the most common pathogen, accounting for 12–16% of cases.” J.A. 105 (cita- tion omitted). Notably, moreover, Chaudhry acknowledged that while C. jejuni infection has been linked to the devel- opment of GBS, a diarrheal illness caused by certain other agents, such as one caused by Campylobacter coli, “does not trigger GBS.” J.A. 98.

2 In his rebuttal report, Chaudhry stated that “infec- tion with [C. jejuni] is one of the most common causes of gastroenteritis worldwide,” J.A. 108 (citation and internal quotation marks omitted), but he did not dispute Rinker’s claim that there were less than 1.5 million instances of gas- troenteritis caused by Campylobacter each year in the United States, J.A. 109. To the contrary, Chaudhry cited to a CDC report stating that there were only “about 1.3 mil- lion cases” of Campylobacter infection each year in this country. J.A. 109. Further, while Chaudhry pointed to an article stating that C. jejuni infections are a common cause of “bacterial gastroenteritis,” J.A. 137 (emphasis added), there is no evidence demonstrating that Winkler’s non-spe- cific diarrheal illness was caused by a bacterial infection. Case: 22-1960 Document: 46 Page: 13 Filed: 12/13/2023

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Further, “the CDC’s Tdap Vaccine Information State- ment lists diarrhea as a possible adverse reaction.” J.A. 17 (footnote omitted); see J.A. 105. Given that: (1) no labora- tory tests showed Winkler had a C. jejuni infection; (2) re- ports indicate that less than 1% of diarrheal illnesses in the United States are the result of such an infection; (3) Chaudhry acknowledged that diarrheal illness from other agents, such as Campylobacter coli, do not trigger GBS; and (4) the Tdap vaccine Winkler received in April 2017 could well have been responsible for his gastrointes- tinal symptoms, the government’s effort to defeat Winkler’s prima facie case by showing that he had been afflicted with a C. jejuni infection fell woefully short. Even assuming arguendo that the government had made a more robust showing that Winkler had experienced a C. jejuni infection, moreover, its evidence linking such an infection to the development of GBS was anemic. In this regard, it is noteworthy that “less than 0.1% of C. jejuni infections result in a case of GBS.” J.A. 13 (citation and internal quotation marks omitted); see J.A. 105. Further, there are various subtypes of GBS, including acute inflam- matory demyelinating polyneuropathy (“AIDP”) and acute motor axonal neuropathy (“AMAN”), and Winkler’s physi- cians repeatedly diagnosed him with the AIDP subtype. See J.A. 90 (noting that Winkler’s “[h]istory, electrodiag- nostic studies, and spinal tap [were] consistent with AIDP”); see also J.A. 37, 118, 121. While there is an estab- lished connection between a C. jejuni infection and AMAN, the link between a C. jejuni infection and AIDP is signifi- cantly weaker. See J.A. 41, 138; Isaac v. Sec’y of HHS, No. 08-601V, 2012 WL 3609993, at *22 (Fed. Cl. Spec. Mstr. July 30, 2012), aff’d, 108 Fed. Cl. 743 (Fed. Cl. 2013), aff’d, 540 F. App’x 999 (Fed. Cir. 2013) (noting that “AIDP . . . has been found not to be caused by cross-reaction with C. jejuni”); Garcia v. Sec’y of HHS, No. 05-0720V, 2008 WL 5068934, at *7 (Fed. Cl. Spec. Mstr. Nov. 12, 2008), adhered to on reconsideration, No. 05-0720V, 2010 WL 2507793 Case: 22-1960 Document: 46 Page: 14 Filed: 12/13/2023

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(Fed. Cl. Spec. Mstr. May 19, 2010) (concluding that the petitioner established that the tetanus vaccine he received led to his GBS, notwithstanding the fact that the petitioner had also experienced a diarrheal illness, and citing expert testimony that “the most prevalent form of GBS in America is the AIDP form” and “C. jejuni is more commonly associ- ated in sources of medical literature with the AMAN form”). In short, the government failed to produce any reliable evidence that Winkler ever had a C. jejuni infection, much less that it triggered his GBS. Winkler, by contrast, pro- duced credible evidence linking his GBS to vaccination. Before the special master, there was little dispute that Winkler presented evidence sufficient to meet prongs one and three of the Althen test. 3 As to Althen prong two, Rinker provided a reasoned explanation of the logical se- quence of cause and effect between Winkler’s vaccination and his GBS. Rinker stated that “GBS is thought to result when an immunological trigger provokes an autoimmune reaction in an affected person that leads to widespread de- myelination of the peripheral nerves” and that vaccination can cause GBS by provoking the immune system to attack healthy tissues. J.A. 66; see also J.A. 12–13. Rinker sup- ported his testimony by citing to medical literature indicat- ing that vaccination, in general, and the tetanus vaccine,

3 The special master here correctly “assum[ed]” that Winkler had “proven a sound and reliable causal mecha- nism” linking his receipt of the Tdap vaccine to the devel- opment of GBS so as to satisfy Althen prong one, given that “the experts agree[d] that molecular mimicry is not a dis- puted theory as it relates to GBS.” J.A. 30. She further correctly concluded that he had satisfied Althen prong three by demonstrating an appropriate temporal associa- tion between his April 26, 2017, vaccination and his devel- opment, approximately ten days later, of GBS. J.A. 34. Case: 22-1960 Document: 46 Page: 15 Filed: 12/13/2023

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in particular, can trigger GBS. 4 See J.A. 14–15. Indeed, even Chaudhry cited to medical literature acknowledging that “epidemiological studies” had “reported development of GBS following vaccinations, including those containing tetanus toxoid.” J.A. 24–25 (citation and internal quota- tion marks omitted). Such evidence was more than ample to satisfy Win- kler’s burden under Althen prong two. In this regard, cau- sation can be established with “circumstantial evidence,” Althen, 418 F.3d at 1280, and Winkler was not required to “submit conclusive proof in the medical literature linking” his vaccination to his illness, Andreu ex rel. Andreu v. Sec’y of HHS, 569 F.3d 1367, 1375 (Fed. Cir. 2009). See Al- then, 418 F.3d at 1277–80 (concluding, based on the testi- mony of the petitioner’s expert, that the petitioner’s central nervous system injury was caused by the tetanus toxoid vaccine she received).

4 Notably, one large-scale study concluded that there was “strong evidence” that a specific flu vaccine had “in- cited the onset of GBS in many adult vaccinees.” J.A. 14 (citation and internal quotation marks omitted); see also J.A. 70. Another article examined reports of GBS following vaccination, finding that 1000 cases of GBS had occurred post-vaccination. J.A. 14, 71. While the development of GBS was most strongly associated with the flu vaccine, there were twenty-eight cases of GBS following tetanus and diphtheria toxoid vaccination and fourteen cases of GBS after a pneumococcal polyvalent vaccination. See J.A. 14, 71. Rinker further noted that there had been at least four individual case reports in the medical literature of per- sons developing GBS following inoculation with vaccines containing tetanus toxoid. J.A. 15–16, 67. Case: 22-1960 Document: 46 Page: 16 Filed: 12/13/2023

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II. The text and structure of the Vaccine Act create a two- stage framework for evaluating causation in off-Table cases. See 42 U.S.C. § 300aa-13(a)(1); Walther, 485 F.3d at 1150. In the first stage, the petitioner has the burden of establishing a prima facie case by demonstrating, by a pre- ponderance of the evidence, that his injury was “caused in fact by the vaccine or vaccines he received.” Paluck ex rel. Paluck v. Sec’y of HHS, 786 F.3d 1373, 1379 (Fed. Cir. 2015) (internal quotation marks omitted); see Andreu, 569 F.3d at 1374. The petitioner, however, “need not show that the vaccine was the sole or predominant cause of [an] in- jury, just that it was a substantial factor.” de Bazan v. Sec’y of HHS, 539 F.3d 1347, 1351 (Fed. Cir. 2008). If the petitioner establishes a prima facie case of causation, the inquiry moves to the second stage, where the government is given the opportunity to demonstrate, by a preponder- ance of the evidence, that the petitioner’s illness was in fact caused by “factors unrelated” to the vaccine. 42 U.S.C. § 300aa-13(a)(1)(B); Walther, 485 F.3d at 1150–51. In certain circumstances, the special master can con- sider evidence of alternative causative agents not only when evaluating the government’s “factors unrelated” de- fense, but also when assessing whether the petitioner has established a prima facie case. See Stone ex rel. Stone v. Sec’y of HHS, 676 F.3d 1373, 1380 (Fed. Cir. 2012) (explain- ing that “the special master is entitled to consider the rec- ord as a whole in determining causation, especially in a case involving multiple potential causes acting in concert, and no evidence should be embargoed from the special mas- ter’s consideration simply because it is also relevant to an- other inquiry under the statute”). This can be appropriate where the petitioner’s evidence linking his injury to a vac- cine is unusually weak and the government’s evidence of an alternative cause, by contrast, is compelling. See id. (stating that “in some cases a sensible assessment of cau- sation cannot be made while ignoring the elephant in the Case: 22-1960 Document: 46 Page: 17 Filed: 12/13/2023

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room—the presence of compelling evidence of a different cause for the injury in question”); see also Doe ex rel. Doe v. Sec’y of HHS, 601 F.3d 1349, 1358 (Fed. Cir. 2010) (affirm- ing a denial of compensation where a special master deter- mined that the claimants had failed to establish a prima facie case because their daughter’s symptoms did not cor- respond to their theory of causation and “not because [the claimants] failed to eliminate [Sudden Infant Death Syn- drome] as an alternative cause of [their daughter’s] death”). Importantly, however, we have made clear that in as- sessing a potential alternative cause, a special master: (1) “may not require the petitioner to shoulder the burden of eliminating all possible alternative causes in order [to] establish a prima facie case”; and (2) “may find that a factor other than a vaccine caused the injury in question only if that finding is supported by a preponderance of the evi- dence.” Stone, 676 F.3d at 1380; see Walther, 485 F.3d at 1151 (explaining that “when there are multiple independ- ent potential causes, the government has the burden to prove that the covered vaccine did not cause the harm”). The special master violated both of these prohibitions here. Even though the special master paid lip service to the notion that a petitioner need not eliminate other potential causes in order to establish a prima facie case, see J.A. 32, the crux of her analysis was that because Winkler could not conclusively demonstrate that he did not have a C. jejuni infection, he could not establish the requisite causal link between vaccination and his GBS. See J.A. 32–33. She stated that while Rinker argued that “the mere presence of diarrhea before the onset of GBS, especially when C. jejuni was never identified, provides an unlikely cause of [Win- kler’s] GBS in comparison to the Tdap vaccination,” Win- kler was not tested for the presence of a C. jejuni infection and therefore could not “explain how the Tdap vaccine [was] the more likely cause of [his] GBS.” J.A. 32. In other words, because no test had ruled out a C. jejuni infection, Case: 22-1960 Document: 46 Page: 18 Filed: 12/13/2023

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Winkler could not eliminate such an infection as the cause of his illness. This analysis has it backwards—Winkler was not required to rule out a C. jejuni infection, but it was instead the government’s burden to “rule in” such an infec- tion. See Walther, 485 F.3d at 1152 (“[W]e have specifically recognized that the government bears the burden on alter- native causation when, as here, the petitioner attempts to establish a prima facie case through the off-Table path of proving actual causation.”). Relatedly, despite the rule that a special master “may find that a factor other than a vaccine caused the injury in question only if that finding is supported by a preponder- ance of the evidence,” Stone, 676 F.3d at 1380, the special master here never determined that there was preponder- ant evidence showing that Winkler had been afflicted with a C. jejuni infection. See J.A. 30–33. Instead, she simply concluded that because there were two “potential” causes of his GBS, he could not establish that vaccination was the “but for” cause of his illness. J.A. 33. In effect, under the special master’s approach, the government can derail a pe- titioner’s prima facie case simply by identifying a “poten- tial” alternative cause for his condition. III. “There is . . . a fine line between a court properly con- sidering evidence in the record and improperly placing the burden on the petitioner to prove that” an illness was not caused or exacerbated by a factor unrelated to vaccination. Sharpe ex rel. Sharpe v. Sec’y of HHS, 964 F.3d 1072, 1082 (Fed. Cir. 2020) (citation omitted). The special master here crossed this line by a wide margin. Instead of holding the government to its burden, she required Winkler to demon- strate that he did not have a C. jejuni infection and that it did not trigger his GBS. Despite ongoing research, the etiologies of many dis- eases and disorders remain poorly understood. See, e.g., Primiano v. Cook, 598 F.3d 558, 565 (9th Cir. 2010) Case: 22-1960 Document: 46 Page: 19 Filed: 12/13/2023

WINKLER v. HHS 11

(“[M]edicine is scientific, but not entirely a science.”). Given that there is frequently no consensus on the factor or factors likely to trigger a particular illness or disorder, the government will, in the great majority of cases, be able to speculate about a potential alternative cause for a mal- ady that emerges in the wake of vaccination. Thus, to the extent that this court sanctions the approach to causation relied upon by the special master here—an approach which countenances the use of mere speculation regarding alter- native causes to defeat a petitioner’s prima facie case—it will erect a nearly insurmountable barrier to the successful pursuit of an off-Table claim. I would reverse and remand for a calculation of the compensation to which Winkler is entitled.