CHRISTIAN J. MORAN, Special Master.
Rhone DePena, the son of the petitioners Bo and Natalie DePena, received a dose of the measles-mumps-rubella (MMR) vaccine when he was seven years old. Within a few weeks, he developed a severe pneumonia for which he was hospitalized for many weeks. During this time, the treating doctors determined that a bacteria, known as pneumococcus, infected his lungs and caused the pneumonia.
The DePenas claim that the MMR vaccine caused Rhone's pneumonia. Through an expert with a background in pediatric pulmonology, Boris Lokshin, they allege that the MMR vaccine weakened a portion of Rhone's immune system and, in his debilitated state, Rhone could not resist the pneumococcus infection. The Secretary has disagreed with this argument and presented the views of an expert with a background in pediatric immunology, Neil D. Romberg. In Dr. Romberg's view, the MMR vaccine does not affect the part of a human being's immune system that responds to pneumococcus infections.
Between the two experts, the Secretary's expert was more persuasive. First, Dr. Romberg has a stronger background in the relevant field, immunology. Second, the Secretary established that his expert's opinions are grounded in immunologic principles that have been established and accepted for decades. Indeed, even Dr. Lokshin did not seriously contest much of Dr. Romberg's opinion. Third, to the extent that Dr. Lokshin presented an innovative theory based on relatively recent mouse models, the Secretary effectively rebutted that evidence by showing that mice do not model what happens to human beings facing a pneumococcal infection. For these reasons, the DePenas have failed to meet their burden of proof.
The course of litigation has been relatively routine. The DePenas filed the petition on September 12, 2013. Within approximately two months, they submitted Rhone's medical records.
On May 28, 2014, the Secretary submitted his report, filed pursuant to Vaccine Rule 4. After a review of the medical records, the Secretary recommended that compensation be denied because the DePenas had not presented any evidence in the form of a medical record from a treating doctor or a medical opinion to demonstrate that a vaccine caused Rhone's pneumonia. Resp't's Rep. at 11.
The DePenas retained Dr. Lokshin. As mentioned previously, Dr. Lokshin's specialty is pediatric pulmonology. Exhibit 19 (curriculum vitae). Before the hearing, they submitted four reports from him. Exhibits 21 (Feb. 28, 2015), 22 (May 31, 2015),
In response to Dr. Lokshin, the Secretary retained Dr. Romberg, a pediatric immunologist.
After unsuccessful efforts to resolve the case informally, it was set for a hearing. Before the hearing, the parties submitted briefs, which narrowed the issues. For example, the Secretary conceded that the Rhone developed pneumonia within a time after vaccination for which it is appropriate to infer causation. Resp't's Preh'g Br., filed Jan. 27, 2016, at 23.
A hearing was held in San Antonio, Texas on February 11, 2016. Both Mr. and Ms. DePena testified about Rhone's health before and after the September 15, 2010 MMR vaccination. The DePenas also called Dr. Lokshin. The Secretary's witness was Dr. Romberg. For various reasons, the hearing did not proceed as expeditiously as anticipated, and the hearing did not conclude despite continuing until the early evening.
After the first session of the hearing ended, the DePenas submitted additional information responding to issues that arose during the February 11, 2016 hearing. Another hearing was held on April 12, 2016, during which the attorneys and the witnesses appeared by videoconferencing.
Following the hearing, the parties made additional submissions. The DePenas filed another report from Dr. Lokshin. Exhibit 30.
The parties' disagreement in this case concerns whether Rhone's MMR vaccination weakened a relevant portion of his immune system, making him more susceptible to pneumococcus. The facts outlined below which underlie that disagreement, however, are largely undisputed. This section outlines Rhone's early health, the operation of pneumococcus, the general operation of the MMR vaccine, Rhone's health following the MMR vaccination, and the overall operation of the immune system. These facts are the foundation for the subsequent evidentiary analysis.
Rhone was born in 2003. Exhibit 9 ¶ 1. Until he was seven years old, Rhone's health was normal.
In his periodic visits to his pediatrician, Rhone received vaccinations, although not on the typically recommended schedule.
Pneumococcus is a type of bacterium.
The body's encounter with pneumococcus is unusual in the sense that the first step is colonization. Tr. 110. Colonization means that a strain of pneumococcus is living in a person's nose and throat. Tr. 186;
During colonization of the mucosal surfaces of the nose and throat, the body's adaptive immune system produces an antibody known as immunoglobulin A. Tr. 344; exhibit 25, tab 12 (Jason W. Rosch et al.,
However, pneumococcus can also migrate from the nasopharynx to other portions of the body. Although the petitioners describe the T cells' role in the change from colonization to infection as a "critical" issue in this case (Pet'rs' Preh'g Br., filed Dec. 15, 2015, at 8), relatively little is known about how this change occurs.
In the United States in 2015, more than one million people suffered from pneumococcal pneumoniae. Tr. 270 (Dr. Romberg);
As previously mentioned, the body's response to a pneumococcal infection is to produce antibodies. For more than 100 years, scientists have believed that antibodies (not T cells) are the way the adaptive immune system responds to pneumococcus. Exhibit 23, tab 4 (Pido-Lopez); Tr. 439, 506.
According to Dr. Lokshin, it is likely that Rhone had pneumococcus in his nasopharynx before receiving the MMR vaccination. Tr. 203.
At an appointment with his pediatrician, Frederick Rhame, on September 15, 2010, Rhone received a series of vaccinations. Exhibit 1; exhibit 5 at 6, 15. For this case, the relevant vaccine is the measles-mumps-rubella vaccine.
The MMR vaccine is an attenuated vaccine, that is, the vaccine contains a weakened form of the live measles virus. In its wild (or natural) state, the measles virus is extremely virulent. Measles causes the death of thousands of unvaccinated people each year.
The people who survive measles infection are more vulnerable to infection from other pathogens for 1-4 weeks. Scientists have recently theorized that the measles virus destroys the memory aspect of the survivor's immune system. Without this memory in their immune system, survivors of the measles virus may be unable to fight off infection and may contract diseases. Exhibit Y (Michael J. Mina et al.,
Dr. Romberg, the Secretary's expert, conceded that the MMR vaccine can have the same consequence as the wild measles virus: a suppression of some parts of the adaptive immune system. Dr. Romberg's concession on this point simplified the litigation.
As just stated, when he was vaccinated, Rhone encountered a weakened form of the measles virus on September 15, 2010. Two days later, Rhone's mother called to report that he had a "bad reaction to shots" and requested a "steroid cream." Exhibit 5 at 31;
On Saturday, September 25, 2010, Rhone's parents brought him to the emergency room at Methodist Children's Hospital because he was having lower back pain. Rhone also had been coughing for two days and his temperature, according to his mother, was "high for him." Exhibit 7 at 32; exhibit 8 at 1. The doctors diagnosed him as having an acute viral syndrome. Exhibit 7 at 35;
Rhone's health did not improve over the next few days. On Tuesday, September 28, 2010, Rhone's mother took him to Dr. Rhame's office because of a high fever, greyish color, and grunting sounds when he was breathing. Tr. 22. Dr. Rhame sent him for testing, including a chest X-ray. Exhibit 5 at 46; exhibit 8 at 1. The chest X-ray showed bilateral pneumonia. Exhibit 5 at 46.
Rhone's pneumonia was severe. He remained at Methodist Children's Hospital for 21 days. Exhibit 7 at 62. His mother described the frightening details in her statement, although the course of how the doctors treated Rhone is not relevant to determining whether the MMR vaccine contributed to the pneumonia.
The doctors determined that Rhone was infected with pneumococcus. Exhibit 7 at 63, 91, 112, 171. There is no doubt that the pneumococcus caused Rhone's pneumonia. Tr. 203. The only question raised in this litigation is whether the MMR vaccine contributed to it.
Near the end of Rhone's hospitalization, the doctors tested Rhone's blood for the presence of titers against 14 serotypes of pneumococcus. For three strands, Rhone had levels of antibodies that exceeded 1.3 µg/mL, which is considered the threshold for protective levels.
After recovering in the hospital, Rhone was discharged on October 18, 2010. Exhibit 7 at 62-64;
Rhone's pulmonologist, Amanda M. Dove, followed his case for several months. Exhibit 3 at 8-17. In June 2013, Dr. Dove assessed Rhone as having mild reactive airway disease. Exhibit 3 at 2. She prescribes medication for an inhaler. Tr. 46.
In August 2015, a CT scan of Rhone's chest was normal, except for some slight scarring. Exhibit 24 at 1. A spirometry test was also normal.
Prompted by questions that arose in this litigation, the DePenas obtained additional information about Rhone's antibody levels in 2016. This testing indicated that Rhone's antibody levels were low to 13 serotypes of pneumococcus. Exhibit 27; Tr. 455, 489.
At the time of the first hearing, Rhone had improved. He sometimes had problems breathing and ran slower than his peers. Tr. 35-35, 60. The DePenas emphasize that after Rhone's 2010 pneumonia, which followed the MMR vaccination, Rhone has not had another episode of pneumonia. Tr. 34, 59, 168.
A body's responses to foreign invaders, often called antigens or pathogens, are controlled by the immune system.
According to Dr. Romberg, the innate immune system contributes to how the body responds when pneumococcus becomes infectious. Exhibit P (Dr. Romberg report) at 3 (citing exhibit S (Brown), exhibit T (Carolyn Mold et al.,
Adaptive Immune System. In comparison to the innate immune system, the adaptive immune system is more advanced. The adaptive immune system recognizes specific antigens. Tr. 266.
The adaptive immune system contains two types of cells: B cells and T cells.
B cells. B cells make antibodies. Tr. 267. Antibodies, in turn, can be classified into different types of immunoglobulin.
T cells. The other part of the adaptive immune system is T cells. T cells derive their name from the thymus, where they mature. Tr. 302;
T cells are further classified. The basic division is into two groups, known as cytotoxic T cells and helper T cells. Cytotoxic T cells, which are also known as CD8+ cells, kill cells that are infected by viruses. Tr. 267, 358. For example, when the body is infected by cytomegalovirus ("CMV"), cytotoxic T cells respond. Tr. 435.
There are multiple types of helper T cells, also known as CD4+ cells. Th1 cells help cytotoxic T cells kill cells infected with infectious agents, especially viruses.
The crux of the disagreement between Dr. Lokshin and Dr. Romberg concerns whether T cells contribute to the body's response to a pneumococcal infection. Dr. Lokshin opines that T cells have a role in the immune system's response. In contrast, Dr. Romberg opines that T cells are expendable. The following sections are reasons why Dr. Romberg's opinion is more persuasive.
In the analysis section below, evidence in this case will be analyzed according to the following standards of adjudication.
Petitioners are required to establish their case by a preponderance of the evidence. 42 U.S.C. § 300aa-13(1)(a). The preponderance of the evidence standard requires a "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."
Distinguishing between "preponderant evidence" and "medical certainty" is important because a special master should not impose an evidentiary burden that is too high.
Special masters are fact finders that use their accumulated expertise to judge the individual merits of claims.
The elements of the DePenas' case are set forth in the often cited passage from the Federal Circuit's decision in
To analyze the petitioners' T cell-centered immunology theory requires both an understanding of both the parties' experts' qualifications and basic principles of immunology. The analysis below first focuses on the experts' qualifications, and second reviews widely accepted principles of immunology related to pneumococcal infection. With the experts' qualifications and the basic principles of immunology as foundations, the analysis goes on to assess the reliability of the petitioners' new immunologic theory.
In considering the value of opinion testimony, special masters may consider the offeror's expertise.
Here, the primary question is how the body responds to pneumococcal colonization or infection. This question is about human immunology. Therefore, the qualifications of the experts are reviewed with an emphasis on immunology.
Dr. Lokshin graduated from medical school and completed a pediatric internship in Russia. He completed a second pediatric internship in California, where he also had a pathology residency and a pediatric residency. Exhibit 19 (curriculum vitae).
From 1988-90, Dr. Lokshin had a joint fellowship in allergy/immunology and pediatric pulmonology at the University of Iowa. In describing his expertise in immunology, Dr. Lokshin emphasized this stage of his medical career. Tr. 64.
After his Iowa fellowship ended, Dr. Lokshin completed another residency in pediatrics and then completed another fellowship, this time in pediatric pulmonology. Both of these fellowships were through the University of Missouri-Columbia School of Medicine, where he also served as an assistant professor in pediatric pulmonology from 1991 through 1993. Exhibit 19. In 1993, the most recent of five articles written by Dr. Lokshin was published.
Dr. Lokshin's next teaching position was in Connecticut at the Yale-New Haven School of Medicine. During this time (1993-95), he also served in the pediatric pulmonology/allergy division within the department of pediatrics at Danbury Hospital. He first became board certified in pediatric pulmonology in 1996, when he was living in Nevada. Exhibit 19;
For some time after May 1996, Dr. Lokshin taught allergy to medical students in large lecture classes at the University of Nevada, Reno. Exhibit 19; Tr. 73. Dr. Lokshin's current teaching involves working with a single student for a few weeks in his office. Tr. 74. His current employment, which started in 1995, is working in a practice consisting of two doctors, called Allergy and Asthma Associates. Exhibit 19; Tr. 63. He usually sees one patient or two patients with pneumococcal pneumonia each year. Tr. 70.
After the petitioners offered Dr. Lokshin as an expert in the relationship between "T cells and invasive pneumococcal disease," the Secretary objected. Tr. 68. The ensuing voir dire brought out that Dr. Lokshin is not board certified in immunology. He has not received any special training on T cells. Tr. 73. He was not performing any research. Tr. 72. His work in treating patients with allergies draws upon his knowledge of immunology because allergy is a subtype of immunology. Tr. 75-79.
Ultimately, he was recognized as an expert in pediatric pulmonology. He possesses the minimum qualifications to testify about immunologic concepts because of his training and experience. However, his testimony on immunologic topics was presented with the risk of being given less weight because of his relative lack of experience in immunology. Tr. 80-81.
Dr. Lokshin's lack of specialized training in immunology affected the quality of his testimony. When Dr. Lokshin presented the articles on which he relied, he frequently stated that he was not presenting his opinion, he was simply presenting a view someone else expressed. Tr. 77, 84, 85, 100, 130, 213. While it is hornbook law that a testifying expert may rely upon the work of another expert if the testifying expert would normally rely upon the second expert's work,
For example, when asked to explain the components of the innate immune system, Dr. Lokshin provided a brief answer, but added that if more information were needed, he would need to research the topic separately. Tr. 214. As another example, Dr. Lokshin used terminology about the immune system that was at least unusual, and possibly incorrect.
Similarly, Dr. Lokshin's presentation of articles was extremely cursory. Despite the undersigned's recommendation that the petitioners and Dr. Lokshin discuss a smaller number of articles with a deep level of analysis, petitioners and Dr. Lokshin more often skimmed the surface of many articles. The petitioners and Dr. Lokshin would have been better served to focus on fewer articles but discuss their complicated immunology more thoroughly. Although the undersigned has reviewed all the articles, more in depth testimony from Dr. Lokshin about the significance of the articles could have promoted the petitioners' case.
The intent of these examples is not to catch Dr. Lokshin in small errors, but explain why he did not appear fluent in the language of immunology. This lack of fluency, again, gave the impression that Dr. Lokshin had limited experience on which to base his opinions. This impression, in turn, diminished the overall value of Dr. Lokshin's testimony.
Dr. Romberg graduated from Pennsylvania State College of Medicine in 2004. He was a resident in pediatrics at New York University School of Medicine from 2004 to 2008, with the last year as pediatric chief resident. He completed a fellowship in allergy and clinical immunology at Yale University from 2008-11. Tr. 257-59; exhibit GG.
In 2011, Dr. Romberg began his teaching career at Yale. He remained at Yale with various titles and responsibilities until 2015. During this time, he obtained his board certification in allergy and immunology. He also wrote at least six papers about immunology, which were published in peer reviewed journals. Some of the papers focus on B cells. Exhibit GG at 3-5. Through grants, the National Institute of Health funded his research on human immunology. Tr. 259.
In 2015, he was appointed to the Jeffrey Modell Chair of Pediatric Immunology Research at Children's Hospital of Philadelphia. Dr. Romberg explained that this position gives him indefinite funding for his research on deficiencies in the immune system. Tr. 260.
Although Dr. Romberg's primary vocation is research, Tr. 259, he also treats children whose immune systems are missing parts. Tr. 275. He estimated that he has treated 40-60 patients with pneumonia, although he did not specify whether the patients with pneumonia also had defective immune systems and did not specify whether pneumococcus caused the pneumonia. Tr. 401.
Overall, Dr. Romberg's knowledge about immunology was impressive. His demeanor and the content of this testimony demonstrated that he understood how the human immune system functions to a level of great detail. He took care to be precise in his wording.
Because the petitioners maintain that the MMR vaccine impaired Rhone's ability to create T cells and the ensuing lack of T cells created a vulnerability to a pneumococcal infection, their case depends on T cells preventing a pneumococcal infection in a human being. As expert testimony unfolded, there was little dispute about the principles underlying the immune system's response to pneumococcal infection. Dr. Lokshin agreed with Dr. Romberg about multiple things that undermine a primary role for T cells in fighting pneumococcal infection.
As outlined below, both Dr. Lokshin and Dr. Romberg agreed that an effective response to pneumococcal infection requires both the innate immune system and antibodies from the adaptive immune system. Additionally, Dr. Lokshin did not dispute that T cells do not respond directly to pneumococcal infection (most likely because the external surface of pneumococcus is primarily composed of polysaccharides). Further, Dr. Lokshin did not dispute Dr. Romberg's observations regarding humans suffering from X-linked agammaglobulinemia and severe combined immune deficiency (SCID), which strongly support the argument that T cells are expendable in the body's response to pneumococcal infection. In short, the following concessions by Dr. Lokshin undermine his ability to maintain that T cells have a significant role in fighting pneumococcal infection in human beings.
Throughout this litigation, Dr. Romberg has maintained that in response to pneumococcal infections, T cells are expendable. In his first report, Dr. Romberg wrote:
Exhibit A at 3. He continued this position in a subsequent report and in his testimony. Exhibit P at 3; Tr. 273, 418, 439-40.
On the other hand, Dr. Lokshin's reports and testimony focused on the role of T cells.
Later still in his testimony, Dr. Lokshin also agreed that the innate immune system also "has [a] very big role in killing pneumococcus. That's not in question." Tr. 467.
With these two passages, Dr. Lokshin has essentially agreed with Dr. Romberg that an effective response to a pneumococcal infection can come from the innate immune system and antibodies. The only remaining question is whether T cells contribute to this response.
On a very simple level, antibodies respond to polysaccharides, and T cells respond to proteins. The capsule of pneumococcus is (mostly) comprised of polysaccharides.
Although the connection between antibodies and polysaccharides and the lack of connection between T cells and polysaccharides was generally not disputed, Dr. Romberg explained some of the highly technical experiments underlying these postulates. For example, he discussed an article reporting on competitive affinity experiments that demonstrated that T cells cannot see polysaccharides.
T cell independence was another way in which the disagreement between Dr. Lokshin and Dr. Romberg was manifest, particularly in regard to exhibit X (James J. Mond et al.,
On the other hand, the same Mond article also discussed pneumococcus specifically. Mond stated: "Early studies with Pneumococcus and other encapsulated and nonencapsulated organisms established the T cell-independence of the antibody response to the polysaccharide component." Exhibit X at 679. After citing Mond and Harding in his second expert report, Dr. Romberg asserted: "Carbohydrate antigens like those on pneumococcus belong to the category named type II T-cell independent antigens." Exhibit P at 3. When asked in the first hearing about Dr. Romberg's classifying pneumococcus as a T cell independent antigen, Dr. Lokshin agreed. Tr. 217-18. Dr. Lokshin's admission that pneumococcus is a T cell independent antigen undermines much of his opinion.
Prior to the second hearing, however, petitioners submitted additional exhibits to further support the possibility that T cells can respond directly to pneumococcus. See Tr. 466; exhibits 25, tab 7 (Qibo Zhang et al.,
Despite the additional articles providing some evidence to the contrary, Dr. Lokshin conceded that T cells do not respond directly to pneumococcal infection. He emphasized that the T cells' alternate role in attacking pneumococcus, testifying: "It's important I think for us because it is not necessarily the T-cells themselves have [sic] to kill something. They may influence other parts of immune [sic] system that will do the job; specifically, innate [sic] immune system." Tr. 466.
In addition to the persuasive immunological studies cited by Dr. Romberg, his experience treating people with dysfunctional immune systems allowed him to add insights about the significance of the difference between T cells and B cells in preventing diseases. Some people do not produce B cells and they suffer from a disease known as X-linked agammaglobulinemia. Tr. 275-76. These people without B cells are vulnerable to pneumococcal infections, which they get repeatedly unless they receive antibodies. Exhibit J (Ogden C. Bruton,
Dr. Romberg interpreted the Bruton article as showing that T cells alone do not prevent pneumococcal infections. If T cells alone were effective, then the child reported in the Bruton article would not have suffered multiple pneumococcal infections. The boy's improvement after receiving antibodies is further evidence that the reason for the repeated pneumococcal infections was due to a problem in the B cells. Tr. 275-76. When asked about this article, Dr. Lokshin agreed that "If somebody gets antibodies, they will stop getting sick [with pneumococcal infections]." Tr. 505.
A different situation occurs with people suffering from severe combined immune deficiency (SCID). People with SCID lack T cells and have either no B cells or defective B cells. When untreated, they get many infections, including fungal, viral, parasitic, and pneumococcal infections. After they receive antibodies, people with SCID do not develop pneumococcal infections, although they continue to develop other types of infections. Tr. 276-77. Again, Dr. Lokshin did not disagree with Dr. Romberg on this point, although Dr. Lokshin noted that the effectiveness of antibodies in responding to pneumococcus does not provide any information about the effectiveness of T cells. Tr. 460.
Against this background of well-established and generally accepted precepts of immunology, Dr. Lokshin proposes a new idea. In Dr. Lokshin's opinion, a human being's response to a pneumococcal infection includes a role for T cells. Tr. 105, 114-16, 181-82.
Before examining the support provided by Dr. Lokshin, it bears repeating that he seems ill-equipped to topple established immunologic ideas, such as T cells do not respond to polysaccharides. Dr. Lokshin does not routinely treat patients with immunologic disorders, he does not teach classes of medical school students in immunology, he does not have any advanced certifications in immunology, and he does not currently author articles on immunology. In short, when the topic is cutting-edge immunology, Dr. Lokshin has less qualifications to present new ideas persuasively.
In Dr. Lokshin's initial reports, he cited several articles that reported on experiments using mice. In these tests, the researchers discovered that mice do produce T cells in response to a pneumococcal infection. At hearing, Dr. Romberg agreed that mice respond to pneumococcus infection by having a particular type of T helper cell, which is known as Th17, produce IL17. Tr. 284, 354, 516.
The Federal Judicial Center ("FJC") has published a series of guides designed to "assist judges . . . in reaching an informed and reasoned assessment concerning the basis of expert evidence." Jerome P. Kassirer & Gladys Kessler,
In this case, although Dr. Lokshin wanted to extrapolate from mice to humans, he did not review the similarities and differences between mice and humans. This leads to a gap in his opinion.
Moreover, Dr. Romberg disagreed with Dr. Lokshin's comparison, stating that with respect to the response to pneumococcal infections, mice differ from people. Tr. 285-86;
An editorial presented a similar point, using less complex language. The authors wrote: "Translation of many other important findings from murine models to humans has been rather disappointing. This is best exemplified by models of autoimmunity and cancer immunotherapy where numerous studies showing promising outcomes in murine models have achieved limited success in a human setting." Exhibit NN (Rajiv Khanna and Scott R. Burrows,
This evidence has undermined the assumption that Dr. Lokshin appears to have made about the transferability of mouse studies on pneumococcus to human beings. Without some reliable showing that an extrapolation from mice to people is appropriate, the studies based upon mice are not useful.
In addition to studies on mice, Dr. Lokshin relied upon human studies to show that a person's response to a pneumococcal infection involves T cells. One person exploring this possible connection is Richard Malley, a researcher at Harvard Medical School and Boston Children's Hospital. Dr. Malley is attempting to develop a vaccine against pneumococcus that stimulates the production of T cells. One advantage to this type of vaccine is that one dose of the vaccine could lead to immunity from many (possibly all) strains of pneumococcus.
There is no doubt that some research is being done in the field. For example, petitioners submitted an excerpt showing that the National Institutes of Health has funded research into a T cell based vaccine against pneumococcus. Exhibit 25, tab 8 (Kristin Leigh Moffitt,
Petitioners also submitted a press release in which a manufacturing company, Genocea, touted its progression to "phase 2" for "a novel T cell vaccine" against pneumococcal colonization. Exhibit 25, tab 9 (
However, the company's phase 2 trials did not show any statistically significant improvement. Thus, the company suspended further development of the vaccine. Exhibit 25, tab 9 (Genocea Biosciences);
Despite the lack of success in developing a T cell based vaccine against pneumococcus, Dr. Lokshin relied upon several other articles either written with Dr. Malley or based upon his work. The goal of developing a T cell based vaccine is certainly laudatory — a successful T cell based vaccine could protect against many (maybe all) strains of pneumococcus. The potential benefits, especially in the regions of the world with less access to medical care, could be immense. However, the worthiness of the pursuit does not automatically make any of Dr. Malley's studies a reliable basis for an expert's opinion.
As previously mentioned, Dr. Lokshin relied upon several articles from Dr. Malley or Dr. Malley's associates. The undersigned reviewed this material multiple times and has considered the testimony from both Dr. Lokshin and Dr. Romberg about those articles.
The previous section explains why Dr. Romberg's opinion was more persuasive than Dr. Lokshin's opinion. These reasons include Dr. Romberg's superior qualifications in immunology, the well accepted and well demonstrated idea that T cells cannot recognize polysaccharides, and the undeveloped effort to overturn immunologic dogma. The remaining task is to place these findings in the context of the
To review, the Federal Circuit set forth the petitioner's burden regarding causation in off-Table cases as "(1) a medical theory causally connecting the vaccination and the injury; (2) a logical sequence of cause and effect showing that the vaccination was the reason for the injury; and (3) a showing of a proximate temporal relationship between vaccination and injury."
The third prong of Althen requires "a showing of a proximate temporal relationship between vaccination and injury."
Before the hearing, the Secretary conceded that Rhone's pneumococcal infection developed within a "medically acceptable timeframe." Resp't's Preh'g Br., filed Jan. 27, 2016, at 23. Thus, the DePenas have met their burden of proof on this prong.
However, a finding in a petitioner's favor on prong 3, by itself, does not mean that the petitioner is entitled to compensation.
The first prong from
For the reasons previously set forth, Dr. Lokshin has failed to establish the reliability of his theory that T cells have a substantive role in a human being's response to a pneumococcal infection. The theory Dr. Lokshin advanced seems contrary to what science knows about the immune system of human beings. It is not persuasive. Therefore, the petitioners have not met their burden regarding prong 1.
Given that the DePenas have failed to establish prong 1, it follows that they have also failed to establish prong 2.
Treating Doctors. In connection with prong 2, the Federal Circuit has instructed special masters to consider carefully the views of treating doctors.
Challenge-Rechallenge. The Federal Circuit defined a rechallenge event as one in which "a patient who had an adverse reaction to a vaccine suffers worsened symptoms after an additional injection of the vaccine."
Here, Dr. Lokshin initially indicated that Rhone's case fell into the challenge-rechallenge paradigm. A foundation for this opinion was an assumption that Rhone developed a rash shortly after receiving his first dose of the MMR vaccine.
On cross-examination, Dr. Lokshin graciously recognized that Rhone did not manifest challenge-rechallenge. Tr. 196. Removing one of the beams of support for Dr. Lokshin's opinion results in a slight weakening of his opinion.
Titer levels after the vaccine and more recently. Before the first hearing, the DePenas submitted the results of testing conducted on October 11, 2010. This testing, which was conducted after Rhone developed pneumonia, showed that his IgG antibody titers were below the level to confer immunity for several strains. Exhibit 7 at 501;
From these two facts, Dr. Lokshin drew the inference that the only difference between Rhone in 2010 and Rhone in the ensuing five years was that Rhone received the MMR vaccine in 2010. This exposure to the MMR vaccine, according to Dr. Lokshin's theory, created a vulnerability in Rhone that was not present in other times of his life. Tr. 144-45.
Dr. Romberg's response included an observation that Rhone's current levels were not known. Tr. 333-34. Therefore, between the first hearing and the second hearing, the DePenas had Rhone tested. His antibody levels from 2016 remained below protective levels for several strains. Exhibit 27;
This reasoning is not persuasive. First, the process from colonization to infection is not understood. Some people develop pneumococcal pneumonia entirely apart from an MMR vaccination. The factor (or factors) that permitted pneumococcal infections in those cases could have been present in Rhone. To isolate the MMR vaccination and consequent decrease in T cells as the reason for Rhone's pneumococcal pneumonia seems to overlook many other potentially contributory factors. For example, the particular bacteria that infected Rhone in 2010 could have been especially virulent and Rhone could have encountered more mild bacteria since then.
Second, Dr. Lokshin appears to misunderstand Dr. Romberg's opinion. Dr. Lokshin asserted that "The `titers' are the antibody levels that, according to Dr. Romberg's theory, is the one and only protection from the pneumococcal infection." Exhibit 31 at 1. Actually, Dr. Romberg listed parts of the innate immune system, such as complement, as contributing to the protection against pneumococcal infection. Exhibit A at 3; exhibit P at 3; Tr. 326-27. These parts of Rhone's innate immune system could have protected him from further pneumococcal infection in the past six years.
Rhone's pneumococcal pneumonia inflicted a toll on him and his parents. His parents demonstrated their concern for Rhone's well-being during their testimony and have reached the belief that the MMR vaccine caused the pneumonia.
However, the evidence does not rise to a "more likely than not" level. The more persuasive evidence is consistent with a finding that the MMR vaccine did not alter the effectiveness of Rhone's innate immune system or his ability to produce antibodies in response to pneumococcus. Thus, the DePenas have not established that the MMR vaccine contributed to Rhone's pneumococcus infection.
The DePenas are not entitled to compensation. The Clerk's Office is instructed to issue judgment in accord with this decision.
