First Three Autism Omnibus Test Cases Dismissed · 2009-02-12 14:00

Court accuses petitioners’ physicians and experts of “gross medical misjudgment”

This morning, the U.S. Court of Federal Claims Office of Special Masters released decisions in the Vaccine Injury Compensation Program (VICP) claims, Cedillo v. HHS (Case No. 98-916V), Hazlehurst v. HHS (Case No. 03-654V) and Snyder v. HHS (Case No. 01-162V), the first three “test cases” in the Omnibus Autism Proceeding.

All three cases have been dismissed in lengthy, complex rulings befitting the extent of scientific evidence and testimony presented to the court regarding the possible causal connection between the measles-mumps-rubella (MMR) vaccine, thimerosal-containing vaccines, and autistic spectrum conditions.

The following passages are excerpted from the 183-page decision in Cedillo v. HHS. Excerpts from the rulings in Hazlehurst v. HHS (Case No. 03-654V) and Snyder will appear on this weblog over the days to come.

Excerpts from
Decision, Cedillo v. HHS
(No. 98-916V; filed February 12, 2009)

Special Master George L. Hastings, Jr.
Ronald Homer and Sylvia Chin-Caplan, Boston, Massachusetts, for petitioners
Vincent Matanoski and Lynn Ricciardella, U.S. Department of Justice, Washington, D.C., for respondent

Summary: “The evidence was overwhelmingly contrary to the petitioners’ contentions”

The petitioners in this case have advanced a causation theory that has several parts, including contentions (1) that thimerosal-containing vaccines can cause immune dysfunction, (2) that the MMR vaccine can cause autism, and (3) that the MMR vaccine can cause chronic gastrointestinal dysfunction. However, as to each of those issues, I concluded that the evidence was overwhelmingly contrary to the petitioners’ contentions. The expert witnesses presented by the respondent were far better qualified, far more experienced, and far more persuasive than the petitioners’ experts, concerning most of the key points. The numerous medical studies concerning these issues, performed by medical scientists worldwide, have come down strongly against the petitioners’ contentions. Considering all of the evidence, I found that the petitioners have failed to demonstrate that thimerosal-containing vaccines can contribute to causing immune dysfunction, or that the MMR vaccine can contribute to causing either autism or gastrointestinal dysfunction. I further conclude that while Michelle Cedillo has tragically suffered from autism and other severe conditions, the petitioners have also failed to demonstrate that her vaccinations played any role at all in causing those problems. (p. 2)

On “genetic hypersusceptibility,” “mercury efflux disorder” and general citations to medical literature

In this case, as to this “genetic hypersusceptibility” theory of petitioners, the main reason that I have rejected it is that Dr. Aposhian’s reasoning concerning the theory was unpersuasive, while Dr. Brent’s reasoning was convincing. The absence of medical literature support for the theory is simply an additional point casting doubt upon the theory. (p. 37, fn. 41)

I find that Dr. Brent’s testimony on this point was persuasive, and that the testimony of Dr. Aposhian was not. I conclude that the Holmes, Bradstreet 2003, and Adams studies are of doubtful reliability, and that the contrary studies cited by Dr. Brent provide better evidence. I conclude that the petitioners have failed to show that their “mercury efflux disorder” theory has any validity. (p. 31)

I have examined all of the items of medical literature cited by petitioners, and those items do contain some evidence indicating that mercury in some forms and dosages can be toxic. However, a thorough examination of the record makes it clear that there is no evidence, beyond Dr. Aposhian’s own assertion, that ethylmercury, in the very small amounts contained in thimerosal-containing vaccines, can damage infant immune systems, or otherwise contribute to autism in any way. For example, none of the medical articles, cited by petitioners at the pages of their brief set forth above, conclude or even suggest that thimerosal or ethylmercury, in the amounts contained in infant vaccines, can damage immune systems or cause other harm. Accordingly, I conclude that those general citations of petitioners to medical literature do not offer any substantial support to their theory that thimerosal-containing vaccines can damage the infant immune system. (pp. 31-32)

On the testimony of Dr. Vera Byers and Dr. Marcel Kinsbourne: “No support for her conclusion… No opinion of his own”

The testimony of Dr. Byers, however, was quite vague… other than her brief discussion of the Goth and Agrawal articles, Dr. Byers did not provide any support for her apparent conclusion that thimerosal-containing vaccines can damage immune systems, saying only that she was relying on Dr. Aposhian for that point. (p. 32)

Additionally, petitioners pointed to the opinion of another of their experts, Dr. Marcel Kinsbourne, asserting that he listed “mercury” as a “possible cause of immune dysregulation.” A close reading of the section of the transcript cited by petitioners, however, indicates that Dr. Kinsbourne was careful to offer no opinion of his own concerning this topic. He stated only that mercury was “one of the possibilities” as a cause for the alleged immune dysregulation of Colten Snyder, and he also noted that even in going that far, he was not stating his own opinion, but was “relying on another expert’s independent opinion on that”. Dr. Kinsbourne also made it quite clear, during his testimony in this Cedillo case, that he does not have an opinion of his own as to whether thimerosal-containing vaccines can cause immune dysfunction.

On the Unigenetics Laboratory: “Testing for measles virus was not reliable”

[A] number of factors have contributed to my conclusion that the Unigenetics testing for measles virus cannot be considered reliable. As explained, the most important factors in my rejection of the Unigenetics testing are that the laboratory failed to publish any sequencing data to confirm the validity of its testing, the failure of the efforts by other laboratories to replicate the Unigenetics testing, and the demonstration by the D’Souza group that the Uhlmann primers were “nonspecific.”

In addition, the testimony of Drs. Bustin, Rima, and MacDonald convinced me that severe problems existed with the procedures, facilities, and equipment of the Unigenetics laboratory, adding a secondary, additional reason to doubt the reliability of the Unigenetics testing. Other important factors are the failure of the petitioners to supply any persuasive evidence that any purportedly detected measles virus material was vaccine-strain measles virus material, the dramatic contrast between the credentials of the expert witnesses for the two sides, and the lack of persuasiveness of the petitioners’ main arguments.

For all of those reasons, I conclude that the Unigenetics testing for measles virus was not reliable. I conclude that the Unigenetics laboratory never reliably detected the presence of measles virus, in the Uhlmann study or in the testing of individual samples of persons such as Michelle Cedillo and Colten Snyder. And, in particular, I conclude that the purported detection by Unigenetics of measles virus in the tissue of Michelle Cedillo was not reliable and cannot be considered valid. (p. 77-78)

Petitioners have not explained why, or pointed to any legal authority explaining why, I should therefore ignore a witness who did provide relevant evidence…. [T]here is no valid reason for me to disregard the evidence supplied by Dr. Bustin, and (2) that even if I did disregard that evidence, my conclusions concerning all of the issues in this case would remain the same. (p. 85)

On the theory that MMR Vaccine can or did cause autism

After a complete analysis of the record, I conclude that I must reject both petitioners’ general theory concerning the causation of autism, and their contention that the measles virus substantially contributed to Michelle’s own autism. Petitioners have failed to demonstrate that it is “more probable than not” either that the MMR vaccine can cause or contribute to autism in general, or that a MMR vaccination did cause or contribute to Michelle’s autism…

First, Dr. Kinsbourne’s general causation theory depends, in any individual case, upon the existence of a reliable laboratory test that finds persisting measles virus in the autistic child’s body. Such a reliable test, however, likely does not exist.

Second, even if in some case a reliable test could demonstrate the existence of persisting vaccine-strain measles virus in an autistic person’s body, the available evidence still does not demonstrate that measles virus persistence in the brain would result in autism.

Third, the fact that the wild measles virus has never been shown to cause autism makes it quite unlikely that the vaccine-strain form of the measles virus can cause autism.

Fourth, Dr. Kinsbourne’s causation theory seems unlikely in light of several accepted understandings concerning the causation of autism. The theory seems doubtful in light of the accepted points that there is a strong genetic component to autism, and that the only non-genetic factors that have ever been conclusively found to contribute to autism are factors that influence development during the early prenatal period. The petitioners’ theory is also directly contradicted by autopsy studies demonstrating that the brains of autistic individuals show abnormal features that, of necessity, would have occurred during specific parts of the prenatal period.

Fifth, there are other difficulties with Dr. Kinsbourne’s theory, especially the contradictions and inconsistencies in Dr. Kinsbourne’s testimony concerning the appropriate time period between MMR vaccination and onset of autism symptoms, under his causation theory.

Sixth, the testimony of Dr. Corbier, Dr. Hepner, and Dr. Kennedy fails to provide any substantial support to Dr. Kinsbourne’s causation theory.

Seventh, the qualifications of the respondent’s experts concerning this issue substantially exceed the qualifications of the petitioners’ expert witnesses.

Eighth, the epidemiologic evidence, consisting of numerous studies by qualified medical researchers around the world, adds another reason to reject the petitioners’ theory that the MMR vaccine can contribute to the causation of autism.

Ninth, two well-qualified committees of medical experts, selected by the Institute of Medicine, have extensively studied the general MMR/autism causation issue, and have concluded that the evidence favors rejection of the proposition that the MMR vaccine can cause autism. (p. 87-88)

On the petitioners’ reasoning process: “A huge leap from the existing evidence”

[T]he petitioners’ causation theory at that point takes a huge leap from the existing evidence, by asserting that, since it is known that autism is not 100% genetic, and that some prenatal exposures seem to contribute to autism, we can therefore infer that the MMR vaccine is another environmental factor that can contribute to the causation of autism. At that point, the petitioners’ argument goes far beyond the existing evidence. Moreover, it seems to me that the three accepted points concerning the causation of autism, set forth above, make the petitioners general causation theory seem unlikely, in two ways. First, we know for certain that genetic factors and prenatal exposures can cause autism, while the evidence concerning the possibility of causation by postnatal factors is weak, as will be discussed. This point, of course, certainly does not rule out the possibility of causation by a particular postnatal factor, such as the measles virus, but it does make one cautious about attributing causation to any postnatal factor. Secondly, […] autopsy studies indicate that autism results from abnormal brain development prior to birth. That finding is consistent with either genetic causation or causation by early prenatal environmental exposures, but it is inconsistent with causation by a vaccine that is received during the second year of life. (p. 95)

[T]he articles and other cited items listed in the previous three paragraphs illustrate this important point that medical science does not at this time completely understand the causation of autism, and is open to evidence of the possibility of postnatal factors playing a causal role. Clearly, some scientists are currently exploring the possibility of a causal role of postnatal factors, and possibly such a role may be confirmed in the future. But in science, general conclusions concerning causation are not usually based upon isolated reports of a single case or a few cases suggesting a causal connection. Moreover, it is significant that none of the petitioners’ experts have discussed those articles and the other cited items at all, failing to explain why such reports might offer any significant support to the proposition that postnatal environmental factors can contribute to the causation of autism. Rather, as noted above, most of the existing data, accumulated over decades of research, supports the conclusion that autism is the result of malformation of the brain during the prenatal period, as a result of genetic factors and/or prenatal environmental exposures. Therefore, a few unconfirmed items of evidence indicating the possibility of postnatal contributions to the causation of autism, while interesting, do not change the strong direction of the large majority of the available data. The balance of the existing evidence still leaves it as simply unclear whether postnatal environmental factors ever cause autism. (pp. 98-99)

On the testimony of Jean-Ronel Corbier: “His reasoning often seemed jumbled at best”

I was present for the oral testimony of Dr. Corbier, and have carefully studied both his expert report and his oral testimony. I conclude that his testimony does not provide any substantial support for the theory that the MMR vaccine can play a role in causing autism. I conclude that Dr. Corbier has provided no persuasive explanation as to why he believes that the MMR vaccine can play a role in causing autism. Dr. Corbier, like Dr. Kinsbourne and many of the respondent’s witnesses, did explain that the measles virus can in some instances cause injury or death in humans, in the form of disorders such as measles encephalitis, SSPE, etc. He seemed to then jump from that evidence to the conclusion that the MMR vaccine-strain form of the measles virus is capable of causing autism in a person with genetic susceptibility. But Dr. Corbier never persuasively explained how he can reasonably make that startling jump, in light of the fact that autism is a disorder quite different from measles encephalitis, SSPE, and the other disorders that are known to be caused by the measles virus.

I also note that after attending Dr. Corbier’s hearing testimony, and carefully studying his opinion, I simply found no reason to conclude that he is a reliable expert. He failed to put forward a logical explanation as to why he holds his views concerning the causation of autism. His reasoning often seemed jumbled at best. He seemed to be unfamiliar with the medical literature upon which he purported to rely. Dr. Corbier has not published, in any peer-reviewed journal, any articles relevant to autism or to the causation issues concerning which he opined. Dr. Corbier seems to be willing to give opinions concerning causation, purportedly to the level of “more probable than not,” based on very scant evidence. He is willing to opine, for example, that a large number of different factors can contribute to the causation of autism. While I do not doubt that Dr. Corbier was sincere in his beliefs concerning the causation of autism, I simply did not find him to be a reliable expert. (pp. 104-6)

On the testimony of Dr. Karin Hepner and Dr. Ronald Kennedy: “Hesitation, wavering, and apparent self-contradiction”

[S]ince Dr. Hepner did not offer an opinion concerning the petitioners’ MMR/causation issue to the level of “more probable than not,” and offered no explanation of why she believes that the petitioners’ theory is “plausible,” I conclude that Dr. Hepner’s opinion offers no support to this causation theory of the petitioners. (p. 107)

[A]fter reviewing all of Dr. Kennedy’s testimony, I conclude that Dr. Kennedy likely does believe that it is probable than the vaccine-strain measles virus can persist in the system of an infant with immune dysregulation, and thereby cause autism in some individuals. But Dr. Kennedy’s hesitation, wavering, and apparent self-contradiction on this point causes me to give his opinion little weight concerning this issue. Further, Dr. Kennedy offered little explanation concerning why he holds this opinion. And while Dr. Kennedy, as a Ph.D. in microbiology and immunology, is well-qualified to opine concerning some points of this case, the fact that he is not a medical doctor means that his testimony concerning this medical causation issue is substantially outweighed by the testimony to the contrary of the medical doctors who testified for respondent concerning this issue. (p. 107)

On epidemiological studies by Mark and David Geier: “Cannot be accorded any weight”

As noted above, all of the studies that have addressed the MMR/autism causation issue published since the Wakefield article in 1998 have found no association between MMR vaccination and autism, with two exceptions. Both exceptions were studies published by the research team of Dr. Mark Geier and his son David Geier. To be sure, the petitioners in this case have not cited or relied upon those two studies, because, as I will discuss below, the petitioners argue that all of the epidemiologic studies done to date are irrelevant to the petitioners’ causation theory in this case. However, since I find that the epidemiologic studies are of relevance, I have found it reasonable to examine those two studies, to see if they afford any significant counterweight to the many contrary studies discussed above.

After careful consideration, I conclude that the Geiers’ studies cannot be given any weight. Those studies were considered by the Institute of Medicine (IOM) committee that fully studied the entire MMR/causation issue in 2004, and that committee concluded that the studies were so flawed as to be “uninterpretable” and to contribute nothing meaningful (“noncontributory”) concerning the causation issue. The committee noted that the studies were based on databases that themselves had “significant limitations”, and that the studies’ methodologies had “serious methodological limitations”. The committee added that the Geiers’ articles describing the analytical methods were “not transparent” and omitted “important details,” so that it was impossible to evaluate the studies. Other specific points of deficiency in the studies were also discussed.

In addition, Dr. [Eric] Fombonne analyzed the Geier studies, and found them to be “seriously flawed in several respects.” None of the expert witnesses for the petitioners vouched for the reliability of the Geier studies. [emphasis added]

I have reviewed the Geier studies, and I agree with the analysis of those studies set forth in the 2004 IOM Report and in Dr. Fombonne’s report. I conclude that those two Geier epidemiologic studies are not reliable, and cannot be accorded any weight. (pp. 116-117)

On Andrew Wakefield’s 1998 study: “Uninformative concerning the MMR/autism causation issue”

I also note that in listing and discussing the epidemiologic studies relevant to the MMR/autism causation issue, the IOM committee also mentioned the above-described original article published by Wakefield and colleagues in 1998. The authors of that article examined the medical records of 12 children who each had a history of loss of developmental skills, and also had intestinal symptoms. Ten of the 12 seemed to have a disorder falling within the autism spectrum, and in most of those individuals the initial autistic symptoms were first noticed within two months after MMR vaccination. The authors concluded from these findings that they had possibly discovered a “unique disease process” or “syndrome” in which children had both developmental disorders and intestinal disorders, both potentially linked causally to the MMR vaccine.

That Wakefield article, however, cannot be considered to offer significant evidence concerning the MMR/autism causation issue. The article was intended to raise a question about a possible causal association—a question that would then be addressed in the future by large epidemiologic studies. (Such studies have in fact taken place, and have failed to find any evidence of association—see discussion […] above). The study examined only 12 individuals, far too few to yield any strong evidence concerning causation. The 2004 IOM Report pointed out that “because of the overlap in timing between the typical age at which ASD symptoms are initially suspected and the [typical] schedule for MMR * * * vaccinations,” it was hardly surprising that the Wakefield authors could find some children whose autistic symptoms were first noted within two months after MMR vaccination. The IOM report concluded that the Wakefield article was simply “uninformative” concerning the MMR/autism causation issue. Dr. Fombonne also pointed out deficiencies in the Wakefield article.

I agree with the 2004 IOM Report that the 1998 Wakefield article is simply uninformative concerning the MMR/autism causation issue. I also note that, after Wakefield himself came under considerable professional criticism, ten of Wakefield’s twelve co-authors on the 1998 article published a letter in which they clarified that a causal link between MMR vaccine and autism had not been established by their study. Furthermore, they formally “retract[ed]” the causation interpretation suggested in the original article. (pp. 117-118)

On epidemiological evidence: “None has yielded the slightest bit of evidence in the petitioners’ favor”

In sum, it is true, as a statistical matter, that the epidemiologic studies detailed […] above, while showing clearly that the MMR vaccination could not be causing any substantial portion of the cases of autism in general, do not completely rule out the possibility that the MMR vaccine might be associated with some small subset of autism, such as regressive autism. Nonetheless, the balance of evidence from those studies weighs against the petitioners’ causation theory. First, it is indeed an exceedingly slight point in the petitioners’ favor for them to claim that these many studies by different researchers in different countries have not completely ruled out the possibility of any merit to their causation claim. The larger point is that none of those many competent studies has yielded the slightest bit of evidence in the petitioners’ favor—and, of course, it is the petitioners’ burden to show that the MMR vaccine does likely cause autism, not the respondent’s burden to show that there is absolutely no possibility of a causal link.

Second, in my view the failure of so many studies to find any association between MMR vaccine and autism, while not completely ruling out a possible causal role with respect to a subset of autism, at least casts considerable doubt upon the proposition that the MMR vaccine ever plays a role in causing any kind of autism, including regressive autism.

Third, and most importantly, at least five studies do provide evidence directly relevant to the petitioners’ “regressive autism only” argument. Those five studies, as detailed […] above, provide significant evidence against the theory that the MMR vaccine plays a causal role even in the subset of autism known as regressive autism. (pp. 120-121)

The numerous epidemiologic studies done over the past ten years, when taken together, make it very unlikely that the MMR vaccination has played any significant role in the overall causation of autism. It is true, as the petitioners argue, that the available epidemiologic studies do not completely rule out the possibility that the MMR vaccine might be associated with some small subset of autism, such as regressive autism. However, there are three reasons why the epidemiologic evidence still must be said to provide significant evidence against the petitioners’ general causation theory set forth in this case. First, none of the numerous competent studies has yielded the slightest bit of evidence in the petitioners’ favor. Second, the failure of so many studies to find any association between MMR vaccine and autism, while not completely ruling out a possible causal role with respect to a subset of autism, at least casts considerable doubt upon the proposition that the MMR vaccine ever plays a role in causing any kind of autism, including regressive autism. And, third, five studies provide evidence that is directly relevant to the petitioners’ “regressive autism only” argument, supplying significant evidence against the theory that the MMR vaccine plays a causal role even in the subset of autism known as regressive autism.

Accordingly, my conclusion is that the epidemiologic evidence does provide yet another strong reason to reject the petitioners’ general causation theory presented in this case. (p. 123)

On the frailty of recall: “Human memories often become less accurate with the passage of time”

I do acknowledge that Michelle’s mother, Theresa Cedillo, has provided statements at various times which offer at least some support to Dr. Kinsbourne’s assumption that Michelle’s first symptoms of autism occurred suddenly, shortly after Michelle’s vaccination of December 20, 1995.

For example, in an affidavit prepared for this litigation, Ms. Cedillo suggests that in late December of 1995 Michelle suddenly stopped talking, stopped playing, stopped responding to her name. However, as explained above, Michelle’s medical records do not support those assertions. Further, during the evidentiary hearing in this case Mrs. Cedillo herself acknowledged that Michelle’s behavior change came on gradually over the following year, rather than abruptly after the fever episodes. And this explanation by Mrs. Cedillo at the hearing is consistent with the fact that Michelle was never taken to any doctor during the year after the pediatric visit of March 15, 1996. Had there been an abrupt, drastic change in Michelle’s behavior, Michelle’s parents would not likely have waited another full year to seek further medical attention.

To be sure, I do not conclude that Mrs. Cedillo was ever, in her affidavits or her hearing testimony, intentionally failing to tell the truth as she remembered it at that time. After observing her testimony during the evidentiary hearing, I certainly have a favorable impression of her as an honest person. It is simply the case that human memories often become less accurate with the passage of time, especially with respect to emotionally-charged events. I conclude that the most accurate account of the progression of Michelle’s early autism symptoms comes from (1) the records made during the pediatric visits in January and March of 1996, when Mrs. Cedillo’s memory was fresh, and (2) the inferences that can be drawn from the lack of any further physician visits over the following year.

In sum, I conclude that Dr. Kinsbourne, in opining that the MMR vaccine contributed to the causation of Michelle’s autism, based his opinion on another significant mistaken assumption of fact—his assumption that Michelle suddenly and abruptly lost all speech, ceased to react to her name, and lost the desire to be held, about seven days after her MMR vaccination. To the contrary, the overall record demonstrates that her family noticed symptoms of Michelle’s autism gradually after the pediatric visit of January 6, 1996, and over the following year. (pp. 131-132)

On Dr. Arthur Krigsman: “Problems relevant to credibility”

One important factor, which influenced my analysis concerning this issue, is the experience and credentials of the experts who presented evidence concerning the alleged causation of gastrointestinal dysfunction by the vaccine-strain measles virus. The petitioners’ expert, Dr. Krigsman, does have important credentials relevant to this issue. He is a board-certified pediatric gastroenterologist, and he has practiced pediatrics or gastroenterology since 1995, when he completed his gastroenterology fellowship.

However, there are problems with Dr. Krigsman’s practice history and his resume that are relevant to the credibility of his expert opinion given in this case. Dr. Krigsman, after working as an attending physician at Lenox Hill Hospital in New York from 2000 to 2004, left that hospital’s employ under questionable circumstances. According to Dr. Krigsman’s own testimony, the hospital restricted his privileges to perform endoscopies (an invasive procedure with some risks) in the belief that Dr. Krigsman was performing medically unwarranted endoscopies on children for research purposes.

Dr. Krigsman later joined a medical practice in Texas, with the same Dr. Andrew Wakefield whose 1998 article initiated the theory that the MMR vaccine can cause autism and GI symptoms. In 2005 Dr. Krigsman was fined $5,000 by the Texas State Board of Medical Examiners, apparently in part because the website of that medical practice had represented that he was available to see patients at a time when he was not yet licensed to practice medicine in that state; in part because of his “disciplinary action” by the Lenox Hill Hospital; and in part because of his “falsification” and “attempted concealment” of a prior disciplinary action by the Florida medical board.

There also were questions concerning Dr. Krigsman’s curriculum vitae (“C.V.”). The C.V. that petitioners introduced into this proceeding stated that he was an “Assistant Clinical Professor” at the New York University Medical School, but Dr. Krigsman acknowledged on cross-examination that he has never taught a class there. His C.V. also listed four items under the heading of “Publications”, but on cross-examination Dr. Krigsman acknowledged that only one of the four items represented an actual publication. (pp. 138-139)

On “autistic enterocolitis”: “Defective or fraudulent science”

As explained above, Dr. Krigsman based his general causation opinion on the reliability of the Uhlmann study’s general conclusion that children with both developmental disorders and gastrointestinal problems are often infected with measles virus in their intestines, while developmentally normal children with GI problems are rarely so infected. However, as previously discussed, I have concluded that the Uhlmann study was unreliable. Therefore, with the Uhlmann study discredited, Dr. Krigsman’s general causation theory is simply left without any evidentiary support.

Dr. Krigsman has not pointed to any other possible basis for his theory. For instance, Dr. Krigsman did not point to examples in medical history of any type of virus persisting in intestinal tissue and causing chronic GI symptoms. To the contrary, Dr. Hanauer, an expert well-qualified concerning GI inflammation, testified that he is unaware of any examples of viral persistence in intestinal tissue causing chronic inflammation. Neither Dr. Krigsman nor any other expert for petitioners contradicted Dr. Hanauer on this point. Moreover, in constructing his general causation theory, Dr. Krigsman clearly based his theory on the “autistic enterocolitis” theory that evolved from Dr. Wakefield’s seminal 1998 article mentioned above. In his expert report, Dr. Krigsman indicated that he sees a causal connection between the MMR vaccine and a disease category that he described as “autistic enterocolitis.” And at the evidentiary hearing, Dr. Krigsman again used the term “autistic enterocolitis” to describe the disease category that he believes to be MMR-caused. Indeed, Dr. Krigsman’s use of the term “autistic enterocolitis,” along with his assertion that Michelle Cedillo’s illness is a “classic” case of “ASD-GI disease,” perhaps might create the impression that “autistic enterocolitis” is a recognized disease category, accepted by the medical community. That, however, is not the case.

To the contrary, Dr. Hanauer, very experienced in the specific area of inflammatory bowel disorders, testified that the term “autistic enterocolitis” is not utilized in any gastrointestinal textbook of which he is aware. Similarly, Dr. Gershon stated that both the terms “autistic enterocolitis” and “ASD-GI” are not recognized by “gastroenterologists as a scientific community.” Dr. Fombonne and Dr. MacDonald both testified that there exists no evidence to support such a diagnostic category. And Dr. Krigsman himself admitted that two leading textbooks on gastroenterology, which he acknowledges to be authoritative, do not use the terms “autistic enterocolitis” or “ASD-GI.”

Thus, it is clear that the diagnostic category of “autistic enterocolitis,” developed by Dr. Wakefield and adopted by Dr. Krigsman, is not a medically-recognized category. In fact, the record indicates that the term “autistic enterocolitis” evolved from Dr. Wakefield’s above-mentioned 1998 article; the term appears in several articles published over the following years by Dr. Wakefield and a small group of his followers. One such article using the term “autistic enterocolitis” was published in 2000 by Wakefield and colleagues. And it is clear that Dr. Krigsman, in developing his causation theory, was influenced by those articles. For example, Dr. Krigsman testified that his initial idea, that autistic children with gastrointestinal symptoms might be suffering from IBD, was triggered when he read that very Wakefield 2000 article. Given that Dr. Krigsman’s general causation theory was influenced by the “autistic enterocolitis” theory developed by Dr. Wakefield and colleagues, it is fair to note that Dr. Wakefield’s “autistic enterocolitis” theory, and his credibility in developing the theory, have come under severe criticism. For example, see the discussion […] above concerning various committees of medical experts who have considered and rejected Dr. Wakefield’s causation theory. Further, respondent’s experts in this case provided much testimony relevant to the credibility of Dr. Wakefield’s procedures in developing his theory.

For example, Nicholas Chadwick in 1996 was a Ph.D. student working in a London laboratory for Dr. Wakefield, performing PCR testing for measles virus. Chadwick’s interactions with Dr. Kawashima’s laboratory, which was collaborating with Wakefield in the area of measles detection, convinced Chadwick that Kawashima’s positive results in measles virus testing were “false positives,” the result of contamination. Chadwick related that conclusion to Dr. Wakefield. Nevertheless, Wakefield submitted for publication a manuscript relying on the purportedly positive results from Kawashima’s PCR testing. Chadwick asked that his own name be taken off the manuscript, because he was not comfortable with the data. Dr. MacDonald described the Wakefield 2000 article as “deception,” in two respects. He opined that the article deliberately described normal findings in the intestines of the autistic children as “pathology”—i.e., abnormality indicative of disease—in order to create the false impression that the autistic children had much more intestinal pathology than the non-autistic children in the study. Dr. MacDonald also testified that the article misrepresented a photograph of a child’s cecum (a part of the large intestine) as being a photograph of the child’s ileum (a part of the small intestine). He opined that it was “highly unlikely” that this misrepresentation was a mistake, as opposed to deliberate deception. Dr. Rima described an interaction with Dr. Wakefield, in which he informed Dr. Wakefield of a specific contamination error in Wakefield’s measles detection efforts. Dr. Wakefield, however, did not retract his claim that measles material had been identified.

Further, as noted above, after public criticism of the “autistic enterocolitis” theory, ten of Wakefield’s twelve co-authors on the original 1998 article published a letter in which they formally “retract[ed]” the causation interpretation suggested in the original article. At the same time, the British medical journal that published the 1998 article, the Lancet, reviewed allegations of impropriety by Dr. Wakefield and his co-authors in the submission of the article. The Lancet editors noted that some of the children described in the article were also part of the legal action against the vaccine manufacturers, in which Dr. Wakefield was also involved. The editors concluded that this circumstance constituted a financial conflict of interest by Wakefield, which Wakefield should have disclosed to the Lancet, but did not. Dr. MacDonald, indeed, went so far as to opine that Dr. Wakefield’s “autistic enterocolitis” theory was merely an “invention” created for litigation purposes. Similarly, Dr. Rust summarized Wakefield’s process of developing and disseminating his general theory, and described it as “scientific fraud.”

To be sure, the petitioners in this case have stressed that they rely upon Dr. Krigsman as their expert concerning the causation of GI symptoms, not Dr. Wakefield. Thus, they argue that criticisms of the personal integrity of Dr. Wakefield are not relevant here. However, because Dr. Krigsman’s general causation approach clearly was strongly influenced by Dr. Wakefield’s theory, criticisms of Dr. Wakefield’s “autistic enterocolitis” theory are relevant, and criticisms relating to Dr. Wakefield’s credibility in developing that theory are of relevance as well. Therefore, it is a noteworthy point that not only has that “autistic enterocolitis” theory not been accepted into gastroenterology textbooks, but that theory, and Dr. Wakefield’s role in its development, have been strongly criticized as constituting defective or fraudulent science. (pp. 141-144)

On the elevation of theory over evidence: “He seems willing to apply his theory to any case”

Dr. Krigsman based his testimony concerning Michelle’s case on a grossly mistaken assumption as to the history of Michelle’s chronic GI symptoms. Clearly, Dr. Krigsman presented an opinion concerning Michelle’s case either without examining Michelle’s medical records at all, or after badly misreading those records. Either way, such a mistake reflects poorly on the general reliability of his expert opinion.

Similarly, Dr. Krigsman’s reliability as an expert witness was also damaged by his application of his general causation theory to Michelle’s case. That is, while his stated theory involves chronic intestinal inflammation caused by a persisting measles virus, he applied his theory to an individual case—Michelle Cedillo—in which there exists no persuasive evidence of chronic intestinal inflammation, as opposed to other, noninflammatory, GI symptoms. I note that, in Dr. Krigsman’s view, Michelle has suffered for many years, beginning about three weeks after MMR vaccination, from chronic intestinal inflammation—i.e., chronic “enterocolitis,” which means inflammation of both her large and small intestines—caused by a persisting measles virus infection. However, on the issue of whether Michelle in fact has suffered from any form of chronic intestinal inflammation, I found that Dr. Krigsman’s testimony was quite unpersuasive, and was substantially outweighed by a combination of the medical records and the testimony of Dr. Hanauer and respondent’s other experts. Dr. Hanauer spent considerable time during his hearing testimony pointing out in detail how the results of Michelle’s gastrointestinal examinations were inconsistent with Dr. Krigsman’s conclusion that Michelle has suffered from chronic intestinal inflammation since her vaccination. I have set forth a full discussion of the evidence concerning the issue of alleged intestinal inflammation […] below. The general point here, however, is that while Dr. Krigsman stated a general theory involving intestinal inflammation (“enterocolitis”), in practice he seems to be willing to apply his theory to a case with no persuasive evidence of intestinal inflammation. He seems willing to apply his theory to any case involving any type of chronic GI symptoms, whether those symptoms involve evidence of intestinal inflammation or not. In my view, this adds further reason to doubt Dr. Krigsman’s general credibility as a witness, and, therefore, to doubt the validity of his general theory that the MMR vaccine can contribute to the causation of chronic GI symptoms. (pp. 145-146)

On regressive autism and gastrointestinal dysfunction: “Both general and specific causation arguments must fail”

First, both Dr. Kinsbourne’s and Dr. Krigsman’s arguments, regarding a combination of the two types of conditions, are based, as stressed above, on the assumption of valid laboratory test results finding evidence of persisting vaccine-strain measles virus in the autistic children’s intestinal tissue. However, since I have concluded above that the Unigenetics testing is not reliable, both the general causation arguments of Drs. Kinsbourne and Krigsman, and their specific causation opinions in Michelle’s case, must fail for that reason alone.

Moreover, after considering the testimony of the petitioners’ experts concerning this “combination” argument in the overall context of the evidence in this case, I simply do not find this argument to be at all persuasive… I have examined in detail both the petitioners’ evidence concerning whether the MMR vaccine can contribute to the causation of autism, and the evidence concerning whether the MMR vaccine can contribute to the causation of chronic gastrointestinal dysfunction, and I have concluded that the overall evidence strongly contradicts the petitioners’ claims on both counts. The fact that some children have both types of conditions does not give me any more reason to conclude that either or both conditions were causally related to MMR vaccinations.

Accordingly, I reiterate that, after considering the argument of the petitioners’ experts pointing to the combination of autism and GI dysfunction in a child as an indication that both conditions were vaccine-related, I must reject that argument. (pp. 163-164)

On the assumption of widespread entitlement: “This case bears no resemblance at all to most”

As another argument in their briefs in this case, the petitioners raise a contention entitled “Michelle is like other vaccine-injured children who have been compensated in the Program.” That argument consists chiefly of a list of 22 Program cases in which a vaccinee’s injury or condition was found to be vaccine-caused. Petitioners contend that Michelle is “like” those vaccinees who were compensated for their injuries, so that therefore Michelle should be compensated for her medical conditions.

I find no merit to this argument. Michelle’s case bears no resemblance at all to most of the cited cases, except for the fact that each case involved an allegation of “causation-in-fact.” It is true that seven of the cited cases involved MMR vaccines which were found to have caused various neurologic conditions, and that Michelle, too, suffers from a neurologic abnormality. However, the theories of proof involved in those seven cases bear no resemblance whatsoever to the petitioners’ theory of causation in this case. Petitioners have not suggested any similarity in the theories of proof, and I have found none. None of those cases involved a theory that the vaccine-strain measles virus, or any vaccine-strain virus, can persist in the body and thereby cause chronic disturbances in the gut or the brain.

In effect, the logic of this final argument of the petitioners seems to be simply that because some injuries or conditions have been found by special masters of this court to be vaccine-caused, based upon expert testimony, temporal relationships, and other circumstantial evidence, then all “causation-in-fact” claims should be found meritorious. This contention is without merit. Petitioners neglect to mention that while it is true that a substantial number of “causation-in-fact” claims have been found meritorious over the 20-year history of the Program, it is also true that many more such claims, numbering in the thousands, have been rejected by special masters. The fact is, of course, that in each case the special masters must evaluate the particular evidence and the particular causation theory presented, and determine whether it is “more probable than not” that the vaccination in question contributed substantially to the causation of the injury alleged. In some cases the special master will find that a causal connection has been shown, to the necessary level of probability, and in some cases the special master will not.

In this case, the petitioners have advanced a theory of causation quite unlike any causation theory that I have previously seen in the 20 years of the Program’s history. I have carefully evaluated that theory. Based upon all of the evidence, I have found that theory to be without merit. (pp. 167-168)

On the burden of proof: “This is not a close case”

I have not required a level of proof greater than “more probable than not,” which has also been described as “50 percent plus a feather.” I understand fully that petitioners are not alleging that the MMR vaccine was the sole cause of Michelle’s disorders, but are alleging only that the vaccine contributed to the causation of her disorders, possibly in concert with an underlying genetic vulnerability. I have looked beyond the epidemiologic evidence to determine whether the overall evidence—i.e., medical opinion and circumstantial evidence and other evidence considered as a whole—tips the balance even slightly in favor of a causation showing as to any of Michelle’s conditions.

This case, however, is not a close case. The overall weight of the evidence is overwhelmingly contrary to the petitioners’ causation theories. The result of this case would be the same even if I totally ignored the epidemiologic evidence, declined to consider the video evidence, and/or excluded the testimony of Dr. Bustin. The result would be the same if I restricted my consideration to the evidence originally filed into the record of this Cedillo case, disregarding the general causation evidence from the Hazlehurst and Snyder cases. The petitioners’ evidence has been unpersuasive on many different points, concerning virtually all aspects of their causation theories, each such deficiency having been discussed in detail above. The petitioners have failed to persuade me that there is validity to any of their general causation arguments, and have also failed to persuade me that there is any substantial likelihood that Michelle’s MMR vaccination contributed in any way to the causation of any of Michelle’s own disorders. To the contrary, based upon all the evidence that I have reviewed, I find that it is extremely unlikely that any of Michelle’s disorders were in any way causally connected to her MMR vaccination, or any other vaccination. In short, this is a case in which the evidence is so one-sided that any nuances in the interpretation of the causation case law would make no difference to the outcome of the case. (pp. 172-173)

Conclusion: A “loving, caring, and courageous” family “misled by physicians who are guilty of gross medical misjudgment”

The record of this case demonstrates plainly that Michelle Cedillo and her family have been though a tragic and painful ordeal. I had the opportunity, in the courtroom during the evidentiary hearing, to meet and to observe both of Michelle’s parents, and a number of other family members as well. I have also studied the records describing Michelle’s medical history, and the efforts of her family in caring for her. Based upon those experiences, I am deeply impressed by the very loving, caring, and courageous nature of the Cedillo family. Those family members clearly have done a wonderful job of coping with Michelle’s conditions, and in caring for her with great love. I admire them greatly for their dedication to Michelle’s welfare.

Nor do I doubt that Michelle’s parents and relatives are sincere in their belief that the MMR vaccine played a role in causing Michelle’s devastating disorders. Certainly, the mere fact that Michelle’s autistic symptoms first became evident to her family during the months after her MMR vaccination might make them wonder about a possible causal connection. Further, the Cedillos have read about physicians who profess to believe in a causal connection between the MMR vaccine and both autism and chronic gastrointestinal problems. They have visited at least one physician, Dr. Krigsman, who has explicitly opined that Michelle’s own chronic gastrointestinal symptoms are MMR-caused. And they have even been told that a medical laboratory has positively identified the presence of the persisting vaccine-strain measles virus in Michelle’s body, years after her vaccination. After studying the extensive evidence in this case for many months, I am convinced that the reports and advice given to the Cedillos by Dr. Krigsman and some other physicians, advising the Cedillos that there is a causal connection between Michelle’s MMR vaccination and her chronic conditions, have been very wrong. Unfortunately, the Cedillos have been misled by physicians who are guilty, in my view, of gross medical misjudgment. Nevertheless, I can understand why the Cedillos found such reports and advice to be believable under the circumstances. I conclude that the Cedillos filed this Program claim in good faith. [emphasis added]

Thus, I feel deep sympathy and admiration for the Cedillo family. And I have no doubt that the families of countless other autistic children, families that cope every day with the tremendous challenges of caring for autistic children, are similarly deserving of sympathy and admiration. However, I must decide this case not on sentiment, but by analyzing the evidence. Congress designed the Program to compensate only the families of those individuals whose injuries or deaths can be linked causally, either by a Table Injury presumption or by a preponderance of causation-in-fact evidence, to a listed vaccination. In this case the evidence advanced by the petitioners has fallen far short of demonstrating such a link. Accordingly, I conclude that the petitioners in this case are not entitled to a Program award on Michelle’s behalf. (pp. 173-174)

Comments


  1. “The study examined only 12 individuals, far too few to yield any strong evidence concerning causation. The 2004 IOM Report pointed out that “because of the overlap in timing between the typical age at which ASD symptoms are initially suspected and the [typical] schedule for MMR vaccinations,” it was hardly surprising that the Wakefield authors could find some children whose autistic symptoms were first noted within two months after MMR vaccination.”

    And yet, he fudged that data.

    — _Arthur    2009-02-12 14:39    #

  2. “On epidemiological studies by Mark and David Geier: “Cannot be accorded any weight””

    I couldn’t have said it better myself.

    — Joseph    2009-02-12 16:58    #

  3. Unremittingly damning.

    — Socrates    2009-02-12 19:01    #

  4. Thank you Kathleen for your relentless and thorough reporting.

    — Mekei    2009-02-12 19:31    #

  5. I read through the Cedillo judgement today and can find no joy in it, just great sorrow for the parents. In various places there’s talk of appeal and applying to civil court. They can’t have thought any of that is easier than vaccine court, though they do have the advantage of persuadable juries.

    — alyric    2009-02-12 20:21    #

  6. Elric, the Petitioners have the opportunity to present 6 other “test cases”, I suppose with further expert testimony.

    The Cedilllos are likely to be still eligible for compensation, for the fever following the vaccine, which is a “Table” injury, as far as I know.

    — _Arthur    2009-02-12 22:54    #

  7. _Arthur, the three test cases for causation theory #2 (thimerosal alone) – the King, Mead and Dwyer cases – have already gone to hearing. The PSC decided not to present any test cases on theory #3 (MMR alone), reasoning that the theory was subsumed in the first set of cases (thimerosal plus MMR). So all the test cases are in.

    The Cedillos won’t get a second bite at the apple in the Court of Federal Claims with a table injury claim, but I do believe that if the medical records had supported a table injury, the Special Master would have awarded compensation regardless of the petitioners’ failure to prove causation in fact.

    The next big deal will be the attorneys’ fees motion. As Kathleen noted in an earlier post, the Cedillos’ attorneys have already submitted a request for payment of over $2 million in “interim” fees and costs. Special Master Hastings’ assessment of petitioner’s expert witnesses bodes ill for the fee request as to their work.

    It is sad – not that the Special Masters ruled the way they did, but that the petitioners got into this litigation situation in the first place due to what Special Master Hastings in his understated way describes as “gross medical misjudgment.”

    — Anne    2009-02-12 23:43    #

  8. Thank you, Anne, without Autism Diva, I didn’t follow the 3 other hearings.

    The Special Masters would probably have explicitey told the parents that they were a good canditates for a table injury claim, you are right again.

    Anne, the comments on several blogs indicate that the antivaxers are unfazed by this adverse decision. They’ll just call the Special Masters “pharma shills” and keep on fighting for the cause. It is not as if their conviction had ever been science-based.

    — _Arthur    2009-02-13 01:03    #

  9. This is one airtight opinion, IMO. Very careful and precise, and clear.

    Tremendous kudos to the Department of Justice for making an enormous amount of technical information understandable to the Court. The DoJ bore a staggering burden of responsibility: had they not effectively portrayed the strength of the science against the idea that vaccines could cause autism, the opinions might not have reflected that science and we might be looking at a scary situation.

    — isles    2009-02-13 22:32    #

  10. _Arthur, although the “vaccines cause autism” horse is nothing more than a bloody pulp, you’re right that the indications so far are that people will continue beating it. I think it’s unfortunate because, if I had my druthers, the energy and resources that are being spent on this would be used in trying to increase assistance for all autistic people regardless of the cause of their autism.

    I have no problem with the idea of the government providing assistance to families of autistic kids. I just don’t think that the families should have to prove the impossible – that vaccines cause autism – in order to get it. I also think that some people, including autistic people, do suffer vaccine damage, and that the limited VICP fund should be used to compensate them. Kathleen has already identified several cases in which autistic kids have received such compensation. But I would like to see more assistance than vaccine injury compensation be made available for the rest of us.

    — Anne    2009-02-14 15:58    #

  11. I applaud all those who fight against bad science and bad medicine with regards to autism and Apserger’s. the courts blew the anti-vaccine camp out of the water. Unfortunately, this won’t stop celebrities from campaigning against vaccines, or the dupes who sponsor them.

    My wife didn’t have the MMR vaccine until she was 13, 11 years after she was diagnosed with autism. Her mother never had the vaccine. So how does the anti-vaccine crowd deal with that?

    Furthermore, if the vaccine causes autism, why doesn’t everyone who had the vaccine have autism? Bad science equals bad medicine. Lets let this one drop once and for all.

    — RRWest    2009-06-22 15:33    #

  12. R.R…You claim your wife has autism since 2 years old. I certainly don’t believe she had the mass injections given since in the 90’s. Big difference. Also..are you an expert to say she has autism or does she have autism like symptoms? What symptoms did she have from birth till 2 years old? Her problem may have been since birth but not diagnosed due to doctors failing to see the problems the first 2 years and she may have the actual ‘autism’. Autism is caused by many other ‘things’. Getting to the seed that caused her problem is the real cause. Let that drop once and for all. If vaccines are not the reason than let’s see the CDC open the VSD for all to see..not just a chosen few like their friends in the health field. Anything hidden or sealed is to hide the truth..just as records in the UK court. This we will not drop once and for all.

    — m. abdilla    2009-08-15 00:35    #

  13. m., the VSD will never be “open for all to see,” because it contains individuals’ private medical information, which is protected under HIPAA — information such as RR’s and his wife’s medical history, which is none of your business or anyone else’s except to the extent that RR or his wife chooses to disclose it.

    — Kathleen Seidel    2009-08-15 06:36    #