See You In (Vaccine) Court
by David Kirby
The Huffington Post
Posted June 7, 2007 | 07:05 PM (EST)
On Monday, one of the most important legal proceedings in American medical history will get underway at the U.S. Court of Federal Claims in Washington. There, a special panel of three judges will begin hearing evidence to support -- and refute -- the hypothesis that mercury in vaccines and/or the live-virus measles-mumps-rubella shot caused autism or autism-like symptoms in some American children.
Monday will mark the first time ever that evidence of autistic harm from childhood vaccines is examined and cross-examined in a court of law. This is far from a slam dunk case for either side, and the stakes - professional, financial, emotional - could not be more intense.
These three judges from the federal "Vaccine Court," as it is called, are about to dip into the raging, contradictory waters of the vaccine-autism contretemps, knowing they must emerge on the other side, each with their own acutely anticipated decision about causation. Ultimately, they must deliver judgment on some 4,800 claims that have been languishing in the system for years.
I do not envy them their task.
Technically, at least, this is not a trial at all; it is an "Autism Omnibus Proceeding" in a no-fault, supposedly non-adversarial adjudication. The judges are not judges, but "Special Masters;" plaintiff families and their lawyers are called "petitioners," and the defendant, called the "respondent," is not some drug giant, but the Department of Health and Human Services, represented by well-funded attorneys at the US Justice Department.
Any claims awarded in Vaccine Court are paid from a 75-cents-per-vaccine tax footed by consumers, leaving vaccine makers free from liability.
But if even one case of causation is determined, then private lawsuits in civil courts - where the drug makers themselves are on trial - would soon flood the dockets. (Ironically, if families lose in Vaccine Court, they are free to sue in civil court. Having autistic kids appear before sympathetic juries is Big Pharma's big nightmare, and it's why a secret rider was attached to the Homeland Security Act of 2002 to bar thimerosal cases from civil court and force them into Vaccine Court).
Over the next three weeks, evidence on both sides of the first "test case" will be picked apart to its bare bones, with one gaping exception. Petitioners were just denied access to the government's vast vaccine safety database of HMO patients, which was used by CDC officials to conduct a four-year study that ultimately found no link between thimerosal and autism. Earlier versions of the study, obtained through the Freedom of Information Act, however, clearly showed increased risks for many neurodevelopmental disorders, depending on the dose of thimerosal administered.
No wonder a special panel convened by the NIH recently issued a harsh critique of the CDC's data collection and management, saying the study contained "several serious problems... weaknesses and limitations" that "reduce its usefulness" in proving or disproving causation.
And so, numbers culled from the government's massive database will be submitted as Exhibit A for the defense, though the other side will be forever barred from seeing the actual raw data, in order to replicate what the CDC researchers found. (Exact replication is impossible because original datasets, culled at taxpayer expense, somehow "went missing" and are no longer available for re-analysis - a possible felony violation of the federal Data Quality Act).
On the other hand, the burden of proof for plaintiffs is lower in Vaccine Court than other federal courts, which could even things out a little.
Nearly all of the government's evidence will be "epidemiological" in nature - based on large population studies of computerized data. These include the CDC study, plus similar research done in Sweden, Denmark and the UK which found that, if anything, thimerosal had a "neuro-protective" effect on children by apparently reducing their risk of autism.
Petitioning attorneys will counter that Federal Court rules regard epidemiology alone as being "insufficient" to disprove causation, and will surely use the NIH panel's critique of the government's own database as a roadmap toward defanging the CDC's conclusions. To begin with, the CDC found an autism rate of just 11-per-10,000 children at the largest participating HMO, where the actual rate is currently 73-per-10,000. Why so many excluded children, they will likely ask, and how did this affect the rate of outcomes?
As for Denmark, petitioning lawyers will argue that autism case numbers increased after 1992, when thimerosal was removed from childhood vaccines, mostly because the Danish government happened to switch from counting inpatient-diagnosed cases only - about 13% of the total - to counting all inpatient AND outpatient cases nationwide. By 1999 the total number had "gone up" to about 200 children a year, in a nation of 6.2 million people - well below the current US rate of 1-in-150 kids, and not exactly a raging epidemic.
The lawyers might also point out that incidence and prevalence rates of autism actually declined in Denmark during 2000, and again (we now know, only through FOIA) in 2001. And they could cite a media quote from Dr. Irva Hertz-Picciotto, professor of public health at UC-Davis School of Medicine and chair of the NIH panel that critiqued the CDC study. Flawed as the CDC analysis was, she called it "an improvement on other studies, including the two in Denmark, both of which had serious weaknesses in their designs."
For their side of the argument, family lawyers will present thousands of pages of published "biological" science, as opposed to epidemiology. They will examine data from animal models, test tube studies, and examinations of children with autism; they will try to present a plausible biological mechanism by which mercury (and to a lesser extent, MMR) could cause autistic-like symptoms -- at the molecular, cellular, and clinical level.
Among this evidence is research suggesting that:
1) Many children with autism, probably due to genetics, are deficient in certain sulfur-based proteins that defend against heavy metal accumulation in humans. The proteins, which include glutathione, are called "thiols," and sometimes "mercaptans," from the Latin mercurium captans, or literally "mercury capturers."
2) Many children with autism show signs of heavy metal accumulation, including elevated levels of proteins called "prophyrins" a bio-marker of lead and mercury toxicity. They also present with low levels of mercury in baby haircuts, (versus control children) suggesting a heavy metal "efflux disorder" that prevents the proper metabolism and excretion of heavy metals.
3) Exposure to extremely low doses (micromolars) of thimerosal, previously thought to be safe, shut down 25% of brain stem cells, in one lab study.
4) In another, low-level exposures of a few minutes duration killed many of the immune system's "dendritic" cells, disrupted production of immune-system messenger chemicals called "cytokines," and caused inflammation.
5) Meanwhile, many children with autism show signs of immune deficiency AND hyperactivity, as well as cytokine imbalances and inflammation, (they also show signs of chronic autoimmunity, where the immune system attacks the body and brain).
6) Organic ethylmercury from thimerosal crosses the blood-brain barrier in primates, where it quickly converts to inorganic mercury, which can remain trapped in the brain for decades.
7) Inorganic mercury trapped in primate brains caused neuro-inflammation (ie, rapid brain growth) by activating "glial" cells in the brain.
8) Autopsies on autistic human brains found chronic inflammation, apparently linked to the brain's immune system and produced by activation of its "glial" cells.
9) Another autopsy study also showed ongoing neuro-inflammation, possibly from heavy metal exposure, and signs of autoimmunity. (Other studies have found rapid brain growth in infants with autism.)
10) Thimerosal can disrupt a chemical process called "methylation," critical for gene expression, neural function, memory and attention, and the production of sulfur-based "thiol" proteins like glutathione.
Plaintiff lawyers will also show data from a study of birthday videos proving that many kids with autism were meeting or exceeding developmental milestones at age one, only to have tumbled into a wordless, autistic world by age two. They will also show home videos of plaintiff children, before and after their own regression, and in many cases, of the same children a few years after experimental treatments - including chelation (for heavy metal removal) and methyl B-12 (for repair of methylation) - that seem to have vastly improved their condition.
At this point, government lawyers will surely try to discredit these biological studies, one-by-one. They could succeed, though it will be tough, given the data's provenance. Lead authors come from institutions such as Harvard, Northeastern, Columbia, UC Davis, Johns Hopkins, and the Universities of Washington, Arkansas, Kentucky and Rochester, and their papers were published in peer-reviewed journals such as Molecular Psychiatry, and the NIH's Environmental Health Perspectives.
The defense also has a few biological studies to support its side, including one showing no difference in the mercury levels of blood and hair of typical vs. autistic kids. But the mean age in this study was four years old, and mercury does not linger around in blood or hair for that long.
Another study showed the thimerosal containing drug Rho-Gam (given to pregnant women, and not a vaccine) did not increase the risk of autism in children, though this study was funded by Johnson & Johnson, the product's manufacturer and a potential thimerosal litigation defendant.
Likewise, the plaintiffs might offer some epidemiology, including one study from the University of Texas showing increased rates of autism in school districts near mercury-emitting coal power plants, and another, funded by the CDC itself, where children with autism in the SF Bay Area were 50% more likely to be born in the region's most mercury-polluted tracts, suggesting "a potential association between autism and estimated metal concentrations."
Finally, expect to hear hours of testimony about California. Mercury was phased out of childhood vaccines (except the flu shot) a few years ago, the argument goes, so there should have been a drop in autism rates by now, especially in California, which keeps the most reliable autism statistics. It's a very powerful contention, but it may be too early to make any final conclusions.
Among the youngest children, 3-to-5-year-olds, the number of cases was still increasing after the first quarter of 2007. These kids were born and vaccinated between 2002 and 2004, after thimerosal was removed from vaccines, right?
It's true, most companies started making preservative-free vaccine in 2001, but they also continued making product with thimerosal, as a backup during the transition period. Little, if any of those mercury-containing vaccines were ever recalled: They remained on the market, until they were finally used up or expired, in 2003.
Government lawyers will likely point to a 2002 survey of vaccine providers, conducted by the CDC, showing that just 2% of the pediatric shots contained thimerosal. But this was a survey of providers under CDC contract only, and CDC had a record of buying mercury-free vaccines for its clients (ie, state, county and other public health clinics) even before 1999, when the federal government called for the removal of thimerosal from the pediatric schedule "as soon as possible."
It's not clear how many of the CDC contract providers surveyed were in California, where the vast majority of children receive care in private practices and large HMOs. Moreover, the CDC survey was merely a "convenience sample," which are so inaccurate in representing the general population they are virtually never used in published data. In fact, the US DOJ itself defines them as "rarely useful in evaluation and usually hazardous."
Meanwhile, the state has quietly been tracking the number of autism cases by birth year, as well as age group, meaning we can look at the very youngest children entering the system. In the first quarter of 2003, there were 170 children with autism in the state system born in 2000 (or, roughly, three-year-olds). In the first quarter of 2004, the number of three-year-olds increased 8.2% to 184. In 2005 the same number went up 13%, to 208, and in 2006 it jumped nearly 27% to 264. But this year, among kids born in 2004, it was 251, a 5% drop.
This could be attributable to some quarterly reporting glitch, and the caseload could easily be made up in the next quarter (that data will be out in mid-July). But if the deficit continues, the 2004 birth cohort could finish out as the first in which case numbers actually fell. (A similar trend might be emerging at Northern California Kaiser, a major HMO).
Of course, it would take tremendous resources to get to the bottom of this, lawyers might argue. One would need full medical records on each of those 251 kids born in 2004. Did any receive thimerosal still left in California vaccines (or prenatally via Rho-Gam)? How many were exposed to mercury in flu shots during pregnancy and as infants? And in a population that is now one-quarter foreign born, how many children immigrated from countries where immunization with thimerosal is now routine? (Vaccination coverage in Mexico is now 92%).
Is immigration helping keep the California numbers up? We don't have that data. But we do know that, since 2003, the rate of increase among white and black children was 48.6% and 51.6%, respectively. Among Asian children, however, it was 79%, and among Hispanics, 84.2%. Probably something worth looking into (as well as the effect of aggressive early intervention campaigns, which have consistently brought down the average age of diagnosis and would likely drive up the number of three year olds in the system).
But again, this is epidemiology coming out of California, and the Special Masters are looking at specific children with specific claims before their court. Officials from the state have been warning all of us (and that includes me) not to read too much into these numbers.
At the International Meeting For Autism Research last month, California health officials presented their data along with this caveat: "Limitations of the database and lack of individual exposure data prevent conclusions, based on these data, about thimerosal as a cause or modifier of autism in a specific subgroup or child."
It is entirely possible that thimerosal itself did not cause the autism epidemic, but that is not what is on trial here. Even so, for the sake of argument, let's say that a "specific subgroup" of people with autism, maybe 1%, was affected by mercury in their vaccines. With an estimated 1.5 million Americans with autism, that would mean 15,000 people severely impacted by thimerosal.
But, if causation can be shown in even 1% of cases, this would provide tremendous hope for the other 99%. Yes, some cases may be purely genetic in nature. But for everyone else, if we can show how thimerosal caused "autism," we might be able to do the same for, say, pesticides, PCBs, flame retardants, jet fuel, environmental mercury in air, water and fish, or any combination thereof.
It's a tough call and, like I said, I don't envy these Special Masters, though I do thank them for opening the proceedings to the public.
And I will see you in Vaccine Court.
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David Kirby is author of the book "Evidence of Harm." Many of the studies cited here can be found on his Powerpoint slides at www.evidenceofharm.com
Showing posts with label Evidence of Harm. Show all posts
Showing posts with label Evidence of Harm. Show all posts
June 7, 2007
Kirby on HuffPo: See You In (Vaccine) Court
November 26, 2006
Kirby on HuffPo: The Other Secret Bush Court?
The Other Secret Bush Court?
David Kirby
The Huffington Post
Next year, a "Special Master" in an obscure Federal court known only to a few Americans will preside over a highly sensitive judicial matter of urgent national importance. The Bush Administration wants to hold the hearings in a sealed courtroom, off limits to the press and public, with stiff "sanctions" for any outsider who attempts to gain unauthorized access to the secretive proceedings within.
Terror trials in faraway Gitmo? Good guess. But these are vaccine trials on New York Avenue, in downtown Washington, at the U.S. Court of Federal Claims.
You may not know it, but there is an official federal "vaccine court," where some 4,750 autism-related cases have been pending for years. Claimants believe the mercury-based vaccine preservative, thimerosal, and/or the MMR vaccine, contributed to their children's autism, and they are seeking compensation from a special vaccine injury fund administered by the federal government.
The long-awaited autism vaccine trial will commence on June 11 in the courtroom of Special Master George Hastings. The plaintiffs and their attorneys have asked for complete transparency in every aspect of the tribunal, including public disclosure of all evidence and unhindered media access to the hearings. The few autism families whose medical records will be scrutinized as legal examples are waiving their right to privacy and confidentiality, so that their stories may finally be told in an open court of law.
But the DOJ (technically, the "defense") has other plans. On November 3rd, the Department wrote to Hastings saying it "would oppose public access to the courtroom and public broadcast of the trial," because such an arrangement. "would pose security and privacy concerns" for those in attendance.
Exactly whose privacy are they trying to protect? It can't be the parents, because they don't want privacy. The only party fretting about privacy is the DOJ itself, and presumably, the vaccine makers. (As for "security" concerns, isn't that why we have court officers?).
The government may call this privacy, but I call it secrecy. In fact, there has been a long and unseemly history of secrecy when it comes to federal data on thimerosal and autism.
And let's face it: People don't hide something unless they have something to hide.
Back in 2002, Health and Human Services lawyers quietly slipped into vaccine court to file a protection order to permanently seal all thimerosal-related documents. They proposed sanctions for any lawyer who shared the secret government information with autism families, the public or the press. All thimerosal data would be banned from use in future civil cases, and any materials already given to plaintiffs would be rounded up by federal agents and destroyed. The motion was withdrawn after appropriate public outcry.
Many of those federal documents pertained to an off-limits database called the Vaccine Safety Datalink (VSD), which tracks the medical records of hundreds of thousands of American children. Lawyers for the families have tried to gain access to the VSD for years, including a 2004 "Motion to Compel" that went nowhere.
In 2005, the Institute of Medicine issued a report slamming the Centers for Disease Control and Prevention, which manages the VSD, for a "lack of transparency" in handling the data. Even more alarming, CDC officials testified that the original datasets they examined had "not been archived in a standard fashion," meaning they were either lost, or destroyed. Take your pick.
If the disappearance of these datasets was intentional, that would be a clear violation of the federal Data Quality Act. No wonder the IOM urged vaccine officials to "seek legal advice" on the status of the missing records.
But those missing datasets could well have been a bonanza to attorneys for the autism parents. Now they are gone.
And, without access to any of the raw data to which government lawyers are privy, the families' cases are woefully, and unconstitutionally, disadvantaged. In what other American court of law are defendants allowed access to evidence that is kept secret from plaintiffs?
Meanwhile, family lawyers have received 216,000 pages of discovery materials, sourced from federal agencies and private companies alike. They might well paint an incriminating portrait of thimerosal's role in autism, and that may be why individuals face a $250,000 penalty for any paper that is leaked.
But some documents have already been leaked, including one published in the Los Angeles Times showing that Merck officials knew of the cumulative and alarmingly high levels of mercury in vaccines way back in 1991, but said nothing about it to anyone.
Are there other incriminating memos from Merck (or Lilly or Glaxo, etc.)? My sources indicate that there are, but we may never get to see them. And now, by barring public access to the trial, we may never get to hear them, either.
If the DOJ has its way, only claimants and their attorneys will be allowed to sit in the courtroom, or receive password-enabled access to a live audio webcast of the trial. The media will be barred, and so will everyone else. And though there will be an official written transcript, such documents are sometimes redacted, or even sealed, after the trial.
As a journalist, I will be subject to "sanctions" if I sit in on a webcast without authorization from the court. In fact, unauthorized access to the proceedings, according to the DOJ proposal, might lead to "termination of the webcast and closing of the courtroom."
What remains unclear is whether journalists will be prosecuted for interviewing families who have access to the webcast, or who attend the trial in person. But if I get arrested for hanging around outside the court with my pen and notepad, don't blame me for trying.
Curiously, a final reason cited for barring reporters and others from vaccine court is that "opening the courtroom to the general public would make it more difficult for claimants themselves to attend." I know plenty of parents who would gladly give up their seat for, say, Wolf Blitzer or Brian Williams, but the DOJ apparently hasn't asked them.
I think it's safe to say that the Bush Administration does not want this trial publicized. That seems curious to me. The entire thimerosal question will likely be left up to just one man: Special Master Hastings. Whether he decides for the parents, or for the DOJ, his ruling will forever be considered within a vacuum, subject to intense criticism from either side, unless he agrees that all thimerosal evidence should at long last be made public.
I hope he rules that his courtroom is not Guantanamo. These parents, and the public at large, deserve no less.
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PS: My last post predicted that most autism parents would be voting Democratic this November, without giving proper credit to two members of the House GOP. Dan Burton (R-IN) and Dave Weldon (R-FL) are among the most open minded members when it comes to the mercury-autism hypothesis, and I apologize for the omission.
Meanwhile, Rep. Henry Waxman (D-CA) has been hostile, at best, to the theory. I congratulate Rep. Waxman on his ascendancy to the House Government Reform Committee Chairmanship, and respectfully ask him to read "Evidence of Harm," and, if possible and when he has time, to offer a response on the Huffington Post.
August 13, 2005
Here's Why the Disdain...
This post is a response to a post by JP on his new blog, SupportVaccination.org.
[Update: JP has decided to leave the vaccine discussion and take his blog down, so the link no longer works. I wish I had saved a copy of the initial post that this was written in response to, but alas, I was not forward thinking enough to save a copy.]
[Update: John Cartan is the man! He found a cashed version for me. Here ya go: http://tinyurl.com/7celt ]
In his post, he ask questions of parents like me, that I am eager to answer. Parents have been accused of being "scientifically illiterate" and dismissing "well designed" population studies that show that there is no link between autism and thimerosal. I thought this was a good opportunity to tell the blogesphere, at least in part, why we are not so hot on the IOM’s epidemiological studies.
Dear JP,
As one of those parents with… well ‘distain’ is a harsh word, lets call it an ‘unwillingness to rely on’ the epidemiological studies cited by the IOM, it probably falls upon the likes of me to answer the question you pose in the title of your piece.
Why the disdain for epidemiology...
Since I am the likes of me, I will take this on and answer your questions and challenges from my point of view.
I am going to break up my response to your post into a few separate posts, as there are several things to address.
I am the mother of an autistic 3 year old boy and a marriage and family therapist, with a masters degree from Johns Hopkins. The statistics courses that I took in grad school were designed to educate me on how to evaluate the research of others to see if it was something we should incorporate into the treatment of a client. This education has turned out to be useful in evaluating the epidemiological studies that have been offered up to prove that thimerosal is safe.
I have been looking at these studies with two basic questions in mind:
I want to start first with what an epidemiological study is and what it can do.
Any question like this starts with case studies. Some one notices two things occurring together (smoking and lung cancer, vaccine reaction and autism) and they look at the plausibility of a relationship (smoke filling the lungs could cause damage, neurotoxic mercury in vaccines could cause brain damage).
Next they want to see if what they are observing in their setting could be happening else where and after conferring with associates and finding that others see the possibility of a link as well, they commission a large population study.
Epidemiological studies are limited in their use. They can be used to spot patterns and trends, but they can almost never be used to prove or disprove anything. They are one of the first stages of a medical inquiry and act as a divining rod to tell researchers where to start digging.
They are very vulnerable to confounders, because they are asking broad questions over huge numbers of people; so they should not be used to make definitive statements as much as to help researchers shape the next question that should be asked.
Those next questions are taken to smaller population studies (where confounders can be more easily controlled), lab studies (in vitro), and actual case studies (in vivo). The results of those studies, helps to further refine the questions being asked, which can be sent back up to large population studies, and so on, and so on until, (hopefully) the results of your epidemiological, in vitro and in vivo studies all line up like tumblers in a lock and the lock opens with one key.
This is not what we are seeing yet when we look at totality of autism/thimerosal research, as the IOM report shows. In fact the large epidemiological studies relied on for the conclusions in the report are at odds with other in vitro and in vivo research also in the report. The tumblers do not line up and therefore all of the research should be scrutinized to see what is throwing things off.
The scrutiny of the epidemiological studies has shown that they do not measure what they purport to measure, and even if they did, they cannot be applied in the way that they are being applied.
Your example of how epidemiological studies were used in the 50’s a nice example of how they can be used well and lead researchers to determine the source of a terrible illness like lung cancer, unfortunately it seems that what is going on today in this inquiry is a very different scenario.
What we know so far about autism tells us that it is not as straight forward as, smoke cigarettes get lung cancer. The thimerosal studies seem to have multiple confounders (genetic, environmental, etc) that cut into the reliability of epidemiological studies.
The two studies that are relied upon the most heavily are the Danish Study and the Verstraten Study. Both of these studies were designed and carried out very poorly and are being used very badly.
Here is why I treat them with such skepticism. (Quoting myself in part from an earlier post that responded to a piece by Dr. Laidler)
One of the problems that complicates the search for the causes and cures of autism is the assumption that it is a single disorder and that all cases are caused by the same thing. This is in contrast to a disease like AIDS in which all cases are brought on by the HIV virus.
What is diagnosed as ‘Autism’ is actually likely to be more than one physical syndrome. Because Autism is a DSM diagnosis and based solely on behavioral criteria, the diagnosis does not address the different sets of physical anomaly clusters that researchers are finding when they look at the biology of ‘autistic’ patients.
One research group has recently made a distinction between two types of autistic profiles. One, labeled complex autism and occurring in about 30% of autism cases, presents with smaller head size, greater chance of low IQ, lower rate of siblings with the disorder and seems to have close to a 1:1 ratio of occurrence between boys and girls.
The other, essential autism, presents with larger head size, few structural brain abnormalities and has a ratio of 7:1 boys to girls.
This is a huge confounder to any epidemiological study, even a well designed one, that looks at all cases of diagnosed autism with out differentiating between groups with different phenotypes.
In discussing research into the causes of autism (in this case the genetic cause), one of the researchers commented, “…Studies haven’t found anything because they’re looking at a big heterogeneous group — a mishmash of people with different etiologies,” Takahashi said.”
One could postulate that only the larger head size group displays autistic symptoms because of mercury poisoning, as mercury toxicity does not always present with impaired IQ; and because in vitro thimerosal toxicity studies preformed at the University of Kentucky showed that estrogen has a protective effect against, and testosterone exacerbates the damage of, ethlymercury as a neurotoxin.
In light of this new information it seems that a better question than, “is autism is caused by mercury toxicity” which is the question largely being asked in these epidemiological studies, would be, “are cases of mercury toxicity being misdiagnosed as autism”.
The answer to that question cannot be found in a large epidemiological study.
The authors of the the final IOM report on the thimerosal/autism relationship in 2004 stated themselves that the epidemiological research it was relying on to clear thimerosal as a cause of autism would not pick up on a sub-set of the population that was genetically vulnerable to mercury poisoning.
If that is the case, then how much more so to these studies fail to give us meaningful data if the children who may be mercury poisoned are members of two different subsets being confused with one another?
Since the working theory in biomedical treatment of autism is that many of the children diagnosed with autism are genetically vulnerable sub set who cannot excrete heavy metals, and since this treatment is bringing about successes in the abatement of many children's autistic symptoms, does that not throw into question the use of these large scale studies to find the correlation between thimerosal and autism as easily as they would between smoking and cancer?
What causes further problems for people who want to use these studies to show that the case is closed on thimerosal and NDDs (as the conclusion in the IOM study does) is that these studies are not well designed and are very poorly applied.
The findings in the Denmark study have come under serious criticism. When the data of study was reviewed, it was found that the sampling presented fatal flaws.
The low incidence of autism during the use of thimerosal can be attributed to the fact that the database that was used only tracked inpatient cases of autism at the time. At the point in time where thimerosal was removed, the database was expanded to include cases that were diagnosed at a large clinic outside of Copenhagen where 20% of the countries autistic patents were diagnosed. At the point in time where thimerosal was no longer used, but the cases of autism seem to have skyrocketed, the database had expanded further to include all cases of autism, inpatient and outpatient, in the country.
The sample size of the study was only 956 children. That is the number of people that their disability database had on record as being diagnosed with autism in Denmark between 1971 and 2000. 956 people in 29 years. That is 33 people a year in the entire country. [Hyperbole warning] I have that many autistic kids in my kitchen right now!
The study is further compromised by the fact that several of the coauthors were employed by the Statens Serums Institut, the countries sole vaccine manufacturer who would presumably be held liable if it was indeed found that the use of thimerosal in vaccines contributed to autism.
[Update: Kristjan has pointed out here that the Danish health care system and liability laws are different from ours and no such legal liability exists for the Statens Serums Institut. I still wonder what might motivate these researchers to stand buy this study and not protest its poor use. More on that in the comments here, here and here.]
Further, even if the study were reliable, applying it to the U.S. population as the IOM has done presents problems. Children in Denmark were administered less than half the amount of thimerosal of US children, and it was administered later and over a longer period of time.
Finally, American children, like my sons, are subject to an autism rate at least 10 times that of Denmark, so this study should not be applied to determine their risk of autism from thimerosal exposure.
It seems to me to be like doing a population study of Sickle Cell Anemia in Denmark and applying it to the population of Baltimore. Clearly U.S. children have some other intervening factors that increases the threat of NDDs, be they genetic, environmental or the thimerosal dosage and age of administration.
The problems with the Verstraten study, the only epidemiological study that the CDC has done in the U.S. to examine the possible link between thimerosal containing vaccines and neurodevelopmental disorders, are severe. It is such a badly designed and executed study that I can hardly do it justice in a blog post. I started working on a review of it about 6 weeks ago for my blog and I still have not finished.
In fact, it is currently the subject of a Senate investigation that may result in hearings on Capitol Hill.
I will try to do a quick review of my ‘distain’ for it, as I actually think the harshness of your term might apply to my attitude in this case.
Verstraten started with a nice, simple study. He had medical records of about 180,000 kids in California, a good sized sample. He broke them up into four main groups, kids who received no thimerosal, a little thimerosal, a moderate amount, and a high amount. He checked to see if the amount of thimerosal that they got, and when they got it (two months of age, six months of age, etc) corresponded to an increased risk for different types of neurodevelopmental disorders, and NDDs in general.
The study began in November of 1999 and was supposed to be finished in 4 months.
What he found was that the more thimerosal a child got, the higher their chance of an NDD, with children who got the highest doses had a huge risk of having a disorder, more than 600% in one case. He also found that the age at which it was administered determined the type of disorder that a child would develop.
Verstraten sent an email to another CDC employee, Dr. Davis, and said that no matter what he tried, could not make the relationship go away.
In December the two men, and additional researchers at the CDC, began to change the parameters of the study. When you do this, you are supposed to document all the changes and justify why they are needed to properly answer the question you are asking. They did not.
The changes they began to make to the statistical analysis of the study are now described by the CDC as “improvements”. How they could see some of these changes as improvements is unbelievable to me. Here are some of the changes:
They took the zero thimerosal group, and tucked them into the low thimerosal group. Now they only have three groups and in effect they have brought up the bottom, so the top does not seem as high.
That did not bring down the risk enough, so they decided to get rid of the no thimerosal group all together, so now you are only comparing the low, middle and high groups, bring up the bottom further.
They got rid of a catch all group of NDDs so the study no longer addressed the question, ‘does an increase thimerosal increase the risk of a neurodevelopmental disorder’. Now it only looked at each disorder separately.
Still not dampening the signal enough, the decided to go into and change some of the actual medical records of the patients they were studying. The CDC reports that these were correcting errors in patient records, but will not offer any proof of this claim, saying instead that the data that would confirm their claim was ‘lost’.
This brought the risk down, but still showed a link between thimerosal and NDDs, so they then started dropping children from the study. They used about 20 different ICD9 codes to exclude any child from the study that had almost any birth complication or whose mother had almost any pregnancy complication. This included serious problems like premature birth and birth defects, but went all the way down to moms who took an antibiotic while pregnant. In effect this removes from the study many children who are likely to go on to develop NDDs.
This is fine to do in your study if you want, but it renders it almost completely useless for application to vaccine policy. This policy covers all U.S. children, and lots and lots of those children were subject to pregnancy and birth complications.
This study now no longer applies to my children as both of my pregnancies had complications.
At this point it is safe to say that this study no longer addressed the question of whether or not an increase in the dose of thimerosal increases the chance of an NDD in American children. But the ‘improvements’ don’t stop there.
Many more people are given a chance to make suggestions, the Simpsonwood meeting was held, comments are made that the study never should have been done in the first place, and the research is further bastardized.
A stop date was put in place so that children who were initially diagnosed with something like a speech delay, were then always considered to be speech delayed, even if they went on to be diagnosed with a more serious disorder like full blown autism. This is important as a large number of kids diagnosed with autism at ages 3 and 4 are diagnosed with some milder developmental delay at 18 months or two years of age. Doctors don’t like giving the autism diagnosis early, and the state of California (where the study was done) won’t even formally evaluate children for autism, or diagnose it before the age of 3.
I live in California. My son was evaluated at 2 and found to have ‘speech delays’ and offered early start services. To all involved in his treatment, he was autistic, but he did not become officially “Autistic” according to the state and his own records until age 3. Chandler would not have been considered Autistic for the purposes of the Verstraeten study.
My favorite ‘improvement’ was to add into the study children who were only a year or so old at the cut off date of the study. No child is diagnosed with autism, or indeed much of anything, this early. They all could have gone on to be diagnosed with a neurodevelopmental disorder but in the Verstraeten study, they are all considered healthy and unaffected by thimerosal.
Even with all these shenanigans, they STILL could not completely get rid of the relationship between thimerosal and NDDs. They then employed a tactic that served to make their own findings in the study irrelevant.
They split the whole group up into two, one large one from one HMO and one smaller group from another HMO (I think it was around 16,000). The small group was now too small to be of any statistical power. They used that group to say that the results in the first group could not be replicated in the second.
Then they bought another database from an HMO in New England, which was odd because they already owned dozens of them at the cost of millions of dollars in tax payer money. The HMO had failed and was in receivership due in part to poor record keeping on out of date computers. The HMO also used their own diagnostic system that didn’t even implement ICD9 codes and the researchers used completely different parameters to study this database than they did in the first. They used this third group of only 12,000 or so patients, as yet another example of how they could not replicate the results of the first, large group, which they were now referring to as ‘the screening study’.
The 4 month study took 4 years and, in my opinion, came out looking like something akin to Frankenstein’s Monster.
This study does not offer a meaningful measure of anything and cannot be applied to any group that I can think of.
Add to this the fact Verstraten himself became an employee of Glaxo (currently being sued by parents of autistic children) half way through the study, which was not disclosed when the study was published, and it becomes easy to see why where the distain comes from.
When asked to justify all the changes and publish the data so that the study could be confirmed and replicated, the CDC repeated the claim that the original data was ‘lost’. A private contractor testified before congress that he had been ordered to destroy the data sets, “to insure patient confidentiality”. This is a violation of federal law and is what sparked the congressional investigation currently underway.
It is practice in the scientific community that if a study can not be confirmed or replicated, that it should be withdrawn. Despite parent requests for such action, the CDC stands by this study and refuses to pull it.
As a parent who is looking at this issue as hard as I can, I am upset that the IOM, who should know better, keeps calling these studies ‘well designed’ and has used them to show that the case is closed on thimerosal and autism.
Verstraeten himself says that the study is a ‘neutral study’ and does not find for or against thimerosal in the implication that it is involved with NDDs.
In grad school, in order to pass statistics we had to take studies and break them down, justifying if and how they could be used for us to make treatment decisions. The Institute of Medicine would have failed my 600 level stats courses.
ADDENDUM:
People have asked for citations. What hasn't been referenced above can be found in David Kirby's book, Evidence Of Harm as this post just attempts to squish his big fat book into a blog post.
Additional addendum:
Julie Gerberding was asked by Congress to defend Verstraeten and had to reply that it was a useless study. She did so in secret, but the document was leaked by a congressional staffer. Even though everyone knows it is garbage, Pediatrics has not retracted it, and some still claim it clears the vaccine/autism theory. However CDC removed it from their list of research that refutes the theory in by the end of 2008 when news of the Congressional/CDC exchange went public.
[Update: JP has decided to leave the vaccine discussion and take his blog down, so the link no longer works. I wish I had saved a copy of the initial post that this was written in response to, but alas, I was not forward thinking enough to save a copy.]
[Update: John Cartan is the man! He found a cashed version for me. Here ya go: http://tinyurl.com/7celt ]
In his post, he ask questions of parents like me, that I am eager to answer. Parents have been accused of being "scientifically illiterate" and dismissing "well designed" population studies that show that there is no link between autism and thimerosal. I thought this was a good opportunity to tell the blogesphere, at least in part, why we are not so hot on the IOM’s epidemiological studies.
Dear JP,
As one of those parents with… well ‘distain’ is a harsh word, lets call it an ‘unwillingness to rely on’ the epidemiological studies cited by the IOM, it probably falls upon the likes of me to answer the question you pose in the title of your piece.
Why the disdain for epidemiology...
Since I am the likes of me, I will take this on and answer your questions and challenges from my point of view.
I am going to break up my response to your post into a few separate posts, as there are several things to address.
I am the mother of an autistic 3 year old boy and a marriage and family therapist, with a masters degree from Johns Hopkins. The statistics courses that I took in grad school were designed to educate me on how to evaluate the research of others to see if it was something we should incorporate into the treatment of a client. This education has turned out to be useful in evaluating the epidemiological studies that have been offered up to prove that thimerosal is safe.
I have been looking at these studies with two basic questions in mind:
Can this study be applied to entire population of children in the U.S. and thereby be useful for guidance in setting vaccine policy? If so, how?
Can I use this study to make a determination as to the safety of vaccinating my sons, one who is autistic and one who is (mostly) neurotypical. If so, how?
I want to start first with what an epidemiological study is and what it can do.
Any question like this starts with case studies. Some one notices two things occurring together (smoking and lung cancer, vaccine reaction and autism) and they look at the plausibility of a relationship (smoke filling the lungs could cause damage, neurotoxic mercury in vaccines could cause brain damage).
Next they want to see if what they are observing in their setting could be happening else where and after conferring with associates and finding that others see the possibility of a link as well, they commission a large population study.
Epidemiological studies are limited in their use. They can be used to spot patterns and trends, but they can almost never be used to prove or disprove anything. They are one of the first stages of a medical inquiry and act as a divining rod to tell researchers where to start digging.
They are very vulnerable to confounders, because they are asking broad questions over huge numbers of people; so they should not be used to make definitive statements as much as to help researchers shape the next question that should be asked.
Those next questions are taken to smaller population studies (where confounders can be more easily controlled), lab studies (in vitro), and actual case studies (in vivo). The results of those studies, helps to further refine the questions being asked, which can be sent back up to large population studies, and so on, and so on until, (hopefully) the results of your epidemiological, in vitro and in vivo studies all line up like tumblers in a lock and the lock opens with one key.
This is not what we are seeing yet when we look at totality of autism/thimerosal research, as the IOM report shows. In fact the large epidemiological studies relied on for the conclusions in the report are at odds with other in vitro and in vivo research also in the report. The tumblers do not line up and therefore all of the research should be scrutinized to see what is throwing things off.
The scrutiny of the epidemiological studies has shown that they do not measure what they purport to measure, and even if they did, they cannot be applied in the way that they are being applied.
Your example of how epidemiological studies were used in the 50’s a nice example of how they can be used well and lead researchers to determine the source of a terrible illness like lung cancer, unfortunately it seems that what is going on today in this inquiry is a very different scenario.
What we know so far about autism tells us that it is not as straight forward as, smoke cigarettes get lung cancer. The thimerosal studies seem to have multiple confounders (genetic, environmental, etc) that cut into the reliability of epidemiological studies.
The two studies that are relied upon the most heavily are the Danish Study and the Verstraten Study. Both of these studies were designed and carried out very poorly and are being used very badly.
Here is why I treat them with such skepticism. (Quoting myself in part from an earlier post that responded to a piece by Dr. Laidler)
One of the problems that complicates the search for the causes and cures of autism is the assumption that it is a single disorder and that all cases are caused by the same thing. This is in contrast to a disease like AIDS in which all cases are brought on by the HIV virus.
What is diagnosed as ‘Autism’ is actually likely to be more than one physical syndrome. Because Autism is a DSM diagnosis and based solely on behavioral criteria, the diagnosis does not address the different sets of physical anomaly clusters that researchers are finding when they look at the biology of ‘autistic’ patients.
One research group has recently made a distinction between two types of autistic profiles. One, labeled complex autism and occurring in about 30% of autism cases, presents with smaller head size, greater chance of low IQ, lower rate of siblings with the disorder and seems to have close to a 1:1 ratio of occurrence between boys and girls.
The other, essential autism, presents with larger head size, few structural brain abnormalities and has a ratio of 7:1 boys to girls.
This is a huge confounder to any epidemiological study, even a well designed one, that looks at all cases of diagnosed autism with out differentiating between groups with different phenotypes.
In discussing research into the causes of autism (in this case the genetic cause), one of the researchers commented, “…Studies haven’t found anything because they’re looking at a big heterogeneous group — a mishmash of people with different etiologies,” Takahashi said.”
One could postulate that only the larger head size group displays autistic symptoms because of mercury poisoning, as mercury toxicity does not always present with impaired IQ; and because in vitro thimerosal toxicity studies preformed at the University of Kentucky showed that estrogen has a protective effect against, and testosterone exacerbates the damage of, ethlymercury as a neurotoxin.
In light of this new information it seems that a better question than, “is autism is caused by mercury toxicity” which is the question largely being asked in these epidemiological studies, would be, “are cases of mercury toxicity being misdiagnosed as autism”.
The answer to that question cannot be found in a large epidemiological study.
The authors of the the final IOM report on the thimerosal/autism relationship in 2004 stated themselves that the epidemiological research it was relying on to clear thimerosal as a cause of autism would not pick up on a sub-set of the population that was genetically vulnerable to mercury poisoning.
If that is the case, then how much more so to these studies fail to give us meaningful data if the children who may be mercury poisoned are members of two different subsets being confused with one another?
Since the working theory in biomedical treatment of autism is that many of the children diagnosed with autism are genetically vulnerable sub set who cannot excrete heavy metals, and since this treatment is bringing about successes in the abatement of many children's autistic symptoms, does that not throw into question the use of these large scale studies to find the correlation between thimerosal and autism as easily as they would between smoking and cancer?
What causes further problems for people who want to use these studies to show that the case is closed on thimerosal and NDDs (as the conclusion in the IOM study does) is that these studies are not well designed and are very poorly applied.
The findings in the Denmark study have come under serious criticism. When the data of study was reviewed, it was found that the sampling presented fatal flaws.
The low incidence of autism during the use of thimerosal can be attributed to the fact that the database that was used only tracked inpatient cases of autism at the time. At the point in time where thimerosal was removed, the database was expanded to include cases that were diagnosed at a large clinic outside of Copenhagen where 20% of the countries autistic patents were diagnosed. At the point in time where thimerosal was no longer used, but the cases of autism seem to have skyrocketed, the database had expanded further to include all cases of autism, inpatient and outpatient, in the country.
The sample size of the study was only 956 children. That is the number of people that their disability database had on record as being diagnosed with autism in Denmark between 1971 and 2000. 956 people in 29 years. That is 33 people a year in the entire country. [Hyperbole warning] I have that many autistic kids in my kitchen right now!
The study is further compromised by the fact that several of the coauthors were employed by the Statens Serums Institut, the countries sole vaccine manufacturer who would presumably be held liable if it was indeed found that the use of thimerosal in vaccines contributed to autism.
[Update: Kristjan has pointed out here that the Danish health care system and liability laws are different from ours and no such legal liability exists for the Statens Serums Institut. I still wonder what might motivate these researchers to stand buy this study and not protest its poor use. More on that in the comments here, here and here.]
Further, even if the study were reliable, applying it to the U.S. population as the IOM has done presents problems. Children in Denmark were administered less than half the amount of thimerosal of US children, and it was administered later and over a longer period of time.
Finally, American children, like my sons, are subject to an autism rate at least 10 times that of Denmark, so this study should not be applied to determine their risk of autism from thimerosal exposure.
It seems to me to be like doing a population study of Sickle Cell Anemia in Denmark and applying it to the population of Baltimore. Clearly U.S. children have some other intervening factors that increases the threat of NDDs, be they genetic, environmental or the thimerosal dosage and age of administration.
The problems with the Verstraten study, the only epidemiological study that the CDC has done in the U.S. to examine the possible link between thimerosal containing vaccines and neurodevelopmental disorders, are severe. It is such a badly designed and executed study that I can hardly do it justice in a blog post. I started working on a review of it about 6 weeks ago for my blog and I still have not finished.
In fact, it is currently the subject of a Senate investigation that may result in hearings on Capitol Hill.
I will try to do a quick review of my ‘distain’ for it, as I actually think the harshness of your term might apply to my attitude in this case.
Verstraten started with a nice, simple study. He had medical records of about 180,000 kids in California, a good sized sample. He broke them up into four main groups, kids who received no thimerosal, a little thimerosal, a moderate amount, and a high amount. He checked to see if the amount of thimerosal that they got, and when they got it (two months of age, six months of age, etc) corresponded to an increased risk for different types of neurodevelopmental disorders, and NDDs in general.
The study began in November of 1999 and was supposed to be finished in 4 months.
What he found was that the more thimerosal a child got, the higher their chance of an NDD, with children who got the highest doses had a huge risk of having a disorder, more than 600% in one case. He also found that the age at which it was administered determined the type of disorder that a child would develop.
Verstraten sent an email to another CDC employee, Dr. Davis, and said that no matter what he tried, could not make the relationship go away.
In December the two men, and additional researchers at the CDC, began to change the parameters of the study. When you do this, you are supposed to document all the changes and justify why they are needed to properly answer the question you are asking. They did not.
The changes they began to make to the statistical analysis of the study are now described by the CDC as “improvements”. How they could see some of these changes as improvements is unbelievable to me. Here are some of the changes:
They took the zero thimerosal group, and tucked them into the low thimerosal group. Now they only have three groups and in effect they have brought up the bottom, so the top does not seem as high.
That did not bring down the risk enough, so they decided to get rid of the no thimerosal group all together, so now you are only comparing the low, middle and high groups, bring up the bottom further.
They got rid of a catch all group of NDDs so the study no longer addressed the question, ‘does an increase thimerosal increase the risk of a neurodevelopmental disorder’. Now it only looked at each disorder separately.
Still not dampening the signal enough, the decided to go into and change some of the actual medical records of the patients they were studying. The CDC reports that these were correcting errors in patient records, but will not offer any proof of this claim, saying instead that the data that would confirm their claim was ‘lost’.
This brought the risk down, but still showed a link between thimerosal and NDDs, so they then started dropping children from the study. They used about 20 different ICD9 codes to exclude any child from the study that had almost any birth complication or whose mother had almost any pregnancy complication. This included serious problems like premature birth and birth defects, but went all the way down to moms who took an antibiotic while pregnant. In effect this removes from the study many children who are likely to go on to develop NDDs.
This is fine to do in your study if you want, but it renders it almost completely useless for application to vaccine policy. This policy covers all U.S. children, and lots and lots of those children were subject to pregnancy and birth complications.
This study now no longer applies to my children as both of my pregnancies had complications.
At this point it is safe to say that this study no longer addressed the question of whether or not an increase in the dose of thimerosal increases the chance of an NDD in American children. But the ‘improvements’ don’t stop there.
Many more people are given a chance to make suggestions, the Simpsonwood meeting was held, comments are made that the study never should have been done in the first place, and the research is further bastardized.
A stop date was put in place so that children who were initially diagnosed with something like a speech delay, were then always considered to be speech delayed, even if they went on to be diagnosed with a more serious disorder like full blown autism. This is important as a large number of kids diagnosed with autism at ages 3 and 4 are diagnosed with some milder developmental delay at 18 months or two years of age. Doctors don’t like giving the autism diagnosis early, and the state of California (where the study was done) won’t even formally evaluate children for autism, or diagnose it before the age of 3.
I live in California. My son was evaluated at 2 and found to have ‘speech delays’ and offered early start services. To all involved in his treatment, he was autistic, but he did not become officially “Autistic” according to the state and his own records until age 3. Chandler would not have been considered Autistic for the purposes of the Verstraeten study.
My favorite ‘improvement’ was to add into the study children who were only a year or so old at the cut off date of the study. No child is diagnosed with autism, or indeed much of anything, this early. They all could have gone on to be diagnosed with a neurodevelopmental disorder but in the Verstraeten study, they are all considered healthy and unaffected by thimerosal.
Even with all these shenanigans, they STILL could not completely get rid of the relationship between thimerosal and NDDs. They then employed a tactic that served to make their own findings in the study irrelevant.
They split the whole group up into two, one large one from one HMO and one smaller group from another HMO (I think it was around 16,000). The small group was now too small to be of any statistical power. They used that group to say that the results in the first group could not be replicated in the second.
Then they bought another database from an HMO in New England, which was odd because they already owned dozens of them at the cost of millions of dollars in tax payer money. The HMO had failed and was in receivership due in part to poor record keeping on out of date computers. The HMO also used their own diagnostic system that didn’t even implement ICD9 codes and the researchers used completely different parameters to study this database than they did in the first. They used this third group of only 12,000 or so patients, as yet another example of how they could not replicate the results of the first, large group, which they were now referring to as ‘the screening study’.
The 4 month study took 4 years and, in my opinion, came out looking like something akin to Frankenstein’s Monster.
This study does not offer a meaningful measure of anything and cannot be applied to any group that I can think of.
Add to this the fact Verstraten himself became an employee of Glaxo (currently being sued by parents of autistic children) half way through the study, which was not disclosed when the study was published, and it becomes easy to see why where the distain comes from.
When asked to justify all the changes and publish the data so that the study could be confirmed and replicated, the CDC repeated the claim that the original data was ‘lost’. A private contractor testified before congress that he had been ordered to destroy the data sets, “to insure patient confidentiality”. This is a violation of federal law and is what sparked the congressional investigation currently underway.
It is practice in the scientific community that if a study can not be confirmed or replicated, that it should be withdrawn. Despite parent requests for such action, the CDC stands by this study and refuses to pull it.
As a parent who is looking at this issue as hard as I can, I am upset that the IOM, who should know better, keeps calling these studies ‘well designed’ and has used them to show that the case is closed on thimerosal and autism.
Verstraeten himself says that the study is a ‘neutral study’ and does not find for or against thimerosal in the implication that it is involved with NDDs.
In grad school, in order to pass statistics we had to take studies and break them down, justifying if and how they could be used for us to make treatment decisions. The Institute of Medicine would have failed my 600 level stats courses.
ADDENDUM:
People have asked for citations. What hasn't been referenced above can be found in David Kirby's book, Evidence Of Harm as this post just attempts to squish his big fat book into a blog post.
Additional addendum:
Julie Gerberding was asked by Congress to defend Verstraeten and had to reply that it was a useless study. She did so in secret, but the document was leaked by a congressional staffer. Even though everyone knows it is garbage, Pediatrics has not retracted it, and some still claim it clears the vaccine/autism theory. However CDC removed it from their list of research that refutes the theory in by the end of 2008 when news of the Congressional/CDC exchange went public.
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