WaPo: Flu Death Risk Often Exaggerated; So Is Benefit of Vaccine

A Shot of Fear
Flu Death Risk Often Exaggerated; So Is Benefit of Vaccine

By Steven Woloshin, Lisa M. Schwartz and H. Gilbert Welch
Special to The Washington Post
Tuesday, October 25, 2005; Page HE01

Medical research often becomes news. But sometimes the news is made to appear more definitive and dramatic than the research warrants. This series dissects health news to highlight some common study interpretation problems we see as physician-researchers and show how the research community, medical journals and the media can do better.

For years, the public health community has used fear as one strategy to promote the flu vaccine. A vaccination poster distributed by the U.S. Centers for Disease Control and Prevention (CDC), for example, emphasizes that "36,000 Americans die of flu-related illnesses each year," implying that the vaccine could prevent many of these deaths.

What was an elderly person's chance of having a flu-like illness in a flu season?
Placebo group Vaccine group
Nursing Home
Study 1 (Russia) 13% 5%
Study 2 (U.S.) 15% 6%
Community
Study 3 (Netherlands) 4% 2%
Study 4 (Britain) 9% 5%
Study 5 (U.S.) 4% 2%
SOURCES: Lancet Online Cochrane Review 2005 and original journal articles

When it became aware of the vaccine shortage last October, the federal government changed course and tried to reassure Americans that going without a shot was no big deal. "We all need to take a deep breath. This is not an emergency," CDC director Julie Gerberding advised the public.

Instead of urging vaccination for everyone age 50 and older, as they had been doing, government officials recommended shots only for people 65 and older, and those in selected high risk groups. The public's response was predictable: People were upset and confused. Our local television news played a story in which a pharmacist was called "a murderer" when his vaccine supply ran out. Ironically, the crisis mentality led some to engage in behaviors that probably increased their risk. Frail elderly people, some with oxygen tanks, stood in long lines in the cold, waiting for the vaccine. Others crowded clinics and doctors' offices, increasing their chance of exposure to flu and other infectious agents.

With uncertainties about this year's vaccine supply, the CDC again recommended that highest-risk people get priority for flu shots, at least until late October. But last year's flu season may have left people confused about essential points: Just how risky is the flu? And just how effective is the vaccine? The answers to these questions may surprise readers.

How Risky Is the Flu?

First, a caveat: The risk calculations we analyze here describe typical flu seasons only. We don't consider here what the picture would be in the event of a deadly flu pandemic -- a worldwide outbreak of a new, highly virulent flu strain, the potential for which has recently drawn considerable media attention. No one really knows how likely such an outbreak is, but the risk profile would certainly change. A pandemic is a fundamentally different situation: The risk of death would be substantially higher, and untested strategies (including new treatments, quarantine and a new vaccine) would need to be implemented rapidly.

We deal here with what is known about typical flu seasons, based on data that form the basis for the federal government's flu-risk figures.

By choosing to highlight the annual number of flu deaths, the CDC employed an attention-grabbing tactic often used by public health and disease advocacy groups. It's a tactic readers should be inoculated against if they want a clear picture of the risks they face. (See "Research Basics: Understanding How Big a Risk Is," right.)

In fact, it is very difficult to know how many people die from any given disease because there is often much uncertainty in determining the cause of death. This is particularly true for the flu. That's because it shares symptoms with so many other diseases, and because people most likely to die a flu-related death are also at high risk for many other causes of death.

Flu deaths are probably undercounted because doctors do not routinely test for the flu, and because some deaths that should be attributed to the flu are given other diagnoses. For example, someone who dies from a heart attack because they are debilitated by the flu might not get counted as a flu death. Some overcounting of flu deaths also occurs: Clearly not all winter pneumonia deaths are caused by the flu.

According to the CDC, 90 percent of flu-related deaths occur among people age 65 years and older. Based on this information and the age distribution of the population, the chance of a flu-related death for people in that age group is about one in 1,000. Another way of saying this is that the chance of not dying from flu for those 65 and older is about 999 out of 1,000. (For context, the chance of a flu-related death is slightly lower than the chance of dying from a fall or other accident.)

For people younger than 65 (including children), the chance of a flu-related death is much smaller -- about one in 100,000. Of course, adults and children might be concerned about flu-related problems besides death, such as being hospitalized or just suffering with unpleasant symptoms (typically three to seven days of fever, muscle aches, headache, weakness, dry cough and runny nose). As you might guess, counting the number of flu-related hospitalizations or the number of people experiencing symptoms from the flu is even more difficult than counting flu deaths.

How Good Is the Vaccine?

Getting a shot does not guarantee you will not get sick from the flu or die from it. Recently, the Cochrane Collaboration, an international group that evaluates the evidence for various medical interventions, reviewed the medical literature on the effectiveness of the flu vaccine in preventing death.

Unfortunately, the evidence on how well the vaccine works to prevent death in the elderly is limited. Few of the existing studies are randomized trials -- considered the gold standard for medical evidence. Instead, most data are from observational studies -- studies in which scientists simply count up outcomes (here, the number of deaths that occur among people who did or did not get the vaccine).

But drawing conclusions about cause and effect from such observations is fraught with problems.

For example, a 2003 study published in the New England Journal of Medicine observed that the flu vaccine was associated with a 50 percent reduction in the overall death rate (that is, death from heart disease, stroke, cancer and all other causes combined). To attribute an effect of this magnitude solely to the flu vaccine is ludicrous: Flu-related deaths make up less than 2 percent of all deaths. If the claim were accurate, the vaccine's power would dwarf that of any other medical intervention. There is, however, a much more likely explanation: People who choose to get a flu shot are much healthier -- and therefore already at much lower risk of death -- than people who do not.

Only five randomized trials have examined the effectiveness of the flu vaccine. In these studies, patients were randomly assigned -- a selection technique equivalent to the flip of a coin -- to get either a flu vaccine or a placebo injection. But none of these studies looked at whether the vaccine prevents death. Instead, the scientists measured who developed a flu-like illness. For a summary of the findings of these studies, see "How Well Does the Vaccine Work in the Elderly?" below.

In the absence of good randomized trial data, it is still possible to gauge the effectiveness of vaccination by looking at time trends in flu vaccine rates compared with flu-related deaths in the elderly. As more people get vaccinated, you would expect the flu-related death rate to decline -- if the vaccine is effective. But, as the graph below, titled "A Windening Gap," shows, despite a dramatic increase in vaccination among the elderly, deaths from the flu and pneumonia have hardly budged. (The calculations have taken into account the aging of the population.)

For younger adults, flu-related death is so rare that it has not been reliably studied: Doing so would require a trial of millions of people.

Of course, the flu shot may have benefits besides reducing the chance of death. Many may get flu shots simply to avoid getting sick. The Cochrane Collaboration identified more than 20 randomized trials addressing this question. The overall chance of developing "clinical" flu (we'll explain in a minute) was 19 percent in those chosen, again by chance, to receive the recommended flu vaccine vs. 23 percent in the control groups.

The careful reader may notice that these percentages are substantially higher than those reported for the elderly. (See "How Well Does the Vaccine Work in the Elderly?") This is because clinical flu is defined as a set of non-specific symptoms including fever, cough and muscle aches -- symptoms shared by many non-flu illnesses like the common cold. These non-flu illnesses may be especially common in younger adults because of their exposure to other people, particularly children. To try to isolate the effect of the vaccine, scientists sometimes use laboratory tests to confirm the activity of flu virus in the blood. Using this measure, the chance of flu in the vaccine group is 2 percent vs. 7 percent in the control group.

Studies have also measured another outcome: how vaccination affects days lost from work. On average, there are about 0.16 fewer days lost from work per person vaccinated. Another way of saying this is that about 5 percent of those vaccinated avoid missing about three days of work because of the flu. (That is, 0.16 days divided by the 5 percent who benefited from vaccination equals 3.2 days.) The other 95 percent vaccinated got no benefit.

Take-Home Messages

To promote vaccine use, many in the public health community have overstated the risk of flu-related death and the effectiveness of the vaccine in preventing it. While the flu vaccine may have some important benefit (less flu-related illness), we really do not know whether it reduces the risk of death. For younger individuals -- for whom the chance of flu-related death is extremely small -- any death-protection benefit can only be very modest (and it is unlikely we will ever reliably know whether it even exists). However, we do know that the vaccine reduces the risk of being sick and time lost from work. But because the effect is small, individuals will have to judge for themselves whether it's worth the bother.

We are not suggesting that Americans forgo flu vaccines. We simply want to help people make informed decisions.

For many people, getting the vaccine is a reasonable choice. And many may reasonably choose not to get it. (Consequently, the use of flu vaccination rates by Medicare and others to measure health care quality probably does not make sense.)

Regardless, public health officials should not exaggerate risks or benefits to promote vaccination. Exaggeration carries a price: Not only do some people get scared and engage in behaviors that increase their risk (like waiting in a crowded clinic for a flu shot). They may also grow cynical and end up ignoring health messages that really matter.

Steven Woloshin, Lisa Schwartz and Gilbert Welch are physician-researchers in the VA Outcomes Group in White River Junction, Vt., and faculty members at the Dartmouth Medical School. They conduct regular seminars on how to interpret medical studies. (Seehttp://www.vaoutcomes.org.) The views expressed do not necessarily represent the views of the Department of Veterans Affairs or the United States Government.

To respond to this article, send e-mail to health@washpost.com.

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:

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.

Beginning at the Beginning

[Updated June 12, 2007]

The following is a summary of the history of thimerosal. It is not a complete list, as there is much more information out there and many more details to the information that I have included, but it hits the high points and gives a good frame of reference for where the discussion of the safety of this product and its relationship to autism and neurodevelopmental disorders should begin.

History of Thimerosal and Autism

Invented in the 1920’s by Eli Lilly, thimerosal is 49.6% ethlymercury by weight, a neurotoxin known to be more than a hundreds times more lethal to tissue than lead.

Eli Lilly’s safety testing of the product consists of a 1930 study of 22 patients dieing from mengiococcal meningitis in an Indiana hospital. Patients are injected with the solutions and followed until their death, which is within days. Because the patients die of meningitis, they are declared to show no adverse reaction to thimerosal and the product is declared safe for use. Thimerosal is subsequently introduced for use in vaccines and in over the counter remedies as a preservative to kill bacteria in the product.

When the FDA is created, Thimerosal is grandfathered in and is not subjected to any additional safety testing. The 1930 study remains the only safety testing done on the substance even after being in use for over 75 years.

Through FOIA requests and documents acquired as a part of discovery process in lawsuits against Lilly, it is clear that they have been warned about, and have been aware of the dangers of the product since at least 1947.

The use of thimerosal in teething powders for infants leads to a fatal out break of Acrodynia, or “Pink’s Disease”, a form of mercury poisoning. This illness has many symptoms in common with Autism. The link to mercury powders was found in the 1940's and by the 1950's Pink's disease was disappearing.

In 1963 Eli Lilly was forwarded an article that read in part: "There is another point of practical significance: does the parenteral injection of thimerosal - containing fluids cause disturbances in thimerosal-sensitive patients?" "It is known that persons that are contact sensitive to a drug may tolerate the same medications internally, but it seems advisable to use a preservative other than thimerosal for injections in thimerosal-sensitive people."

On August 17, 1967 the Medical/Science department requests that the claim "non-toxic" on thimerosal labels be deleted in next printing run. Two weeks later the label is changed to "non-irritating to body tissues," and the phrase non-toxic omitted.

In 1972 The British Medical Journal reports case of skin burns resulting from the chemical interaction of thimerosal and aluminum. "Mercury is known to act as a catalyst and to cause aluminum to oxidize rapidly, with the production of heat." The manufacturers who supply us with thimerosal have been informed." [Thimerosal is being used in vaccines which also contain aluminum].

In the 1970’s six newborns at one hospital die as a result of having a thimerosal containing antiseptic wiped on their wounds.

In 1982 the FDA reviews the use of thimerosal. Their statement reads in part: “At the cellular level, thimerosal has been found to be more toxic for human epithelial cells in vitro than mercuric chloride, mercuric nitrate, and merbromim (mercurichrom). "It was found to be 35.3 times more toxic for embryonic chick heart tissue than for staphylococcus areus." [a pathogen that the thimerosal is intended to kill]. A 1950 study showed that thimerosal was no better than water in protecting mice from potential fatal streptococcal infection." "The Panel concludes that thimerosal is not safe for over the counter topical use because of its potential for cell damage if applied to broken skin and its allergy potential. It is not effective as a topical antimicrobial because its bacteriastatic action can be reversed." Additional language added to some Lilly labels: "As with any drug, if you are pregnant or nursing a baby, seek the advice of a health professional before using this product." The FDA orders the withdrawal of over the counter, thimerosal containing products within a 6 month period. It does not order removal from vaccines, but recommends that the issue be studied and that the incidence of neurological problems in unvaccinated populations like the Amish be compared to the vaccinated population. [22 years later no such study has yet been done. On July 19, 2005 Dr. Julie Gerberding, head of the CDC says that such a study would be difficult to undertake because of genetic confounders. This seems contrary to the scientific process because if indeed such a study is done and it is found that the Amish have a lower incidence of neurodevelopmental disorders, the next step would be to undertake genetic studies to see if their genes differ dramatically from the general population and if their differences can help us locate the genetic component of autism. In addition studies designed to see if the small number of vaccinated Amish differ in their risk for NDDs to the larger Amish population would offer information about increased risk from thimerosal.]

In the 1930’s the average child only received three vaccines in their young life. Many vaccines are added to the schedule over the years, with an increase in the 1980’s and with 3 vaccines added to the schedule in 1991 alone. The current vaccine schedule calls for 31 vaccines in the first 18 months of life, 48 with full flu vaccination by 72 months of life.

A Merck internal memo is obtained during discovery discloses that in 1991 a Merck researcher added up the amount of mercury that is in the new vaccine schedule and sounded an alarm at the company that children who are vaccinated according to it would receive amounts of mercury far and above that considered to be safe by the EPA. Merck takes no action in regard to the information.

During the 1990’s, autism rates begin to rise dramatically. Parents complain to the health authorities that they believe that their children’s developmental disorders are related to their vaccines.

In 1998, a researcher at the CDC does the same math that Merck did 7 years previously. She finds that children are getting as much as 125 times the EPA limit of mercury for their weight. The EPA limit is based on the ingestion of methlymercury in food by a healthy adult. Because 90% of ingested mercury is excreted in the digestive track and never enters the blood stream, so even the EPA limit may be drastically lacking considering that thimerosal is injected directly into the blood stream and is not subject to the bodies natural defenses against toxic poisoning.

In 1999, the CDC and the American Association of Pediatrics issue a joint statement saying that although they find no “evidence of harm” from the mercury exposure that children are getting in their vaccines, they are calling on vaccine manufacturers to remove it from vaccines on a voluntary basis as a precautionary measure because “some children may” get more than the EPA limit for mercury at their 6 month visits. Manufactures begin the process in 1999, but do not remove it from all vaccines.

No legal ban on thimerosal is issued.

No recall of the mercury laden vaccines is issued and companies continue to sell lots already manufactured. Some of these vaccines containing full doses of thimerosal have been found in doctors’ offices, by parents who request to read package inserts, with expiration dates as late as 2007.

No independent or government testing of vaccines is done to confirm that thimerosal has been removed. FDA denies parents request that they set up a system to verify manufacturers claims of low dose or thimerosal free vaccines.

No statement is issued to pediatricians to alert them to the symptoms of mercury poisoning.

No recommendation is made to pediatricians to screen children who suffered the onset neurological impairment after vaccination for mercury toxicity.

Vaccines with 25mcg of thimerosal are still shipped to developing countries Most flu shots still contain a full dose of thimerosal as of this writing in 2007. (The EPA estimates that a person must weigh 550 lbs. to safely tolerate this amount of mercury.)

In November of 1999, the CDC commissions one of its new employees, a Belgian named Thomas Verstraten, to study the Vaccine Safety Datalink to find the risk of autism and other NDDs in relation to thimerosal exposure. Verstraten’s first draft of the study finds a relative risk above 7 for children who receive the highest dose of thimerosal to develop autism. In simple terms, such children have a more than a 600% higher chance of developing autism than children who don’t receive any thimerosal. (A relative risk of 2 is sufficient proof in U.S. courts to find for vaccine injury) Verstraten and other scientists at the CDC spend 4 years trying to change the study so that the relationship between the preservative and NDD’s is significantly reduced or eliminated. The Center for Disease Control will later describe these changes to the study as “improvements”. When the study is published in 2003, it concludes that “no consistent significant associations are found between thimerosal containing vaccines and neurodevelopmental outcomes.” By this time Thomas Verstraten, who is listed as a CDC employee on the study, has been an employee of GlaxoSmithKlein (a defendant in thimerosal law suits) for more than 2 years.

In November of 2000, despite being born almost two months prematurely and despite the assurance of my pediatrician that thimerosal had been removed from vaccines, my son Webster is injected with a DTaP vaccine that was 74.5 times the EPA limit for mercury exposure for his weight, just two weeks past his due date. He will go on to develop verbal apraxia and sensory integration disorder.

In 2001 Bernard et. al. publish their hypothesis: Autism: A Novel Form of Mercury Poisoning. It reads in part: “Exposure to mercury can cause immune, sensory, neurological, motor, and behavioral dysfunctions similar to traits defining or associated with autism, and the similarities extend to neuroanatomy, neurotransmitters, and biochemistry. Thimerosal, a preservative added to many vaccines, has become a major source of mercury in children who, within their first two years, may have received a quantity of mercury that exceeds safety guidelines. A review of medical literature and US government data suggests that: (i) many cases of idiopathic autism are induced by early mercury exposure from thimerosal; (ii) this type of autism represents an unrecognized mercurial syndrome; and (iii) genetic and non-genetic factors establish a predisposition whereby thimerosal’s adverse effects occur only in some children.”

In 2001 the Institute of Medicine is commissioned by the CDC to undertake a comprehensive review of all research into the thimerosal/autism connection. At their first meeting, Dr Stratton, head of the commission, when discussing what the process and product of the working group would be states that, “We said this before you got here, and I think we said this yesterday, the point of no return, the line we will not cross in public policy is to pull the vaccine, change the schedule. We could say it is time to revisit this, but we would never recommend that level. Even recommending research is recommendations for policy. We wouldn’t say compensate, we wouldn’t say pull the vaccine, we wouldn’t say stop the program”. When the transcript of the meeting is made public through a FOIA request, many interpret this to mean that no matter what they find, they will not publicly say that there is any link between the thimerosal and autism. Dr. Harvey Fineberg, head of the IOM, states that this is an incorrect interpretation of the comments, but will not offer any alternate interpretation of what else they could mean.

In 2001 Verstraten presents a version of his study to the IOM. He begins his presentation by telling the panel that as of 8 am that morning, he had become an employee of Glaxo Smith Klein. Despite the conflict of interest and the drastic changes made over the course of the study, the IOM will rely heavily on the study in making their determination. Dr. Verstraten returns to Belgium and except for a letter published in Pediatrics, little is heard from him again.

In March of 2002 my son Chandler, who was born one month early, is injected with Hepatitis B vaccine containing a “trace amount” of thimerosal (currently still on the schedule), despite the fact that he has no risk factors for Hepatitis B, and he is still two weeks from reaching his due date. Within days he develops fevers and uncontrollable crying that lasts for three months and bowel problems that persist for two years until he is placed on the GFCF diet. He will go on to be diagnosed with both Autism and mercury poisoning at age 2. I later discover that the “trace amount” of thimerosal is still just over the EPA limit of mercury for his weight.

In 2003 the Verstraten Study is published in Pediatrics with no mention of the conflict of interest of the lead researcher. Later a private contractor would testify before congress that he was ordered to destroy the original data sets used in the 1999 version of the study that found the dramatic link between thimerosal and autism in the interest of “patient confidentiality”. The entire Vaccine Safety Datalink is eventually moved to an offshore private company and can no longer be accessed by FOIA request.

In February of 2004, the IOM rushes to hold public hearings where researchers on both sides of the issues present their studies. The meeting is considered to be a “draw” between the two sides by many of those in attendance. A link is neither proved nor disproved, but new research in to the mechanism of how mercury can trigger autism and NDDs in a genetically vulnerable sub population is presented, along with case studies of successful treatment of autistic symptoms based on the new research.

In May of the same year, the IOM issues their final conclusion on the link between Thimerosal and NDDs. They state that, “the body of epidemiological evidence favors rejection of a causal relationship between thimerosal-containing vaccines and autism. The committee further finds that potential biological mechanisms for vaccine-induced autism that have been generated to date are theoretical only.” They then go on to take the unusual step of recommending that research into a link between the two be abandoned and funds be spent on other lines of inquiry. The conclusion relies heavily on Verstraten and several other epidemiological studies that are considered to implement fatally flawed methods and to be riddled with conflict of interest by members of the autism community. Parent groups are enraged. The IOM panel disbands.

Later that year, Thomas Verstraten publishes a letter in Pediatrics in response to those who criticize his study and his conflict of interest. His letter does not address the substance of the charges made against the study and the changes that were made to it over it’s 4 year evolution, but instead says that continuing the debate the validity of the 1999 study would be a “waste of scientific energy and not to the benefit of the safety of US children or of all the children world wide that have the privilege of being vaccinated.” He goes on to say that any suggestion of impropriety on the part of himself, the CDC or GSK is an insult and accuses his critics of having “pitiable attitudes”.

In July of 2005, in the face of continuing criticism of the IOM findings, the head of the IOM, Dr. Harvey Fineberg, issues a letter stating that Dr. Stratton’s 2001 comments that they would not say “pull the vaccine” or “change the schedule” were taken out of context and did not suggest that the IOM decision was compromised. Dr. Fineberg has not, despite requests, offered an alternative interpretation of what her comments meant in context.

In March of 2005, Author David Kirby released his book, “Evidence of Harm - Mercury in Vaccines and the Autism Epidemic: A Medical Controversy” detailing the history of thimerosal in vaccines and its relationship to autism.

In April of 2005 the CDC posts a notice on their web site stating that they were in the process of reviewing “Evidence of Harm” and would be responding to the book.

In June of 2005 Robert F. Kennedy Jr. echoed the information found in the book and charged the CDC and Eli Lilly of malfeasance in covering up evidence of a causal effect between thimerosal and autism in an article published in Rolling Stone and Salon.com. It is entitled “Deadly Immunity: Robert F. Kennedy Jr. investigates the government cover-up of a mercury/autism scandal”.

July 19, 2005. The CDC holds a press conference to: “communicate the importance of infants and children receiving their recommended vaccinations on time, and reassure parents that vaccines are safe. The renewed attention to the potential causal link between thimerosal, a vaccine preservative, and autism will also be addressed during the press conference.” Vaccine safety groups are not informed of the press conference nor invited. The conference presents no new information and does not answer important questions raised in Evidence of Harm or Deadly Immunity about the conduct of the CDC the IOM or the reliability of the research that continues to be used to show no link between thimerosal and autism.

As of this writing June 26, 2007 the CDC has yet to issue its response to “Evidence of Harm” or to “Deadly Immunity”.

In June of 2007 the first vaccinated v. unvaccinated study is finally done... by parents. Generation Rescue funded a survey using the CDC's techniques for determining incidence of a disorder and found that vaccinated children are two and a half times more likely to have a neurodevelopmental disorder. CDC spokesman Curtis Allen said, "We look forward to learning more about the survey," . If the CDC responds to the survey this paper will be updated to reflect their response.

On June 25, 2007 Congresswoman Carolyn Maloney (D-NY) introduced the "Comprehensive Comparative Study of Vaccinated and Unvaccinated Populations Act of 2007" (H.R. 2832), legislation that would require the National Institutes of Health (NIH) to conduct a comprehensive comparative study of vaccinated and unvaccinated populations. Her stated purpose is to resolve the controversy about the possible link between autism and mercury or other vaccine components.