Tuesday, January 27, 2009

Response to Anti-Vaccination Parent

Ginger Taylor, the parent of a six-year-old son with autism, wrote a lengthy response to my previous post, "The Disappointment of Hearing 'Your Results Don't Matter.'" Ms. Taylor sounds like a woman who is truly dedicated to her son's successful development. However, I still find a number of Ms. Taylor's contentions to be unfounded. I am responding to her comments, albeit with a bit of hesitation. I am not an expert on the subject of autism, and do not wish to misrepresent the scientific community. If there are any mistakes, they are solely my own. Here goes:

You seem to have made an assumption here, that certainly would be a reasonable one if Paul Offit and his compadres are your main source of information on biomedical intervention for autism. And that seems to be that just because Jenny McCarthy didn't present the kind of evidence you are looking for to prove the efficacy of the treatments she used when she was on Oprah, and just because Offit says there is none, that they don't exist.


Perhaps it's true that there is better evidence than that which Jenny McCarthy presents("My science is Evan, and he's at home. That's my science1"). However, I honestly haven't seen such evidence. I've read a lot of anecdotal accounts of "miraculous" recoveries, "immediate" personality changes following administration of the MMR vaccine, and emotional appeals to the public's sense of outrage, but nothing that comports to the standards of science. Advocacy groups, such as Autism Speaks, the Autism Research Institute, and Generation Rescue, all feature many studies of very poor quality, and I can only assume that what they present is the "best evidence they've got."


I am the mother of a 6 year old that regressed into autism following his 18 month vaccinations and have gotten him about halfway back with the evidence based interventions that Offit has derided.
How do you know that you haven't gotten him "back" (I assume you don't mean "cured") simply due to good parenting? Effective behavior modification techniques? A good social environment? There is no way to know if your child improved due to any specific intervention. Don't sell yourself so short. I'm sure that your son's success has a lot more to do with the time and devotion you dedicate to him than to anything that anybody's selling you. There is a long history of blaming autism on "bad mothering2."Parents should feel pride in their children's progress, rather than (unfounded) guilt due to a feeling that they've exposed their children to something harmful.

Offit is not a good source on autism treatment (he does not even treat children with autism, he is an infectious disease specialist), and his vast conflicts of interest should be raising huge red flags for you.

-He is a vaccine patent holder who won't say exactly how many millions he made from RotaTeq, but says it was like "winning the lottery".

-He was reprimanded by Congress for his ethical breaches and conflicts of interest when as a member of the ACIP failed to abstain, but rather voted to put RotaShield on the CDC schedule, effectively creating a market for his own vaccine by insuring that it would go directly into doctors offices nationally the day after it was approved.

-RotaTeq is arguably the least important vaccine on the schedule for children to receive as Rota virus represents a minimal health threat to American children. (CDC's web site recommends that it be treated with rest and Pedialite). If Jenny's message that kids are getting "Too Many, Too Soon" is taken seriously and adopted, and the vaccine schedule is paired down, certainly RotaTeq will be the first to go as it has been confirmed that it causes Kawasaki's disease and fatal Intussusception.

-He has been publicly and repeatedly corrected for spreading misinformation and inaccurate statements about the cases in the vaccine injury compensation program, most notably this past year in both the Wall Street Journal and the NEMJ.

-He is currently being sued for libel by at least one person he wrote about in the book.

-Although he is quoted at least weekly claiming that vaccines have no relationship to autism, he almost never discloses that he is a vaccine patent holder and has major conflicts of interest. CBS News even did a piece on his failure to disclose (Along with AAP and Every Child By Two. And it turns out Amanda Peet is even being paid by Wyeth for her vaccine promotional spots).

-He routinely makes outlandish and irresponsible remarks such as his famous, "theoretically a baby can receive 100,000 vaccines at once safely" absurdity (I wrote to him the first time I saw this in print and was sure it was a misquote, and asked for a corrected quote from him. He replied that it was a correct quote and "that is probably a conservative number".)

(To be frank, we can't under stand why anyone takes him seriously, and suspect that it is his mere bravado that has prevented people from cluing in to the fact that he is not responsible physician.)

So given all the potential for bias here, don't you think that it might be wise to take a hard look at the other side and make sure that the information he is giving you is reliable and complete?


Perhaps Offit is a mean, greedy man, who enjoys slandering people, and who is simply trying to make more money from his Rotavirus vaccine. I don't know him personally, so I have no specific objections to these claims. The problem is, I don't care about Offit's personality or accomplishments or lack thereof. My only concern is whether or not the statements about autism that he states in his book are factual. Luckily, if I'm suspicious about potential conflicts of interest, I can investigate all of his claims independently, as Offit has provided 32 1/2 exhaustive pages of footnotes in his book, all of which refer me to all of the relevant papers and transcripts. If you can show me a place in his book where Offit

1) Falsifies information from these references AND
2) Such falsification is so damning that it undercuts his basic argument (i.e. invalidates the heap of evidence that he provides in the other 246 pages in his book),

then I would certainly take this objection seriously. But none of the arguments presented above satisfy either of those conditions, as they only address why Offit might want to falsify information, not whether or not he actually did so.

(Parenthetically, please know that intussusception occurs
spontaneously in approximately 1 out of 2,000 healthy young infants and children per year. The fact that Rotateq may cause intussusception (bowel obstruction) in 1 out of 12,000 patients must be weighed against the fact that the vaccine is generally administered in developing countries, where approximately 475,000–580,000 children die from rotavirus infection each year, according to the WHO. All treatments (and human actions) have costs. You must compare these costs to the corresponding benefits).

Because it is not like you have just one mom, Jenny McCarthy, standing up in public and claiming that she recovered her son from autism using these methods, the same year that her book came out, 2007, the Autism Research Institute documented more than 1,100 cases of kids loosing their autism diagnosis following biomed.

The plural of anecdote might not be data, but is a hell of a clue that any honest, earnest, evidence based loving clinician would be remiss not to examine, to put it politely. Criminal might be a better characterization.

Unfortunately, the studies propagated by the Autism Research Institute do not nearly satisfy the conditions of evidence based medicine. Let's look at one oft-cited ARI-sponsored article: "Effect of pioglitazone treatment on behavioral symptoms in autistic children4" in Journal of Neuroinflammation, written with co-contributors Stephen Edelson and James Adams of ARI.

Even after a cursory reading of this article, I find that the study included only 25 children, with no indication about whether the research subjects were recruited randomly or from a population that already subscribes to the researchers' theories. Most importantly, the study featured no control group. Scientific Method 101 says that you can't test a hypothesis without having a control. P values were not reported, so there is no way of determining whether the findings were statistically significant or simply occurred due to random chance. In fact, the authors themselves only conclude only that there should be "further testing," a viewpoint that they presumably shared even before writing the article.

Some people outright deny that the scientific method is a meaningful means of testing alternative medicine. In certain ways, I find the "research" of the ARI to be more pernicious. Their work has the cloak of science, and would seem quite convincing to someone who has no background in basic study design. I probably just prefer the people who outright claim that the scientific method is irrelevant, because at least they're being honest about their beliefs.

I know that you believe that it is "criminal" not to further investigate the claims of people who believe in the vaccine/autism link, because of the shear number of complainants. However, these claims have been investigated (Ten studies to show MMR doesn't cause autism. Six that show thimerosal doesn't cause autism, etc.) 5 More importantly, even if there hadn't been so many studies, I reject the notion that "any honest, earnest, evidence based loving clinician would be remiss not to examine" this issue, simply because many people believe in it. I will not "investigate" the claims of HIV denialists. Mass hysteria is a common historical phenomenon. If you are interested in reading an account of hundreds of people who were (erroneously) so convinced that they had been infected by a virus, that they actually began to experience symptoms of nausea and vomiting, please refer to Desenclos, J.C., Gardner, H., & Horan, M. (1992). "Mass Sociogenic Illness in a Youth Center." Revue D'Epidemiologie et de Sant, Publique, 40, 201-208.

Even if i had not reviewed some of the relevant literature, one hint to me that these vaccination claims are baseless would be the fact that the proposed pathophysiology constantly changes, while the culprit remains the same. Originally, it was proposed that the virulence of MMR stems from an infection caused by harmful proteins from the attenuated measles virus that reach the brain6. Others then said that MMR induced autism via an "autoimmune phenomenon7." Then others started to relate autism to thimerosal, saying it was due to mercury neurotoxicity, or perhaps thimerosal's binding to testosterone, which leads to hyperandrogenism8. Today, many activists acknowledge (or at least don't deny) that the vaccines are generally safe, but say that they just should not be administered to kids below a certain age, or that too many vaccines should not be administered during a short period of time (i.e. "Too Many, Too Soon"). The proposed mechanism and subsequent recommendations constantly shift and adapt with new evidence, but never actually disappear.

"her case is scientifically irrelevant, so long as it was not added to long list of comparable patients of a similar demographic."

So ask yourself, if Offit and CDC and AAP and the vaccine industry are so keen on insuring vaccines don't cause autism, and why have then not take Evan and those 1,100 kids, put them in a long list and compare them to patients of a similar demographic? (Why is there no study comparing kids with an autism diagnosis who undergo biomed with those who don't to see how functional they are at age 10 or so?) Jenny has repeatedly called CDC and asked them to examine her son and all the kids like her son, yet they have never contacted her or ARI or any of the parents who have before and after videos all over the internet showing their recovery stories.

Does that lack of curiosity raise any red flags for you?

Do you think that if one medical practice (much less several dozen) announced they had 1,100 cases of people who recovered from HIV/AIDS, all with evaluations, test results, medical records and videos to prove it, that CDC et all would collectively yawn, quote Brinner, claim it is not data and never even pick up the phone to see if an actual cure had been found? Even for just some cases of HIV/AIDS?

Not in a million years.

(...and if that ever happened, San Francisco would burned to the ground by protesters).

So why is it that with all the claims of vaccine regression and subsequent recovery, are you satisfied with the "no association, no know cause or cure" line from the very people, Offit, HHS, CDC, AAP et al, who would be held responsible and be out of their collective posteriors for causing the autism epidemic if it turned did out to be the vaccines?

Especially when they are not showing up in our community to evaluate our claims and examine our kids?

Especially when they are doing everything possible to prevent REAL vaccine research from being done. Like just three days ago when the Federal members of the IACC voting NOT to study vaccine causation" with the funding from the Combating Autism Act (in opposition to the community members, autism parents, who wanted the research done), one of the regional intents of which was to study the possible association between vaccines and autism.

Ask yourself, why won't health authorities do a simple study comparing vaccinated and unvaccinated children, to look for overall health out comes and see if kids vaccinated according to the CDC schedule have more autism, ADD, asthma, diabetes, arthritus and other neurological and immune disorders?

Why does a Congresswoman have to propose a bill to force NIH to do the study? Shouldn't they want to do it? Certainly there are more and more unvaccinated kids out there to study, and if in fact Offits claim that there is absolutely no association is true, then it can only improve vaccination rates to put a study out that can make the claim with authority.

And why... when no such study exists, can anyone make the claim that vaccines don't cause autism? Vaccines as a whole have never been studied, merely a few different aspects of the vaccine program. And they have been studied quite poorly in many cases.

I do not know why you believe the vaccination-autism claim has not been and is not being investigated. The NIH currently has four studies being performed on the subject, in addition to the many studies that already have been performed in a number of different countries. Many thousands of records have been analyzed, with every study concluding that there is no link between autism and MMR or autism and thimerosal. Japan, when it discontinued the use of MMR, did not see any subsequent decrease incidence of autism diagnoses.9 Additional studies might be initiated when the six “Centers for Excellence in Autism Research" are created with money from the Children's Health Act of 2000. Millions and millions of dollars have been and will be spent to investigate this unfounded assertion. This money could be better spent on studies that would investigate credible "leads" about the causes of autism (such as the excellent work of the Autism Genome Project).10

If you feel that these studies are still insufficient, all I can say is that there is only so much money we can use to chase after every proposed claim. If we performed studies to investigate each person's purported "cancer cure," we'd be left with non-useful confirmations of what we already know (i.e. that virtually all of these claims are bunk). Such studies have enormous opportunity costs, as they take away potential funding from plausible hypotheses that stem from prior research and well-reasoned pathophysiological mechanisms, rather than from conjecture. For example, it is a waste of money to study whether or not diluted duck liver cures the flu, (as homeopaths contend)11. At least eating duck liver is harmless. Non-vaccination has led to numerous preventable deaths in developed countries in the 21st century.

I erred when I said, "her case is scientifically irrelevant, so long as it was not added to long list of comparable patients of a similar demographic," because I implied that it would make sense to now add Evan's case to a scientific study. A good study would be double-blind randomized, controlled, trial including a random sample of kids with autism, rather than a cherry-picked selection of kids whose parents oppose vaccines, or whose parents who have already used alternative "treatments." Certain information can be obtained from a cohort study (a study where random children with certain conditions who have or have not had certain exposures are simply "followed" to determine outcomes), but these more necessarily require repeated investigation others, as they introduce a greater number of potential sources of error than randomized control trials.

Numerous randomized controlled trials have been conducted on kids with autism to test "natural," "biological" materials. These include the gluten-free casein-free “special diet" (which has only shown to cause bone density loss),12dimethylglycine13, and (hot off the presses, published just last week!) human immunoglobulin therapy 14. Needless to say, none of these treatments have proven to be effective. An NIH-sponsored study is underway to study the effects of cod liver oil, Vitamin B6, and Magnesium on kids with autism 15 (These vitamins are currently repackaged and sold -with a trumped up price- as "
Super Nu Thera," to parents of autistic children).

You assert that the testimony of thousands of parents satisfied with "biomed" treatment should be more discomfiting to clinicians. However, thousands of parents swore by "facilitated communication," as well as by secretin, and those thousands of parents were proven to have been influenced by the placebo effect (I am not blaming parents. Nearly everyone, including myself, are at least somewhat influenced by the placebo effect). At least 15 studies were performed to test secretin therapy, a treatment once heavily promoted by the Autism Research Institute.16 All randomized controlled trials demonstrated that the hormone caused no improvement in autism symptoms, in comparison to the placebo.

Some studies simply cannot be performed, because the proposed intervention is already known to be potentially lethal. For example, chelation therapy can be dangerous, even for someone in an acute condition who is already known to be suffering from heavy metal poisoning. When used on healthy children with autism, who have no measurable increase of "heavy metal toxicity," we put children at risk for the fate of Abubakar Tariq Nadama. Indeed, the NIH
extensively planned to perform a randomized controlled trial of chelation therapy, and called it off only when the initial animal testing demonstrated that the treatment caused extensive brain damage in rats.

As for the challenge of how we can "make the claim that vaccines don't cause autism?," my answer is we cannot make this claim, just as no one can make any claim with 100% certainty. We use science-based medicine to diminish our levels of uncertainty, until they become extraordinarily low. The fact that we can not, in any study, conclude that the "null hypothesis (in this case, that vaccines don't cause autism) is accepted," does not mean that it makes any sense to favor the alternative hypothesis (i.e. that vaccines do cause autism). For example, let's say someone made a claim that "Xenu...was the dictator of the "Galactic Confederacy" who, 75 million years ago, brought billions of his people to Earth in DC-8-like spacecraft, stacked them around volcanoes and killed them using hydrogen bombs17." My null hypothesis would be that this event didn't happen. However, I can never affirm this null hypothesis with 100% certainty, just as I can never state "vaccination doesn't cause autism" with 100% certainty.


So... at the conclusion of my long winded comment, I would like to call your attention to Bryan Jepson's book, "Changing the Course of Autism: A Scientific Approach to Parents and Physicians". I would like to encourage you to read it and then look back at Offit's book and see if he actually is taking apart the case for biomedical research or just going after the easy targets like McCarthy, while ignoring the actual biomedical approach to autism and the science to back it up.

You owe it to your future patients to have actually teased out the truth on this for yourself rather than just swallowing what those who quite obviously and transparently protecting professions and individual careers tell you the truth is.

Upon your recommendation, I read parts of Jepson's book. To buttress his arguments, Jepson heavily cites the work of Dr. Andrew Wakefield. Many of Wakefield's co-writers testified in court [CORRECTION 1.29.09: It was not a court trial but an omnibous proceeding for the Vaccine Injury Compensation Program, for which Wakefield was not on trial. I confused this with the British General Medical Council, which is holding a hearing to examine charges of professional misconduct] that he had falsified data, and 10/13 authors retracted their names from portions of Wakefield's most significant study, stating "We wish to make it clear that in this paper no causal link was established between the MMR vaccine and autism, as the data were insufficient." One witness at Wakefield's trial, Nicholas Chadwick, was the research assistant who had actually carried out the tests for the Wakefield's 1998 Lancet paper. He testified in court that, despite the fact that he informed Dr. Wakefield of the negative PCR test results, Dr. Wakefield reported positive findings in his paper.18 There were a number of such testimonies, despite the fact that Wakefield gave $30,000-$180,000 to expert witnesses who testified on his behalf19.

(Parenthetically, Wakefield is also under investigation for subjecting children to unnecessary and risky tests, such as lumbar punctures and colon biopsies, which would be inappropriate for any study, so long as these procedures were not medically indicated. An associate affiliated with the study ended up perforating a child's colon in a number of places.20 Some of the actions that Mr. Wakefield is accused of performing, such as handing out cash to children who attended his son's birthday party, and then collecting their blood as samples, are downright bizarre. He failed to use a random sample of children in his studies, using mostly clients of a trial lawyer, Richard Barr, from whom Wakefield had received, on his own admission, at least $50,00021).

In other words, I do not find Jepson's book, which heavily references Wakefield's papers (as well as the work of the Geiers, who also performed poor research), to be particularly reliable.


You clearly, clearly want to make the right decisions for your patients. What if the right decision for some of your patients was not to vaccinate them according to the current CDC schedule (clearly it was the wrong decision for Hannah Poling, Madison Hiatt and the thousands of others who have received a billion of dollars from the Vaccine Injury Compensation Fund)? And the right decision for some of your patients with ASD was exactly what Jenny McCarthy did for her son? And what if you never looked into it because Offit etc told you not to bother?
In terms of the Vaccine Court, the fact that those girls got money from the Vaccine Compensation Fund is not particularly relevant, because the cases are not judged based on scientific evidence. A team of lawyers (called "special masters") with no medical background, rather than a judge, jury, scientists, or medical professionals, preside over the cases. The court's guidelines state that “special masters are not bound by formal rules of evidence” and that both sides should “be creative” in presenting their arguments “quickly and less expensively22.”

The court had no way of verifying whether or not Hannah Poling's autism (caused by an underlying mitochondrial disorder) was indeed aggravated by vaccination. Even Poling's doctor, John Shoffner, an expert in mitochondrial disease, was
"genuinely puzzled" by the verdict. As far as I'm concerned, the findings of this court have little to do with science.



Bottom line, if you don't look all sides on this and make your own decision (rather than just joining the Orac insult-o-rama), then you risk taking on their crime of injuring children and withholding needed treatment if 'my side' is right.

I urge you, while you are still very early in your career, to take this subject very seriously and listen to autism parents and see if their concerns, questions and challenges are actually being answered by those you are taking your advice from currently. Are they really dealing with them, or just setting up straw men and knocking them down?
I (and many other parents) would be happy to talk to you about what we have learned and experienced and why we believe as we do, should you earnestly want to investigate autism causes and treatments on your own.
As I wrote on my other post, learning about the experiences of my patients and their families will be crucial for my providing good care, but is not relevant to science-based medicine (excepting in the use of case studies, which have limited value, and which are generally only used to develop hypotheses).

I know that "look at all sides on this" sounds neutral and unbiased, and that I should not "risk taking on their crime of injuring children and withholding needed treatment if 'my side' is right." The problem is that I am confident that I would cause more harm if I spent time to "look at all sides on this" and continued to pore over everyone's counterpoint for these debunked claims. I can spend a lot of time investigating whether or not HAART causes AIDS, or whether oleander defeats cancer, and any other medical claim ever proposed. Nobody can independently investigate every contention. However, doing so would detract from learning to read EKGs or chest X-rays, or performing other tasks that are crucial to avoiding future medical errors and providing excellent patient care.

Every one needs a gestalt about which resources to trust, and on what basis to accept information. A method may occasionally fail, but one chooses it because, compared to all other strategies for acquring information, it provides the greatest accuracy for the most important issues, with the greatest efficiency. To me, trusting a random website would be quick, but unreliable. Doing my own experiments on every issue might be reliable, but extremely inefficient. The best method available for clinicians to acquire scientific information is to use books and journals edited by people whom we know subscribe to a similar epistemoligical approach (i.e. commitment to the scientific method), and whom we know are held accountable for their claims, by the scrutiny of peer review. Will people sometimes falsify data or make errors? Yes. However, after a while, repeatability of experiments stops bad or mistaken research in its tracks.

I figure you might think that this is just a battle of "my favorite studies" versus "your favorite studies," and that the abundance of conflicting papers means that we can't know who is correct (which would theoretically render scientific research to be quite useless, on the whole). While controversy and uneven results can indeed be frustrating, I must say that this isn't a matter of my preferentially selecting studies that would help my case. The scientific method requires "appropriate design and analytic methods...critical to achieve meaningful results." Such methods include "definition of exposures and outcomes, validation of developmental diagnoses, provision of sample size calculations and/or discussion of study power, and statistical methods including techniques to control for potential confounding." One study compared a number of epidemiological cohort studies that investigated a possible vaccination-autism correlation, and found that only the study by the Geiers, (which was also the only study that reported a correlation between vaccination and autism) fulfilled zero out of eight epidemiological criteria. There are a lot of seductive "studies," that we may hope to rely upon, but we can still distinguish the good from the bad, especially with the power of repeatability.

Good luck, Ms. Taylor, and I hope your son's development continues to be successful. I have a family member with an autism-spectrum disorder, and I have observed firsthand the amazing dedication and love that parents put in to careing for these wonderful kids.

Footnotes:

1. Jenny McCarthy on Oprah. Interview by Oprah Winfrey, Oprah Winfrey Show, NBC, September 18, 2007. Source from Offit, Paul A. Autism's False Prophets (Columbia: New York, 2008).
2. Bettelheim, Bernard. The Empty Fortress: Infantile Autism and the Birth of the Self (New York: Free Press, 1972). Source from Offit.
3. Offit. 110-111.
4. Boris, Martin and Claudia C. Kaiser, et. al. "Effect of pioglitazone treatment on behavioral symptoms in autistic children." Journal of Neuroinflammation 2007, 4:3.
http://www.jneuroinflammation.com/content/4/1/3
5. Please see the pages-long list of studies in Offit 256-7 and 266-7.
6. Letter from Dr. Wakefield to journalist Brian Deer. 12.2.04.
http://briandeer.com/mmr/wakefield-st-statement.htm
7. Waisbren, Burton A. "It is time to face up to the problems of MMR vaccination and its possible relationship to Autism."
http://www.waisbrenclinic.com/mmr-autism.html
8. Geier, David A. and Mark R. Geier. "The Biochemical Basis and Treatment of Autism: Interactions between 3 Mercury, Transsulfuration, and Androgens." Autoimmunity Reviews. Retracted by publisher before publication. Available at
http://briandeer.com/wakefield/geier-mark.pdf
9. Honda, Hideo and Yasuo Shimizu. "No effect of MMR withdrawal on the incidence of autism: a total population study" Journal of Child Psychology and Psychiatry. 46:6. 572-579.
http://www3.interscience.wiley.com/cgi-bin/fulltext/118735419/HTMLSTART Source from Offit.
10. The Autism Genome Project (AGP) Consortium. "Mapping autism risk loci using genetic linkage and chromosomal rearrangements." Nature Genetics. Published online: 18 February 2007, doi:10.1038/ng1985.
11. Vickers AJ, Smith C. "Homoeopathic Oscillococcinum for preventing and treating influenza and influenza-like syndromes.", Cochrane Database Syst Rev. 2006, Issue 3. Art. No.: CD001957.
12. "Autism in Celiac Disease: Failure to Validate the Hypothesis that a Link Might Exist." Biological Psychiatry. 42(1997):72-75. See other sources in Offit 270.
13. 5. Bolman, William N., John A Richmond. "A Double-Blind, Placebo-Controlled, Crossover Pilot Trial of Low Dose Dimethylglycine in Patients with Autistic Disorder," Journal of Autism and Developmental Disorders 29:3 (1999) 191-194
14. 7. Handen, Benjamin L. and Raun D. Melmed. "A Double-Blind, Placebo-Controlled Trial of Oral Human Immunoglobulin for Gastrointestinal Dysfunction in Children with Autistic Disorder," Journal of Autism and Developmental Disorders
DOI 10.1007/s10803-008-0687-y. http://www.springerlink.com/content/r741394286415x84/
15. "Treating Oxidative Stress and the Metabolic Pathology of Autism" Arkansas Children's Hospital Research Institute. ClinicalTrials.gov Identifier: NCT00572741.
In recruitment stage.
16. A.D. Sandler, K.A. Sutton, et. al. "Lack of Benefit of a Single Dose of Synthetic Human Secretin in the Treatment of Autism and Pervasive Developmental Disorder," New England Journal of Medicine 341 (1999):1801-6. See other studies mentioned in Offit 251-2.
17. Wikipedia article on the Scientology figure, "Xenu."
http://en.wikipedia.org/wiki/Xenu
18. United States Court of Federal Claims. Docket Number 98-916V
ftp://autism.uscfc.uscourts.gov/autism/transcripts/day10.pdf
19. Full Legal Services Commission Report obtained by Brian Deer via Freedom of Information Act. Available at
http://briandeer.com/wakefield/legal-aid.htm
20. R. Ellis, "₤500,000 Payout for Autistic Boy Left Fighting for Life After Being Used as an MMR Guinea Pig." Daily Mail. December 8, 2007. Source from Offit.
21. MP3 audio available at
http://briandeer.com/mmr/wakefield-archive.htm and sources cited in Offit page 258.
22. "Guidlines for Practice Under the National Vaccine Injury Compensation Fund." The Office of Special Masters. United States Court of Federal Claims. Available at
http://www.docstoc.com/docs/831292/Guidelines-for-Practice-Under-the-National-Vaccine-Injury-Compensation-Program Source obtained from Grant, Andrew. "Inside the 'Vaccine Court.'" Scienceline. http://scienceline.org/2008/07/25/policy-grant-autismvaccinecourt/

57 comments:

Shay said...

Bravo.

Anne said...

Excellent work! Thank you for applying scientific thinking to a bunch of nonsense.

I'm old enough to remember a bad measles outbreak in my elementary school. Several kids got very seriously ill, one died and one suffered permanent brain damage. A bunch of us were just miserable for a couple of weeks before we got over it.

Polio was another horrible illness. While I do not remember the pre-vaccine scares I do remember kids who wore leg braces because of polio.

And my kids were vaccinated for everything I could get them vaccinated for. I could not have lived with it if I'd not vaccinated them and something horrible had happened.

whispers said...

Very nice post.

You've gotten a very positive review from Orac at Respectful Insolence, in case that kind of thing interests you.

Linden Rathen said...

An excellent blog.

Keep it up.

Torgo said...

Excellent post. I'll be sure to forward this to anyone I know who has concerns regarding vaccination which is, unfortunately, a number of people.

Scott said...

Excellent work.

I hope the 'Anti-Vax Parent' returns and comments on this rebuttal.

mayhempix said...

Excellent. You politely and effectively addressed Ginger's issues and systematically tore down her house of cards card by card.

I too will be curious to see if she returns to comment.

M2 said...

Nicely done.

Maria said...

Very nicely done, good for you.

I agree with you about the apparent lack of good evidence for the efficacy of treatments for autism and it is disturbing that some anti-vaccine parents are so desperate that, while arguing that vaccines are being inflicted on children without sufficient testing, are willing to allow experiments on their children of treatments that - unlike vaccines - really haven't been subjected to proper scientific trials. They will accept anecdotal evidence that the therapies are effective while rejecting a mountain of evidence that vaccines don't cause autism. If there are reports of proper controlled trials that prove these therapies work, let's have the references for them so we can read them for ourselves.

Your comments about Offit are spot-on. The constant protestations about conflicts of interest and doctors being funded by 'Big Pharma' are ironic. I suppose nobody is making a penny out of these so-called 'healing therapies'? Or out of being 'expert witnesses' (on subjects about which they know little) in cases against vaccine manufacturers in court? As you say, Offit's book is meticulously referenced. Nobody has to take him at his word - check the evidence for yourself. I have done and it holds up. But if your correspondent doesn't like Offit, she might like to read Michal Fitzpatrick instead. He's a doctor with a young autistic son and his books (MMR and Autism & Defeating Autism - a damaging delusion) are even more thorough than Offit in exposing all the nonsense.

Infidel Rooster said...

Kudos.

Anonymous said...

Very thorough and convincing. You have practically demolished every aspect of the anti-vax movement and were polite at the same time!

I hope that some of the misled people out there will take note even though there are many who prefer to stick their fingers in their ears.

Scott (a different one) said...

Kudos for a detailed, well, referenced response. Orac sent me over, I'll be adding you to my RSS reader.

mezzobuff said...

Excellent post and very easy for a non-MD like myself to read and understand. While I am not old enough to remember when polio was a very real concern, my grandmother was wheel-chair bound because of that illness. I think of her when I notice my little polio vaccine scar and wonder what her life might have been had she had been immunized against it.

Joseph said...

That was very good.

Ginger clearly doesn't understand what "evidence based" means. I'd challenge her to name one autism treatment validated by at least 2 randomized trials.

Also, her story about her son regressing into autism after his shots was not that way some years back.

Anonymous said...

Excellent post. I have two points- 1) I think Offit's statement that developing the vaccine was like winning the lottery was a reference to how elated he was; I think his institution gets the money.

B) Among your reasons for children improving with doubtful therapies, I think you missed the fact that some kids spontaneously improve.

Joe

Sigivald said...

Spell check bit you; I'm pretty sure "timorously" should be "thimerosal".

Dawn said...
This comment has been removed by the author.
Anonymous said...

Ginger Taylor is a non-entity, and I am surprised you took the time to deal with her. She needs to go back to doing what she does best, which is acting as apologia for the mercury militia.

Anonymous said...

I understand that Dawn's accusing you of being a sockpuppet (and invoking the tiresome "pharma shill" argument) is specious and irritation, but was comment deletion the best answer? Surely that will just reinforce their paranoia, and in their eyes support their hypothesis?

Heal Spieler said...

Hi Everyone,
Thanks for the really great responses. I'm honored that you're reading my blog.

Hi Anonymous,
I didn't remove Dawn's comment, so I'm guessing that she removed it herself. Thanks for the tip on that, because I wouldn't want anyone to think that I'd remove a comment with which I disagree.
AC

Jennifer said...

I'm your first bloglines subscriber? No way. With this post alone, you have earned my reading. Bravo, and good luck to you.

l33t MD said...

Let me just skip the long list of this post's points of excellence and proceed directly to the summary: simply awe-inspiring.

That must have taken quite some time. Please keep doing it! :)

Becky said...

Ooh, I wish I was so eloquent.

That's just... fantastic.

Kind regards,

Becky

Landru said...

Nice work. I suspect you didn't know what you were stepping in when you took on this post. While you appear to be far too nice for my personal taste in blogging, that's a me problem, not a you problem.

Alternatively, you didn't know what you were stepping in, you've done a marvelous job of not showing it, and you're an evil genius.

Nice, patient, and thorough work here either way. Congrats on the Orac hat-tip; that's quite an accomplishment.

AnthonyK said...

I too came to this post from Orac. I've recently become a bit obsessed by the anti-vax nuts following an incident when I got thrown out of a friend's house for arguing with the mother of a "vaccine damaged" child - cerebral palsy, apparently. So I'm learning all I can.
Two quick points: first, as you can see, the anti-vaxxers feel that people like you (us?) are just in the pay of the pharmaceutical companies - "it's all money" - and are convinced we're all part of a conspiracy. So everything we say is a lie.
Second, when anyone tells you that homeopathy is harmless, if nonsense, I've found that they activly discourage vaccination for some spurious reason - ironically because to the uninitiated it would seem to correspond to its founding principles.
But one question - I assume that some children are vaccine affected, through auto-immune responses or other mechanisms(after all not all children are claimed to be suitable). Who determines who they are, and what kind of compensation is paid, if any? In short, which children aren't considered suitable by doctors and why?
I'm curious on this point.
But thanks for this great post.

RickK said...

Thank you for this - very well done. Your writing is thoughtful and caring. You are going to make many lives better than they otherwise would have been.

Thank you especially for providing citations. Passion supported by facts and reason leads to truth and change. Passion without facts and reason leads to the Gaza.

tgibbs said...

Reading the literature on secretin treatment of autism is quite instructive, and illustrates how easily parents and even physicians can be deceived by placebo effects. After some early case reports claiming a dramatic improvement in autism after a single injection of secretin, there was a secretin craze among parents of autistic children, with thousands of children being treated with the stuff. Eventually, a randomized, placebo-controlled study was completed, matching the conditions of the early positive reports. The secretin kids got better. So did the placebo kids. No difference. Even many scientists couldn't believe that it didn't work. There were more studies--different forms of secretin, more doses, higher doses. I saw one study that actually made it into an ointment and rubbed it on the skin. The results were always the same--no significant improvement over placebo. At this point, we know more about secretin than just about any treatment for autism, and what we know is that it doesn't work. Yet even to this day, there are parents treating their autistic children with secretin.

Huge sums of money were wasted, by desperate parents buying secretin off-label, and to fund research studies of a worthless drug--money that might otherwise have been invested into learning more about autism or providing services to autistic children. The only bright point in the whole sad story is that it seems that secretin was essentially harmless, and probably didn't hurt the children, beyond the minor trauma of an unnecessary injection. That is more than one can say for many of the "cures" being pursued today by parents of autistic children.

Anonymous said...

Great Post! Keep up the good fight for Science and evidence based medicine.

Judi said...

From the mum of a 4 year old boy on the spectrum, I applaud this post. Fantastic!

MXH said...

Wow... well done. It's amazing that people completely ignore the diseases that these vaccines prevent. What worries me is that there are plenty of fairly good scientists (and MDs) who are otherwise very smart, but when it comes to vaccines, believe in Jenny McCarthy and ignore actual evidence (and they get mad at you for bringing it up). Glad there are people like you educating them.

Schwartz said...

Adina,

Your method of debate is a refreshing change from the usual vitriol. Thank you.

I have a couple of initial questions I'll get out of the way first:

1) Do have experience in statistical analysis or epidemiology?
2) Did you read the details or any critical reviews of the epidemiology you broadly reference?

I would like to point out a few points that I disagree with or think you presented in a biased way. I apologize for the length.

(Parenthetically the third world application of Rota vaccine is relevant but so is the fact that it is currently recommended as a childhood vaccine in the US. The US recommendation is justified as a reduction in cost due to reduced hospitalization, not death. This is far more relevant to your readers when considering the risks.)

"However, these claims have been investigated (Ten studies to show MMR doesn't cause autism. Six that show thimerosal doesn't cause autism, etc.)"

In order to support the notion that the claims of damage have been vaccinated, you would have to produce case studies or at least detailed followup for the affected group OR at least you have to illustrate that enough study of children with similar risk profiles were studied en masse. Neither you or Dr. Offit have provided them so right off the bat, the definitive statement that the topic has been studied is not justified in my opinion. In general, you will find that in the cases of vaccine damage very little documentation is available and there certainly is no large cumulative study of affected children. That alone should raise red flags in a system that mandates a medical intervention.

It shouldn't be a surprise that Hannah Poling's case was actually investigated in detail likely only because her father was a neurologist with both the power and wherewithal to ensure her case was studied in detail.

"In terms of the Vaccine Court, the fact that those girls got money from the Vaccine Compensation Fund is not particularly relevant, because the cases are not judged based on scientific evidence"

I might have missed it, but I don't see anywhere they state that the decisions are not based on scientific evidence. Medical records and expert assessment were provided in this case, and certainly expert assessment qualifies as scientific evidence. Your definitive statement here is not justified.

"A team of lawyers (called "special masters") with no medical background, rather than a judge, jury, scientists, or medical professionals, preside over the cases."

The Poling case was conceeded after a review by the HHS scientists. It never went to a hearing before the Special Masters. The HHS scientists examined the scientific evidence presented and determined that a hearing was not required, as they concluded the act of vaccination contributed to her brain damage (encephalitus) leading ultimately to a diagnosis of Autism. Your own statements don't match the facts and display the bias of Dr. Offit's opinion pieces (where it is difficult to evaluate the level of bias).

You seem to make more factual errors about the case of Andrew Wakefield:
"Many of Wakefield's co-writers testified in court that he had falsified data, and 10/13 authors retracted their names from portions of Wakefield's most significant study, stating "We wish to make it clear that in this paper no causal link was established between the MMR vaccine and autism, as the data were insufficient.""

I am interested in which trial of Dr. Wakefield anyone testified that data was falsified? I suspect you're incorrectly referring to the Omnibus hearing (which you yourself stated was unscientific) which did not involve Dr. Wakefield at all. Allegations against him were made despite the fact he was not a participant in the hearing, and thus he had no opportunity to rebutt the accusations. It would be good for you to clear up this allegation of yours, because as it stands, your statement does not match the facts that I am aware of.

You also make two further misleading statements: First, your wording infers that the retraction was significant despite the fact they only retracted the interpretation not for scientific reasons, but public relational ones as they noted in the section of their statement that you ommited. Second, you infer that the lack of a causal finding between MMR and autism was a new revelation, when it was already explicitly stated in the original paper (discussion section page 641). Your selective quoting makes a big deal out of very little just like the misleading press releases on the topic.

Given the diligence of most of your post, you seem to be making quite a few errors around the legal and personal aspects. I can only assume that you have been swayed by the many biased writings of these events without actually understanding the details of the events that unfolded. Wakefield is currently undergoing a GMC fitness hearing in the UK but no transcripts have been published and no verdict delivered so your conclusions appear a bit premature.

"However, these claims have been investigated (Ten studies to show MMR doesn't cause autism. Six that show thimerosal doesn't cause autism, etc.)"
Going back to this quote, I want to continue driving into the studies you reference through Dr. Offit. First, I'm surprised at your use of such a definitive statement (doesn't cause autism) that really can't be supported by any scientific studies of epidemiology. The conclusion that doesn't cause Autism isn't even that interesting really. We want to know if it contributes to damage including autism (or other problems). The case of Hannah Poling is a great illustration that vaccination alone did not cause the damage, but it certainly appears to have triggered and exacerbated it.

This is particularly pertinent with Thimerosal and this leads to my original questions at the top. If you read the details of these studies, you'll find that the two founding components are data on the prevalence of Autism and the estimated cumulative exposure of Thimerosal during infancy. I hope you've read critical reviews of the studies quoted by Offit, and the data they're based on. If you aren't aware, there is wide disagreement on the reliability of the Prevalence data, and there are significant known issues with the Danish Registry, the UK's GPRD, and the US databases over the period of time studied. I recommend at least finding and reading some of the statistical arguments against the use of prevalance numbers in these studies. As you should know, the role (and bias') of the statistician is critical in influencing the outcome because numerous assumptions and adjustments must be made in these studies which are already subject to a high risk of false positives and negatives. When working with difficult, inconsistent, or incomplete data (sometimes withheld from independent public analysis) the knowledge of conflict of interest is quite important.

The other issue is that these studies only look at the cumulative exposure over a long period of time. We know that the timing toxic exposure to virus' (CRS is a great example) or toxins in fetus' or infants can be quite significant in determine the outcome of damage. We also know that very low levels of heavy metal exposure can also have a significant effect neurological outcomes (ex. lead: http://www.ehponline.org/docs/2005/7688/abstract.html). None of these factors are even remotely considered in these studies, yet you and others including Offit make definitive statements like "doesn't cause Autism". They only studied cumulative dose to be the defining factor, an assumption that does not hold up all the time on it's own. Another aspect that is often ignored (and Contrary to Dr. Offit's published opinion in peer-reviewed journals) the concomitant application of vaccines (MMR and Thimerosal containing) are not actually required study for pre-regulatory approval and generally remain unstudied from a safety perspective. (http://www.cdc.gov/vaccinesafety/00_pdf/draft_agenda_recommendations_080404.pdf)

From my perspective that type of language is unsubstantiated by the reality of the limitations of the studies. The fact that Dr. Offit regularly makes public statements of this type (in addition with factual error that require correction) significantly hurts his credibility and I argue exposes his bias. Overstating the conclusions of scientific study, especially ones based on weak data is a reccuring issue.

As for MMR, I suggest you read the Cochrane systematic review of MMR studies from 2005/2006: http://www.cochrane.org/reviews/en/ab004407.html. After reviewing an extensive list of "definitive" MMR studies performed over several decades, they concluded that the study of both efficacy and safety was inadequate. If you read the details, (I suspect you'll find several of Dr. Offit's references in there) you'll see findings of serious methodological issues with seemingly "credible" study also heralded historically by regulatory bodies as "definitive". From this perspective you might understand why I remain skeptical of definitive claims issued by the likes of Dr. Offit.

Overall, I think there is plenty of justification of continued study. None of these studies you referenced ever examined the long term effects of either MMR or Thimerosal exposure in any RCTs (or as close as we can get given ethical limitations). We know from recent history (HRT being a prime example) that large long term studies often reveal unexpected negative outcomes in treatments assumed and shown to be safe by previous regulatory studies.

"As I wrote on my other post, learning about the experiences of my patients and their families will be crucial for my providing good care, but is not relevant to science-based medicine (excepting in the use of case studies, which have limited value, and which are generally only used to develop hypotheses)."

This is an interesting opinion which I would like to examine outside of the vaccine discussion. Expert opinion still plays a role in evidence based medicine (which is what I assume you meant when using the term "science based medicine"). Cumulative clinical experience forms the heart of expertise. I am concerned that you also dismiss the value of clinical experience in detecting problems. It is exactly the detection of patterns of anecdote that usually lead to further study of issues. The other important factor is that repeated followup into similar individual cases may reveal biological mechanisms which can (and should) also be used to form a hypothesis. The fact that disease reporting is mandated by law, yet pharmaceutical adverse event followup outside of research settings is voluntary are rife with error is a sad reflection on our priorities in my opinion.

Again, thank you for bringing a refreshingly politeness to the discussion. I wish you success in your studies. My only suggestion is to drill into the details of the assumptions underlying the evidence you use to justify closing the door on further research. Given the significant challenges facing our newer generation of doctors, I think you should drill into the well documented issues (plenty of peer review studies on this topic) with industry funded peer-review studies, and into the details of the impact that bias can have on statistical analysis. You might find (like I did) that the conclusions you're quoting are based on a lot more assumptions and questionable source data than you would like. (the latter not the fault of the authors, but on the lack of interest/diligence by medical regulatory authorities).

Potential Bias: I have two healthy NT children, one partially vaccinated (older), one unvaccinated (younger)

Bronze Dog said...

Haven't gotten to all of it yet, since I felt on commenting on one thing before finishing:

The proposed mechanism and subsequent recommendations constantly shift and adapt with new evidence, but never actually disappear.

Just the other day, I read an anti-vaxxer (Was it Dawn?) trying to blame it on the combination of vaccines and Tylenol.

What's it going to be next week?

Rich Charlebois said...

Wonderful post Adina! Excellent summary of the current science surrounding autism, and review of the pseudoscience competing for attention.

Anonymous said...

You go, girl!

DLC said...

A well done and precise refutation.
Now if refuting pseudoscience were only a vaccine. I fear this one will not "take".

PS. HT to Orac for linking to this.

Rhoadan said...

Great article, but may I make a couple of suggestions for the blog generally? One, please use larger type. My aging eyes have trouble with the type size you use. Two, higher contrast, especially for the quotes. Same reason as the larger type.

My eyes will thank you.

Jason L. Harris, PT, DPT said...

Great post. Truly enjoyed reading it.

Heraclides said...

Rhoadan:

Most of the recent web browsers allow you to "zoom" the page. Some only enlarge (or reduce) the size of the text, others also scale the graphics (e.g. Opera).

Schwartz:

Your reply is, to be polite, rather dismissive! I'm too busy to deal with all you say, but a few quick points:

"In order to support the notion that the claims of damage have been vaccinated [...]"

There are studies of putative "vaccine injury" with case follow-ups; my understanding is that these showed that most of the putative cases proved not to arise from the vaccination and confirm the rarity of "vaccine injury". If "vaccine injury" is rare, there aren't the numbers to do a large-scale study.

(We all make typing mistakes--me too--but I'd like to think that we don't vaccinate against "claims of damage"! Hmm, vaccines against legal opinions... could be useful...! Just kidding.)

Poling studying his daughter can just as easily be considered a case of Dr. Poling pushing his own barrow inappropriately. Poling's study of his daughter received considerable attention from the editors of the publication that presented the findings owning to his not declaring his conflicts of interest. His collaborators also wrote to the journal dissociating themselves from the lack of declaration of conflict of interest. Case studies of that general nature are routinely published in medical journals (your remark implies the work was only done because he "pushed" it). The work was done in collaboration with others, and could, and almost certainly should, have been done without Dr. Poling being involved.

re "doesn't cause autism", if the putative cause is removed and the disease continues to happen after a period time much longer than when it is first observed to occur, then deductively the cause must lie elsewhere.

re "listening to parents", I get the impression that you are confusing "science-based medicine" (i.e. the practice of medicine) with forming hypotheses. Heal said that anecdotal accounts (and case studies) are useful for forming hypotheses, as you also did. I believe her point was not against hypotheses, but that hypothetical ideas are not a sound basis for medical practice.

cannonballjones said...

That was a wonderful, intelligent, controlled and eloquent response, I tip my hat to you! It must be tempting in your position just to ruthlessly rip into anti-vaxxers but you handled that in real tetbook fashion. Will have to keep an eye on your blog in the future :)

Anonymous said...

Wonderful work. Taking the time to refute all that nonsense is worthy of some kind of award.

BTW, Ginger Taylor has shown up at the other location of your piece. She's annoyed that you didn't contact her first before you posted.

http://culture11.com/diary/36706

DT said...

Absolutely fantastic. (Will you have my babies?)

Just a word of caution. You have dipped your foot into a seething cauldron of vindictive antivaccine spitefulness. Unless you are blogging under a pseudonym and disguising your origins, you are visible, traceable and presumably contactable. I have no doubt that some who get directed here will feel the need to react inappropriately, as they have done to other bloggers their disagreed with.

PS. You might even wish to modify some of your claims for legal reasons regarding Wakefield and the Geiers, true as they may be. Examples:

"Wakefield also subjected children to unnecessary and risky tests, such as lumbar punctures and colon biopsies, which would be inappropriate for any study" - this is what the UK GMC case is deciding, so don't prejudge the issue.

"He even ended up perforating a child's colon in a number of places.20" Turns out this actually wasn't Wakefield, but a junior gastroenterologist on the unit who performed the procedure.

"...the Geiers, who performed similarly fraudulent research" ....Careful now....

Please feel free to remove my post once you've read it. I wouldn't want to give anyone else any ideas.

William the Coroner said...

Nice work. I don't have the patience for this stuff.

Rev. BigDumbChimp said...

Fantastically thorough and polite take down.

Sunil said...

Excellent post, thank you. I'm bookmarking it for future use and am also adding your feed.

I got a start when I read one of the early commenters Anne talk about Polio in past-tense ("Polio was another horrible illness"). We here in India have yet to eradicate polio; you see polio sufferers quite often. So when I see these people in the US campaigning *against* vaccination, it makes me want to bang my head against a wall. Hopefully better sense will prevail. Keep up the good work!

ouini said...

Amazing. Thank you for being so thorough. This is a keeper for future reference.

passionlessDrone said...

Your tone is appreciated, and sadly, as mentioned, you may get some unwanted attention from this. Many might consider my attention unwanted in the same vein. So it goes.

In any case, I think that the moving goalposts argument is a bit worrisome, because in the last few years more and more observations tell us that children with autism show signs of a dysregulated immune system such that the control of inflammatory immune responses is abnormal. By way of example, children with autism were found to have increased levels of macrophage migratory inhibitory factor (MIF) when compared to non diagnosed peers; and as levels increased, so did measures of autism severity. Other populations with increased levels of MIF include asthma, type 1 diabetes and others. It turns out, MIF is a participates in the expression of the toll like receptors; and as such, directly correlates to how we will respond to an immune challenge, including vaccinations.

http://pediatrics.aappublications.org/cgi/content/abstract/122/2/e438?rss=1

Inversely, people with autism have also been found to be relatively deficient in TGF-B1 when compared to others without a diagnosis. Similar to MIF, decreases in TGF-B1 are associated with chronic inflammatory diseases. I believe there are two studes in TGF-B1 in autism, one in adults and another in children. The one with children again showed a correlation between circulating levels and behavioral severity.

http://www.ncbi.nlm.nih.gov/pubmed/18762342
http://www.ncbi.nlm.nih.gov/pubmed/17030376?ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

When cytokines in the CSF or brain are measured, we find increased levels of inflammatory messengers; something which would seemingly be consistent with a hindered ability to control an inflammatory response. Increased levels of TNF-alpha in the CSF, increased levels of cytokines in the brain, and neruoinflammation have all been observed.

http://www.ncbi.nlm.nih.gov/pubmed/17560496?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
http://www.ncbi.nlm.nih.gov/pubmed/15546155?ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
http://www.ncbi.nlm.nih.gov/pubmed/19157572?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

There are many other observations of disturbed immunological profiles in this cohort, but for the sake of brevity, I am not posting them.

Interestingly enough, the group led by Pardo was able to duplicate activated microglia in an animal model of autism by administering an agent known to increase concordance of autism in twins when given to pregnant mothers. What they found, however, was that they were able to generate persistent behavioral and physiological differences found in autism when giving the agent after birth, but only if the agent was given within a narrow timeframe. Later administration was found to have no effect on either behavior or physiology.

http://www.ncbi.nlm.nih.gov/pubmed/17400887?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

You may or may not know that children with autism have been shown to have larger brains than their undiagnosed peers at age 2; it is generally thought that this is a result of a failure of the pruning process that happens in this timeframe. However, we also have evidence, that instead, this is the result of an ongoing inflammatory process, instead of a generalized failure of the pruning process.

http://www.ncbi.nlm.nih.gov/pubmed/16924017?ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
http://www.autismconnect.org/news.asp?section=00010001&itemtype=news&id=5882 [news article on same; where author discusses inflammatory component not mentioned in abstract.]

Unfortunately, the effect of early and more aggressive initiation of inflammatory responses is completely invisible to the overwhelming majority of our existing studies concerning autism and vaccination. Looking for differences in thimerosal tells us nothing about the result of initiating immune responses; likewise, MMR studies only evaluate a single insult in a series of a dozen or more; most of which have occurred much earlier in life.

Please consider that most of the papers referenced above were published in 2008 (one in 2009), the oldest having come out in 2005. Given that most of our existing suite of vaccine research regarding autism was never designed to take inflammatory regulation into account with what we now understand about this subset of peoples ability to control such responses, you might give pause before applying such scorn to different hypothesis; though I can understand how that thought process takes hold. I find it a very unfortunate fact that, in general, the discussion on vaccines and autism is centered around a single preservative or single shot.

Anyways, I would be interested in your thoughts. Take care!

- pD

Schwartz said...

Heraclides,

"Your reply is, to be polite, rather dismissive! I'm too busy to deal with all you say, but a few quick points:"

I appreciate the candor. Aside from being one of the more hypocritical statements I've read, I'm a bit surprised you thought my post was dismissive, especially when you followup with a post that talks around most of the key points I made.

"There are studies of putative "vaccine injury" with case follow-ups;"

I would love to see any regulatory documentation which outlines any details of these followups. We certainly know that many vaccine damage awards have been dished out by VICP but those records are all sealed. I've never seen any generalized analysis of those outcomes either, but I would be happy to be proven wrong on that point. Any reference would be helpful.


Your discussion about the person Dr. Poling really has no bearing on the point that I made about the Hannah Poling case unless you are disputing the case study results and conclusions which are published for all to read -- as the author pointed out there is no need to worry about an Author's bias if you can evaluate the facts yourself. Since you didn't actually address any of the published evidence, I can only conclude you intended to fuzzy the waters by talking about the person.

"if the putative cause is removed and the disease continues to happen after a period time much longer than when it is first observed to occur, then deductively the cause must lie elsewhere."

Again, you didn't address the main point being that the conclusions drawn from the references provided can't be used to make a definitive statement. I can only assume you missed the point and applied the wrong logical statement.

Seeing as I can't find "Science based medicine" in the official definition of medicine, I assumed we're talking about Evidence Based Medicine which is well defined.

I also searched my post to find the phrase "listening to parents" and didn't find a single reference to it. Since I was clearly refering to clinical work which involves a lot more than listening to parents, I can only hope you didn't intend to be dismissive of clinical work.

"Heal said that anecdotal accounts (and case studies) are useful for forming hypotheses, as you also did. I believe her point was not against hypotheses, but that hypothetical ideas are not a sound basis for medical practice."

Contrary to what you just described, Heal states quite clearly that the ONLY value of clinical work to "science based medicine" is the forumulation of hypothesis.

Given that the forumulation of good hypothesis is the starting point for gaining useful scientific knowledge in the practise of evidence based medicine, the author's clear dismissal of it being of limited value is what I find troubling.

Heraclides said...

Schwartz,

I have too much on my plate to reply in any real depth; my comments are brief pointers that you should take up in your own time.

Please don't accuse me of talking around you; I did not. I looked at what lay behind your points.

There are studies of putative "vaccine injury" with case follow-ups;

I was talking about studies, as you can see; in your reply you are talk about "vaccine damage awards ": two different things.

My points about Dr. Poling are relevant: you presented an opinion about person. I picked that up and I pointed out his actions can just as readily be seen other ways. The issue in the publication was one of not declaring a conflict of interest, not "author bias" as the editors made clear (although that can be viewed an another, separate, issue). As for try to make out that I was "talking about the person": you did that, that's why I wrote what I did!

Again, you didn't address the main point being that the conclusions drawn from the references provided can't be used to make a definitive statement. I can only assume you missed the point and applied the wrong logical statement.

My short remark was very much of the essence. Yes, you can't say "100%" in principle. You can say it cannot be a major cause, or is exceptionally unlikely to be a cause as to not be realistic to consider it. You can qualify it with the appropriate p-values and whatnot, but it won't change the essence of what I wrote.

I also searched my post to find the phrase "listening to parents" and didn't find a single reference to it. Since I was clearly refering to clinical work which involves a lot more than listening to parents, I can only hope you didn't intend to be dismissive of clinical work.

This a real straw-man effort. I didn't refer to this, you make out that I did, then you set up an artificial "test" that "of course" fails. I would politely ignore it, but very quickly: scientific literature tends to use formal phrases, you need to use appropriate language So, for example, "patient survey vaccine" gives 3442 publications.

Contrary to what you just described, Heal states quite clearly that the ONLY value of clinical work to "science based medicine" is the forumulation of hypothesis.

This is not what she wrote, she wrote: excepting in the use of case studies, which have limited value, and which are generally only used to develop hypotheses She referred to "case studies", not "clinical work". Case studies are valuable, and are generally limited to drawing hypotheses as she wrote.

Given that the forumulation of good hypothesis is the starting point for gaining useful scientific knowledge in the practise of evidence based medicine, the author's clear dismissal of it being of limited value is what I find troubling.

That is not what my reading of what she wrote. My original reply addressed that. I think you can confusing "limited value" with some sort of dismissive remark that they have no value: this is not what this phrase means in this context.

Heraclides said...

'I think you are', not 'I think you can' in my last paragraph. Excuse any others errors, I didn't have time to proof read.

Schwartz: Just so you don't waste time on it: I'm very unlikely to have time to take this further. (I've got 12+ hours days at the moment, and I'd prefer to spend what little free time I have with more relaxing things.)

Schwartz said...

Heraclides,

"Please don't accuse me of talking around you; I did not. I looked at what lay behind your points."

You have an interesting approach to debate if you feel you can respond to something you assume exists behind my actual points without ever addressing them.

"I was talking about studies, as you can see; in your reply you are talk about "vaccine damage awards ": two different things."

If you read my response carefully, my reference to damage awards is only to show that there is plenty of data to work with despite your assertion that there aren't enough cases to justify study. To recall what you said:
"If "vaccine injury" is rare, there aren't the numbers to do a large-scale study."

I notice you still don't provide any indication where these case studies exist that document the followups. From here, it still looks like an assumption.

"My points about Dr. Poling are relevant: you presented an opinion about person. I picked that up and I pointed out his actions can just as readily be seen other ways."

I am confused by this. I never stated any of Dr. Poling's opinions in my post. I merely pointed out that the likely reason her case was followed up was because of who he was. Any other references to her case have nothing to do with his opinion.

To remind you of what I wrote about Dr. Poling:
"It shouldn't be a surprise that Hannah Poling's case was actually investigated in detail likely only because her father was a neurologist with both the power and wherewithal to ensure her case was studied in detail."

Your post attacking his character still has nothing to do with any arguments I made as I never quoted his opinion.

"My short remark was very much of the essence. Yes, you can't say "100%" in principle."

Again, you miss the point. My point is exactly that you can't make definitive statements based on this type of science. To do so is illogical and unscientific.

"You can say it cannot be a major cause, or is exceptionally unlikely to be a cause as to not be realistic to consider it."

Now you enter with your personal opinion. That is your perogative, but there is far more science left in that debate. To jump to strong conclusions based on those references is highly debateable given the similarity of the types of studies done, the weak data sources used, and the large amount of avenues ignored as I pointed out in my first point -- none of which you addressed.

"This a real straw-man effort. I didn't refer to this, you make out that I did, then you set up an artificial "test" that "of course" fails. I would politely ignore it, but very quickly: scientific literature tends to use formal phrases, you need to use appropriate language So, for example, "patient survey vaccine" gives 3442 publications."

...

"This is not what she wrote, she wrote: excepting in the use of case studies, which have limited value, and which are generally only used to develop hypotheses She referred to "case studies", not "clinical work"."

I made the incorrect assumption that her response was a reference to clinical work which upon re-reading it is a reference to listening to stories about Autism. Although it weakens my initial reaction, it
does not really change the given impression of the lack of importance of case study or providing clinical care for Evidence Based Medicine. Perhaps it's just the wording.

"Just so you don't waste time on it: I'm very unlikely to have time to take this further. (I've got 12+ hours days at the moment, and I'd prefer to spend what little free time I have with more relaxing things.)"

Thank you for the discussion.

Heraclides said...

Schwartz,

Several times you have made me out to do or say things I didn't. A kind reading of this is that you misunderstand what was said. I can think of several less kind interpretations, too! I have no easy way of knowing what is true, but some of your remarks make it hard for me to want to give you the benefit of the doubt. Could I suggest in future that you not be so quick to accuse others of "talking around you", etc., and try understand what they are saying first?

You have an interesting approach to debate if you feel you can respond to something you assume exists behind my actual points without ever addressing them.

This is not right and is like your earlier claim that I was was trying to "talk around" you. (Who said it was a "debate"? You can't dictate people's contributions and you shouldn't accuse them of "avoiding", etc., you when their replies don't suit you.)

I never stated any of Dr. Poling's opinions

I never said you did. (Excuse me for this, but you have this backwards, quite literally. I said you presented an opinion about Poling, not Poling's opinion.)

Your post attacking his character still has nothing to do with any arguments I made as I never quoted his opinion.

Quickly: no my post didn't; it may not be your opinion, but it was relevant; I know (see above).

Now you enter with your personal opinion.

It was not an opinion. My kindest reading of your response is that you think I am talking about something else (but I have to admit I find it hard to see why you would think that). I referred to what statements you can make from statistical results, following from your lead in writing "you can't make definitive statements". (Results in epidemiology are from statistics.)

I made the incorrect assumption that her response was a reference to clinical work which upon re-reading it is a reference to listening to stories about Autism.

No offence, but that's not correct either. In medicine, 'case studies' has a particular meaning. It's not "listening to stories".

Anonymous said...

Beautiful post.

Schwartz said...

Heracledes,

"Several times you have made me out to do or say things I didn't. A kind reading of this is that you misunderstand what was said. I can think of several less kind interpretations, too! I have no easy way of knowing what is true, but some of your remarks make it hard for me to want to give you the benefit of the doubt."

Interesting. I have been quite specific in each of my posts about exactly which of your points I'm talking about. I can't really address a general accusation like you made above.

"This is not right and is like your earlier claim that I was was trying to "talk around" you. "

Well, you said it yourself when I noted that you failed to address my key points:

"Please don't accuse me of talking around you; I did not. I looked at what lay behind your points."

You don't address my key points, but you address what you thinks lies behind them. OK, you interpret that as you want.

"(Who said it was a "debate"? You can't dictate people's contributions and you shouldn't accuse them of "avoiding", etc., you when their replies don't suit you.)"

This is of course ironic. I am not dictating anything. You are clearly the one stating what one should and shouldn't say here. I am merely making very specific observations of your posts, which is exactly what this type of forum is for.

"I never said you did. (Excuse me for this, but you have this backwards, quite literally. I said you presented an opinion about Poling, not Poling's opinion.)"

This is obtuse as usual since you don't provide a quote. I expressed no opinion about the person of Dr. Poling. I only expressed the hypothesis that his daughter's case was followed up because of who he was. How you feel attacking his person addresses any of my points is puzzling.

I suggest that you should be specific on what relevance your attack on his person had to my post at all.

"Quickly: no my post didn't; it may not be your opinion, but it was relevant; I know (see above)."

Hmmm, still no specifics.

"It was not an opinion. My kindest reading of your response is that you think I am talking about something else (but I have to admit I find it hard to see why you would think that). I referred to what statements you can make from statistical results, following from your lead in writing "you can't make definitive statements". (Results in epidemiology are from statistics.)"

Ah, but it is an opinion based on your interpretation of the statistics. Statistics can't be used to state what you did independent of an analysis of the methodology and source data. Your interpretation of the strength of the data directly affects any statements of conclusion. Your interpretation is your opinion.

There is a lot more to statistics than numbers. All of the assumptions and details about the collection and correction of source data comes into play. That directly affects the conclusion.

"No offence, but that's not correct either. In medicine, 'case studies' has a particular meaning. It's not "listening to stories"."

No offense taken, but you must have misunderstood.

She stated: "As I wrote on my other post, learning about the experiences of my patients and their families will be crucial for my providing good care,"

In response to:
"I (and many other parents) would be happy to talk to you about what we have learned and experienced..."

That sure reads like listening to parents (that made the offer) to tell their stories about Autism.

Anonymous said...

@scwartz:

We certainly know that many vaccine damage awards have been dished out by VICP but those records are all sealed. I've never seen any generalized analysis of those outcomes either, but I would be happy to be proven wrong on that point.

I would just point out that looking to court cases to provide relevant data for scientific conclusions is a dangerous game.

surely you know, if you ever have actually read the motivations behind any particular court decision, that awards are not always granted on the results of scientific analysis. Indeed, awards are often given based on a purely cost/benefit model, and have absolutely nothing at all to do with any underlying data in support or contention. In short: beware utilizing the results of court cases in support of any generalized conclusion.

Moreover, you claim general knowledge of the danger of statistics interpretation ("statistics are not just numbers"), but entirely fail to provide any specific reference to any statistical model or analysis used in any paper under contention that has attempted to research side effects of vaccinations. Have you actually read the papers listed by the original author of this post? If so, where are the specific flaws in model or analysis used in each study?

Anonymous said...

That sure reads like listening to parents (that made the offer) to tell their stories about Autism.

then you have a very poor understanding of how doctors conduct case histories.

Schwartz said...

Anonymous:

"I would just point out that looking to court cases to provide relevant data for scientific conclusions is a dangerous game."

First, they aren't court cases. These are VICP hearings which are different.

Second, you'll also note that my raising them here did not draw any scientific conclusions. I raised them to illustrate that there is no public documentation of the scientific/medical followup of individual cases of vaccine damage.

"Moreover, you claim general knowledge of the danger of statistics interpretation ("statistics are not just numbers"), but entirely fail to provide any specific reference to any statistical model or analysis used in any paper under contention that has attempted to research side effects of vaccinations."

My comments on the statistics did not refer to a specific study at all. You are taking my comments out of context.

If you follow the discussion I noted that the statement made by Heraclides is opinion because "statistics" is not just numbers, but the personal interpretation of the numbers, assumptions, and methodologies involved.

"then you have a very poor understanding of how doctors conduct case histories."

I suggest you read the comments in context. You again quote me out of context.

1) There was an offer for parents to tell their story 2) The author made a comment about the invitation.

Clearly the discussion revolves around "listening to the parents" that made the offer.

sahm3k said...

As a mom of a son on the spectrum...THANK YOU!!!!