Secretin Rises from the Grave!
September 30th, 2008
From time to time, I receive comments like:
"Why are you so opposed to studying ‘alternative’ therapies that have a low probability of working? If the study shows the therapy doesn’t work, people will stop using it."
Oh, if that were only true!
Let’s take – for example – the use of secretin as a therapy for autism. This has been repeatedly shown to be ineffective (no better than placebo), yet it keeps rising from the grave like some unquiet corpse.
Although it’s a bit early for Halloween, Stephen M. Edelson (PhD) of the Autism Research Institute has once again raised the "secretin-cure-autism" hypothesis from the dead. It is now roaming the "alternative" autism therapy community, munching on the brains of the "reality challenged". You can read it yourself in the ARI newsletter, Autism Research Review International (volume 22, number 2, pages 3 and 6).
In his editorial, Dr. Edelson starts with an abbreviated (and redacted) timeline of the secretin "controversy" (he says "controversy", I say "debacle"). He then goes on to explain why his unscientific parent survey of treatment effectiveness is a significantly better measure of the effectiveness of secretin than the over twenty studies that have been done to date. Among his "reasons" are:
[1] The largest studies (including the Repligen Corporation’s Phase 3 study) used human secretin instead of porcine secretin. Porcine secretin, you see, was what was used in the earlier, smaller, less well-designed studies that showed some effect. More about this later.
[2] The studies didn’t focus on the children with gastrointestinal problems – specifically chronic diarrhea and chronic constipation – which (again, in the few studies that showed an effect) were the children who showed the most effect.
Secretin Timeline
For those who are new to the scene, let me give you a capsule summary of the rise, fall, and (at least for a while) death of the "secretin-cures-autism" hypothesis. You’ll notice that many of the details I cover are not included in Dr. Edelson’s timeline. Case reports and studies showing that secretin is an effective treatment for autism are in red , studies that show that secretin is no better than placebo are in blue .
A few definitions that might come in handy:
Double-blind : Neither the subjects (or their parents) nor the researchers knew which treatment the subjects were receiving until after the final evaluations were recorded. This keeps the patients/parents and researchers from unconsciously "shading" their interpretation of the results based on their knowledge of which subjects are getting the drug.
Randomized : The subjects were assigned to the treatment (secretin) or placebo group at random. This helps to prevent a certain "type" of patient from being assigned to the drug or placebo groups. Without randomization, "sicker" children might be assigned to the drug group (or, conversely, they might be shunted over to the placebo group to keep from "screwing up" the results).
Crossover study : In a crossover study, the subjects are assigned to one of two (or more) groups. One group receives the study drug (secretin, in this case) and the other group receives the placebo. After a suitable "washout" period to allow the effects of the drug (if any) to dissipate, the group that initially received the drug gets a placebo and the group that initially received the placebo gets the drug. This allows the subjects to act as their own "controls" (sort of – there are some problems with this assumption).
1996
1996 – Parker Beck undergoes an upper GI endoscopy at the University of Maryland hospital. During this procedure he receives – as is typical – an injection of secretin to stimulate pancreatic secretion so that the gastroenterologist can confirm that the pancreatic duct is open (patent) without having to inject X-ray contrast, which carries the risk of causing pancreatitis.
A few days later, Parker – who was autistic – began to talk for the first time. [Note: at least one source – written by Bernie Rimland – states that Victoria Beck (Parker’s mother) had to INSIST on the secretin injection. This seems unlikely, since secretin is a routine part of upper GI endoscopy AND because she would have had no reason to insist on secretin, as it had never before been associated with improvement in autism.]
According to Ms. Beck – documented in numerous interviews – Parker remained verbal with improved social interaction even though he received only a single dose of secretin until a approximately year later.
1997
1997 (approx) – Parker Beck begins receiving repeated secretin injections.
December 1997 – Repligen Corporation stock trading at $0.78 on volumes of 65,600 shares.
1998
A case report of three (3) autistic children who received secretin as part of endoscopy and showed improvement.
May 19th, 1998 – Victoria Beck and Dr. Karoly Horvath file a patent (#6,020,310) on the use of secretin for the treatment of autism and for the use of secretin levels in the diagnosis of autism. This patent was later sold to the Repligen Corporation.
September 1998 – Repligen Corporation stock selling at $1.31 a share with volumes of about 41,000 shares.
October 1998 – Victoria Beck – Parker Beck’s mother – appears on both "Dateline" and "Good Morning America" to reveal to the world how secretin cured her child.
October 16, 1998 – Ferring Pharmaceuticals - the only manufacturer of secretin at the time – sells its last vial of secretin. The company had decided earlier to stop manufacturing secretin due to the low demand, a decision which should go down in economic texts as an example of epic bad timing.
November 1998 – Repligen stock trading at $1.69 on volumes of 37,000 shares.
1999
January 13, 1999 – Victoria Beck and Bernie Rimland file a patent (#6,197,746) on methods of administering secretin for treating autism that includes (besides injection):
"Other methods and compositions for administering the effective amount of secretin include other transdermal carrier substances, such as gels, lotions, or patches; oral carriers, such as tablets, capsules, or lozenges; inhalation through the nose or mouth (e.g., as an aerosol); suppository forms of secretin and secretin compositions; and using acoustic waves to cause the secretin to penetrate the skin."
This patent was later sold to the Repligen Corporation
March 1999 – Bernie Rimland publishes an "update" on secretin in the ARI newsletter . In it, he mentions how Victoria Beck patented the use of secretin for the treatment of autism and how she fought off attempts by the "university medical school doctors" to try to patent it.
He fails to mention that he is also a holder of a patent on the use of secretin for autism (see above). Dr. Rimland mentions in passing that the Becks sold their patent to Repligen Corporation and donated the proceeds and royalties to ARI, which at that time was owned and operated by Bernie Rimland.
March 1999 – Repligen stock trading at $3.06 on volumes of over 200,000 shares.
1999 – Victoria Beck’s book, "Confronting Autism: The Aurora on the Dark Side of Venus: A Practical Guide to Hope, Knowledge, and Empowerment" is published.
A study of 56 children with autism. Randomized, double-blind placebo controlled, single dose. No effect seen from secretin.
2000
February 2000 – Repligen stock trading at $13.13 per share on volumes of 1.3 million shares.
A study of 56 autistic children. Open label (both researchers and parents knew what the child was getting), single injection. A second double-blind placebo-controlled study was done with 17 children who had responded the most in the first study and 8 new subjects who got an additional injection of secretin or placebo with crossover at four weeks.
"Results of both inquiries indicate that although treatment with secretin was reported to cause transient changes in speech and behavior in some children, overall it produced few clinically meaningful changes when compared to children given placebo injections."
A study of 95 autistic children. Placebo-controlled, randomized, double blind – single injection of either secretin or placebo. "No significant differences in language or autistic behaviour measures were observed at the 3-week follow-up between the groups."
2001
March 5, 2001 – Victoria Beck and Bernie Rimland file a patent (#6,790,825) for "Method of using secretin and compositions made therefrom for the treatment of autism and other neurological, behavioral and immunological disorders". This patent was later sold to the Repligen Corporation.
April 2001 – The Repligen Corporation, which makes recombinant human secretin, completes a Phase 2 study of secretin in autistic children.
May 2001 – Coniglio et al. A randomized, double-blind, placebo-controlled trial of single-dose intravenous secretin as treatment for children with autism. J Pediatr . 2001 May;138(5):649-55.
A study of 60 children with autism. Placebo-controlled, randomized, double-blind – single dose of either secretin or placebo.
"A single dose of intravenous secretin does not appear to have significant effects on either parents’ perception of autistic behaviors or language skills at 6 weeks after injection. Transient, marginally significant improvements in autistic behaviors may occur in some children."
A study of 64 autistic children. Randomized, placebo-controlled, double-blind – each child received either two doses of porcine secretin or two doses of placebo. "No evidence is provided for the efficacy of repeated doses of porcine secretin in the treatment of children with autism."
“Secretin hormone given daily in transdermal cream was associated with marked and sustained developmental progress in an aphasic two-and-a-half year old child diagnosed with autism.”
A study of 12 autistic children. Randomized, placebo-controlled, double-blind – single dose crossover study. Outcome measures included gastrointestinal problems.
"Statistically significant differences were observed on measures of positive affect and activity level following secretin infusion. In general, the autistic children did not demonstrate the improvements described in the initial retrospective report."
October 2001 – Dr. Walter Herlihy of Repligen Corporation (the company trying to get FDA approval to label its recombinant human secretin for the treatment of autism) gave a presentation at the "Defeat Autism Now!" conference in San Diego, CA.
In this presentation, he reported that the Phase 2 trials [Note: Phase 2 trials are intended to show that the proposed treatment is safe in the intended patient population] did not show a statistically significant difference (in safety or efficacy) between secretin and placebo. He argued that the criteria for statistical significance were "arbitrary" and that secretin had shown more effect on younger children with gastrointestinal problems like chronic diarrhea and constipation.
A study of 56 autistic children. Randomized, double-blind, placebo-controlled – crossover study of one injection of either placebo or secretin followed in four weeks by the opposite treatment.
"There was no evidence for efficacy of secretin in this randomized, placebo-controlled, double-blind trial."
2002
April 2002 – Repligen Corporation starts a Phase 3 trial of secretin in autistic children. Based on preliminary (and statistically non-significant) results from their Phase 2 trial, they focus the trial on children ages 32 – 59 months (2 ½ - 5 years) and looked specifically at gastrointestinal problems – primarily chronic diarrhea and chronic constipation.
April 5, 2002 - Repligen obtained FDA approval to market its brand of synthetic porcine secretin (SecreFlo TM) for use in pancreatic assessment.
A study of 6 autistic children. Randomized, placebo-controlled, double-blind crossover study. Each child received six injections – three placebo and three secretin – in random order every four weeks. "In this placebo-controlled study, multiple doses of secretin did not produce any symptomatic improvement."
A study of 19 autistic children, 5 with "chronic diarrhea". Randomized, placebo-controlled, double-blind crossover study – single injection of either secretin or placebo followed by the opposite treatment at three weeks.
Analysis of the entire group showed no statistically significant effect. Limiting analysis to the five (5) children with chronic diarrhea (but not the two with chronic constipation) gave statistically significant results.
A study of 85 autistic children. Randomized, placebo-controlled, double-blind – single dose. The children were divided into trios matched by age and communication level – one child from each trio received porcine secretin; one received synthetic (human) secretin and one received placebo.
"No evidence that either biologic or synthetic secretin provided amelioration of symptoms beyond placebo was observed. This held true when children with and without gastrointestinal problems were examined separately ."
December 20, 2002 – Victoria Beck and Dr. Karoly Horvath file a patent (#7,091,182) for "Method for assisting in differential diagnosis and treatment of autistic syndromes" which is described as "comprising the administration of a therapeutically effective, preferably intravenous, dose of secretin to an individual with autistic syndrome" and "an analysis of an individual’s blood and/or intestinal tissue for the presence of secretin and comparison of the level of secretin to known norms". This patent was later sold to the Repligen Corporation.
A study of 42 autistic children. Randomized, placeb-controlled, double-blind – crossover study. Each child received either placebo or secretin and then the opposite treatment at six weeks. "There were no significant differences in the mean scores on any measure of language, behavior, or autism symptom severity after treatment with secretin compared to treatment with placebo."
2003
A study of 62 autistic children. Randomized, placebo-controlled, double-blind – crossover study. "Five children showed clinical improvement in standard scores: two after HSS [human synthetic secretin] and three after placebo. There were no significant changes in gastrointestinal symptoms after HSS or saline placebo."
From Part II:
"At the conclusion of the study, parents were asked to guess their child’s group assignment. Twenty seven families guessed their child’s group assignment correctly and 27 guessed incorrectly."
September 2003 – Repligen stock trading at $7.47 a share on volumes of about 400,000 shares. Its cash value is estimated at about $1 per share.
December 2003 – Repligen stock trading at $4.37 a share on volumes of 740,000 shares.
2004
January 5, 2004 – Repligen announces that there were no significant differences between the treatment and placebo groups in its Phase 3 study of secretin for autism. This study – although Dr. Edelson seems unaware of the fact – focused on younger children and also looking at chronic gastrointestinal problems.
January 2004 – Repligen stock trading at $3.33 on volumes of over 2 million shares.
Early 2004 (exact date difficult to determine) – Dr. Rimland sends a letter to Walter Herlihy of the Repligen Corporation essentially denouncing their decision to declare that secretin was no more effective than placebo.
July 2004 – Repligen stock bottoms out at $1.62 a share on volumes of 200,000 shares.
2005
A study of 15 autistic children. Randomized, placeb-controlled, double-blind – crossover study. Transdermal secretin or placebo was applied daily to the backs of children for four weeks. After a six-week "washout" period, the groups switched treatments.
"Overall, there were no statistically significant differences in speech, sociability, sensory, and health scores for treatment versus placebo periods. In addition, there were no differences in such scores for children with a history of diarrhea."
November 2005 – Repligen Corporation starts a Phase 2 trial of secretin for the treatment of schizophrenia.
Present
September 25, 2008 – Repligen stock trading at $4.89 on volumes of 45,000 shares. The company has a little over 31 million shares outstanding.
Human vs Porcine Secretin:
Between 1998 and today, over 20 studies have been done (and published) to determine the effect of secretin on autism. At least nine (9) used porcine secretin and at least four (4) used human secretin. For the others, the methods section didn’t specify or was unclear (initially, only porcine secretin was available, so there was no need to specify). The results of the Repligen Phase 3 study have never been published.
Only three secretin studies (with a total of 23 subjects – really only 9 if you consider that Kern et al found a positive effect only among the 5 children with chronic diarrhea) found any effect on autism. At least twelve other studies – with a total of 609 children enrolled – showed that secretin had no effect in the treatment of autism. Despite this, Dr. Edelson is convinced that secretin "works" for autism. He attributes the discrepancy to the "fact" that the largest studies (by Repligen) used synthetic (recombinant) human secretin instead of the porcine secretin used in the earlier studies.
Well, he’s wrong on a couple of counts.
To begin with, many of the larger studies used porcine secretin – one even compared it to both synthetic (recombinant) human secretin and placebo (all three were equally effective).
Secondly, the difference between human and porcine secretin is only two amino acids out of twenty-seven. Only dogs have a secretin molecule that’s closer to ours than the porcine secretin. In addition, the two substitutions – aspartate for glutamate and serine for glycine – would have minimal effect on the function or structure of the protein. Aspartate and glutamate both have carboxylic acid side chains and serine’s higher affinity for water – compared to glycine – would be masked by the fact that it’s situated right next to aspartate, which is very hydrophilic.
In fact, if Dr. Edelson had bothered to check, he would have found that porcine and human secretin were found to be functionally interchangeable. Of course, he could have guessed that from the fact that porcine secretin was used in humans for years to produce the same effect as human secretin. Think about the "good old days" when diabetic people used porcine or bovine insulin. The few amino acid differences didn’t change the function of the insulin, although they did lead to a few people developing antibodies to bovine insulin.
On more thing to ponder before you go off to read Dr. Edelson’s editorial. There are only two manufacturers making secretin these days (in the US, anyway):
Manufacturers of human secretin:
ChiRhoClin – ChiRhoStim (human secretin - $415 per 16 mcg/160 U vial)
Manufacturers of porcine secretin:
Repligen – SecreFlo (porcine secretin - $425 per 16 mcg/160 U vial)
Both products are recombinant – meaning that they are made by bacteria or yeast that contain the gene for human or porcine secretin. Since there is no conceivable reason why Repligen shouldn’t use its "house brand" of human secretin (RG1068) for pancreatic imaging, I wonder if they are positioning themselves for a "replay" of the "secretin-cures-autism madness of a few years ago. Unlike Ferring in 1998, Repligen would be in good position to profit from a resurgent interest in PORCINE secretin.
The Gastrointestinal Issue:
Dr. Edelson is also convinced that his survey of parental impressions is correct about the effectiveness of secretin because the Kern et al (July 2002) study showed that (porcine) secretin was significantly more effective in children with autism AND chronic diarrhea.
Let’s examine this claim, shall we?
The Kern et al study looked at 19 autistic children and was a double-blind, randomized crossover study of a single dose of porcine secretin. Of the 19 children in the study, five (5) had chronic diarrhea. These five (5) children apparently showed more improvement that the others (in whom secretin was no better than placebo).
That’s right – Dr. Edelson is basing his defense of secretin on the results seen in five (5) autistic children with chronic diarrhea (five out of nineteen in the Kern et al study).
Just a few months after the Kern et al study came out, Unis et al published their study of porcine (that’s right – porcine ) and recombinant human secretin in autism. They had eighty-five (85) autistic children in their study (one third received porcine secretin) and concluded:
"No evidence that either biologic or synthetic secretin provided amelioration of symptoms beyond placebo was observed."
"This held true when children with and without gastrointestinal problems were examined separately."
So, a larger study (to be fair, only about 28 received porcine secretin) found no difference, even when looking at children with gastrointestinal problems.
And what about Dr. Edelson’s parent survey?
The parent survey that Dr. Edelson keeps referring to is posted on the ARI website. Parents fill it out and mail, fax or e-mail the form back to ARI. There is no attempt to get a representative sample of parents of autistic children and the "data" are inclusive to the beginning of the survey, several years ago. Here’s what visitor’s to the ARI website see when they look at the survey’s assessment of secretin (dated February 2008):
Intravenous secretin (468) Got worse: 7%; Got better: 44%; No change 49%
Transdermal secretin (196) Got worse 10%; Got better: 37%; No change 54%
To "help" the parents in their assessment of the various treatment options listed, the survey gives a ratio of the number of children who "got better" to the number who "got worse" - this completely ignores the children who had "no change", which is often a large number. Now, Dr. Edelson’s better:worse ratio makes secretin look like a magic bullet, with a better:worse ratio of 6.3 for intravenous secretin and 3.6 for transdermal secretin.
However, if we look at "better" vs "not better" (i.e. either no change or got worse), the numbers don’t look so rosy: 0.8 for intravenous and 0.6 for transdermal secretin.
As luck would have it, I happen to have saved ARI’s survey results from last year:
IV secretin (422) Got worse: 7%; Got better 45%; No change 48%
TD secretin (176) Got worse 10%; Got better 37%; No change 53%
If we use these numbers to "dissect" that past year’s activity, the survey reports from Feb 2007 and Feb 2008 show that, in the course of a year, ARI received reports that after treatment with IV secretin:
3 children got worse
3 children got better
39 children showed no change
This is about what you’d expect from a treatment that doesn’t work.
What I find particularly disappointing is that Dr. Edelson has a PhD in psychology and should know that his survey results are meaningless. He should also know how to read the scientific literature and interpret the data. There are all of these things that he should know , and yet he acts as though he was unaware of them.
I’ll let you draw your own conclusions about why Dr. Edelson is trying to breathe life back into this dead hypothesis. As for the validity of his arguments, I think Dean Yeager in Ghostbusters (I) said it best:
"Your theories are the worst kind of popular tripe, your methods are sloppy and your conclusions are highly questionable."
Prometheus
ADDENDUM:
I forgot to mention that Dr. Edelson, at the conclusion of his editorial on secretin, puts out a call for researchers willing to do a study of porcine secretin in autistic children with chronic GI problems. He offers ARI funding, but I doubt that he realizes how expensive such a study would be.
I’d be willing to act as Principle Investigator for such a research project, even though I doubt that negative results would get people to stop injecting (or rubbing) autistic kids with secretin. This passed from a scientific issue to a religious one years ago. Still, there’s nothing I love more than a futile effort in a lost cause.
I happened to mention this idea to the head of the university IRB (the body that approves and monitors human research) and asked her to give me an unofficial opinion on the study. I gave her the available published research and a brief outline of a study design. Her response, which appeared in my e-mail this morning, was that the IRB would not likely approve such a study for the following reasons:
[1] The published research indicates that there is no reason to suspect that secretin would be helpful in the treatment of autism (minimal to zero chance of benefit).
[2] There is a small, but non-zero, risk of harm.
[3] The study population is an "at risk" group (minor and disabled); they cannot give informed consent AND their parents are likely to be willing to accept risks that parents of "typical" children would not.
[4] The proposed research is unlikely to significantly increase the scientific knowledge on the subject. As a result, the risk to the subjects, although it is very small, would exceed the benefit of the knowledge gained.
Filed under: Autism Policy, Autism Practitioners, Myths About Science, Uncategorized | 17 Comments »
Let’s do a study!
July 19th, 2007
A reader wrote in with concerns that I was overlooking a key point of the abysmal telephonic autism “survey” - namely, showing how many unvaccinated children were available to study the interaction of vaccines and autism… or “neurological disorders” (AKA autism spectrum and ADD/ADHD).
Actually, I think that the folks at the CDC and university medical centers all over the country (and in other countries) are acutely (even painfully) aware of the number of people who aren’t vaccinated.
What GR and other advocacy groups have been agitating for is a study comparing groups that don’t vaccinate their children (e.g. the Amish, although they actually do vaccinate their children) with vaccinated children. The folks at GR are pushing for this despite the fact that their baloney “survey” showed no connection between autism and vaccination.
Here are a few reasons why that study wouldn’t work, followed by my own “modest proposal” for a study that would work.
[1] The unvaccinated population is not necessarily the same as the vaccinated population: People who don’t vaccinate their children may not be the same as those who do. In fact, studies have shown that those who don’t vaccinate their children tend to be at either end of the socioeconomic and educational spectrum. It would not be valid to draw any conclusions about the impact of vaccines on autism (or ADD/ADHD) with such marked differences between the groups (apples and oranges).
[2] Selection biases: Recruiting people for a study is one of the biggest sources of error, especially when looking for something that is a public controversy. You will tend to attract more people who believe in a connection than those who do not.
[3] Inadequate power: If the GR survey is correct, about 3% of the overall population in the 4 - 17 year age range is completely unvaccinated. On the other hand, the prevalence of autism is only 0.65% in the same age range. It will be easier to detect a statistically significant difference in unvaccinated children between autistic and non-autistic groups than it will be to detect a difference in autism prevalence between vaccinated and unvaccinated children.
[4] Loss of useful information: It would be a shame to spend the time and money to do a study and only be able to answer a single question. After all, if there is no connection between autism and vaccination - as the GR “survey” suggests - wouldn’t it be nice to be able to “mine” the data for other possible connections? By looking for subjects based on their vaccination status, the only question that can be answered is whether there is a correlation between the two.
My Modest Proposal:
This is a study that could be done rather quickly and with a minimum of expense. It would eliminate many of the sources of bias and would fairly easily generate balanced study populations that would be a good match to most of the general population.
[a] Contact a large HMO with actual facilities (e.g. Humana or Kaiser) and arrange to get access to their patient medical records. This is routinely done, although the HMO will want assurances that patient confidentiality will be maintained.
[b] Obtain a list of patients with autism diagnosis in the proper age range (I would suggest 6 - 12 years).
[c] Select one thousand of these patients at random. This would allow you to detect a difference if the prevalence of unvaccinated children is less than 1/3 that in the general population (alpha error level 5%, beta error level 5%). If the difference is less than that, you’ll need to select more subjects.
[d] Confirm the diagnosis by having a child psychiatrist or psychologist review the records.
[e] For each of the remaining children, select a non-autistic control child from the HMO database that is of the same age, sex, geographical region, etc.
[f] Determine how many of the children in each group have received all, none or some of their vaccinations (keep track of which vaccines, when, etc.). If the GR “survey” was right (a very big “if”) about the number of children unvaccinated, each group should have around 30 unvaccinated children, unless there is a correlation between vaccination and autism.
[g] If the autism and non-autism groups have statistically significant differences in their vaccination rates, then a correlation can be claimed. If the study shows no correlation, then the relative risk is less than 3. You’d have to have twice as many subjects to bring the minimal relative risk to below 2.
Using HMO patients eliminates any issues of affordability (which is minimal) or access to health care. Although the population of people who have HMO coverage is not necessarily the same as the overal US population, using the case control design ensures that the two groups are as similar as possible.
This study could have been done in the time - and for the reported cost - of the GR “survey”. If they had done a real study - like the one I’ve outlined above - the answer would already be here.
If anybody would like to fund such a study, please contact me. If I can’t find anyone else to do it, I’d be willing to coordinate it myself.
I doubt that any of the federal funding agencies will be interested in funding this study - not because of any conspiracy, but because the only people who want the study will probably not believe the likely outcome (i.e. no association - just as in the GR “survey”).
So, this is my challenge to those who want this study: if you want it, do it. The advocacy groups have the money - all they need to do is find the will to take a chance. And make no mistake - this is a risk. There is a better than even chance that the study - if it isn’t “fudged” - will show no correlation.
If they really want to know, they can find out for less than the cost of a full-page ad.
Prometheus
Filed under: Uncategorized | 27 Comments »
Survey says….. Nothing!!!
June 27th, 2007
Generation Rescue just published their long-awaited telephone survey results that showed - surprise! - that vaccinations cause autism.
Well, actually, it doesn’t really show that vaccines cause autism, what it shows is that vaccines cause “neurological disorders”, loosely defined as autism (or autistic spectrum disorder) and/or ADD/ADHD.
Except that it really doesn’t show that, either.
So what does the survey show? Well, let’s just take a look.
Not surprisingly, they did not publish the questions they asked, which would have given us the opportunity to analyze their survey for systematic bias. What they did do was publish the raw data, which allows us to analyze their results.
Assessing the survey:
When looking at a survey, the first step is to examine the survey structure - particularly the questions, but also the area covered and population contacted - for any flaws or biases. This survey was conducted in nine counties of California and Oregon - generally the more populous counties - which gives it a West Coast bias. Since autism, ADD/ADHD, asthma and diabetes do not show a coastal preference, this bias should not create a serious problem for the survey.
Next, looking at the data, we need to see if there are age or sex biases. Since the data do not include a detailed breakout of the ages year-by-year, it is impossible to analyze for age biases, but the sex ratio (52% male, 48% female) - although it is close to the US Census Bureau data for that age range - shows a statistically significant difference from the US population.
Looking at the sex ratios of the unvaccinated and vaccinated (both fully and partially) groups, the differences are not statistically significant, so the imbalance in the sex ratio is equal in both groups.
It would be helpful to know how many people they had to call to get the number of responses they did - this gives a good measure of how skewed the responses might be. The higher the percentage of people refusing to take the survey, the more likely that the people who do answer are not a representative sample of the population.
Unfortunately, we are not provided this information, so we have no way of knowing how many of the people who were called hung up or otherwise refused to participate, which makes it impossible to know the degree of participation bias. We’ll just have to soldier on.
Assessing the data:
Looking at the data, one thing that pops up as an immediate red flag is that the prevalence of autism is greater than the prevalence of PDD-NOS. This is an inversion of the usual finding, which is that autism (with stricter diagnostic criteria) is less common than PDD-NOS (which is essentially some of the criteria for autism but not enough to diagnose autism). This suggests that the people involved in the survey may not be asking the right questions.
Looking a bit closer, the prevalence of the autistic spectrum disorders is way out of line with the most recent data. In February of this year, the CDC published a report on the prevalence of autism in six states. This prevalence was widely reported and was frequently cited as more evidence of the “autism epidemic” by the chelationistas, so it should be familiar.
This CDC report found that the prevalence of autistic spectrum disorders ranged from 4.5 to 6.5 per 1000 children, which would be 0.45 - 0.65%.
The GR survey found that the prevalence of autistic spectrum disorders was 4.7% in their overall sample and ranged from 1.3% (female, fully vaccinated) to 8.4% (male, partially vaccinated). This is nearly ten times the CDC prevalence.
To put the number into perspective, the CDC data say that somewhere between 1 in 222 to 1 in 154 children have an autistic spectrum disorder. The GR survey would suggest that 1 in 21 children have an autistic spectrum disorder. Ridiculous!
Clearly, there is a serious problem with this survey.
This is reminiscent of the infamous Holmes et al study, which found that their control subjects had over ten times the amount of mercury in their hair than the NHANES study found in children of similar ages less than a year later.
Now, the people who ordered this survey may argue that it’s the difference between the two groups - not the absolute number - that is important. This sounds reasonable, but it isn’t. There is no way to know if the degree of error is the same in all the groups.
If the “over-reporting factor” is only 5% less in the “unvaccinated” group than in the other groups, the difference between the groups disappears. This completely invalidates the “results”.
So, with this glaring evidence of error, is there any point in looking any further?
No, not really. But we should examine the major claim being made about the survey results, just to be thorough.
“Vaccinated boys have a 155% greater chance of having a neurological disorder like ADHD or autism…”
Let me start off by saying that - even if the survey was accurate, which it clearly is not - an increase in autism and ADD/ADHD would not constitute an increase in “neurological disorders”, which their conclusion implies. There may, in fact, be neurological disorders (e.g. measles inclusion-body encephalitis) that are reduced by vaccination. So, even without looking at the data, this assertion is pure nonsense.
But, back to the survey data.
To get a statistically significant difference between the unvaccinated and vaccinated boys, they had to lump the partially vaccinated and the fully vaccinated boys together and they also had to lump autism, PDD-NOS, Asperger’s syndrome, ADD and ADHD together.roups, with the partially and fully vaccinated boys having - as a group - 55% more reported “neurological disorders”.
However, if you look at the “autistic spectrum disorders” by themselves, there is no statistically significant difference between unvaccinated and vaccinated (partially plus fully) boys.
Curiously, there is a statistically significant difference between the partially vaccinated boys and both the unvaccinated and fully vaccinated boys. Partially vaccinated boys have a higher prevalence of autistic spectrum disorders than either the unvaccinated or fully vaccinated boys.
Now, if you want to show that an exposure causes a disorder, it is generally a good idea to show a dose-response relationship. In the case of this survey, a little vaccination is worse than none or a lot. This doesn’t sound like a dose-response relationship to me.
Well, so the autism-vaccine connection doesn’t work - how about ADD/ADHD?
Out of 17,674 children in the survey, 1,875 had either ADD or ADHD. That works out to a prevalence of 106 per thousand or 10.6%.
That seems a bit high.
If you look at the USDE data from 2005, the percentage of children ages 4 - 17 years with “other health impairment” (the catch basin for ADD/ADHD and many other disorders) was 9.5 per thousand or 0.95%. This is over ten times lower than reported in the GR survey. And remember - the USDE “other health impairment” category includes a variety of diagnoses other than ADD/ADHD.
So, it seems that there are some serious problems with the GR survey data. I don’t know what the cause of the problem is (although I have my suspicions), but one thing is painfully clear:
The survey data is garbage.
So, what does the GR survey show?
Absolutely nothing.
Prometheus
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The Next Revolution?
May 29th, 2007
As the chelationistas rediscover/redefine/remarket themselves, surely there are parents who are feeling a little misled, deceived or perhaps even exploited. Maybe it’s time for another “revolution” in autism? And this time, it’s the chelationistas who need to be overthrown.
For years, the various organizations representing the chelationistas have been telling parents that they are their advocates, that they respect parents, listen to parents and learn from parents. It’s the “other side” - the doctors, “the government” and, worst of all, Big Pharma (cue spooky music) that lies to parents, disrespects parents, ignores parents.
Now, it turns out, the chelationistas are admitting that they don’t respect parents - they don’t even trust the parents’ intelligence enough to tell them the whole truth. And telling less than the whole truth is….that’s right; lying.
The chelationistas are now claiming that they knew all along that autism wasn’t just mercury poisoning - despite earlier claims to the contrary (see here, also). The fact that they didn’t tell parents is explained as “not wanting to confuse the issue”. Or, it could be argued, not wanting to risk losing parents’ support on a complicated and complex issue.
So, the chelationistas respect parents, but not enough to tell them the truth.
And the chelationistas listen to parents, but don’t hear them when they say, “we want the facts”.
And the chelationistas learn from parents, but only in order to better market their product.
Many people may now find themselves unsure when the chelationistas are telling the truth (hint: only when their lips aren’t moving).
After all, if it is true - as the chelationista revisionistic propaganda says - that the chelationistas hid the full scope of possible causes of autism from the parents, then those parent have the right - no, the duty - to ask a simple question:
In other words, they are claiming that they lied to parents in order to further the chelationista movement.
Funny - that’s pretty much what the chelationistas accuse the government and “mainstream medicine” of doing.
Of course, another possibility is that the chelationistas really did believe that mercury caused autism (and may still believe so) but are afraid that parents will start to doubt them as the mountain of data refuting the mercury-causes-autism hypothesis bears down. So, in order to keep from looking like uninformed dolts, they lie about having known “all along” that autism was “more complex than just mercury poisoning”.
Either way, the chelationistas have been caught in a lie.
Now, the majority of parents caught up in the chelationista’s web will buy the “clarification” and will not be offended by the blatant condescension that it contains. A few will have their eyes opened and will leave. Most will leave quietly, burning in silent resentment, but we can only hope that a couple of parents are angry enough at this travesty to lead a revolt.
After all, the only way to bring down a cult is from the inside.
I have a theme song in mind for this revolt:
Devo, Jerkin’ back ‘n’ forth
(from the album “New Traditionalists”)I know I let you tell me what to do
You were confident, you knew best
Now things aren’t working like you want them to
Your confidence is what I detestYou got me lookin’ up high
You got me searchin’ down low
You got me - I know you know
You got me jerkin’ back ‘n’ forth
That pretty much sums it up, doesn’t it?
It’s time for parents of autistic children to stand up and say they won’t be manipulated, deceived or dismissed - not even by organizations that claim to represent them. It’s time for parents of autistic children to demand the truth - especially from organizations that claim to represent them.
It’s time for a new revolution.
Prometheus
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A Crisis of Faith or "Bait and Switch"?
May 19th, 2007
Over the past year, I’ve noticed an odd trend among the supporters of the mercury-causes-autism hypothesis. It began gradually, as trends often do, with a few seemingly random phrases like “…and other toxins…”, “…and environmental exposures…”, “…other vaccine components…”, “…formaldehyde, aluminium and benxyl alcohol…” and “…viruses and bacteria…”.
But now, the shift in emphasis is unmistakeable. Kev, Orac and others have blogged about specific attempts at historical revisionism among the chelationistas, but I’d like to assess the “bigger picture” and what it means to the hypothesis-formerly-known-as-mercury-causes-autism.
For those who are not intimately familiar with the daily ins and outs of the chelationistas’ arguments (you lucky people!), the Central Dogma of the chelationista faith has been - since the infamous Bernard et al paper, in which a group of people who had never seen mercury poisoning compared it to autism - that mercury causes autism. Period. Full stop. The end.
Apparently, that is no longer true.
In a move reminiscent of George Orwell’s 1984, the chelationistas have changed their minds about mercury being the cause of autism, but they are claiming that they haven’t actually changed their minds - they’re simply “clarifying their position”.
That’s newspeak for “the data don’t support our position, so we’re doing our darndest to keep from having to admit we were wrong.”
So, what does cause autism, according to the chelationistas?
- “Heavy metals” (does this include Def Leppard?)
- Aluminium (not a “heavy metal”)
- Live viruses
- Bacteria
- “Maternal toxic load” (perhaps from watching Oprah?)
- Antibiotics
The advantage of this “clarification” (translation: “obfuscation“) is to make it impossible (or at least highly impractical) to ever prove them wrong. Let me demonstrate.
In order to show that the mercury-causes-autism hypothesis was wrong, we just needed to show that there was no correlation between mercury exposure (i.e. thimerosal exposure, environmental mercury, etc.) and autism. While correlation does not equal causation, a lack of correlation is essentially equal to a lack of causation.
That was relatively easy to do, although many of the chelationistas are still struggling with that unpleasant lump of reality.
However, in order to definitively squash the new “heavy metals”-aluminium-live viruses-bacteria-etc.-cause-autism hypothesis, you would need to explore all possible combinations of these “exposures”. If you don’t, it is a sure bet that the next “hypothesis” will be that the one combination you didn’t check is the real cause of autism.
Just like mercury was… until it wasn’t.
So, how many combinations would that be? It seems simple enough - there are only six items on the list. Except that some of the items are a bit broad.
You could lump all “heavy metals” together (if you can get a ruling from the chelationistas on exactly which metals are included in this group), which would leave you with a manageable number, right?
The “live viruses” could just be the ones in vaccines, or they could be any live virus that the chelationistas care to claim (without having to provide data) are in vaccines. Or they could be any live virus in “the environment”. It is a number with a great potential for flexibility.
“Bacteria” is another ambiguous category. Are they referring to the killed bacteria in vaccines, or will they want to expand that into all environmental bacteria (a number in the millions, if not billions)? Or will they want to reserve the right to claim that vaccines - or any other product with a manufacturer they can sue - are contaminated with bacteria that only the DAN! doctors and their faithful laboratories can detect?
Of course, the “maternal toxic load” is another extremely broad (one might even say deliberately vague) category. We’d need to get a ruling from the chelationista high court on which “toxins” they have in mind. And we’d better get that in writing, in case they try to “clarify their position” later. I suspect that this is another “trapdoor” they’ve left in their new “hypothesis” in order to allow them to escape again.
Simply defining the problem is impossible, given the vague and fuzzy nature of the new “causes of autism”. And even if we were to get the problem defined - and get it to stay defined - there is another factor to consider.
If we were to assume (naively) that there were only six variables to examine, how many combinations would that make? If we have n items (”n” is a variable) and we group k (”k” is another variable) of them at a time, the number of possible combinations (where order doesn’t matter) is: [see here for a tutorial]
n! / (n - k)! k!
(the “!” stands for “factorial”)
But, we have to count all possible combinations, including groups from one to six of the possible causes. This gives us a grand total of sixty-three (63) possible combinations.
And that’s what we get by considering “heavy metals” and “maternal toxins” as one category. What happens if we expand “heavy metals” to the “big five” of toxic metals (mercury, lead, arsenic, cadmium, antimony)?
Total combinations = 1023
And if we expand “maternal toxins” to include the five toxic metals?
Total combinations = 16,383
Mind you, we haven’t even begun to exhaust all of the potential “maternal toxins”, “live viruses” or “bacteria” - the potential number of those could be in the thousands, if not the millions.
So now you see the shrewd cunning of the chelationistas. By making their “position” more vague, they have ensured that they will never again find themselves in the bind they are now. Never again will science be able to say - with any certainty - that the chelationistas’ “hypothesis” about the cause(s) of autism is unfounded.
That’s because it is practically untestable. It is not absolutely untestable - if we were to commit the entire scientific resources of the world to searching various combinations, it would probably take slightly less than an infinite amount of time to check them all. But it will never happen.
And that’s exactly what the chelationistas want.
Prometheus
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