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2011 – The Last Year For ARI’s DAN! Doctors

2 Jan

As late as just a few months ago, The Autism Research Institute (ARI), promoted their upcoming Fall 2010 Defeat Autism Now! conference in a monthly newsletter. Note the name of the conference:

“Fall 2010 ARI/Defeat Autism Now! Conference”
http://www.ariconference.com/enews/enewsletter_201010.html

Now look at ARI’s promotion of their Spring 2011 conference.

“Spring 2011 ARI Conference
(formerly known as Defeat Autism Now!)”
http://www.ariconference.com/enews/enewsletter_201011.html

Do you see the difference? It’s pretty hard to miss. What about all those practitioners (physicians, nurses, chiropractors, nutritionists, naturopaths, and homeopaths, etc.) who want to participate in the “DAN! Physician Training”, you know, become “DAN! Practitioners”? How does one become a DAN! doctor, if Defeat Autism Now! is a former identity?

A quick look at the ARI Conference website answers that right away.

The Autism Research Institute Conference Formerly known as Defeat Autism Now!

The practitioner seminars are still part of the conference. But there’s something potentially newsworthy here too.

As of 12/31/11, ARI will no longer be maintaining a clinician registry (a.k.a “the DAN list”). No new names will be added to the registry in 2011.

Source

You read that correctly – no new names in 2011, and at the end of this year, it’s over. No more list of DAN! Doctors.

According to ARI’s website, one is best served in finding a “talented clinician” by way a support group – local, or you know, out there on the interwebs.

As recently as 10 years ago it was nearly impossible for parents to find clinicians who approached treating patients with autism from a medical point of view, so ARI started keeping a clinician registry (the “DAN list”). We tried a number of measures to ensure that every clinician on our list provided high-quality care, but we are a small non-profit with limited resources. We have determined that those seeking a talented clinician are best served by connecting with support groups—either locally or online—instead of choosing from a list that cannot be vetted.

Source

I’m not sure what they mean by having tried “a number of measures to ensure that every clinician on our list provided high-quality care”. I understand that there were special “clinician training” sessions at DAN! conferences in the past, but as far as I understood it in the past, becoming a listed DAN! practitioner might have required little more than attend a conference, sign a statement pledging to “conduct their practice in accordance with DAN! philosophy”, and ask to be listed. Although I could be wrong, I find it incredibly difficult to believe that there were in fact any significant measures taken by ARI to ensure the provision of high quality care by clinicians on its list. I seem to recall that Roy Kerry was added to ARI’s list of DAN! practitioners in 2006 after the death of Tariq Nadma in 2005.

ARI’s notes and disclaimers for the remaining year of life for the list of DAN! doctors seem pretty careful:

If someone claims to be “DAN-certified,” they’re overstating; neither ARI nor Defeat Autism Now! has ever had a certification program.

The following are practitioners who have asked to be listed as providing Defeat Autism Now!®- based interventions for patients with autism. Most are physicians, others are licensed health-care professionals in related fields.

ARI has no means of certifying the competence nor quality of practice of any practitioner. The lists are provided as a community service. The Autism Research Institute disclaims and does not endorse or support any individual or entity listed; makes no representations, warranties, guarantees or promises on behalf of or for those listed, and assumes no liability nor responsibility for any service or product provided. ARI does not ‘certify’ practitioners or guarantee competence, skill, knowledge, or experience.

Source

So is that it? Is this really the end of DAN! doctors in less than a year? Isn’t there a D-List celebrity with apparent anti-vaccine leanings , who can save (or may have already saved) the day for all the poor physicians, nurses, chiropractors, nutritionists, naturopaths, and homeopaths who need be available to all those parents who are desperate to recover an “epidemic” of kids from autism, mercury poisoning, or “vaccine-induced” whatever?

Aha! Jenny McCarthy’s Generation Rescue! Where, from the home page, a parent can click on “Find A Doctor” and learn about the NGMD’s.

JMGR

What’s an NGMD according to Jenny McCarthy’s Generation Rescue?

Answer: According to Jenny McCarthy’s Generation Rescue website, an NGMD is a “New Generation Medical Doctor”, and “These clinicians share Generation Rescue’s ideologies, practices, and philosophies of treating the underlying medical issues of individuals with autism.”

Source

I think this is potentially an interesting development, because in the past, a parent brand-new to an autism diagnosis might have assumed scientific credibility from a movement’s (Defeat Autism Now!) list of practitioners associated with a name like “Autism Research Institute”. If nothing, ARI is a scientific sounding name. I don’t think that’s as likely to be the case for the “NGMD’s”, who could be seen by many as simply associated with a fringe anti-vaccine group promoted by Jenny McCarthy.

What do you think?

Safeminds defends treatments the FDA deemed “dangerously misleading”

18 Oct

The United States Food and Drug Administration (FDA) recently announced that they had sent warning letters to eight groups who were promoting chelation products without prescriptions and with unproven claims of efficacy.

Chelation is a mainstay of many alternative medical practitions, especially in autism. There is a hypothesis that autism is caused by mercury poisoning. Autism symptoms don’t look like mercury poisoning and multiple studies have been performed testing the hypothesis and shown no link. But the idea lives on. Autistics, mostly children, are subjected to chelation “therapy” to remove heavy metals from the body. After over a decade of this practice, there is still no demonstration that chelation does anything to help autistics. There are studies on Peruvian hamsters which are used to support the idea that autism is caused by mercury poisoning. No, seriously, one of the supports for the mercury/autism link is a study on Peruvian Hamsters. Just goes to show how tenuous the “science” backing chelation is.

Here is part of the FDA statement:

Federal regulators are warning eight companies to stop selling so called ‘chelation’ products that claim to treat a range of disorders from autism to Alzheimer’s disease.

The Food and Drug Administration (FDA) says the companies have not proven their products are safe and effective in treating autism spectrum disorder, cardiovascular disease, macular degeneration, Parkinson’s disease or any other serious illness. Some of the companies also claim their products can detect the presence of heavy metals in the body in an attempt to justify the need for chelation therapy.

One of the more vocal organizations promoting the mercury/autism “link” is a group called SafeMinds. So it isn’t a surprise that they would respond to the FDA warnings..

Here is the opening paragraph from the SafeMinds response:

The FDA issued a media release and held a press conference on over-the-counter chelating products. A recording of the press conference was made available this afternoon (recording available at 800-839-7073). FDA issued warning letters to 8 companies promoting over-the-counter nutritional supplements for chelation therapy (HERE). Chelation is a method of removing heavy metals from the body. The FDA warning has no bearing on prescription chelation drugs which are used under the supervision of medical professionals.

“Nutritional Supplements”? How does a chelator count as a “nutritional supplement”? The human body does not produce chemicals like DMSA which are used for chelation. SafeMinds is well aware of the falacy of the “nutritional supplement” argument after the recent debacle over the chelator turned “supplement” OSR, which had to be pulled from production.

So, SafeMinds starts downplaying the fact that chelators are drugs and, as such, should be regulated.

But they quickly change the tune and acknowledge that these are drugs: “The FDA warning has no bearing on prescription chelation drugs which are used under the supervision of medical professionals.”

As I read this, I had to ask myself “Why did SafeMinds chose such imprecise language?” Let me explain:

Assume a medical professional, say a chiropractor or a nutritionist, “supervises” my use of the prescription drug DMSA, but sells the drug to me without a prescription (as these professionals can not write prescriptions). That would fit into the SafeMinds interpretation, but is clearly not the intent of the FDA statement.

Here is an accurate statement: The FDA warning does not have bearing on the use of chelation drugs prescribed by and supervised by a medical professional.

Continuing with the SafeMinds statement:

In its press conference, the FDA implied that chelation products were being used by parents of children with autism without a doctor’s supervision, but on questioning by reporters, FDA representatives were unable to back up the claim with any evidence of use of OTC chelation products by autism parents or of their use without medical supervision. The FDA asserted that the OTC products being promoted were dangerous and could lead to kidney damage, dehydration and death. On questioning by reporters, the FDA admitted that it had received no reports of adverse reactions to the products or to chelation in general, other than 1 death 5 years ago which was due to a medical error and in which a prescription drug was used.

Note that SafeMinds chose their words carefully. They don’t state that the practice doesn’t occur. SafeMinds just states that the FDA didn’t have the evidence on hand of the “use of OTC chelation products by autism parents or of their use without medical supervision.”

Is Safeminds so out of touch with the online autism community that they can’t find groups promoting over-the-counter (OTC) chelators by autism families? The practice is common. Surely SafeMinds members peruse the exhibitor booths at the parent-conventions (like Autism One).

Google search: “how to buy DMSA without a prescription”. Lot’s of hits.

Here is hit #2: dmsachelation.com/autism/. Pretty clear they are targeting autism treatment there, just from the URL. The blurb on Google for this site? “This page IS intended to show you where to buy DMSA without a prescription. You can get DMSA prescribed, however the cost will range from $2-3 per pill. …”

I didn’t capitalize “IS” in that statement, they did. They wanted to emphasize that one could buy chelators without a prescription.

SafeMinds states that the FDA has received no reports of adverse events from chelation in general. I find this odd. The FDA must not follow online autism parent groups such as those on Yahoo. The FDA must not have read transcripts of the Omnibus Autism Proceeding, which included a description of a child who regressed after being given chelation therapy (under the watchful eye of a prominent alt-med doctor). The FDA must not have performed a google search on chelation deaths with site set to CDC.gov.

First hit, “Deaths Associated with Hypocalcemia from Chelation Therapy — Texas, Pennsylvania, and Oregon, 2003–2005“.

When it comes to the question of “why” adverse events are not commonly reported I am again reminded of the OSR fiasco. The company that sold OSR specifically told their clientele to contact the company in case of adverse reactions. No mention was made of contacting the FDA (which can be done here). I guess I could search the websites of the groups that promote OTC chelators to see if they inform their clients of the ability to report their drug/supplements to the FDA. Somehow I feel confident that I would be able to find groups (possibly many or most) do not give that information.

SafeMinds posted their statement on the blog they sponsor, The Age of Autism. Another sponsor of that blog is Lee Silsby, a compounding pharmacy. They list chelators such as DMSA and EDTA under the category “autism treatments” (Specialties | Autism Treatments | Transdermal DMSA Cream, or Specialties | Autism Treatments | EDTA (calcium)). Not under “heavy metal poisoning” treatments, autism treatments.

The Autism Research Institute, a group which promotes much in the way of alternative medicine as therapies for autism, has a chart that is often used to promote chelation. In their survey, they claimed that over 70% of parents reported that their child got better with chelation. The survey has been often criticized as being unscientific and very biased. Even with this biased sample, 3% of parents reported that their child “got worse” with chelation.

A couple side notes are worth mentioning. First, in that survey the ARI list chelation under “Biomedical/Non-Drug/Supplements”. Non drug? Supplement? I doubt the FDA will agree. Second, the ARI survey lists secretin therapy as beneficial for autism. Secretin hit the news in the 1990′s as a potential autism therapy and has since been shown to be no more effective than a placebo. The survey is very, very biased towards “biomedical” treatments.

Surely SafeMinds is aware of this survey. As in, definitely they are aware of it. Just as Safeminds are certainly aware of the child in the Omnibus proceeding who suffered after chelation. But SafeMinds pretend as though there are no adverse reactions. It is disingenuous, to say the least.

SafeMinds ends their statement with this paragraph:

SafeMinds agrees with the FDA that products being promoted as drugs and biologics should have thorough and unbiased assessments for safety and that parents should work with their healthcare professionals when considering health interventions. SafeMinds feels that FDA has tried to cast autism parents in a negative light without any supporting evidence, by implying that autism parents were giving their children dangerous products without medical oversight. Only on questioning by the media did the FDA have to back off from its wild claims. SafeMinds feels the FDA owes the autism community an apology.

Basically, SafeMinds have taken the Human Shield defense. Rather than actually discuss the facts, SafeMinds attacks the FDA for “wild claims” and claims that the FDA owes the autism community an apology.

From the perspective of this autism parent I would say, yes, the FDA owes us an apology: for taking so damned long to address this issue. The abuse of chelation as a “treatment” for autism has been going on for many years. It is about time that the FDA cracked down and made the “wild claim” that a prescription drug should be given by perscription.

Heck, the FDA isn’t even making the “wild claim” that toxicology treatments should be performed by toxicologists. Just someone with a prescription pad.

Why isn’t SafeMinds telling autism families to seek out medical toxicologists to test and treat heavy metal poisoning? The answer is painfully clear. The methods of diagnosis and treatment that groups like SafeMinds promote do not compare to the methods used by those trained specifically to treat heavy metal intoxication.

Should make one pause to wonder.

Nature Fubar

13 May

Nature, the usually reputable Science magazine have launched a Scitable Autism section and with it screwed up their usual impeccable attention to detail.

Who for example thought it necessary to put:

Determining the cause of — and the cure for — autism is crucial for our society

I wonder. And who thought it necessary to link to no less than three anti-vaccine links on the home page of this….blog? Wiki? Two links to Autism Speaks whose controllers recently attended a DAN! conference and one link to ARI itself.

Its a ridiculous and desperately sad state of affairs when even Nature, that bastion of good science resorts to scaremongering about autism and promoting an anti-vaccine viewpoint.

Listen to parents…except when they say things you don’t want to hear

25 Mar

How many times do we hear, “Listen to the parents” on medical issues involving their autistic kids? Usually this comes from alternative medical groups who don’t have the science to back up the safety and efficacy of their therapies. What happens when a parent disagrees with these groups?

In Lawsuit against alternative medical practitioners Usman and Rossignal we discussed a father who has brought suit against prominent Defeat Autism Now (DAN) doctors Usman and Rossignol, and the laboratory Doctor’s Data.

Orac, at Respectful Insolence, has discussed this case as Suing DAN! practitioners for malpractice: It’s about time, where he uploaded the actual complaint.

In that complaint the father is alleging many things. High amongst them is the question of whether the “challenge” chelation tests are valid, These were used on his child and supposedly showed heavy metal poisoning. In a challenge chelation test, a chelator drug is given to a child before a urine test is taken. Chelators are designed to draw metals out of the body and allow them to be excreted through the urine (and other ways). There are no standardized references for metal contents in challenge testing. The American College of Medical Toxicology has made a very clear statement about challenge chelation testing. Here is their conclusion:

It is, therefore, the position of the American College of Medical Toxicology that post-challenge urinary metal testing has not been scientifically validated, has no demonstrated benefit, and may be harmful when applied in the assessment and treatment of patients in whom there is concern for metal poisoning.

Recall, challenge testing is noted in the lawsuit. From the section of claims against the Doctor’s Data (who are also defendents in the lawsuit):

The non-standardized method of testing that Defendant utilized on or about April 22, 2004, January 27, 2006, January 13, 2007, February 26, 2007, May 26, 2007, August 6, 2007, October 30, 2007, November 13, 2007, January 12, 2008, January 26, 2008, April 26, 2008, October 29, 2008, and March 27, 2009, wherein specimens were collected after the administration of a provoking agent and compared to unprovoked or unchallenged specimens was an improper method of determining whether A.J. had a potentially toxic level of heavy metals in his system

So, challenge chelation testing isn’t scientifically validated, has no benefit, but was used to justify certain therapies on this child. How did the Autism Research Institute respond to this? They blame the parent’s marital situation.

No, really, I’m not making this up. Rather than accept the complaints on their face and give this autism parent respect, they dismiss his multiple complaints as being…well, you read it:

Recent articles by ABC News and the Chicago Tribune on M.D.s who subscribe to the Defeat Autism Now! approach to treatment indicate the spread of misinformation and misunderstanding in recent months. The complaints about Drs. Usman and Rossignol resulted from a custody case– a painful situation for any family, one that can lead to accusations that must be sorted out in a court of law—not the media

Yes, it isn’t because the father is really annoyed that he was told challenge chelation testing is valid, or that his family spent lots of money on testing and on chelation. It couldn’t be that the father has not seen benefit from these therapies. It isn’t any of that. It is a custody battle issue. For the record, the defendants in the case do not include his wife.

ARI defends their approach in rather vague terms:

The Defeat Autism Now! approach to autism invites the medical community to be more responsive, inquisitive, and knowledgeable about treating these disorders.

The approach is not in itself a source of controversy, since many treatment interventions are commonly prescribed by traditional health professionals.

My view differs from the ARI statement. It would seem to this observer that the approach is the source of controversy. From their own website:

The best diagnostic test for toxic metal overload is the chelation challenge test. The chelation drug is administered, followed by a timed urine test to help assess the body’s burden of toxic elements.

This is in direct contradiction to the statement from the American College of Toxicologists. The ARI approach (including challenge testing) is a key point of the lawsuit. I am not able to reconcile this with the idea that the “approach itself a source of controversy”.

The great problem is rather that chronic, unaddressed illness plagues many, if not most, of the children and adults on the autism spectrum. These conditions, thoroughly documented in the scientific literature, often involve the gastrointestinal system and/or the immune system, but the medical establishment has been professionally insensible to what is a desperate situation in the expanding autism population.

Odd. If anyone outside of the alternative medical community ever makes a statement that the is driven by “desperation”, they are sure to get jumped on.

The focus of the Defeat Autism Now! approach is twofold: to provide patients with allergen-free nutritional support, to uphold and to repair the immune system as needed, and, if appropriate, to reduce the body burden of environmental toxins; to provide clinicians in-depth medical and scientific information, with Continuing Medical Education credits.

There is the mention of what is a main crux of the lawsuit, “body burden of environmental toxins”. That’s it. No mention of challenge testing. They mention that the approach includes reducing “the body burden of environmental toxins”, but doesn’t address the key question: when is this approach “appropriate”. How is that decided? The challenge testing approach has not, to my knowledge, ever been defended in court. This case is

The ARI press release doesn’t discuss the real questions here. Brushing this off as a custody issue is not doing anyone any good and is rather insulting to the parent bringing this suit forward and his child.

Lawsuit against alternative medical practitioners Usman and Rossignal

5 Mar

A lawsuit has been filed in Chicago claiming that a child has been harmed by the treatments prescribed by Dr. Dan Rossignol and Dr. Anju Usman.

This is being reported in a story, Father of 7-year-old autistic boy says treatment harmed son. (also now on the Chicago Tribune’s website)

Doctor’s Data has also been named:

Coman also alleged that Doctor’s Data Inc., the St. Charles laboratory that performed the tests Usman and Rossignol used to justify these treatments, was negligent for using an “improper method” of testing.

We here at LeftBrainRightBrain have commented many times about the concept of “challenge” testing to “prove” heavy metal toxicity.

The suit spotlights a test often used to diagnose metal poisoning in children with autism. To conduct the test, doctors give children a chelation drug that forces the body to let go of some of the metals that exist in everyone – healthy or sick – in trace amounts. Those metals show up in urine, which is sent to a lab for screening.

In the case of Coman’s son, Doctor’s Data then compared those drug-provoked results to a reference range calculated for people who had never been given a chelation drug. Based on this apples-to-oranges comparison, Coman’s son was found to have elevated levels of lead, aluminum, tin and mercury – some with results Doctor’s Data listed in the “90% range of metal contamination,” according to the lawsuit.

According to the story, there are no comments from Doctor’s Data, Dr. Rossignol’s office nor Dr. Usman’s office.

Age of Autism to Autism Families: Make your children suffer

24 Nov

Your pretty red house is engulfed in a roaring fire. You keep feeding the fire. Maybe petrol will help. Pour it on. Maybe some oil. Pour that on too. You don’t know. Nobody knows. Some guy you met on the internet tells you he’s a fireman and that the best way to stop a fire is to try and smother it with bone dry hay.

Your burns are bad. Your kids burns are worse. Do you throw them out of a window where a few other ‘firemen’ are holding on to a sheet made of melting plastic? Or do you push them down the stairs, where the rest of the injured and dead families are?

Thats my response to the utterly asinine response Kim Stagliano posted on the Age of Autism blog today to the Chicago Tribune’s series of articles on the quacks and hacks infesting the autism community. She wheels out the same old strawmen…

That’s my response to the Chicago Tribune accusing us of performing “uncontrolled studies” on our kids. (Our medical doctors are thorough and safe, by the way.)

I know of at least two doctors associated with the biomed movement who are on sex offenders registers. I know of one DAN! doc who is associated with the death of a child. I know of one other who hospitlaised a child. I know another who performed exorcism on autistic kids. I know another who is under investigation for more than one complaint.

And why does it bother journalists like Trine Tsouderos and Pat Callahan that some of us are improving our children’s lives?

I can’t speak for these journalists but I’ll speak as the parent (and step-parent) of two autistic kids. You’re not improving your childs autism. Thats the claim that these journalists are challenging. I challenge Kim Stagliano or Mark Blaxill to show the autism community where a biomed treatment discussed by the Tribune led to a measurable and scientifically documented improvement in their child’s autism. In fact, I can’t think of a child belonging to the founders of Autism FAIR Media, Generation Rescue, Age of Autism, SAFE MINDS or the NAA that has either been cured of their autism or made any sort of progress towards that end result as a sole consequence of biomed treatments. Why? Because in terms of curing/recovering/treating autism *they do nothing* . As a direct consequence of that obvious fact, parents continuing with detox, urine injections, exorcism et al are – as the Tribune indicate – experimenting on their children.

The war on Tom Insel and the IACC

23 Oct

Tom Insel is director of the National Institute of Mental Health (NIMH) but he is better known to readers of this blog as the chair of the Interagency Autism Coordinating Committee. If you read other autism blogs, he’s probably very well known to you, as he has been the target of a concerted attack from the vaccines-cause-autism groups for a few months now. They even got the publicist, David Kirby, to take their battle to the public in a CBS interview.

Let me take a moment to make a side point. The vaccines-cause-autism groups (SafeMinds, Generation Rescue, the National Autism Association, Talk About Curing Autism (TACA)…I’m probably missing one or two), are basically a single consortium as evidenced by their single blog and their shared membership. I don’t see the need to treat them as separate entities. I really don’t see that they should be given multiple representations on the IACC.

I’ve been watching the IACC pretty closely for some time. I’ve also been watching the vaccines-cause-autism consortium. I’ve been watching the consortium build pressure against Dr. Insel.

One thing I’ve noticed: this level of pressure directed at Dr. Insel wasn’t always the case. Less than a year ago, Dr. Insel was not their target.

Take a look at one of the classic pieces of IACC intimidation: a piece called “Grinkers Stinker“. This is dated January, 2008. It was timed to coincide with a 4-day workshop that was the kick-off for the Strategic Plan process.

“Grinker’s Stinker” was a piece about the Dr. Joyce Chung, the former IACC coordinator. She is the wife of Prof. Roy Richard Grinker, anthropologist and author of the book Unstrange Minds. Dr. Grinker has publicly stated that he accepts the scientific consensus that vaccines did not cause an epidemic of autism. Dr. Chung has made no public statements (at least that I can find), but the lack of actual information about her or her opinions didn’t stop a blog post decrying her position on the IACC. From the blog post:

Does Joyce Chung agree with her husband? Did they ask her this question before she took the job?

Oddly, the last comment to that blog piece, by Generation Rescue’s “DC Liason” Kelli Ann Davis, starts with the question, “Can I suggest that we try and put an end to all the mudslinging?”

History has proven that, no, the Age of Autism can’t put an end to the mudslinging. Unfortunate, that.

Take a look at the blog post. There is no mention of Dr. Insel. No one decrying his “lack of leadership”, no one claiming “collusion” or “malfeasance”. None of the mudslinging terms currently used against members of the IACC, especially Dr. Insel. In fact, the first mention of Dr. Insel is in the comment by Ms. Davis. In her comment Ms. Davis suggests that Dr. Insel will be watching out for conflicts of interest.

Times certainly have changed. The Age of Autism likes to demonize those it disagrees with, and Dr. Insel certainly has been a recent target.

What happened?

Dr. Insel (a) had the IACC reconsider an initiative to call for a vaccine-autism study to be included in the Strategic Plan and (b) spoke before a congressional hearing about why vaccine/autism studies are not a high priority.

Not surprising to many of the readers here, I am sure, the vaccines-cause-autism consortium have a single issue (vaccines). As long as Dr. Insel’s position on vaccine/autism research, there was hope for the consortium and they left him alone. Once his current opinion formed and was public, he was public enemy number one. Yes, Dr. Paul Offit (vaccinologist and outspoken critic of the notion that vaccines cause autism) has been superseded.

Recently, Dan Olmsted (owner of the Age of Autism website) called for Dr. Insel to resign. Again, it boils down to the single issue: vaccines.

So, here we are. The vaccines-cause-autism consortium has declared war on Tom Insel for opposing their single-item agenda. If you think “war” is too strong a word, take it up with Mr. Olmsted. In referring to the recent incident where notes from an IACC member were made public:

…notes dropped on the floor (see the notes here) at the IACC, recovered by friendly forces and reported on our blog…

Yes, the Age of Autism people are “friendly forces”.

Here’s my perspective on Dr. Insel, for whatever it may be worth. He is the chair of the IACC. In my opinion, his role is to run the meetings and manage the staff. He should be getting good people in to serve on the IACC and the subcommittees and good people to consult on the topics that are discussed. Basically, his role is that of a facilitator–get good people together with the tools they need to do their job. He needs to be knowledgeable enough on the subject (autism) to do this.

You know what? Given the fact that his full time job is director of the NIMH, he’s actually done a pretty good job.

Is there room for improvement? Heck yeah. How about putting a greater emphasis on research into the needs of autistic adults? The majority of autistics are adults. And yet only 5% of the funding is being applied to this critical area.

But, of course, the squeaky wheels (the vaccines-cause-autism consortium in this case) get the grease. The squeaky wheels have been calling for research into environmental causes of autism. Tens of millions of dollars are being focused on this. Why are the squeaky wheels unhappy? Because the squeaky wheels didn’t really mean “environmental causes”. That was only a code word for vaccines.

This level of tension is not just sad. It is detrimental to the progress of the IACC. There are a lot of autistics, parents, professionals and organizations who are interested in working with the IACC. Why spend any more effort on the groups that have declared war?

(note, I made a number of changes in this piece shortly after publishing it)

More Hot Air about HBOT

6 Apr

A few weeks ago, BMC Pediatrics published an article that purports to show that Hyperbaric Oxygen Therapy (HBOT) can produce “…significant improvements in overall functioning, receptive language, social interaction, eye contact, and sensory/cognitive awareness..” in autistic children. This study (Rossignol et al, 2009) is billed as a “…multicenter, randomized, double-blind, controlled trial.”

It’s all that and much, much less.

Let’s start by looking at the six “centers” where this research was carried out.

The Centers

The International Child Development Research Center (ICRDC):

This imposing name is attached to a rather less imposing edifice. The ICRDC, brainchild Dr. Jeffrey Bradstreet, is located in a strip mall in Melbourne, Florida, where it not only carries out “cutting-edge research” but also sells a complete line of “supplements” and treats autistic children with a dizzying array of “alternative”, “biomedical” and “integrative” therapies, including HBOT.

Daniel Rossignol MD (Family Practice), Lanier Rossignol (Nurse Practitioner) and Scott Smith (Physician’s Assistant) were the authors from the ICDRC.

The Center for Autism Research and Education (CARE):

This “center” is located in Phoenix, Arizona and has – according to its website – a single practitioner, Cynthia Schneider, MD (OB/Gyn), who is also an author on this paper. One of the “integrative” therapies this “center” offers is HBOT.

One of the other authors, Sally Logerquist, is a PhD psychologist who – according to the paper – is also associated with CARE, but also appears to run social skills therapy groups for autistic children using the “Logerquist Excellent Attitude Program” (LEAP).

True Health Medical Center:

It’s rather difficult to find anything about this “center”, apart from the fact that it is located in Naperville, Illinois – in what appears to be an office complex. Anju Usman, MD (Family Practice) is the author associated with this location.

Neubrander Center:

Although not officially called a “center”, the office of James Neubrander, MD (Pathology) is apparently one of the “centers” of this study. His office is located in the Menlo Park Mall (near Macy’s) and offers – you guessed it! – HBOT as a treatment for autism.

Princess Anne Medical Associates:

A Family Practice medical group in Virginia Beach, Virginia, this “center” is the home of Eric Madren, MD (Family Practice). It’s not clear if this four-physician practice offers HBOT.

The Rimland Center for Integrative Medicine:

A small, one-physician “center” in Lynchburg, Virginia, this is practice location of author Elizabeth Mumper, MD (Pediatrics). Not surprisingly, this “center” sells HBOT services for autistic children.

So, of the six “centers” involved in this study, five are single-physician operations. The remaining “center” has two physicians (three, if you count the naturopath).

I’m underwhelmed.

Well, what about the research itself? Maybe that’s better than the “facilities” might suggest. Let’s take a look.

The Subjects

This study initially enrolled 62 children (33 treatment; 29 control), but only 29 of the treatment group and 26 of the control group finished all 40 sessions. For reasons that pass my understanding, one treatment subject who only finished 9 sessions was included in the analysis. The authors stated that including this subject did not alter results, which begs the question: “Why did they include this subject if it made no difference?”

Outcome measures

The authors used the Aberrant Behavior Checklist (ABC), the Clinical Global Impression (CGI) scale and the Autism Treatment Evaluation Checklist (ATEC) as their outcome measures. All except the ATEC are widely accepted for use in autism treatment trials.

The ABC is a 58-question checklist of – surprise! – aberrant behaviors which are each given a score from “0” (“not at all a problem”) to “3” (“severe problem”). This test has been use – and validated – in a number of disorders, including autism. It gives a global score as well as five subscales: a total of six measures.

The CGI is a generic rating scale used in a variety of clinical trials. For each parameter (e.g. “overall functioning”, “sleep pattern”), the rater gives a score of between “1” (“very much improved”) and “7” (“very much worse”). The authors had both the treating physician and the parents rate the subjects on overall improvement and eighteen discrete parameters: a total of 38 measures in all (19 by the physician and 19 by the parents).

The ATEC was developed by Bernie Rimland and Stephen Edelson and has not been validated. In fact, it has only been used in two published studies – one by Rossignol et al. The ATEC has 25 questions on which the evaluator rates the subject on either a three-point (“not true”, “somewhat true”, “very true”) or four-point (“not a problem”, “minor problem”, “moderate problem”, “serious problem”) scale. It provides a total score and four subscales: a total of five measures.

In all, each subject had a total of 49 evaluation measures (CGI scores and the change in ABC and ATEC scores), of which 47 are independent. The importance of this will become apparent in the section on statistical analysis.

Analysis

As I mentioned above, the decision to include one treatment subject who only completed nine sessions was curious. Why they included this subject and not any of the other three treatment subjects and three control subjects who also failed to complete the entire course of the study is concerning. The smart thing – and the proper response – would have been to drop this subject from analysis.

The authors’ method of analyzing the CGI scales was also curious. Rather than simply using the scores as they were provided, they took the scores and subtracted them from four (the “no change” score). There are a few problems with this.

For starters, the scores are not linear – the difference between “much improved” and “very much improved” is not necessarily the same as between “no change” and “minimally improved”. Nor is the difference between “no change” and “much improved” twice the difference between “much improved” and “very much improved”. For that reason, these types of numerical scores are often referred to as “pseudo-numbers”.

This may seem like nit-picking, but it is a serious concern. Imagine, if you will, that the numbers were replaced by colors. Is the difference between green and orange twice the difference between orange and red? If half of a population of birds are blue and the other half are yellow, is the “average” bird green? The simple fact is that it is not appropriate to treat these “scores” as though they were real numbers, to be added, subtracted and averaged.

Secondly, it appears that the authors used parametric statistics for their analysis of the CGI scores. This is a problem since – as I indicated above – it is nonsensical to do math on pseudo-numbers. I don’t have the raw numbers, so it isn’t possible for me to calculate the absolute impact of this mistake for all of the CGI subclasses, but I can figure out the raw numbers for one group, so let’s look at that one.

It took a little work, but the authors gave enough clues to tease out the raw numbers in the physician “overall functioning” CGI score. The treatment group had an “average” of 2.87 and the control group’s “average” was 3.62; using the unaltered data, a t-test [Note: not an appropriate use of the t-test] gives p-value of 0.0006, not far from what the authors report. When a more appropriate statistical test [Mann-Whitney U-test] is used, the p-value is 0.002, very different from the reported 0.0008. While this is still less than the threshold p-value of 0.05, see below for a discussion of multiple comparisons.

All of these statistical analyses of the CGI scores ignore the fact that these are pseudo-numbers and need to be treated as discrete groups rather than as actual numbers. In truth, even the ABC and ATEC scores should have been treated this way, as well, although it is fairly common practice to treat such multi-factor scores as real numbers. A Chi-square test or Fisher Exact test would be the ideal test, but the problem with that is that the treatment group has one score of “1″ (very much improved) and the control group doesn’t. Likewise, the control group has two subjects with a score of “5″ (minimally worse) and the treatment group has none. This prevents a Chi-square or Fisher test from comparing each score independently.

One solution is presented by the authors themselves, although they apparently didn’t use it. In their discussion of the CGI, the authors said:

“Children who received a score of ‘very much improved’ or ‘much improved’ on the physician CGI overall functioning score were considered to be ‘good responders’ to treatment.”

If we “bin” the scores into “good responders” and “others”, we find that there were 9 (out of 30 – 30%) “good responders” in the treatment group compared to 2 (out of 26 – 8%) in the control group. Unfortunately, this is not a statistically significant difference (p = 0.08) in the (Yates) Chi-square test and barely reached significance (p = 0.05, but see below) in the Fisher Exact test.

An even bigger problem in the statistical analysis was the failure to correct for multiple comparisons. This problem was brought up by one of the reviewers, and the authors responded by eliminating a table. They did not make the appropriate corrections.

The reason that multiple comparisons are a problem is that the analysis for statistical significance is based on probability. If the probability (the p-value) that the differences between the two groups (treatment and control) is due to random chance is equal to or less than 5%, that difference is considered to be “statistically significant” and accepted as real. That means that there is still a 5% (or less – look to the p-value) chance that the difference is due to chance and not real.

If multiple comparisons are made on the same group of subjects, the probability that one (or more) of them will be “statistically significant” by chance starts to climb. If 14 comparisons are made, the chance of an erroneous “statistical significance” is over 50%. If 47 independent comparisons are made – as in this study – the chance of an erroneous “statistical significance” is over 90%.

For this reason, it is standard procedure to apply a correction for multiple comparisons. The most well-known (and simplest) of these is the Bonferroni Correction, which changes the threshold for statistical significance by dividing it by the number of comparisons. In the case of this study, the threshold (normally p less than or equal to 0.05 or 5%) is reduced to 0.001.

Applying the appropriate correction for multiple comparisons changes the results of this study significantly. Only the physician CGI scores for overall functioning and receptive language reach significance – and these numbers are already suspicious because they were improperly handled to begin with. In fact, as I have shown above, the CGI “overall functioning” p-value wouldn’t reach significance. It is possible that – if the proper statistical tests were used – that the CGI score for “receptive language” would also not reach significance.

Another curious thing. The authors asked the parents after the study whether they thought their child was in the treatment or the control group. Rather than say that the parent’s guesses were no better than random chance (i.e. 50%), the authors stated:

“…there was no significant difference between the two groups in the ability of the parents to correctly guess the group assignment of their child.”

As I said, this was a curious way to put it. As I read this, all it says is that each group of parent were equally able to guess which group their child was assigned to. That could be a 50% accuracy (which would be equal to chance), but a 90% or 99% accuracy – if both groups were that accurate – would also fit that description.

Now, this could simply be an clumsy phrasing by the authors, or it could be a way to make it sound like their blinding was successful when it actually was not.

Summary

This study may have collected some useful data, but its analysis of that data rendered it useless. The CGI scores – where the only statistically significant result was (possibly) seen – were improperly manipulated and the wrong statistical analysis was used.

The other issue is that there is no discussion of why HBOT is thought to be superior to providing the same partial pressure of oxygen at room pressure. This study used 24% oxygen at 1.3 atm, which gives the same partial pressure of oxygen as 31% at sea level. This concentration of oxygen can be easily attained with an oxygen mask or simple oxygen tent – both of which are vastly less expensive than HBOT.

If the authors are arguing that the mild pressure of their inflatable HBOT chambers contributes to the treatment effect, they need to look at the literature on cell membrane compressibility. For those who want to do the calculations at home, the bulk modulus of water (the major component of cells) is 21,700 atm. This means that a 0.3 atm increase in pressure will reduce the cell volume by 0.0014%. The bulk modulus of the lipid bilayer in cell membranes is around 30,000 atm. This means that an increase of 0.3 atm pressure causes a 0.0010% reduction in membrane volume. These are well below the threshold for any clinical effects.

Real pressure effects on the central nervous system are seen at pressures over 19 atm. These effects are:

dizziness
nausea
vomiting
postural and intention tremors
fatigue and somnolence
myoclonic jerking
stomach cramps
decrease intellectual and psychomotor performance
poor sleep with nightmares
increased slow wave and decreased fast wave activity in EEG

None of these effects could be construed as “improvements”, even in autism.

So, this study fails to answer the following questions about HBOT and autism:

[1] Does HBOT improve any feature of autism?
[2] If so, is HBOT any better than supplemental oxygen (which is much cheaper)?

The only real effect of this study was to give a cover of legitimacy to practitioners who are already using HBOT to “treat” autism.

Prometheus

Mild hyperbaric therapy for autism – Shh!…don’t say it’s expensive

30 Mar

When I recently wrote about the new HBOT-for-autism study (Rossignol et al. 2009)1, I took issue with unlikely claimed treatment pressures for at least one of the study locations. While a potential methodological weakness, this is probably a fairly small problem in light of potential issues with blinding and interpretation of the results as quantitatively and objectively meaningful with respect to autism. But let’s set those potential issues aside for a moment.

Let’s assume that treatment with slightly enriched air (24% vs. 21% oxygen) in an inflatable hyperbaric chamber pressurized to 4 PSI2,3 above ambient atmospheric pressure, could confer some sort of benefit to an autistic child.

I’m not suggesting assumption that it does confer benefit. I’m asking readers to set aside any knowledge of hemoglobin’s role in oxygen transport, as well as any knowledge of real hyperbaric oxygen therapy (breathing 100% oxygen at greater than 1 ATA)4, and evaluate a simpler proposition. Accept the proposal that some sort of benefit is scientifically possible, but then ask yourself a fairly simple question:

Compared to 24% O2 at 4PSI above ambient atmospheric pressure in an inflatable hyperbaric chamber, equivalent oxygen delivery can be achieved with simple oxygen therapy (an oxygen mask) at a fraction of the cost5 – why is a study of the hyperbaric version of this increased oxygen important?

One possibility: studying what’s already for sale

While some might call it being on the “cutting edge”, others may consider it putting the cart before the horse. No matter how you see it, it’s no secret that some Defeat Autism Now practitioners were already selling this type of hyperbaric oxygen therapy well before this study came out. It should be noted that this study’s authors did disclose this conflict of interest with respect to derivation of revenue in their clinical practices from HBOT.

DAR, LWR, SS, CS, AU, JN, EMM, and EAM treat individuals with hyperbaric treatment in their clinical practices and derive revenue from hyperbaric treatment.

Lisa Jo Rudy over at autism.about.com6 had additional comments about the subject:

Dr. Rossignol is “the” proponent of HBOT, and has been speaking at conferences all over the world in support of the treatment. Clearly, he has a personal and professional stake in seeing that the outcomes of a research study are positive.

The present study was funded by the International Hyperbarics Association, a trade group of private hyperbaric therapy centers. Clearly, they have a similar stake in seeing positive outcomes.

While there may certainly be an aspect of genuine scientific interest in understanding if this type of hyperbaric oxygen therapy is beneficial for autistic kids, I think there may also be a certain degree of assumption that it is. After all, why would a practioner already be selling something if they didn’t “believe” it worked? Given the stated conflicts of interest, it doesn’t seem implausible that the authors might have an interest in seeing a long-term revenue stream that could come from additional, and deeper pockets than those of parents willing to “believe” and pay – despite the lack of really convincing scientific evidence at this point.

Consider the following portions of an interview with Dr. Dan Rossignol7:

We chose 1.3 ATA because a lot of children with autism are currently receiving this dose and we are hoping to prove that it works.

“Hoping to prove that it works.”

Dr. Rossignol’s point does not seem unclear. HBOT is popular, and he is, in his own words, “hoping to prove that it works”. This is a valid reason, I suppose, if he is also open to the possibility that it may not, or that it may be a completely moot point if something on the order of one tenth of the cost can do the same thing. Following Dr. Rossignol’s communication about the hope to “prove that it works”, the interviewer asks:

How is the insurance situation coming along?

Insurance situation? Coming along? Was this situation already a well-known “work in progress” back in 2006 (e.g. had it been decided by some, prior to the science, that “mild” HBOT for autism does work, and that insurance reimbursement is really the goal now? Let’s see if we can get Dr. Rossignol’s take on this.

Well, obviously, HBOT is not approved for autism, but we hope to get there. Interestingly, if you take the ABC scale and look at the lethargy subset score, we saw a 49% improvement in symptoms at 1.5 ATA with a p-value of 0.008. If you look at the New England Journal of Medicine study on risperidone from 2002, there was a 56.9% improvement on the ABC irritability subscale with a p-value < 0.001. So the results we had on these 6 children with 1.5 ATA approached the percentage improvement seen with a drug approved for the use in autism. We just need to be able to reproduce these type of findings in a placebo study.

Hopefully when we finish these studies and show that hyperbaric therapy works, then insurance reimbursement will follow.

I don’t necessarily see a geniune scientific perspective here, but that could just be me. I get more of a vibe (at least from this interview), that the interest may lie more in “finishing” the studies and showing “that hyperbaric therapy works”, rather that actually finding out, with really good quality scientific methodology, whether or not it really does work. I’ll acknowledge that I could be wrong about this. Do you think readers will have noticed that the study result mentioned for comparison, was from 1.5 ATA, and probably totally irrelevant to the 1.3 (or less) studies?

Is it just me, or would it seem naive to wish that a few studies like the recent one, are really going to catalyze insurance reimbursement in the long run? I get the impression that many parents may believe this. Insurance companies work to achieve cost efficiencies. One of the ways they do this is by reimbursing at higher rates for equivalent things at lower costs – hospital stays in contracted facilities, generic drugs as compared to name-brand versions, etc. Why on earth would an insurance company reimburse for a 4-5% increase in blood oxygen content for a couple of hours at a time, in an inflatable hyperbaric chamber (at a few thousand dollars a month), when the identical oxygen increase could be delivered with a simple oxygen mask (for under $200 a month)?

You don’t have to take my word for this comparison of oxygen delivery, you can take Dr. Rossignol’s acknowledgement in that same interview:

Some people have criticized using mild hyperbarics at 1.3 ATA because they state that when compared to this pressure, you can get just as high an oxygen concentration in the blood with oxygen by face mask without a chamber. And this may be true in some cases.

In fact, it’s true in most (if not all) cases. The physics of partial pressures does not discriminate. But there may be more to the story.

Squeeze in some hope

After acknowledging the reality of the partial pressure comparison problem, Dr. Rossignol continues:

However, we must remember we are dealing with 2 separate components with HBOT — the oxygen and the pressure. So it appears that many of the effects of HBOT are from the increased oxygen, but we cannot dismiss the pressure effect. I think we need more studies on this as well.

So “many of the effects” are from the oxygen increase, but we can’t dismiss the pressure effect? What pressure effect? Is there a demonstrated significant clinical effect for autism from a very slight, and very temporary, increase in atmospheric pressure alone?

Although I suppose it is possible, a clinically significant effect for autism at such low pressures doesn’t seem likely at all. If it turns out that I am incorrect, this may be good news for some of the parents of autistic children in several U.S. cities: Albuquerque, NM (5312′ AMSL), Aurora, CO (5471′ AMSL), Colorado Springs, CO (6035′-7200′ AMSL), Denver, CO (5280′ AMSL), Reno, NV (4505′ AMSL), and Salt Lake City, UT (4226′ AMSL), to name a few. Something as simple as a move to a closer to sea-level city might provide increases in atmospheric pressure not a lot unlike those provided by the inflatable hyperbaric chambers. If there were some beneficial effect of slight additional atmospheric pressure for autism, certainly there would have been some observations (anecdotal or media reports) over the years, of families with autistic children who moved from states like Colorado to lower elevation states like California – and noticed. Who knows? Perhaps this is something to yet be uncovered.

So, aside from the fact that an identical oxygen increase can be achieved with simple O2 therapy without a hyperbaric chamber at all (and at a fraction of the cost). And, aside from the point that the minute pressure increase (while certainly possible in a strict scientific sense) isn’t known to be a likely candidate to significantly clinically impact autism, is there anything else about this newest HBOT-for-autism study that may merit some critical thought? Maybe, but it’s really just a side-note (perhaps interesting to some, but not terribly relevant to the science itself).

Who farted in the HBOT chamber? (Shh!…Don’t say it’s expensive)

The original manuscript8 for this study contained what I thought was an appropriately realistic comment from the authors in the conclusion. This comment has value in terms of practical knowledge that readers who are not familiar with hyperbaric oxygen therapy would probably find useful. What follows is the first-draft conclusion of this study with that comment emphasized.

Hyperbaric treatment is a relatively time-intensive treatment and can be costly. However, given the positive findings of this study, and the shortage of proven treatments for individuals with autism, parents who pursue hyperbaric treatment as a treatment for their child with autism can be assured that it is a safe treatment modality at the pressure used in this study (1.3 atm), and that it may improve certain autistic behaviors. Further studies are needed by other investigators to confirm these findings; we are aware of several other planned or ongoing studies of hyperbaric treatment in children with autism.

Again, Lisa Jo Rudy over at autism.about.com notes:

No insurance company will cover the very high cost of HBOT for autism, as it is considered an experimental and unproven therapy.

But the above conclusion is not the conclusion that appeared in the peer-reviewed, edited version. Here it is:

Given the positive findings of this study, and the shortage of proven treatments for individuals with autism, parents who pursue hyperbaric treatment for their child with autism can be assured that it is a safe treatment modality at the pressure used in this study (1.3 atm), and that it may improve certain autistic behaviors. Further studies are needed by other investigators to confirm these findings; we are aware of several other planned or ongoing studies of hyperbaric treatment in children with autism.

Why would the authors remove that valuable bit of practical knowledge about time requirements and high cost? Apparently due to a comment from referee #3 for this paper.

Discretionary Revisions

Page 24 In view of the highly positive findings of this study and the fact that no other trial has demonstrated such benefits under strictly controlled conditions to open the conclusions with negative comments demeans the study. Many other inventions used for ASD children are equally time consuming and hyperbaric treatment need not be expensive.

Authors: “The negative comments were removed from the conclusion.”

Opening the conclusion with negative comments demeans the study? Such comments don’t really touch the content of the study itself, and what the now absent comment did do, was provide some practical perspective – quite likely, very accurate practical perspective. Why would it be suggested by referee #3 that the practical comments demean the study? Perhaps it was meant that the comments demean the use of mild hyperbaric oxygen therapy as an autism treatment (therefore actually demeaning a desired interpretation of this study)? That would seem a real possible concern, since the justification offered, has absolutely nothing to do with the study itself, and doesn’t amount to much more than logical fallacy and simple assertion.

“Many other inventions used for ASD children are equally time consuming…”

This is about as basic an example of the “two wrongs make a right” fallacy as can be presented. Two wrongs don’t make right. Just because other interventions are also time consuming, does not mean a researcher is unjustified, or shouldn’t add the point about practicality that HBOT is relatively time consuming. Further, if the authors are aware of such a potential practical issue, it could be argued that ethics would dictate that it is mentioned. Other treatments presenting similar impracticalities do not automatically relieve any potential ethical responsibility in this regard.

“…hyperbaric treatment need not be expensive.”

Compared to what? Hyperbarics in a gold-plated hyperbaric chamber? If there is no significant effect for autism from the brief, and small increase in added pressure in one of these inflatables, the increased oxygen delivered by providing 24% O2 at 4 PSI above ambient atmospheric pressure, is easily matched (or exceded) with simple O2 therapy. In short, this type of hyperbaric treatment would be the hard way, and the expensive way to achieve the results.

Referee #3 also added the following comment:

The reviewer has a preference for the word treatment rather than ‘therapy’. In view of the proven changes that relate to increased inpsired fractions of oxygen it is suggested that treatment would be preferable.

Authors: “The word “therapy” has been replaced with “treatment” throughout the paper.”

The “T” in the acronym “HBOT” does, in fact, represent the word “therapy” in medical usage. I happen to think the terms “treatment” and “therapy” are fairly interchangeable in the context of drug delivery, but I do wonder if there is any significance to such a preference. Is this a semantics issue that has the potential to impact perceptions of those who make decisions about insurance coverage for autism? But I digress. So what’s up with these comments from referee #3, comments with a little fallacious reasoning, that express possible concern about the perception of a high price tag for mild hyperbaric oxygen therapy, and a commment that communicates a preference for the word “treatment” over “therapy”?

I honestly don’t know. What I can tell you is that referee #3 was Philip James, MD. Dr. James is a professor in the field of hyperbaric medicine and hails from the U.K. He appears to have published quite a bit in the field of hyperbaric medicine as well.

According to the International Hyperbarics Association website:

Dr. James is responsible for founding the Hyperbaric Trust in the United Kingdom which promotes the treatment of cerebral palsy and the brain injured child and was responsible for having the National Health Service pay for this therapy.

Dr. James (Referee #3) appears to have been categorized (with a doctor profile) as a medical advisor to International Hyperbarics Association back in February of 2006 (shortly before this study9 began). Hey wait a minute, there’s that name again – International Hyperbarics Association. Where have I seen that before? Oh yeah, in the study itself:

We are grateful for the work of Shannon Kenitz of the International Hyperbarics Association (IHA) for an unrestricted grant which funded this study, which included use of hyperbaric chambers and funding for all hyperbaric technician salaries during the study. The IHA had no involvement in the study design, collection, analysis, interpretation of data, writing of the manuscript, or in the decision to submit the manuscript for publication.

I’m not sure how the International Hyperbarics Association defines itself exactly – are its listed medical advisors excluded from that definition? That would seem likely.

As of this writing, Dr. Rossignol is listed as a medical advisor at the IHA website. 10
As of this writing, Dr. Neubrander is listed as a medical advisor at the IHA website. 10
As of this writing, Dr. James (referee #3), is categorized as a medical advisor at the IHA website with a physician profile page.11,12

Side notes aside, where to, from here

So all in all, it seems that “mild” HBOT-for-autism researchers may have their work cut out for them. Although probably not very likely, it is possible that a small temporary change in atmospheric pressure could do something for autism, and that should be studied next, then, better replications should follow.

In the long run, it will be difficult to ignore the scientific fact that simple oxygen therapy alone can easily provide identical increases in blood oxygen content, at a fraction of the cost of mild hyperbaric oxygen therapy (as it currently being studied for autism). If HBOT-for-autism proponents think insurance companies should step up to pay for an expensive treatment that provides a 4-5% increase in blood oxygen (without scientifically establishing benefit of the small and temporary pressure increases), they might do well to consider these famous words (most recently from Barack Obama) – “You can put lipstick on a pig. It’s still a pig.”

Notes:

1 Hyperbaric treatment for children with autism: a multicenter, randomized, double-blind, controlled trial

http://www.biomedcentral.com/content/pdf/1471-2431-9-21.pdf

2 Medical device pre-market notification (FDA-cleared)

http://www.accessdata.fda.gov/cdrh_docs/pdf/K001409.pdf

3 Manufacturer product sheet

http://www.oxyhealth.com/pdfs/vitaeris-lowres2007-8.pdf

4 Definition of Hyperbaric Oxygen Therapy

http://www.uhms.org/ResourceLibrary/Indications/tabid/270/Default.aspx

5 Hyperbarics and Hypotheses

http://www.autismstreet.org/weblog/?p=60

6 Hyperbaric Oxygen as a Treatment for Autism: Let the Buyer Beware

http://autism.about.com/b/2009/03/14/hyperbaric-oxygen-as-a-treatment-for-autism-let-the-buyer-beware.htm

7 Interview with Dr. Dan A. Rossignol: Hyperbaric Oxygen Therapy Improves Symptoms in Autistic Children

http://www.icdrc.org/documents/Rossignol%20HBOT%20Medical%20Veritas%202.pdf

8 Pre-publication history

http://www.biomedcentral.com/1471-2431/9/21/prepub

9 ClinicalTrials.gov Identifier: NCT00335790

http://clinicaltrials.gov/ct2/show/NCT00335790

10 Medical Advisors

http://www.ihausa.org/

11 Index of /docs

http://www.ihausa.org/docs/

12 International Hyperbarics Association Medical Advisor – Professor Philip B. James, M.D.

http://www.ihausa.org/docs/james.html

Autism, HBOT, and the new study by Rossignol et al.

21 Mar

I recently read the BMC Pediatrics article, “Hyperbaric treatment for children with autism: a multicenter, randomized, double-blind, controlled trial1. I know this paper is attracting a lot of attention in the media, and it is certainly being ballyhooed about the internet. Hell, I’ve even received e-mail spam about this study! But I’m sorry to say, I don’t really share the excitement. In fact, I see what looks like a pretty significant error in the methodology of this study. It’s one of those types of potential errors that stand out like a strobe light or a siren – it’s really tough for me to pretend it’s not there.

Once again, I’m going to ask readers to set aside, for the moment, anything they may know about the role of hemoglobin in oxygen transport and how the minute increases (probably around 3-4%) in total blood oxygen content afforded by this kind of hyperbaric therapy, or simple O2 therapy for that matter, are probably pretty likely to be insignificant.

Both the paper and ClinicalTrials.gov2 list the Center for Autism Research and Education, Phoenix, Arizona, as a study location. This is a problem, because the stated treatment pressure in the study (1.3ATM) seems highly unlikely to actually be achievable in Phoenix with the equipment that was apparently used for this study.

As described in the section titled, “Interventions”:

“These procedures included covering control switches, inflating and deflating the chambers to simulate pressure changes, and masking the sounds from the chambers.”

The use of inflatable monoplace hyperbaric chambers, is a clear indication that the actual total pressures (and quite likely results of this study) would have been affected by the ambient air pressures at the times and locations of treatment. In fact, the ambient air pressure is the largest component of the stated treatment pressure in this study (ambient pressure + added treatment pressure = total treatment pressure).

Ambient pressure

Local atmospheric pressure is typically reported as sea-level pressure3 for its utility to aviation, and the meaningful interpretation of weather maps, etc., but the actual station pressure is affected by the elevation. The expected ambient atmospheric pressure, corrected for altitude, (or station pressure) in Phoenix, Arizona4 is 28.69 in Hg (where there is a modest elevation of 1161’ AMSL). Wanting to give this paper the benefit of the doubt, and knowing that “high pressure” weather is typical of the Phoenix climate, I looked at 30-day data5 for actual station pressure in Phoenix at a station of slightly lower altitude than the Center for Autism Research and Education. The 30-day mean station pressure is 28.81 in Hg, so I’ll use that one for calculations, as it will yield results more likely to be in the study’s favor.

Added treatment pressure

The actual operating pressure of the inflatable chambers, as stated by the manufacturer, is 4 PSI. 6,7 This pressure is also indicated on the Center for Autism Research and Education’s website:

“The chambers used at care utilize a pressure of 4 psi.”8

Total treatment pressure

The total treatment pressure can be easily calculated with the following conversions:
in Hg * 0.491 = PSI
PSI + PSIG = Total PSI
Total PSI * .068 = ATA

For Phoenix, Arizona, this gives a calculated total treatment pressure of 1.23 ATA.

28.81 * 0.491 = 14.15 PSI
14.15 PSI + 4 PSIG = 18.15 PSI
18.15 PSI * .068 = 1.23 ATA

Damn, that’s a pretty big difference from the paper’s stated 1.3 ATM – representing an addition of only .23 ATM (instead of .30 ATM) above mean sea-level pressure of 1 ATM.

I’ve corresponded with the lead author of this study in the past, and he stated that he observes gauge pressure of 4.15 PSI. Despite the manufacturer specs, the FDA-cleared medical device premarket notification, and the Center for Autism Research and Education’s website (which all indicate operating pressure of 4 PSI), and wanting to give the benefit of the doubt, I’ll use 4.15 PSI for the next calculation, as it will be more likely to yield results in the study’s favor.

28.81 * 0.491 = 14.15 PSI
14.15 PSI + 4.15 PSIG = 18.30 PSI
18.30 PSI * .068 = 1.24 ATA

It could be argued that treatment pressure for the other study locations were properly rounded up to 1.3 ATM (even though the actual pressures were quite likely to be considerably lower), however, even with all the calculations purposely leaned in favor of a higher number for Phoenix, Arizona, the study’s stated treatment pressure, there, should have properly rounded to 1.2 ATA! This suggests an overstatement of the added treatment pressure for the Phoenix location of 50% (.3 ATM is 150% of .2 ATM). Even if given the benefit of the doubt yet again, and an exception to proper rounding were made for solely for the Phoenix location in this study, the study’s likely overstatement in added treatment pressure for Phoenix is still a full 25%. (.3 ATM is 125% of .24 ATM – 25% more added pressure above 1 ATM was claimed in this paper, than was probably delivered).

I think this is a big enough boo-boo, that the editors of BMC Pediatrics should call for detailed errata. In the interest of scientific accuracy, it would seem prudent for BMC Pediatrics to:

1. Clarify for its readership and the scientific community, that the stated pressure of 1.3 ATM in this study is rounded up, and includes the ambient air pressure, or alternatively, state the estimated pressure in terms of ATA.

2. Clarify for its readership and the scientific community, that the stated pressure of 1.3 ATM in this study is an estimated pressure, since no actual measurements of ambient station pressure for the locations, and dates/times of treatments were reported.

3. Note for its readership and the scientific community, that the stated pressure of 1.3 ATM was not likely to be uniformly achievable across all study locations due to the use of inflatable hyperbaric chambers and changes in elevation (and atmospheric pressure) across study locations, potentially confounding the results of this study.

4. Note for its readership and the scientific community, that estimated pressures in the placebo control group are affected by these same issues that affect the treatment group, potentially confounding the results of this study further.

What do you think?

1 BMC Pediatrics 2009, 9:21doi:10.1186/1471-2431-9-21

http://www.biomedcentral.com/1471-2431/9/21/abstract

2 http://clinicaltrials.gov/ct2/show/NCT00335790

3Federal Meteorological Handbook No. 1 – Table 11-2

http://www.nws.noaa.gov/oso/oso1/oso12/fmh1/fmh1ch11.htm

4 LAT/LON 33.5º N 118.08º W

5 http://www.wrh.noaa.gov/mesowest/getobext.php?wfo=psr&sid=KPHX&num=720

6 Medical device pre-market notification (FDA-cleared)

http://www.accessdata.fda.gov/cdrh_docs/pdf/K001409.pdf

7 Manufacturer product sheet

http://www.oxyhealth.com/pdfs/vitaeris-lowres2007-8.pdf

8 http://www.center4autism.org/therapyHBOT.asp

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