Hyperbaric Oxygen Therapy (HBOT) has grown in popularity over the last few years. This growth has occurred without any evidence that HBOT is at all beneficial.
A recent study, published in the journal Research in Autism Spectrum Disorders entitled Randomized trial of hyperbaric oxygen therapy for children with autism, explores this question.
The study was performed by CARD, the Center for Autism and Related Disorders and ICDRC the International Child Development Resource Center. CARD is a very large ABA provider run by Doreen Granpeesheh. Dr. Granpeesheh is also associated with Thoughful House, the Clinic founded by Dr. Andrew Wakefield. Dr. Wakefield, is the prime proponent of the notion that the MMR vaccine causes autism. ICDRC is the clinic run by Dr. Jeffrey Bradstreet, a prominent name in the autism alternative medical community.
As you might surmise from their press release, Center for Autism and Related Disorders Study Finds Hyperbaric Oxygen Therapy Ineffective Treatment for Children with Autism, they did not find HBOT to be effective.
Children were given 80 1 hour sessions in a Vitaeris 320 inflatable chamber (a model used commonly in HBOT treatment). 6-10 sessions/week were performed. Children were split into two groups matched by age and number of ABA hours already received. Parameters like supplement use and diets remained unchanged during the time of the study. For the treatment group the chambers were inflated to 1.3 atm, with enriched oxygen air (24-28% O2, compared to 21% for regular air).
The children were given multiple assessments:
All assessments were conducted by trained assessors who were blind to group assignment. To maximize the study’s ability to detect change in any symptom area relevant to autism, a large variety of assessments were used, including the following: the ABC (Aman & Singh, 1994), ADOS (Lord et al., 1999), Behavior Rating Inventory of Executive Functioning (BRIEF; Gioia, Isquith, Guy, & Kenworthy, 2000), Clinical Global Impression Scale (CGI; Guy, 1976), Parent Stress Index (PSI; Abidin, 1995), Peabody Picture Vocabulary Test (PPVT-III; Dunn & Dunn, 1997), Repetitive Behavior Scale (RBS; Bodfish, Symons, & Lewis, 1999), SRS, Vineland Adaptive Behavior Scales—Second Edition (VABS-II; Sparrow, Cicchetti, & Balla, 2005), and the Beery-Buktenica Developmental Test of Visual-Motor Integration—5th edition (VMI-5; Berry and Berry, 2004 K.E. Berry and N.A. Berry, The Berry-Buktenica developmental test of visual-motor integration: Administration, score, and teaching manual, NCS Pearson, Minneapolis, MN (2004).Berry & Berry, 2004). The ADOS, BRIEF, PPVT-III, SRS, VABS, and VMI-5 were administered pre and post-treatment. The ABC, CGI, and RBS were administered weekly. The PSI was administered four times, once at baseline, twice during treatment, and once at completion.
The study was relatively small, with 46 participants.
Forty six participants began the study and 12 withdrew, resulting in 18 previous HBOT participants and 16 placebo participants completing all 80 sessions and follow-up measures. The primary reason reported for withdrawal was the travel required to the clinic. One participant in the placebo group withdrew after having a seizure for the first time. Mean participant age was 6.18 (previous HBOT 6.11; placebo 6.25) and mean number of ABA treatment hours per month was 109 (previous HBOT 114.7; placebo 103.3).
I won’t go into details about the specific outcomes, but the conclusion was pretty straightforward: HBOT had no effect.
No significant differences between the previous tHBOT and placebo groups were found on any of the outcome measures. Thus, the results of this study indicate that previous HBOT delivering 24% oxygen at 1.3 atm did not produce a therapeutic effect for the children who participated in our study. Therefore, previous HBOT at this dose is not recommended for the treatment of ASD symptoms.
I found it interesting how they referred to a previous HBOT study by Rossignal (another prominent member of the autism alternative medical community):
The results of this study corroborate the findings of the only other published study on previous termHBOTnext term which included a control group (Rossignol et al., 2009 D.A. Rossignol, L.W. Rossignol, S. Smith, C. Schneider, S. Logerquist and A. Usman et al., Hyperbaric treatment for children with autism: a multicenter, randomized, double-blind, controlled trial, BMC Pediatrics 9 (2009) 10.1186/1471-2431-9-21.Rossignol et al., 2009)—albeit, not the study authors’ interpretations of their findings. In both the Rossignol et al. (2009) study and the current study, both treatment and control groups improved over time, but the difference in improvement between groups appeared insignificant. In addition, the current study employed dependent measures which were far more comprehensive than in previous research on previous HBOT for ASDs, thereby increasing the probability that a therapeutic effect would have been detected if indeed one had been present.
Yes, the current study is consistent with the Rossignol group’s results, just not their interpretation.
Commentary:
There was much discussion and excitement earlier this year when the Rossignol group study came out. Do’C at the Autism Street blog compiled a list of many of the skeptical discussions. There has not been anywhere near the interest in the newer CARD study.
Will this mean the end of HBOT treatments for Autism? I sincerely doubt it. Take a look at Dr. Bradstreet’s website (Dr. Bradstreet being one of the coauthors of the current study showing no effect). The first page of the site still links to the older study by Dr. Rossignol’s group (claiming that HBOT is effective) and not his own study (which shows HBOT to be not effective).
Of course, it is all the more complicated since Dr. Rossignol is also one of the ICDRC doctors. The alternative-medical community is a pretty small pond, isn’t it?
Back to the question: will this mean the end of HBOT in autism? I wish I could make bets this safe. Of course not. No alternative therapy is abandoned. As shown above, one of the authors of this study showing that HBOT is not effective for treating autism and he hasn’t stopped.
Left Brain Right Brain 
Could these results go some way to explaining why the clinical trial “Effects of Hyperbaric Oxygen Therapy on Children With Autism”, with Thoughtful house listed as “Sponors and Collaborators” and Dr Wakefield as the “Study Director”, still has “no study results posted” more than two years after the study concluded!
http://clinicaltrials.gov/ct2/show/NCT00406159
Don’t understand Oriel’s question about why the Thoughtful House study has no results posted yet. They don’t offer HBOT at Thoughtful House.
The reason that no one is really talking about this study is because it has significant flaws. The randomization was just done on 2 factors – age and hours of ABA. They did take into consideration other factors like gender, initial severity of autism, or other styles of therapy currently being used (the Rossignol group did).
Even ignoring that, the study lost 25% of its participants sometime during the study. That simple fact alone would almost certainly have broken the randomization of the study. Yet the authors don’t really go into any details about what this did to the study. They simply say that they used an intent-to-treat analysis and leave it at that.
So the results of this “RCT” are really questionable.
MJ, when have significant flaws stopped the biomed community from accepting a study? People are touting the “chelation is safe and effective” study recently published, even though the idea that it is effective is clearly not supported by the evidence in the paper. The first HBOT study was seriously flawed. This study has some of the same flaws–for example, the idea that the two groups were really blinded is silly. The difference between 1atm and 1.3atm pressure is easily detected by the participants.
The concept that HBOT should be helpful for autism is really questionable. Doesn’t stop it from being a thriving business.
Okay, someone help me out here because I’m totally confused: to the best of my knowledge, Bradstreet and Rossignol share the same office space. Rossignol offers HBOT treatments, but Bradstreet’s study shows HBOT as having no effect on the study’s participants. So, is there something deeper here that I’m missing? Some kind of falling out between the two of them?
I doubt there is any falling out. I doubt that either of them will react to this paper, though.
The soft chambers were donated for the study. My guess is that they are still in use by Bradstreet, and will continue to be in use. Just speculation.
Sullivan, the subjects in the Granpeesheh study dove with their therapists, not their parents–the parents dropped them off at the front door of the center. Those therapists weren’t questioned for the study. Since the subjects themselves weren’t asked to fill out surveys and in all likelihood had a limited ability to assess 1 vs. 1.3, I think that qualifies as “blinded,” no?
Paige Wentworth,
I would suggest that this study design is blinded only if the autistic kids didn’t understand that they were in a study and didn’t understand what the study was about.
I would suggest that this study design is blinded only if the autistic kids didn’t understand that they were in a study and didn’t understand what the study was about.
ZING!
I wonder how many Wakefield-style birthday parties they hold there?
It also matters whether the parents and evaluators couldn’t tell between a pressured chamber and a placebo one.
In the Rossignol study, as I recall, some children went into the chambers accompanied by their parents. I don’t know if the rest were present during sessions.
About that, I don’t think so. It’s simply that the results were not as expected, and there were several researchers other than Bradstreet who were part of the study. If it had been just Bradstreet, a cynical assumption is that we’d never known about these results.
Joseph (quote): About that, I don’t think so. It’s simply that the results were not as expected, and there were several researchers other than Bradstreet who were part of the study. If it had been just Bradstreet, a cynical assumption is that we’d never known about these results.
I’ll be very interested to see if the Bradstreet/Rossignol office continues to offer HBOT when Bradstreet’s name is on a study refuting its effectiveness.
I wouldn’t say that they’re refuting the treatment altogether, merely the combination of pressure and oxygen concentration that has currently been assumed to be therapeutic/marketable.
Unfortunately I could see this as a way to up the ante, get people to come into hard chamber treatment facilities, (like the one that burned two folks last year?) and charge for the higher pressures or oxygen concentrations (and ‘professional’ service level) that can be provided there.
Sullivan, you really think an eight-year-old with autism is going to go home and say, “Mommy, I suspect I was in one of the chambers with 1.3 ATM, not 1.0”?
Frankly I think it’s a million-to-one shot an NT eight-year-old could make that assessment.
Paige Wentworth,
A 1.3Atm “dive” is like going to the bottom of the deep end of a swimming pool. I don’t know about you, but my ears hurt when I do that. I need to clear them.
MJ,
“This particular study is an example of an RCT done poorly to the point where the results don’t say anything significant.”
I agree that this isn’t a well done study. Funny, I’ll call out a study that isn’t good even when I agree with the conclusions. I don’t see the same from people (like yourself) who promote such unfounded therapies. Or, would you like to join me in pointing out that the recent chelation study was junk and the conclusions are not supported by the data? How about the huge problems with the Rossignol HBOT study? Didn’t think so.
Could you give us the reasoning behind HBOT for autism? Please, I’d love to hear an explanation beyond “Oxygen is good”, which is basically what the proponents have to say.
This study isn’t perfect, far from it. It is an indication that HBOT is useless, though. I am very interested to see if Dr. Bradstreet can sign on to a conclusion like the one in this paper and still promote HBOT. His website still does.
“As always” you try to bait. Not rising this time.
What if the parent asked “did your ears pop?” Is that also a million-to-one shot?
It’s a while since I read Rossignol et al. I don’t recall if the parents and evaluators were present during sessions. That would matter as well. The “placebo effect” is not necessarily a real effect. It could simply present itself as assessment bias.
Sullivan, as always your rebuttal is completely without merit and doesn’t even address what I said. It does not matter what other people have said about some other study nor does it matter that this study agrees with your preconceived notion of whether HBOT is helpful for people with autism.
The reason that research like this is done is to look at whether a treatment works. A RCT, when done properly, is one best tools available. This particular study is an example of an RCT done poorly to the point where the results don’t say anything significant.
@MJ: You do realize that a flawed RCT with a negative result is not evidence of a positive result, right?
Either way, neither of your objections struck me as limitations the authors would not have been aware of when they wrote the conclusions, nor do they look like problems that would change a negative result into a positive result if they didn’t exist. You probably need to elaborate to convince me, since I haven’t read this particular paper.
When you say they didn’t randomize on certain variables, do you simply mean they didn’t check if the variables matched after randomization? Is there any reason to think they wouldn’t have matched, or is that just speculation?
Of the 25% who dropped out, did they specify if they were from the placebo or treatment group? Why should the groups have different drop-out rates, unless HBOT had some problematic side-effects?
Joseph,
the paper states:
“Forty six participants began the study and 12 withdrew, resulting in 18 HBOT participants and 16 placebo participants completing all 80 sessions and follow-up measures. The primary reason reported for withdrawal was the travel required to the clinic. One participant in the placebo group withdrew after having a seizure for the first time. Mean participant age was 6.18 (HBOT 6.11; placebo 6.25) and mean number of ABA treatment hours per month was 109 (HBOT 114.7; placebo 103.3).”
As to randomization, there were no criteria given in the Rossignol study, contrary to what MJ stated before:
Thanks, Sullivan. It looks like the drop-outs were evenly split, and the main reason for drop-outs was not treatment side-effects and/or effectiveness. I thought that was MJ’s best objection, but now I see it probably has little merit.
A reminder of the matching of 3 variables from Rossignol et al.:
90.9% vs. 75.9% male.
48.5% vs. 34.5% on meds.
45.5% vs. 37.9% on ABA.
The differences were not statistically significant, and that’s fine, but then you also have possible problems with blinding, and the fact that the paper results were probably not significant once you consider multiple comparisons.
Joseph,
I do realize quite well that a flawed negative is not evidence of a positive. But the negative is still flawed and can’t be relied on.
As for the dropouts, they were mostly evenly split, I think 5 HBOT, 7 placebo. However, the authors write that they used an intent-to-treat analysis but do not give any details on when the participants droped out nor to they break out in any way which part of the conclusions is based on intent to treat participants. Or in simple terms about 25% of the data points look like they could be from people who dropped out at some point (at least in the part of the data, see the study for more details).
There was one drop out from the placebo group because the child developed seizures.
When I say they didn’t randomize, I mean the HBOT and control groups were not matched on any criteria other than age and hours of ABA. For all we know of the data all of the females were in one group and the males in the other – or even worse they put all of the children with the most severe autism in one group or the other.
And contrary to what Sullivan said (shocking), the Rossignol study did try to make sure that the groups were aligned based on a variety of variables (age, gender, severity, etc) before randoming. See Table 1 in the PDF of the report here http://www.biomedcentral.com/content/pdf/1471-2431-9-21.pdf
As I am sure you know, this is what an RCT should do if we want the result to be reliable.
Sullivan, in response to your comment –
“I don’t see the same from people (like yourself) who promote such unfounded therapies.”
Stop being a twit and attempting to put words in my mouth. Just because I don’t agree with you does not mean that I think that HBOT is a good treatment. If you think that I am promoting HBOT please provide a quote of exactly where I said that.
With or without the study, I doubt the efficacy of HBOT.
But for all who decry the existance of questionable autism therapies, know this: They flourish because the medical community has NOTHING to offer.
There are suspect medical differences between autistic children and the rest of the population. But the medical community is concentrating on genetics. It is safer. Genetics won’t impugn the practice of vaccinating our children for everything.
Sullivan, in answer to your question regarding what exactly HBOT is used for, I found Rossignol on the Scientific American site saying it had something to do with lowering “irritability levels” in autistic children by somehow relieving pressure in blood vessels located in the brain.
But really, who knows? This DAN! cabal are constantly on the search for bizarre/ off-label uses of otherwise effective therapies (chelation, HBOT, GFCF)used for other conditions I really believe that we’ll be seeing these guys advertising the efficacy of leeching and cupping in the near future.
You’re not directly promoting HBOT, MJ, but when Prometheus posted his critique of Rossignol et al. you appeared quite upset and accused him of manipulating the data from the paper. Now you’re putting the current “RCT” in scare quotes, suggesting it’s not a real RCT or something to that effect.
I guess it’s possible you’re just a stickler for good science, who knows 🙂
So basically your objections to the study can be summarized as follows:
– There might not have been matching on some variables after randomization. We just can’t be sure there was.
– Even though the drop-outs were split evenly, it’s possible the authors left out some details from their intent-to-treat analysis that could potentially be relevant in showing that the drop-outs were significantly of a different nature between groups.
That’s pretty much it, isn’t it?
“Stop being a twit ”
Still not going to rise to the baiting. Why do you continue.
I note that your response was missing actual substance. You defend yourself by pointing me to the paper that I just quoted from.
If you have something from that paper you would like to quote that I missed, please do.
Here’s what they say about table 1:
At the onset of the study, the use of nutritional supplements, medications, and applied behavioral analysis (ABA) therapy was similar in both the treatment and control groups (p = ns), see Table 1.
The fact that the two groups had similar characteristics is very different from being able to say that the researchers randomized based on those factors–which is what you said:
Just below Table 1 is the section “Randomization and Allocation”
This may seem familiar, as I quoted it above.
Joseph, you said -=
“You’re not directly promoting HBOT, MJ, but when Prometheus posted his critique of Rossignol et al. you appeared quite upset and accused him of manipulating the data from the paper.”
And where exactly did I do all of this?
“Now you’re putting the current “RCT” in scare quotes, suggesting it’s not a real RCT or something to that effect.”
That is exactly what I am saying, minus the “scare”. The goal of any RCT is to measure the change from one variable while all others are held constant. If you have a large enough effect, a large enough group, or a set of well balanced groups you can get close to this. This particular study fails on all accounts.
“I guess it’s possible you’re just a stickler for good science”
No, I just dislike nonsense.
“There might not have been matching on some variables after randomization. We just can’t be sure there was”
If there were it would have been reported in the text of the, like almost every other RCT out there.
“Even though the drop-outs were split evenly”
It was not actually even – 30% of the placebo group dropped out while 21% of the HBOT group did. But even if the numbers were dead even, losing that many of the partipants would distort the makeup of the groups. And even if it didn’t, I would expect the authors to deal with the problem directly and talk about it, which they did not in this case.
“That’s pretty much it, isn’t it?”
And you don’t think the things you mentioned would greatly weaken the results?
Sullivan, you said –
“I note that your response was missing actual substance.”
Sullivan, talking to you sometimes is like talking to a child. I make a comment, you reply to something else. I point out that your response is lacking substance – so you reply that my response was lacking substance. It is like child repeating “I know you are but what I am” over and over again.
“If you have something from that paper you would like to quote that I missed, please do.”
You said –
“Although where he got the idea that gender was considered in that study is not clear to me. They only mention “male/female” once, and never mention gender in the text.”
Which is one of the reasons I pointed out Table 1 in the Rossignol study – when you look at the table you can see that gender was taken into account.
“The fact that the two groups had similar characteristics is very different from being able to say that the researchers randomized based on those factors”
Do yourself a favor and go read up on how a RCT should work. I would recommend this book – http://www.amazon.com/gp/product/052170958X/
@MJ: In this comment.
There’s no requirement that any group variables remain constant, as far as I’m aware. What I think you’re trying to say is that variables should match across groups at the beginning of the trial.
Is there any evidence that some variable was unmatched?
You seem to be suggesting that variables were unmatched, but the authors just didn’t report this very important finding.
After a randomization, roughly only 5% of any variables you can come up with should be unmatched statistically.
They are both very speculative. They attempt to argue for hypothetical and unlikely scenarios (e.g. non-matching of characteristics after randomization) which the researchers were either too lazy to check, or withheld information on.
“@MJ: In this comment.”
Ok, first of all, that was directed to Sullivan, not Prometheus. Second, that is hardly “quite upset” unless you and I have very different meanings for the word upset. Third, this was the third post on the HBOT study and a third attempt to discredit it, using a third angle – which is what the comment was referring to.
“What I think you’re trying to say is that variables should match across groups at the beginning of the trial.”
They should match at beginning and at the end. Some characteristics are going to be constant (ie gender) while others should be held constant (other treatments). For example, what would happen to the results of the study if the participants started another new therapy in the middle of the trial, one that was not controlled for? That would invalidate the results.
“Is there any evidence that some variable was unmatched?”
There is no evidence that they matched on ANY variable other than age and hours of ABA. If the groups were matched on any other criteria is wasn’t published with the results.
“You seem to be suggesting that variables were unmatched, but the authors just didn’t report this very important finding.”
You are correct, it is possible that they did match and just failed to report this. I just don’t find it very likely that they did and somehow just forgot to publish it. My best guess is that the dropouts basically destroyed the matching between the groups so the matching was omitted rather than call attention to the fact.
Sullivan, are you deleting your comments now? Here is a hint, they still are sent in e-mail. But let me make this simple for you.
1. I am not a troll.
2. I have read the text of both studies, both the current one (CARD) and Rossignol, several times in fact. Have you?
3. You seem to be confused about which study you are talking about.
a) The CARD study is matched on age and hours of ABA but did not publish any data about the makeups of the HBOT and placebo groups. This is commonly published as Table 1 in RCTs but was not published with this study.
b) Rossignol did match/randomize on other criteria. This list included age, gender, severity of symptoms, and other treatments. They did publish the makeups of their groups as a Table 1. I linked to the Rossignol study and pointed out Table 1.
As a result, while the Rossignol study is on the weak side, the CARD study is much weaker because they either did not publish the data on the matching/randomizing on other criteria or they did not perform said matching/randomizing. Either way is a problem.
That critique was written by Prometheus, BTW. You’ll note that the critique did raise a number of valid points, e.g. there was no controlling for repeated measures. This is not a hypothetical.
Meanwhile, your critiques raise hypothetical and unlikely points, e.g. maybe some relevant variable did not match after randomization.
Yet, you are able to conclude that the new RCT is not a real RCT, but the Rossignol RCT is a good RCT; a target of mean attempts to discredit it.
You do realize that the normal expectation after randomization is that variables match, right? There’s little chance that an arbitrary variable will not match.
To say that there’s no evidence that some variable matched is misleading. Chances are that it did.
For that matter, there’s no evidence of matching in Rossignol et al. of a number of variables, such as:
– Prevalence of intellectual disability in each of the groups.
– Hours of TEACCH, RDI, etc.
– Performance in the embedded figures test.
– CARS score.
– ADOS score.
Let’s imagine that one or more of these variables did not match. Wouldn’t that completely throw off the numbers? Yet, there’s no evidence that they did match. Therefore, by MJ’s reasoning, Rossignol et al. can be dismissed in its entirely simply because of this. My imagination tells me so.
BTW, it’s clear from the post that the study employed multiple assessments, including ADOS and ABC. Evidently, the researchers would’ve noticed if the groups differed considerably in their baseline measures. Additionally, in the analysis they would’ve looked only at children who completed the study.
Both of MJ’s objections are, therefore, completely spurious.