Saturday, October 27, 2007

Dr. Adams: Is there a paper in the horizon?

Back in June, 2006, Dateline NBC did a story titled The unorthodox practice of chelation which was primarily about a small double-blind trial on chelation therapy that Jim Adams and colleagues had designed. The following is an excerpt of the interview where Dr. Adams is asked about publishing potential negative results of the trial.

John Larson: What happens in the end, after all this hard work? If you find that there really is no relation between mercury and autistic behavior. Will you be disappointed?

Jim Adams: Disappointed, yes. But whatever way it turns out, we’ll report it. If it doesn’t help, we’ll report it. And if it does, we’re gonna report that, too.
When were the results expected? End of 2006.

Jim Adams predicts he'll have the final results of his study by the end of the year, and we'll have them first, here on Dateline.
Whatever flaws the trial might have had, it is worrisome that this much time has elapsed since the results were supposed to be made available either to the media or in the form of a paper. I don't know the reasons for the delay. Maybe there are valid justifications, maybe there aren't. D'oC over at Autism Street already discussed the delay back in June.

There are surely ethical questions as to whether such a trial should be done in the first place. But it seems to me that more serious ethical questions are raised by a failure to publish results.

Why do I say this? First, there's a general issue of scientific ethics. Imagine what would happen if researchers had the habit of sitting on results they don't like. The literature would be filled with self-selected results and random noise beyond what would be expected by mere chance.

Second, suppose the study had found there are therapeutic effects to chelation therapy. It would appear to me that the sooner the results are published, the sooner bigger and better replications of the study could be carried out to identify responders, and the sooner children could be treated.

Third, suppose the study determined there are adverse effects to the treatment. Considering the popularity of chelation therapy, it would certainly be wrong to withold this kind of information.

Is it plausible that chelation with DMSA was found to have adverse effects? Yes, in fact, a trial of DMSA with rats had found that, in the absense of lead intoxication, it could contribute to cognitive deficits (source).

Additionally, even though a paper has not been published, preliminary results from the trial are known because of presentations Jim Adams has done, e.g. Preliminary Results of 3rd DMSA Study (2007).

Dr. Adams compares a group receiving 7 rounds of DMSA vs. another getting 1 round of DMSA. In a global impression scale, 8% of the children getting 7 rounds are found to be doing slightly worse or worse vs. 0% of the children who got 1 round of DMSA. Of those who got 7 rounds, 87% are found to be doing slightly to much better vs. 84% of those who got 1 round. In the "No Change" category we find 17% of children who got 1 round vs. 4% of those who got 7. (You'll note that those percentages don't add up, but that's how they are reported in the presentation.)

This brings up a question as to whether about 8% of the children suffered adverse effects after only 7 rounds.

Dr. Adams also finds that DMSA increases excretion of potassium and chromium, and that it raised glucose and triglycerides.

23 comments:

  1. Thank you for keeping up on this. I have been wondering and wondering when these promised results will be publicized. I have sent emails to Dateline which have been ignored. If I were a parent who had been persuaded to try chelation (I am not but I have friends who have done it) I would be even more eager to find out the results. What is going on here? If this is all on the up and up, what is the big hold up?

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  2. Hi Bink. If the results had been exceedingly positive, I have no doubt Dr. Adams would've been yelling about them from the rooftops, to be honest.

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  3. I guess Dr. Adams went to the Sallie Bernard College of Science, where they teach that you only need to stand behind results that agree with your preconceptions.

    Or maybe the study is so full of crap that not even "Medical Hypotheses" or the "Journal of American Physicians & Surgeons" will publish it. No, on second thought I'm pretty sure there's nothing too loony for that latter one to print.

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  4. Just a suggestion, if you want to know the status of the study, why don't you ask the researchers performing the study?

    I assume that the study is this one

    Matt Baral, ND

    DMSA Treatment of Children with Autism and Heavy Metal Toxicity, Matt Baral, ND and Jim Adams, PhD 2005-7

    I would assume that Mr. Baral's contact information is on the site somewhere.

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  5. Hi Joseph,

    I'm inclined to agree with MJ on this one. Although Jim Adams never returned the last couple of e-mails I sent him last year, prior to that, he did exchange e-mails with me extensively. Although his communications seemed chock-full of fallacious logic, poor references, and unsupported assertions, he was extremely polite and willing to discuss the study in great detail.

    As for the study itself, my bet would be that it ends up published in a journal like this one:

    Journal of Toxicology and Environmental Health, Part A
    Editor-in-Chief: Sam Kacew

    More on that here.

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  6. Another study that kind of got buried was the replication of the Rain Mouse study by Hornig et al. A researcher at UCD replicated it and apparently presented the results at a conference, but that's all. The title of the presentation or poster didn't say anything specific about the outcome.

    I once sent an email to this guy and he didn't respond. I guess I could try again.

    I'm guessing it didn't show anything that could be twisted into saying that autoimmune sensitive mice can be made into autistic mice with injections of thimerosal.... and what ever happened to Hornig's, memorial Liz Birt "Go for the Gold" mouse study? She was supposed to be given money to do the study in memory of Birt....

    And how come the results of the garbage MIND b12 study were never published, just made into an ugly and nonsensical poster presentation. I think they stopped recruiting for "phase 2" but don't want to admit it.

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  7. I just emailed Jim Adams at his ASU address. I'll post here if I get an answer.

    I've emailed researchers before and I always get an answer. I think the only time my email was ignored was when I asked SafeMinds to source their "Generation Zero" document.

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  8. Dr. Adams replied. He says they should finish the paper within a month or two. Then they will submit it and hope it will be published within a year.

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  9. Jim Adams seems to have given a presentation at the fall DAN! meeting. As stated in the ARI newsletter:

    "Jim Adams, Ph.D. shared the results of the DMSA - Autism Treatment Study he conducted at Arizona State University. He reported DMSA was found to clearly increase the excretion of some metals and resulted in some improvements in behavior. Watch for Dr. Adams' presentation on the ARI website in November."

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  10. Joseph,
    Perhaps you could reply to Dr. Adams and ask him to e-mail you a copy of his DAN! presentation?

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  11. Dr. Adams attached his presentation in his email. It's in PPT format. I thought it was the same 2007 presentation available on the web. I'll have to take a look. Maybe the data changed?

    I'll email it to you.

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  12. Ok, I'm reading the new presentation. It does have a lot more information. It starts out with data about heavy metal excretion and metabolid changes. I don't think the metabolic changes are that interesting - obviously DMSA will produce these.

    In "severity of autism" scale, both groups have a -18% improvement.

    In "ATEC results" there appears to be some improvements in favor of the 7 round group, but not statistically significant.

    In "Parent global impressions" it's not clear which is which; there's a bar graph. There don't appear to be significant differences between the groups.

    A second slide with a bar graph on global impressions appears to show the same data I discussed in this post.

    In the ADOS scale, 7 rounds seem to be slightly better, but not statistically significant. Communication was better with 1 round. (Those numbers seem different than in the previous presentation, though.)

    Summary: I don't think ARI is honestly representing the results of the trial as far as "improvements in behavior".

    I do think Dr. Adams is trying to sell the idea that both groups improved because both got the initial round of DMSA. Group differences are what count though. If you make an uncontrolled claim about both groups and piggyback it as part of the results of a "double-blind placebo-controlled trial", that would simply be wrong. I'm sure Dr. Adams realizes this, and either way, peer reviewers should notice it.

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  13. Dr. Adams also makes a claim that children with low glutathione made the most improvement, whereas 2 children with high glutathione got worse.

    Check out slide 53, Jennifer. Does that trend line look like it can be derived from the dots in the graph?

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  14. Why do I remember that they were giving glutathione along with DMSA?

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  15. Joseph,

    It could be that the peer review is also delaying things. I've read that the review process itself can be arduous in some circumstances.

    Perhaps there are problems with the methodology itself?

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  16. Swartz - From what I heard from Dr. Adams, the paper is not finished or submitted.

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  17. NM - I don't think they were giving glutathione, but some autistic kids are given that. See this.

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  18. Oh, see also this. Parents believe they are able to breach the double-blinding of the study because they know the symptoms of chelation. I don't know if that's true or not, but it's interesting.

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  19. On this consent for they talk about transdermal DMSA and Glutathione lotion.
    http://www.scnm.edu/forms/AutismConsentform.pdf

    Of course here they have glutathione in quotes:
    http://www.autism.com/danwebcast/presentations/alexandria/Saturday/Adams.pdf

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  20. If they followed through with what the consent form states, it would seem this is a trial of not only chelation but chelation in combination with glutathione cream. That would seem to be a marginally relevant thing to mention.

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  21. Now published:
    http://www.biomedcentral.com/1472-6904/9/16
    http://www.biomedcentral.com/1472-6904/9/17

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  22. Yep, I heard. It took a while, and it was spinned just as I thought. Basically, no significant between-group differences in outcome, but still it's sold as showing that DMSA helped both groups.

    If anyone is wondering "how did this get past peer review with this spin?" check out who the peer reviewers were in the prepublication history: Richard Deth and Ray Palmer.

    How in the heck did that happen?

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