Damn you, Kathleen.
Every time I think that I can give the whole mercury/autism thing a rest for a while and move on to less infuriating pastures, you keep finding things that keep dragging me back to the pit of pseudoscience inhabited by Dr. Mark Geier and his son David. The first time around, Kathleen found the Geiers misrepresenting David Geier’s credentials on published journal articles to make it appear that David Geier had done the work reported in the articles at George Washington University when in fact he had not. I found David Geier’s appropriation of the name of George Washington University distasteful, and said so, elaborating a bit on why such misrepresentations are frowned upon in the world of science. The second time around, what Kathleen reported was much more disturbing to me, namely that the Geiers had formed a dubious (at best) Institutional Review Board to rubberstamp their “studies” involving measuring androgen levels in children with autism based on their scientifically and chemically implausible and unsupported idea that somehow testosterone interferes with chelation therapy because (they claim) testosterone binds mercury and prevents if from being eliminated from the body. (Never mind that the existing scientific evidence does not support a role for mercury in the pathogenesis of autism.) Presumably, if the Geiers are bothering to use an IRB at all to examine it, this is the same IRB that would oversee the Geiers’ “Lupron protocol,” in which they give a powerful drug that inhibits the production of sex steroids, a protocol that they are trying to patent. Between the patent, the dubious IRB that contained both David and Mark Geier, Mark Geier’s wife, anti-thimerosal activists, and a woman whose child was in the Geiers’ study, I was beginning to see a pattern, a pattern that, as a medical researcher, I did not like at all.
And the pattern continues, and, my annoyance at being assaulted with yet another example of the Geiers’ lack of concern for sound research aside, I’m glad Kathleen is on the case.
This time around, Kathleen reports on how the Geiers are “justifying” their use of Lupron to treat autistic children. All I can say is: Just when I thought it couldn’t get worse after the business of the dubious IRB, it gets worse. In this installment, we learn how the Geiers have been publicizing their new “Lupron protocol” among desperate parents who had swallowed the chelation therapy Kool Aid before. Of course, my spin on the receptiveness of these parents to something as ridiculous and dangerous as Geiers’ Lupron protocol is that they are starting to realize that chelation therapy doesn’t work, but that’s a topic for another day. Ditto the disconnect between parents who are deeply suspicious of “conventional medicine” and “big pharma” who are willing to subject their precious children to powerful drugs that completely shut down the synthesis of sex hormones. A more “big pharma” overkill approach to autism I for one can’t think of, but because it comes from the Geiers it’s all too frequently accepted.
Kathleen’s account is quite comprehensive; so I’m going to zero in on select aspects of it that I think I can elaborate on sufficiently to make it worth your while to read. One problem that using Lupron for an indication for which medical science does not support its use causes is due to the fact that it’s an expensive drug. As one parent reported:
My son’s Lupron Depot was $1538.00 pre shot, given every 30 days. Dr Geier did the shots on my son since my insurance would only cover them if they were done in a doctor’s office. My Carefirst PPO did cover it but it was a real fight. (March 21, 2006)
Insurance companies often don’t pay for “off-label” uses of drugs. They certainly don’t pay for off-the-wall uses of drugs like the use of Lupron for autism. How will parents pay for this very expensive treatment protocol being administered by Dr. Geier? The Geiers appear to have the answer. They try to make a diagnosis of precocious puberty on these children. Unfortunately for this approach, precocious puberty is a pretty rare condition, as both Kathleen and I have discussed before, even having led me to ask: “Anyone want to take any bets on how long it is before there is a flood of autistic boys with the diagnosis of “precocious puberty?” (The answer, apparently, is “a few months.”) The problem with this approach is that there are very specific diagnostic criteria for a diagnosis of precocious puberty, and among these are symptoms of the onset of secondary sexual characteristics before age 8 in girls and age 9 in boys coupled with increased bone age. In girls, that means the growth of breasts, wider hips, and the growth of pubic and underarm hair. In boys, it means the growth of facial, chest, underarm, and pubic hair; deepening of the voice; and enlargement of the penis and testes. In the absence of the premature onset of these secondary sexual characteristics, there is no real reason to do a workup for precocious puberty. Moreover, as mentioned before and as Kathleen emphasizes, precocious puberty is a rare condition:
Central precocious puberty (CPP) is the only pediatric condition for which sufficient evidence of safety and efficacy of Lupron exists to support FDA approval. With an estimated prevalence rate of 1:5,000 to 1:10,000 — 90% of whom are female — CPP is rare enough that a European endocrinological research consortium found it necessary to pool data from The Netherlands, Italy and France in order to accumulate 26 male subjects for a study of the effect of gonadotropin-releasing hormone agonist treatment on height.
Of course, none of this has stopped the Geiers from applying the diagnosis of CPP, medical appropriateness be damned, and if you ever ask one of these parents that inhabit the Evidence of Harm list who are supporters of the Lupron protocol to tell you the difference between CPP and peripheral precocious puberty (PPP), you’ll generally get blank stares. Has anyone ever heard of confirmation bias? Basically, it’s the human tendency to look for evidence that supports preexisting beliefs and to discount evidence that does not, all often on a subconcious level. Kathleen’s account suggests that the Geiers, whether consciously or not, are using confirmation bias to their advantage by designing an interview guaranteed to plant the suggestion in parents that there are indeed signs of precocious puberty:
One year later, in his 2006 Autism One presentation, David Geier described a “novel” diagnostic interview in which parents were asked to report “signs of premature puberty” in their children, and offered examples of supposed behavioral and physical indicators of the condition: “This is an area that’s very novel. We’ve now asked an awful lot of patients, and it’s something that mainline physicians and other doctors aren’t asking, which is, we asked for these patients, “do your children have signs of premature puberty?” And a fair number answered, “Yes.” And then we start talking in our interview, asking for specific questions. And these are things that if your child is, say, under eleven or ten, if they are showing early sexual changes, meaning masturbation behaviors, they’re showing aggressive behaviors, hair on their legs, mustache growing in, all of these things, growth spurt — these are things that are not normal.” (May 26, 2006)
Aggressive behaviors and self-stimulation are not necessarily abnormal in children under 9, and, in the absence of genital development and pubic hair, leg hair and growth spurts are not indicators of precocious puberty either. Worse, the Geiers are screening a series of over 30 lab values, looking for at least one that’s abnormal. Kathleen didn’t explain this (probably because she isn’t a medical professional involved in clinical research), but if you screen for 30 lab values in almost anyone, you have a good chance of finding at least one that’s abnormal. The reason for this is that “normal” for most laboratory values is defined as the range that encompasses 95% of the normal population without conditions that could be expected to change the lab value. Consequently, 5% of “normal” patients will have an abnormal value in any single lab test. If you screen for 20 lab values, there’s a close to a 100% probability that one of the tests will be abnormal. Testing for 30 or more lab values, there’s a pretty good chance that two or more of them will be abnormal. (Indeed, when peer reviewing papers, I have rejected papers that were guilty of looking at many variables without using statistics to control for multiple measured lab values or parameters for that very reason.) By using a “shotgun” workup, the Geiers almost guarantee that almost every child they test will fit into their diagnostic criteria. Whether this is simply because they do not understand how normal lab values are defined and the basic statistics that guarantee that testing large numbers of lab values will turn up at least one “abnormal” value that probably means nothing, I don’t know. But Dr. Geier is a physician, and this is the sort of stuff I was taught in medical school when learning how to interpret panels of lab tests. I can’t believe that Dr. Geier didn’t also learn this in medical school himself, although diagnostic panels with multiple lab values in a single run were not as common back in the 1960′s and 1970′s. Or perhaps he’s forgotten it. Another thing they taught me in medical school is that you don’t treat lab values; you treat the patient. If the patient has no definitive physical signs of precocious puberty, there is no need to “treat” that patient for “precocious puberty” almost regardless of the lab values. Indeed, it is not even always necessary to treat children with a definitive diagnosis of CPP based on clinical signs, imaging studies, and lab values:
It is important to keep in mind that not all children with precocious puberty require treatment, especially if their bone age is not very advanced and they have a normal rate of growth. They will require frequent visits to their doctor to monitor their growth and development and to see if treatment is required at a later time.
Clearly, as Kathleen pointed out, all this testing seems as though it’s designed to get insurance companies to pay for the Geiers’ protocol to “lower testosterone” to make chelation therapy “work better,” not to confirm a true diagnosis of CPP:
“Working with” a diagnosis of precocious puberty to justify prescriptions for Lupron administered in conjunction with chelation may serve to temporarily insulate Dr. Geier and Mr. Geier from criticism from “mainline medicine.” A diagnostic interview in which parents are encouraged to regard common behaviors with a wide range of possible causes, such as aggression and masturbation, as indicative of a rare condition, may enable parents to be persuaded to consent to pharmaceutical treatment of their children for a nonexistent problem. A diagnostic process that is “not that restrictive” may enable parents of autistic children who might not meet criteria for CPP according to professional practice guidelines to “try out” Lupron on their children, and acquire the drug without incurring substantial out-of-pocket expenses; it may also facilitate recruitment of subjects for the Geiers’ research, and minimize their costs in conducting it.
I have a real problem with that. The diagnosis of CPP is intentionally designed to be restrictive, because there’s a fairly wide range of normal ages for children to begin to enter puberty and because the treatment for CPP is not benign. As evidence of the Geiers “not that restrictive” criteria for the diagnosis of CPP, Kathleen presents examples in which parents are urged not to tell their insurance companies that their child is also undergoing chelation therapy, presumably because that would be a red flag. Even worse, she describes examples of the diagnosis of CPP being given to children 9 or older who by definition can’t have CPP–period.
Going through Kathleen’s report, I have to congratulate her on how well-documented, detailed, and comprehensive her takedown of the Geiers is. If there were a Pulitzer Prize for blogging, she should be nominated for it. Three times now, she has exposed the dubious “research” practices of Mark and David Geier. In each new installment, the story gets worse than what was described in the installment before. At the end of this third installment, Kathleen finishes, as she has with the previous installments, with a big “to be continued.”
That promise makes me afraid of what I’ll read when next she posts.