In going back to their data and reanalyzing by subgroup I notice they specifically avoided looking at the subgroup “nearsighted albino pagans”. Significant?
That IS a good question, I agree. :: cough cough ::
There was no “revised study”. The authors did subgroup analysis of their data, the collection of which was flawed as previously noted. To recap:
*"Unfortunately, the efforts of these investigators fell short of the minimum level of quality necessary to adequately answer the question they sought to investigate…The evolution of clinical trial design over the past 4 decades is based on the principle that a high-quality RCT must effectively minimize bias and variability…
Execution of a high-quality RCT requires skilled investigators and study coordinators who understand these critical scientific principles. For TACT, more than 60% of patients were randomized at enrolling centers described as complementary and alternative medicine sites. Many of these centers have websites that describe their services, which include an array of unproven therapies ranging from stem cell therapy to regrow breasts after mastectomy, high-dose intravenous vitamin C to treat cancer, and use of cinnamon for treating diabetes to treatment of influenza with antimicrobial essential oils or homeopathic remedies (while warning patients not to undergo immunization). Other sites offer chelation to treat or cure a variety of conditions including autism in children. A common theme of these centers is evident—they appear to attempt to appeal to vulnerable patients who have challenging diseases by offering a variety of unscientific and unproven therapies. Whether a high-quality RCT can be performed at such sites is questionable.
Not surprisingly, with a high fraction of such study sites, TACT showed some important deviations from adherence to the scientific principles of a well-controlled trial. The study randomized 1708 patients, but 311 (18%) were lost to follow-up, nearly all because of withdrawal of consent (289 patients), and importantly, these withdrawals were not equally distributed between the treatment groups. Significantly more patients (n=174) withdrew from the placebo group compared with the chelation group (n=115; hazard ratio, 0.66; P = .001). A similar imbalance in discontinuation from randomized treatment was observed—281 in the placebo group and 233 in the chelation group.
In some RCTs, more patients stop study treatment in the active treatment group because of toxicity or adverse drug effects. However, in TACT, why would patients differentially withdraw in such large numbers from the placebo group? A logical explanation is unmasking of treatment assignments. If either the investigators or the patients knew who was receiving chelation, patients assigned to the placebo group would likely be influenced to withdraw or stop study treatment, particularly when some investigators were advocates for chelation therapy.
The substantial nonretention of study participants is sufficient to compromise the validity of the study results…
Differential dropout in TACT suggests unmasking, but the problem of intentional unblinding is more concerning. The sponsors of the trial, the National Heart, Lung, and Blood Institute (NHLBI) and the National Center for Complementary and Alternative Medicine (NCCAM), were unblinded throughout the trial. The National Institutes of Health policy unwisely allows the sponsor access to unblinded trial data, and both organizations sent observers to the closed sessions of the data monitoring committee. This gave them access to confidential data during each of the 11 interim analyses. The unblinding of the study sponsor represents a serious deviation from acceptable standards of conduct for supervision of clinical trials. If a pharmaceutical company sponsoring a trial were allowed access to actual outcome data during the study, there would be major objections."*
And on and on.
I do not see where any of these serious objections have been addressed by the massaging of the data just announced by the study authors.
As to the role of NCCAM, it is noteworthy that this division of NIH has been under heavy criticism recently because after years of funding studies into alternative treatments and billions spent, virtually nothing has come of it. It does not surprise me that NCCAM’s director apparently thinks more money should be plowed into chelation therapy research. That would keep her organization going at a time when budget constraints threaten it.
Just woke up and got my coffee. Can’t really muster enough interest to respond to any of you though. Sorry.
The official approved response in woo-land after an online beatdown is “I have better things to do with my time.” 
I most definitely don’t have anything better to do. 
Jackmannii,
I’ve given up on any hope that our op will appreciate much if he does not get why that XKCD cartoon is so appropriate. Your post however makes me want to keep this study around to use with medical students as an illustration of the many things that researchers can and do do wrong.
In the subgroup analysis the problems that your post points out (those above and beyond the problems inherent in post hoc analysis data dredging) are even more pronounced. There were 322 diabetics randomized into the treatment arm and 311 into the “placebo” (diabetics given a glucose infusion 40 times, as opposed to a heparinized vehicle). In the treatment arm 216 completed the course of 40 IV infusions (69%). In the “control” arm 171 completed the course (55%). Put another way 45% of the controls failed to complete the study compared to 33% of the treatment arm. (In terms that our op understands this means that getting active medicine was associated with a 27% reduction in completing the study despite both patients and investigators being allegedly blinded to what was active or not.) The smoking gun is that 11 of those who dropped out of the control arm did so in order to recieve open-label EDTA (compared to* none* in the treatment arm) and “physician preference” as a cause for dropping out was given 66% more of the time in the control than in the treatment arms, or phrased another way there was a 40% decrease in the outcome of physicians preferring the patient drop out of the study asociated with being given active medication. Putting the opt out for open-label EDTA and the “physician preference” groups together being on active medicine was associated with 18% of the likelihood of dropping out for either of those reasons. Only 18% of the chance! If a 40% reduction of an outcome is, to our op, “extraordinary” and “highly significant” then I wonder what superlative could suffice for this!
By far the most likely explanation for those numbers is that the blinding was blown. Cheating, a.k.a. “intentional unblinding”, is not the only way blinding gets blown. The lack of side effects associated with active treatment, is one way that an investigator or patient can deduce which is active and which is placebo, i.e. “unmasking”. (EDTA typically causes some stinging on IV infusion; glucose in normal saline does not.)
A prime example of crap and great vehicle for teaching critical analysis of journal articles!
Well what did you expect after a night of heavy drinking with a bunch of snake oil salesmen?
Really guys? Just because I want to keep an open mind you’re going to start the ad hominem attacks? That’s so typical of the mindset of dogmatists.
I take back what I said before about not having anything better to do. If the choice is defending myself or ignoring you, I’ll happily ignore you.
Oh c’mon. Take a joke. You brought up the drinking, happy dancing, and partying.
But sure ignore away. More importantly don’t reconcile how being on a blinded active medicine is associated with an 82% reduction of the risk of leaving the study either because your doctor told you to or to get on open-label medication compared to being on the “placebo.” That is one highly significant result. More than extraordinary!
Oohhh. It was a joke. Gee. How many times have I heard that bullshit line. :rolleyes: But sure. Whatevs. It’s not like I really care what you or anyone else here thinks of me. After 4000 posts, if THAT much hasn’t become clear, you need to pay more attention.
But no reponse to the issue of an 82% reduction of the outcome of dropping out due either because your doctor told you to or to get on open-label medication? Why do you not find that extraordinary and clearly highly significant? The medicine apparently clearly causes people to not be told to drop out or want to switch to being sure they are getting the medicine in a highly significant way. Why?
Where is your awe? Or have you moved into the shock phase?
Nope. You seem intent on continuing this train wreck and I’m intent on frustrating you.
edit: How am I doing boss?
I worked in a neurophysiology lab undergrad and coauthored several papers that were published in respected journals. When I spent a year collecting data and it was unexciting, looking for ways to create publishable data (subgroup comparrison) was the next step. And often it was rewarding. Cause of statistics.
ETA: just sayin.
:dubious:
:eek: :rolleyes: 
Not frustrated … mildly amused. In a sad shaking of the head sort of way.
I was pretty confident that you would not attempt any explanation of those numbers as there really is not any (although one could accuse me of doing a post hoc analysis and of not including confidence intervals ;)) and I was also pretty sure that you would not be one of the posters who would be able to admit they were just plain and simply wrong.
Awww. I’m so sorry to hear that. Somehow I’m sure that you’re recover though. :rolleyes: