With a little help from its friends, NCCIH funds Son of TACT to study chelation quackery again

One of the things that first led me to understand the dangers of quackademic medicine was a trial known as the Trial to Assess Chelation Therapy, or TACT. Chelation therapy, as you might recall, is the infusion of a chelating agent, or a chemical that binds heavy metals and makes it easier for the kidney to secrete them, in order to treat acute heavy metal poisoning. Unfortunately, quacks of all stripes have latched on to chelation therapy to treat a number of diseases and conditions. For instance, antivaccine quacks like to use chelation therapies to treat autistic children using the rationale that their autism is a manifestation of “vaccine injury” due to the mercury in the thimerosal preservative that used to be in several childhood vaccines. The evidence is overwhelming that mercury in vaccines is not associated with autism, but that is one of the two pseudoscientific beliefs behind the belief by antivaccinationists that vaccines cause autism, the other being that the MMR vaccine somehow causes autism. Of course, thimerosal was removed from vaccines nearly 15 years ago, but that never stopped autism quacks from continuing to use it as a part of “detoxification.” Never mind that, because of its ability to reduce the concentration in the blood of critical minerals like magnesium and calcium so much that heart rhythm disturbances result, chelation therapy is potentially dangerous and at least one child has died due to chelation therapy. Once latched on to, quackery is never abandoned.

I’m not actually going to discuss chelation therapy for autism (due to “vaccine injury,” according to antivaccine activists), though. It turns out that the other major use of chelation therapy in alternative medicine is to treat heart disease, the rationale being that there is calcium in some atherosclerotic plaques, the thought being that you could chelate the calcium out and cause the “softening” and regression of these potentially life-threatening plaques. Unfortunately, it doesn’t work that way, but that didn’t stop chelationists from Gish galloping away with ever more fanciful and less plausible explanations about how chelation “works.” Not only is chelation therapy implausible based strictly on chemistry and stoichiometry, but there is no good evidence that it actually causes regression of atherosclerotic plaques.

Sadly, none of this stopped believers from undertaking a large, multi-institutional study of chelation therapy for cardiovascular disease. Thus was TACT born. Kimball Atwood wrote the definitive explanation as to why TACT was unethical, bad science, and highly unlikely to produce usable results way back in 2008. You really should read the whole thing for background, but among the reasons given by Atwood included:

  • At least 30 deaths associated with chelation since the 1970s, while not one death is noted in the TACT literature.
  • TACT was promoted mainly by a group called the American College for Advancement in Medicine (ACAM), a highly dubious organization devoted to the promotion of alternative medicine.
  • The study was rejected by the National Heart, Lung, and Blood Institute (NHLBI) in 2000, but a year later the NHLBI and the National Center for Complementary and Alternative Medicine (NCCAM), now known as the National Center for Complementary and Integrative Health) jointly issued a Request for Applications (RFA) for a chelation trial “expected [to] investigate the EDTA Chelation treatment protocol recommended by ACAM.” The winning application – the 2001 TACT protocol – was approved a year later by an NCCAM “Special Emphasis Panel” that included an ACAM officer among its 6 members.
  • There were no good animal studies or human phase I or II trials to support doing such a large multicenter randomized, double blind, placebo-controlled clinical trial.
  • TACT included nearly 100 “chelation site” co-investigators who were unsuitable to care for human subjects or to report trial data. Most espoused (and continue to espouse) implausible health claims while denigrating proven methods; several have been disciplined, for substandard practices, by state medical boards; several have been involved in insurance fraud; at least three were convicted felons. Dr. R. W. Donnell once did what he called a “magical mystery tour” of several of the TACT sites. Basically, they were quacks.Only 12 of the 110 TACT study sites were academic medical centers, and many of the study sites were highly dubious clinics touting even more dubious therapies, including heavy metal analysis for chronic fatigue, intravenous infusions of vitamins and minerals, anti-aging therapies, assessment of hormone status by saliva testing, and much more. Dr. Donnell also points out that the blinding of the study groups to local investigators was likely to have been faulty.

Unfortunately TACT marched on. Over $30 million later in 2012 its results were revealed. Let’s just say that they were...underwhelming. You can read the details in the two links I just listed, but the CliffsNotes version is this. TACT tested chelation therapy versus placebo. Actually, it was more complicated than that. The TACT study was set up with a 2 x 2 factorial design:

  • Chelation plus high oral high dose vitamin and mineral supplement
  • Chelation placebo plus oral high dose vitamin and mineral supplement
  • Chelation plus oral high dose vitamin and mineral supplement placebo
  • Chelation placebo plus oral high dose vitamin and mineral supplement placebo

The regimen was described in detail in an earlier publication. The vitamin supplements included doses ranging from 25% to 6,667% of the RDA for various vitamins. For example, the dose of vitamin C was 2,000% of the RDA; thiamin, 6,667%; and vitamin A, 500%. The previous presentation looked at the chelation therapy aspect of the study. This study looks at the oral high dose vitamin and mineral supplement treatments.

Now let’s get to the results. They were, in essence, negative. There was no difference between any of the chelation groups in the composite endpoint that consisted of death, MI, stroke, coronary revascularization and hospitalization for angina. There was only one subgroup that showed a seemingly positive result: Diabetics. There were no statistically significant differences in any of the events aggregated to form the composite endpoint, including among diabetics. It was a result that could well have been spurious. So, in reality, the appropriate way to report the results was that chelation therapy doesn’t work, with the possible (slightly possible) exception of in diabetics, particularly diabetics with previous cardiac events. In reality, given the extreme implausibility that chelation therapy has any therapeutic effect against atherosclerotic heart disease based on chemistry, the most parsimonious interpretation of TACT is that it was a negative study. Unfortunately, my saying so led to some rather harsh attacks against me, with one characterizing criticism of the results of TACT as “shrill and brutish.”

So, after wasting $30 million funding a sham of a study, what’s next? I note that when Steve Novella, Kimball Atwood, and I met with Dr. Josephine Briggs, the director of NCCAM, in 2010, one of the things I remember most about our conversation was the discussion of TACT. Basically, Dr. Briggs did everything she could to distance the herself from TACT, pointing out that it was funded before her tenure as director began and it had been turned over to NHLBI, in essence shutting down conversation about just how unethical and pseudoscientific the study was from its very inception.

Apparently times have changed, because the other day there was a press release announcing that the NIH is funding TACT2. Yes, there will be a sequel to the misbegotten, unethical mess of a study that was TACT. The Son of Frankenstein rises again. And how much will it cost? Let’s go to the press release:

The National Center for Complementary and Integrative Health (NCCIH) of the National Institutes of Health (NIH) has awarded $37M to Mount Sinai Medical Center of Florida and the Duke Clinical Research Institute to initiate the second Trial to Assess Chelation Therapy (TACT2). The trial is also co-funded by the National Heart, Lung and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute of Environmental Health Sciences.

TACT2 will examine the use of intravenous chelation treatments in combination with oral vitamins in diabetic patients with a prior heart attack to determine if they reduce recurrent heart episodes, such as heart attacks, stroke, death, and others, by removing toxins from the blood. Chelation is a process by which a medication, such as edetate disodium (Na2EDTA), can "grab" and remove toxic metal pollutants - like lead or cadmium - which are present in most individuals.

Ah, yes. Spread the blame around by having more than one institute and center in the NIH fund the thing. Can you say “plausible deniability” for each institute? Sure, I knew you could. Apparently Dr. Briggs, for all her effort to distance herself from what she appeared (to us, at least) to know was, scientifically speaking, a flaming pile of fetid dingos’ kidneys, has either had a “come to Jesus” moment, swallowed her scientific credibility, and drunk deep of the Kool Aid. After all, there’s no way a study this big gets funded without the directors of the relevant centers and institutes all signing off on it, which means Dr. Briggs must personally have signed off on this study. Yes, these studies do go through peer review in NIH study sections, but there is a second tier of review, where final decisions are made regarding what grants to fund. These rely heavily on the study section findings, but for very large grants the relevant directors will definitely need to sign off. And, make no mistake, $37 million is a very large grant indeed. By way of comparison, a typical R01 is on the order of $1.25 million plus indirect costs, which still leave it under $2 million.

So let’s see how the Mount Sinai Medical Center of Florida is spinning this in its press release:

"If TACT2 is positive, it will forever change the way we treat heart attack patients and view toxic metals in the environment," said Lamas. "Therefore, with NIH support and in collaboration with the Duke Clinical Research Institute, Columbia University, New York University, Mount Sinai (NYC), and hundreds of physicians and nurses throughout the U.S. and Canada, we are moving forward with TACT2."

A one-year planning phase for TACT2 was conducted and included finalizing the research protocol for the trial as well as gaining NIH approval. During this phase, the investigators also identified over 100 clinical research sites in the US and Canada that aim to enroll 1,200 cumulative patients in the trial.

Yes, Dr. Lamas is deluded enough to think that it would be a good thing if quackery like chelation therapy becomes accepted. That’s how far down the rabbit hole he’s gone. He also thinks that it would be a good idea to spend even more than what was spent on the original TACT trial on a sequel that is not scientifically indicated.

Seeing this press release, I was curious. So I went to the RePORT website and found what TACT2 entails:

The purpose of the Trial to Assess Chelation Therapy 2 (TACT2) is to perform a pragmatic and efficient replication of TACT1 in patients with diabetes and a prior heart attack.

OK, stop right there. Whenever I hear the term “pragmatic” applied to a clinical trial, my skeptical antennae start twitching. As I’ve described so many times before, “pragmatic” means “in the real world.” Here’s the problem. Pragmatic trials can be useful, as they can give an indication of how well a treatment might work “in the real world” or “on the ground” or whatever analogy you want to use to describe taking an effective treatment and applying it to real patients. However, you have to show that a treatment is truly efficacious before a pragmatic trial can be justified.

But let’s check out the rest:

The results of this trial will determine whether disodium ethylene diamine tetraacetic acid (Na2EDTA) chelation therapy receives approval from the US Food and Drug Administration (FDA) and is subsequently accepted to reduce the risk of major adverse events from coronary artery disease (CAD) in patients with diabetes. TACT2, if positive, will also promote research into the mechanism(s) of benefits and provide novel insights into the pathobiology of CAD. The Trial to Assess Chelation Therapy (TACT1) was developed in response to a Request for Applications from NCCAM and the National Heart Lung and Blood Institute (NHLBI) to address the concern that chelation use was widespread but there were no reliable data on either safety or efficacy.

Holy hell. Just because a lot of quacks are using chelation therapy does not mean that there has to be a study! After all, there aren’t even any good animal studies to support the use of chelation therapy. In general, the progression of evidence goes from cell culture to animal studies to early human clinical trials to phase 3 clinical trials. Then, only then, is a drug approved for use. In any case, let’s look at the design:

The three Specific Aims of TACT2 are: 1) To determine if the chelation-based strategy in patients with diabetes and prior MI improves event-free survival; 2) To determine if the chelation-based strategy in patients with diabetes and prior MI reduces mortality; 3) To perform a cost-effectiveness analysis of the TACT2 chelation strategy. TACT2 will enroll 1200 diabetic patients 50 years of age or older with a prior MI and a serum creatinine of 2.0 mg/dL or less. Patients will be randomly allocated (1:1) to receive either chelation + OMVM or double placebo and followed for clinical events until the end of the 5 year trial. The primary endpoint will be a composite of all-cause mortality, recurrent MI, stroke, coronary revascularization, and hospitalization for unstable angina. A Clinical Events Committee masked to treatment assignment will adjudicate events. Principal secondary endpoints will include: (1) all-cause mortality; (2) a composite of cardiovascular mortality, recurrent MI, or stroke; and (3) safety.

Here we go again. Instead of looking at “hard” (i.e., objective) endpoints like all cause mortality, recurrent MI, and stroke, TACT2 will be looking at the same composite endpoint that includes endpoints with a lot of judgment behind them, such as hospitalization and the need for coronary revascularization. If Dr. Lamas were truly serious about determining if chelation therapy worked, he’d drop the composite endpoint and look only at all cause mortality, myocardial infarction, and stroke as primary endpoints without creating this Franken-endpoint.

I realize from my previous discussions of TACT that other cardiology studies have used composite endpoints, and such endpoints are not uncommon in cardiology clinical trials, but that does not mean I accept them. Let’s just put it this way. composite endpoints are not in general a good thing. There’s a way but they can be made less bad, so to speak, by not including subjective endpoints like coronary revascularization and hospitalization, both of which are subject to a great deal of clinical judgment in deciding who requires them. More problematic is the variation in usage of such interventions that has nothing to do with whether the treatment works or not. For instance, in the state of Michigan, there is up to a 2.4-fold variation in rates of percutaneous coronary interventions (PCI; i.e., angioplasty) between the highest use and lowest use areas. That’s just one state. Similar studies have shown wide variability in coronary revascularization rates just on geography alone. Adding such a variable to a composite endpoint is thus a bad idea on a scientific basis alone. At best, it adds unnecessary variability to the composite outcome measure for no useful benefit; at worse it adds significant bias, particularly if subjects being treated in academic centers, where patients are more likely to be referred for appropriate coronary revascularization interventions were in areas with significantly different PCI usage rates than areas where subjects being treated in “complementary and alternative medicine” (CAM) centers, where one might reasonably expect that referral for revascularization might be a bit less—shall we say?—expeditious. I could see a composite endpoint in which the components were all “harder” endpoints, such as the triple endpoint of death, nonfatal MI, and nonfatal stroke, but even such endpoints are not without problems.

In the end, you and I (at least those of us in the US who pay taxes) are funding an even larger boondoggle of a quackademic study than TACT was in the form of TACT2. I predict (as Atwood did for TACT) that TACT2 will be just as large of a fiasco as TACT was, particularly if the same centers are used to recruit patients for it. Unfortunately, I also predict that it will, like TACT, end up appearing to be “positive” enough to “justify” the next study. Remember, if you look at objective endpoints only, TACT was actually resoundingly negative. It took the composite endpoint to make it appear positive.

My final word is directed at Dr. Josephine Briggs and NCCIH. Whatever my problems with NCCIH, I always thought that Dr. Briggs was trying to steer it towards more scientific accountability, even though by its very nature NCCIH can’t ever truly be scientific. NCCIH’s funding of TACT is a large step backward in terms of making NCCIH less pseudoscientific. In fact, it’s a big step back towards the “bad old days” when NCCIH (then NCCAM) funded studies of reiki distant healing and homeopathy. Apparently the interest in promoting scientific rigor proclaimed in the last two NCCIH strategic plans (or, as I put it, “let’s do some real science for a change”) couldn’t withstand the buzzsaw of quackery demanded by NCCIH’s stakeholders, such as ACAM.

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I thought quacks said simple lifestyle changes that they alone can get you to do were all that's needed for heart disease. Why do quacks keep rolling out this Edsel?

By DevoutCatalyst (not verified) on 29 Sep 2016 #permalink

Almost $80 million to study a chemical beloved by quacks. It is really odd how quacks like this one chemical so much. I guess its association with quackery around vaccines has made this a good synthetic chemical so therefore it can be used to treat all kinds of diseases in the quack world.

The mindset that if a chemical is good to "treat" vaccine injured kids, therefore that chemical can be used to treat various other diseases seems rather primitive or magical. In contrast, I would assume that a chemical specific enough to treat one disease is highly unlikely to be the treatment for other diseases.

Statistician says: "at worse it adds significant bias" - I don't see how, cause I'm presuming that randomization to the arms will be balanced within each center.

That's a big assumption for TACT. Also, try reading some of Dr. Donnell's magical mystery tour of TACT sites and his post about how blinding was probably compromised at a lot of them. That's actually only a small piece of what was wrong with dozens of sites signing up TACT patients. I could easily have doubled or tripled the length of this post detailing the other—shall we say?—oddities in how patients were signed up and the trial run at many of these sites.

@ Mike

I would assume that a chemical specific enough to treat one disease is highly unlikely to be the treatment for other diseases.

There are notable exceptions, so I'm not sure about this. Aspirin has plenty of applications, and in a recent post here at RI I learned that a number of anti-cancer drugs are used - with some level of success - to treat lupus.

But I would admit that in these cases the different susceptible illnesses share some common modality, so this explains that. You are using your hammer because there is really a nail here.

I think the real assumption to be challenged here, in the first place, is the usefulness of chelation therapy on autism.

By Helianthus (not verified) on 29 Sep 2016 #permalink

$80 Million, in an age where legitimate research is starved of funds....got to love it.

And where are the IRBs that are supposed to derail unethical studies involving human subjects?

I've never applied for funding on a project that was subject to IRB approval, but my recollection from the internal forms is that, at least at my institution, a prospective PI or institutional PI is required to apply to the IRB before submitting the proposal. In some cases a proposal can be submitted while IRB approval is still pending, but if you haven't applied for IRB approval on a project that requires it, our sponsored projects office will not let your proposal out the door. Admittedly, we don't have a medical school on this campus. How does this policy compare to other institutions: stricter, looser, or comparable?

And yes, where is Sen. Proxmire when we need him? Bad enough to spend $30M on a dubious study that produces null results, when at least such a study hasn't been done before. To spend an additional $37M on a follow-up study to which we already know the answer? That's 20-ish R01s on plausible topics that didn't get funded. Maybe some of even most of those would have turned out to be dead ends, but even so that's a better return on scientific investment than this turkey.

By Eric Lund (not verified) on 29 Sep 2016 #permalink

No-one could have anticipated that trying to placate a pack of skeezy grifters by paying them off would simply encourage them to come back and grift some more.

By herr doktor bimler (not verified) on 29 Sep 2016 #permalink

While it does have to do with the brain, many drugs to prevent migraines are anti-seizure or anti-depressants medications used at lower doses.

And of course, the big (heh, heh) example of this is Viagra.

And where are the IRBs that are supposed to derail unethical studies involving human subjects

Actually, apparently there were some IRB shenanigans associated with TACT as well, but I don't know enough of the details and the sources to write about them authoritatively. So I left out that part.

And yes, where is Sen. Proxmire when we need him?

As I recall, the most notable thing to emerge from the "Golden Fleece" awards was Hutchinson v. Proxmire, 443 U.S. 111 (1979).

Thank you NIH for funding another worthless study. Removing the calcium seems pointless, but maybe that is the point: keep the scientists busy doing something that is bound to fail; delay the cure from being known for as long as possible.

CVD can be reversed with diet, and probably has something to do with Vitamin C.

Does anyone want to hear Dr. Linus Pauling's take on CVD? If you do, look no further than this!: A Unified Theory of Human Cardiovascular Disease Leading the Way to the Abolition of This Disease as a Cause for Human Mortality

Thank you NIH for funding another worthless study. Removing the calcium seems pointless, but maybe that is the point: keep the scientists busy doing something that is bound to fail; delay the cure from being known for as long as possible.

CVD can be reversed with diet, and probably has something to do with Vitamin C.

Does anyone want to hear Dr. Linus Pauling's take on CVD? If you do, look no further than this!!!: A Unified Theory of Human Cardiovascular Disease Leading the Way to the Abolition of This Disease as a Cause for Human Mortality

And you were doing so well until you got into the vitamin C woo.

It was obvious from the get-go.

@Eric Lund - I've been part of a team that went through the IRB process twice, for epi projects at a local university's school of nursing. They put our proposasl under a microscope -- it was quite a process getting all of our ducks in a row for approval.

And this was for one-page surveys on vaccine uptake in a rural county.

By shay simmons (not verified) on 29 Sep 2016 #permalink

I don't know much about ACAM and chelation. However, one nice, spry old friend in his 80's, a retired judge whose spouse stroked out on Vioxx, swears by it - feels much better and some other claims I need to ask again to quote. Being a lawyer, science was not the major component of his education. Just another favorable testimonial by a person not stupid or insane...

Realizing that some of the adverse history concerns disodium EDTA content (vs tetrasodium EDTA or some degree of protonation in between), I would probably be a little paranoid about precise formulation and experience of a practitioner. Ditto magnesium and vitamin sources, many flavors are possible and could be very important in some cases. I myself wonder about stray heavy metal depletion effects and also cations above divalents.

Personally, I think a thorough phase IV type longitudinal study might be most productive at this point, if each patient could be tagged with their precise particular Formulation and tracked. Even a fraction of patients from 1-2 years of reported treatment would be a vast set of data that could be capped with SSDI results in 5-10 years, a least amongst the older retirees.

True or not, the Pauling theory of CVD does make sense. Linus Pauling didn't get a PhD in Woo!

Linus Pauling didn’t get a PhD in Woo!

Didn't get one in biology either.

By Helianthus (not verified) on 29 Sep 2016 #permalink

True or not, the Pauling theory of CVD does make sense

Plausibility only trumps accuracy in fields such as politics, car-dealing and trolling. I am sufficiently old-fashioned to prefer Truth over Truthiness.

By herr doktor bimler (not verified) on 29 Sep 2016 #permalink

So, are they still claiming the same mechanism of action (removing calcium)? Or are they just throwing patients at the wall to see who sticks?
I'm pretty sure that's not science.

By JustaTech (not verified) on 29 Sep 2016 #permalink

@prn #18: So we're supposed to be impressed by a "my friend" anecdote by someone who's not in the medical field relayed by someone else not in the medical field?

Feeling different is not the same thing as getting better.

A phase IV study would be done only after the treatment is approved by the FDA. It is preposterous to think about studying patients getting this as part of routine care when we haven't even proved the treatment does anything, and when in fact the study that's been done shows that it doesn't work.

Did the Herr Doktor read the paper?

This is the best theory for CVD that I have come across. Does anyone here have a better theory?

Do go away, Fucklesworth.

You're the one admitting that it makes no difference to you whether Pauling's theory is "true or not".

By herr doktor bimler (not verified) on 29 Sep 2016 #permalink

The Pauling theory is like a metatheory that explains why high Lp(a) and salt intake are both risk factors for CVD.
•The higher the blood pressure the more damage.
•The higher the Lp(a), the more plaque deposition
•The lower the Vitamin C, the lower the collagen, and the more sensitive the arteries are to damage.

Can one person take enough Vitamin C to mitigate a lifetime of McDonalds eating and stress? I don't know, but I think that it would delay the inevitable by a few years at least.

Perhaps for all you omnivores out there, you should try to eat one orange for every hotdog.

Blimey! The chelation as therapy believers want to keep researching until their biases are confirmed, looks like.
That's not how it works (I know, preaching to the choir).
And the IRBs are just as delusioned.
What a monumental waste of money, and there is not an insignificant risk to participants I would think.

My Aunt, (who loved every conspiracy theory she could find and was a proud John Bircher) had chelation therapy to prevent heart disease. I have no idea if it did, I just know that by the time she died her arthritis was so severe she had to wear a custom made plastic exoskeleton in order to sit or stand, and suffered from dementia--probably Alzheimer's.
Heart disease sounds preferably to me.

Panacea@23
...So we’re supposed to be impressed by a “my friend” anecdote
Actually P, I was citing it as my lack of experience and insight, including not knowing what kind of formula he got. Along with my general disinclination toward disodium EDTA based formulas as likely problematic.

A phase IV study would be done only after the treatment is approved by the FDA. It is preposterous to think about studying patients getting this as part of routine care when we haven’t even proved the treatment does anything
I said a phase 4 type of study. Say what you will, the stuff is in commercial use.

...when in fact the study that’s been done shows that it doesn’t work.
Generally, I believe that MSM trials related to CAM show how not to use materials. I totally believe that if some idiot does it the way a failed trial did it, they can expect to fail too. Typically negative trials on the CAM items I'm interested in have been designed wrong several ways - with no possibility of success to someone who already knows what has worked historically.

Pretty much I can read trials for myself, often figure out what was biased, what was wrong, and adjust or add the parameters, or just discard accordingly. It has become a real survival skill these last dozen years or so. Fortunately I had some similar industrial experience IRL with detecting more subtle commercial biases done for monetary gain.

Lest you think I'm all negative on negative trials, let me assure that I am dependent on some of them to dodge bullets, like on little published but significant drug interactions. Some times I've gone for months looking for a suspected negative.

Generally, I believe that MSM trials related to CAM show how not to use materials. I totally believe that if some idiot does it the way a failed trial did it, they can expect to fail too. Typically negative trials on the CAM items I’m interested in have been designed wrong several ways – with no possibility of success to someone who already knows what has worked historically.

Pretty much I can read trials for myself, often figure out what was biased, what was wrong, and adjust or add the parameters, or just discard accordingly. It has become a real survival skill these last dozen years or so. Fortunately I had some similar industrial experience IRL with detecting more subtle commercial biases done for monetary gain.

Lest you think I'm all negative on negative trials, let me assure that I am dependent on some of them to dodge bullets, like on little known on interactions. Some times I've waited months looking for a suspected negative.

@prn #31: well you definately succeeded in relating your lack of knowledge on the subject.

There is no such thing as a phase IV "type" of study. There are Phase IV clinical trials, which study the use of a medication in the general population after it is approved, and there different types of quantitative and qualitative research.

The population who gets chelation therapy is small, because treatment for heavy metal poisoning that is actually done for real heavy metal poisoning (ie not quackery) is a small and limited population. They don't get this therapy for anything else, and it's not a routine therapy. Once the heavy metal poisoning is treated that's it. So trying to study this population for the supposed benefits on CVD is simply preposterous. In any event, Phase IV trials study side effects and safety. To gain approval for a new clinical indication, you have to do a whole new Phase III trial.

The only reason the drug companies bother with that is to keep a drug under patent. Off label use is pretty common once other evidence shows a drug can be used for other things. Which is why quacks can use chelation in the first place; they're basically using it off label.

The rest of your post is pure nonsense.

Szilard:

Perhaps for all you omnivores out there, you should try to eat one orange for every hotdog.

Eating more fruit and veg in general is a good objective for most of us, for so many reasons. But that said . . . there actually is vitamin C in meat. Mostly because, unlike humans, most animals can synthesize it. A return to more "traditional" sausages might help increase vitamin C consumption. Organ meats have a lot more vitamin C than mere skeletal meat has. ;-) Maybe if we weren't so picky, we'd have a better diet, and each cow would go further.

By Calli Arcale (not verified) on 30 Sep 2016 #permalink

Panacea,
What we have here is a failure to communicate.

...which study the use of a medication in the general population after it is... [marketed]
That's the type part, @#$w^&.

EDTA is of course capable of moving and removing metals, especially polyvalents, in lower than immediately, clinically symptomatic amounts.

In real research, Panacea, people sometimes actually go looking for things that are not already known or well understood. Preferably with better tools and minds.

@prn: No, in real research, people form a hypothesis, develop a testable prediction, gather data, and refine, alter, or reject the hypothesis. We don't go fishing in stock pond hoping to find a fish other than what was stocked.

This isn't about what EDTA can move or remove. It isn't even about whether or not the assertion that it can affect CVD is true or not.

It's about ethics, and use of human beings as experimental subjects. What you want to do is completely unethical and puts patients at risk so you can go on a fishing expedition.

We don’t go fishing in stock pond hoping to find a fish other than what was stocked.

Nor do we go fishing in the ocean with no clear idea what we might catch. Fishing expeditions tend to fare poorly in proposal panel reviews, for good reason.

We know that EDTA can remove various metals from the body, some of which are toxic and others even essential. For somebody with a serious case of heavy metal poisoning, it's worth while, because the benefits of removing the heavy metals outweigh the risks that more beneficial metals will also be removed. So these patients get EDTA treatments.

What TACT did, and TACT2 proposes to do, is give EDTA treatments to people who are not known to be suffering from heavy metal poisoning, in hopes that their condition might improve. There doesn't seem to be a rationale behind this other than the standard toxins gambit of woo-pushers, and there doesn't seem to be a physiologically plausible mechanism. On the contrary, there is a demonstrable risk to the treatment, as noted in TACT by the fact that many subjects had to be dropped due to adverse outcomes. The original TACT investigators could at least make feeble arguments from ignorance about the ethical situation (not that these arguments are persuasive, but at least they exist). The TACT2 investigators have no such excuse.

Orac mentioned above that the relevant IRBs for TACT seem to have been either asleep at the switch or subverted. I'll repeat my question upthread: Where are the IRBs that should be derailing TACT2?

By Eric Lund (not verified) on 30 Sep 2016 #permalink

Re: Numerous comments about Linus Pauling. I saw him on TV, a live interview/call-in show, taking about vitamin C and the common cold.. He was ,asked about vitamin C and AIDS. He said, "Well it's proved effective against viruses and AIDS is a virus so it should work." I think he was senile.

By DANIEL GAUTREAU (not verified) on 02 Oct 2016 #permalink

Who makes your favorite brand of broccoli hot dogs, Lewis?

By squirrelelite (not verified) on 02 Oct 2016 #permalink

broccoli hot dogs

Border broccollies.

By herr doktor bimler (not verified) on 02 Oct 2016 #permalink

Linus Pauling is one of the greatest chemists ever. Doesn't ORAC have a chemistry degree?

ORAC, who is you favourite chemist? You can't name yourself.

By Ms. Rogers (not verified) on 02 Oct 2016 #permalink

A return to more “traditional” sausages might help increase vitamin C consumption.

That's what the fries and ketchup are for.

ORAC, who is you favourite chemist?

Not ORAC, but I've always had a soft spot for Antoine Lavoisier. Why you ask?

Not ORAC, but I’ve always had a soft spot for Antoine Lavoisier.

Ah, "Ms. Rogers," a new sock. I won't bother with the perfunctory Timmeh answer, although it's not bad.

Linus Pauling is one of the greatest chemists ever

Who is only mentioned on this thread because a sock-puppetting numptie keeps popping up with new nyms to whinge about his limited list of obsessions.

By herr doktor bimler (not verified) on 03 Oct 2016 #permalink

Personally, I was rather fond of Isaac Asimov. At least he distinguished between fact and fiction.

By squirrelelite (not verified) on 03 Oct 2016 #permalink