Update on the NIH “Trial to Assess Chelation Therapy”

(Some of the following is identical to a post on Science-Based Medicine dated 9/26/08.)

A few days ago, while gathering information for a post on Science-Based Medicine about intravenous hydrogen peroxide, I noticed this:

ACAM Supports NIH Decision to Suspend TACT Trial

September 3, 2008, Laguna Hills, Calif. — The American College for Advancement in Medicine, ACAM today announced its support for the National Institute for Health’s (NIH) decision to suspend patient accrual of the Trial to Assess Chelation Therapy (TACT) Trial until allegations of impropriety can be proven false. ACAM believes that the TACT trial represents a important milestone in assessing the role of chelation therapy in modern healthcare and respects the decision of the NIH.

ACAM continue to work with Dr Tony Lamas to answer the unfounded allegations of impropriety.

“We believe that the Office of Human Research Protection (OHRP) will find that the allegations are of a political nature. To serve the best interests of participants enrolled in the TACT trial and all patients and their physicians who seek answers about chelation therapy, we call for a swift end to the moratorium and resumption of the trial,” said Jeanne Drisko, MD, President of ACAM.

I alerted a few others, including Stephen Barrett of Quackwatch, who queried the news room of the National Heart, Lung and Blood Institute (NHLBI: the joint sponsor, along with the NCCAM, of the trial) and got this reply:

The investigators and institutions performing the Trial to Assess Chelation Therapy (TACT), in conjunction with their Institutional Review Boards, have temporarily and voluntarily suspended enrollment of new participants in the study. NIH has not issued any announcement or press release about this action. To contact the Office for Human Research Protections’ (OHRP) press office, call Pat El-Hinnawy, (202) 253-0458.

The “allegations of impropriety” mentioned in the ACAM press release had been made by my co-authors and me in a comprehensive article previously introduced on Health Care Renewal here. The article is available in its entirety here. In June, we made a formal complaint to the federal Office of Human Research Protections (OHRP), citing that article and additional information posted on Science-Based Medicine here. That our complaint was the instigating factor for the recent “decision to suspend patient accrual” is suggested by an email that I received last week:

I would like to know who is paying you guys off. Finally we have a chance to assess Chelation therapy and put the issue to rest and to find out whether or not it really works and you bozos screw it all up. I know that the trial was stopped and it is your fault. What are you afraid of? Why are you not decrying all of the injuries caused by medications and unnecessary surgeries? Why are we the citizens of the US deprived of a trial of EDTA so that we can judge for ourselves?

Anyone who is a thinking man, can only be disappointed in you. [sic]

Binyamin Rothstein, D.O.

Rothstein, unlike many of his fellow ACAM members, does not appear to be a TACT investigator. Like them, however, he touts chelation, intravenous hydrogen peroxide, and other baseless and dangerous treatments. He has harmed patients, his protestations nothwithstanding. His medical license was revoked in 2005, but that hasn’t hindered him from using smoke and mirrors in his relentless pursuit of profit from nonsense. He’s even managed to promote himself to the public without revealing key items from his resumé—one of the many reasons that even the most diligent regulation can’t always protect the public from scoundrels.

At least two reporters have recently covered the story (here and here). They mostly get it right. The AP report, however, states that chelation "is mainly used to treat lead poisoning." That is not technically false, but is misleading because disodium EDTA (Na2EDTA), the drug used in the TACT, has never been approved for lead poisoning and is considerably more dangerous than calcium EDTA, the drug that is so approved. Ironically, one of our objections to the TACT is that its literature---including protocols, consent forms, and subject recruitment pitches---conflates the two drugs so as to make the study drug appear safer than it is.

Indeed, the FDA has recently withdrawn its approval of Na2EDTA, citing "important safety information" and the possibility that it may be confused with the less dangerous CaEDTA:

As noted in the January 16, 2008, Public Health Advisory, there have been cases where children and adults have died when they were mistakenly given edetate disodium instead of edetate calcium disodium (calcium disodium versenate) or when edetate disodium was used for indications other than those approved by FDA.

Readers might remember that we at HCR have previously discussed the important distinction between the two EDTA salts, after a 5-year old boy was killed in Pennsylvania when a quack administered Na2EDTA to him as a treatment for autism. At the time a CDC expert was so surprised that anyone would infuse Na2EDTA that she concluded, erroneously, that it must have been a drug error: "a case of look-alike/sound-alike medications." The PA medical board's investigation subsequently confirmed that the practitioner had intended to give Na2EDTA, exactly as we had predicted.

The TACT should now be stopped altogether. Contrary to the ACAM press release, our objections to the TACT are scrupulously documented and not “of a political nature.” They are of a scientific and ethical nature. They will not be proven false, because the evidence for them is overwhelming.

Post Title → Update on the NIH “Trial to Assess Chelation Therapy”

The NIH Trial to Assess Chelation Therapy (TACT): an unethical study sponsored by taxpayers

Two occasional HCR bloggers are co-authors of an article published this week:

Why the NIH Trial to Assess Chelation Therapy (TACT) Should Be Abandoned

Kimball C. Atwood IV, MD; Elizabeth Woeckner, AB, MA; Robert S. Baratz, MD, DDS, PhD; Wallace I. Sampson, MD

Medscape J Med. 2008;10(5):115. ©2008 Medscape
Posted 05/13/2008

Abstract:

The National Institutes of Health (NIH) Trial to Assess Chelation Therapy (TACT) was begun in 2003 and is expected to be completed in 2009. It is a trial of office-based, intravenous disodium ethylene-diamine-tetra-acetic acid (Na2EDTA) as a treatment for coronary artery disease (CAD). A few case series in the 1950s and early 1960s had found Na2EDTA to be ineffective for CAD or peripheral vascular disease (PVD). Nevertheless, a
few hundred physicians, almost all of whom advocate other dubious treatments, continued to peddle chelation as an office treatment. They claim that chelation dramatically improves symptoms and prolongs life in 80% to 90% of patients. In
response, academics performed 4 controlled trials during the 1990s. None favored chelation, but chelationists repudiated those findings.

We have investigated the method and the trial. We present our findings in 4 parts: history, origin and nature of the TACT, state of the evidence, and risks. We present evidence that chelationists and their organization, the American College for Advancement in Medicine, used political connections to pressure the NIH to fund the TACT. The TACT protocols justified the trial by misrepresenting case series and by ignoring evidence of risks. The trial employs nearly 100 unfit co-investigators. It conflates disodium EDTA and another, somewhat safer drug. It lacks precautions necessary to minimize risks. The consent form reflects those shortcomings and fails to disclose apparent proprietary interests. The trial's outcome will be unreliable and almost certainly equivocal, thus defeating its stated purpose.

We conclude that the TACT is unethical, dangerous, pointless, and wasteful. It should be abandoned.

The entire article is available at: http://journal.medscape.com/viewarticle/570625_print

You may be asked to "register"; don't worry, it's free. The article is very long, but the Introduction, Executive Summary, Discussion, and Conclusion are reasonably succinct and make the important points. Readers who want to learn more details, who want to see more evidence for our assertions, or who are compelled by an odd fascination with crackpotism (my own weakness) will want to read more.

I've posted a similar announcement on Science-Based Medicine.

Post Title → The NIH Trial to Assess Chelation Therapy (TACT): an unethical study sponsored by taxpayers

Conflicted Bioethicists

Carl Elliott also recently wrote an article in Dissent on bioethicists with conflicts of interest.

His main points were:

• Contemporary bioethicists often get funding from commercial sources, particularly pharmaceutical companies.
• Bioethicists have discounted the effects of commercial support on their own writing and behavior. For example, two American bioethics societies commissioned a task force to examine for-profit bioethics consultation. The task force did not find such consultation problematic, but eight of its ten members had previously performed such for-profit consultations themselves.
• Bioeticists own conflicts of interest may explain why "at a time when the pharmaceutical industry is coming under heavy public criticism for unethical practices - illegal marketing, Medicare fraud, research abuse, ghostwritten journal articles, unexplained deaths in research studies - it is striking how little of the criticism has come from bioethicists."

He concluded:

Bioethicists who accept money from the pharmaceutical and biotechnology industry are not impartial arbiters on the question of whether industry funding constitutes a conflict of interest for academic researchers.
At a bare minimum, bioethicists writing on conflicts of interest need to disclose their industry ties in their scholarly publications on the topic
More important, however, industry-funded bioethicists should not be writing the guidelines under which their own financial activities will be regulated, or serving on the conflict of interest committees that enforce these guidelines.

Again, read the whole thing. I have wondered for a while why professional bioethicists seem so uninterested in the unethical practices that now afflict many parts of health care, beyond even the list of practices Elliott attributed to the pharmaceutical industry above. Bioethicists' own conflicts of interest may be one explanation. Thus, yet another defensive line against unethical and corrupt health care leadership has been breached.

Post Title → Conflicted Bioethicists

"Pharma Goes to the Laundry"

And nobody is left feeling clean....
Thanks for Sue Pelletier's blog Capsules for discovering an article written in 2004 entitled "Pharma Goes to the Laundry." (Full citation: Elliott C. Pharma goes to the laundry: public relations and the business of medical education. Hastings Center Rep 2004; 34: 18-23.) The article suggested that pharmaceutical companies "launder" their marketing message through medical education and/or communication companies to produce medical education or scholarly articles that appear to be independent and unbiased, and that these practices are much more frequent than even I previously thought.
In particular, Elliott, in turn, pointed out a 2003 article by David Healy (Healy D, Cattell D. Interface between authorship, industry and science in the domain of therapeutics. Br J Psych 2003; 183: 22-27) which took advantage of documents released during litigation from a medical communications company (Current Medical Directions) used by Pfizer to market sertaline (Zoloft). Healy and Cattell compared Current Medical Directions' log of the "scholarly" articles it wrote and PubMed searches. The results suggested that the majority of articles on sertaline from 1998-2000 were ghost-written by Current Medical Directions. If this data is generalizable, then the majority of apparently independent, scholarly articles in the medical literature related to the use of pharmaceuticals may have been ghost-written. Yikes!
Elliott also summarized how Wyeth allegedly marketed Fen-Phen via a "medical education" campaign designed to convince physicians that obesity was causing a "public health crisis," a few strategically placed articles ghost-written by Excerpta Medica, and an additional $100 million campaign to minimize the adverse effects of the drug (all derived from the book Dispensing with the Truth, by Alicia Mundy).
Finally, Elliott suggested that bioethicists have not helped, because "we forfeited any credibility we may have had when we started taking pharma money ourselves." As examples, he juxtaposed Healy's data about how Pfizer supported ghost-written articles about sertaline with the company's support for the Pfizer Hall for Medical Humanities at New York University Medical School, the Pfizer Lectureship in Medical Humanities at Royal Free and University College Medical School (in the UK), and the Center for Bioethics at the University of Pennsylvania. (And he noted that Hasting Center Reports are funded by Merck.)
More yikes! Read it, and read Sue Pelletier's post here.

Post Title → "Pharma Goes to the Laundry"

Pogo at the NIH

If we, as health professionals, want health care to be more honestly and rationally managed, we must be prepared to do our best to conduct ourselves honestly and rationally. Of course, dealing honestly with others is a fundamental value for physicians, and is codified in, for example, the AMA Principles of Medical Ethics, and the ACP-ASIM-ESIM Physician Charter.

Today's Washington Post has a disturbing report about NIH staff reactions to the new ethics policy, (first reported on Health Care Renewal here and here.) According to the Post, "nary a positive word had been uttered about the new policy, and there was more vented spleen around than a busy medical center like the NIH might normally see in a year." For example, Chief of Clinical Bioethics Ezekiel Emanuel "fumed" that his secretary would have to sell her stock, (presumably because the rules require that lower-ranking NIH employees limit individual stock holdings in drug, biotechnology, and similar companies to those valued at less than $15,000), and later asked "if we want to reassure the public, why don't we apply these [rules] to everyone who gets an NIH grant." There was indignation that the rules didn't apply to other federal departments, like Energy, Agriculture, and Defense, and that they didn't apply to grant reviewers.

These comments seem to reflect a troubling lack of knowledge about how the NIH funds research outside of its walls. Hardly any individuals get NIH grants. The money goes to their institutions. Many research universities have had strict conflict of interest policies in place for quite a while. NIH grant reviewers have also had to follow strict conflict of interest rules going back to at least the 1980's. These rules, unlike those that applied to NIH full-time employees, were never, to my knowledge, relaxed.

The comments also seem to exaggerate the hardships imposed by the new rules for NIH full-time employees. NIH employees are not being asked to give their stock holdings away. They are being asked to sell them, and they get to keep the money. Nor are they being barred from most kinds of investment. They can own stock in any kind of company that is not directly involved with pharma, biotech, and the like, and they can own any mutual fund or other diversified holding.

But it is most discouraging to hear high level NIH employees, and particularly their head of bioethics, complain that they should only be subject to the lowest common denominator of ethical rules, rather than at least acknowledge the need to set an example after their organization has been tarred by scandal.

As Pogo said, "we have met the enemy and he is us."

Post Title → Pogo at the NIH