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”

An Idiotic Review Board? AKA The Office for Human Research Protections

Another view on this post "Why was this QI Project Shut Down":

It is possible to adhere to institutional "process" so blindly and so obstinately, ignoring common sense (which may not be all that common) as to impair medical progress.

It has been also said that "process" is no substitute for smart people, but tries to be, based upon beliefs in management theories (a.k.a. "management mysticism") and simplistic, mechanistic views about how the world really works. Unfortunately, any theory, rule, or process taken too far or adhered to too rigidly can have major downsides.

The case below is such an example of this, where process trumps common sense, cleverness trumps wisdom:

A Lifesaving Checklist
By ATUL GAWANDE
New York Times, Dec. 30, 2007

In Bethesda, Md., in a squat building off a suburban parkway, sits a small federal agency called the Office for Human Research Protections. Its aim is to protect people. But lately you have to wonder. Consider this recent case.

A year ago, researchers at Johns Hopkins University published the results of a program that instituted in nearly every intensive care unit in Michigan a simple five-step checklist designed to prevent certain hospital infections. It reminds doctors to make sure, for example, that before putting large intravenous lines into patients, they actually wash their hands and don a sterile gown and gloves.

The results were stunning. Within three months, the rate of bloodstream infections from these I.V. lines fell by two-thirds. The average I.C.U. cut its infection rate from 4 percent to zero. Over 18 months, the program saved more than 1,500 lives and nearly $200 million.

Yet this past month, the Office for Human Research Protections shut the program down. The agency issued notice to the researchers and the Michigan Health and Hospital Association that, by introducing a checklist and tracking the results without written, informed consent from each patient and health-care provider, they had violated scientific ethics regulations. Johns Hopkins had to halt not only the program in Michigan but also its plans to extend it to hospitals in New Jersey and Rhode Island.

The government’s decision was bizarre and dangerous. But there was a certain blinkered logic to it, which went like this: A checklist is an alteration in medical care no less than an experimental drug is. Studying an experimental drug in people without federal monitoring and explicit written permission from each patient is unethical and illegal. Therefore it is no less unethical and illegal to do the same with a checklist. Indeed, a checklist may require even more stringent oversight, the administration ruled, because the data gathered in testing it could put not only the patients but also the doctors at risk — by exposing how poorly some of them follow basic infection-prevention procedures.

For the love of god ... perhaps only a bureaucrat is capable of such idiotic thinking? Most if not all of the items on the checklist could be read in any introductory text on medicine or The Washington Manual. They were reminders of the obvious, not experimental protocols.

The overly litigious and predatory nature of U.S. healthcare also affected the thinking of the Office for Human Research Protections, I'm sure, and this idiocy is perhaps another example of the pernicious effects of the litigiousness. Predatory lawyers and bumbling bureacrats are not among my list of primary actors for creation of sound medical policy.

... Excellent clinical care is no longer possible without doctors and nurses routinely using checklists and other organizational strategies and studying their results. There need to be as few barriers to such efforts as possible. Instead, the [checklist] endeavor itself is treated as the danger.

If the government’s ruling were applied more widely, whole swaths of critical work to ensure safe and effective care would either halt or shrink: efforts by the Centers for Disease Control and Prevention to examine responses to outbreaks of infectious disease; the military’s program to track the care of wounded soldiers; the Five Million Lives campaign, by the nonprofit Institute for Healthcare Improvement, to reduce avoidable complications in 3,700 hospitals nationwide.

... Scientific research regulations had previously exempted efforts to improve medical quality and public health — because they hadn’t been scientific. Now that the work is becoming more systematic (and effective), the authorities have stepped in. And they’re in danger of putting ethics bureaucracy in the way of actual ethical medical care. The agency should allow this research to continue unencumbered. If it won’t, then Congress will have to.

Atul Gawande, a surgeon at Brigham and Women’s Hospital in Boston and a New Yorker staff writer, is the author of “Better."

The "process fanatic" will be the death of good medicine, including those who believe that all of medicine can be deterministically modeled and cybernetic miracles worked with EHR's.

Speaking of religion, and considering the above report came out just after Christmas, the following humorous but meaningful piece comes to mind. Ironically, both the NYT story and the piece below were sent to me by different parties independently at around the same time:

IRB Global Observational Study of Behavior in Children review

Dr. K Kringle
Adjunct Professor of Child Psychology
Far Northern University

Dear Dr. Kringle (Ph.D, M.D., D.O.? Please verify your credentials):

At the regularly scheduled December 24 meeting, the IRB reviewed your protocol, "A Global Observational Study of Behavior in Children" While we believe it has many good features, it could not be approved as submitted. If you choose to revise your study, please address the following IRB concerns:

1. You propose to study "children of all ages." Please provide an exact lower and upper age limit, as well as the precise number of subjects. Provide a statistically valid power calculation to justify this large of a study.

2. Your only inclusion criterion is "belief in Santa Claus." Please provide a copy of the screening questionnaire that determines such a belief. Provide a Waiver of Authorization under MPAA in order to record these beliefs prior to enrollment in your study. The Board recommends that you obtain a Certificate of Confidentiality as beliefs are sensitive and personal information.

3. You propose to "know when they are sleeping and know when they are awake." How will this be done? Will children undergo video monitoring in their beds? Will they have sleep EEGs? You list 100 elves as research assistants. Are any of them sleep physiologists? Please provide credentials of elves.

4. Your primary outcome measure is to "know when they've been bad or good." What standard is being used to determine "goodness"? Do children have to be good all year or just most of the time? Please specify required duration and provide the instrumentation, with appropriate consent forms, that will be used for operationally defining "goodness."

5. You propose to conduct your research by entering the subjects' homes through the chimney. Have you considered the liability potential, i.e., damage to the roof, carpeting, etc., that this will cause? Moreover, children are likely to be startled by your appearance late at night. Please revise your protocol to conduct your home visits between 9 am and 5 pm Monday through Friday with at least one parent being present and all risks and benefits carefully described.

6. You state that compensation for participation will be "sugarplums, candy, and toys" for the good little girls and boys. This may not be appropriate for the children with obesity, dental cavities, and hyperactivity. Also, your proposal to leave a lump of coal in the stockings of the bad children will be unfairly stigmatizing to them individually and as a group. In general, the Board suggests a small token of appreciation for all participants. Perhaps a $5 Toys-R-Us gift card would be more appropriate in order to avoid potential coercion.

7. The database of good and bad children will be kept "on a scroll at the North Pole." Please describe the location of the scroll and the security provisions you have in place to protect the data Is the scroll kept in a locked cabinet in a locked room? Who has access to the scroll? Are there backup copies of the scroll and how often are they compared to the original?

8. You mention the participation of "eight tiny reindeer" in your protocol. Please provide the Board with documentation of Institutional Animal Care and Use Committee approval.

9. Please provide the Human Subjects Protection training dates for Mrs. Claus and the elves.

10. As this study involves prospective data collection and is more than minimal risk without prospect of direct benefit to the subjects, informed consent signed by both parents will be required. Please have the consent form translated into every language spoken by children and ensure that assent forms are signed by all.

Please submit 25 copies of your revised protocol to the IRB. The IRB will be on Holiday Season schedule for the next two weeks. If approved, you will be able to conduct your study sometime in the spring, if all items are appropriately addressed.

Sincerely,
E. Scrooge, MD

Chair, Institutional Review Board

Copyright 2006, David R. Karp

-- SS

Post Title → An Idiotic Review Board? AKA The Office for Human Research Protections