Wednesday, May 14, 2008

Medscape article blows the lid off of NCCAM’s chelation study

A Medscape article on the National Center for Complementary and Alternative Medicine (NCCAM) sponsored Trial to Asses Chelation Therapy (TACT) declares:

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

Orac has already written a wonderful post this morning in which he opines:

As I go to my office and lab this morning, to try to do high quality scientific research based on good science designed to improve our understanding of cancer and hopefully lead to more effective therapies, it galls me to no end to see the equivalent of 15-20 R01 grants going to fund this woo. Worse, it's TACT is not the only example of an unethical and scientifically worthless trial being funded not because the science is compelling but because powerful lobbies and legislators who are true believers in woo applied pressure to the NIH to do them.

I’ll take this opportunity to put in my two cents---not that I really have anything to add other than to say “I told you so” not only about this study but also about the under appreciated conflicts of interest in government funded research. When I first read about this study a couple of years ago I smelled a rat and have since written a number of posts, several of which Orac linked to this morning. The Medscape article reinforces some of the points I made in those posts, particularly regarding the dubious credentials and obvious conflicts of interest of many of the study site investigators. Just look at this jaw dropping paragraph from the article:

The TACT includes nearly 100 "chelation site" co-investigators who, in our opinion, are unsuitable to care for human subjects or to report trial data. Most 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 3 are convicted felons. Several were members of the ACAM or GLACM IRBs mentioned above. Few appear to have real expertise, required by TACT literature, in treating patients with CAD or in conducting clinical trials. Most continue to promote chelation while the TACT is in progress, contrary to good science, to human studies ethics, and to US Federal Code. The TACT consent form gives no hint of these points.

WOW!! Worse than even I imagined! This stuff belongs in the health pages of the New York Times. (I won’t hold my breath, though. They’re probably too busy exposing the pharmaceutical companies to notice. I hope I’m wrong!). If those ethical issues aren’t egregious enough consider that the study isn’t even securely blinded from the investigators, a concern I raised here and in other posts. The Medscape article describes the problem:

The experimental solutions must be mixed on-site. The 2003 TACT protocol describes a method to preserve blinding and reports that this "has been piloted successfully," presumably in a supervised, academic setting.[5] Nevertheless, the mixing procedure presents simple opportunities for distinguishing between the chelation and placebo solutions. For example, the site coordinator must inject 14 mL of concentrated ascorbate or sham solution into a 500-mL IV bag. The plan calls for the 14-mL solutions to have similar viscosity and to appear similar in color, but a tiny drop applied to the tongue during transfer would instantly identify the ascorbate by its sour taste. Ascorbate goes exclusively with the Na2EDTA solution.

Orac faithfully reported the same concern:

Not only was the protocol itself scientifically implausible, a mix of disodium EDTA and a bunch of supplements, as well as procaine and heparin added for unclear reasons. it is placebo-controlled, but the protocol stipulates that the chelation solution must be mixed on site, allowing ample opportunity for investigators to break blinding, either purposely or even inadvertently.

That may just be the tip of the iceberg concerning TACTs’ design problems. The authors note that the NCCAM was not entirely forthcoming with information in response to their FOIA requests:

Through FOIA requests, we obtained "redacted" copies of the original (2001) and 2003 TACT protocols,[4,5] the roster of the committee that approved the grant application,[39] and the June 2003 consent form.[6] Because the trial had already begun and because our initial FOIA requests were frustrated by delays and incomplete responses, we did not seek further revisions of the protocol or consent form, or other documents that are not available on the NCCAM Web site.

I knew from the get-go this trial was questionable. I didn’t know how bad it really was until I read the Medscape piece. This tops any example you can trot out about the corrupting influence of Big Pharma. What I didn’t cover in my posts was the extent of the pseudoscientific agenda and conflicts of interest that prevailed throughout the planning and implementation of the study. If you think government funding is the answer to Pharma involvement in research this article will give you pause.

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