Dr. Rajiv Chandra

Dr. Rajiv Chandra, standing, with three of his patients that received chelation therapy. (Jacob Langston/Orlando Sentinel)

After the FDA announced it would review edetate disodium's safety and efficacy, its manufacturers voluntarily recalled the drug in 2007 and 2008. The FDA removed it from the agency's list of approved drugs in 2008.

Yet the chelation study continued, and subjects were not immediately told that the FDA had delisted the drug over safety concerns.

After the Medscape critique came out in 2008, the Office for Human Research Protections told study coordinators they would have to change the consent form for new subjects and tell patients already enrolled what information had been left out.

The federal office said it was "concerning" that "several of the TACT study investigators have been accused of substandard practices by state medical boards, involved in insurance fraud, and at least three are convicted felons" but concluded that didn't necessarily mean subjects were put at risk.

The office recommended that institutional review boards overseeing the study re-examine the way they evaluate researchers signing on to the project.

Shurin, of the National Heart, Lung, and Blood Institute, told the Tribune that trial leaders have closed clinic sites or changed investigators at sites where concerns exist over medical licensing. In 2007, Lamas initiated a policy of checking regularly with medical boards for any concerns about active TACT investigators, she wrote.

In an email, Lamas wrote that researchers did not consider death to be a potential side effect of the therapy because the safety of clinical trials is closely monitored. "NIH, FDA and dozens of independent institutional review boards agreed and approved the form," he wrote. "In 2009, in an abundance of caution, OHRP asked us to revise the consent form, and, of course, we did."

The study continues, Lamas noted, despite scrutiny by the Office of Human Research Protections, the FDA, the NIH and other groups. A data safety monitoring board looks at data from TACT every six months, he wrote. "At every meeting, they have recommended continuing the trial," he wrote.

Shurin wrote that in the setting of a well-monitored trial, in which the infusion rate is tightly controlled, the disodium form of EDTA is very safe. "Our experience in TACT has reinforced our confidence in the safety of this drug in the setting of a well-conducted trial," she wrote.

In Melbourne, Fla., cardiologist Rajiv Chandra said he welcomes evidence that will help him decide whether to offer chelation therapy to heart patients or not.

Chandra, one of the most successful recruiters for TACT, had offered chelation therapy to some patients before the study began but suspended treatments until the results of the research come in.

"If it comes back negative, we ought to stop," he said.

But negative results may not sway heart patients who strongly believe chelation therapy helped them.

One is Chet Jenkins, a 76-year-old Korean War veteran who volunteered for TACT through Chandra's practice. Several years before joining TACT, Jenkins had undergone chelation and said he felt improvement.

"I don't know if it was psychological or not," he said. "But I am a believer."

Atwood, first author of the critique of TACT, said the Office of Human Research Protections and other oversight groups have let down volunteers like Jenkins and allowed a flawed study to continue even though the results will mean little or nothing. "They agreed with our points and then let everyone off the hook," he said.

"You still have criminals," he said. "You have the vast majority of subjects enrolled up to this point based on wildly inaccurate statements in the consent form, and you think it can proceed? … If you already have data from, say, 1,000 subjects and they all came in under false pretenses, that is it. It's over."

ttsouderos@tribune.com

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