|Full article reprinted from "The Gray Sheet" - March 30, 2009 |
Find out how house legislators may seek stricter criteria for Institutional Review Board registration at the Department of Health and Human Services and require greater disclosure from IRBs following a study that revealed operational shortcomings.
|Full article reprinted from "The Gray Sheet" - March 30, 2009|
At a March 26 hearing, both HHS and Coast IRB took heat from the House Subcommittee on Oversight and Investigations for lapses in their watchdog roles. HHS registered a fraudulent IRB and Coast IRB approved a fraudulent trial protocol - both submissions fabricated by Government Accountability Office agents.
"I can't tell you whether our two undercover successful tests are isolated cases or the tip of the iceburg," GAO Managing Director Forensic Audits and Special Investigations Gregory Kutz testified to the committee. "What I can tell you is that given the history of human subject testing, it's hard to believe that anybody could be comfortable with the integrity of the current system."
The hearing was a rough ride for Coast CEO Daniel Dueber. His firm's board unanimously approved a trial protocol of a made-up product ("Adhesiabloc") by a made-up company ("Device Med Systems") to be carried out by a fake doctor with an expired medical license. Two other firms (Argus IRB and Fox IRB) had rejected the protocol, calling it "awful," a "piece of junk" and the "riskiest thing I've ever seen on this board."
The disparity in the approaches by the IRBs could lead to efforts to prevent "IRB shopping."
Subcommittee Chairman Bart Stupak, D-Mich., noted that in 2002 FDA considered regulations to reign in IRB shopping - when researchers shop protocols around to different IRBs until they get approval - by requiring disclosure of prior decisions in order to alert other boards of past study rejections. The proposal was withdrawn in 2006 after FDA concluded that IRB shopping was not a problem that warranted rule-making. Stupak indicated that the present situation illustrated that it is still a concern.
One member of the subcommittee, Rep. Diana Degette, D-Colo., has already put forward legislation on standards for IRBs. Introduced March 25, the Protection for Participants in Research Act (H.R. 1715) would expand the number of trials that are subject to federal regulation to all research that is "in or affects interstate commerce." It also charges HHS with trying to better harmonize clinical study rules for FDA-regulated and government-funded trials, and includes some additional requirements for training IRB members and for federal monitoring of IRBs.
FDA's device center says it is already targeting IRBs that oversee agency-regulated trials for enhanced oversight (1"The Gray Sheet" Jan. 5, 2009, p. 3).
Trying To Coast Through
In contrast to the dismissive comments about the fake GAO protocol from the other IRBs, according to Coast board meeting minutes, the doctor with primary responsibility for reviewing the study said the protocol "looks fine" and that the one-liter substance - the ingredients of which were not detailed in full in the protocol - to be injected into the abdominal cavity of study subjects was "probably very safe."
Dueber maintained in questioning from subcommittee staff prior to the hearing that Coast's medical review of the protocol was adequate, that none of the board members raised concerns with the protocol, and that his sense remained that the study was not particularly risky.
The committee was put off by Dueber's testimony, in which he claimed the federal government unfairly perpetrated an extensive fraud against Coast without probable cause and wasted five weeks of his time and $100,000 of Coast's money.
"I think it's pretty clear that the GAO and this subcommittee are providing a real service to your company sir," Rep. Edward Markey, D-Mass., said. "I think we are trying to help to protect against such a lackadaisical system upon human beings, and yet you seem to be outraged, actually, at our pointing out this deficiency in the way in which your company conducts business."
Should HHS Check Zip Code For Cheteville, AZ?
GAO's investigation also raised flags about the registration process of IRBs with HHS. The fake IRB that GAO submitted was called "Maryland Hause," advertised through a fake Web site, and its president was actually a three-legged dog named Trooper. Kutz said after registering with HHS, GAO's fake IRB received real inquiries from real researchers and had one research protocol submitted for review.
"What in the devil is going on in your agency that allows you to think you can ignore the law and regulations governing the adequacy of IRBs and simply enter whatever is emailed your way and put the U.S. government stamp of approval on an IRB?" asked Ranking Member Greg Walden, R-Ore.
"Nobody picked up on names like 'Phake Medical Devices,' 'April Phuls,' 'Timothy Wittless,' and 'Alan Ruse?' Or the town of 'Chetesville, Arizona'?" he queried.
HHS Director Office for Human Research Protections Jerry Menikoff told the committee that current regulations do not charge his office to in any way approve of IRB registrations. The IRB registration rules, finalized in January, are intended simply to make it easier for the government to stay in contact and inspect IRBs (2"The Gray Sheet" Jan. 19, 2009, p. 13).
"We do not have the staff going through the names to see whether people have put funny names on the list," he notes. "Unless someone sat there and tried to pronounce the names and addresses, they would not pick up on those things."
FDA And OHRP Defend Process
Both Menikoff and FDA's Joanne Less, director of the agency's Good Clinical Practice Program, defended the effectiveness of the current oversight system to the subcommittee. OHRP and Less' group share the federal oversight function of IRBs and human subject protections - OHRP for federally funded studies and FDA for FDA-regulated studies.
Menikoff pointed out that GAO missed a big step required to initiate a trial under its jurisdiction, namely to apply for federal funding, which requires rigorous review of the protocol, he said.
And Less noted that because Adhesiabloc, as identified by GAO, was a "significant risk" product, in addition to IRB review, FDA would have needed to approve an investigational device exemption for the product prior to clinical study.
- Jamie Hammon
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