On Wednesday, a spokeswoman for the New England Journal said the study's lead author, Dr. Rabih Darouiche, was asked to provide evidence of approval from an independent Institutional Review Board and patient consent for the study. He was also asked if he had failed to disclose financial conflicts of interest, as alleged in a whistleblower lawsuit against CareFusion.
“We received adequate documentation of IRB approval and patient consent and received no evidence of undisclosed conflicts of interest,” the journal spokeswoman said in a statement. “The authors disclosed relevant financial relationships at the time of submission, and they are listed at the end of the published article. We are satisfied that these matters were handled appropriately.”
CareFusion paid for the study of its product, the surgical antiseptic ChloraPrep, and it was accused in a whistle-blower lawsuit of disregarding rules intended to safeguard sponsored trials from bias. The company was also accused by the U.S. Justice Department of paying Denham $11.6 million to influence recommendations published by NQF regarding the same antiseptics.
Darouiche said in a phone call Tuesday that the allegations regarding his CareFusion research are false. Denham has not done interviews, but has said through a spokesman that he denies the kickback allegations.
Denham's lawyer, Larry Gondelman, said the NQF relied on a report in the New England Journal of Medicine to support changes in the infection-prevention guidelines that are used by hospitals nationwide.
Indeed, minutes from the Aug. 19, 2009 meeting of the NQF's Safe Practices Committee, which Denham co-chaired, show that Denham referred to the results of a “major study” on surgical antiseptics when he recommended the NQF endorse a specific formula of alcohol and 2% chlorhexidine included in CareFusion's ChloraPrep products.
But the timing has raised questions. The NQF committee's discussion of the study took place in August 2009 (PDF), and the results of the clinical trial comparing alcohol-chlorhexidine versus traditional iodine-based surgical antiseptics didn't appear in print in the New England journal until January 2010. Journals typically prohibit release of data in peer-reviewed studies before publication.
Furthermore, Grassley contends that CareFusion didn't even have Food and Drug Administration approval for that specific indication of ChloraPrep at the time the NQF was talking about it.
“It is concerning that a prominent expert at NQF was encouraging non-approved uses during a review of patient safety best practices while being paid millions of dollars by the manufacturer of ChloraPrep,” Grassley wrote in a letter Monday (PDF) to NQF President and CEO Dr. Christine Cassel.
Cassel said the NQF is responding to Grassley, and she noted that the group cut ties to Denham in 2010 after it appeared that he had “undue interest” in a recommendation on surgical antiseptics.
“When the Department of Justice contacted NQF in 2012 as part of its investigation about alleged kickbacks from CareFusion to Dr. Denham, we cooperated fully,” Cassel said. “Our interests are aligned with the DOJ and Sen. Grassley.”
Beyond the issue of the study's timing, the former vice president of regulatory affairs at CareFusion, Cynthia Kirk, said in her 2010 whistle-blower lawsuit that the clinical trial was hopelessly tainted by legal and ethical failures that made it impossible to conclude that the study contained unbiased evidence to support the 2% chlorhexidine formula.
The lawsuit against CareFusion (PDF), which was settled last month without anyone admitting wrongdoing, alleges 16 ways that study was invalid. It accuses principle investigator Dr. Rabih Darouiche of failing to meet federal requirements that he allow access to study data, and of failing to disclose patient deaths.
“During the study, there were seven patient deaths, which were not reported to the sponsor by the investigator or by the sponsor to the FDA, as required by” federal law (PDF), the lawsuit says.
Further, the study was supported financially by CareFusion, but the full nature of the payments to Darouiche were not disclosed, the suit alleged. The company appointed its own vice president of medical affairs to serve as a compliance monitor, even though she was not a medical doctor and lacked previous clinical experience.
Neither Denham nor Darouiche has been charged or sued over the allegations. CareFusion paid $40 million on Jan. 9 to settle the case.
Reached by phone Tuesday, Darouiche declined to comment except to note that “these are all false allegations.” He said the New England Journal of Medicine would release a report on the results of its investigation into the study soon.
In a Jan. 30 statement, CareFusion said the Justice Department investigated the allegations regarding the clinical trial and didn't take action on them. The company added that the use of chlorhexidine and isopropyl alcohol to kill microorganisms has been acknowledged as a “superior agent” by many organizations in recent years, including the Centers for Disease Control and Prevention.
“There is a large body of evidence supporting these recommendations that has been published, peer reviewed and recognized by some of the best scientific minds in the world.”
The Justice Department alleges in its settlement with CareFusion that the company attempted to influence the NQF by paying Denham an inflated contract totaling $11.6 million for services from his for-profit company, Health Care Concepts. While some work was provided, the Justice Department said the cost was too far above fair-market value to have been for those services alone.
The NQF took pains to note that the endorsement of CareFusion's specific antiseptic formula to fight surgical-site infections was stricken from the final report because of a complaint from 3M (PDF)—which manufactures a competing product.
However, two patient-safety experts who served on the NQF Safe Practices Committee with Denham have told Modern Healthcare that Denham influenced a second recommendation involving the use of 2% chlorahexidine solution to fight central-line-associated bloodstream infections. That recommendation, No. 21, was published even though it's not clear from the minutes that the committee even voted to do so.
“He slipped in the 2% and none of us picked it up,” said Johns Hopkins patient-safety expert Dr. Peter Pronovost. “I was surprised.”
At the time, a not-for-profit foundation called Texas Medical Institute of Technology, which Denham founded and chairs, was doing extensive work on behalf of the NQF committee to research new recommendations and update existing ones. A TMIT staff member named Hayley Burgess attended the Aug. 19 meeting, and was specifically thanked for her “hard, hard work in the background.”
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