Editors at the New England Journal of Medicine are reviewing the publication of data from a 2010 study on CareFusion‘s (NYSE:CFN) ChloraPrep antiseptic, prompted by a federal complaint that called the trial "off label" and "invalid," the journal told MassDevice.com today.
The research, published 4 years ago in NEJM as "Chlorhexidine–Alcohol versus Povidone– Iodine for Surgical-Site Antisepsis," is central in a controversy swirling in patient safety circles that’s embroiled some of the area’s most influentual voices. The study compared disinfection using ChloraPrep with disinfection using Betadine in clean-contaminated surgical wounds. The study claimed that the ChloraPrep solution, of 2% chlorhexidine-gluconate and isopropyl alcohol, was effective in preventing infections by 41%.
But allegations made in the lawsuit that led to its settlement with the Justice Dept., that CareFusion paid lead author Dr. Rabih Darouiche to promote its results and act in a sales capacity for ChloraPrep, prompted NEJM to begin a review.
"We take any allegations of scientific misconduct seriously, and the editors are investigating the allegations listed in the complaint," Jennifer Zeis, media relations manager for the medical journal, wrote in an email. "We anticipate it will take some time to collect the requisite information."
A controversy in the patient safety world
The ChloraPrep trial is key to a scandal in the patient safety world that’s embroiled the National Quality Forum, which helps determine national standards for hospitals, and a prominent safety expert connected with Darouiche who inked $11.6 million worth of contracts with CareFusion. The 2010 whistleblower lawsuit that led to the $41 million CareFusion settlement alleged that the company used the contracts, with groups led by the expert, Dr. Charles Denham, to influence NQF’s deliberations over patient safety standards. That lawsuit led to the $41 million settlement this month.
A transcript of a 2009 meeting of NQF’s patient safety committee reveals that Denham twice referred to the Darouiche study as an endorsement for using the ChloraPrep formulation to help prevent surgical site infections. Two members of the NQF panel Denham co-chaired said this week that they’re "uncomfortable" with the way was run. Staffers from Denham’s Texas Medical Institute of Technology administered the panel, selecting the studies reviewed by the panel and drafting versions of the proposed patient safety guidelines, according to ProPublica.
As first reported by MassDevice.com, the NQF asked Denham to step away from his role as co-chair of the Safe Practices Committee 2 years ahead of the federal probe, alarmed at "inordinate interest" in including the ChloraPrep formulation in national standards.
"There was discomfort in [Denham’s] engagement with the process, which led us to want to sever our relationship with him in 2010," Ann Grenier, NQF’s vice president of public affairs, told us.
The group began a review of its entire 2010 Safe Practices Report after the federal accusations involving Denham surfaced last week. Denham never disclosed he was receiving financial support from the company, according to transcripts from NQF.
According to the whistleblower lawsuit, the Darouiche study was suspect for several reasons, including the fact that Cindi Crosby, CareFusion’s medical affairs vice president at the time, is listed as an author and was allegedly responsible for analyzing and editing the reports data. Investigators failed to "review, evaluate and report safety information" and failed to obtain and maintain accurate records showing all financial transactions from CareFusion to Darouiche, plaintiff Cynthia Kirk alleged the the suit, which was later joined by the Justice Dept., the attorneys general of 30 states, the District of Columbia and federal medical assistance programs.
"CareFusion failed to secure the required contracts with Darouiche. To ensure that no improper payments or kickbacks are being made to the study investigators, drug manufacturers that sponsor clinical studies must have contracts with the investigators that detail the scope of services that the investigator is to provide and the fair market value of those services," Kirk alleged. "CareFusion is using Darouiche as a sales vehicle by securing speaking engagements for him around the world to promote ChloraPrep products with the invalid and off-label study. CareFusion also pays for Darouiche to entertain doctors on these trips. These actions are in violation of statutes prohibiting kickbacks to doctors and investigators."
Denham, a high-profile patient safety advocate who’s editor-in-chief of the Journal of Patient Safety, helped produce a 2010 documentary called Chasing Zero: Winning the War on Healthcare Harm. The documentary featured several patient safety advocates, including actor Dennis Quaid, whose twin children were accidentally overdosed in a hospital shortly after their birth. Quaid merged his foundation into TMIT in 2010. CareFusion financed the film and also owns the trademark to the term "Chasing Zero."
Denham has not spoken publicly about the controversy, but in a statement published on the TMIT website, he said he was "very surprised by the recent events and have had to take the time to collect documents and facts to respond to what has been reported in the press since I was never a part of the whistleblower lawsuit between DOJ and CareFusion. I was as surprised as all of you when the DOJ press release came out. I want to reassure you that I am absolutely dedicated to bringing clarity to the issues at hand. In the meantime, I want to thank all of our collaborators and partners on projects for their tremendous outpouring of support and prayers and for their acknowledgment of our core values and body of our work."
Denham’s lawyer, Larry Gondelman of Powers Pyles Sutter & Verville in Washington, added that reports that the underlying lawsuit named Denham were "blatantly false."
It was Denham’s company, Health Care Concepts, Inc., which received 2 contracts from Cardinal Health in 2008, Gondelman added.
"The first was signed on June 28, 2008, with an effective date of Jan. 1, 2008, and pertained to development of performance models, care path development, and software addressing Surgical Site Infections, MRSA infections, Blood Stream Infections, Urinary Tract Infections, Ventilator Acquired Pneumonia, and Clostridium difficile infections. The second contract signed and effective on Oct. 1, 2008, was a research grant agreement to address automated infection identification systems and measures. Neither contract mentions ChloraPrep or its ingredients. Both contracts pre-dated the existence of CareFusion as a company," the attorney said in a statement.
Prosecutors contend that those contracts far exceeded far market value and did not include defined deliverables, making them little more than window dressing to cover the alleged kickbacks.
*Correction, Jan. 30, 2014: Due to an editor’s mistake, this article inadvertently mis-attributed allegations made in the lawsuit and in statements from federal prosecutors. We regret the error. Return to the corrected sentence.