A review by the New England Journal of Medicine of data from a 2010 study it published on CareFusion‘s (NYSE:CFN) ChloraPrep antiseptic found that both the company and the doctor in charge of the study acted appropriately, the journal told MassDevice.com today.
MassDevice.com learned last week that NEJM editors began a review of a study led by Dr. Rabih Darouiche after allegations made in a federal lawsuit called the trial "off label" and "invalid."
"After we were made aware of the allegations in the legal complaint, we asked Dr. Darouiche to provide evidence of IRB approval and patient consent, and we asked if there were any undisclosed conflicts of interest," Jennifer Zeis, NEJM‘s medial relations manager, told us via email. "We received adequate documentation of IRB approval and patient consent and received no evidence of undisclosed conflicts of interest. 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."
The decision appears to confirm San Diego, Calif.-based CareFusion’s assertion that it met appropriate clinical trial protocols when it submitted the study for publication.
"CareFusion’s funding of the study was fully disclosed by the well-regarded principle investigator leading the research and analysis," vice president of corporate communications Kristen Cardillo told MassDevice.com in an email last week. "As we’ve said before, our products are safe and effective. In particular, our skin prep product, ChloraPrep, has been proven effective when used in conjunction with best clinical practices to effectively kill microorganisms prior to surgery or injection. The active molecule in ChloraPrep, chlorhexidine gluconate (CHG), has been acknowledged for years by multiple independent clinical organizations, including the Centers for Disease Control and Prevention, as a superior agent in prepping skin prior to an invasive procedure. There is a body of evidence supporting these recommendations that has been published, peer reviewed and debated by some of the best scientific minds in the world."
The research, published 4 years ago in NEJM as "Chlorhexidine–Alcohol versus Povidone– Iodine for Surgical-Site Antisepsis," 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%. It’s central to a scandal in the patient safety world that’s embroiled the influential National Quality Forum.
The lawsuit alleged that CareFusion paid Darouiche to promote its results and act in a sales capacity for ChloraPrep. Federal prosecutors claimed that CareFusion inked $11.6 million worth of contracts with prominent patient safety advocate Dr. Charles Denham to influence the NQF’s deliberations over patient safety standards. CareFusion agreed to a $41 million settlement to put the federal charges to rest, but admitted no wrongdoing in the case.
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 recently said that they were "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 his "inordinate interest" in including the ChloraPrep formulation in national standards. A slew of patient safety groups have also cut ties with Denham. The Leap Frog Group, a non profit group conducts an annual hospital survey and acts to insure health care systems are using the latest standards in patient safety said in a statement that Denham was appointed as Chair of Leapfrog’s Safe Practices Committee in 2006.
This week Sen. Charles Grassley (R-Iowa) demanded copies of contracts and conflict of interest policies from NQF, citing "serious concerns" raised by the Denham flap.
"This case calls into question NQF’s due diligence and its obligation to prevent conflicts of interest or recommendations that violate officially approved uses," Grassley wrote in a letter to NQF president Dr. Christine Cassel. Guidelines recommended by the group are widely adopted as standards of care by healthcare providers.
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.