Medical Device Daily

Blood substitute manufacturer Northfield Laboratories (Evanston, Illinois) is once again being buffeted by criticisms concerning the protocols used in one of its key clinical trials.

The result has been an up and down movement of its stock, dipping 5.5% early this week following a Wall Street Journal article reporting continuing critical statements by Senator Charles Grassley (R- Iowa) and also an alert about “urgent ethical concerns“ sent to the FDA by the Office for Human Research Protections.

Following the company's rebuttal, the stock rebounded and closed yesterday at $9.98, up 4.3%.

The WSJ story focused primarily on two issues: the study's reliance on a waiver of informed consent by patients, with Grassley saying he was concerned that these patients were not fully informed of its risks – primarily deaths in a previous trial conducted by the company; and the use of a blood substitute in a study when real blood is available.

In its statement, Northfield said that it has “adhered scrupulously“ to FDA regulations that were issued in 1996, which allow a waiver of informed consent “when patients are in a life-threatening situation, when obtaining individual informed consent is impossible, and when current therapy is unproven or unsatisfactory.“

It said that this rule holds true when “there is the potential for direct benefit to the patients enrolled, which FDA has interpreted to mean survival benefit. Our study meets these criteria.“ And it said that the agency had approved this protocol for the company's trial in 2003 and that it was further reviewed by 32 institutional review boards “at Level I trauma centers.“

The company cited two “life-saving“ benefits of this approach: the ability to provide oxygen-carrying fluid to a severely injured patient immediately at the scene of injury, and the avoidance of the use of blood in “the early hospital period.“

While it acknowledged the availability of blood once the patient gets to the hospital, Northfield said this “may not be the optimal treatment for the early care of trauma.“

Northfield backed its discussion of the safety of the trial by noting reviews and approvals by an Independent Data Monitoring Committee (IDMC) and said that group “recently reiterated its recommendation to complete the trial based on four separate reviews of mortality and adverse event data from the first 500 patients enrolled.“

And it said the IDMC stated: “As has been reported to Northfield Laboratories regarding the final assessment of the interim data, including 500 randomized patients, there were no statistically significant trends or safety issues identified to warrant modification or other changes in the current protocol and patient recruitment.“

The company also reported that while informed consent is often not obtainable from injured patients, the protocol provides clear guidelines for attempting to contact family members – from every 20 minutes for the first two hours after treatment to once a week “through day 30, if not previously accomplished.“

The WSJ also reported that two hospitals participating in the study using Northfield's blood substitute product Polyheme have suspended further enrollment.

Responding to that, Northfield said that “a few sites“ have suspended trial enrollment to review “their activities“ and that “three are once again enrolling.“

Earlier this year, Northfield had to respond to comments made by Grassley – also reported primarily by the WSJ, which was critical of the company's handling of a trial using PolyHeme to treat abdominal aortic aneurysm, in which two of 81 patients died within a week of receiving the product (Medial Device Daily, Feb. 28, 2006).

That story said that the company had “quietly shut down the trial and made no attempt to publicly disclose the results.“

The company also responded to that attack, claiming that the newspaper report had contained several errors of fact and that it had made no attempt to hide the results.

Steven Gould, MD, CEO and chairman of Northfield, at the time said that three publications had reported on the study, that the patients in the trial were highly complex and that the deaths were most likely the result of fluid management issues rather than any “pharmacologic effect“ of Polyheme.

Also at the time, an FDA spokeswoman defended the trial, noting the critical need for a blood substitute for survival, “particularly in emergency and battlefield situations.“

No Comments