Governement Agencies Disagree on Artificial Blood Trial

WASHINGTON - The Food and Drug Administration has brushed aside ethical warnings from officials in another agency over a clinical trial in which trauma patients are being given transfusions of artificial blood without their knowledge when human blood is available.

Under rules governing the trial, trauma centers can withhold human blood from patients without their knowledge and give them the artificial blood, known by the trade name "PolyHeme," instead.

Documents made public by Sen. Charles Grassley, R-Iowa, this week show that officials in the Office of Human Research Protections have repeatedly raised objections to FDA about the trial.

For months, FDA officials brushed aside requests for meetings from the human protection officials to discuss ethical issues, the documents show.

"I'm concerned that the FDA approved what the Office of Human Research Protections considers an unethical study," Grassley said Friday in a statement issued by his Senate Finance Committee.

He said his staff would meet Wednesday with FDA officials and representatives of Northfield Laboratories Inc. of Evanston, Ill., the company that manufactures PolyHeme and is sponsoring the trials.

Under trial rules approved by FDA, PolyHeme can be given by emergency responders to people who are in shock because of sustained blood loss. However, once a patient is in a hospital where whole blood is available, blood can be withheld without his or her knowledge in favor of more transfusions of PolyHeme.

Northfield Laboratories says that PolyHeme, manufactured from whole blood, is an oxygen-carrying fluid with a "shelf-life" of more than 12 months.

It does not require cross-matching and can be carried on ambulances and medical evacuation aircraft, where whole blood normally is not kept.

Since the patients likely will be unconscious, the trial rules allow emergency personnel to waive "informed consent" requirements in which a drug trial must be explained to human subjects and their permission obtained.

Federal regulations allow clinical investigators to invoke an "emergency informed consent waiver" only when an alternative treatment is either unsatisfactory or unproven.

In correspondence with the FDA, officials of the Office of Human Research Protections said they believe that whole human blood is not "unsatisfactory or unproven."

People who are aware of the ongoing trial can opt out in advance by obtaining a plastic hospital bracelet bearing the words: "I Decline The Northfield PolyHeme Study."

Northfield officials had said they would publicize the availability of the plastic bracelets before starting the trial.

Trauma centers in 18 states, including Georgia, Texas, North Carolina and Ohio are participating in the trial. They include:

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The Medical Center of Central Georgia at Macon.

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Duke University Medical Center at Durham, N.C.

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MetroHealth Medical Center in Cleveland, University of Cincinnati Medical Center and Miami Valley Hospital in Dayton, Ohio.

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Memorial-Hermann Hospital in Houston, the University of Texas Health Science Center in San Antonio and Brook Army Medical Center at Fort Sam Houston, Texas.

Grassley has recently been a vocal critic of how the FDA carries out its responsibilities for ensuring the public's safety from both experimental and licensed drugs.

He said he became interested in the PolyHeme trial after reading a Feb. 22 article about it in the Wall Street Journal.

Correspondence subsequently turned up by investigators for Grassley's Senate Finance Committee indicate that beginning in June, 2004, the Office of Human Research Protections repeatedly asked for a meeting with FDA to discuss ethical problems with the trial. However, by late 2005, the meeting had not taken place.

"We will contact you when we have sufficiently progressed in our internal review to formulate any questions we may have that may benefit from a broader discussion," an unnamed FDA official said in November, 2005.