San Diego Reader

It reads like a bad science fiction novel: A small Illinois biotech company cuts a deal with UCSD. The university agrees to test a substitute for human blood on comatose patients -- victims of gunshots and car crashes -- without the patients' consent. Within the city of San Diego, the experiment is targeted at several neighborhoods south of I-8, where many poor and minority residents are unlikely to have heard of the study and unlikelier still to have the resources to sue if something goes awry. The university conceals the identity of the city's paramedic units who carry the blood substitute. When a curious reporter asks for the names of the neighborhoods where the study is being carried out, a research coordinator working for the university tells him that the Chicago sponsor doesn't want the information made public because Wall Street moneymen -- hoping to reap a financial windfall from their investment in the company -- might sell if they discover the experiment is not going well. When the reporter asks university officials to provide details of two "adverse event" reports involving the study, the officials stonewall, saying the information is "nonpublic" because the university has signed a confidentiality agreement with the laboratory. But if Hollywood wouldn't buy that scenario, the University of California and the City of San Diego already have. A little more than two years ago, officials at UCSD signed an agreement with Northfield Laboratories for clinical trials of PolyHeme.

Despite repeated studies, PolyHeme has yet to be approved by the Food and Drug Administration, and this May, Forbes magazine told its predominantly Wall Street audience that researchers at Walter Reed Army Institute of Research had "published a study suggesting PolyHeme might not be so safe after all. Comparing resuscitative fluids, it found that hemorrhaging lab rats treated with PolyHeme experienced higher mortality rates than those that received two commonly used solutions."

The founder of Northfield labs is Steven Gould, a 57-year-old physician from Chicago who has worked on blood substitutes for more than 25 years. In 1979, after obtaining a grant from the Army, he and several other doctors at the University of Chicago developed a technique to separate hemoglobin, the oxygen-carrying protein, from blood, then link the hemoglobin molecules together into polymers, hence the name PolyHeme.

"Initially a project of the United States Army following the Vietnam War," Northfield's website says, "the objective was to develop a preparation that could be infused rapidly and in massive quantities to injured battlefield combatants in far-forward areas and mobile surgical theaters before the injured could be evacuated to more sophisticated field hospitals for definitive care."

Northfield's promotional material describes PolyHeme as "a solution of chemically modified human hemoglobin, which simultaneously restores lost blood volume and hemoglobin levels and can be rapidly and massively infused." The advantages of PolyHeme are that it "requires no cross-matching. It is compatible with all blood types and therefore immediately available for infusion. It has an extended shelf life of over 12 months."

The Army continued to fund Gould until 1984, when it began supporting his larger rival, Baxter International, in its own quest for a blood substitute. At that point, Gould shifted his aim and put together $1 million in funding from private investors. A decade later, in 1994, with several small clinical trials under his belt, Gould took Northfield public, raising $15 million at $6.50 a share.

But in 2001, according to the Forbes article, the Food and Drug Administration rejected Northfield's application to approve PolyHeme for general use, citing lack of sufficient clinical studies. The stock tanked, sinking from $13.25 to $3.05.

Gould held on, sacking the company's chief executive and eventually reaching an agreement in 2003 with the FDA to allow a new kind of clinical trial that could be run without getting the patient's consent. Employing a little-used exemption in FDA regulations, Gould proposed having paramedics in cities across America infuse PolyHeme into 360 patients. San Diego was one of those cities.

Under Northfield's deal with the FDA, the company and its research partners agreed to conduct public information campaigns in each city where PolyHeme was to be deployed. They were to arrange newspaper, radio, and television coverage advising the public of the tests and of the opportunity to opt out by wearing a special bracelet. They were to set up a website containing voluminous information about the nature of the study and the right to opt out. In San Diego, much of this didn't come to pass.

Notice of the trial was posted on an obscure part of a website run by the UCSD Human Research Protections Program. Today, those who click on a link labeled "Public Notices" are taken to another link labeled "PolyHeme Trauma Trial" and thence to the study's information page. Readers are told that "This groundbreaking study is being conducted in accordance with federal regulations permitting an exception from informed consent requirements under 21 CFR 50.24." The statement says that a public information meeting, where "comments and concerns" were to be solicited, would be held August 6, 2003, at the UCSD Medical Center in Hillcrest. "Members of the media are invited to cover this event," it added.

The only major newspaper story covering the trial was spun heavily in favor of the wonders of the experimental substance and made light of its possible hazards. "A new hope for saving of lives," said the headline over the March 23, 2004, story in the Union-Tribune. "Paramedics to conduct test of blood substitute."

"These are people who are facing death in a few hours," the story quoted Dr. David Hoyt, trauma director at UCSD Medical Center and principal investigator of the local PolyHeme study. "Giving them this blood substitute might just save them when conventional treatment wouldn't." The paper added that "In a study of PolyHeme from the late 1990s, 75 percent of those treated with it survived, compared with 30 percent treated only with saline solution."

The paper went on to report that "the blood substitute will only be available to paramedics working south of Interstate 8." Specific paramedic and ambulance units carrying PolyHeme were not identified. "Designated paramedic units in San Diego and the South County and the Mercy Air helicopter crew will have a cooler containing bags of the substitute," the story added.

The clinical trial began in San Diego County on May 20, 2004, when a Mercy Air emergency-services helicopter, based at Gillespie Field, started carrying PolyHeme. On June 11, 2004, seven ground ambulances serving cities outside of the city of San Diego joined the trial. The ground ambulances are owned by a private company, American Medical Response, which serves 11 cities in the county as well as unincorporated areas. According to the company's spokesman, Devon Price, the ambulances participating in the study operate in National City, Chula Vista, Bonita, and Imperial Beach. Earlier this week, Hoyt, of UCSD, said six paramedic rigs outside the city of San Diego were equipped with PolyHeme.

But according to records obtained from the City of San Diego, at the time the U-T story appeared, city officials and UCSD administrators were still negotiating when and where the city's paramedics would use PolyHeme.

Northfield wanted to limit the PolyHeme trial to neighborhoods with the highest trauma rates. On May 2, 2003, Beth Romeril, the research coordinator of the UCSD study, wrote Hoyt, the principal investigator. "My biggest concern at this time is that in conversation with Bob McGinnis from Northfield on Wednesday, he indicated to me that Northfield would not have enough product to stock even the 12 or so ambulances in UCSD's catchment area, that part of the reason for the TREG [San Diego County Regional Trauma System Registry] search would be to identify the '3 or 4' ambulances that would be most likely to encounter appropriate patients.

"I have asked him to confirm the maximum number of ambulances they would be able to supply for us and waiting to hear back," Romeril wrote, adding that her geographic survey of trauma data was complicated. "Most of the time the location (zip code) where the encounter took place is not available, so we can't identify specific medic rigs in most cases."

At the City of San Diego, officials worried about possible lawsuits in case PolyHeme didn't work as advertised. They wanted to isolate the city's possible financial liability by demanding that the study's sponsor indemnify the city for $15 million against malpractice claims.

Why might there be malpractice claims?

By the very definition of the study, all patients are in hemorrhagic shock and unable to refuse the PolyHeme. As noted by Northfield: "It is expected that patients enrolled in this trial will be unable to provide informed consent because of the nature and extent of their injuries." The lack of consent was justified on the grounds that the existing blood substitute currently used by paramedics is simple saline solution and that almost anything, even an experimental substance like PolyHeme, would be an improvement for desperate trauma patients.

And there was another reason for the city to fear lawsuits. Even after arriving at the hospital, patients would not receive real blood.

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