A small, unprofitable company that has been in business for nearly 20 years seems to be within striking distance of achieving its single-minded but elusive goal: to develop a human blood substitute.
But don't expect the product to shutter the local blood bank. If anything, it may actually rev up collections.
With a green light from the Food and Drug Administration, Northfield Laboratories in Evanston, Ill., has launched its pivotal phase 3 clinical trial testing of PolyHeme, an oxygen-carrying blood substitute. The trial, which is expected to take about a year to complete, is designed to treat trauma patients with urgent, life-threatening blood loss at the scene of the injury. Northfield ultimately plans to enroll 720 patients at more than 20 Level 1 trauma centers throughout the country. Half of the participants will randomly receive the blood substitute while the other half in the control group will receive the standard of care, a saline solution.
If effective in the trial, PolyHeme stands to revolutionize trauma treatment throughout the world, says Steven Gould, Northfield's chairman and chief executive officer. A surgeon by training, Gould is one of the company's scientific founders, joining the research team in 1978 and moving to Northfield full time in 1993-one year before the company went public-from Michael Reese Hospital and Medical Center in Chicago where he was chief of surgery. "This is my life's work," Gould says. "If successful, this will have enormous impact on the way transfusion and trauma care are conducted around the world."
Saving lives, not costs
Just the mention of a potential human blood substitute infuses a frenzy of excitement in the universe touched by blood banking. But like most medical advances, far from promising a substitute for an existing technology, it more likely will result in another cost layer. For all of its clinical promise to save countless lives, PolyHeme could eventually put even greater demands on the nation's blood suppliers, whose seasonal plaintive wails regarding blood shortages are as expected as Christmas cards in December and fireworks in July.
Made from outdated human blood, "The rest is basically an electrolyte solution," Gould says. PolyHeme's clear advantages over human blood are that it can be universally administered without blood typing, it does not cause transfusion reactions and it reduces the risk of disease transmission. It also has a long shelf life: more than 12 months compared with 42 days for blood.
In pursuit of FDA approval for the first of what is hoped to be many indications for its use, Northfield has targeted trauma care, which offers perhaps its greatest opportunity. Gould estimates that tens of thousands of people die of trauma each year, many of them from bleeding to death before they have access to blood. Northfield estimates that approximately 14 million units of blood were transfused in the U.S. in 2001 with more than half of that-8.5 million units-given to patients suffering from acute blood loss. Patient charges for the blood used for the treatment of blood loss were approximately $2.5 billion, according to Northfield. Though it's premature to talk about pricing, Gould says a unit of PolyHeme, which requires about two units of blood to make, will likely be priced at a "premium," justified by the survival benefit it offers to the critically injured. "If there is a choice between saving a life or a dollar, I don't think there is any choice," he says.
As a practical matter, ambulances cannot be equipped with blood for trauma emergencies. Under the current standard of care, paramedics will start IVs for trauma patients with saline solutions that may replace the volume of blood, helping to raise the blood pressure but not the oxygen, which is needed to keep vital organs vital. At hospitals participating in the trial, paramedics will assess trauma patients and if they meet the criteria, a sealed envelope will be opened containing either PolyHeme or a saline solution. Those getting PolyHeme will be administered up to six units of it over 12 hours.
Still, PolyHeme only substitutes for blood in its oxygen-carrying ability. "This is a small but relatively unique niche that won't change the need for blood," says Ed Bartkus, medical director of emergency services for Methodist Hospital, Indianapolis, one of the teaching hospitals participating in the trial. "(PolyHeme's) oxygen-carrying capacity is just one small part of what blood does. It's such an incredibly complex liquid."
Louis Katz, president of America's Blood Centers, the umbrella organization for the nation's independent blood suppliers, notes that blood substitutes have been under development for decades without success, but PolyHeme seems to have turned a corner.
"Clinically, I think it's wonderful. It's going to be an opportunity to save lives in the field that would have been lost," he says. That said, as a so-called HBOC-hemoglobin-based oxygen carrier-PolyHeme will tide many trauma patients over until they can be brought to a hospital for treatment, but it won't diminish the ultimate need for whole blood.
Neutral effect
Many trauma patients, including countless patients that would not have survived without PolyHeme, will likely still need whole blood transfusions, he says. "In terms of getting people from the field to hospitals, this is superb," Katz says. "But it's not going to kill blood transfusions." He guesses that PolyHeme's impact will be at best neutral on the nation's blood supply and it may even increase the need.
Mississippi Valley Regional Blood Center in Davenport, Iowa, where Katz is medical director, has been providing Northfield with outdated blood for some time, Katz adds, but as a matter of policy, the center considers it bad management if there is too much outdated blood on hand. "If PolyHeme is the stuff that makes it to approval, we'll have to be the source and we'll have to manage that," Katz says.
Gould says he doesn't foresee PolyHeme exercising any strain on the blood supply, which "is based on minimal outdate rather than maximal collection." Concerned with minimizing the amount of unused blood they collect, blood suppliers are driven more by the anticipated demand, he explains. As many as 2 million units of blood are not transfused each year because of positive screen tests or some other reason and perhaps as many as 1 million units of that blood could be used by PolyHeme, he says. Blood collectors have indicated to Northfield that, if necessary, they could scale up blood collections.
Gould says he believes there is a compelling business case for PolyHeme, which is the only product Northfield has developed-at a cost so far of about $137 million-since it was founded in 1985. "We do have the best blood supply in the world, but every day there are situations where blood is not available for patients like the scene of injury whether civilian or military," he says. There are 17,000 U.S. ambulance services, he notes, and if a product like PolyHeme is approved, nearly every ambulance would need some. In addition, 44% of the nation's roughly 5,000 hospitals are rural facilities "where resources are less well-developed," he says.
Unique demands
Patient criteria place some unique demands on the clinical trial. Since the patients by definition will be suffering from hemorrhagic shock because of the loss of blood, many of them presumably will be in no condition to give their informed consent to participate in the trial. To circumvent the problem, the FDA allowed a rarely invoked exception under a 1995 regulation. In lieu of patient consent, the FDA regulations stipulate that researchers must first obtain community consent-a tricky enterprise for any hospital seeking to participate in the study. The FDA left it up to the hospitals under the supervision of their institutional review boards to figure out what their comfort level is for such community consent. To date, 22 hospitals in 18 cities have published public notices indicating an interest in obtaining community consent to conduct the trial, Gould says.
At Methodist, which is participating in the trial with its publicly owned neighbor, Wishard Health Services, the study was advertised in local newspapers, radio and television and researchers also visited community groups at churches and town meetings. Bracelets were made available to anyone who did not want to participate in the event they found themselves a candidate for the trial. Methodist's Bartkus says he "was impressed with the research" that many people did ahead of the community meetings. A marketing group hired to assess the public's response concluded that the community was "overwhelmingly" in favor of the trial and few bracelets were mailed out, Bartkus says.
Researchers at Memorial Hermann Hospital in Houston visited the local Jewish community center; the Hispanic coalition; the Chinese community; two Rotary clubs; gay and lesbian organizations; and hospital volunteers and chaplains throughout the 11-hospital Memorial Hermann Healthcare System, says Tom Flanagan, the system's assistant vice president of emergency services. Public notices were published in the local papers, which included a telephone number that anyone not interested in participating could call to obtain a wristband. Flanagan says that to date 75 people called to opt out of the trial.
Unlike Methodist Hospital, which is still waiting for final approval from its review board, Memorial Hermann is already a month into the trial. The hospital is considering only patients who are transported by its helicopter system, which includes three helicopters available to fly within a 150-mile radius of the hospital 24 hours a day and averaging eight to 10 flights a day. So far, Flanagan says, five patients have been enrolled in the trial, and two received PolyHeme. One patient who was not on PolyHeme died.
Both Bartkus and Flanagan say their hospitals are participating in the trial in part to fulfill their research missions. As healthcare professionals, they are personally excited by it. Flanagan says if the trial proves successful, it would have a huge impact on healthcare beyond trauma care, preserving the blood supply at critical periods. Businesswise, it will offer "tremendous cost savings" and help to mitigate risk management issues in terms of avoiding adverse reactions to blood transfusions, he says.
"What I've seen so far in the design of the product and the way they have worked out avoiding problems previous products have had, I am heartened," Bartkus says. "I think this has strong potential. I would have no hesitation to have it given to me. I really think this is going to work. I'm on board absolutely."
