Yet the U.S. Food and Drug Administration allows for medical experiments without consent under a special waiver provision passed in 1996, and that provision may soon be in play in Durham. Duke University Medical Center researchers hope to test an artificial blood substitute on trauma victims, joining parallel studies already being conducted at urban medical centers around the country. If Duke goes forward with the project, area residents may soon become unwitting guinea pigs.
Before researchers can proceed, Duke's Institutional Review Board (IRB) must first give the go-ahead. Though the IRBs at 11 institutions have approved the study, Boston University rejected it on ethical and other grounds. In fact, the study falls well short of meeting ethical standards on several fronts, and Duke's IRB should kill it.
The search to find a blood substitute that can be used in a trauma setting has been going on for years, and for good reason: Blood cannot be transported in ambulances, and trauma victims who lose a significant amount of blood must wait until they reach the hospital in order to get a transfusion. Saline solution is currently used to maintain blood pressure, but saline does not transport oxygen, and the delay in getting blood replaced often proves fatal.
The product Duke wants to test is PolyHeme, manufactured by Northfield Laboratories of Evanston, Ill. Derived from human hemoglobin, the oxygen-carrying component of blood, PolyHeme showed life-sustaining promise in several earlier clinical trials, and hopes are high that it represents a significant medical advance. Ernest Moore, who heads the Department of Surgery at Denver Health Medical Center and has been leading a PolyHeme trial there, stated in 2002, "I believe the day in which the clinical benefit of blood substitutes will finally be realized has arrived."
The federal consent-waiver rule allows for non-consensual testing only in strictly limited circumstances. In particular, the subjects must be in a life-threatening situation, "available treatments are unproven or unsatisfactory," and the collection of the data is necessary to demonstrate the effectiveness of a given treatment. That would seem to be the case for the PolyHeme trial, or at least part of it--no good alternative exists for PolyHeme in the field, between the time trauma victims are injured and their arrival at the hospital. Northfield, in fact, is calling its trial an "ambulance study."
But the study protocol allows for administration of PolyHeme for up to 12 hours, most of which occurs in the hospital setting after the victim has arrived. There, of course, a well-proven and satisfactory substitute is readily available--whole blood. This aspect of the study has drawn fire from medical ethicists and others who say it's immoral to test PolyHeme on people unless they say it's OK. "It is not until after artificial blood is proven to be equivalent to real blood, using consenting subjects, that it should be used experimentally in non-consenting patients," says Leonard Glantz, a professor of health law at the Boston University School of Medicine.
Northfield Labs' own press releases seem to raise the same questions. Quoting Denver's Moore, the Northfield Web site notes that PolyHeme shows the most promise in maintaining high hemoglobin levels "in the absence of red cell transfusion [...] until critical bleeding can be surgically controlled and red cell transfusions are available."
Trauma surgeon Steven Vaslef, who is Duke's principal investigator for the PolyHeme study, says that continuing the PolyHeme for 12 hours is needed because blood transfusions have been linked to complications that include the transmission of diseases and multiple organ failure. Transfusions are satisfactory, he says, "only in that nothing better has been proven to exist."
But if blood transfusions, one of the most common medical procedures on the planet, can be considered unproven and unsatisfactory because they carry an element of risk, so can almost any treatment--including aspirin.
Other researchers have different explanations for why most of the so-called ambulance study must take place in the hospital. The research coordinator at Lehigh Valley Hospital in Pennsylvania says that PolyHeme has potential for use in situations where real blood may not be available for a long period of time--the battlefield, for example, or a rural area with few medical facilities. The studies must be done in urban research centers, she says, because that's the only place where sufficient staff, facilities and potential subjects can be found.
Northfield won't comment on the matter, using the fall-back position invoked by Vaslef and others: The FDA looked at all these issues and approved the study, and IRBs serve as an additional, independent screening layer. If they all say the study is fine, says a company official, then fine. Questions about the study's approval should be directed to them.
On the other hand, the FDA approved a no-consent trial in 1998 for a blood substitute, HemAssist, manufactured by Baxter Healthcare. That trial was aborted after almost half the subjects receiving HemAssist died, far more than those receiving blood.
Once in the hospital, critics say, PolyHeme should be tested only on consenting subjects. Vaslef objects that it would be difficult if not impossible to test PolyHeme in a consent-based environment. Yet Duke was doing exactly that in a late 1990s study that Northfield ultimately closed before it was completed. "This is research that doesn't need to be done on non-consenting people," says Glantz.
The use of PolyHeme for 11 or more hours in the hospital isn't the only aspect of the study that flunks the smell test. Those conducting no-consent studies must undertake an extensive process of public disclosure and community consultation. And to minimize the chance of enrolling people who would object to the experimental treatment, they must create an opt-out mechanism.
That sounds fine, but the requirements are vague, and the practical application of these safeguards amounts to very little. To date, Duke has set up a hotline, held four public meetings, spoken to a Rotary Club gathering and set up information tables, twice at Northgate Mall and at the July 4 Bulls game. (Attempts to set up a table at Southpoint mall and speak to the congregations of two black churches in Durham were rebuffed.) In addition, Duke placed notices in the local dailies and a few public service announcements on the radio. Calls to the hotline are rare; Vaslef admits that few showed up at the public meetings (though he calls the 15 people who showed up at El Centro Hispano "pretty good attendance"), and he says that only a tiny fraction of those who happened to be at Northgate or the Bulls game for those few hours actually stopped by to check it out.
Nevertheless, Vaslef says, their efforts have yielded about 500 "contacts," of which only a handful have opposed the PolyHeme trial. One can extrapolate from this, he says, and conclude that the community generally accepts the idea. "There's no way you can reach everyone, so it'll have to be a sampling," he says.
Here's another way to look at it: 500 contacts means there's 100,000 people in the Durham metro area who have no clue they might get PolyHeme instead of blood if they need it.
Even more absurd is the idea that the opt-out option has any practical value. As do all the PolyHeme sites, Duke will offer a blue plastic bracelet (Carolina blue, it should be noted) to anyone who chooses not to participate. Objectors can wear the bracelet 24/7, and if they happen to suffer a life-threatening traumatic injury, emergency personnel will recognize the bracelet and keep the PolyHeme out of their veins.
Duke is also providing wallet-sized cards, like organ donor cards, and is compiling a do-not-test list that ambulance attendants will allegedly have on hand and allegedly check when trauma victims are picked up--as long as the list doesn't get too long and unwieldy. But Duke needn't worry much about that, because no one wants to wear an uncomfortable plastic bracelet all day (only one has been requested via the hotline), and few are sticking biz cards in their wallets. And to date, the do-not-test list is only about five names long.
It's understandable why Northfield wants to test PolyHeme as broadly and quickly as possible. PolyHeme is the company's only product, and Northfield is locked in a race with two competitors to bring its blood substitute to market first. Being first is worth hundreds of millions, as the makers of Viagra will confirm.
But Northfield's interests do not trump those of the general public. And while Vaslef and others believe that PolyHeme will prove to be superior to blood in certain applications, and that it would be unethical not to test it on severe trauma patients (who by definition can't consent to the procedure), that has yet to be proven. Until it is, and until it's proven that a no consent-based testing option exists, Duke should avoid joining the long list of collaborators who violate the most basic human right--the sanctity of one's own body.