Many patients taken to the University of Maryland's Shock Trauma Center in Baltimore cling to life, barely able to breathe, much less consent to participate in a medical trial, a reality that makes trauma research extremely difficult.
With life-saving advances so hard to identify, researchers at Shock Trauma now hope to get around that problem — and answer one of trauma medicine's vexing questions — by declaring nearly everyone a potential test subject.
The Baltimore hospital is one of 12 trauma centers around the country aiming to use a controversial bureaucratic tool to bypass individual consent and conduct the type of large-scale medical experiment that has proved elusive in the messy, life-and-death specialty of trauma care.
When the trial is finished sometime in 2015, researchers hope to finally answer the question of how best to transfuse blood products into a patient who is bleeding to death.
Until that answer surfaces, every accident victim, gunshot victim or other severely bleeding patient in the Baltimore area could become a test subject. Anyone who does not want to participate would need to wear an armband, announcing their intention to opt out.
Funded by the Army, the study seeks to determine the proper ratio of blood products that an emergency transfusion patient should receive. Patients brought into trauma centers would be randomly placed into groups, each given a different mixture.
The study's leaders point out that all of the blood products used — red blood cells, plasma, platelets — are approved by the U.S. Food and Drug Administration and used routinely in trauma rooms. Because treatments vary so broadly among doctors and hospitals, none of the treatments being studied is vastly different from what a patient might receive randomly anyway.
"The process of community consultation has gone through rigorous FDA review," said Dr. Thomas Scalea, head of Maryland Shock Trauma Center and principal investigator in Baltimore. "I think it is vital that we do these studies. I could be putting you at risk right now because I don't know the answer to what works best."
The FDA adopted rules in the 1990s allowing hospitals to consult with the community before conducting medical experiments for those situations when seeking patient consent isn't realistic. Community consultation furthers research on human subjects in life-threatening situations where decisions on treatment are made quickly, according to the FDA.
While the rule is not new, medical ethicists still debate its use. Some argue people should have the choice whether to participate in trials that could harm, or even kill them, no matter how slim the chances.
A study sponsored by the National Heart Lung and Blood Institute testing use of a salt solution in trauma patients without consent was shut down in 2009 because patients appeared to die more quickly and the treatment seemed to offer no health benefit.
"Can you have rules that say we're all research subjects unless we're not?" asked George J. Annas, a Boston University bioethicist and critic of community consultation. "Consent is really important."
Annas and other bioethicists said the multistate shock trauma study that includes Maryland is not as troubling because it does not involve experimental treatments. But they still question the concept of using community consultation to bypass individual consent for medical research.
"This is taking two accepted things we know work and seeing which one works best," said Daniel O'Connor, a research scientist at the Johns Hopkins Berman Institute of Bioethics. "This is not experimental. It's not like injecting Coca-Cola in subjects to see what works."
The study will look specifically at what ratio of plasma to platelets to red blood cells should be used by hospitals when transfusing blood into patients with severe injuries. One group of patients will receive one unit of plasma and platelets for every unit of red blood cells. Another group will receive one unit of plasma and platelets for every two units of red blood cells.
Trauma hospitals around the country use different ratios and studies on which works best are inconclusive. The military uses the 1:1:1 mix and has reported anecdotal success from the battlefield.
The 1:1:1 ratio also gives doctors the closest approximation of a unit of whole blood, which is used rarely for transfusions in developed countries. Donated blood is instead broken into components so doctors can prescribe for patients the components they need, each of which has different characteristics.
Red blood cells, for instance, transport oxygen from the lungs, and are prescribed often to replace lost blood. Platelets help blood to clot. Plasma carries blood proteins that also aid in the clotting process.
While it has become more common and many doctors argue it has saved lives, the use of plasma in transfusions is itself controversial. In particular, studies have linked plasma to increased risk of acute lung injury, or respiratory distress after the transfusion. The lung disorder is one of the more common causes of transfusion-related deaths and at the very least lands most patients on a ventilator.
"It's one of those things that is a double-edged sword," said Dr. Elliott R. Haut, a trauma surgeon at Johns Hopkins. "Certainly it saves lives when it is needed. If your blood is not clotting right and if you need plasma there is absolutely no question about it. It can save your life. It also brings around extra risks."
But Haut said the risks aren't as bad as they once were, and doctors have come up with better ways of determining good plasma matches. For instance, women who have had multiple children are not good plasma donors, he said.
Nearly 40 percent of patients who end up at shock trauma need blood transfusions, and bleeding complications are a leading cause of early death among trauma patients.
"What we need is the hard evidence on whether one ratio is better than the other," said Col. Dallas Hack, director of the Combat Casualty Care Research Program for the Army and Defense Health Program, which is funding the study. "This is the final major step to give us that evidence."
Maryland Shock Trauma Center has used community consultation for at least three studies in the past decade and a half, Scalea said. Without community consultation, real-time testing on patients would be nearly impossible, he said. Instead, researchers would have to rely on data collected on past cases, a method of research he argued is less reliable.
Scalea said a trial in the 1990s that used community consultation led to changes in procedures he believed eventually saved lives. Before the study doctors gave patients fluid to try to normalize low blood pressure, but researchers determined giving fluid had no benefit and that normalizing blood pressure led to more bleeding.
"We [now] will allow your blood pressure to stay low for a while so you won't hemorrhage," Scalea said.
But there is no guarantee every trial will have positive results, raising concerns among some ethicists about the use of community consultation.
Shock Trauma researchers have started reaching out to people through newspaper and radio advertisements directing them to a website about the study, umm.edu/shocktrauma/bloodstudy. They will spend at least the next month or so trying to reach people at community meetings, churches and events.
They planned for a booth at the Baltimore Running Festival, and to inform people at farmers' markets. They also are working with government agencies, such as the state Department of Health and Mental Hygiene, on ways to reach people.
Because the FDA allows so few studies to use community consultation, there are strict guidelines. The studies are reviewed carefully by the FDA and require approval and oversight of an institutional review board throughout the investigation. The study at Maryland Shock Trauma Center already has spent two years getting the proper approvals.
The FDA requires such studies to be disclosed publicly and the IRB must approve community consultation activities. The FDA doesn't say specifically what amounts to sufficient community consultation.
The study will be halted immediately if it is found patients are being harmed. It also will be stopped early if no significant results are found. Scalea said he feels the process protects patients while allowing for cutting-edge research.
"The FDA has determined this is an ethical way to do this." Scalea said.
Despite the efforts to spread word of the study, some ethicists say it is impossible to reach enough of the community to gather consensus. Maryland Shock Trauma Center treats a large number of gunshot victims involved in Baltimore city's drug trade, for instance. Will Maryland researchers be able to reach this population?
"There is no way you can reach everybody," Annas said. "It's more symbolic than real. You're trying to say consent is important when it really is not."
Scalea conceded that it is impossible to reach everyone, but said a good cross-section of the population is achievable.
"Are we going to get to all 5 million people in the state of Maryland? No," Scalea said. "Are we going to do our very best to do this ethically with all the best intentions? Absolutely."
Scalea said armbands are a good tool for identifying people who don't want to participate and that citizens have to take a personal responsibility to stay informed.
"If you don't want to play all you have to do is wear the armband," Scalea said. "We are happy to give you as many armbands as you want. You can change them every day."
Others doubted people would consider wearing armbands to be a serious option.
"This notion that you can refuse consent with an armband is hilarious," said Leonard Glantz, a professor of health law, bioethics and human rights at the Boston University School of Public Health. "The whole idea is silly. There is no evidence that a lot of people will wear an armband."
Bioethicists said community consultation also raises concern in African-American communities where distrust of medical studies is ingrained. And many others, no matter their race, don't want to be the subject of an experiment.
"There is some apprehension, which I frankly think is for the most part misplaced," Scalea said. "I think people say, 'I don't want you to experiment on me.' But if you come in here and I'm on call you get this, and if my partner is on call you get that."
Hopkins' Haut agrees that community consultation in lieu of individual consent is a valid way of conducting research. He expects more studies to use the tool.
"There are really important questions in trauma and emergency research that are hard to do without community consent," he said.
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