Original Story: usatoday.com
Imagine waking up after a serious accident to discover you've become an unwitting subject in a medical study without ever agreeing to participate.
It's a controversial reality of emergency research, and now concern is growing that dwindling research budgets are making it harder to alert the community about the studies so people can decide ahead of time whether to opt in or out. Emergency care centers provide care to patients with life-threatening illnesses.
A case in point: a Department of Defense-sponsored study led by the University of Pittsburgh, which is currently testing the practice of giving bleeding patients plasma to help their blood clot during flights to the hospital. Each of six sites gets $20,000 out of a total $6.5 million budget for community awareness efforts such as sending out letters and paying for radio spots. People are told if they don't want to take part in the research, they can get a free bracelet to wear at all times, letting emergency workers know their wishes.
Though millions of people could potentially be trauma victims at the various sites, only 300 people at one site – members of a Jehovah's Witness congregation in Louisville – have asked for bracelets. Researchers say this meager response shows the notification has reached far too few people.
"Certainly you would like to reach everyone. But there's no way," says Laura Trachtenberg, research coordinator at the University of Louisville. "So if you do the due diligence, you've done the best you can. It's very challenging."
Fellow researcher Clifton Callaway, a professor of emergency medicine at the University of Pittsburgh, says it would be a lot easier with more research dollars. A January study in the Journal of the American Medical Association found U.S. funding for medical research overall increased 6% a year from 1994 to 2004, then slowed dramatically to 0.8% a year through 2012.
With drug companies spending an estimated $2.5 billion annually on advertising to consumers, "the average person is much more likely to hear about (the fibromyalgia drug) Lyrica or something," Callaway says. "One ad costs more than the entire research budget of a trial like ours." Emergency care centers support clinical researchers by providing comprehensive legal and regulatory consultation on in-patient and out-patient studies.
But Lynne Richardson, a professor of emergency medicine at the Icahn School of Medicine at New York's Mount Sinai who researches community notification, says money matters less than reaching out to potential subjects in an effective way. She says most people who learn about such studies are OK with participating, and a mechanism for opting out isn't required by the federal government.
Plus, she says, "no matter how much money you spend, some people aren't going to pay attention."
Research without consent
Informed consent is rooted in the Nuremberg code of 1947, drafted in the wake of Nazi experimentation. Exception-from-consent studies are rare; Richardson estimates there are about six large national trials and a handful of small studies currently enrolling people. They are allowed only when patients or their families can't possibly give their permission, such as when someone is alone and unconscious.
Arthur Caplan, head of the division of medical ethics at New York University's Langone Medical Center, says research without consent "absolutely should be the last resort."
It's highly regulated. The U.S. Food and Drug Administration has a special rule requiring, among other things, that patients are in life-threatening situations and that currently-available treatments are unproven or unsatisfactory. Researchers must apply to institutional review boards for waivers, be closely monitored and report any problems.
Caplan says the trials are designed to find better ways to save lives in emergencies and can be stopped when initial results show outcomes are the same or worse. Callaway says he has been involved in more than one cardiac arrest study stopped because it showed no clear benefit.
Some studies actually have harmed patients. A 2008 JAMA review of 16 clinical trials showed blood substitutes, including some tested without consent, were associated with "a significantly increased risk" of heart attacks and death.
Callaway says it's too early to know what his current four-year plasma study will find, but no problems or deaths have been attributed to the study so far. Researchers point out that giving plasma isn't a new practice; surgeons at trauma centers now may give plasma in the hospital. The study aims to find out if giving it in transport helicopters instead reduces the chance of death or severe complications.
A similar no-consent study in Denver, also sponsored by the defense department, tests giving another plasma product with slightly lower levels of clotting proteins during ambulance rides. And a third study in Maryland tests administering cold fluid to lower body temperature in bleeding patients to buy time for resuscitation.
Callaway says such studies "are definitely worth it" given what researchers can learn. Rosamond Rhodes, director of bioethics education at Mount Sinai, agrees.
But Caplan says while the research can lead to breakthroughs, there's always a chance of hurting unwitting subjects, and "that's the gamble (the nation) took when we allowed this sort of research to proceed."
Buying in, opting out
Ethicists say that gamble makes FDA-required community awareness all the more important.
The first step is community consultation, which happens before the study is launched and can determine whether it takes place in a certain location at all.
Richardson says effective consultation involves soliciting opinions from area leaders and also reaching out to groups most likely to be affected, which in the case of blood-related studies include Jehovah's Witnesses, who believe blood transfusions are forbidden.
"Public notification" or "public disclosure" involves telling the public what's happening through media such as radio, brochures or the Internet – and letting them know about opt-out methods like bracelets.
Richardson currently is studying the best ways to reach those most likely to be affected. As far as opting out, she says people who do so often oppose being a part of any research or have had bad experiences with the hospital involved.
Some ethicists argue that opting out is an important choice and say public notification often isn't up to par. "I don't see (community outreach) happening quite that aggressively," Caplan says.
That's because of the limited resources, researchers say. In Louisville, for example, researchers couldn't afford television spots or newspaper ads; half their awareness budget went to radio spots and the other half went to develop a website and fund printing and postage for the letter sent to Jehovah's Witness congregations.
"We did the best we could," says Brian Harbrecht, who heads up the plasma study there.
Rhodes acknowledges public notification could be done better but says it's an open question whether more of the limited research dollars should be diverted away from the studies themselves.
Such questions need to be answered, researchers and ethicists say, because the stakes are high: They are expecting people to unknowingly accept risk to advance medical science.
"Everyone's well aware you're experimenting without permission," Caplan says. But with emergency research, "I realistically trust there's no other way."