End-of-life research: IRBs queasy about studies with dying patients
Broad restrictions and concern for family often impede research
The goals of palliative and end-of-life research are unimpeachable — discovering methods to ease the suffering of dying patients and their families.
But there are obstacles to achieving those goals. Patients in such studies are only available to researchers for a short time. They may lose the ability to participate in research due to incapacitation. Family members may not wish to burden them with research activities when time is short and hours are precious.
Experts in the field say another significant obstacle to end-of-life studies is the reluctance of IRBs to allow them or their tendency to unnecessarily restrict them in the name of protecting a vulnerable population. They argue that the issues involved in dealing with dying patients are often no different than those that arise with other vulnerable populations, such as mentally ill patients or cancer patients recruited for Phase 1 trials. And they say that patients in hospice and other end-of-life settings may actually benefit from the knowledge that their experience will help others.
"There can be a risk of assuming that they are too sick to participate, and that’s not true," says Charles von Gunten, MD, PhD, FACP, editor-in-chief of the Journal of Palliative Medicine and medical director of the Center for Palliative Studies at San Diego Hospice and Palliative Care. "The reason people in a palliative care population participate in research is strongly related to their desire to give back, to want to be of service, particularly at a time of life when they are thinking about final gifts and What was my life worth?’ Participation in research is a very important part of that for some patients."
Von Gunten’s hospice has its own IRB and works with researchers, both inside and outside the institution as part of its mission to improve end-of-life care. The need for good evidence-based information about palliative care is great, he says.
"This is a population that has by and large been neglected and yet it’s large 2 ½ million people in the country die every year," von Gunten says. "Their medical care is important and most of the medical evidence base rests on extrapolation from other populations."
David Casarett, MD, MA, assistant professor of medicine at the University of Pennsylvania’s Division of Geriatric Medicine and a researcher into end-of-life decision-making, says that in general, IRBs do a "pretty awful job" when presented with protocols for patients in hospice or other end-of-life settings.
Too often, he says, they place overly broad restrictions on access to such patients out of fear of distressing them or their families.
"As we all know from our personal lives, the idea of talking to somebody who is dying is kind of scary," he says. "I think we’re all sort of queasy at getting too close and causing distress. So we tend to avoid situations like that in our own personal lives. And as people become IRB members, they worry about actually talking to a family member about the death of their loved one and the possibility that those conversations might cause somebody to break down and cry. IRBs just think that’s the most awful thing in the world."
However, the following are serious concerns that IRBs should rightly weigh when presented with end-of-life protocols, von Gunten and Casarett say.
Time burden. Dying patients do face risks, including the simple passage of time. A survey that takes too long to administer isn’t just an inconvenience, it robs the patient of precious time spent with family and friends.
"To some degree, time and inconvenience are burdens for anybody," Casarett says. "But hour for hour, it may be a bigger burden for somebody who has fewer hours."
He notes that patients and their families are usually very straightforward about telling researchers when the study for which they’re being recruited would take more time than they’re willing to give.
Von Gunten says his institution’s IRB focuses more on instrument burden than other IRBs might. A long survey instrument that might take hours to complete might be considered too burdensome in this population, he says.
He says his IRB also is willing to take on the science of a proposed protocol.
"Our IRB would say that they are supposed to protect patients from risk," von Gunten says. "And if the science is not good, then no risk, even if it’s a minimal risk, is worth it, because it’s a vulnerable population, which has limited time, and they don’t want to waste subjects’ time on studies that won’t produce good research. I’ve never encountered that with other IRBs."
Causing distress. Many end-of-life studies are surveys in which patients and their families are asked about issues related to death and dying. A common concern of IRBs reviewing these studies is the possibility that they might cause patients or family members emotional distress. Casarett believes that concern is overblown by many IRBs.
While he says that it’s true that patients and family members may respond to a survey about their feelings and attitudes by crying, it doesn’t necessarily mean that the questions are unwelcome or the emotions are viewed negatively.
"Family members may say, Yes, it was really distressing to talk about my father’s last weeks of life, but it was also really valuable, because it gave me a chance to talk those things over with somebody. It was really valuable to know that his experiences would help other patients. And overall, I’m really glad I did this interview,’" Casarett says. "But IRBs don’t see those parts; they just see the fact these interviews might cause distress."
Von Gunten says the San Diego Hospice IRB requires that the researcher present a plan for how he or she will deal with a situation in which a person being surveyed becomes distraught.
"A researcher is not absolved of responsibility for the distress they might cause," he says. "So even if the interview is over and the researcher leaves, and the study is done, they have to have a plan for ensuring there’s counseling and support in the wake of the study."
Although counseling is among the services offered to all patients at the hospice, "they have to have a system or a plan for how it would get operationalized," von Gunten says. "You can’t just assume that somebody will do it. That’s really not taking responsibility for your actions."
Informed consent. Von Gunten says informed consent issues in end-of-life care are not any different than they are in other settings.
"We use the same standards as everybody else, which reduces the size of the population, because they have to be able to give consent," he says.
Casarett says that informed consent creates challenges among dying patients because of the high prevalence of conditions that impair decision-making judgment. But the issues themselves are no different than in other vulnerable populations, and the same rules apply.
"If you’re concerned about informed consent in end-of-life populations and you take seriously concerns about decision-making capacity, then you should exercise exactly those same concerns with Phase 1 trials, oncology trials and other similar trials," he says. "Psychiatry research, dementia research there are plenty of other situations in which there are significant problems with informed consent."
He says that a little-used method of gaining advance consent for specific studies could help facilitate the trickiest of all end-of-life research working with patients who are only days, or even hours from death.
"There are a lot of terminal symptoms, such as terminal delirium in the last days of life," Casarett says. "We don’t know much about how to manage that effectively because it’s very hard to enroll people. If somebody has to be delirious and dying to be enrolled, you can’t wait until they’re delirious and dying and then try to get consent."
In advance consent, a patient could sign a study-specific consent form stating that in the event the patient develops a particular condition during a hospitalization or hospice admission, he or she consents to participation in the study.
"The study has been explained to me, I understand exactly what would happen, I understand who’s doing it," Casarett says. "It’s very specific to this hospitalization, or nursing home admission. And it’s very study-specific."
Casarett says more IRBs soon may be introduced to the challenges of handling end-of-life research proposals, as interest grows in this area of research.
Last year, the NIH held a three-day state-of-the-science conference on improving end-of-life care. A panel of experts recommended increased federal funding for end-of-life research, creating new networks of researchers in the field and supporting existing networks.
"They really see end-of-life research now as a priority," Casarett says. "And I think in the very near future, that will trickle down to more funding and more good research, so it’s something that IRBs really need to become familiar with and comfortable with very quickly."
Among those existing networks currently engaged in end-of-life studies is the Population-Based Palliative Care Research Network (PoPCRN), a Denver-based research group that links organizations providing hospice and palliative care.
Its director, Jean Kutner, MD, MSPH, works with both university-based IRBs and hospice IRBs such as San Diego Hospice’s board to conduct multi-site studies of end-of-life issues.
She says relations with both types of IRBs have been smooth, although she notices that the hospice-based IRB understands some nuances of end-of-life care that a more general IRB might not.
For example, her university IRB’s consent form contains standard language offering medical care to anyone injured by research. Kutner notes that some patients may not want such treatment, if they have advance medical directives limiting interventions at the end of life.
"I can’t get them to let me modify it to say, consistent with palliative care goals,’" she says. "San Diego Hospice templated forms contain standard language that is more relevant for the population."
Von Gunten and Casarett say that IRBs approaching end-of-life studies should be sure to seek out the right expertise for the board.
"It doesn’t necessarily have to be a physician, but it needs to be somebody who knows the clinical field, knows the patient population and has clinical experience," Casarett says.
Von Gunten suggests bringing other stakeholders to the conversation as well, including family members of patients, or nursing representatives for a study that focuses on hospice nursing.
He says seeking out IRBs that do a lot of end-of-life care can help provide a better idea of logistical issues that may come up. For example, he says, IRBs should be prepared for large numbers of serious adverse event (SAE) reports from end-of-life, because of the unique characteristics of the study population.
"It’s a unique challenge to us, particularly in new drug studies, where all adverse events need to be reported and death is a serious adverse event by definition, and you’re working in a population where death is expected," von Gunten says.
"We have lots of SAEs that have to be processed. They all are thought to be not related to the therapy but it’s still a huge paperwork burden. This is a group that only lives on average 41 days."
Casarett says that ideally, he’d like to see a national IRB, set up by national organizations devoted to end-of-life care, which could handle multisite studies.
While such an undertaking might be expensive, "it would pay off in the long run because it would make possible a lot of research that is really pretty prohibitive to do right now," he says.
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