By Stacey Kusterbeck
Research on recently deceased humans is important to conduct, but there are many challenging ethical considerations. “A key ethical concern is the length of the experiment,” says Rebecca D. Pentz, PhD, a professor of research ethics at Emory University School of Medicine’s Winship Cancer Institute.
Early guidelines limited the research to several days at most.1 “This was out of respect for the grieving family, so that they would not need to postpone memorial services to honor their deceased loved one,” explains Pentz.
Pentz’s first involvement with such research, at MD Anderson Cancer Center, was limited to just a few hours. That particular experiment was not performed on the recently deceased, but, rather, on patients who were going to undergo a terminal wean from the ventilator since the ventilator was no longer effective and there were no alternative measures. “The experiment was very short, so we only had to delay the terminal wean by several hours,” reports Pentz.
However, some studies on the recently deceased require longer time frames. For instance, one of the key issues in xenotransplantation is the possibility that the organ will carry infectious agents resulting in xenozoonosis. That could happen weeks after xenotransplantation. “So the xenotransplant folks want to observe the deceased person for at least six weeks. How that is done in a way respectful to the deceased and to their grieving family is a major concern,” says Pentz.
In a recent paper, Pentz and colleagues called attention to the need for immediate investigation on important ethical issues about research involving recently deceased humans.2 For researchers, these are important considerations, assert the authors:
• Researchers need to consider whether the research could be better conducted in animals or in living persons.
• Researchers need a robust procedure for identifying subjects.
• Researchers need to be able to explain the study clearly (either to the person before death, or to the family after death).
• Researchers need to be clear on how long the recently deceased person will be involved in the study so the family can plan accordingly.
• Researchers must clarify whether the family can visit the recently deceased person during the experiment.
Institutional review boards (IRBs) will not be reviewing the study protocol, since IRBs are limited in their oversight to research involving human subjects, and a dead person is not a human subject. “However, there does need to be an appointed independent review committee,” says Pentz. Pentz says these are important questions for committee members to ask researchers:
• Is this the best population for your type of research? Have you considered live persons or animals?
• What is the justification for the length of the study?
• Where will the procedures be conducted? If it is the intensive care unit (ICU), will that affect the care of living persons?
• What is the procedure if nurses or attending physicians do not want to participate in the research? What is the process for their ability to refuse? Who will then conduct the procedures?
• Who will make the contact with the person before death, or with the family after death?
• How will consent be obtained?
• Can the family visit the deceased during the experiment? If so, how will that be handled?
• How will the procedures be conducted so there is minimal disfigurement to the body?
• Do you have any plans for ensuring that the public is informed of what you are doing? How will you address any community concerns?
Researchers also must be prepared to address family concerns. In Pentz’s experience, these are some questions family members commonly ask:
• Will there be any disfigurement to the body? “The researchers should very carefully describe any disfigurement and how they will attempt to minimize disfigurement,” says Pentz.
• How long will the experiment take, and when can we plan memorial services? “The researchers should be very specific about the timeline,” advises Pentz.
• Why is this research important? “Be sure to very carefully explain the benefit to science and the public, so the family knows that their sacrifice will be beneficial to others,” recommends Pentz.
• Can I visit my loved one during the experiment? The answer depends on the institution’s policies. If it is permitted, researchers need to explain the specifics, such as how often and whether the visitor will need to be monitored long-term for infections.
• Why can’t we donate our loved one’s organs instead?
Research on the recently dead only takes place if the participant cannot donate organs due to their medical condition. “Explain this in detail to the family,” says Pentz.
• Who will take care of the body during the experiment? Researchers need to explain where the experiment will be done (in the ICU or in a special room, for example) and who will monitor the body (regular nurses, specially trained nurses, or just the investigators).
• How will the body be returned to us? “Explain if the family will need a funeral home to pick up or if there are other arrangements,” says Pentz.
The main unresolved ethics question in research involving recently deceased humans is the “declaration of death” and by what criteria that should be assessed, according to Currien MacDonald, MD, CIP, medical chair director at WCG. “Neurologic criteria are the widely accepted standard, but even that term has different interpretations. Even legal definitions vary between the states in the U.S.,” notes MacDonald.
As technology advances, whole-brain death, neocortical death, or other ways of measuring brain function to define neurologic criteria will continue to evolve. “Families are usually not consulted on the declaration of death and may have objections for various reasons,” notes MacDonald.
The specific method of declaring death, which neurologic criteria are employed if used, and attention to the surrogates of the deceased are all important considerations for a researcher intending to include the recently dead in studies, says MacDonald. IRBs must consider those same issues. “However, IRBs may tend to conflate research on the recently dead with human subjects research,” says MacDonald. If the study only starts after the person is declared dead by the appropriate legal means, there is no human subject. Thus, consent of the family (as if the person were alive but needed surrogate consent) does not apply. “It is a difficult situation for research institutions,” says MacDonald. “It would appear that the IRB would provide the best oversight, but most of the IRB tools don’t apply and may restrict ethical research.” For studies that start when the person is alive, IRBs would do well to focus on the standard IRB concerns of recruitment, future use, and secondary subjects in DNA-based and similar research. “Ensuring appropriate criteria and the methods to monitor the declaration of death are also critical,” adds MacDonald.
- Pentz RD, Cohen CB, Wicclair M, et al. Ethics guidelines for research with the recently dead. Nat Med 2005;11:1145-1149.
- Parent B, Kates OS, Arap W, et al. Research involving the recently deceased: Ethics questions that must be answered. J Med Ethics 2023; Dec 8:jme-2023-109413. [Online ahead of print].
