Winship Bio-Ethicist Develops Research Guidelines for Terminal-Wean
and Brain-Dead Patients
Research into any promising new drug therapy eventually reaches a point
where the investigation moves from the laboratory to humans. As medical
science reaches new heights, the ethical protocols that guide research
on human subjects must keep pace.
Rebecca Pentz, Ph.D., Research
Ethicist for Hematology and Oncology at Emory Universityís Winship Cancer
Institute, is lead author on a paper that is presented in the January/February
Issue of The Hastings Center Report entitled, Revisiting Ethical
Guidelines for Research with Terminal Wean and Brain-Dead Participants.
The Hastings Center is one of the countryís leading think tanks on ethical
Dr. Pentz and her colleagues
developed these guidelines so that her colleagues could proceed ethically
with important translational research while allowing families of patients
to be involved and supportive. For example, many terminal cancer patients
offer to serve as organ donors. With most cancer patients, however,
that cannot happen because of the extent of cancer within the body.
Offering them a research opportunity might be another way to meet the
patientís and familyís goals.
In the case discussed in
this article, cancer researchers Renata Pasqualini, Ph.D. and Wadih
Arap, MD, research biologists in the Department of Genito-Urinary Medical
Oncology, University of Texas M.D. Anderson Cancer Center, had shown
that if peptides--short sequences of amino acids--are gentically attached
to a simple virus known as phage, the phage will bind to the vasculature
of specific organs. In addition, certain peptides will attach to the
vasculature of tumors, which would make it possible to deliver targeted
cancer drugs. Continued research would lead to possible development
of mechanisms for the targeted delivery of cancer therapies, gene therapies
and imaging agents. While Drs. Pasqualini and Arap had demonstrated
the potential in mice, it had not in been demonstrated humans, and the
risk to humans could not accurately be determined from animal studies.
Injection of millions of
phage into humans had never been done. In addition, multiple biopsies
would have to be taken shortly after the phage injection to determine
the extent of distribution. Therefore, the investigators determined
that the burden of research would be unacceptable for anyone with a
life expectancy of more than a few hours.
The potential benefit of
the research for cancer patients, however, compelled the investigators
to search for an appropriate population, and they decided to look to
brain-dead individuals, whose circulatory and ventilatory systems are
being maintained mechanically, and "terminal-wean" patients, whose life
support equipment or drugs will imminently be withdrawn. The primary
reason to approach this population was the experience both doctors had
with families in intensive care units who expressed a dying patient's
wish to donate organs or contribute in some way to the fight against
Dr. Pentz, a widely published
bio-ethicist, worked with Drs. Paqualini and Arap as well as another
ethicist at MD Anderson, Anne Flamm, JD, to develop ethical guidelines
1. Conditions for the proposed research,
2. Eligibility guidelines for appropriate patients, and
3. Guidelines on implementing the protocol.
"Expanding the pool of potential
research participants to include terminal wean and brain-dead participants
may enhance our ability to test new agents with minimal harm," writes
Dr. Pentz in the Hastings article. "Yet we are sensitive to the possibility
that including this vulnerable population may erode respect for humans
as ends in themselves. Our guidelines are intended to prevent this erosion
by limiting both the type of research performed and the eligibility
Among the guidelines is the
stipulation that "participants must have indicated to the health care
team or surrogates that they have end-of-life altruistic goals consistent
with such research." In addition, in recognition of the stress and grief
of family members after they have authorized a terminal wean, the guidelines
stipulate a one-hour limit on any research procedures.
Investigators also included
follow-up interviews with family members of participants in the study
as well as family members of terminal wean patients who were eligible
for the study but did not participate. Three themes emerged from these
interviews: honoring the patientís altruistic wishes is important to
family members; a research study is an acceptable alternative to organ
donation; and the decedentís motives often specifically include the
desire to benefit cancer research, the treating physician or the hospital.
Dr. Pentz, Dr. Flamm, Dr.
Pasqualini and Dr. Arap conclude that research on terminal-wean and
brain-dead patients can be performed ethically providing specific guidelines
are followed. They recommend continued discussion of the issue with
a panel of ethicists, researchers, and patient representatives. "We
also believe," writes Dr. Pentz, "that the evaluation begun by this
protocol be expanded to consider the impact of such research on families,
care providers, and the public."
Dr. Pentz is a widely published
investigator and author in bioethics. Her research focuses on ethical
issues involved in oncology research, genetic testing, informed consent
and privacy. She received her Doctorate of Philosophy in Philosophy
from the University of California at Irvine.