EXECUTIVE SUMMARY
Research on how to improve the quality and quantity of organs available for transplant poses multiple ethical challenges. A new report recommends that:
• clear and consistent information be used to inform potential donors that donated organs may be used for both research and transplant;
• a single IRB be used for review, approval, and oversight;
• recipients of organs subjected to research interventions should be considered as human subjects.
More than 115,000 transplant candidates are on a waiting list for organs — but only about 33,500 organs were transplanted in 2016. These numbers tell an unfortunate story: that every year, thousands of people die waiting for an available organ.
“We are all aware of the substantial gap between organs that are needed and organs that are available. There is a huge gap between supply and demand,” says James F. Childress, PhD, John Allen Hollingsworth professor of ethics and emeritus/founding director of the Institute for Practical Ethics and Public Life at University of Virginia in Charlottesville.
Much of the discussion to date has centered on how to increase the number of organ donors. Few people are aware of the need to improve the quality of the organs that already are available.
“Many in the transplant community have proposed that we research ways to improve donated organs for transplantation, in order to improve transplant outcomes and reduce the gap,” says Childress.
Almost 5,000 organs from deceased donors were discarded in 2015 because they were deemed unsuitable for transplantation.1 Some donated organs are used solely for research because they don’t meet the criteria for transplantation. “Research is needed on how to best optimize organs for transplantation,” says Childress.
Interventions on the organs while they are still in the donor’s body or shortly after removal could improve the chances of a good outcome for the recipient. “Some research has been done, with some good results. But there are some perceived obstacles to doing this research,” says Childress.
A Delicate Balance
In 2016, The National Academies of Sciences, Engineering, and Medicine assembled an expert panel to examine the ethical, legal, regulatory, policy, and organizational issues related to research in the United States involving deceased organ donors. The committee looked at how this important research can be performed ethically, in adherence with the regulatory and legal rules currently in place.
“Our task was to determine: Can this research be conducted ethically, within those frameworks? And if so, how? It’s a delicate balance,” says Childress, chair of the study committee.
The resulting October 2017 report, Opportunities for Organ Donor Intervention Research: Saving Lives by Improving the Quality and Quantity of Organs for Transplantation, offers recommendations for conducting organ donor intervention research in a way that maintains high ethical standards, ensures dignity and respect for deceased organ donors and their families, and provides transparency and information for transplant candidates who might receive a research organ.2,3
Trustworthiness of the organ donation system, and of research involving human subjects, is heavily emphasized. “We depend on the public to donate organs and to participate in research to generate knowledge and benefit others,” says Childress. Some of the committee’s recommendations include the following:
• The Uniform Anatomical Gift Act should be clarified to allow people to understand that donated organs might be used for research and transplantation.
“It’s not a single purpose, but a combined purpose,” says Childress. “People need to understand as much about this as possible so they don’t end up feeling that their trust has been violated.”
• Donor registries and departments of motor vehicles should use consistent language to communicate about this type of research to potential donors and surrogates.
• Recipients of organs that have been subjected to research interventions and are now being studied for their function, efficacy, and safety should be treated as research participants.
Deceased organ donors are not characterized as research subjects because federal regulations for research protection only apply to living individuals.
“Nevertheless, it’s important to respect individuals and surrogates in making decisions about organ donation, and to determine if they are willing to donate for this purpose,” says Childress.
The committee contended that under most research protocols, patients who receive organs that were subject to a research intervention are research subjects. “This raised a lot of issues,” says Childress. “For instance, research informed consent may be very difficult to obtain when organs need to be transplanted quickly.”
Realities of Transplantation
A robust clinical informed consent process that includes specific regulatory requirements already exists for transplantation, says Alexandra K. Glazier, Esq., president and CEO of New England Donor Services in Waltham, MA.
For donor research where the transplant recipient does not fall under the regulatory definition of human subject, the clinical consent model — rather than the consent model used for human research subjects — best balances clinical innovation, transparency, and protection of patients, she argued in a recent paper.4
“The ability to conduct research trials to evaluate interventions on the deceased donor, or donor organ, remains complicated and fraught with regulatory ambiguity,” says Glazier, who co-authored the paper.
Characterizing recipients of organs that have been subjected to a research intervention under existing regulatory requirements is one example. “The need for a precise legal and ethical analysis that maps the regulatory language and the complex process of donation and transplantation was needed,” says Glazier.
Facilitate Informed Consent
Much of the discussion in the field regarding deceased donor intervention research has been predicated on the assumption that recipients of these organs are human subjects — even if no research intervention or interaction will take place after transplantation. “The implications of that conclusion are numerous,” says Glazier.
Regulatory requirements for institutional review board (IRB) review and human research subject informed consent emphasize beneficence, autonomy, and transparency. “While these goals are appropriate, the process required does not comport with the realities of transplantation,” says Glazier.
Many ethical concerns will not be resolved merely by categorizing transplant recipients as human subjects. For example, the time-critical process of organ offers and the transplant candidate’s health status greatly reduce the ability for effective informed consent. Many individuals are incapacitated at the time of organ offer.
“Requiring human research subject informed consent at the time of organ offer could raise issues of undue influence, when the ability to receive an organ transplant is predicated on consent to participate in human subject research,” says Glazier.
Glazier would like to see changes that allow for vital research to be conducted, while addressing recipient informed consent in an ethically meaningful and realistic manner, given the complexities of the transplantation process.
“Although we conclude that transplant recipients of research organs may not be human subjects if no research intervention or interaction will take place, the need for effective informed consent remains ethically paramount,” says Glazier.
To expedite organ donor intervention research, the committee recommended that a centralized review process with a single IRB be used. “This would eliminate the need to have a separate IRB for each transplant center sign-off on it,” explains Childress.
To reduce delays, the committee recommended the following two-stage process of disclosing information to potential transplant recipients:
• The first stage would consist of informing potential recipients, at the time of intake or listing, about the possibility of being offered organs that were part of a research project, the different levels of risk associated with such organs, and the risks of declining an offer of a research organ.
Potential transplant recipients can indicate at that time whether they would be willing to consider a research organ, if offered. “Or, it could be more nuanced than that. For instance, the person might be willing to consider a minimal-risk organ,” says Childress. If a potential recipient declines, he or she will not be notified when a research organ becomes available.
• Transplant candidates who have agreed to consider research organs will be notified when a research organ becomes available, and will be informed about its risk level.
Giving patients the option of accepting a research organ mirrors the ongoing debate regarding older organ donors.5 “This is another factor like that, but in the research setting,” says Childress.
Currently, if a person wouldn’t consider a research organ at all but is offered one without anyone knowing the person’s preference, the organ is declined. The transplant team has lost a lot of time — and the organ is likely to be discarded.
“What this proposal does is reduce the chance that someone will decline an available organ when it is offered,” says Childress.
REFERENCES
1. Organ Procurement and Transplantation Network. National data. Available at: http://bit.ly/29MwOt8. Accessed Dec. 14, 2017.
2. National Academies of Sciences, Engineering, and Medicine. Opportunities for organ donor intervention research: Saving lives by improving the quality and quantity of organs for transplantation. Washington, DC: The National Academies Press, 2017.
3. Childress JF. Organ donor research: Overcoming challenges, increasing opportunities. JAMA 2017 Oct 10. doi: 10.1001/jama.2017.16442. [Epub ahead of print]
4. Heffernan KG, Glazier AK. Are transplant recipients human subjects when research is conducted on organ donors? Hastings Cent Rep 2017; 47(5):10-14.
5. Querard AH, Foucher Y, Combescure C, et al. Comparison of survival outcomes between expanded criteria donor and standard criteria donor kidney transplant recipients: a systematic review and meta-analysis. Transpl Int 2016; 29(4):403-415.
SOURCES
• James F. Childress, PhD, John Allen Hollingsworth Professor of Ethics and Emeritus/Founding Director of the Institute for Practical Ethics and Public Life, University of Virginia, Charlottesville. Phone: (434) 924-6724. Email: [email protected].
• Alexandra K. Glazier, Esq., President & CEO, New England Donor Services, Waltham, MA. Email: [email protected].
Research on how to improve the quality and quantity of organs available for transplant poses multiple ethical challenges.
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