Concerns over ethical, logistical, and regulatory issues have hindered organ donor intervention research, but there is hope on the horizon via a new study designed to pinpoint how to advance this field. In this issue of “The AJT Report,” we look at the controversy surrounding donor intervention research and ways to address it. We also talk to the two transplant professionals who were awarded lifetime achievement awards from the AST and the ASTS at the American Transplant Congress this year. Concerns over ethical, logistical, and regulatory issues have hindered organ donor intervention research, but there is hope on the horizon via a new study designed to pinpoint how to advance this field. In this issue of “The AJT Report,” we look at the controversy surrounding donor intervention research and ways to address it. We also talk to the two transplant professionals who were awarded lifetime achievement awards from the AST and the ASTS at the American Transplant Congress this year. Concerns with ethical, logistical and regulatory issues have thwarted organ donor intervention research, but a new study from the IOM may offer hope As the field of transplantation continues to grapple with organ shortages, donor intervention research offers the potential to increase organ supply and quality. The process of brain death begins an injury to organs that is then exacerbated by procurement, storage and transplantation. Treating the donor provides an opportunity to reduce the severity of any injury. In an editorial published in this issue of AJT, Sandy Feng, MD, PhD, professor of surgery in the division of transplant surgery at the University of California, San Francisco, and Peter Abt, MD, associate professor of surgery at the University of Pennsylvania Perelman School of Medicine in Philadelphia, describe the “tantalizing potential” of donor intervention research; however, tremendous complexities surrounding these studies have brought this potentially life-saving research to a near halt.2.Abt PL Feng S Organ donor research: It is time for much needed clarity.Am J Tranplant. 2016; 16: 2508-2509Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar Fortunately, hope is on the horizon. The National Academy of Sciences Institute of Medicine (IOM) is planning an extensive study to examine the ethical, policy, regulatory and operational issues relevant to the conduct of research involving deceased organ donors. The aim is to identify and examine the current barriers and opportunities for clinical research in this area. In a briefing document provided for potential study funders, the IOM noted that donor intervention studies represent a paradigm shift in research, but the conduct of rigorous trials in deceased donors is problematic and, in most circumstances, impossible to perform. The IOM also stated that, currently, properly conducted research in deceased donors cannot be accomplished, adding that the issues are too great for the agencies that oversee organ donation and transplantation, healthcare, and research to overcome. “The IOM study will hopefully knock down some of the barriers and hurdles that are currently in place that prevent researchers from advancing the science in organ donation management and intervention,” says Richard Hasz, vice president of clinical services at the Gift of Life Donor Program in Philadelphia. He adds that an IOM study will assist organ procurement organizations in developing standards to inform donor families and effectively communicate with transplant professionals about donor intervention. Douglas W. Hanto, MD, PhD, director of the Vanderbilt Transplant Center in Nashville, Tenn., hopes that the IOM will address ways to obtain informed consent from recipients of organs from donors who have been part of a donor intervention study that protects the recipient, but also balances safety with mechanisms to facilitate donor intervention studies. In materials sent to potential funders, the IOM says it wants to overcome “the parochial vision of numerous individual governmental and nongovernmental organizations that have some degree of influence in research, healthcare, organ donation and organ transplantation but do not internally contain the vision required to establish a framework that crosses numerous spheres of regulation and influence.” Even if the IOM provides approval and guidance to continue donor intervention research, researchers still need an infrastructure and an oversight mechanism to conduct their studies.Key Points•Donor intervention research offers the potential to increase organ supply and quality, but concerns over how the research is conducted have stymied many efforts.•The IOM is planning an extensive study to identify and examine the current barriers and opportunities for clinical research in this area. •Donor intervention research offers the potential to increase organ supply and quality, but concerns over how the research is conducted have stymied many efforts.•The IOM is planning an extensive study to identify and examine the current barriers and opportunities for clinical research in this area. Following several years of informal meetings and a 2013 Donor Management Research Consensus Conference sponsored by the Health Resources and Services Administration (HRSA) and the Organ Donation and Transplantation Alliance (ODTA), workgroups were formed to study donor-focused issues, recipient-focused issues (such as informed consent, the requirement for institutional review board [IRB] approval at transplant centers and communication with transplant physicians) and oversight mechanisms. The Donor Intervention Research Expert Panel (DIREP) arose from these efforts. In September 2015, the ODTA and the DIREP wrote to Robert Walsh, then director of HRSA’s Division of Transplantation, to request the development of an oversight process that would enable and facilitate interventional research in deceased donors and donor organs. In addition to assuring scientific merit, a central oversight board could review all deceased-donor intervention protocols, make a determination of risk, identify steps necessary to minimize risk and approve (or reject) the protocol, says James Rodrigue, PhD, director of the Center for Transplant Outcomes and Quality Improvement at The Transplant Institute at Beth Israel Deaconess Medical Center in Boston. “Donor hospitals and transplant centers would then have confidence that the protocol has been vetted and meets regulatory requirements, and could cede the review and decision to this central body … it would reduce the uncertainty, ambiguity and inconsistencies that we know to exist in having multiple IRBs reviewing the same protocol.” In a report recently published in AJT, Dr. Rodrigue describes the results of a national survey of transplant surgeons, organ procurement organizations and IRB members regarding donor intervention research.3.Rodrigue JR Feng S Johansson AC Glazier AK Abt PL Deceased donor intervention research: A survey of transplant surgeons, organ procurement professionals, and institutional review board members.Am J Transplant. 2016; 16: 278-286Crossref PubMed Scopus (23) Google Scholar While the study highlights similarities and differences in the groups’ perceptions, the study findings strongly underscores the need to clarify ethical, legal and regulatory requirements and their application to deceased-donor research. Most respondents favored recipient informed consent, either at waitlisting, at time of transplant or both. However, some in the transplant community worry that the logistics of consenting potential recipients throughout the United States would hamper—and possibly negate—a recipient’s opportunity to receive an organ. This might be true if each transplant center’s IRB were required to give consent each time a donor-intervention organ became available. If a national oversight board has reviewed the research and found it ethically sound and scientifically meritorious, this should speed the process, says Dr. Feng. “Just like any waitlisted candidate today can prespecify willingness to consider a Public Health Service high-risk organ and hear about the details of the high-risk behavior at the time of an organ offer, a waitlisted candidate can prespecify whether they would consider a ‘research’ organ and hear about the details and risks of the research at the time of offer. As long as the research has been thoroughly vetted by a national oversight board, we might be able to do this, with a lot of safeguards in place.”AN EXAMPLE OF STYMIED RESEARCHIn 2010, Douglas Hanto, MD, PhD, Director of the Vanderbilt Transplant Center, in Nashville, Tenn., published a study demonstrating that, in pigs, treating the organ recipient with low-dose inhaled carbon monoxide reduced delayed graft function in kidney allografts.1.Hanto DW Maki T Yoon MH Intraoperative administration of inhaled carbon monoxide reduces delayed graft function in kidney allografts in swine.Am J Transplant. 2010; 10 (et al): 2421-2430Crossref PubMed Scopus (45) Google ScholarHe says that the research he and his colleagues performed also suggested that the early ischemia–reperfusion injury seen after transplant might be further prevented by treating the donor with carbon monoxide prior to preservation of the kidney. However, he says, the company that supported the original research did not support the experimental work necessary to demonstrate this in pigs, because the company thought it would be too difficult to study carbon monoxide in human deceased donors due to concerns over recipient informed consent.Dr. Hanto also says that, because these organs would travel to various centers locally, regionally and nationally, it would be an insurmountable obstacle to obtain IRB approval from all centers and informed consent from all potential recipients to treat the donors with carbon monoxide. In 2010, Douglas Hanto, MD, PhD, Director of the Vanderbilt Transplant Center, in Nashville, Tenn., published a study demonstrating that, in pigs, treating the organ recipient with low-dose inhaled carbon monoxide reduced delayed graft function in kidney allografts.1.Hanto DW Maki T Yoon MH Intraoperative administration of inhaled carbon monoxide reduces delayed graft function in kidney allografts in swine.Am J Transplant. 2010; 10 (et al): 2421-2430Crossref PubMed Scopus (45) Google Scholar He says that the research he and his colleagues performed also suggested that the early ischemia–reperfusion injury seen after transplant might be further prevented by treating the donor with carbon monoxide prior to preservation of the kidney. However, he says, the company that supported the original research did not support the experimental work necessary to demonstrate this in pigs, because the company thought it would be too difficult to study carbon monoxide in human deceased donors due to concerns over recipient informed consent. Dr. Hanto also says that, because these organs would travel to various centers locally, regionally and nationally, it would be an insurmountable obstacle to obtain IRB approval from all centers and informed consent from all potential recipients to treat the donors with carbon monoxide. “I don’t know what the IOM is going to say about whether and how donor intervention research can be conducted,” Dr. Feng adds, “but we need that clarity, one way or the other.” Research in donor management is one of the most fertile areas for research in transplantation, says David Nelson, MD, chief of heart transplant medicine at Integris Baptist Medical Center in Oklahoma City, and a DIREP member. “There are enormous resources to be had once this process with the IOM and HRSA is completed. I believe there will be rapid and important growth in donor intervention research,” he adds. The American Society of Transplantation (AST) and the American Society of Transplant Surgeons (ASTS) bestowed their highest level of achievement awards to two transplant professionals at the American Transplant Congress this year, held June 11–16, 2016, in Boston. Thomas Gonwa, MD, was awarded the AST Lifetime Achievement Award, which honors a senior investigator whose work has advanced the field of transplantation. A prolific clinical investigator, nephrologist and professor of medicine at the Mayo Clinic in Jacksonville, Fla., Dr. Gonwa is most known for his seminal work on chronic kidney disease in patients undergoing liver transplantation. He is also interested in regenerative medicine and the development of new immunosuppressive drugs, including phase 1–4 trials of newly developed drugs at local and national sites. Prior to his work at the Mayo Clinic, Dr. Gonwa helped bring the Baylor University Medical Center renal and liver transplant programs to prominence in the 1990s. The ASTS Pioneer Award for a significant contribution to the field of transplantation was awarded to Oscar Salvatierra, Jr., MD, a nephrologist and professor emeritus of surgery and pediatrics at Stanford University School of Medicine in Stanford, Calif. Much of his transplant career was spent at the University of California, San Francisco. In the 1980s, Dr. Salvatierra worked with U.S. Vice President Al Gore in the development of the National Organ Transplant Act, which established the infrastructure of the U.S. organ transplantation system and provided a central national registry for ongoing evidence-based research and future policy direction. Dr. Salvatierra has served as president of ASTS, The Transplantation Society, the United Network of Organ Sharing and several additional organizations.