Michael Green, MD, MPH and Emily A. Blumberg, MD

The practice of giving a person in need someone else's blood, tissue or organs has improved and prolonged the lives of millions of people. Unfortunately, the use of blood, tissue and organs carries a clear potential for unanticipated disease transmission. In practice, clinicians caring for patients receiving these biologic materials are well acquainted with the concept of donor-derived disease transmission. Whether considering the long recognized donor-to-recipient transmission of cytomegalovirus (CMV) or the more recent recognition of transmission of emerging pathogens such as West Nile Virus (WNV), possible donor-derived disease transmission is inherent to the field of organ transplantation. While the risks are typically known, and are generally acceptable (e.g. CMV), the unanticipated transmission of pathogens such as HIV or occult malignancies has resulted in tragic outcomes, and raises the concern that existing processes for the evaluation of potential donors and communication of potential risk may not be optimal.

The term "biovigilance" has been used to describe efforts aimed at developing a comprehensive and integrated patient safety program to collect, analyze and report on the outcomes of transfusion and/or transplantation of blood products, cells, tissues and organs with respect to disease transmission. In a previous "white paper" on biovigilance, a Department of Health and Human Services (HHS) working group concluded that the result of an effective biovigilance program should be to provide an early warning system concerning safety issues, provide for an exchange of safety information, and promote education and the application of evidence for practice improvement.

A number of recent highly publicized unanticipated transmissions of HIV and Hepatitis C Virus (HCV) to organ transplant recipients have served to drive efforts to improve biovigilance as it relates to organ transplantation. In 2007, the transmission of both HIV and HCV to four recipients of organs from a donor whose original screening tests failed to identify the presence of these pathogens led to some enhancements in patient safety processes within the OPTN/UNOS system. The UNOS ad hoc Disease Transmission Advisory Committee was already in existence as an advisory group prior to this transmission event, but became an ad hoc committee in 2008. The DTAC has worked to monitor and assess potential donor-derived disease transmissions, and to analyze data generated by these efforts, to both educate the organ transplant community, and develop policies within UNOS to optimize organ recipient safety. Of note, the Centers for Disease Control and Prevention (CDC) (through its Office of Blood, Organ and Other Tissue Safety) has partnered with the DTAC since the creation of this working group. By any measure, the work of OPTN/UNOS/DTAC has been a great success. As a consequence of their ongoing efforts, awareness and understanding of issues related to donor-derived disease transmission within the organ transplant community has rapidly grown, and a number of OPTN/UNOS policy changes have been implemented to enhance patient safety.

Parallel to the efforts within the OPTN/UNOS, HHS has also worked to develop plans and programs to address issues of biovigilance in the United States. In contrast to the focus on biovigilance as it relates to organ transplantation by OPTN/UNOS, efforts within HHS have taken a more global view. Within HHS, issues relating to donor-derived disease transmission fall under the authority of multiple agencies. The Food and Drug Administration (FDA) has regulatory responsibility for blood and blood products, while the Centers for Medicare and Medicaid Services (CMS) has oversight of hospital transfusion services. Responsibility for the oversight of organ transplantation falls to Health Resources and Services Administration (HRSA) and to the OPTN/UNOS, through its contract to manage the country's organ procurement system. CMS also provides regulatory oversight of organ transplant programs. The CDC has become increasingly active in the area of donor-derived disease transmission, often taking on a leadership role in interagency efforts within HHS to address the issue of biovigilance as it relates to blood, tissue and organs. Most recently, the HHS Advisory Committee on Blood Safety and Availability (ACBSA) has begun to expand its focus from issues specifically related to blood products, to now include consideration of issues related to tissues and organs. Separately and together, these various agencies and groups within HHS have begun to lay the groundwork for potentially dramatic changes in the biovigilance system within the United States. Taken together, these efforts may dramatically affect the practice of organ transplantation in the United States.

While efforts by HHS to enhance patient safety as it relates to biovigilance would seem desirable, major differences in perceptions of risk-benefit analyses have emerged between those responsible for the development of programs and policies relating to biovigilance within HHS and the organ transplant community. The HHS "white paper" on biovigilance in the United States appeared to call for levels of "patient protection" for organ transplantations that are similar to those for blood transfusions. While in the latter circumstance, exclusion of a potential donor would not result in untoward consequences (the patient could receive a blood transfusion from an alternate donor), elimination of a potential organ donor in an effort to eliminate all risk of disease transmission for certain pathogens could lead to patients being removed from the waiting lists due to disease progression, or dying while waiting. Similarly, while screening of potential blood products is not impacted by any time limitations, decisions on whether or not to accept organs from a potential deceased donor must be made within a relatively short time window. Accordingly, experts from within the organ transplant community have argued that biovigilance, as applied to organ transplantation, must account for these differences, and hence requires a separate approach and philosophy than that of blood products and tissue.

The American Society of Transplantation has become increasingly interested in and involved with efforts relating to donor-derived disease transmission and biovigilance. AST, along with the American Society of Transplant Sugeons (ASTS), the Association for Organ Procurement Organizations (AOPO), The Organization for Transplant Professionals (NATCO), and others, have carried out a series of consensus conferences evaluating critical issues relating to donor-derived disease transmission. AST and ASTS have also increasingly become active in advocating for the unique role of organ transplantation in the context of discussions of biovigilance within HHS and on Capitol Hill. We have been invited to have representation as the ACBSA meetings as they expand their focus into the area of organ transplantation. AST also met with Assistant Secretary of Health Howard Koh to specifically express our concerns regarding the current approach to biovigilance as well as our willingness to participate in the ongoing discussion and evolution of biovigilance policies within HHS. We will critically review and advocate for our position in response to the soon to be released updated PHS guidelines for reducing transmission of HIV, HBV and HCV through solid organ transplantation. As these issues evolve, AST will continue to be actively involved in an effort to address the unique safety issues of our patient population.