Formulation of Committee Findings and Recommendations
Committee Members and HHS Support Staff
Committee Business
Call to Order
Jacquelyn (Jackie) Fredrick, MT(ASCP)SBB, PhD, retired CEO of Versiti, Inc., Chair of the Advisory Committee on Blood and Tissue Safety and Availability (ACBTSA), welcomed all attendees to the second day of the 50th ACBTSA meeting. She stated that the Committee will focus the second day of the meeting on discussions and making recommendations. At the end of the day, the Committee will also discuss topics related to the Committee’s work in the coming years.
James (Jim) Berger, MS, MT(ASCP)SBB, Senior Advisor for Blood and Tissue Policy, Office of the Assistant Secretary for Health (OASH), Department of Health and Human Services (HHS), Designated Federal Officer for ACBTSA, conducted roll call (see Appendix for ACBTSA member attendance) and stated that the meeting had a quorum.
Recap of the First Day of the Meeting
Emily Blumberg, MD, FACP, Director, Transplant Infectious Diseases, University of Pennsylvania; Professor of Medicine, Division of Infectious Diseases, Perelman School of Medicine, University of Pennsylvanian
Dr. Blumberg, Co-Chair of ACBTSA, briefly summarized yesterday’s meeting. She stated that the meeting started with an overview of the history of the role of Public Health Service (PHS) in blood and tissue safety and availability. Through presentations, the Committee learned more about
- Roles of the Organ Procurement and Transplantation (OPTN) and the United Network for Organ Sharing (UNOS),
- The development of the original PHS guidelines,
- Different views of the guidelines,
- Experiences of the Disease Transmission Advisory Committee (DTAC),
- Outcomes of clinical trials investigating human immunodeficiency virus (HIV) and hepatitis C virus (HCV) in organ transplantation,
- Ethics of informed consent of potential recipients of organs from “increased risk donors (IRD),” and
- Perspectives from 3 societies, including the American Society of Transplantation (AST), the American Society of Transplant Surgeons (ASTS), and the Association of Organ Procurement of Organizations.
Dr. Blumberg noted that the presentations will help the Committee answer the questions they have been asked to address. She added that informed consent might be incorporated in the recommendations as well.
Committee Discussion
Committee Address
Eric D. Hargan, Deputy Secretary of HHS
Deputy Secretary Eric D. Hargan welcomed all meeting attendees to HHS and thanked all Committee members for their dedication to their work. He stated that HHS Secretary Azar sends his regards. He emphasized that the HHS and the government are committed to improving policies around organ transplants, especially kidney, so that American people who need an organ transplant can have a better chance.
Deputy Secretary Hargan briefly highlighted 3 areas that the HHS is working on to address kidney disease, which, he stated, is one of the most daunting diseases facing the country today and is a priority for HHS.
First, HHS is going to examine new efforts to prevent and ways to slow chronic kidney disease. The more effectively we can slow down the progression of the disease, the smaller gap we’ll have between the number of kidneys available and the number of patients who need a transplant.
Second, Patients with kidney diseases deserve more treatment options. As we improve the quality and options for kidney care and expand patient education, more patients may be in better health and more likely to be capable of receiving a transplant.
Third, which is more relevant to ACBTSA, we are going to look into how to deliver more organs for transplants, including wearable and transplantable artificial kidneys, to help more Americans escape dialysis all together. One key step is to reorient HHS’s incentive for payment policies.
One of the key overall priorities at HHS is build a system that pays for health and outcome instead of procedures. In kidney space, that means providing incentives for transplants, not against it. Today we don’t have enough organs to meet the demand. One way to increase the number of available organs is to support living donors. Last fall, the HHS put out 2 funding opportunities through the Health Resources and Resources Administration (HRSA) to support living donors. HHS also wants to ensure best practices in procurement policies.
He noted that new technology and data have become available since the PHS guidelines were last updated in 2013 and many other new possibilities are on the horizon. For example, the donor pool may be expanded because of the advancement in treatment for HCV and HIV.
He said that the HHS team is hopeful because of the remarkable science being done every day to save patients’ lives and the Committee’s commitment to maximizing the science. He and the HHS Secretary are looking forward to hearing recommendations and in coming years to harnessing science and helping American people live better and longer lives.
Discussion of PHS Guidelines
Led by Dr. Blumberg, the Committee discussed a wide range of topics related to the following 3 questions the Committee has been asked to address.
Question 1: Does the available information support a reduction of the current 12-month risk behaviors time frame for determining “Increased Risk Donor” designation?
Questions 2: Is there a more appropriate term than “Increased Risk Donor” to designate donors with risk factors for undetected HIV, hepatitis B virus (HBV), or HCV infection?
Question 3: Should some criteria for increased risk donors be modified (eg, hemodilution of specimen used for HIV, HBV, or HCV testing, history of sexually transmitted diseases [STD], or outpatient hemodialysis)?
Key Discussion Points
Terminology
The Committee members first discussed the term “Increase Risk Donor” included in the second question.
The Committee members generally agreed that collecting data through the medical-social history questionnaire is using; however, a few members were not convinced that identifying donors would lead to optimal outcomes. Dr. Richard Benjamin commented that from the blood side of view, differentiation does not have much impact. He expressed his preference of using neutral terms because the term “Increase Risk” can cause confusion.
Daniel Brennan, MD, Professor of Nephrology, Division of Nephrology, Johns Hopkins University School of Medicine; Medical Director, the Comprehensive Transplant Center, suggested asking donor families’ perspective on the impact of the term. Dr. Skinner noted that assessing risk is more important than changing the terminology, and that changing the language will change the patient or clinician’s behavior and decision making.
Dr. Blumberg noted that language matters and a careful thought process is necessary. Other Committee members suggested gathering such information through existing focused groups.
After further discussion, the Committee suggested replacing “increased risk” with “possible risk.”
Informed consent and risk communication
The Committee then discussed informed consent and how to communicate risks with potential recipients, donor families, and clinicians during the consent process. The Committee members acknowledged the consent process in organ transplantation is unique and challenging, and they raised concerns over the variability of consent and processes used by different centers.
Sridhar Basavaraju, MD, FACEP, CDR, USPHS, Director, Office of Blood, Organ, and Other Tissue Safety, Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, voiced concern over the consequences of potential transmissions if risk assessments of donors were not conducted. Other members agreed that the consequence would be damaging, and that potential risks need to be explained to all potential recipients and their families, especially if data are collected.
The Committee also suggested using lay person language during the consent process. Dr. Fredrick suggested asking experts about how to craft the language.
Dr. Basavaraju pointed out there are other infections (eg, West Nile virus, tuberculosis) for which there is no cure. He wanted to know if recipients are told about all the potential risks, in addition to HIV, HBV, and HCV.
Dr. Fredrick noted that classification might be needed across risks, including HIV, HBV, HCV, and others.
Dr. Blumberg agreed it is necessary to classify risks. She noted that, like other Committee members she does not like the terminology of “Increase Risk Donors”, but she does think it is important to identify donors. She added that the situation might be different years later. She pointed out that consent is difficult in this process. She expressed her preference for changing the terminology but keeping identification.
Universal testing
The Committee debated the pros and cons of testing all recipients. While some Committee members believed that post-transplantation monitoring and testing should be conducted for all recipients, others were concerned that universal testing would result in false-positive results. A few members preferred focused testing to universal testing, considering that no test is perfect. Carlos Villa, MD, PhD, Medical Officer, Division of Blood Components and Devices, Office of Blood Research and Review, the U.S. Food and Drug Administration (FDA), pointed out the importance of standardized testing.
Regarding a timeframe for patient follow-up, Michael Ison, MD, MS, FIDSA, FAST, Professor, Division of Infectious Disease and Organ Transplantation, Transplant & Immunocompromised Host Infectious Diseases Service, Northwestern University Feinberg School of Medicine, commented that a timeframe between 2 and 4 weeks would capture both HIV and HCV.
The committee members agreed that universal assessment for all donors with nucleic acid test (NAT) for HIV, HBV, and HCV should be supported.
Medical-social questionnaire
Scott Brubaker, CTBS, Director, Division of Human Tissues, Office of Tissues and Advanced Therapies, Center for Biologics Evaluation and Research, FDA, shared the history of the development of the questionnaire. The original goal was to identify suitable donors and reduce complexity. It took years to develop the final lists of questions for donors and potential recipients. The final list was reviewed by stakeholders in collaboration with government agencies such as HRSA and was released in September 2014. He noted that if everyone uses the same tool, it would help collect data.
Some members questioned how much value the medical/social questionnaire could provide in addition to the medical recorders and testing results. Others argued that the questionnaire is a valid tool and should be used to gather valid data.
The Committee discussed what criteria from the current medical-social questionnaire could be removed. It was generally agreed that hemodilution should be removed, at least for the pediatric population.
Data collection
The Committee members agreed that data collection is helpful. A few Committee members suggested asking the Secretary to support longitudinal collection of data to further assess donor-associated risks as well as risks for recipients.
Dr. Blumberg agreed that it is perhaps time for the Secretary to provide funding to gather data using the tools that have already vetted by many different organizations as well as government agencies.
Education
The Committee members generally agreed that it is important to educate patients as well as clinicians and transplant providers. They discussed educating patients and their families during the consent processes. They also discussed educating clinicians about risks and how to effectively communicate the risks with patients and their families during the consent process. The Committee agreed that such education efforts should be supported.
Safety and availability
Dr. Ison commented that the real question is about organ availability and safety. On the one hand, donor identification is needed to ensure safety. On the other hand, to improve availability, donor identification may not be needed. He said that it is often the clinician’s decision of using or not using a specific organ, and he thought changing the terminology could change the clinician’s behavior. He pointed out that there is real risk associated with transplanting organs from increased risk donors. He noted that data will need to be gathered, otherwise it would affect consenting. He challenged the Committee members to think about which one to focus on, safety or availability? And he asked the Committee to keep clinicians and patients in mind while proposing a new term.
Dixon B. Kaufman, MD, PhD, President, ASTS, commented that from transplant surgical perspective, safety is important. He was concerned about potential risks associated with not screening recipients. He pointed out that regardless of an individual’s choice, standard should still be followed.
Dr. Brennan pointed out that all centers are rated, and they are careful about their outcomes and consequences.
Consent process
Dr. Fredrick asked what the Committee can recommend on improving the consent process. Dr. Skinner suggested promoting education on consent process. Dr. Ison shared that they had previously developed a web-based tool on education, and that their study suggested processes at different centers. When seeking solutions to organ underutilization, he asked the Committee members to think about where the problem comes from, the patient or the physician? Other Committee members agreed that tremendous variabilities exist between centers.
Dr. Kaufman commented that for the pediatric population, it could be the clinician or other members of the care providing team who refuse listing patients for receiving organs from IRDs. He noted that screening all recipients and improving the consent process could lead to increased utilization.
Donor designation and risk classification
Dr. Blumberg asked the Committee members to answer the question: if donors should continue to be identified.
The Committee members discussed the current system and debated the pros and cons of donor identification. While some members questioned the value of donor identification and voiced concerns over its negative impact on organ utilization, other members pointed out that donor designation does help ensure patient safety. The majority of the voting members agreed that donor identification is still needed but the term “increased risk donor” should be revised. A few members expressed their view that donor designation should be removed to improve organ availability and utilization.
Dr. Fredrick noted that she thinks designation is still needed, especially in the face of opioid crisis. However, the consent process needs to be improved and universal screening is needed for certain period of time.
Dr. Blumberg also preferred keeping donor designation. She cautioned that without risk assessment and donor identification, one transmission could set the field back drastically. She noted that ongoing assessment is needed and the Committee can come back to revisit the topic in a few years.
Risk behavior timeframe
The Committee members agreed that the current 12-month period is too long. They debated over a suitable timeframe. While many members agreed that a 1- or 2-month period is sufficient, they ultimately agreed on a 3-month timeframe for donors to ensure safety and to align with other policies.
Access to treatment
In addition to the PHS guidelines on IRD, the Committee also briefly discussed payment, especially for unexpected diseases and conditions derived from transplants. While some Committee members was concerned that the topic is outside the Committee’s charge, other members think it is appropriate for the Committee to discuss the topic because it affects the patient’s access to treatment.
Formulation of Committee Findings and Recommendations
At the end of the discussion, the Committee proposed a list of recommendations and together they drafted the following letter to the Secretary.
The ACBTSA met on April 15-16 to receive presentations on updating the PHS Guideline on Reducing HIV, HBV, and HCV Transmission Through Organ Transplantation. The Committee took note of data highlighting a significant gap between organs available for transplantation, organ utilization, and organs needed. The Committee learned that 119,000 individuals are on a transplant waiting list with 200 being added each day. Although increasing, the number of transplants per year is only 35,000. It is estimated that 20 Americans die each day while waiting for a transplant. The deficit presents a significant public health crisis and requires urgent actions to enhance options for transplant and make more organs available, by providing incentives for, not against transplant.
To improve policies around transplant so that Americans in need of organs have the greatest possible chance of receiving one, the ACBTSA recommends the following actions be taken immediately.
Recommendation 1: That there be continued recognition and designation of a category of potential organ donors with an augmented chance of transmission of HIV, HBV, and HCV
Recommendation 2: All organ donors should be tested for HIV, HBV, and HCV, using NAT along with serology
Recommendation 3: That the terminology of “increased risk donor” be changed because
- Current nomenclature causes cognitive bias, potentially discouraging use of these donors and needs to be reframed not to do so
- It allows recalibration of the discussion with the organ transplant team, the deceased donor families, living donors, and transplant candidates based on newer science with the goal of improved, shared decision making.
- Therefore, additional discussions should be had with donor families, transplant candidates and recipients regarding terminology prior to modification of the “increased risk donor” terminology. One suggestion made by the Committee was to change the term to “possible risk donor.”
Recommendation 4: Remove the following as medical/social criteria resulting in an augmented chance of donor designation
- Women who have had sex with men with a history of MSM behavior
- Newly diagnosed or have been treated for syphilis, gonorrhea, Chlamydia, or genital ulcers
- Hemodialysis
- Hemodiluted blood specimen use for infectious disease testing
- Child (age ≤18 months) born to a mother at increased risk for HIV, HBV, or HCV
- Child breastfed within the preceding 12 months by mother at increased risk for HIV infection
Recommendation 5: That the current 12-month risk behavior timeframe be changed to 3 months
Recommendation 6: The Committee strongly endorses universal implementation of the Uniform Donor Risk Assessment Interview (UDRAI) forms
Recommendation 7: The Secretary mandate and fund a longitudinal collection of data by the OPTN from the UDRAI to determine donor and recipient risk, as well as the impact of risk assessment on the donor pool and organ utilization
Recommendation 8: That the Secretary support efforts to enhance the process of transplant candidate counseling for these donor organs. This should include not just information provided to centers and transplant candidates, but also the ongoing shared decision making and the consent process from initial evaluation to post-transplant
Recommendation 9: The Secretary should support the development and use of tools and processes to educate transplant providers to enhance organ utilization
Recommendation 10: All recipients regardless of donor risk profile should be tested for HIV, HBV, and HCV using NAT between 2 and 4 weeks following transplantation in order to better identify disease transmission patterns
Recommendation 11: Separate from the PHS Guideline, the Committee strongly supports the Secretary taking action to remove barriers to rapid access to treatment for unanticipated donor-derived HIV, HBV, and HCV infections
We recognize the tremendous progress that has been made to enhance transplant safety and availability since implementation of the 2013 PHS Guideline. Because the Committee appreciates the dynamic nature of the field, we think it is imperative to have ongoing review of accumulated data and scientific advancements that will guide evidence-based decisions. We look forward to hearing the response to our recommendations.
Voting Results
All voting members of the Committee voted in favor of the recommendations.
New Business and Next Steps
Dr. Fredrick thanked all speakers. She noted that the recommendations cannot be made without the information provided, and she anticipated some changes to the PHS guideline in the areas discussed.
Dr. Frederick reminded the Committee members that at the last ACBTSA meeting in September 2018, the Committee discussed and reached a general consensus that there is still a lot to learn in blood safety. After discussing the pros and cons of different approaches, the Committee decided to form a work group to address risk tolerance for donor-derived infectious diseases in blood safety and to develop recommendations for the Committee to debate and vote on. However, the Committee members did not have time to vote on it at the time, and they decided that the topic should be further discussed and voted on at this meeting. She explained that they already have a Charter, but to make it a formal recommendation, they now need to take a vote.
Recommendation 12: That the Committee form a Risk Tolerance Work Group to develop recommendations to proceed with a plan for addressing risk tolerance for infectious diseases in blood from the patient’s perspective.
Voting Results
Dr. Blumberg made a motion. Dr. Brennan seconded. All members voted in favor of forming such a work group.
Dr. Fredrick stated that they will then send the recommendation to the HHS Secretary.
Dr. Fredrick briefly updated the Committee on blood sustainability. She explained that meetings have been conducted between the OASH, the Biomedical Advanced Research and Development Authority (BARDA), and the American Red Cross. BARDA is still working on cost-related data and research capacity in the events of natural disaster. The data hopefully will be presented at the next ACBTSA meeting, she said. She encouraged the Committee members to provide feedback.
Adjournment
The meeting was adjourned at 2:43 pm.
Appendix: Committee Members and HHS Support Staff
Public Members
Chair
Jacquelyn (Jackie) Fredrick, PhD, Retired CEO, Versiti, Inc.
Vice Chair
Emily A. Blumberg, MD, FACP, Director, Transplant Infectious Diseases, University of Pennsylvania; Professor of Medicine, Division of Infectious Diseases, Perelman School of Medicine, University of Pennsylvania
Daniel Brennan, MD, Professor of Medicine, Division of Nephrology, Johns Hopkins University School of Medicine; Medical Director, the Comprehensive Transplant Center
Brian S. Custer, PhD, MPH, Director, Epidemiology and Health Policy Sciences; Vice President, Research and Scientific Programs, Blood Systems Research Institute
Cassandra D. Josephson, MD, Professor, Pathology, Laboratory Medicine and Pediatrics, Emory University School of Medicine; Medical Director, Transfusion, Tissue and Apheresis Services, Children’s Healthcare of Atlanta (called in)
Mark W. Skinner, JD, President and CEO, Institute for Policy Advancement, Ltd.
Representative Members
Richard J. Benjamin, MBChB, MS(HCM), PhD, FRCPath, Chief Medical Officer, Cerus Corporation
Marian Macsai, MD, North Shore University Health System, Glenbrook Hospital; Eye Bank Association of America
Louis Katz, MD, Chief Medical Officer, Biomedical Services, America’s Blood Centers (Called In)
Mary Gustafson, Vice President, Global Regulatory Policy, Plasma Protein Therapeutic Association
Stefan Riedel, MD, PhD, D(ABMM), FCAP, Associate Professor, Pathology, Harvard Medical School; Associate Medical Director, Clinical Microbiology Laboratories, Beth Israel Deaconess Medical Center (Absent)
Gary F. Marklin, MD, Chief Medical Officer, Mid-America Transplant
Lynne Uhl, MD, Director, Division of Laboratory and Transfusion Medicine, Department of Pathology, Beth Israel Deaconess Medical Center
Frank S. Wilton, CAE, IOM, President and Chief Executive Officer, American Association of Tissue Banks (Absent)
Ex-Officio Members
Sridhar V. Basavaraju, MD, FACEP, CDR, USPHS, Director, Office of Blood, Organ, and Other Tissue Safety, Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention
Scott A. Brubaker, CTBS, Director, Division of Human Tissues, Office of Tissues and Advanced Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration
Marilyn E. Levi, MD, Director, Division of Transplantation, Health Resources Services Administration
Carlos Villa, MD, PhD, Medical Officer, Division of Blood Components and Devices, Office of Blood Research and Review (alternate)
Diane H. Corning, RN, JD, Health Insurance Specialist, Center for Clinical Standards and Quality, Clinical Standards Group, Centers for Medicare and Medicaid Services (Absent)
Harvey Klein, MD, Chief, Department of Transfusion Medicine, Clinical Center, National Institutes of Health (Absent)
HHS Support Staff in Attendance
James Berger, MS, MT(ASCP), SBB, Designated Federal Officer, ACBTSA, Senior Blood and Tissue Policy Advisor, Office of HIV/AIDS and Infectious Disease Policy, Office of the Assistant Secretary for Health, U.S. Department of Health and Human Services
Nicole Greene, Senior Public Health Advisor, Office of HIV/AIDS and Infectious Disease Policy, Office of the Assistant Secretary for Health, U.S. Department of Health and Human Services
Richard Henry, ML, MPH, MT(ASCP), Office of HIV/AIDS and Infectious Disease Policy, Office of the Assistant Secretary for Health, U.S. Department of Health and Human Services
Debbie Seem, RN, MPH, Public Health Analyst, Office of HIV/AIDS and Infectious Disease Policy, Office of the Assistant Secretary for Health, U.S. Department of Health and Human Services
