1. Michael G. Ison, MD MS Associate Professor Divisions of Infectious Diseases & Organ Transplantation Update on Consensus Conference for the Advisory Committee on Organ Transplantation August 28, 2012 – Rockville, Maryland Achieving Consensus on Increased Risk Donors to Improve Access to Organ Transplantation Funded by AHRQ Grant: 1R13HS021060-01

2. Overview Background and Grant Development Meeting Process and Work Groups Goals of Meeting Findings of Workgroups & Recommendations Outputs of Meeting Funded by AHRQ Grant: 1R13HS021060-01

3. Reason for the Meeting

4. Background and Grant Development Winter 2010/Spring 2011 o PHS guidelines undergoing revision o Concern within the transplant community about increased risk donors and donor screening  Live donor screening recommendations  Live donor increased risk consensus conference o General sense within the transplant community that the donor screening issue was addressed by NAT consensus conference Ison/Pruett applied to AHRQ for Small Grant Program for Conference Support (R13; PA-09-231) o Reviewed by Special Emphasis Panel June 9, 2012 o Award Notice: September 15, 2011 o Organizational calls for meeting initiated in October 2011 o Sought and obtained co-sponsorship by ASTS and AST Funded by AHRQ Grant: 1R13HS021060-01

5. Background and Grant Development Aggressive meeting planning after PHS Guideline public comment period completed o Selection of meeting date to minimize conflicts o Selection of 2 chairs for work groups (one each from ASTS & AST) o Invitation to work group members Stated goals of meeting per grant application 1.Disseminate research findings and evidence-based information about optimal evaluation, classification of donors at increased risk of disease transmission in addition to optimal informed consent and post-transplant evaluation of recipients of organs from such donors with the goal of improving the outcomes, quality, access to, and utilization of such organs 2. Define issues and problems in the practice and delivery of solid organ transplant related to donors at increased risk of disease transmission and to develop a rational research agenda or strategy for studying these problems Funded by AHRQ Grant: 1R13HS021060-01

6. Meeting Specific Aims Aim 1: To develop a consensus definition of donors at increased risk of transmission of HIV, HBV, and HCV o Review current research findings and evidence-based information to inform a standard definition of donors at increased risk of transmission of HIV, HBV, and HCV and disseminate these findings to the transplant community. o To identify gaps in defining a standard definition of donors at increase risk of transmission of HIV, HBV, and HCV and develop a rational research agenda or strategy to address these gaps. Aim 2: To define the optimal evaluation of living donors to mitigate against infectious disease transmission, with a focus on HIV, HBV, and HCV o Review current research findings and evidence-based information to inform the optimal evaluation of living donors to mitigate against infectious disease transmission, with a focus on HIV, HBV, and HCV and disseminate these findings to the transplant community. o To identify gaps in the evaluation of living donors to mitigate against infectious disease transmission, with a focus on HIV, HBV, and HCV and develop a rational research agenda or strategy to address these gaps. Funded by AHRQ Grant: 1R13HS021060-01

7. Meeting Specific Aims Aim 3: To define the optimal timing, content, and method of informed consent of candidates considering accepting an organ from an increased risk donor o Review current research findings and evidence-based information to define the optimal timing, content, and method of informed consent of candidates considering accepting an organ from a donor at increased risk of HIV, HBV, and HCV transmission and disseminate these findings to the transplant community. o To identify gaps in standardizing the timing, content, and method of informed consent of candidates considering accepting an organ from a donor at increased risk of HIV, HBV, and HCV transmission and develop a rational research agenda or strategy to address these gaps. Aim 4: To develop consensus on the optimal evaluation of recipients of organs from an increased risk donors o Review current research findings and evidence-based information to inform the optimal evaluation of recipients of organs from donors at increased risk of HIV, HBV, and HCV transmission and disseminate these findings to the transplant community. o To identify gaps in standardizing the optimal evaluation of recipients of organs from donors at increased risk of HIV, HBV, and HCV transmission and develop a rational research agenda or strategy to address these gaps. Funded by AHRQ Grant: 1R13HS021060-01

8. Work Group 1: Increased Risk Definitions MemberExpertiseProgram Michael GreenTID/PedsU Pittsburgh Dorry SegevTransplant SurgeryJohns Hopkins Michael AbecassisTransplant SurgeryNorthwestern David CohenTransplant NephrologyColumbia William HasskampCoordinatorLifeShare of Carolinas Dan LebovitzOPO/PulmonologyCleveland Clinic/LifeBanc Jeff OrlowskiOPOCtr for Donation & Tx Peter Reese*Transplant NephrologyU Pennsylvania David ReichTransplant SurgeryDrexell John Roberts*Transplant SurgeryU California-San Fran Michael VolkTransplant HepatologyU Michigan Charles WrightOPOLifeLink of Florida *Unable to attend in-person meeting. Funded by AHRQ Grant: 1R13HS021060-01

9. Work Group 2: Live Donor Evaluation MemberExpertiseProgram Connie DavisTransplant NephrologyU Washington Chris FreiseTransplant SurgeryU California – San Fran Talia BakerTransplant SurgeryNorthwestern Sandi CohenSocial WorkerU Chicago Carrie ComellasCoordinatorSUNY – Stony Brook Stuart FlechnerTransplant SurgeryCleveland Clinic Jami HannemanSocial WorkerNorthwestern Kevin KorenblatTransplant HepatologyWashington U Dianne LaPointe-RudowCoordinatorMt. Sinai David MulliganTransplant SurgeryMayo Clinic – Arizona Doug PenrodTransplant Donor/TCNorthwestern Dorn SandersTransplant DonorPatient Funded by AHRQ Grant: 1R13HS021060-01

10. Work Group 3: Informed Consent MemberExpertiseProgram Emily BlumbergTIDU Pennsylvania Rich FreemanTransplant SurgeryDartmouth Mark BarrTransplant SurgeryU Southern California Mary Amanda DewPsychU Pittsburgh Nicole Beauvais*CoordinatorNorthwestern James EasonTransplant SurgeryU Tennessee Robert GastonTransplant NephrologyU Alabama Elisa GordonEthicsNorthwestern Doug HantoTransplant SurgeryHarvard – BID Mitch HenryTransplant SurgeryOhio State U Bev Kosmach-ParkCoordinator/PedsU Pittsburgh Gwen McNatt*AdministratorNorthwestern Michelle Vogel*Alliance for Pt Advocacy *Unable to attend in-person meeting. Funded by AHRQ Grant: 1R13HS021060-01

11. Work Group 4: IR Recipient Evaluation MemberExpertiseProgram Jay FishmanTIDHarvard/MGH Tim PruettTransplant SurgeryU Minnesota Peter AbtTransplant SurgeryU Pennsylvania Amy BobrowskiTransplant Neph/PedsNorthwestern Peter Chin-HongTIDU California – San Fran Tracy Evans-WalkerCoordinatorCleveland Clinic Bob Higgins*Transplant SurgeryOhio State U Dan KaulTIDU Michigan Alan LangnasTransplant SurgeryU Nebraska Martha PavlakisTransplant NephrologyHarvard – BID Stephen RayhillTransplant SurgeryU Washington *Unable to attend in-person meeting. Funded by AHRQ Grant: 1R13HS021060-01

12. Outcomes of This Meeting Summary of Meeting o Slides and work group documents available for attendees o Key findings and Work Group slides available to the public  http://www.feinberg.northwestern.edu/transplant/Increased%20Risk%20Con sensus%20Conference/index.html o Preliminary findings of the meeting and attendee survey submitted to AHRQ and available on the public website Publication of Meeting o An executive summary of the meeting with all approved recommendations and gaps will be submitted to the American Journal of Transplantation o Groups may prepare individual publications based on their own groups work Funded by AHRQ Grant: 1R13HS021060-01

13. Risk Factor in last 12 months*Abilty to Identify Risk Factor? Strength of Risk for Infection? What is estimated Risk? Proportion of Donors Affected? ≥ 2 PartnersVery WeakWeakCannot Tell> 10% Sex with known of suspected infected partnerVery WeakWeakCannot Tell1-5% Men who had sex with MSMWeakStrong1:1000 -1:100001-5% Women who had sex with MSMVery Weak Cannot Tell< 1% Sex in exchage for $$ or drugsVery WeakWeak>1:10001-5% Sex with someone who had sex in exchange for $ or drug Very WeakWeak> 1:10005-10% Sex with someone who injected drugs for non- medical reasons Very WeakStrongCannot Tell1-5% Infants ≤ 2 years born to infected mother*Very StrongStrong> 1:1000< 1% Person who injected drugs for non-medical reasons Very StrongStrong> 1:10001-5% Intranasal use of illicit drugVery WeakWeak1:10,000 – 1:100,000 1-5% Inmate for ≥ 3 Days*Strong vs Weak? Strong Vs Weak 1:1000-1:10,000< 1% Person treated for syphilis, gonorrhea or genital ulcers Very WeakWeakCannot Tell> 10% Person on hemodialysisVery StrongStrong> 1:10001-5% Immigration to US from country with higher HBV prevalence Very Strong/Strong Weak/Very WeakCannot Tell< 1%

14. Work Group 2: Live Donor Perform testing consistently for all donors o Screen all live donors for risk behavior for HIV, HBV, and HCV as defined by this conference o Screening pre-transplant (any time point): HIV, HBV, and HCV serology o Testing within 30 days, but preferably within 14 days, prior to surgery: HIV NAT, HCV NAT, HBsAg  Vote for recommending for testing 29 For, 10 Against (reasons to vote against: not worth it, risk/benefit – loss of donors/pairs; heightened fear)  Votes on XX days (First round with 3 options in ()) o (30 Days: For 7) o 14 Days: For 18 (Without 30 days option = 18) o Within 30 days but preferably within 14 days For 13 (Without 30 days option = 21) Funded by AHRQ Grant: 1R13HS021060-01

15. Work Group 2: Live Donor Psychosocial Issues o Provide all donors education on how to avoid contracting HIV, HBV, and HCV at any point o Place in context of total risk Funded by AHRQ Grant: 1R13HS021060-01

16. Work Group 3: Consent Live donors should consent for disclosure of their relevant medical and social information to recipients o 5 individuals voted no against this recommendation Risk is a continuum – donor issues should be placed within the full context of risk Recipient consent process should be the same for deceased and live donors Consent should be obtained by knowledgeable, trained personnel Consent should be comprehensible to recipient, utilizing format and language appropriate to recipient Encourage involvement of recipient social support (family, significant other, etc) in the consent process Funded by AHRQ Grant: 1R13HS021060-01

17. Work Group 3: Consent At least 2 discrete times for education o Prior to listing and at time of offer o Reinforcement of education throughout the waiting period Risk described in comprehensible terms (same as before) Explain post transplant testing Protect patient (donor and recipient) confidentiality Documentation of process There is a need for an educational tool for training professionals delivering consent discussions with talking points Funded by AHRQ Grant: 1R13HS021060-01

18. Work Group 4: Recipient Testing Diagnostic tests should be used Nucleic acid tests (NAT) are preferred for HIV and HCV (HBsAg adequate for HBV) Recommended testing paradigm would include testing of recipients of organs from “donors at increased risk for transmission of infection” o Pre-transplantation (baseline) and o 1 and 3 months after transplantation o HBV testing at a later time point (between 6 and 12 months) All data on these tests should be collected centrally Funded by AHRQ Grant: 1R13HS021060-01

19. Identified Gaps Limited data on the optimal screening of live and deceased donors for HIV, HBV and HCV. A prospective study could be designed to determine how many donors were positive by antibody and NAT at different timing to assess the relative yield of screening There is currently no data on post-transplant screening results of recipients of standard and increased risk donor organs to assess the incidence of donor-derived disease transmission. A prospective study which tested recipients at fixed intervals post-transplant could inform optimal recipient screening and yields. Assessment of the cost of implementation of testing by serology and/or NAT in live and deceased organ donors Potential factors related to false positive serologic and nucleic acid testing results for live and deceased organ donor screening. The number and impact of false positive tests on the number of transplants performed, recipient transmissions, wait list time and potential donor psychological, medical and financial outcomes. Assessment of yield and false positive and negative results if FDA-approved, licensed or cleared diagnostic or monitoring NAT assays were utilized for live and deceased donor screening. There is limited data of the impact of the informed consent process on transplantation, especially with regard to use of increased risk donors. Funded by AHRQ Grant: 1R13HS021060-01

20. Identified Gaps There are currently no standardized tools to assess comprehension of the informed consent in transplantation, particularly with regard to the use of organs from an increased risk donor. There is currently limited data on how best to tailor the content and level of detail of consent from the patients point of view (patient-centered consent) with regard to the use of organs from an increased risk donor. There is a need for a decision analysis which quantitatively weighs the magnitude of harm associated with window period infections against the magnitude of unused organs. Such analysis would have to take into account that variations in utilization of organs by identified risk, accepting center, and type of organ being transplanted. There are currently limited data to address the strength of risk for unsuspected window period infection for many of the potential risks which limits the ability to assess the net value of including the risk factor. Can we identify more precisely the “times” associated with proposed risks to enhance their specificity to identify window period infections? Incidence studies of people in various putative risk groups, particularly those where high-­ ‐ quality incidence studies do not currently exist. Expanded national data collection on the specific risk factors underlying "CDC high risk" designation. Funded by AHRQ Grant: 1R13HS021060-01

21. Identified Gaps Studies of patient attitudes, concerns, and priorities regarding infectious risk and the specific categories used to define higher infectious risk. Improvements in efficiency, accuracy, and availability of nucleic acid testing. Better quantification of false-­ ‐ positive rates of nucleic acid tests. National consensus and homogeneity among OPO's regarding nucleic acid testing methods. Comparative Risk analysis: between risk of infection and risks of turning down an organ or donor withdrawing (i.e. no transplant) Funded by AHRQ Grant: 1R13HS021060-01

22. Opinions of Attendees of Meeting Opinion of attendees about the quality and outcome of the meeting was assessed via SurveyMonkey 32 (65% of invited attendees) individuals responded Attendees felt that the meeting was well managed and achieved the stated goals o 93.8% of respondents felt that the meeting was productive o 90.6% felt that the meeting accurately reflects the transplant community's opinion on issues related to the increased infectious diseases risk donor Nearly all attendees felt that the 4 work groups reviewed the existing data All respondents felt that the identified gaps in knowledge accurately reflect the gaps in existing knowledge Funded by AHRQ Grant: 1R13HS021060-01

23. Special Thanks Sue Benning Mike Abecassis, MD MBA Tim Pruett, MD American Society of Transplant Surgeons & American Society of Transplantation o For co-sponsoring the meeting The Work Groups and their chairs o For putting in the work and attending this meeting! Everyone who is attending the meeting AHRQ for funding the meeting (1R13HS021060-01) Funded by AHRQ Grant: 1R13HS021060-01

24. Questions? Michael G. Ison, MD MS mgison@northwestern.edu I am a registered organ donor! Are you?