Achieving Consensus on Increased Risk Donors to Improve Access to Organ Transplantation

Michael G. Ison, MD MSAssociate Professor

Divisions of Infectious Diseases & Organ TransplantationUpdate on Consensus Conference for the

Advisory Committee on Organ TransplantationAugust 28, 2012 – Rockville, Maryland

Achieving Consensus on Increased Risk Donors to Improve Access to

Organ Transplantation

Funded by AHRQGrant: 1R13HS021060-01

Overview

• Background and Grant Development

• Meeting Process and Work Groups

• Goals of Meeting

• Findings of Workgroups & Recommendations

• Outputs of Meeting


Reason for the Meeting

Background and Grant Development

• Winter 2010/Spring 2011o PHS guidelines undergoing revisiono 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, 2012o Award Notice: September 15, 2011o Organizational calls for meeting initiated in October 2011o Sought and obtained co-sponsorship by ASTS and AST


Background and Grant Development

• Aggressive meeting planning after PHS Guideline public comment period completedo Selection of meeting date to minimize conflictso Selection of 2 chairs for work groups (one each from ASTS & AST)o Invitation to work group members

• Stated goals of meeting per grant application1. 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


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.


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 donoro 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 donorso 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.


Work Group 1: Increased Risk Definitions

Member Expertise Program

Michael Green TID/Peds U Pittsburgh

Dorry Segev Transplant Surgery Johns Hopkins

Michael Abecassis Transplant Surgery Northwestern

David Cohen Transplant Nephrology Columbia

William Hasskamp Coordinator LifeShare of Carolinas

Dan Lebovitz OPO/Pulmonology Cleveland Clinic/LifeBanc

Jeff Orlowski OPO Ctr for Donation & Tx

Peter Reese* Transplant Nephrology U Pennsylvania

David Reich Transplant Surgery Drexell

John Roberts* Transplant Surgery U California-San Fran

Michael Volk Transplant Hepatology U Michigan

Charles Wright OPO LifeLink of Florida

*Unable to attend in-person meeting.


Work Group 2: Live Donor Evaluation


Connie Davis Transplant Nephrology U Washington

Chris Freise Transplant Surgery U California – San Fran

Talia Baker Transplant Surgery Northwestern

Sandi Cohen Social Worker U Chicago

Carrie Comellas Coordinator SUNY – Stony Brook

Stuart Flechner Transplant Surgery Cleveland Clinic

Jami Hanneman Social Worker Northwestern

Kevin Korenblat Transplant Hepatology Washington U

Dianne LaPointe-Rudow Coordinator Mt. Sinai

David Mulligan Transplant Surgery Mayo Clinic – Arizona

Doug Penrod Transplant Donor/TC Northwestern

Dorn Sanders Transplant Donor Patient


Work Group 3: Informed ConsentMember Expertise Program

Emily Blumberg TID U Pennsylvania

Rich Freeman Transplant Surgery Dartmouth

Mark Barr Transplant Surgery U Southern California

Mary Amanda Dew Psych U Pittsburgh

Nicole Beauvais* Coordinator Northwestern

James Eason Transplant Surgery U Tennessee

Robert Gaston Transplant Nephrology U Alabama

Elisa Gordon Ethics Northwestern

Doug Hanto Transplant Surgery Harvard – BID

Mitch Henry Transplant Surgery Ohio State U

Bev Kosmach-Park Coordinator/Peds U Pittsburgh

Gwen McNatt* Administrator Northwestern

Michelle Vogel* Alliance for Pt Advocacy*Unable to attend in-person meeting.


Work Group 4: IR Recipient Evaluation


Jay Fishman TID Harvard/MGH

Tim Pruett Transplant Surgery U Minnesota

Peter Abt Transplant Surgery U Pennsylvania

Amy Bobrowski Transplant Neph/Peds Northwestern

Peter Chin-Hong TID U California – San Fran

Tracy Evans-Walker Coordinator Cleveland Clinic

Bob Higgins* Transplant Surgery Ohio State U

Dan Kaul TID U Michigan

Alan Langnas Transplant Surgery U Nebraska

Martha Pavlakis Transplant Nephrology Harvard – BID

Stephen Rayhill Transplant Surgery U Washington

*Unable to attend in-person meeting.


Outcomes of This Meeting

• Summary of Meetingo Slides and work group documents available for attendeeso Key findings and Work Group slides available to the public

http://www.feinberg.northwestern.edu/transplant/Increased%20Risk%20Consensus%20Conference/index.html

o Preliminary findings of the meeting and attendee survey submitted to AHRQ and available on the public website

• Publication of Meetingo 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


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 Partners Very Weak Weak Cannot Tell > 10%

Sex with known of suspected infected partner Very Weak Weak Cannot Tell 1-5%

Men who had sex with MSM Weak Strong 1:1000 -1:10000 1-5%

Women who had sex with MSM Very Weak Very Weak Cannot Tell < 1%

Sex in exchage for $$ or drugs Very Weak Weak >1:1000 1-5%

Sex with someone who had sex in exchange for $ or drug

Very Weak Weak > 1:1000 5-10%

Sex with someone who injected drugs for non-medical reasons

Very Weak Strong Cannot Tell 1-5%

Infants ≤ 2 years born to infected mother* Very Strong Strong > 1:1000 < 1%

Person who injected drugs for non-medical reasons

Very Strong Strong > 1:1000 1-5%

Intranasal use of illicit drug Very Weak Weak 1:10,000 – 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 Weak Weak Cannot Tell > 10%

Person on hemodialysis Very Strong Strong > 1:1000 1-5%

Immigration to US from country with higher HBV prevalence

Very Strong/Strong

Weak/Very Weak Cannot Tell < 1%

Work Group 2: Live Donor

• Perform testing consistently for all donorso Screen all live donors for risk behavior for HIV, HBV, and HCV

as defined by this conferenceo Screening pre-transplant (any time point): HIV, HBV, and HCV

serologyo 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)


Work Group 2: Live Donor

• Psychosocial Issueso Provide all donors education on how to avoid

contracting HIV, HBV, and HCV at any pointo Place in context of total risk


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


Work Group 3: Consent

• At least 2 discrete times for educationo Prior to listing and at time of offero 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


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 transplantationo HBV testing at a later time point (between 6 and 12

months)• All data on these tests should be collected centrally


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.


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.


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)


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 productiveo 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


Special Thanks

• Sue Benning• Mike Abecassis, MD MBA• Tim Pruett, MD• American Society of Transplant Surgeons &

American Society of Transplantationo For co-sponsoring the meeting

• The Work Groups and their chairso For putting in the work and attending this meeting!

• Everyone who is attending the meeting• AHRQ for funding the meeting (1R13HS021060-01)


Questions? Michael G. Ison, MD [email protected]

I am a registered organ donor!Are you?

Documents

Achieving Consensus on Increased Risk Donors to Improve Access to Organ Transplantation