Organ Allocation in the US: The Science, Technology, Demographics, Economics, Ethics, and Politics of Organ Sharing

Organ Allocation in the US: The Science, Technology, Demographics, Economics, Ethics, and Politics of Organ Sharing Tom Mone CEO, OneLegacy May 18, 2012

Introduction Allocation issues appeared as soon as the first surgeon began trying to save lives through transplantation, with informal sharing beginning almost immediately I have a second kidney that doesn t match my patient, can you use it?

Introduction This informal sharing became an issue as transplant programs began creating referral arrangements with donor hospitals, sometimes right next door to another transplant center: and the debates focused on which center, which surgeon, which recipient should get those organs and this quickly begat debates about the best use an organ

Introduction Allocation issues appeared as soon as the first surgeon began trying to save lives through transplantation, with informal sharing beginning almost immediately, I have a second kidney that doesn t match my Underlying the issue of organ sharing is the fundamental conflict of purposes among the players Doctors have a primary responsibility to a patient Hospitals have a primary responsibility to patients and communities Governments have a responsibility to citizens of the nation And all these parties have overlapping purposes and the need to ensure the viability of their practices/businesses/organizations

Introduction From the start the medical, patient, and governmental communities have strived to identify the best balance of these conflicting priorities In the US, the federal government determined in 1984 that the over-arching priority should be the recipient with the greatest need and ever since the community has been engaged in a never-ending effort to accomplish and refine sharing to fulfill this goal while respecting the other priorities

Introduction From the start the medical, patient, and governmental communities have strived to identify the best balance John Abrams will explain how this issue has been dealt with in the US through the creation of UNOS I will come back at the end to share some of the continuing areas of debate

Transplant Donation Global Leadership Symposium Organ Allocation in the United States John Abrams Gift of Life Donor Program

Transplant Recipients

Awaiting Life-Saving Transplant in the U.S. May 11, 2012 Kidney 92,258 Lung 1,651 Pancreas 1,268 Heart 3,191 Liver 16,094 Heart and Lung 53 Kidney and Pancreas 2,154 Intestine 265 114,247 TOTAL WAITING Source: Based on OPTN data as of May 11, 2012.

Active Patients Awaiting Life-Saving Transplant in the U.S Kidney 55,859 Lung 1,313 Pancreas 385 Heart 2,219 Liver 12,888 Heart and Lung 32 Kidney and Pancreas 1,128 Intestine 187 74,011 TOTAL WAITING Source: Based on OPTN data as of January 20, 2012. Count based upon active candidates.

Organs Recovered U.S. 2011 Kid Liv Heart Panc Lungs All Deceased 14,784 6,684 2,382 1,562 3,299 28,711 Living 5,770 248 0 0 2 6,020 All 20,554 6,932 2,382 1,562 3,301 34,731 OPTN data

Organs Transplanted U.S. 2011 Kid Liv Heart Panc Lungs All Deceased 12,140 6,030 2,365 1,142 3,160 24,837 Living 5,770 248 0 0 2 6,020 All 17,910 6,278 2,365 1,142 3,162 30,857 OPTN data

An International Challenge! U.S * EuroTX^ C.A.T# U.K. + Aust/NZ ** Pop (M) Waiting (1/2012) Tx d (2011) 310 120 34 62 22 112,905 15,510 4,539 7,557 1,633 30,857 6,545 1,065 3,740 1,041 * UNOS/AOPO ^ Eurotransplant # Canadian Association of Transplantation + NHS Blood & Tx ** ANZDATA

Early Allocation (Pre-UNOS) Primarily kidneys with an occasional heart or liver Driven by donor location: Each Transplant Center could claim their center and designated donor hospitals in which to perform recoveries (usually based on academic affiliation or patient referrals for transplant by local nephrologist, cardiologist, or hepatologist) Recovery Surgeon could choose organs from donors at their designated hospitals for any patient at his/her center Recipient selection was at surgeon s discretion

Regional/National Sharing (Pre-UNOS) NATCO 24-Alert Matching System 1-412-24-ALERT Telephone answering system Based on system developed by SEOPF Eventually became 1 st UNOS system which sorted kidney recipients by 4 HLA antigens (HLA-A and HLA-B) Recipients added on a daily basis Voice activated machine would give a list of potential recipients, organ required, and center There was no requirement to share with listed recipients and recipient selection remained at the discretion of the transplant surgeon

Life Magazine December 1967

Life Magazine September 1971

National Organ Transplant Act (P.L. 98-507) Signed into law 1984; first federal transplant law Established a Task Force on Organ Transplantation Established a entity in PHS now DOT Established a grant program to OPOs; encouraged consolidation Established the Organ Procurement and Transplantation Network (OPTN) Established the Scientific Registry of Transplant Patients (SRTR) Prohibited the buying and selling of organs

Used as the blueprint for transplant policies Task Force on Organ Transplantation (1986 Report) Mandated to conduct comprehensive examinations of medical, legal ethical, economic, and social issues presented by human organ procurement Resulted in over 70 recommendations including: Initial attempt to standardize donor chart Standard serology testing Organs were characterized as national resource for the public good

Organ Procurement and Transplantation Network (OPTN) Congress intent that activities for coordinating transplant sharing should be in the private sector First OPTN contract ($379,000) awarded to UNOS in 1986; they continue to hold the federal contract Second contract ($1.2M) awarded in 1987 to combine the UNOS and NATCO database Single, nationwide computerized system of matching donor organs with waiting recipients Authoritative body for policy formation

UNOS/SEOPF Richmond, VA UNOS Offices, circa 1986 John Persons Walter Graham Pat Daily Gene Pierce Cindy Sommers, Esq. Pictures courtesy of UNOS Update UNOS Offices, today

U.S. Organ Donation & Transplantation Structure - Current 57 Organ Procurement Organizations (OPO) Non-profit, federally designated, report to Medicare (CMS), coordinating organizations between acute care (donor) hospitals and transplant centers, representing more than 300 MM people 242 Transplant Centers w/ 800+ approved organ programs United Network for Organ Sharing (UNOS) U.S. Donation & Transplantation Statistics (2011): Deceased organ donors 8,126 Living organ donors 6,019 U.S. total transplants performed 30,985

Board of Directors: 41 elected members with no more than 50% transplant professionals; meets quarterly. United Network For Organ Sharing 16+ committees (e.g. organ specific, ethics, patients, OPO, etc.) Each of 11 regions represented By Councilor All allocation policies developed by UNOS are subject to final approval by the Secretary of DHHS. In 1987, the DHHS (federal government) contracted with UNOS to operate the OPTN (organ procurement and transplantation network)

United Network for Organ Sharing (UNOS) Regional designations as basis for representation and allocation

UNOS Organ Center Pictures courtesy of UNOS Update Assisting Organ Procurement Organizations With Organ Allocation since 1986

UNOS Policy Development Transplant Community Committee Issue Policy Public Comment UNOS Board of Directors

Objectives of the UNOS Allocation System Maximize the availability of organs by: Promoting consent for donation Minimize organ discards Promote efficiency in organ allocation Maximize patient and graft survival rates Maximize opportunity for those with medical or biologic disadvantages

Objectives of the UNOS Allocation System Minimize deaths while waiting Minimize disparities in waiting time Minimize effects related to geography Provide for flexibility in policy making Provide for accountability and public trust

Principles for an Organ Allocation System* Efficiency Transparency Credibility Equality * Council of Europe Recommendations

Basic Principles of the Organ Allocation System Justice Equal respect and concern for all patients Fairness in distribution Medical Utility Most net medical good overall Making best use of scarce resources

Geographic Sequence of Offers Thoracic Local patients, then Within 500 miles Within 1,000 miles Within 1,500 miles Within 2,500 miles Greater than 2,500 miles Abdominal* Local Regional National * Status 1A/1B livers initially offered to Local patients then Regional patients then less critical Local, Regional, National patients

Waiting Time Used in every organ system policy Calculated within each Status or MELD score Return to zero time when modified to higher status Can accumulate time from higher Status or MELD/PELD score Can be re-instated under certain circumstances Clerical error Primary graft failure Is tie breaker if Status or Score of recipients are equal

Allocation to Children All organ systems, to some extent, give extra consideration to children to maximize organ offers: Most have inherited, not self-inflicted, diseases In their growth years Have a full lifetime (maximum benefit) ahead of them For example kidney allocation offers from donors age 35 and under go to children first

UNOS Waiting List All patients must be registered for each organ Double verification of blood group at listing Multiple listings permitted (different start times) Transfers permitted (one start time) Objective Medical Criteria to determine medical urgency Status Medical Criteria must be timely MD sign off that patient listing criteria is accurate

Reassessment & Recertification Criteria Liver Status 1A Meld 25 & up Meld 24 18 Meld 17 11 Meld 10 & less Recertification Every 7 days Recertification Every 7 days Recertification Every 1 month Recertification Every 3 months Recertification Every 12 months Lab Values < 48 hrs Lab Values < 48 hours Lab Values < 8 days Lab Values < 15 days Lab Values < 31 days

UNOS Waiting List Health Care Team decides acceptable: Age range Weight range Height range Travel distance Accept reactive serology? Accept ECD? Accept DCD?

Basic Rule In Criteria Stable Urgent Age range 10 50 yrs 0 75 yrs Weight range 75 200 lbs 50 300 lbs Height range 48 80 inches 40 100 inches Travel distance 1,500 miles 4,000 miles Accept HCV + No Yes Accept ECD? No Yes Accept DCD? No Yes This example shows how basic rule-in parameters can be changed as patient s condition deteriorates

DonorNet Overview

Organ Matching

DonorNet 2007 All OPOs and Transplant Centers on-line April 2007 Mandate from the Department of Health to develop electronic system to notify transplant centers of available organs Electronic review of donor information Not a medical record or used to make final decision of acceptance

DonorNet Electronic Notifications Process Overview

OPO Begins Organ Offer Process OPO sends an electronic notification to a selected range of potential recipients. The primary contact for each transplant center will receive a voice and text notification. OPO sends out electronic notifications on the match results page. Prominent display of donor blood type. The candidate with the primary offer is highlighted.

Transplant Center Responses Automatically Updated

Lessons Learned Final allocation still via phone Allows OPO management to monitor allocation process Allocation process is more transparent DonorNet transitioned to electronic donor record vs. driving the no Enhancements needed as an acceptance tool Standardization in OPO practice

Organ Specific Criteria - Kidney Recipients accumulate a point score based on: HLA-DR mismatch with donor (0,1,2 points) Calculated PRA (4 points if > 80%) Waiting Time (1 point to longest waiting patient, fractions to others) Donation Status (4 points if patient previously donated a vital organ) Mandatory sharing of zero antigen mismatches To Local patients Then to 80% PRA patients Regional/National Then to 21% - 79% PRA patients Reg/National Payback incurred if zero antigen kidney accepted

Expanded vs. Standard Donors Expanded (ECD) All donors > 59 years old Any donor 50 59 years old with 2 of the following: COD = cerebrovascular accident History of hypertension Creatinine at allocation 1.5 or greater Recipients must consent to accepting ECD Patients sorted by waiting time Standard (SCD) All other donors Recipients accumulate a point score

Kidney Allocation Process OPO enters donor information to DonorNet Offers made to all LOCAL centers Hitting the Button Physician reviews information on BB Enters a Provisional Yes or declines OPO reviews donor with MD at Yes centers Recipient checked and crossmatch started If no LOCAL interest OPO makes REGIONAL offers If no REGIONAL interest OPO makes NATIONAL offers

SCD Kidney Match, Age 39 Center Name CPRA HLA Score Code PAHH Marti 99 2,2,2 9.9 Ill PALV John 97 1,2,1 8.9 Size PAUP Tom 92 1,2,2 6.7 Match DECC Axel 0 2,1,2 6.0 Quality PAAE Susan 0 2,2,1 5.9 Quality PATJ Howie 0 2,2,1 5.8 Quality PAUP Clyde 87 1,2,1 5.6 Yes

Organ Specific Criteria - Liver Medical Criteria Serum Creatinine/On dialysis? Serum Sodium Level of encephalopathy Level of ascities Bilirubin (mg/dl) Albumin (g/dl) INR Information entered above calculates the patient s MELD/PELD score (mortality risk) A patient in fulminant failure or with a failed transplant is listed as Status 1A

Sequence of Liver Offers LOCAL and REGIONAL 1A LOCAL MELD score > 29 NATIONAL Liver-Intestine by MELD LOCAL MELD score 15 29 REGIONAL MELD score > 14 LOCAL MELD < 15 REGIONAL MELD < 15 NATIONAL 1A NATIONAL all other candidates

Liver Match Run Center Name ABO St/Score Code PATJ Glenn O 1A Yes PATU Kris A 1A Yes MDUM Walter O 1A Yes PAUP Eric O 40.00 Yes PAHE Tim O 35.00 Yes

Organ Specific Criteria - Heart Status 1A valid for 14 days Mechanical circulatory support LVAD or RVAD < 30 days? Total artificial heart IABP ECMO Mechanical support with complication Continuous ventilation Continuous high-dose inotropes with monitoring of LV filling pressures Status 1B LVAD/RVAD > 30 days or continuous infusion of inotropes Status 2 all other patients Offers first to LOCAL recipients, then by 500 mile Zones

Sequence of Heart Offers LOCAL Status 1A, then 1B ZONE A Status 1A, then 1B LOCAL Status 2 ZONE B Status 1A, then 1B ZONE A Status 2 ZONE B Status 2 ZONE C Status 1A, 1B, 2 ZONE D Status 1A, 1B, 2 ZONE E Status 1A, 1B, 2

Heart Match Run Center Name ABO Status Code LOCAL PAHM Jeffrey A 1A Ill PAHE Carl AB 1B Size PAUP Juan A 1B Quality ZONE A MANM Edward A 1A Yes KYJH Patrick A 1A Yes

Organ Specific Criteria Lung* Factors to predict risk of death Forced Vital Capacity PA systolic pressure O2 required at rest Age BMI Diabetes Functional Status Six-minute walk distance Continuous ventilation Diagnosis/PCO2/Bilirubin * Recipients age > 11 years

Organ Specific Criteria Lung* Lung Factors that Predict Survival after Transplant Forced Vital Capacity PCW pressure greater than or equal to 20 Continuous ventilation Age Serum Creatinine Functional Status Diagnosis * Recipients age > 11 years

LAS Calculation Recipient Age > 11 years Candidate X Candidate Y Post Tx Survival 286.3 262.9 W/list Survival 101.1 69.2 Tx Benefit 185.2 193.7 Raw Score 84.1 124.5 LAS* 74.3 78 Lung is the first organ to consider estimated benefit in organ allocation * LAS is normalized to a continuous scale of 0-100

Lung Candidates Age 0-11 Priority 1 Respiratory Failure defined as: Requiring continuous ventilation Requiring supplemental oxygen to achieve FiO2 greater than 50% in order to maintain oxygen saturation of 90% Having an arterial or capillary PCO2 > 50 mmhg or venous PCO2 > 56 mmhg Pulmonary Hypertension defined as: Pulmonary vein stenosis involving 3 or more vessels Exhibiting suprasystemic PA pressure on catheterization or cardiac index less than 2 L/min/M2m, syncope, or hemoptysis An exception case approved by Lung Review Board Priority 2 All other candidates

Sequence of Lung Offers LOCAL ABO identical >11yrs by LAS LOCAL ABO compatible > 11yrs by LAS LOCAL ABO identical Priority 1 by w/time LOCAL ABO compatible P 1 by w/time LOCAL ABO identical Priority 2 by w/time LOCAL ABO compatible P 2 by w/time ZONE A ABO identical > 11 yrs by LAS ZONE A ABO compatible > 11 yrs by LAS ZONE A ABO identical Priority 1 by w/time ZONE A ABO compatible P 1 by w/time ZONE A ABO identical Priority 2 by w/time ZONE A ABO compatible P 2 by w/time ZONE B as above Zones C, D, and E as above

Regional Review Boards Purpose: Provide a quick review for specific urgent status patient registrations on UNOS heart and liver waiting lists. Determination whether or not the patient listing is appropriate and is in compliance with current policies based on review of current clinical information. Two RRB s per UNOS Region Make-up: Surgeons, physicians, coordinators, health care providers outside of transplant, non-medical (public) representatives. Each Region determines the number of representatives (minimum of 3), length of service, and the role of the Chair.

Alternative Allocation/Distribution System A System that is different from Standard and designed to: Increase organ availability and/or organ quality Address an inequity unique to a local area Examine a variation intended to benefit the overall system Known as: Variances Committee-Sponsored Alternative System Local and Alternative Units

Deviate from Policy? Organs that are difficult to place or organs declined in the O.R. may require deviation from policy for utilization Unstable 4 month old donor, no local interest, no time to make Regional calls, from past collaboration a National center with probable interest Interest found in New England for a liver recovered but declined in Philadelphia Place organ for transplant, then document circumstances in writing to UNOS

Scientific Registry of Transplant Patients Continuous collection of clinical and scientific data to evaluate the status of transplantation in the U.S. Originally awarded/held by UNOS; current contractor is Minneapolis Medical Research Foundation Ongoing development of statistical and simulation models to determine transplant policies; ongoing evaluation of policy impact www.ustransplant.org www.srtr.org

UNOS/OPTN Data Collection OPOs & Transplant Centers Organ Offer / Potential Transplant Recipient (PTR) validation of organ offer patient refusal codes & organ recipient OPOs Donor Disposition/Feedback organ-specific outcomes & consent not recovered outcome Deceased Donor Registration demographic & clinical data based on organs recovered submitted for every organ donor Death Notification Registration demographic, consent and hospital referral process data submitted for every imminent neurological or eligible death Transplant Centers Transplant Candidate Registration organ-specific, demographic and clinical information regarding patient and status at listing for transplant Transplant Recipient Registration organ-specific, demographic and clinical information regarding recipient and graft function at transplant Transplant Recipient Follow-up organ-specific, given at 6 months and each year post-transplant, and at death or graft failure, clinical information regarding recipient and graft function at time of follow-up

SRTR Transplant Center Reports

SRTR Donor Hospital Reports

SRTR OPO Reports

SRTR Simulation Allocation Models Source: SRTR

Example of OPO Driving Increased Efficiency in Allocation

ATN Rate 50% 45% 40% 35% 30% 25% 20% 15% 10% 5% 0% Local SCD Kidney ATN Rates by CIT 2006 2010 46% 44% 39% 37% 37% 31% 19% 15% 15% 4 to 6 6 to 8 8 to 10 10 to 12 12 to 14 14 to 16 16 to 18 18 to 20 20+ CIT (Hours)

Introduction & Purpose Cold Ischemic Time Clamp Renal Distribution Time Transplant Center Time Renal Distribution Time (RDT) (OPO driven) RDT is defined as the time from cross-clamp to when a kidney is available to a center for a specific recipient including complete donor history and compatible final crossmatch. Transplant Center Time (TxT) (Center driven) TxT is defined as the time a center requires to implant the kidney from renal distribution time.

Improving Renal Distribution Times HLA identification process starts using peripheral blood immediately after family consent Blood routinely sent to all local HLA Labs Specialized OPO renal allocation staff initiate kidney distribution Final crossmatches performed by all local Transplant Centers Couriers alerted and present at donor hospital to transport kidneys to accepting center

14 12 10 8 6 4 2 SCD Median Times (Hours) 2006 2010 13 12.8 12 11.8 7.6 8.7 7.3 8.2 10 7.7 5.1 4.6 2.9 2.5 2 2006 2007 2008 2009 2010 CIT TxT RDT

Conclusion OPO re-design of core process for renal allocation reduced median CIT by SCD by 3 Hours 23% (actual time) ECD by 1.8 Hours 14% (actual time) Reduction in RDT by: 39% (SCD) to 2 hours 39% (ECD) to 2.8 Hours Median TxT (from 15 centers) varied by center from 4 hours, 44 minutes to 8 hours 54 minutes Transplant centers should examine their practices after accepting a kidney to ensure lowest possible CIT OPOs should measure RDT to improve kidney allocation

Future Challenges Revision of Kidney Allocation Policy Allocation protocols: To include predicted graft survival? To include predicted life years from transplant? Maintaining organ allocation: Efficiency Transparency Credibility Equality

Kidney Committee Concepts Utilize KDPI to better characterize donor kidneys and to provide additional clinical information for patients and providers. Allocate the highest quality kidneys, KDPI 20% and below, to candidates with the highest EPTS. Allocate the remaining 80% of kidneys such that candidates within 15 years (older/younger) of donor age have priority. Older donor kidneys to older recipients

More Kidneys For Transplants May Go to Young Wall Street Journal March 10, 2007 Laura Meckler Kidney distribution from deceased organ donors presents a conflict between utility and equity A new policy is being developed by UNOS The share of kidneys going to patients in their 20 s would rise to 19% from 6% today. 2.7% of kidneys would go to patients 65 and up, versus nearly 10% today. Many expect the final proposal will rely on the concept of "net benefit," which seeks to give kidneys first to those who will benefit most from them.

Kidney Donor Profile Index The KDPI is based on 10 variables - donor age, height, weight, ethnicity, presence of hypertension, presence of diabetes, cause of death, creatinine, HCV status, and DCD status. The KDPI will be shown as a percentage (0-100). Since it is a risk index 0 is the best score possible (no risk associated with the donor) and 100 is the poorest score. Difference - rather than the current designations of SCD and ECD (based solely on 4 variables -age, COD = CVA, creatinine > 1.5, and Hx of HTN) this is an attempt to more accurately quantify donor quality using 10 variables, it is for informational purposes only, and is NOT used in the allocation in any way.

Challenges What factors should be considered in KDPI and EPTS? What thresholds (top 20%, top 30%, etc.) should be established? How can we be sure that older candidates receive kidneys that can be expected to last their estimated lifetime? Moving from concepts to reality!

Wrap-up Current Challenges in Organ Sharing in the US Regional Sharing of Livers for Status 1 patients Broader liver sharing and Transplant Centers engaging the US Congress to protect their interests Old-to-Old matching of Kidneys and the KDPI Misallocation, cover-up, and federal court trials over organ allocation