1 Nonsimultaneous Chains and Dominos in Kidney Paired Donation – Revisited Running Title: NEAD Chains and DPD Chains in Kidney Paired Donation American Journal of Transplantation, 11, 5, May 2011, pp984-994. Itai Ashlagia, Duncan S. Gilchristb, Alvin E. Rothb, and Michael A. Reesc,d ,e a Department of Operations Management, Sloan School of Management, Massachusetts Institute of Technology, 50 Memorial Drive, Cambridge, MA 02142 b Department of Economics and Harvard Business School, Harvard University, 25 Harvard Way, Boston, MA 02163 c Department of Urology, University of Toledo Medical Center, 3000 Arlington Avenue, Mailstop 1091, Toledo, OH 43614 d Alliance for Paired Donation, Inc. 3661 Briarfield Boulevard, Maumee, OH 43531 e Corresponding Author: Office: 419-383-3961; FAX: 419-383-3344; email: [email protected] Key Words: Paired Kidney Exchange, Simulation Models, ABO incompatibility, Allosensitization, Transplantation Policy, Regional Sharing Word Count: 3,955 words2 Abbreviations: NEAD (nonsimultaneous extended altruistic donor), DPD (domino paired donation), KPD (kidney paired donation), NDD (non-directed donor), APD (Alliance for Paired Donation), PRA (panel reactive antibodies), UNOS (United Network for Organ Sharing), CIC R/D (computer-identified compatible recipient/donor), NDPD-k (non-simultaneous long DPDs of length k), NEAD-k (non-simultaneous long NEAD chain of length k), HLA (human leukocyte antigen).3 Abstract Since 2008 kidney exchange in America has grown in part from the incorporation of non-directed donors in transplant chains rather than simple exchanges. It is controversial whether these chains should be performed simultaneously (―domino paired donation‖, DPD) or nonsimultaneously (―nonsimultaneous extended altruistic donor chains‖, NEAD). NEAD chains create ―bridge donors‖ whose incompatible recipients receive kidneys before the bridge donor donates, and so risk reneging by bridge donors, but offer the opportunity to create more transplants by overcoming logistical barriers inherent in simultaneous chains. Gentry et al. simulated whether DPD or NEAD chains would produce more transplants when chain segment length was limited to three transplants, and reported that DPD performed at least as well as NEAD chains. As this contrasts with the experience of several groups involved in kidney paired donation, we performed simulations that allowed for longer chain segments and used actual patient data from the Alliance for Paired Donation. When chain segments of 4-6 are allowed in the simulations, NEAD chains produce more transplants than DPD. Our simulations showed not only more transplants as chain length increased, but also that NEAD chains produced more transplants for highly sensitized and blood type O recipients. Introduction Kidney exchange (also called kidney paired donation, KPD) allows patients with incompatible living donors to obtain transplants from other living donors, such as non-directed donors (NDDs) or donors belonging to other incompatible pairs.(1-8) NDDs can either be matched to a recipient on the waiting list or to an incompatible pair, but in the latter case, the donor of the incompatible pair can be further matched to another incompatible pair and so forth. (2, 6) Thus, through appropriate matching, a single NDD can facilitate more than one transplant.(2, 6, 9) A sequence of matches initiated by a NDD is called a chain. Until recently, all the surgeries in a chain were done simultaneously.(2, 6, 10, 11) However when a chain begins with a NDD, the cost of a break in the chain is less than when an exchange is conducted entirely among patient-donor pairs, since no patient-4 donor pair needs to give a kidney before they receive one.(6, 9) Following the first report of a non-simultaneous chain, a substantial number of non-simultaneous NDD chains have been reported.(10, 11) Non-simultaneous chains can be longer than simultaneous chains, since the larger number of operating rooms and surgical teams required by a long chain do not need to be assembled simultaneously. The desire to extend chains beyond the logistical capacity for simultaneous surgeries seems to be one of the motivations for some of the recently reported non-simultaneous chains, along with the additional motivation of further extending the chain to as yet unidentified patients by recruiting the last donor in the chain to be a ―bridge donor‖ who can extend the chain at a later time. Gentry et al. evaluated whether the risk of reneging in non-simultaneous chains was justified by increased numbers of transplants compared with simultaneous chains by simulating these different methods for matching NDDs.(12) In the first method, called domino paired donation (DPD), the NDD starts a simultaneous chain among incompatible pairs, with the donor in the last pair donating to a candidate on the waiting list without a willing, but incompatible donor.(2, 6) In the second method, the NDD initiates a non-simultaneous extended altruistic donor (NEAD) chain consisting of several segments.(9) Each segment is a short simultaneous chain, where the last donor of each segment becomes a bridge donor. Thus, instead of giving to a candidate on the waiting list without a willing, incompatible donor, the bridge donor waits to be matched to another incompatible pair and initiate another segment. Gentry et al. compared DPDs that involve at most 2 incompatible pairs and end with a simultaneous donation to a candidate on the deceased donor waiting list (for a total of 3 transplants) with NEAD chains in which each simultaneous segment contains at most 3 incompatible pairs and ends with a bridge donor that could continue the chain (also for a total of 3 transplants).(12) Their simulations suggested that DPDs would provide as many if not more transplants than NEAD chains and raised important questions about whether the risk of reneging in NEAD chains is warranted. In this paper, we utilize the actual clinical database of all pairs enrolled in the Alliance for Paired Donation (APD) to build a5 simulation model to test whether simultaneous DPD chains or NEAD chains would result in more transplants. Our simulation is built on the output of the matching software of the APD using the entire dataset of all the incompatible pairs and non-directed donors that have been enrolled in the APD system since its inception in 2006. This APD matching software identifies potential matches as