Materials and Methods
The Pancreas Allocation Task Force
The Pancreas Allocation Task Force comprised representatives of the whole organ transplant centers together with representatives of the islet purification laboratories, islet transplant centers' histocompatibility and immunogenetics laboratories, and national commissioners together with statisticians from the Organ Donation and Transplantation Directorate of NHSBT.
Pancreas Transplant Waiting List Data for Modeling
OPTN data on 5101 adult patients joining the waiting list for a pancreas transplant in the US between 1 January 2005 and 31 December 2006 were compared with 398 adult patients joining the active pancreas transplant waiting list in the UK over the same time period. Survival analyses considered time from listing to receiving a transplant. Patients who died or were removed from the list within the first year, or were still waiting for a transplant at 1 year were censored at the relevant time point.
The association between patient characteristics and estimated time to transplant of patients on the pancreas transplant list was investigated for both the UK and US data. Univariate analyses used the Kaplan–Meier method of estimation and comparisons between groups of patients were made using the log-rank test.
To examine fully the factors associated with waiting time before pancreas transplantation in both the UK and the US, independent multifactorial Cox proportional hazards regression models were developed. The hazard ratios from this analysis are interpreted as the relative chance of transplant within 1 year of listing. The baseline group for each factor has a relative chance of 1.0. For the purposes of the analysis, ethnicity was coded as white, nonwhite and not known, in order that the two national datasets could be compared.
Pancreas Transplantation Data for Modeling
Data on 3568 first pancreas transplants donated by adults after brain death (DBD) (either transplanted alone or combined with a kidney) performed in the US between 1 January 2004 and 31 December 2008 were obtained from OPTN. These data were compared with the 667 first adult DBD donor pancreas transplants performed in the UK in the same time period.
Survival analysis considered time from transplant to the earlier of pancreas graft failure or patient death. The transplant survival times of patients still alive with a functioning graft beyond 90 days were censored. To help maximize the number of transplants analyzed, follow-up was restricted to 90-day posttransplant outcome.
The term solitary pancreas is used to denote either a pancreas transplanted alone (PTA) or pancreas transplanted after a previous kidney transplant (PAK).
Islet Transplant Data
Expert opinion within the UK was sought and the literature was reviewed, including annual reports of the Collaborative Islet Transplant Registry, to identify factors that were considered to influence outcomes following islet transplantation.
Development of a National Allocation Scheme
The results of the analyses informed the allocation task force about factors influencing waiting times and posttransplant outcomes and led to the agreement on those factors to be considered in an allocation scheme. Once the factors were agreed, different weightings were applied to reflect variable importance attached to the identified factors. Computer simulations of different allocation protocols and weightings of factors were then run using real data of historic donors and waitlisted patients to understand the benefits and limitations of a number of different algorithms. The proposed scheme was subject to a number of iterative changes until the final scheme was agreed.
Evaluation of the National Allocation Scheme Over the First 3 Years
Data on all patients on the UK national waiting list for a whole pancreas or islets for the 12 months before the scheme started were compared to those for the first 3 years of the scheme, up until 30 November 2013. Data for all transplants performed in the same time period were also compared.
Graft failure for whole pancreas transplants was defined as a return to insulin or oral hypoglycemic agents; for islet transplants it was defined as a C-peptide level of less than 50 pmol/L 90 min after a standard mixed meal tolerance test. Reported graft failure for US patients had been used in analysis of the modeling cohort.