Evaluation of Opening Offers Early for Deceased Donor Kidneys at Risk of Nonutilization.

BACKGROUND: Reducing nonutilization of kidneys recovered from deceased donors is a current policy concern for kidney allocation in the United States. The likelihood of nonutilization is greater with a higher kidney donor risk index (KDRI) offer. We examine how opening offers for organs with KDRI >1.75 to the broader waitlist at varying points of time affects usage rates. METHODS: We simulate kidney allocation using data for January 2018 to June 2019 from Organ Procurement and Transplantation Network. For the simulation experiment, allocation policy is modified so that KDRI >1.75 organs are offered to all local candidates (same donation service area) after a set amount of cold time simultaneously. Open offers to candidates nationally are similarly examined. RESULTS: Simulation results ( n =50 replications) estimate that opening offers locally for KDRI >1.75 after 10 hours yields a nonutilization rate of 38% (range: 35%-42%), less than the prevailing rate of 55% of KDRI >1.75 kidneys. Opening offers after 5 hours yields 30% (range: 26%-34%), reducing the prevailing nonutilization rate by 45%. Opening offers nationally after 10 and 5 hours yields nonutilization rates of 11% (range: 8%-15%) and 6% (range: 4%-9%) for KDRI >1.75 kidneys, respectively. CONCLUSIONS: Simulation findings indicate that opening offers and adjusting their timing can significantly reduce nonutilization of high-KDRI kidneys.

Implications of Accumulated Cold Time for US Kidney Transplantation Offer Acceptance.

BACKGROUND AND OBJECTIVES: Reducing discard is important for the US transplantation system because nearly 20% of the deceased donor kidneys are discarded. One cause for the discards is the avoidance of protracted cold ischemia times. Extended cold ischemia times at transplant are associated with additional risk of graft failure and patient mortality. A preference for local (within the same donor service area) or low-Kidney Donor Risk Index organs, the endogeneity of cold ischemia time during organ allocation, and the use of provisional offers all complicate the analysis of cold ischemia times' influence on kidney acceptance decision making. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using January 2018 to June 2019 Organ Procurement and Transplantation Network data, we modeled the probability of accepting an offer for a kidney after provisional acceptance. We use logistic regression that includes cold ischemia time, Kidney Donor Risk Index, and other covariates selected from literature. Endogeneity of cold ischemia time was treated by a two-stage instrumental variables approach. RESULTS: Logistic regression results for 3.33 million provisional acceptances from 12,369 donors and 108,313 candidates quantify trade-offs between cold ischemia time at the time of offer acceptance and donor-recipient characteristics. Overall, each additional 2 hours of cold ischemia time affected acceptance for nonlocal and local recipients (odds ratio, 0.75; 95% confidence interval, 0.73 to 0.77, odds ratio, 0.88; 95% confidence interval, 0.86 to 0.91; P<0.001). For Kidney Donor Risk Index >1.75 (Kidney Donor Profile Index >85) kidneys, an additional 2 hours of cold ischemia time for nonlocal and local recipients was associated with acceptance with odds ratio, 0.58; 95% confidence interval, 0.54 to 0.63 (nonlocal) and odds ratio, 0.65; 95% confidence interval, 0.6 to 0.7 (local); P<0.001. The effect of an additional 2 hours of cold ischemia time on acceptance of kidneys with Kidney Donor Risk Index ≤1.75 (Kidney Donor Profile Index ≤85) was less pronounced for nonlocal offers (odds ratio, 0.82; 95% confidence interval, 0.80 to 0.85; P<0.001) and not significant for local offers. CONCLUSIONS: The acceptability of marginal organs was higher when placements were nearer to the donor and when cold ischemia time was shorter.

Functional status-based risk-benefit analyses of high-KDPI kidney transplant versus dialysis.

Yearly, over half of deceased-donor kidneys with kidney donor profile index (KDPI) > 85 were discarded, yet they could improve survival outcomes for dialysis patients. The potential risk of high-KDPI kidney transplant (KT) depends on the patient's overall health summarized by functional status, which should be examined. The analyzed cohort consisted of adult deceased-donor KT candidates on dialysis listed in 2005-2014. A multivariate Cox proportional hazards model was fitted with functional status, measured using Karnofsky Performance Score (KPS), and transplant status as time-varying covariates. Derived from the Cox model, survival curves were analyzed to compare the survival outcomes between dialysis and transplant with different kidney qualities across three different KPS strata: 10-40, 50-70, and 80-100. With KDPI 0-99 KT, KPS 10-40 patients will survive ≥4.38 years median compared with 3.21 years median if they remained on dialysis. For KPS 50+ patients, the median survival years increase from 5.82 to 6.60 years on dialysis to ≥7.83 years after KDPI < 100 KT. The risk-adjusted analyses suggested that patients are expected to benefit more from KDPI 81-99 KT than from remaining on dialysis.

Evaluation of Accepting Kidneys of Varying Quality for Transplantation or Expedited Placement With Decision Trees.

BACKGROUND: Underutilization of marginal-quality kidneys for transplantation produced ideas of expediting kidney placement for populations with decreased opportunities of receiving transplants. Such policies can be less efficacious for specific individuals and should be scrutinized until the decision-making for accepting marginal-quality organs, which has relied on experiential judgment, is better understood at the individual level. There exist rigorous tools promoting personalized decisions with useful and objective information. METHODS: This article introduces a decision-tree methodology that analyzes a patient's dilemma: to accept a kidney offer now or reject it. The methodology calculates the survival benefit of accepting a kidney given a certain quality now and the survival benefit of rejecting it. Survival benefit calculation accounts for patients' and donors' characteristics and transplant centers' and organ procurement organizations' performances and incorporates patients' perceived transplant and dialysis utilities. Valuations of rejecting an offer are contingent on future opportunities and subject to uncertainty in the timing of successive kidney offers and their quality and donor characteristics. RESULTS: The decision tree was applied to a realistic patient profile as a demonstration. The tool was tested on 1000 deceased-donor kidney offers in 2016. Evaluating up to 1 year of future offers, the tool attains 61% accuracy, with transplant utility of 1.0 and dialysis utility of 0.5. The accuracy reveals potential bias in kidney offer acceptance/rejection at transplant centers. CONCLUSIONS: The decision-tree tool presented could aid personalized transplant decision-making in the future by providing patients with calculated, individualized survival benefits between accepting and rejecting a kidney offer.

Patient Functional Status at Transplant and Its Impact on Posttransplant Survival of Adult Deceased-donor Kidney Recipients.

BACKGROUND: Recorded at the time of transplant and reported to the Organ Procurement and Transplantation Network, patient's functional status is measured using the Karnofsky performance score (KPS), ranging 0 to 100. Functional status analysis may provide insights on candidate listing and posttransplant survival outcomes for deceased-donor kidney transplants. METHODS: The cohort consisted of adult deceased-donor kidney transplant recipients transplanted beginning January 2007. One-year and 3-year Cox models for posttransplant survival were fitted with current Scientific Registry of Transplant Recipients (SRTR) variables and KPS. Comparative analyses were performed between the SRTR model without KPS and augmented model with it. Using the augmented model, we examined the impact of Kidney Donor Profile Index on posttransplant survivals for 5 different KPS strata: 10 to 30, 40 to 50, 60 to 70, 80 to 90, and 100. RESULTS: Comparative analyses showed that KPS was a statistically significant predictor for posttransplant survival: it improved model calibration, discrimination, and predictive accuracy. From the augmented model, the survival curves illustrated that recipients with KPS 40 to 50 and kidneys with Kidney Donor Profile Index as high as 99 have expected survival probabilities of above 90% in 1 year and above 80% in 3 years. The expected survival probabilities improve as KPS increases. Recipients with KPS 10 to 30 have the worst survival probability, even if they received high-quality kidneys. CONCLUSIONS: Insights from the survival analyses recommend possible inclusion of functional status into SRTR's risk-adjusted models. Moreover, they invite further examination of its use to improve current listing and transplantation strategies at transplant centers and potentially reduce deceased-donor kidney discard rate.

Effect of Age on Opioid Prescribing, Overdose, and Mortality in Massachusetts, 2011 to 2015.

OBJECTIVES: To examine the effect of age on the likelihood of PIP of opioids and the effect of PIP on adverse outcomes. DESIGN: Retrospective cohort study. SETTING: Data from multiple state agencies in Massachusetts from 2011 to 2015. PARTICIPANTS: Adult Massachusetts residents (N=3,078,163) who received at least one prescription opioid during the study period; approximately half (1,589,365) aged 50 and older. MEASUREMENTS: We measured exposure to 5 types of PIP: high-dose opioids, coprescription with benzodiazepines, multiple opioid prescribers, multiple opioid pharmacies, and continuous opioid therapy without a pain diagnosis. We examined 3 adverse outcomes: nonfatal opioid overdose, fatal opioid overdose, and all-cause mortality. RESULTS: The rate of any PIP increased with age, from 2% of individuals age 18 to 29 to 14% of those aged 50 and older. Older adults also had higher rates of exposure to 2 or more different types of PIP (40-49, 2.5%; 50-69, 5%; ≥70, 4%). Of covariates assessed, older age was the greatest predictor of PIP. In analyses stratified according to age, any PIP and specific types of PIP were associated with nonfatal overdose, fatal overdose, and all-cause mortality in younger and older adults. CONCLUSION: Older adults are more likely to be exposed to PIP, which increases their risk of adverse events. Strategies to reduce exposure to PIP and to improve outcomes in those already exposed will be instrumental to addressing the opioid crisis in older adults. J Am Geriatr Soc 67:128-132, 2019.

A Concentric Neighborhood Solution to Disparity in Liver Access That Contains Current UNOS Districts.

BACKGROUND: Policymakers are deliberating reforms to reduce geographic disparity in liver allocation. Public comments and the United Network for Organ Sharing Liver and Intestinal Committee have expressed interest in refining the neighborhoods approach. Share 35 and Share 15 policies affect geographic disparity. METHODS: We construct concentric neighborhoods superimposing the current 11 regions. Using concepts from concentric circles, we construct neighborhoods for each donor service area (DSA) that consider all DSAs within 400, 500, or 600 miles as neighbors. We consider limiting each neighborhood to 10 DSAs and use no metrics for liver supplies and demands. We change Model for End-Stage Liver Disease (MELD) thresholds for the Share 15 policy to 18 or 20 and apply 3- and 5-point MELD proximity boosts to enhance local priority, control travel distances, and reduce disparity. We conduct simulations comparing current allocation with the neighborhoods and sharing policies. RESULTS: Concentric neighborhoods structures provide an array of solutions where simulation results indicate that they reduce geographic disparity, annual mortalities, and the airplane travel distances by varying degrees. Tuning of the parameters and policy combinations can lead to beneficial improvements with acceptable transplant volume loss and reductions in geographic disparity and travel distance. Particularly, the 10-DSA, 500-mile neighborhood solution with Share 35, Share 15, and 0-point MELD boost achieves such while limiting transplant volume losses to below 10%. CONCLUSIONS: The current 11 districts can be adapted systematically by adding neighboring DSAs to improve geographic disparity, mortality, and airplane travel distance. Modifications to Share 35 and Share 15 policies result in further improvements. The solutions may be refined further for implementation.

Improving Liver Allocation Using Optimized Neighborhoods.

BACKGROUND: Geographic disparities persist in access to liver transplantation. Candidates with similar urgency experience varying opportunities for transplants across the United States. Policymakers are poised to act and 1 proposal entails reorganizing the current Organ Procurement and Transplant Network (OPTN) of 11 regions into 8 districts. However, redistricting has the shortcomings that Organ Procurement Organizations (OPOs) are disconnected from their immediate neighbors by district borders and that it is not easily responsive to uncertainty resulting from variability in donor and listing rates. METHODS: We introduce the notion of an OPO's neighborhood-a collection of donor service areas (DSA) surrounding the OPO that acts as the OPO's region in the current local-regional-national framework. Districts and concentric circles are special cases. We design 58 neighborhoods for the DSAs with several attractive properties and optimize them to balance supplies and demands using 10 years of Organ Procurement and Transplant Network data. We conduct a simulation experiment comparing current allocation, redistricting, and neighborhoods under current sharing policies with respect to the following metrics: total mortalities, DSA-average model for end-stage liver disease (MELD) at transplant, DSA-average MELD standard deviation, and average organ transport distance. Liver-simulated allocation model cannot accommodate neighborhoods, so we programmed a discrete-event simulator, LivSim, to approximate liver-simulated allocation model. RESULTS: We exhibited a neighborhood solution. Compared with the current allocation, simulation results showed that neighborhoods reduce the DSA-average MELD standard deviation by 29% and save about 65 lives annually. Compared with redistricting, the neighborhoods had smaller average transport distances that were more uniform across DSAs, saved about 20 additional lives, and reduced DSA-average MELD standard deviation by an additional 17%. CONCLUSIONS: Alternatives to redistricting with desirable properties and performance are possible and should be considered.

Modeling the allocation system: principles for robust design before restructuring.

The United Network for Organ Sharing is poised to resolve geographic disparity in liver transplantation and promote allocation based on medical urgency. At the time of writing, United Network for Organ Sharing is considering redistricting the organ procurement and transplantation network so that patient model for end-stage liver disease scores at transplant is more uniform across regions.We review the proposal with a systems-engineering focus and find that although the proposal is promising, it currently lacks evidence that it would perform effectively under realistic departures from its underlying data and assumptions. Moreover, we caution against prematurely focusing on redistricting as the only method to mitigate disparity. We describe system modeling principles which, if followed, will ensure that the redesigned allocation system is effective and efficient in achieving the intended goals.

Valuations of genetic test information for treatable conditions: the case of colorectal cancer screening.

BACKGROUND: The value of the information that genetic testing services provide can be questioned for insurance-based health systems. The results of genetic tests oftentimes may not lead to well-defined clinical interventions; however, Lynch syndrome, a genetic mutation for which carriers are at an increased risk for colorectal cancer, can be identified through genetic testing, and meaningful health interventions are available via increased colonoscopic surveillance. Valuations of test information for such conditions ought to account for the full impact of interventions and contingent outcomes. OBJECTIVES: To conduct a discrete-choice experiment to elicit individuals' preferences for genetic test information. METHODS: A Web-enabled discrete-choice experiment survey was administered to a representative sample of US residents aged 50 years and older. In addition to specifying expenditures on colonoscopies, respondents were asked to make a series of nine selections between two hypothetical genetic tests or a no-test option under the premise that a relative had Lynch syndrome. The hypothetical genetic tests were defined by the probability of developing colorectal cancer, the probability of a false-negative test result, privacy of the result, and out-of-pocket cost. A model specification identifying necessary interactions was derived from assumptions of risk behavior and the decision context and was estimated using random-parameters logit. RESULTS: A total of 650 respondents were contacted, and 385 completed the survey. The monetary equivalent of test information was approximately $1800. Expenditures on colonoscopies to reduce mortality risks affected valuations. Respondents with lower income or who reported being employed significantly valued genetic tests more. CONCLUSION: Genetic testing may confer benefits through the impact of subsequent interventions on private individuals.

Changes in geographic disparity in kidney transplantation since the final rule.

BACKGROUND: The national organ allocation system for deceased-donor kidney transplant will endure increased burden as the waitlist expands and organ shortage persists. The Department of Health and Human Services issued the "Final Rule" in 1998 that states "Organs and tissues ought to be distributed on the basis of objective priority criteria and not on the basis of accidents of geography." However, it has not been addressed whether the rule was effective in encouraging regions to share the additional burden equitably. OBJECTIVE: To assess the significance of changes of geographic disparities for four metrics since the rule's adoption: waiting times, transplant rates, pretransplant mortality, and organ quality. METHODS: Using Organ Procurement and Transplant Network data from 1988 through 2009, annual ranges of the metrics were calculated for all donor service areas and United Network for Organ Sharing regions. Time series analyses were used to compare the metrics before and after the enactment of the Final Rule. RESULTS: A total of 412,127 kidney transplant candidates and 178,163 deceased-donor recipients were analyzed. Demographics varied significantly by region. The ranges of the four metrics have worsened by approximately 30% or more after the Final Rule at both the regional and donor service area levels. CONCLUSION: Increasing geographic disparity in allocation procedures may yield diverging outcomes and experiences in different locations for otherwise similar candidates. Consensus for measuring allocation discrepancies and policy interventions are required to mitigate the inequities.

The effect of the Statewide Sharing variance on geographic disparity in kidney transplantation in the United States.

BACKGROUND AND OBJECTIVES: The Statewide Sharing variance to the national kidney allocation policy allocates kidneys not used within the procuring donor service area (DSA), first within the state, before the kidneys are offered regionally and nationally. Tennessee and Florida implemented this variance. Known geographic differences exist between the 58 DSAs, in direct violation of the Final Rule stipulated by the US Department of Health and Human Services. This study examined the effect of Statewide Sharing on geographic allocation disparity over time between DSAs within Tennessee and Florida and compared them with geographic disparity between the DSAs within a state for all states with more than one DSA (California, New York, North Carolina, Ohio, Pennsylvania, Texas, and Wisconsin). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A retrospective analysis from 1987 to 2009 was conducted using Organ Procurement and Transplant Network data. Five previously used indicators for geographic allocation disparity were applied: deceased-donor kidney transplant rates, waiting time to transplantation, cumulative dialysis time at transplantation, 5-year graft survival, and cold ischemic time. RESULTS: Transplant rates, waiting time, dialysis time, and graft survival varied greatly between deceased-donor kidney recipients in DSAs in all states in 1987. After implementation of Statewide Sharing in 1992, disparity indicators decreased by 41%, 36%, 31%, and 9%, respectively, in Tennessee and by 28%, 62%, 34%, and 19%, respectively in Florida, such that the geographic allocation disparity in Tennessee and Florida almost completely disappeared. Statewide kidney allocations incurred 7.5 and 5 fewer hours of cold ischemic time in Tennessee and Florida, respectively. Geographic disparity between DSAs in all the other states worsened or improved to a lesser degree. CONCLUSIONS: As sweeping changes to the kidney allocation system are being discussed to alleviate geographic disparity--changes that are untested run the risk of unintended consequences--more limited changes, such as Statewide Sharing, should be further studied and considered.

Patient preferences for surgical versus medical therapy for ulcerative colitis.

BACKGROUND: Therapy options for mesalamine-refractory ulcerative colitis (UC) include immunosuppressive medications or surgery. Chronic immunosuppressive therapy increases risks of infection and cancer, whereas surgery produces a permanent change in bowel function. We sought to quantify the willingness of patients with UC to accept the risks of chronic immunosuppression to avoid colectomy. METHODS: We conducted a state-of-the-art discrete-choice experiment among 293 patients with UC who were offered a choice of medication or surgical treatments with different features. Random parameters logit was used to estimate patients' willingness to accept trade-offs among treatment features in selecting surgery versus medical treatment. RESULTS: A desire to avoid surgery and the surgery type (ostomy versus J-pouch) influenced patients' choices more than a specified range of 10-year mortality risks from lymphoma or infection, or disease activity (mild versus remission). To avoid an ostomy, patients were willing to accept a >5% 10-year risk of dying from lymphoma or infection from medical therapy, regardless of medication efficacy. However, data on patients' stated choice indicated perceived equivalence between J-pouch surgery and incompletely effective medical therapy. Patient characteristics and disease history influenced patients' preferences regarding surgery versus medical therapy. CONCLUSIONS: Patients with UC are willing to accept relatively high risks of fatal complications from medical therapy to avoid a permanent ostomy and to achieve durable clinical remission. However, patients view J-pouch surgery, but not permanent ileostomy, as an acceptable therapy for refractory UC in which medical therapy is unable to induce a durable remission.

Constructing experimental designs for discrete-choice experiments: report of the ISPOR Conjoint Analysis Experimental Design Good Research Practices Task Force.

Stated-preference methods are a class of evaluation techniques for studying the preferences of patients and other stakeholders. While these methods span a variety of techniques, conjoint-analysis methods-and particularly discrete-choice experiments (DCEs)-have become the most frequently applied approach in health care in recent years. Experimental design is an important stage in the development of such methods, but establishing a consensus on standards is hampered by lack of understanding of available techniques and software. This report builds on the previous ISPOR Conjoint Analysis Task Force Report: Conjoint Analysis Applications in Health-A Checklist: A Report of the ISPOR Good Research Practices for Conjoint Analysis Task Force. This report aims to assist researchers specifically in evaluating alternative approaches to experimental design, a difficult and important element of successful DCEs. While this report does not endorse any specific approach, it does provide a guide for choosing an approach that is appropriate for a particular study. In particular, it provides an overview of the role of experimental designs for the successful implementation of the DCE approach in health care studies, and it provides researchers with an introduction to constructing experimental designs on the basis of study objectives and the statistical model researchers have selected for the study. The report outlines the theoretical requirements for designs that identify choice-model preference parameters and summarizes and compares a number of available approaches for constructing experimental designs. The task-force leadership group met via bimonthly teleconferences and in person at ISPOR meetings in the United States and Europe. An international group of experimental-design experts was consulted during this process to discuss existing approaches for experimental design and to review the task force's draft reports. In addition, ISPOR members contributed to developing a consensus report by submitting written comments during the review process and oral comments during two forum presentations at the ISPOR 16th and 17th Annual International Meetings held in Baltimore (2011) and Washington, DC (2012).

Patient and parent preferences for immunoglobulin treatments: a conjoint analysis.

OBJECTIVES: The purpose was to quantify patient and parent preferences for administration attributes of immunoglobulin (IG) treatments; and determine which administration attributes were most important to users of IG treatment and whether patients and parents have similar preferences for administration attributes. METHODS: US adult patients and parents of children with a self-reported physician diagnosis of a primary immunodeficiency disorder completed a best-practice web-enabled choice-format conjoint survey that presented a series of 12 choice questions, each including a pair of hypothetical IG-treatment profiles. After reviewing current therapies, each profile was defined by mode of administration, frequency, location, number of needle sticks, and treatment duration. Before answering the choice questions, respondents were told to assume all treatments worked equally well. Choice questions were based on a D-efficient experimental design. Preference weights for attribute levels were estimated using random-parameters logit for each sample (adult patients and parents). Tests were performed to determine potential interactions among the administration attributes. All respondents provided online informed consent. RESULTS: In total, 252 patients and 66 parents completed the choice questions appropriately. Overall, both groups preferred a home setting, monthly frequency, fewer needle sticks, and shorter treatment durations of IG treatment relative to alternative choices (p<0.05). Mode of administration was the least important attribute to both samples; however, parents strongly preferred self-administration to an appointment with a healthcare professional (p<0.05), whereas patients slightly preferred self-administration but were indifferent to the two modes. LIMITATIONS: Respondents evaluate hypothetical treatments and differences can arise between stated and actual choices. CONCLUSIONS: Considering the hypothetical treatments evaluated, IG treatments that provide the option of a home setting, monthly frequency, fewer needle sticks, and shorter treatment durations may address the needs of both patients and parents. Patients and parents have different preferences for administration attributes of IG treatments.

Eliciting benefit-risk preferences and probability-weighted utility using choice-format conjoint analysis.

This study applies conjoint analysis to estimate health-related benefit-risk tradeoffs in a non-expected-utility framework. We demonstrate how this method can be used to test for and estimate nonlinear weighting of adverse-event probabilities and we explore the implications of nonlinear weighting on maximum acceptable risk (MAR) measures of risk tolerance. We obtained preference data from 570 Crohn's disease patients using a web-enabled conjoint survey. Respondents were presented with choice tasks involving treatment options that involve different efficacy benefits and different mortality risks for 3 possible side effects. Using conditional logit maximum likelihood estimation, we estimate preference parameters using 3 models that allow for nonlinear preference weighting of risks--a categorical model, a simple-weighting model, and a rank dependent utility (RDU) model. For the second 2 models we specify and jointly estimate 1- and 2-parameter probability weighting functions. Although the 2-parameter functions are more flexible, estimation of the 1-parameter functions generally performed better. Despite well-known conceptual limitations, the simple-weighting model allows us to estimate weighting function parameters that vary across 3 risk types, and we find some evidence of statistically significant differences across risks. The parameter estimates from RDU model with the single-parameter weighting function provide the most robust estimates of MAR. For an improvement in Crohn's symptom severity from moderate and mild, we estimate maximum 10-year mortality risk tolerances ranging from 2.6% to 7.1%. Our results provide further the evidence that quantitative benefit-risk analysis used to evaluate medical interventions should account explicitly for the nonlinear probability weighting of preferences.