Greater Transplant-Free Survival in Patients Receiving Obeticholic Acid for Primary Biliary Cholangitis in a Clinical Trial Setting Compared to Real-World External Controls.

BACKGROUND & AIMS: The Primary Biliary Cholangitis (PBC) Obeticholic Acid (OCA) International Study of Efficacy (POISE) randomized, double-blind, placebo-controlled trial demonstrated that OCA reduced biomarkers associated with adverse clinical outcomes (ie, alkaline phosphatase, bilirubin, aspartate aminotransferase, and alanine aminotransferase) in patients with PBC. The objective of this study was to evaluate time to first occurrence of liver transplantation or death in patients with OCA in the POISE trial and open-label extension vs comparable non-OCA-treated external controls. METHODS: Propensity scores were generated for external control patients meeting POISE eligibility criteria from 2 registry studies (Global PBC and UK-PBC) using an index date selected randomly between the first and last date (inclusive) on which eligibility criteria were met. Cox proportional hazards models weighted by inverse probability of treatment assessed time to death or liver transplantation. Additional analyses (Global PBC only) added hepatic decompensation to the composite end point and assessed efficacy in patients with or without cirrhosis. RESULTS: During the 6-year follow-up, there were 5 deaths or liver transplantations in 209 subjects in the POISE cohort (2.4%), 135 of 1381 patients in the Global PBC control (10.0%), and 281 of 2135 patients in the UK-PBC control (13.2%). The hazard ratios (HRs) for the primary outcome were 0.29 (95% CI, 0.10-0.83) for POISE vs Global PBC and 0.30 (95% CI, 0.12-0.75) for POISE vs UK-PBC. In the Global PBC study, HR was 0.20 (95% CI, 0.03-1.22) for patients with cirrhosis and 0.31 (95% CI, 0.09-1.04) for those without cirrhosis; HR was 0.42 (95% CI, 0.21-0.85) including hepatic decompensation. CONCLUSIONS: Patients treated with OCA in a trial setting had significantly greater transplant-free survival than comparable external control patients.

Defining a minimal clinically meaningful difference in 12-month estimated glomerular filtration rate for clinical trials in deceased donor kidney transplantation.

BACKGROUND: A Minimal Clinically Meaningful Difference (MCMD) has not been defined for Estimated glomerular filtration rate (eGFR). Our goal was to define the MCMD for eGFR anchored to kidney graft failure. METHODS: A systematic review of studies with 12-month eGFR and subsequent renal graft failure was conducted. For observational studies, we calculated hazard ratio (HR) differences between adjacent eGFR intervals weighted by population distribution. Interventional trials yielded therapeutically induced changes in eGFR and failure risk. OPTN data analysis divided 12-month eGFR into bands for Cox regressions comparing adjacent eGFR bands with a death-censored graft survival outcome. RESULTS: Observational studies indicated that lower eGFR was associated with increased death-censored graft failure risk; each 5 ml/min/1.73 m2 12-month eGFR band associated with a weighted incremental HR = 1.12 to 1.23. Clinical trial data found a 5 ml/min/1.73 m2 difference was associated with incremental HR = 1.16 to 1.35. OPTN analyses showed weighted mean HRs across 10, 7, and 5 ml/min/1.73 m2 bands of 1.47, 1.30, and 1.19. CONCLUSIONS: A 5 ml/min/1.73 m2 difference in 12-month eGFR was consistently associated with ~20% increase in death-censored graft failure risk. The magnitude of effect has been interpreted as clinically meaningful in other disease states and should be considered the MCMD in renal transplantation clinical trials.

Phase 3 trial Design of the Hepatocyte Growth Factor Mimetic ANG-3777 in Renal Transplant Recipients With Delayed Graft Function.

INTRODUCTION: One-third of kidney transplantation patients experience acute kidney injury (AKI) resulting in delayed graft function (DGF), associated with increased risk of graft failure and mortality. Preclinical and phase 2 data indicate that treatment with ANG-3777 (formerly BB3), a hepatocyte growth factor (HGF) mimetic, may improve long-term kidney function and reduce health care resource use and cost, but these data require validation in a phase 3 randomized controlled trial. METHODS: The Graft Improvement Following Transplant (GIFT) trial is a multicenter, double-blind randomized controlled trial, designed to determine the efficacy and safety of ANG-3777 in renal transplantation patients showing signs of DGF. Subjects are randomized 1:1 to ANG-3777 (2 mg/kg) administered intravenously once daily for 3 consecutive days starting within 30 hours after transplantation, or to placebo. RESULTS: The primary endpoint is estimated glomerular filtration rate (eGFR) at 12 months. Secondary endpoints include proportion of subjects with eGFR >30 at days 30, 90, 180, and 360; proportion of subjects whose graft function is slow, delayed, or primary nonfunction; length of hospitalization; and duration of dialysis through day 30. Adverse events are assessed throughout the study. CONCLUSION: GIFT will generate data that are important to advancing treatment of DGF in this medically complex population.

Renal Function Improvement Following ANG-3777 Treatment in Patients at High Risk for Delayed Graft Function After Kidney Transplantation.

BACKGROUND: Patients (20%-50%) undergoing renal transplantation experience acute kidney injury resulting in delayed graft function. ANG-3777 is an hepatocyte growth factor mimetic that binds to the c-MET receptor. In animal models, ANG-3777 decreases apoptosis, increases proliferation, and promotes organ repair and function. METHODS: This was a randomized, double-blind, placebo-controlled, phase 2 trial of patients undergoing renal transplantation with <50 cc/h urine output for 8 consecutive hours over the first 24 hours posttransplantation, or creatinine reduction ratio <30% from pretransplantation to 24 hours posttransplantation. Subjects were randomized as 2:1 to 3, once-daily IV infusions of ANG-3777, 2 mg/kg (n = 19), or placebo (n = 9). Primary endpoint: time in days to achieve ≥1200 cc urine for 24 hours. RESULTS: Patients treated with ANG-3777 were more likely to achieve the primary endpoint of 1200 cc urine for 24 hours by 28 days posttransplantation (83.3% versus 50% placebo; log-rank test: χ2 = 2.799, P = 0.09). Compared with placebo, patients in the ANG-3777 arm had larger increases in urine output; lower serum creatinine; greater reduction in C-reactive protein and neutrophil gelatinase-associated lipocalin; fewer dialysis sessions and shorter duration of dialysis; fewer hospital days; significantly less graft failure; and higher estimated glomerular filtration rate. Adverse events occurred in a similar percentage of subjects in both arms. Events per subject were twice as high in the placebo arm. CONCLUSIONS: There was an efficacy signal for improved renal function in subjects treated with ANG-3777 relative to placebo, with a good safety profile.

Hepatocyte Growth Factor Mimetic ANG-3777 for Cardiac Surgery-Associated Acute Kidney Injury.

INTRODUCTION: Nearly one-third of patients undergoing cardiac surgery involving cardiopulmonary bypass (CPB) experience cardiac surgery-associated (CSA) acute kidney injury (AKI); 5% require renal replacement therapy. ANG-3777 is a hepatocyte growth factor mimetic. In vitro, ANG-3777 reduces apoptosis and increases cell proliferation, migration, morphogenesis, and angiogenesis in injured kidneys. In animal models, ANG-3777 mitigates the effects of renal damage secondary to ischemia reperfusion injury and nephrotoxic chemicals. Phase 2 data in AKI of renal transplantation have shown improved renal function and comparable safety relative to placebo. The Guard Against Renal Damage (GUARD) study is a phase 2 proof of concept trial of ANG-3777 in CSA-AKI. METHODS: GUARD is a 240-patient, multicenter, double-blind, randomized placebo-controlled trial to assess the efficacy and safety of ANG-3777 in patients at elevated pre-surgery risk for AKI undergoing coronary artery bypass graft (CABG) or heart valve repair/replacement requiring CPB. Subjects are randomized 1:1 to receive ANG-3777 (2 mg/kg) or placebo. Study drug is dosed via 4 daily intravenous 30-minute infusions. The first dose is administered less than 4 hours after completing CPB, second at 24 ± 2 hours post-CPB, with two subsequent doses at 24 ± 2 hours after the previous dose. RESULTS: The primary efficacy endpoint is percent change from baseline serum creatinine to mean area under the curve from days 2 through 6. Secondary endpoints include change in estimated glomerular filtration rate from baseline to day 30, the proportion of patients diagnosed with AKI by stage through day 5, and the length of CSA-AKI hospitalization. Safety will include adverse events and laboratory measures. CONCLUSION: This phase 2 study of ANG-3777 provides data to develop a phase 3 registrational study in this medically complex condition.

Financial impact of delayed graft function in kidney transplantation.

Increased utilization of suboptimal organs in response to organ shortage has resulted in increased incidence of delayed graft function (DGF) after transplantation. Although presumed increased costs associated with DGF are a deterrent to the utilization of these organs, the financial burden of DGF has not been established. We used the Premier Healthcare Database to conduct a retrospective analysis of healthcare resource utilization and costs in kidney transplant patients (n = 12 097) between 1/1/2014 and 12/31/2018. We compared cost and hospital resource utilization for transplants in high-volume (n = 8715) vs low-volume hospitals (n = 3382), DGF (n = 3087) vs non-DGF (n = 9010), and recipients receiving 1 dialysis (n = 1485) vs multiple dialysis (n = 1602). High-volume hospitals costs were lower than low-volume hospitals ($103 946 vs $123 571, P < .0001). DGF was associated with approximately $18 000 (10%) increase in mean costs ($130 492 vs $112 598, P < .0001), 6 additional days of hospitalization (14.7 vs 8.7, P < .0001), and 2 additional ICU days (4.3 vs 2.1, P < .0001). Multiple dialysis sessions were associated with an additional $10 000 compared to those with only 1. In conclusion, DGF is associated with increased costs and length of stay for index kidney transplant hospitalizations and payment schemes taking this into account may reduce clinicians' reluctance to utilize less-than-ideal kidneys.

Real-world utilization of once-daily extended-release abuse deterrent formulation of hydrocodone: a comparison with the pre-approval randomized clinical trials.

BACKGROUND AND OBJECTIVE: Hydrocodone bitartrate extended release (Hysingla® ER, HYD) was previously studied in a 12-week randomized, double-blind, placebo-controlled trial and a 52-week open-label safety study. Both of these preapproval studies allowed dose titration to efficacy. The purpose of the present analysis was to compare dosing and utilization patterns in these previous clinical trials with real-world data (RWD) usage in a retrospective claim analysis performed 12-14 months post approval in the US. METHODS: In the claim analysis (Truven Health Analytics MarketScan® Research Database), patients prescribed HYD between January 1, 2015, and April 30, 2016, were followed for up to 6 months of continuous HYD use. Daily average consumption (DACON), initial dose, rescue opioid use and total milligram dose over time were also evaluated. RESULTS: HYD daily dose stabilized at ~60 mg dose once daily across all three studies. There was also a reduced need for rescue medication with HYD, resulting in a lower total opioid milligram dose over time. In the claim analysis, the mean monthly HYD dose increased from 49 to 55 mg in month 2 and then remained stable through month 6. The mean (standard deviation [SD]) time on drug was 79.5 days (61.42 days), and DACON was 1.04 pills/day, corresponding to the approved full prescribing information (FPI) and once-daily dosing. CONCLUSION: In 12-14 months post approval, real-world dosing and utilization of HYD mirrored registration and open-label study findings, with stable once-daily dosing of ~60 mg and no increase in rescue medicine utilization.

The Economic Burden of Opioid Abuse: Updated Findings.

BACKGROUND: Opioid pain relievers can be highly effective in providing relief for patients suffering from pain. At the same time, prescription opioid abuse, dependence, overdose, and poisoning (hereinafter "abuse") have become a national public health concern. Opioid abuse is also costly: previous estimates of the annual excess costs of opioid abuse to payers range from approximately $10,000 to $20,000 per patient. OBJECTIVES: To (a) provide a comprehensive, current estimate of the economic burden of opioid abuse to commercial payers and (b) explore the drivers of these excess costs of abuse. METHODS: Administrative claims from beneficiaries covered by large self-insured companies throughout the United States were used to identify patients diagnosed with opioid abuse, dependence, and overdose/poisoning ("abuse") between 2012 and 2015. Sample selection criteria identified patients most likely to be misusing opioids. Abusers and nonabuser controls were matched using propensity scores. Excess health care costs were assessed over the 18-month study period. Drivers of excess costs were then evaluated by place of service and medical condition (identified as 3-digit ICD-9-CM groupings). RESULTS: 9,342 matched abuser/nonabuser pairs were analyzed. Relative to nonabusers, abusers had significantly higher annual health care resource utilization, leading to $14,810 in per-patient incremental annual health care costs. Excess costs began accumulating 5 months before the formal, incident diagnosis of abuse, driven by alcohol and nonopioid substance abuse. Major drivers of excess costs of abuse included opioid and other substance abuse disorders, mental health conditions, and painful conditions. Many patients had diagnoses for other substance abuse that predated their opioid abuse diagnoses. CONCLUSIONS: Opioid abuse imposes a substantial economic burden on payers and often occurs in the context of other substance abuse. Poly-substance abuse often precedes the diagnosis of opioid abuse. DISCLOSURES: This study was funded by Purdue Pharma. Mayne is an employee of Purdue Pharma. Kirson, Scarpati, and Birnbaum are employees of Analysis Group, which received funding from Purdue Pharma to conduct this study. Enloe and Dincer were employees of Analysis Group at the time this research was conducted. Study concept and design were contributed by Kirson, Birnbaum, Mayne, and Scarpati, along with Enloe and Dincer. Enloe and Dincer took the lead in data collection, along with Birnbaum and assisted by Kirson and Scarpati. Data interpretation was performed by all the authors. The manuscript was written and revised by Kirson and Scarpati, along with Mayne and Birnbaum.

Secular trends in opioid prescribing in the USA.

Opioid abuse and misuse in the USA is a public health crisis. The use of prescription opioid analgesics increased substantially from 2002 through 2010, then plateaued and began to decrease in 2011. This study examined prescriptions of branded and generic immediate- and extended-release opioid analgesics from 1992 to 2016. This was juxtaposed against state and federal policies designed to decrease overutilization and abuse, as well as the launch of new opioid products, including opioids with abuse-deterrent properties (OADPs). The data indicate that these health policies, including the utilization and reimbursement of OADPs, have coincided with decreased opioid utilization. The hypothesis that OADPs will paradoxically increase opioid prescribing is not supported.

Reduced use of erythropoiesis-stimulating agents and intravenous iron with ferric citrate: a managed care cost-offset model.

BACKGROUND: Ferric citrate (FC) is a phosphate binder in development for the treatment of hyperphosphatemia in patients with end-stage renal disease (ESRD). In clinical trials, FC improved patient serum phosphorus levels and increased serum ferritin and percent transferrin saturation. Because nephrologists respond to increases in these iron measures by reducing intravenous (IV) iron and erythropoiesis-stimulating agent (ESA) doses, the decreased use of iron and ESA associated with FC may reduce costs. OBJECTIVES: To develop a cost-offset model from a managed care perspective estimating the cost savings associated with FC use. METHODS: We created a cost-offset model from the managed care payer perspective that compared the treatment costs of ESRD for patients given FC. The model considered the number of dialysis sessions per month; number of ESRD patients enrolled in the health plan; cost of ESAs, iron, and dialysis sessions; and the proportion of patients on phosphate binder therapy. The model assumed equivalent efficacy and cost neutrality between FC and other phosphate binders. Monte Carlo simulations were conducted by varying model inputs. RESULTS: When FC was compared to other phosphate binders, the monthly cost of ESA and IV iron per 500 patients with ESRD (85% treated with phosphate binders) was reduced by 8.15% and 33.2%, respectively. When incorporated into the total cost of dialysis for patients with ESRD (dialysis, ESA, and IV iron), the decrease in the monthly cost of dialysis care was US$80,214 per 500 ESRD patients. Monte Carlo simulations suggest that a plan serving 500 dialysis patients could save between US$626,000 and US$1,106,000 annually with the use of FC. CONCLUSION: The use of FC in ESRD patients with hyperphosphatemia may help reduce treatment costs.

CathAway fistula vascular access program achieves improved outcomes and sets a new standard of treatment for end-stage renal disease.

Hemodialysis patients using central venous catheters (CVCs) for vascular access are at greater risk of infection and death vs. arterial venous fistula (AVF). In 2008, DaVita initiated the CathAway quality improvement initiative, a multidisciplinary program to reduce CVC use in favor of AVF. Our retrospective analysis examined CVC use for incident (≤90 days) and prevalent (>90 days) patients receiving hemodialysis in the years 2006 to 2010. Outcomes included annual mean percentage of patients with CVCs, new CVC placements per 100 patient years, CVC survival, and percentage patient days with CVC. Over 152,000 patient records were reviewed. Between 76.2% and 79.7% of incident patients used a CVC annually, but for prevalent patients, the proportion decreased from 41.1% in 2006 to 33.5% in 2010. The number of new CVC placements per 100 patient years increased slightly for incident patients but fell annually from 64.8 in 2006 to 55.2 in 2010 for prevalent patients. The percentage of treatment days with CVCs was stable among incident patients (70.4%-74.3%) but fell among prevalent patients from 26.1% in 2006 to 16.5% in 2010. The mean duration of CVC use in incident patients was between 53.0 days (SD, 27.8) in 2006 and 54.1 days (SD, 28.1) in 2009, and for prevalent patients between 158.9 days (SD, 123.0) in 2006 and 128.1 days (SD, 112.0) in 2010. CathAway significantly decreased CVC use in prevalent hemodialysis patients. Decreasing incident patient use will require improvements in predialysis care.

The IMPACT (Incident Management of Patients, Actions Centered on Treatment) program: a quality improvement approach for caring for patients initiating long-term hemodialysis.

BACKGROUND: Patients beginning dialysis therapy are at risk of death and illness. The IMPACT (Incident Management of Patients, Actions Centered on Treatment) quality improvement program was developed to improve incident hemodialysis patient outcomes through standardized care. STUDY DESIGN: Quality improvement report. SETTING & PARTICIPANTS: Patients who started hemodialysis therapy between September 2007 and December 2008 at DaVita facilities using the IMPACT program (n = 1,212) constituted the intervention group. Propensity score-matched patients who initiated hemodialysis therapy in the same interval at DaVita facilities not using the IMPACT program (n = 2,424) made up the control group. QUALITY IMPROVEMENT PLAN: IMPACT intervention included a structured intake process and monitoring reports; patient enrollment in a 90-day patient education program and 90-day patient management pathway. OUTCOMES: Mean dialysis adequacy (Kt/V), hemoglobin and albumin levels, percentage of patients using preferred vascular access (arteriovenous fistula or graft), and mortality at each quarter. RESULTS: Compared with the non-IMPACT group, the IMPACT group was associated with a higher proportion of patients dialyzing with a preferred access at 90 days (0.50 [95% CI, 0.47-0.53] vs 0.47 [95% CI, 0.45-0.49]; P = 0.1) and 360 days (0.63 [95% CI, 0.61-0.66] vs 0.48 [95% CI, 0.46-0.50]; P < 0.001) and a lower mortality rate at 90 days (24.8 [95% CI, 19.0-30.7] vs 31.9 [95% CI, 27.1-36.6] deaths/100 patient-years; P = 0.08) and 360 days (17.8 [95% CI, 15.2-20.4] vs 25.1 [95% CI, 20.7-25.2] deaths/100 patient-years; P = 0.01). LIMITATIONS: The study does not determine the care processes responsible for the improved outcomes. CONCLUSIONS: Intense management of incident dialysis patients with the IMPACT quality improvement program was associated with significantly decreased first-year mortality. Focused attention to the care of incident patients is an important part of a dialysis program.

Accountable care organizations and ESRD: the time has come.

Accountable care organizations (ACOs) are a newly proposed vehicle for improving or maintaining high-quality patient care while controlling costs. They are meant to achieve the goals of the Medicare Shared Savings Program mandated by the Patient Protection and Affordable Care Act (PPACA) of 2010. ACOs are voluntary groups of hospitals, physicians, and health care teams that provide care for a defined group of Medicare beneficiaries and assume responsibility for providing high-quality care through defined quality measures at a cost below what would have been expected. If an ACO succeeds in achieving both the quality measures and reduced costs, the ACO will share in Medicare's cost savings. Health care for patients with end-stage renal disease is complex due to multiple patient comorbid conditions, expensive, and often poorly coordinated. Due to the unique needs of patients with end-stage renal disease receiving dialysis, ACOs may be unable to provide the highly specialized quality care these patients require. We discuss the benefits and risks of a renal-focused ACO for dialysis patients, as well as the kidney community's prior experience with an ACO-like demonstration project.

Results of a pilot program to improve phosphorus outcomes in hemodialysis patients.

OBJECTIVE: End-stage renal disease causes dysregulation of bone and mineral metabolism, including increased serum phosphorus levels. Kidney Foundation Kidney Disease Outcome Quality Initiative 2003 guidelines recommend maintaining phosphorus levels between 3.5 and 5.5 mg/dL in dialysis patients. We examined the effects of a focused phosphorus management pilot program designed to improve the percentage of hemodialysis patients achieving phosphorus levels <5.5 mg/dL. DESIGN, SETTING, SUBJECTS, AND INTERVENTION: We conducted a prospective, multicenter, single-arm study at 8 geographically diverse at-risk facilities (n = 702 hemodialysis patients) in a large U.S. dialysis organization. The focused phosphorus management program provided in-service training to staff members, and provided patients with diet and phosphorus management through in-center, 1:1 education and support, direct-to-patient adherence communications, benefit management assistance, and adherence support specific to lanthanum carbonate over a 6-month period. MAIN OUTCOME MEASURE: Facility-level markers of bone and mineral metabolism (phosphorus, parathyroid hormone, corrected calcium) and nutritional status (serum albumin, normalized protein catabolic rate) were assessed before and after program implementation. RESULTS: There was a significant increase in the percentage of patients per facility achieving phosphorus levels <5.5 mg/dL (mean ± SD at baseline = 61.6% ± 5.2%; month 6 = 71.3% ± 9.0%; P < .01) and parathyroid hormone (150 to 300 pg/mL; mean ± SD at baseline = 39.1% ± 2.4%; month 6 = 44.5% ± 7.0%; P = .04). During the course of the evaluation, mean calcium, albumin, and normalized protein catabolic rate levels did not change significantly. CONCLUSIONS: These results show proof-of-concept that a focused phosphorus management program targeting both staff members and patients can significantly improve patient outcomes without compromising nutritional status.

Electronic medical records: a survey of use and satisfaction in small dialysis organizations.

Little is known about electronic medical record (EMR) use in small dialysis organizations (SDOs). The objective was to determine the prevalence of EMRs in SDOs in the United States. A random sample telephone survey of SDOs was conducted in October, 2008. Approximately 60.7% of the facilities was found to be using an EMR, but only 33.5% had comprehensive systems that recorded medications, tests, and clinical notes. While 75.3% of the respondents indicated they were satisfied or very satisfied with their EMRs, just over one-third of those said they were planning to upgrade or replace their current systems.

A review of the costs and cost effectiveness of interventions in chronic kidney disease: implications for policy.

Given rising healthcare costs and a growing population of patients with chronic kidney disease (CKD), there is an urgent need to identify health interventions that provide good value for money. For this review, the English-language literature was searched for studies of interventions in CKD reporting an original incremental cost-utility (cost per QALY) or cost-effectiveness (cost per life-year) ratio. Published cost studies that did not report cost-effectiveness or cost-utility ratios were also reviewed. League tables were then created for both cost-utility and cost-effectiveness ratios to assess interventions in patients with stage 1-4 CKD, waitlist and transplant patients and those with end-stage renal disease (ESRD). In addition, the percentage of cost-saving or dominant interventions (those that save money and improve health) was compared across these three disease categories. A total of 84 studies were included, contributing 72 cost-utility ratios, 20 cost-effectiveness ratios and 42 other cost measures. Many of the interventions were dominant over the comparator, indicating better health outcomes and lower costs. For the three disease categories, the greatest number of dominant or cost-saving interventions was reported for stage 1-4 CKD patients, followed by waitlist and transplant recipients and those with ESRD (91%, 87% and 55% of studies reporting a dominant or cost-saving intervention, respectively). There is evidence of opportunities to lower costs in the treatment of patients with CKD, while either improving or maintaining the quality of care. In order to realize these cost savings, efforts will be required to promote and effectively implement changes in treatment practices.

Dialyzer reuse with peracetic acid does not impact patient mortality.

BACKGROUND AND OBJECTIVES: Numerous studies have shown the overall benefits of dialysis filter reuse, including superior biocompatibility and decreased nonbiodegradable medical waste generation, without increased risk of mortality. A recent study reported that dialyzer reprocessing was associated with decreased patient survival; however, it did not control for sources of potential confounding. We sought to determine the effect of dialyzer reprocessing with peracetic acid on patient mortality using contemporary outcomes data and rigorous analytical techniques. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a series of analyses of hemodialysis patients examining the effects of reuse on mortality using three techniques to control for potential confounding: instrumental variables, propensity-score matching, and time-dependent survival analysis. RESULTS: In the instrumental variables analysis, patients at high reuse centers had 16.2 versus 15.9 deaths/100 patient-years in nonreuse centers. In the propensity-score matched analysis, patients with reuse had a lower death rate per 100 patient-years than those without reuse (15.2 versus 15.5). The risk ratios for the time-dependent survival analyses were 0.993 (per percent of sessions with reuse) and 0.995 (per unit of last reuse), respectively. Over the study period, 13.8 million dialyzers were saved, representing 10,000 metric tons of medical waste. CONCLUSIONS: Despite the large sample size, powered to detect miniscule effects, neither the instrumental variables nor propensity-matched analyses were statistically significant. The time-dependent survival analysis showed a protective effect of reuse. These data are consistent with the preponderance of evidence showing reuse limits medical waste generation without negatively affecting clinical outcomes.