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.

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.

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.

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.

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.

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.

Changes in hemoglobin level distribution in US dialysis patients from June 2006 to November 2008.

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) have had a positive effect on anemia treatment in dialysis patients. However, several events in recent years, including new clinical study results, ESA product label revisions, and coverage and reimbursement policy changes, have had an impact on ESA dosing patterns and consequently on hemoglobin (Hb) distribution characteristics in this patient population. STUDY DESIGN: Retrospective observational study using patient-level data from approximately 87% of dialysis centers in the United States. SETTING & PARTICIPANTS: Dialysis patients who were receiving outpatient care at dialysis facilities during June 2006-November 2008 were included in this study. PREDICTOR: Recent events affecting ESA treatment practice patterns in US dialysis patients. OUTCOMES & MEASUREMENTS: Hb level distribution. RESULTS: Mean Hb level decreased by 0.37 g/dL during the indicated period. Additionally, standard deviation (SD) of the Hb level distribution decreased by 0.14 g/dL and skewness increased by -0.10. Hb measurements in specific ranges changed as follows: >12 g/dL, decreased by 11.3 percentage points;10-12 g/dL, increased by 9.4 percentage points; and <10 g/dL, increased by 1.9 percentage points. The percentage of patients with Hb level >13 g/dL for > or =3 months decreased by 2.9 percentage points. LIMITATIONS: Potential bias in dialysis center selection and lack of information for patient characteristics. CONCLUSIONS: Recent events affecting ESA use in dialysis patients have had the desired effect of increasing the proportion of Hb measurements within the US Food and Drug Administration recommended target range of 10-12 g/dL and decreasing the proportion of Hb measurements >12 g/dL. However, the proportion of Hb measurements <10 g/dL also has increased. Benefits of a decrease in Hb measurements in the >12 g/dL range need to be considered, together with risks of having low Hb levels.

Systematic review and meta-analysis of exercise tolerance and physical functioning in dialysis patients treated with erythropoiesis-stimulating agents.

BACKGROUND: The role of erythropoiesis-stimulating agents (ESAs) in treating the anemia of chronic kidney disease has been reevaluated in view of recent studies suggesting that the use of these agents may be associated with increased morbidity and mortality. This potential increased risk needs to be weighed against the potential benefit of ESAs in improving various aspects of health-related quality of life, in particular, exercise tolerance and physical functioning. STUDY DESIGN: A systematic review and meta-analysis of exercise tolerance and physical functioning. SETTING & PARTICIPANTS: Adults on maintenance dialysis therapy. SELECTION CRITERIA FOR STUDIES: Outcomes measured before and after ESA treatment were required. Studies of physical function were required to include at least 25 participants. INTERVENTION: Treatment with any ESA. OUTCOMES: Exercise tolerance measured using VO(2peak) (oxygen consumption per minute at the peak workload during the test), duration of exercise, or 6-minute walk distance or physical functioning assessed using > or = 1 patient- or clinician-reported outcome measure that included a physical function domain. RESULTS: 28 articles met criteria for inclusion for evaluation of exercise tolerance, and 14 articles, for physical function. Meta-analysis showed a 23.8% increase in VO(2peak) from before to after erythropoietin therapy initiation (15 studies) and a nonsignificant 8.2% increase comparing a higher with a lower hemoglobin target (3 studies). For physical functioning, 4 studies met criteria for inclusion in the meta-analysis: there was a 10.5% increase in Karnofsky score from before to after erythropoietin therapy initiation. LIMITATIONS: Many studies of exercise tolerance did not include control groups. A wide variety of instruments was used to assess physical function. CONCLUSIONS: Partial correction of anemia through ESA treatment has a consistent and positive impact on VO(2peak). ESA treatment improves patient- and clinician-assessed physical functioning.

Characterizing hospitalizations of end-stage renal disease patients on dialysis and inpatient utilization of erythropoiesis-stimulating agent therapy.

BACKGROUND: In 2006, there were over 350,000 patients with end-stage renal disease (ESRD) receiving dialysis therapy. Studies have found that hemoglobin concentrations are often low among dialysis patients after hospital discharge, yet little is known about inpatient anemia treatment. OBJECTIVE: To characterize hospitalizations among patients with ESRD on dialysis, specifically, inpatient utilization of erythropoiesis-stimulating agent (ESA) therapy. METHODS: A cross-sectional, retrospective study of claims data from 5 commercial health plans for the years 2004-2006 was conducted. Inclusion criteria included 1 or more ESRD-specific International Classification of Diseases Ninth Edition (ICD-9) codes, 3 or more ESRD-specific Current Procedural Terminology/Healthcare Common Procedure Coding System (CPT/HCPCS) procedures on different days, or 3 or more dialysis ICD-9 codes or CPT/HCPCS dialysis procedures on separate days. ESRD patient and hospital characteristics were outlined. RESULTS: ESRD patients were hospitalized an average of 1.8 times in both 2004-2005 and 2005-2006. The mean +/- SD hospital length of stay (LOS) was 13.3 +/- 20.5 and 12.8 +/- 19.0 days for 2004-2005 and 2005-2006, respectively. For each year, LOS greater than 7 days occurred in 44% of hospitalizations. Many of these patients were admitted for kidney-related comorbidities and ultimately received procedures and services relevant to dialysis care. For each year, ESA utilization was 13% in year 1 and 11% in year 2 across any LOS. For ESRD patients with a 4- to 7-day LOS (the most common LOS), less than 20% received ESA treatment. ESA utilization increased correspondingly with longer hospital LOS (p < 0.001). CONCLUSIONS: Although ESRD patients are commonly hospitalized and claims recognize that kidney-related conditions exist, the utilization of ESAs is low.

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.

Psychometric evaluation of the National Kidney Dialysis and Kidney Transplantation Study symptom checklist: reliability and validity.

BACKGROUND: Patient-reported outcomes (PROs) are critical in the evaluation of treatment effectiveness. The National Kidney Dialysis and Kidney Transplantation Study (NKDKTS) symptom checklist was developed in the 1980s as a means to better understand the relationships amongst end-stage renal disease (ESRD), anaemia symptoms and multiple quality of life indicators. Unfortunately, key components of validity and reliability were not established at the time of the study. The present study helps fill this void by evaluating the psychometric properties of the 13-item NKDKTS symptom checklist, a measure of anaemia symptom frequency, in a dialysis population. METHODS: The NKDKTS symptom checklist was administered to 104 dialysis patients in three dialysis units at baseline, 48 h and 7 days. Internal consistency, test-retest reliability and construct validity via known-groups responsiveness were evaluated. RESULTS: Principal components factor analyses produced a single factor at each time point, with all items loading >0.50 across time points, and accounting for 37%, 44% and 46% of the variance at each time point (respectively). Forcing a 2-factor solution across time points yielded a single instance of an item loading more highly on factor 2 (0.57) than on factor 1 (0.53). Internal consistency was good at all three time points (Cronbach's alpha = 0.86, 0.89 and 0.90, respectively). Known-groups validity was evaluated by examining the symptom scores of subjects categorized by haemoglobin level. Subjects with lower haemoglobin levels reported significantly more symptoms, and the point estimates and variance at each haemoglobin level were stable over time. CONCLUSION: The results of this study provide further evidence supporting the validity and reliability of the NKDKTS symptom checklist.

Factors affecting anemia management in hemodialysis patients: a single-center experience.

The difficulty maintaining hemoglobin (Hgb) within the targets recommended by KDOQI is widely recognized. While factors responsible for erythropoietin resistance have been widely studied, factors responsible for the marked fluctuations and the inability to maintain Hgb within the target range have only begun to be investigated. This study was a cross-sectional review of anemia management in hemodialysis patients. The purpose was to evaluate factors responsible for Hgb decreases of 0.5 or 1.0 g/dL and to determine the primary factors responsible for Hgb decreases below 11 g/dL. Hgb values and clinical events were extracted from patient management databases between January 1, 2005 and November 30, 2006. Isolated events were defined as events that occurred at least 30 days after any previous event and had Hgb measurements within 2 weeks before and after the event. Increasing hospital length of stay and surgical access intervention were the most common events that resulted in a decrease in Hgb. The most common factor present in patients with Hgb decreases below 11 g/dL was the withholding of recombinant human erythropoietin (rHuEPO) within the preceding 2 months. This was the only explanation for the decrease in Hgb to <11 g/dL in 38.5% of such events. The ability to maintain dialysis patients' Hgb in the target range is complicated by intervening acute events that require hospitalization or surgical access interventions. The withholding of rHuEPO appears to be a major factor in Hgb decreases below 11 g/dL.

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.

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.

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.

Annualized was found better than absolute risk reduction in the calculation of number needed to treat in chronic conditions.

BACKGROUND AND OBJECTIVE: Recent studies have calculated number needed to treat (NNT) estimates based on annualized rates; however, the ramifications of altering the NNT statistic have not yet been explored in the literature. Here we introduce the concept of annualized NNT (ANNT), and apply it to data from randomized controlled trials (RCTs). METHODS: Incidence rates from RCTs for serious adverse events for three medicines were compared to an older class of drugs. NNT and ANNT were calculated from the event rates for these events. RESULTS: Based on the data, the NNT to prevent one adverse event a year vs. older medications was drug A, ANNT = 88; drug B, ANNT = 77; drug C, ANNT = 68. Equivalent calculations based on Bayesian statistics are drug C, ANNT = 54; drug B, ANNT = 49. Drug A produced a bimodal distribution, with one mode within the NNT range and the other in the number needed to harm range. CONCLUSIONS: NNT can erroneously inflate differences between treatments when based on absolute and not differential safety. We propose that NNT be limited to acute conditions with short-term, well-defined treatment courses, and that ANNT be used for chronic conditions.