Real-World Effectiveness of 8-Week Glecaprevir/Pibrentasvir in Treatment-Naïve, Compensated Cirrhotic HCV Patients.

INTRODUCTION: The EXPEDITION-8 clinical trial has demonstrated that treatment-naïve patients with compensated cirrhosis (TN/CC) of HCV genotypes 1-6 can achieve a 98% intent-to-treat sustained virologic response rate 12 weeks post-treatment with an 8-week glecaprevir/pibrentasvir (G/P) regimen. Further real-world evidence is needed to support the effectiveness of 8-week G/P in a clinical practice setting and to consolidate these treatment recommendations. The aim of this study is to contribute real-world evidence for the effectiveness of an 8-week G/P treatment in TN/CC patients with HCV genotypes 1-6. METHODS: Retrospective real-world data from 494 TN/CC patients with HCV genotypes 1-6 were collected between August 2017 to December 2020 from the Symphony Health Solutions administrative claims database. Demographic and clinical characteristics were collected at baseline. Patients were required to have a follow-up HCV ribonucleic acid level at least 8 weeks or more after the end of treatment. The percentage of patients achieving a sustained virologic response (SVR) is reported. RESULTS: The majority of patients were male (58%) and Caucasian (40%), with a mean age of 58 years; 74%, 12%, 12%, and 1% of patients were HCV genotype 1, 2, 3, and 4-6 infected, respectively. SVR was achieved in 95.5% of all patients. Across patient subgroups, SVR was achieved in 95.6% of patients with HCV genotype 3 and in 93% of HCV patients with a recent diagnosis of illicit drug use or abuse (within 6 months prior to G/P initiation). CONCLUSION: Early real-world evidence indicates high effectiveness of the 8-week G/P regimen in TN/CC patients of HCV genotypes 1-6 from a large US claims database.

Shorter Duration Hepatitis C Virus Treatment is Associated with Better Persistence to Prescription Refills in People Who Inject Drugs: A Real-World Study.

INTRODUCTION: Direct-acting antiviral (DAA) therapy is highly effective in curing hepatitis C virus (HCV) infection in people who inject drugs (PWID). Previous studies showed declining persistence to DAA therapy over the course of treatment. This study compares real-world medication persistence to prescription refills for 8- versus 12-week DAA in treatment-naïve PWID with chronic HCV with compensated cirrhosis or without cirrhosis. METHODS: Symphony Health's claims database was used to collect data from patients with chronic HCV aged ≥ 12 years who were prescribed 8- or 12-week DAA therapy between August 2017 and November 2020 and had a diagnosis of addicted drug use within 6 months prior to index date. Eligible patients had medical/pharmacy claims in the 6 months before and 3 months after the first index medication fill date (i.e., index date). Patients completing all refills (8-week = 1 refill, 12-week = 2 refills) were deemed persistent. The percentage of persistent patients in each group, and at each refill step, was determined; outcomes were also assessed in a subgroup of Medicaid-insured patients. RESULTS: This study assessed 7203 PWID with chronic HCV (8-week, 4002; 12-week, 3201). Patients prescribed 8-week DAA treatment were younger (42.9 ± 12.4 vs 47.5 ± 13.2, P < 0.001) and had fewer comorbidities (P < 0.001). Patients receiving 8- versus 12-week DAA had greater refill persistence (87.9% vs 64.4%, P < 0.001). Similar percentages of patients missed their first refill (8-week, 12.1% vs 12-week, 10.8%); nearly 25% of patients receiving 12-week DAA missed their second refill. After baseline characteristics were controlled, patients prescribed 8- versus 12-week DAA were more likely to be persistent (odds ratio [95% confidence interval] 4.3 [3.8, 5.0]). Findings in the Medicaid-insured subgroup were consistent. CONCLUSION: Patients prescribed 8- vs 12-week DAA therapy had significantly greater prescription refill persistence. Most nonpersistence was due to missed second refills, highlighting the potential benefit of shorter treatment durations in this population.

Awareness and Epidemiology of Chronic Hepatitis C Virus Infections in Florida.

INTRODUCTION: Progress towards achieving hepatitis C virus (HCV) elimination in Florida has been hampered by barriers to screening, linkage to care, and treatment. This study aims to describe the HCV care cascade and patient characteristics in Florida. METHODS: This analysis combined HCV-related laboratory data and patient characteristics from two, large US laboratory datasets that included individuals tested for HCV antibody (Ab) and HCV ribonucleic acid (RNA) viral load between January 2015 and December 2019. A decline in sequential HCV RNA viral loads was used to impute HCV treatment. Machine-learning algorithms were used to identify cured patients. The actual number of individuals with HCV Ab screening, and the number and percentage of persons who were HCV RNA-positive and treated, were calculated. RESULTS: The number of persons in Florida diagnosed as HCV RNA-positive was 31,659 in 2019. The number of individuals HCV Ab screened in 2019 was 1,024,379, an increase of 82.5% from 2015. The percentage of HCV Ab-positive individuals was 4.1%, demonstrating a 16.2% decrease from 2015. The percentage of HCV RNA-positive patients who were treated was 27.0%, a 10.5% decrease from 2015 to 2019. CONCLUSION: An Ab positivity rate > 4-times higher than national estimates with increased screening among baby boomers, but decreased screening among younger individuals, suggests risk-based screening is still common practice in Florida, despite universal screening recommendations. Public health efforts to decrease barriers to screening, linkage to care, and treatment are needed to reduce the burden of HCV in Florida and to ensure progress toward virus elimination.

Epidemiology and Clinical Characteristics of Individuals with Hepatitis C Virus Infection in the United States, 2017-2019.

INTRODUCTION: Hepatitis C virus (HCV) is the most common bloodborne chronic infection in the US. Following approval of highly effective, direct-acting antivirals in 2014, the diagnostic and treatment rates for HCV infection in the US have evolved. This study assessed the number of individuals with HCV screening or diagnostic testing and the clinical characteristics and treatment of HCV-infected individuals between 2017 and 2019. METHODS: Individuals screened for HCV antibody and/or tested for HCV ribonucleic acid (RNA) from 2017 to 2019 by two large US laboratory companies were included in this analysis. Clinical characteristics, such as HCV genotype, fibrosis stage, HIV coinfection and demographics, were assessed in HCV RNA-positive individuals. HCV treatment and subsequent achievement of sustained virologic response were imputed using data-driven algorithms based on successive viral load decline and negativity. RESULTS: From 2017 to 2019, the number of individuals tested for HCV antibody increased by 5.7%, from 7,580,303 in 2017 to 8,009,081 in 2019. The percentage of individuals tested who were HCV antibody positive was stable, ranging from 5.0% in 2017 to 4.9% in 2018 and 2019. The number of HCV RNA-positive individuals decreased by 5.0% from 382,500 in 2017 to 363,532 in 2019. Of HCV RNA-positive individuals, the proportions with genotype (GT) 3 and minimal fibrosis increased over time; proportions of individuals aged < 40 years increased, while the proportion aged 50 to 59 years decreased. Treatment rates increased from 23.4% in 2017 to 26.8% in 2019. CONCLUSIONS: The percentage of HCV antibody-positive individuals remained stable from 2017 to 2019. The number of individuals tested HCV RNA positive decreased over the years. Demographics shifted toward a younger population with less fibrosis and higher rates of GT3. More than 70% of diagnosed individuals were not treated during this interval, highlighting a need for unfettered access to treatment.

Effectiveness of 8-Week Glecaprevir/Pibrentasvir for Treatment-Naïve, Compensated Cirrhotic Patients with Chronic Hepatitis C Infection.

INTRODUCTION: Glecaprevir/pibrentasvir (G/P) was approved on 26 September 2019 by the US Food and Drug Administration for 8-week duration in treatment-naïve (TN) hepatitis C virus (HCV)-infected patients with compensated cirrhosis (CC). Evidence from the EXPEDITION-8 study demonstrated that 8 weeks of G/P achieved a 98% intent-to-treat (ITT) sustained virologic response rate 12 weeks post treatment (SVR12) in 343 TN/CC patients. The aim of this study is to demonstrate the first US real-world effectiveness of G/P 8-week treatment in genotype 1-6 TN/CC HCV patients. METHODS: Data from 73 TN/CC patients who initiated 8 weeks of G/P treatment between August 2017 and November 2018 were collected electronically from providers and specialty pharmacies of the Trio Health network and analyzed. Cirrhosis was determined by FIB-4 > 5.2 or was physician reported. The primary outcome was Per Protocol (PP) SVR12. RESULTS: The majority (60%) of patients were male, with (mean values): age 59 years, body mass index (BMI) of 30, aspartate aminotransferase (AST) 105, and alanine aminotransferase (ALT) 101 IU/ml. HCV genotypes (GT) were: GT1 81% (59/73), GT2 10% (7/73), GT3 5% (4/73), GT4 3% (2/73), and GT6 1% (1/73). Eight percent (6/73) of patients had concurrent proton pump inhibitor (PPI) use, and 15% (11/72) had a baseline viral load > 6 MM IU/ml. Zero patients discontinued, two patients were reported as lost to follow-up, and there was one virologic failure. PP sustained virologic response at 12 weeks (SVR12) rate was 99% (70/71), and the intent-to-treat (ITT) SVR12 rate was 96% (70/73). CONCLUSIONS: Early real-world experience indicates high effectiveness of the 8-week G/P regimen in a diverse treatment-naïve, compensated cirrhotic US population.

Development of a Comprehensive Dataset of Hepatitis C Patients and Examination of Disease Epidemiology in the United States, 2013-2016.

INTRODUCTION: Chronic infection with hepatitis C virus (HCV) is a leading cause of liver disease and infectious disease deaths. While recent and emerging treatment options for HCV patients have enabled higher rates of sustained virologic response (SVR), the demographic, clinical, geographic, and payer characteristics of the estimated 3.4 million chronic HCV patients in the USA are poorly understood. The goal of this study was to create a dataset describing the current HCV patient landscape in the USA. METHODS: Data from two large national laboratory companies representing the majority of US patients screened for HCV antibody and/or tested for HCV RNA from 2013 through 2016 were organized into the present study dataset. Age, gender, payer channel, 3-digit ZIP code and ordering physician specialty, and 3-digit ZIP code information were available for all patients. Among RNA-positive patients, additional clinical characteristics included HCV genotype, fibrosis stage, renal function, and HIV status. Initiating treatment and attaining cure were imputed using data-driven algorithms based on successive RNA viral load measurements. RESULTS: The number of RNA-positive HCV patients increased from 200,066 patients in 2013 to 469,550 in 2016. The availability of clinical data measurements and rates of treatment initiation increased over the study period, indicating improved care engagement for HCV patients. Treatment and cure rates varied by age, disease severity, geographic location, and payer channel. Sensitivity and specificity of the cure prediction algorithms were consistently above 0.90, validating the robustness of the data imputation approach. CONCLUSION: This is the largest, most comprehensive dataset available to describe the current US HCV patient landscape. Our results highlight that the epidemiology of HCV is evolving with an increasing number of patients who are younger and have milder disease than described in previous years. Results of this study should help guide efforts toward the elimination of HCV in this country. Future work will focus on factors associated with varying treatment and cure patterns and describing recent changes in the HCV patient landscape. FUNDING: AbbVie. Plain language summary available for this article.

The wider public health value of HCV treatment accrued by liver transplant recipients.

OBJECTIVES: Organs for transplantation are scarce, but new medical therapies can prevent organ failure and the need for transplants. We sought to describe the unique value created by treatments that spare organs from failure and thus conserve donated organs for transplant into others, using hepatitis C virus (HCV) as a case study. STUDY DESIGN: Epidemiologic-economic model. METHODS: Using data on trends in chronic liver disease, liver disease progression, and liver transplant allocation models, as well as the effectiveness of new HCV treatments, we estimate the potential effects of systematic HCV screening and treatment on the demand for liver transplants in the United States. We estimate the spillover benefits to patients with all-cause liver disease in terms of increased availability of transplants and life-years gained. RESULTS: We estimated that systematic HCV screening and treatment could spare 10,490 liver transplants to HCV-infected patients from 2015 to 2035. An estimated 7321 transplants would accrue to patients with end-stage liver disease without HCV and 3169 transplants to those with uncured HCV, providing approximately 52,700 and 22,800 additional life-years, respectively. CONCLUSIONS: Treatment advances for HCV have the potential to generate considerable spillover benefits to patients awaiting transplants for non-HCV-mediated liver failure. For other diseases in which organ transplants are in short supply, our study provides a novel pathway by which positive spillovers may accrue from treatments that prevent end-stage organ disease.

Value of expanding HCV screening and treatment policies in the United States.

OBJECTIVES: To investigate the value of expanding screening and treatment for hepatitis C virus (HCV) infection in the United States. STUDY DESIGN: Discrete-time Markov model. METHODS: We modeled HCV progression and transmission to analyze the costs and benefits of investment in screening and treatment over a 20-year time horizon. Population-level parameters were estimated using National Health and Nutrition Examination Survey data and published literature. We considered 3 screening scenarios that vary in terms of clinical guidelines and physician awareness of guidelines. For each screening scenario, we modeled 3 approaches to treatment, varying the fibrosis stage of treatment initiation. Net social value was the key model outcome, calculated as the value of benefits from improved quality-adjusted survival and reduced transmission minus screening, treatment, and medical costs. RESULTS: Expanded screening policies generated the largest value to society. However, this value is constrained by the availability of treatment to diagnosed patients. Screening all individuals in the population generates $0.68 billion in social value if diagnosed patients are treated in fibrosis stages F3-F4 compared with $824 billion if all diagnosed patients in stages F0-F4 are treated. Moreover, increased screening generates cumulative net social value by year 8 to 9 under expanded treatment policies compared with 20 years if only patients in stages F3-F4 are treated. CONCLUSIONS: Although increasing screening for HCV may generate some value to society, only when paired with expanded access to treatment at earlier disease stages will it produce considerable value. Such a "test and treat" strategy is likely to entail higher short-term costs but also yield the greatest social benefits.

Costs and spillover effects of private insurers' coverage of hepatitis C treatment.

OBJECTIVES: Hepatitis C virus (HCV) treatment incentives for private payers may be misaligned because payers must bear immediate costs and may not realize long-term benefits. However, these benefits may accrue to future payers, including Medicare. We examined how and to what extent private payers' current HCV treatment coverage decisions impact Medicare's and private payers' future costs. STUDY DESIGN: Discrete-time Markov model. METHODS: We modeled HCV disease progression and transmission to simulate the economic and social effects of different private-payer HCV treatment scenarios on Medicare. The model examined differences between a baseline scenario (current practice guidelines) and 2 alternative scenarios that expand treatment coverage. Spillover effects were measured as reduced HCV treatment costs and medical expenditures in Medicare. We calculated the spillover effects and net social value of each scenario (total value of quality-adjusted life-years accrued over time minus cumulative treatment and medical costs). RESULTS: With expanded HCV treatment coverage, private payers experience reduced medical expenditures in the 3-to-5-year time horizon; however, they still face higher treatment costs. Over a 20-year horizon, private payers experience overall savings of $10 billion to $14 billion after treatment costs. The expansion of coverage by private payers generates positive spillover benefits to Medicare of $0.3 billion to $0.7 billion over a 5-year horizon, and $4 billion to $11 billion over a 20-year horizon. CONCLUSIONS: When private payers increase HCV treatment coverage, they may achieve significant savings while inducing spillover benefits to Medicare. Future savings, however, may not motivate immediate treatment investments among private payers who experience high beneficiary turnover.

Cost-effectiveness of currently recommended direct-acting antiviral treatments in patients infected with genotypes 1 or 4 hepatitis C virus in the US.

OBJECTIVE: This study compared the cost-effectiveness of direct-acting antiviral therapies currently recommended for treating genotypes (GT) 1 and 4 chronic hepatitis C (CHC) patients in the US. METHODS: A cost-effectiveness analysis of treatments for CHC from a US payer's perspective over a lifelong time horizon was performed. A Markov model based on the natural history of CHC was used for a population that included treatment-naïve and -experienced patients. Treatment alternatives considered for GT1 included ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin (3D ± R), sofosbuvir + ledipasvir (SOF/LDV), sofosbuvir + simeprevir (SOF + SMV), simeprevir + pegylated interferon/ribavirin (SMV + PR) and no treatment (NT). For GT4 treatments, ombitasvir/paritaprevir/ritonavir + ribavirin (2D + R), SOF/LDV and NT were compared. Transition probabilities, utilities and costs were obtained from published literature. Outcomes included rates of compensated cirrhosis (CC), decompensated cirrhosis (DCC), hepatocellular carcinoma (HCC) and liver-related death (LrD), total costs, life-years and quality-adjusted life-years (QALYs). Costs and QALYs were used to calculate incremental cost-effectiveness ratios. RESULTS: In GT1 patients, 3D ± R and SOF-containing regimens have similar long-term outcomes; 3D ± R had the lowest lifetime risks of all liver disease outcomes: CC = 30.2%, DCC = 5.0 %, HCC = 6.8%, LT = 1.9% and LrD = 9.2%. In GT1 patients, 3D ± R had the lowest cost and the highest QALYs. As a result, 3D ± R dominated these treatment options. In GT4 patients, 2D + R had lower rates of liver morbidity and mortality, lower cost and more QALYs than SOF/LDV and NT. LIMITATIONS: While the results are based on input values, which were obtained from a variety of heterogeneous sources-including clinical trials, the findings were robust across a plausible range of input values, as demonstrated in probabilistic sensitivity analyses. CONCLUSIONS: Among currently recommended treatments for GT1 and GT4 in the US, 3D ± R (for GT1) and 2D + R (for GT4) have a favorable cost-effectiveness profile.

Early View of the Effectiveness of New Direct-Acting Antiviral (DAA) Regimens in Patients with Hepatitis C Virus (HCV).

INTRODUCTION: Clinical trials have demonstrated the efficacy of all-oral direct-acting antiviral (DAA) regimens in the treatment of patients infected with hepatitis C virus (HCV). This study assessed real-world effectiveness of two recently approved regimens; paritaprevir/ritonavir/ombitasvir; dasabuvir (3D), and sofosbuvir/ledipasvir (SOF/LDV) in patients with HCV genotype 1. METHODS: A retrospective analysis of administrative claims data (IMS Health Patient-Centric Data Warehouse/Medivo database) from October 1, 2013 to August 14, 2015 was conducted. Patients ≥19 years of age with a HCV genotype 1 infection, a prescription fill for 3D or SOF/LDV, and ≥1 HCV viral load (VL) assessment from weeks 4-30 post-treatment were selected for analysis. Percentages of patients achieving sustained virologic response (SVR; defined as HCV RNA ≤43 IU/mL) were determined. Unadjusted SVR rates were compared between treatment groups using Fisher's exact tests. SVR rates were also assessed using multivariate regression with adjustment for age group, sex, and treatment history. Analyses were repeated for a subset of patients with VL assessment from 12 to 30 weeks post-treatment. RESULTS: A total of 1707 (44 3D and 1663 SOF/LDV) patients were included. The majority (60%) were male, 49% were aged 55-64 years, and 97% were treatment-naïve 1 year prior to index. The unadjusted relative risk (RR) for achieving SVR in patients treated with SOF/LDV compared with 3D was 0.98%, 95% confidence interval (CI): 0.93-1.02. After adjusting for the baseline covariates, the RR was 0.98%, 95% CI: 0.94-1.03. CONCLUSIONS: In this early view of real-world data, effectiveness of all-oral DAA regimens in HCV genotype 1 patients was concordant with results from registration trials. SVR rates were similar for the two regimens. Further studies are needed to confirm these results. FUNDING: AbbVie, Inc.

Medical resource use and costs related to central precocious puberty: a retrospective cohort study.

OBJECTIVE: To evaluate the economic burden of central precocious puberty (CPP) by examining direct health care resource utilization and costs. METHODS: Administrative claims from the Medstat MarketScan Commercial Claims database were analyzed, and 2 cohorts of children ≤ 12 years of age were identified. The CPP cohort included patients newly diagnosed with precocious sexual development and puberty (International Classification of Diseases, Ninth Revision, Clinical Modification code 259.1x) between January 1, 2004, and June 30, 2006 (date of the initial diagnosis of CPP was designated as the "index date") who used gonadotropin-releasing hormone agonists during the 12 months after diagnosis. Each patient with CPP was matched with 4 control patients without CPP on the basis of age, sex, geographic region, and type of health insurance plan. Resource utilization and costs during the 12 months before and the 12 months after the index date were examined. RESULTS: A total of 172 patients with CPP and 688 control patients were identified after matching. Approximately 62% of patients were 7 to 9 years of age, and 87% were female. The patients with CPP had higher annual health care costs than did the control patients during the 12-month pre-index ($10,968 versus $783; P<.001) and the 12-month post-index ($21,071 versus $849; P<.001) periods, primarily attributable to outpatient and pharmacy costs. For the patients with CPP, annual health care costs increased by $10,103 after diagnosis. On average, annual CPP-related costs were $10,605. Monthly total health care costs for the patients with CPP increased sharply during the first month after diagnosis and remained high throughout the post-index period. CONCLUSION: In this study, health care resource use and costs among patients with CPP were substantial before and after the initial diagnosis of CPP.

Comparative effectiveness of paricalcitol versus cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis.

BACKGROUND/AIMS: Parathyroidectomies are performed when medical therapy fails to control secondary hyperparathyroidism in hemodialysis patients. The objective of this study was to compare parathyroidectomy rates in secondary hyperparathyroidism patients treated with paricalcitol or cinacalcet. METHODS: Retrospective cohort study using health insurance claims from January 2001 through June 2007 for adult hemodialysis patients who were new users of paricalcitol or cinacalcet. Subjects had a minimum of 12 months' enrollment prior to initiation of treatment and at least 30-day follow-up. RESULTS: We identified 1,387 paricalcitol- and 1,317 cinacalcet-treated patients. The parathyroidectomy incident rate was 74% lower in the paricalcitol (0.58 per 100 patient-years) compared to the cinacalcet (2.24 per 100 patient-years) cohort, with an unadjusted rate ratio of 0.26 (95% CI 0.12-0.52). The time to parathyroidectomy from medication initiation was longer for paricalcitol than cinacalcet; however, it was not statistically significant (535 vs. 443 days, p = 0.377). A Cox proportional hazard model that adjusted for age, gender, obesity, significantly different comorbidities, and duration of hemodialysis resulted in an adjusted risk reduction for parathyroidectomy of 79% (HR = 0.21, 95% CI 0.10-0.46) for paricalcitol compared to cinacalcet. CONCLUSION: These data suggest that long-term treatment with paricalcitol is associated with fewer parathyroidectomies when compared to cinacalcet. Further comparative studies are needed to validate these results.

Cost Effectiveness of Paricalcitol versus a non-selective vitamin D receptor activator for secondary hyperparathyroidism in the UK: a chronic kidney disease markov model.

BACKGROUND: secondary hyperparathyroidism (SHPT) is a common complication of chronic kidney disease (CKD) and a frequent cause of clinically significant bone disease. Non-selective vitamin D receptor (VDR) activator treatment has been used to treat the condition but is ineffective for many patients with hypercalcaemia and hyperphosphataemia and may precipitate worsening of their condition. Compared with non-selective VDR activator treatment, use of the VDR ligand paricalcitol may increase survival and reduce the risk of morbidities in patients with SHPT, which may have health economic consequences. OBJECTIVE: the objective of this study was to determine the cost effectiveness of paricalcitol versus a non-selective VDR activator for the treatment of SHPT in patients with CKD in the UK setting. METHODS: A Markov process model was developed employing data sources from the published literature, paricalcitol clinical trials and observational studies, official UK price/tariff lists and national population statistics. The comparator was alfacalcidol, a non-selective VDR activator medication. The primary perspective of the study was that of the UK National Health Service (NHS). The efficacy outcomes (reductions in SHPT, proteinuria, complications and mortality) were extrapolated to: number of life-years gained (LYG) and number of quality-adjusted life-years (QALYs). Clinical and economic outcomes were discounted at 3.5%. The year of costing for costs determined in the study was 2006. RESULTS: the reference case analysis was a 10-year time horizon, based on a comparison of paricalcitol with a non-selective VDR activator, which is started in CKD stage 3 (moderate reduction in glomerular filtration rate [GFR] with kidney damage) and continued in CKD stage 4 (severe reduction in GFR) and CKD stage 5 (established kidney failure). The use of paricalcitol leads to an additional medical cost of pound3224 ($US5970). The health benefits of paricalcitol lead to an increase in LYG of 0.52 and a gain in QALYs of 0.465. Therefore the use of paricalcitol results in an incremental cost-effectiveness ratio of pound6933/QALY ($US12 840/QALY) from the primary perspective of the NHS. One-way sensitivity analyses and probabilistic sensitivity analyses confirmed the robustness of the model. CONCLUSION: this model showed that the favourable clinical benefit of paricalcitol results in positive short- and long-term health economic benefits. This study suggests that the use of paricalcitol in patients with early CKD may be cost effective from the UK NHS perspective versus non-selective VDR activator medication.

Add-back therapy use and its impact on LA persistence in patients with endometriosis.

OBJECTIVES: Persistence and compliance in women with endometriosis who are receiving gonadotropin-releasing hormone agonists (GnRH-a) may be limited by its hypoestrogenic side effects. Use of concomitant therapy with norethindrone acetate (NA), estrogen, estrogen/progestin combinations, or other progestin (i.e., 'add-back therapy' [ABT]) is recommended to alleviate these side effects. This retrospective study evaluated ABT utilization and its effect on compliance and persistence in patients with endometriosis taking the GnRH-a leuprolide acetate (LA) depot suspension. METHODS: A retrospective analysis of a large pharmacy claims database identified patients who started LA therapy from 2002 to 2004 for the treatment of endometriosis. Patients were identified as having received ABT if they started 7 days before, or within 45 days of the last LA fill. RESULTS: A total of 1285 women with endometriosis who began using LA were identified with 12 months of evaluable data: 211 (16.4%) used concomitant NA therapy, 116 (9.0%) used concomitant estrogen-based therapy, 28 (2.2%) used concomitant combination estrogen- and progestin-based therapies, 56 (4.4%) used concomitant progestin-based therapy, and 874 (68.0%) did not use any ABT. Mean (+/-SD) LA persistence in women receiving NA-based ABT was 5.83 +/- 2.98 months, compared with 4.25 +/- 2.62 months for those not using ABT (P < 0.0001). Average medication possession ratio was 0.43 +/- 0.20 for women receiving NA-based ABT versus 0.32 +/- 0.18 for those not receiving any ABT (P < 0.0001). Patients < 30 years of age were most likely to continue therapy longer and have greater compliance compared with the older age group cohorts (P < 0.01). Patients who used ABT continued to do so for 3.79 +/- 3.21 months. LIMITATIONS: Limitations of this study include those associated with the use of retrospective claims databases: It does not include any information regarding the patient's pain symptoms, disease severity, or other factors, which could correlate to compliance and persistence. CONCLUSIONS: Among women using LA therapy for endometriosis, only 32% used any type of ABT, and these patients had significantly higher persistence and compliance with LA therapy compared to no ABT user group.

The ISPOR Good Practices for Quality Improvement of Cost-Effectiveness Research Task Force Report.

OBJECTIVES: The International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Health Science Policy Council recommended and the ISPOR Board of Directors approved the formation of a Task Force to critically examine the major issues related to Quality Improvement in Cost-effectiveness Research (QICER). The Council's primary recommendation for this Task Force was that it should report on the quality of cost-effectiveness research and make recommendations to facilitate the improvement of pharmacoeconomics and health outcomes research and its use in stimulating better health care and policy. Task force members were knowledgeable and experienced in medicine, pharmacy, biostatistics, health policy and health-care decision-making, biomedical knowledge transfer, health economics, and pharmacoeconomics. They were drawn from industry, academia, consulting organizations, and advisors to governments and came from Japan, the Netherlands, Canada and the United States. METHODS: Face-to-face meetings of the Task Force were held at ISPOR North American and European meetings and teleconferences occurred every few months. Literature reviews and surveys were conducted and the first preliminary findings presented at an open forum at the May 2008 ISPOR meeting in Toronto. The final draft report was circulated to the expert reviewer group and then to the entire membership for comment. The draft report was posted on the ISPOR Web site in April 2009. All formal comments received were posted to the association Web site and presented for discussion at the Task Force forum during the ISPOR 14th Annual International Meeting in May 2009. Comments and feedback from the forums, reviewers and membership were considered in the final report. Once Task Force consensus was reached, the article was submitted to Value in Health. CONCLUSIONS: The QICER Task Force recommends that ISPOR implement the following: * With respect to CER guidelines, that ISPOR promote harmonization of guidelines, allowing for differences in application, regional needs and politics; evaluate available instruments or promote development of a new one that will allow standardized quantification of the impact of CER guidelines on the quality of CER studies; report periodically on those countries or regions that have developed guidelines; periodically evaluate the quality of published studies (those journals with CER guidances) or those submitted to decision-making bodies (as public transparency increases). * With respect to methodologies, that ISPOR promote publication of methodological guidelines in more applied journals in more easily understandable format to transfer knowledge to researchers who need to apply more rigorous methods; promote full availability of models in electronic format to combat space restrictions in hardcopy publications; promote consistency of methodological review for all CER studies; promote adoption of explicit best practices guidelines among regulatory and reimbursement authorities; periodically update all ISPOR Task Force reports; periodically review use of ISPOR Task Force guidelines; periodically report on statistical and methodological challenges in HE; evaluate periodically whether ISPOR's methodological guidelines lead to improved quality; and support training and knowledge transfer of rigorous CER methodologies to researchers and health care decision-makers. * With respect to publications, that ISPOR develop standard CER guidances to which journals will be able to refer their authors and their reviewers; lobby to establish these guidances within the International Committee for Medical Journal Editors (ICMJE) Requirements to which most journals refer in their Author Instructions; provide support in terms of additional reviewer expertise to those journals lacking appropriate reviewers; periodically report on journals publishing CER research; periodically report on the quality of CER publications; and support training and knowledge transfer of the use of these guidelines to researchers and reviewers. * With respect to evidence-based health-care decision-making, that ISPOR recognize at its annual meetings those countries/agencies/private companies/researchers using CER well, and those practitioners and researchers supporting good patient use of CER in decision-making; and promote public presentation of case studies of applied use of CER concepts or guidelines.

Association of secondary hyperparathyroidism with CKD progression, health care costs and survival in diabetic predialysis CKD patients.

BACKGROUND/AIMS: The objective of this study was to examine health care costs and utilization and the risks of dialysis or mortality among diabetic predialysis chronic kidney disease (CKD) patients with and without secondary hyperparathyroidism (SHPT). METHODS: This retrospective, matched cohort study examined insurance claims from 703 adult diabetic predialysis CKD patients with and without SHPT during a 72-month follow-up period. Annualized estimates of health care service utilization, costs and disease progression to dialysis or death following index CKD diagnosis were compared. RESULTS: Preindex (baseline) characteristics were similar between the cohorts. Postindex numbers of prescription utilization, outpatient service utilization and hospitalizations were all higher (p < 0.0001) in diabetic CKD patients with SHPT compared to those without SPHT in both unadjusted and adjusted analyses even after multivariate adjustment for known confounders. The rate of progression to dialysis or death was higher for diabetic CKD patients with SHPT compared to those without SPHT. Those with SHPT were at higher risk of requiring dialysis treatment [hazard ratio (HR) = 6.7; 95% confidence interval (CI) = 4.3-10.6] and death (HR = 2.3; 95% CI = 1.1-4.9) compared to those without SHPT. CONCLUSION: In diabetic predialysis CKD patients, the presence of SHPT is associated with significantly greater health care resource utilization and costs, and a faster rate of disease progression.

Chronic kidney disease Markov model comparing paricalcitol to calcitriol for secondary hyperparathyroidism: a US perspective.

OBJECTIVE: The objective of this study was to determine the cost effectiveness of paricalcitol versus calcitriol for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease in the United States setting. METHODS: A Markov process model was developed employing data sources from the published literature, paricalcitol clinical trials and observational studies, official US price/tariff lists and national population statistics. The comparator was calcitriol, a non-selective vitamin D receptor activator (VDRA) medication. The primary perspective of the study was that of the third-party payer in the US. The efficacy outcomes (reduction in secondary hyperparathyroidism (SHPT), reduction in proteinuria, complications and mortality) were extrapolated to: number of life-years gained (LYG) and number of quality-adjusted life-years (QALYs). Clinical and economic outcomes were discounted at 3.5%. RESULTS: The reference case analysis was a 10-year time horizon based on a comparison of paricalcitol with calcitriol, which is started in chronic kidney disease (CKD) stage 3 and continued in CKD stage 4 and CKD stage 5. The use of paricalcitol leads to a cost saving of US$1941. The inclusion of indirect costs leads to a cost saving of US$2528. The use of paricalcitol leads to an increase in life-years gained (0.47 years) and a gain in QALYs (0.43). The use of paricalcitol results in a dominant outcome from the perspective of the third-party payer, as well as from the societal perspective. One-way sensitivity analyses and probabilistic sensitivity analyses confirmed the robustness of the model. CONCLUSION: This model showed that the favorable clinical benefit of paricalcitol results in positive short and long-term health economic benefits. This study suggests that the use of paricalcitol in patients with early chronic kidney disease may be cost-effective from the third-party payer perspective in the US versus calcitriol. Additional comparative studies are necessary to validate these results.

Health-economic comparison of paricalcitol, calcitriol and alfacalcidol for the treatment of secondary hyperparathyroidism during haemodialysis.

This study evaluated the health-economic consequences of use of intravenous paricalcitol (Zemplar), oral calcitriol or oral and intravenous alfacalcidol for the treatment of patients with secondary hyperparathyroidism, focusing on a third-party payer perspective through inclusion of medication and hospital costs, survival rates and utilities. Cost values were based on German treatment recommendations and prices. Reference values for survival rates and utilities were based on the results of a MEDLINE search. The analysis showed a clear advantage for intravenous paricalcitol with respect to costs, effectiveness and utilities compared with treatment with oral calcitriol or intravenous alfacalcidol. Since the results were very cost sensitive with respect to selected diagnosis-related groups (DRGs) for kidney disease with dialysis, a sensitivity analysis was performed. This demonstrated first-order dominance of intravenous paricalcitol for a wide range of hospitalisation costs. In conclusion, this analysis suggested a clear benefit from the perspective of a third-party payer for intravenous paricalcitol compared with oral calcitriol and intravenous alfacalcidol in the treatment of patients with secondary hyperparathyroidism.

Paricalcitol-treated patients experience improved hospitalization outcomes compared with calcitriol-treated patients in real-world clinical settings.

BACKGROUND: Abnormalities of serum calcium, phosphorous and intact parathyroid hormone (PTH) are associated with morbidity and mortality in haemodialysis patients. Pharmacologic parenteral vitamin D administration is used to correct these abnormalities; however, the relationship between vitamin D therapies and hospitalizations has never been addressed. METHODS: Healthcare data from January 1999 to November 2001 were analysed for 11,443 adult haemodialysis patients who received at least 10 doses of vitamin D therapy. Multivariate models were used to evaluate the effects of vitamin D therapy on: (i) total number of hospitalizations, (ii) total number of hospital days and (iii) risk of first hospitalization after initiation of vitamin D therapy. RESULTS: When compared with the calcitriol group, the paricalcitol group had a lower risk of first all-cause hospitalization (14% less likely, P<0.0001), fewer hospitalizations per year (0.642 fewer, P<0.001) and fewer hospital days per year (6.84 fewer, P<0.001). In the paricalcitol and calcitriol groups, respectively, 5.6 and 41.3% patients switched to another vitamin D compound. For those patients who started and remained on the same vitamin D product, paricalcitol-treated patients experienced 0.846 fewer hospitalizations per year and 9.17 fewer hospital days per year, P<0.001 for both. The paricalcitol group also had a lower risk of first PTH-related hospitalizations, fewer PTH-related annual hospitalizations and fewer days per year. CONCLUSION: Paricalcitol-treated patients experienced fewer hospitalizations and hospital days per year when compared with calcitriol-treated patients. Initiating vitamin D therapy with paricalcitol may result in overall savings of approximately 7600-11,000 US dollars per patient per year. A randomized, controlled, blinded study would be valuable in confirming and understanding these results.