Cost-effectiveness model of abiraterone plus prednisone,cabazitaxel plus prednisone and enzalutamide for visceral metastatic castration resistant prostate cancer therapy after docetaxel therapy resistance

Abstract

Aims: Among patients diagnosed with prostate cancer, 10–20% will develop castration-resistant prostate cancer (CRPC) within 5?years; for 70%, CRPC will metastasize, mostly to the lungs and/or liver. We performed a cost-effectiveness model comparing abiraterone plus prednisone (ABI?+?PRD), cabazitaxel plus prednisone (CAB?+?PRD) and enzalutamide (ENZ) for visceral metastatic CRPC post-docetaxel therapy resistance.

Methods: A three-state (Progression-Free, Progression, Death) lifetime Markov model was constructed to compare ABI?+?PRD, CAB?+?PRD, and ENZ from a United States healthcare payer perspective (2019?US$; discount rate 3%/yr.). Effectiveness was measured in life-years (LYs) and quality-adjusted life years (QALYs). Inputs included treatment costs, grade III/IV adverse events with incidence ≥5%, physician follow-up, lab and imaging tests. Phase III trial Kaplan-Meier curves were extrapolated to estimate overall survival and Progression-Free transition probabilities. Incremental cost-effectiveness ratios (ICERs) and utility ratios (ICURs), probabilistic sensitivity analyses (PSAs) and cost-effectiveness acceptability curves at willingness-to-pay (WTP) thresholds were estimated.

Results: Models estimated 3-year overall survival rates of 1.3% for patients treated with ABI?+?PRD, 16.2% for CAB?+?PRD, and 13.2% for ENZ. Estimated Progression-Free rates at 1.5?years were 0.51% for ABI?+?PRD, 0.27% for CAB?+?PRD, and 14.47% for ENZ. LYs and QALYs were 1.20 and 0.58 respectively for ABI?+?PRD, 1.48 and 0.56 for CAB?+?PRD, and 1.58 and 0.79 for ENZ. Total treatment costs were: $115,433 for ABI?+?PRD, $85,337 for CAB?+?PRD and $109,213 for ENZ. CAB?+?PRD and ENZ dominated ABI?+?PRD due to higher LYs gained. Incremental QALYs for ENZ vs. CAB?+?PRD were larger than incremental LYs. The ICUR for ENZ was $103,674/QALY compared to CAB?+?PRD.

Conclusions: This analysis found ENZ provided greater LYs and QALYs than both ABI?+?PRD and CAB?+?PRD, at a lower cost than ABI?+?PRD, but at a higher cost compared to CAB?+?PRD. For patients with visceral mCRPC after docetaxel therapy resistance, ENZ was cost-effective 92% of the time with a WTP threshold of $100,000/QALY.     

Economic evaluation of ombitasvir/paritaprevir/ritonavir and dasabuvir for the treatment of chronic genotype 1 hepatitis c virus infection

Objectives: To estimate clinical outcomes and cost-effectiveness of ombitasvir/paritaprevir/ritonavir and dasabuvir?±?ribavirin (OMB/PTV/r?+?DSV?±?RBV) compared with treatment regimens including pegylated interferon (PegIFN) for patients with chronic genotype 1 hepatitis C virus (HCV) infection.

Methods: An Excel spreadsheet Markov model tracking progression through stages of liver disease was developed. Costs and patient utilities for liver disease stages were taken from published studies. Rates of disease progression were based on studies of untreated HCV infection and long-term follow-up of those achieving sustained virologic response (SVR) after drug treatment. Impact of OMB/PTV/r?+?DSV?±?RBV and other drug regimens on progression was estimated through SVR rates from clinical trials. Analyses were performed for treatment-naive and treatment-experienced patients. Impact of alternative scenarios and input parameter uncertainty on the results were tested.

Results: For genotype 1 treatment-naive HCV patients, for OMB/PTV/r?+?DSV?±?RBV, PegIFN?+?ribavirin (PegIFN/RBV), sofosbuvir?+?PegIFN/RBV, telaprevir?+?PegIFN/RBV, boceprevir?+?PegIFN/RBV, lifetime risk of decompensated liver disease was 5.6%, 18.9%, 7.4%, 11.7%, and 14.9%; hepatocellular carcinoma was 5.4%, 9.2%, 5.7%, 7.0%, and 7.4%; and death from liver disease was 8.7%, 22.2%, 10.4%, 14.8%, and 17.6%, respectively. Estimates of the cost-effectiveness of OMB/PTV/r?+?DSV?±?RBV for treatment-naive and treatment-experienced patients indicated that it dominated all other regimens except PegIFN/RBV. Compared with PegIFN/RBV, the incremental cost-effectiveness ratios were £13,864 and £10,258 per quality-adjusted life-year (QALY) for treatment-naive and treatment-experienced patients, respectively. The results were similar for alternative scenarios and uncertainty analyses.

Limitations: A mixed-treatment comparison for SVR rates for the different treatment regimens was not feasible, because many regimens did not have comparator arms; instead SVR rates were based on those from recent trials.

Conclusions: OMB/PTV/r?+?DSV?±?RBV is a cost-effective oral treatment regimen for chronic genotype 1 HCV infection compared with standard treatment regimens and is estimated to reduce the lifetime risks of advanced liver disease.     

Healthcare costs and resource utilization in patients with severe aplastic anemia in the US

Abstract

Purpose: This study aimed to evaluate the healthcare resource utilization (HCRU) and costs for patients with severe aplastic anemia (SAA) using US claims data.

Methods: This retrospective, observational database study analyzed claims data from the Truven MarketScan databases. SAA patients aged ≥2?years identified between 2014 and 2017 who were continuously enrolled for 6?months before their first SAA treatment or blood transfusion, with a ≥6-month follow-up, were included. Baseline demographics and comorbidities were evaluated. Monthly all-cause and SAA-related HCRU and direct costs in the follow-up period were analyzed and differences were presented for all patients and across age groups.

Results: With an average follow-up period of 21.5?months, 939 patients were included in the study. Monthly all-cause and SAA-related HCRU [mean (SD)] were 1.65 days (2.61 days) and 0.18 days (0.70 days) for length of stay, 0.18 (0.23) and 0.01 (0.04) for hospital admissions, 0.25 (0.30) and 0.02 (0.07) for ER visits, 2.24 (1.40) and 0.46 (0.99) for office visits, and 2.90 (2.64) and 0.55 (1.31) for outpatient visits, respectively. On average, SAA patients received 0.15 (0.57) blood transfusions per month. Mean monthly all-cause direct costs were $28,280 USD ($36,127) [US dollars, mean (SD)]. Direct costs related to admissions were $11,433 USD (SD $25,040), followed by $624 USD ($1,703) for ER visits, $528 USD ($694) for office visits, $7,615 USD ($13,273) for outpatient visits, and $5,998 USD ($11,461) for pharmacy expenses. Monthly SAA-related direct costs averaged $7,884 USD (SD $16,254); of these costs, $1,608 USD ($7,774) were from admissions, $47 USD ($257) from ER visits, $127 USD ($374) from office visits, $1,462 USD ($4,994) from outpatient visits, and $4,451 USD ($10,552) from pharmacy expenses.

Conclusion: SAA is associated with high economic burden, with costs comparable to blood malignancies, implying that US health plans should consider appropriately managing SAA while constraining the total healthcare costs when making formulary decisions.     

Cost-effectiveness of combination daclatasvir-sofosbuvir for treatment of genotype 3 chronic hepatitis C infection in the United States

Background: A phase III trial evaluated the efficacy and safety of Daklinza (daclatasvir or DCV) in combination with sofosbuvir (SOF) for treatment of genotype (GT) 3 hepatitis C virus (HCV) patients.

Aim: This study evaluated the cost-effectiveness of DCV?+?SOF vs SOF in combination with ribavirin (RBV) over a 20-year time horizon from the perspective of a United States (US) payer.

Methods: A published Markov model was adapted to reflect US demographic characteristics, treatment patterns, costs of drug acquisition, monitoring, disease and adverse event management, and mortality risks. Clinical inputs came from the ALLY-3 and VALENCE trials. The primary outcome was the incremental cost-utility ratio. Life-years, incidence of complications, number of patients achieving sustained virological response (SVR), and the total cost per SVR were secondary outcomes. Costs (2014 USD) and quality-adjusted life years (QALYs) were discounted at 3% per year. Deterministic, probabilistic, and scenario sensitivity analyses were conducted.

Results: DCV?+?SOF was associated with lower costs and better effectiveness than SOF?+?RBV in the base case and in almost all scenarios (i.e. treatment-experienced, non-cirrhotic, time horizons of 5, 10, and 80 years). DCV?+?SOF was less costly, but also slightly less effective than SOF?+?RBV in the cirrhotic and treatment-naïve population scenarios. Results were sensitive to variations in the probability of achieving SVR for both treatment arms. DCV?+?SOF costs less than $50,000 per QALY gained in 79% of all probabilistic iterations compared with SOF?+?RBV.

Conclusion: DCV?+?SOF is a dominant option compared with SOF?+?RBV in the US for the overall GT 3 HCV patient population.     

Pharmacological control of secondary hyperparathyroidism in hemodialysis subjects: a cost consequences analysis of data from the FARO study

Abstract

Background and objectives:

Secondary hyperparathyroidism (SHPT) is a frequent complication of CKD with incidence, prevalence, and costs increasing worldwide. The objective of this analysis was to estimate therapy cost of SHPT in a sub-population of the FARO study.

Materials and Methods:

In the FARO study, an observational survey aimed to evaluate patterns of treatment in patients with SHPT who had undergone hemodialysis, pharmacological treatments and biochemical parameters evolution data were collected in four surveys. Patients maintaining the same treatment in all sessions were grouped by type of treatment and evaluated for costs from the Italian National Health Service perspective.

Results:

Four cohorts were identified: patients treated with oral (PO) calcitriol (n?=?182), intravenous (IV) calcitriol (n?=?34), IV paricalcitol (n?=?62), and IV paricalcitol?+?cinacalcet therapy (n?=?20); the cinacalcet monotherapy group was not analysed due to low number of patients (n?=?9). Parathyroid hormone (PTH) level at baseline and effectiveness of treatments in suppressing PTH level were assessed to test comparability among cohorts: calcitriol PO patients were significantly less severe than others (PTH level at baseline lower than 300?pg/ml; p?<?0.0001); calcitriol IV patients did not reach significant reduction in PTH level. Paricalcitol and paricalcitol?+?cinacalcet treatment groups results were comparable, while only the IV paricalcitol cohort’s PTH level, weekly dosage, and cost decreased significantly from the first to the fourth survey (p?=?0.020, p?=?0.012, and p?=?0.0124, respectively). Total costs per week of treatment (including calcium-based phosphate binder and sevelamer) were significantly lower in the paricalcitol vs paricalcitol?+?cinacalcet cohort (p?<?0.001). Major limitations of this study are related to the survey design: not controlled and lack of comparability between cohorts; however, reflective of true practice patterns.

Conclusions:

The IV Paricalcitol cohort had significantly lower treatment costs compared with patients treated with paricalcitol?+?calcimemtics (p?<?0.001), without a significant difference in terms of baseline severity and PTH control.     

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.     

Healthcare utilization and costs among chronic bronchitis patients treated with maintenance medications from a US managed care population

Abstract

Objectives:

This study aimed to examine the real-world healthcare resource utilization (HCRU) and direct costs among chronic bronchitis (CB) patients treated with chronic obstructive pulmonary disease (COPD) maintenance medications.

Methods:

This retrospective analysis utilized administrative claims data from 14 US commercial managed care plans. Eligible patients were ≥40 years old, had ≥2 years of continuous enrollment, ≥1 CB (ICD-9-CM code 491.xx) hospitalization or emergency department (ED) visit or ≥2 office visits between 1/1/2004 and 5/31/2011, and had ≥2 pharmacy fills for COPD medications during follow-up (first fill served as the index date). All-cause and COPD-related HCRU and costs were assessed during follow-up. Multivariate models were utilized to identify predictors of total costs.

Results:

Treated CB patients (n?=?17,382; 50.6% female; mean age 66.7 (SD?=?11.4) years) had a mean of 7.6 (SD?=?6.3) COPD maintenance medication fills during follow-up. Overall, 32.6% of patients had ≥1 COPD-related inpatient hospitalizations, 12.9% had ≥1 ED visit, and 81.8% had ≥1 office visit. Mean all-cause and COPD-related total costs were $25,747 (SD?=?$51,105) and $12,609 (SD?=?$36,801), respectively, during follow-up. Among the sub-group with ≥1 exacerbation during baseline year, 42.3% had ≥1 COPD-related inpatient hospitalization, 18.5% had ≥1 ED visit, and 88.2% had ≥1 office visit. Mean follow-up all-cause and COPD-related total costs were $29,861 (SD?=?$49,799) and $16,784 (SD?=?$34,170), respectively. The number of baseline exacerbations was a significant predictor of all-cause and COPD-related total costs during follow-up.

Limitations:

This study lacked standard measures of CB severity; however, severity proxies were utilized.

Conclusion:

HCRU and costs among CB patients were substantial during follow-up, despite treatment with COPD maintenance medications. Additional interventions aiming to prevent or reduce HCRU and costs among CB patients warrant exploration.     

Quality-adjusted survival with combination nab-paclitaxel + gemcitabine vs gemcitabine alone in metastatic pancreatic cancer: a Q-TWiST analysis

Objectives:

To use the Quality-Adjusted Time Without Symptoms or Toxicities (Q-TWiST) methodology to compare the quality-of-life and survival benefits associated with the combination of albumin-bound (nab)-paclitaxel and gemcitabine vs gemcitabine alone in the first-line treatment of metastatic pancreatic adenocarcinoma.

Methods:

Total survival time through 45 months was partitioned into time before disease progression without toxicity grade ≥3 (TWiST), time with adverse event grade ≥3 (TOX), and time of disease progression (REL). Mean Q-TWiST was calculated by multiplying time spent in each health state by its respective utility (i.e., TWiST?=?1.00; TOX/REL?=?0.50, 0–1 in sensitivity analyses). Non-parametric bootstrap 95% confidence intervals (CI) were derived to assess the significance of between-treatment differences in TOX, TWiST, REL, and Q-TWiST. A relative gain in Q-TWiST (vs mean overall survival of gemcitabine) of ≥10% and ≥15% was defined as clinically important and clearly clinically important, respectively.

Results:

Patients on nab-paclitaxel?+?gemcitabine spent a significantly longer time in every state and experienced significantly greater overall Q-TWiST (+1.7 months [95% CI?=?0.8, 2.7]) than those receiving gemcitabine alone (8.2 months [95% CI?=?7.5, 8.9] vs 6.5 months [95% CI?=?5.8, 7.0]), assuming base-case utilities of TOX/REL?=?0.50. This Q-TWiST gain ranged from 1.0 month (95% CI?=?0.1, 1.9), when REL/TOX utilities were both 0, to 2.5 months (95% CI?=?1.3, 3.7), when REL/TOX utilities were both 1. Relative gains in Q-TWiST were 21% in favor of nab-paclitaxel?+?gemcitabine in the base case, and ranged from 12–30% in sensitivity analyses.

Conclusions:

There are limitations to Q-TWiST analyses, e.g., imprecision when defining duration/severity of TOX and lack of prospective collection of utilities. This analysis addressed these issues via sensitivity analyses and conservative assumptions to show that nab-paclitaxel?+?gemcitabine results in statistically significant and clinically important gains in quality-adjusted survival, when compared to gemcitabine alone, in treatment-naive metastatic pancreatic adenocarcinoma patients.     

Estimating the quality-of-life impact and cost-effectiveness of alpha-blocker and anti-muscarinic combination treatment in men with lower urinary tract symptoms related to benign prostatic hyperplasia and overactive bladder

Abstract

Objective:

A 12-week clinical trial (TIMES) demonstrated that therapy with tolterodine extended release (TOL)?+?tamsulosin (TAM) provides clinical benefits vs TOL or TAM monotherapy or placebo (PBO) in men with lower urinary tract symptoms (LUTS) including overactive bladder (OAB). The present analysis estimated the costs and quality-adjusted life-years (QALYs) associated with these therapies from the perspective of the UK healthcare system.

Methods:

TIMES cohorts receiving TOL, TAM, TOL?+?TAM, or PBO were followed from therapy initiation to 12 weeks. A decision-tree model was used to extrapolate the 12-week results to 1 year (including need for surgery owing to treatment failure at 12 weeks) and to track patients’ outcomes (symptoms, utility, and costs). Because TIMES did not include costs and QALYs, data from the EpiLUTS epidemiologic survey (12,796 males) were used to model a mathematical relationship between LUTS (daytime and nocturnal frequency, urgency episodes, urgency urinary incontinence episodes, and International Prostate Symptom Score [IPSS]), quality-of-life, and utility. This was used to convert improvements in TIMES patients’ LUTS into utility scores and QALYs. The model included drug and surgery procedure costs and hospital length of stay.

Results:

Incremental QALYs of TOL?+?TAM vs PBO, TAM, and TOL were 0.042, 0.021, and 0.013, and corresponding incremental costs were £189, £223, and ?£70, respectively, resulting in cost-utility ratios for TOL?+?TAM of £4508/QALY gained compared with PBO and £10,381/QALY gained compared with TAM. TOL?+?TAM combination therapy was both more effective and cost-saving compared with TOL. Univariate sensitivity analyses showed that patient utility was most responsive to changes in drug efficacy on IPSS and urgency episodes. Changing the percentage of patients undergoing surgery did not substantially affect model outcomes. The main limitation of the study was that the relation between LUTS and patient utility was based on an indirect association.

Conclusions:

TOL?+?TAM combination therapy appears to be cost-effective compared with TOL or TAM monotherapy or PBO in male patients with LUTS.     

Cost-effectiveness of daclatasvir plus sofosbuvir-based regimen for treatment of hepatitis C virus genotype 3 infection in Canada

Objective:

New regimens for the treatment of chronic hepatitis C virus (HCV) genotype 3 have demonstrated substantial improvement in sustained virologic response (SVR) compared with existing therapies, but are considerably more expensive. The objective of this study was to evaluate the cost-effectiveness of two novel all-oral, interferon-free regimens for the treatment of patients with HCV genotype 3: daclatasvir plus sofosbuvir (DCV?+?SOF) and sofosbuvir plus ribavirin (SOF?+?RBV), from a Canadian health-system perspective.

Methods:

A decision analytic Markov model was developed to compare the effect of various treatment strategies on the natural history of the disease and their associated costs in treatment-naïve and treatment-experienced patients. Patients were initially distributed across fibrosis stages F0–F4, and may incur disease progression through fibrosis stages and on to end-stage liver disease complications and death; or may achieve SVR. Clinical efficacy, health-related quality-of-life, costs, and transition probabilities were based on published literature. Probabilistic sensitivity analysis was performed to assess parameter uncertainty associated with the analysis.

Results:

In treatment-naive patients, the expected quality-adjusted life years (QALYs) for interferon-free regimens were higher for DCV?+?SOF (12.37) and SOF?+?RBV (12.48) compared to that of pINF?+?RBV (11.71) over a lifetime horizon, applying their clinical trial treatment durations. The expected costs were higher for DCV?+?SOF ($170,371) and SOF?+?RBV ($194,776) vs pINF?+?RBV regimen ($90,905). Compared to pINF?+?RBV, the incremental cost-effectiveness ratios (ICER) were $120,671 and $135,398 per QALYs for DCV?+?SOF and SOF?+?RBV, respectively. In treatment-experienced patients, DCV?+?SOF regimen dominated the SOF?+?RBV regimen. Probabilistic sensitivity analysis indicated a 100% probability that a DCV?+?SOF regimen was cost saving in treatment-experienced patients.

Conclusion:

Daclatasvir plus sofosbuvir is a safe and effective option for the treatment of chronic HCV genotype 3 patients. This regimen could be considered a cost-effective option following a first-line treatment of peg-interferon/ribavirin treatment experienced patients with HCV genotype-3 infection.     

The economic burden of common adverse events associated with metastatic colorectal cancer treatment in the United States

Aims: Adverse events (AEs) associated with treatments for metastatic colorectal cancer (mCRC) may compromise the course of treatment, impact quality-of-life, and increase healthcare resource utilization. This study assessed the direct healthcare costs of common AEs among mCRC patients in the US.

Methods: Adult mCRC patients treated with chemotherapy or targeted therapies were identified from administrative claims databases (2009–2014). Up to the first three mCRC treatment episodes per patient were considered and categorized as with or without the AE system/organ category during the episode. Total healthcare costs (2014 USD) were measured by treatment episode and reported on a monthly basis. Treatment episodes with the AE category were matched by treatment type and line of treatment to those without the AE category. Adjusted total cost differences were estimated by comparing costs during treatment episodes with vs without the AE category using multivariate regression models; p-values were estimated with bootstrap.

Results: A total of 4158 patients with ≥1 mCRC treatment episode were included (mean age?=?59 years; 58% male; 60% with liver and 14% with lung metastases; 2,261 [54%] with a second and 1,115 [27%] with a third episode). On average, two treatment episodes were observed per patient with an average length of 166 days per episode. Adjusted monthly total cost difference by AE category included hematologic ($1,480), respiratory ($1,253), endocrine/metabolic ($1,213), central nervous system (CNS; $1,136), and cardiovascular ($1,036; all p?Limitations: Claims do not include information on the cause of AEs, and potentially less severe AEs may not have been reported by the physician when billing the medical service. This study aimed to assess the association between costs and AEs and not the causation of AEs by treatment.

Conclusions: The most costly AEs among mCRC patients were hematologic, followed by respiratory, endocrine/metabolic, CNS, and cardiovascular.     

Cost–consequence analysis of a hemostatic matrix alone or in combination for spine surgery patients

Background: A five-year retrospective database analysis comparing the use of Floseal¹ flowable topical hemostat alone (F) and in combination with gelatin/thrombin (F?+?G/T) to achieve hemostasis and control surgical bleeding showed higher resource utilization for F?+?G/T cases relative to F matched pairs during spinal surgery. Lower resource use in the F group was characterized by shorter hospital length of stay and surgical time as well as fewer blood transfusions and less hemostat agent used per surgery.

Objective: To evaluate the cost–consequence of using F compared to F?+?G/T in minor, major and severe spinal surgery from the US hospital perspective.

Methods: A cost–consequence model was developed using the US hospital perspective. Model inputs include clinical inputs from the literature, cost inputs (hemostatic matrices, blood product transfusion, hospital stay and operating room time) from the literature, and an analysis of annual spine surgery volume (minor, major and severe) using the 2012 National Inpatient Sample (NIS) database. Costs are reported in 2017?US dollars. One-way and probabilistic sensitivity analyses address sources of variability in the results.

Results: A medium-volume hospital (130 spine surgeries per year) using F versus F?+?G/T for spine surgeries is expected to require 85 less hours of surgical time, 58 fewer hospital days and 7 fewer blood transfusions in addition to hemostat volume savings (F: 1?mL, thrombin: 1994?mL). The cost savings associated with the hospital resources for a medium-volume hospital are expected to be $317,959 (surgical hours?=?$154,746, hospital days?=?$125,237, blood transfusions?=?$19,023, hemostatic agents?=?$18,953) or $2445 per spine surgery.

Conclusions: The use of F versus F?+?G/T could lead to annual cost savings for US hospitals performing a low to high volume of spinal surgeries per year.     

Cost-effectiveness of obinutuzumab plus bendamustine followed by obinutuzumab monotherapy for the treatment of follicular lymphoma patients who relapse after or are refractory to a rituximab-containing regimen in the US

Aims: Obinutuzumab (GA101, G) was approved in February 2016 by the US Food and Drug Administration to treat follicular lymphoma (FL) patients who relapsed after, or are refractory to (R/R), a rituximab-containing regimen (R/R-rituximab). In the GADOLIN trial, R/R-rituximab patients who received G plus bendamustine (B) followed by G-monotherapy (G?+?B) for up to 2 years had significantly improved progression-free survival and overall survival compared to patients receiving B-monotherapy. This study estimated the cost-effectiveness of G?+?B vs B-monotherapy for R/R-rituximab FL patients from a US payer perspective.

Materials and methods: Patient outcomes were simulated using a 3-state area under the curve model including progression-free survival, progressive disease, and death. This study used R/R-rituximab data from the National LymphoCare Study to extrapolate the GADOLIN trial’s refractory FL progression-free and overall survival data to a R/R-rituximab FL population. Drug utilization and adverse events were based on trial data, and costs were based on Medicare reimbursements and drug wholesale acquisition costs in 2016. Utility estimates were derived from published literature. Post-progression treatment costs were based on observed post-progression therapies in GADOLIN. Sensitivity analyses were conducted to assess model uncertainty.

Results: G?+?B resulted in an increase in quality-adjusted life years relative to B-monotherapy of 1.24 (95% CR?=?0.61–1.87); the incremental total cost was $58,100 (95% CR?=?$54,500–$61,500). The incremental cost-effectiveness ratio was $47,000 per QALY gained, and, based on probabilistic simulations, there was a 98% probability that G?+?B was cost-effective at the $100,000 per QALY threshold.

Limitations and conclusions: This US-based analysis suggests that treatment with G?+?B compared to B-monotherapy is likely cost-effective in R/R-rituximab FL patients. Modeling a R/R-rituximab population based on a synthesis of GADOLIN and the National LymphoCare Study data introduces uncertainty in the analysis. However, the findings were robust to sensitivity analyses.     

Compliance and persistence with Alzheimer’s disease treatment: a retrospective analysis of multiregional hospital databases in Thailand

Aims: Due to the lack of studies evaluating compliance or persistence with Alzheimer’s Disease (AD) treatment outside High-Income Countries (HICs), this study aimed to assess compliance, persistence, and factors associated with non-compliance and non-persistence by utilizing existing “real-world” information from multiregional hospital databases in Thailand.

Materials and methods: Study subjects were retrospectively identified from databases of five hospitals located in different regions across Thailand. AD patients aged ≥60 years who were newly-prescribed with donepezil, galantamine, rivastigmine, or memantine between 2013 and 2017 were eligible for analysis. The Medication Possession Ratio (MPR) was used as a proxy for compliance, while the Kaplan–Meier survival analysis was employed to estimate persistence. Logistic and Cox regressions were used to assess determinants of non-compliance and non-persistence, adjusted for age and gender.

Results: Among 698 eligible patients, mean (SD) MPR was 0.83 (0.25), with 70.3% of the patients compliant to the treatment (having MPR?≥?0.80). Half of the patients discontinued their treatment (having a treatment gap >30 days) within 177 days with a 1-year persistence probability of 21.1%. The patients treated in the university-affiliated hospital were more likely to be both non-compliant (OR?=?1.71; 95% CI?=?1.21–2.42) and non-persistent (HR?=?1.33; 95% CI?=?1.12–1.58). In addition, non-compliance was higher for those prescribed with single AD treatment (OR?=?2.52; 95% CI?=?1.35–4.69), while non-persistence was higher for those unable to reimburse for AD treatment (HR?=?1.34; 95% CI?=?1.11–1.62).

Limitations: By using retrospective databases, a difficulty in validating whether the medications are actually taken after being refilled may over-estimate the levels of compliance and persistence. Meanwhile, possible random coding errors may under-estimate the strength of association findings.

Conclusions: This study reveals the situation of compliance and persistence on AD treatment for the first time outside HICs. The determinants of non-compliance and non-persistence underline key areas for improvement.     

The direct medical costs of Huntington’s disease by stage. A retrospective commercial and Medicaid claims data analysis

Abstract

Objective:

This study quantified the direct healthcare costs and major cost drivers among patients with Huntington’s disease (HD), by disease stage in commercial and Medicaid databases.

Methods:

This retrospective database analysis used healthcare utilization/cost data for HD patients (ICD-9-CM 333.4) from Thomson Reuters’ MarketScan Commercial and Medicaid 2002–2009 databases. Patients were classified by disease stage (Early/Middle/Late) by a hierarchical assessment of markers of disease severity, confirmed by literature review and key opinion leader input. Costs were measured over the follow-up time of each patient with total costs per patient per stage annualized using a patient-year cost approach.

Results:

Among 1272 HD patients, the mean age was similar in commercial (752 patients) and Medicaid (520 patients) populations (48.5 years (SD?=?13.3) and 49.3 years (SD?=?17.2), respectively). Commercial patients were evenly distributed by stage (30.5%/35.5%/34.0%; Early/Middle/Late). However, most (74.0%) Medicaid HD patients were classified as Late stage. The mean total annualized cost per patient increased by stage (commercial: $4947 (SD?=?$6040)–$22,582 (SD?=?$39,028); Medicaid: $3257 (SD?=?$5670)–$37,495 (SD?=?$27,111). Outpatient costs were the primary healthcare cost component. The vast majority (73.8%) of Medicaid Late stage patients received nursing home care and the majority (54.6%) of Medicaid Late stage costs were associated with nursing home care. In comparison, only 40.6% of commercial Late stage patients received nursing home care, which contributed to only 4.6% of commercial Late stage costs.

Conclusions:

The annual direct economic burden of HD is substantial and increased with disease progression. More late stage Medicaid HD patients were in nursing homes and for a longer time than their commercial counterparts, reflected by their higher costs (suggesting greater disease severity). Key limitations include the classification of patients into a single stage, as well as a lack of visibility into full long-term care/nursing home-related costs for commercial patients.     

Evaluating the length of stay and value of time in a pediatric emergency department with two models by comparing two different albuterol delivery systems

Abstract

Objective:

Asthma is one of the most common childhood illnesses and accounts for a substantial amount of pediatric emergency department visits. Historically, acute exacerbations are treated with a beta agonist via nebulizer therapy (NEB). However, with the advent of the spacer, the medication can be delivered via a metered dose inhaler (MDI?+?S) with the same efficacy for mild-to-moderate asthma exacerbations. To date, no study has been done to evaluate emergency department (ED) length of stay (LOS) and opportunity cost between nebulized vs MDI?+?S. The objective of this study was to compare ED LOS and associated opportunity cost among children who present with a mild asthma exacerbation according to the delivery mode of albuterol: MDI?+?S vs NEB.

Methods:

A structured, retrospective cross-sectional study was conducted. Medical records were reviewed from children aged 1–18 years treated at an urban pediatric ED from July 2007 to June 2008 with a discharge diagnosis International Classification of Disease-9 of asthma. Length of stay was defined: time from initial triage until the time of the guardian signature on the discharge instructions. An operational definition was used to define a mild asthma exacerbation; those patients requiring only one standard weight based albuterol treatment. Emergency department throughput time points, demographic data, treatment course, and delivery method of albuterol were recorded.

Results:

Three hundred and four patients were analyzed: 94 in the MDI?+?S group and 209 in the NEB group. Mean age in years for the MDI?+?S group was 9.57 vs 5.07 for the NEB group (p?<?0.001). The percentage of patients that received oral corticosteroids was 39.4% in the MDI?+?S group vs 61.7% in the NEB group (p?<?0.001). There was no difference between groups in: race, insurance status, gender, or chest radiographs. The mean ED LOS for patients in the MDI?+?S group was 170 minutes compared to 205 minutes in the NEB group. On average, there was a 25.1 minute time savings per patient in ED treatment time (p?<?0.001; 95% CI?=?3.8–31.7). Significant predictors of outcome for treatment time were chest radiograph, steroids, and treatment mode. Opportunity cost analysis estimated a potential cost savings of $213,532 annually using MDI?+?S vs NEB.

Conclusion:

In mild asthma exacerbations, administering albuterol via MDI?+?S decreases ED treatment time when compared to administering nebulized albuterol. A metered dose inhaler with spacer utilization may enhance opportunity cost savings and decrease the left without being seen population with improved throughput.

Limitations:

The key limitations of this study include its retrospective design, the proxy non-standard definition of mild asthma exacerbation, and the opportunity cost calculation, which may over-estimate the value of ED time saved based on ED volume.     

Real-world evidence of improved healthcare utilization in patients with schizophrenia or schizoaffective disorder after early treatment of paliperidone palmitate once-monthly treatment in Hong Kong

Background: Very few data are available to demonstrate the economic benefit of early paliperidone palmitate once-monthly long-acting injectable (PP1M) treatment in patients with schizophrenia or schizoaffective disorder.

Methods and materials: This study has retrospectively compared the healthcare utilization and associated costs of pre- and post-PPIM treatment in 413 patients with schizophrenia or schizoaffective disorder recruited from three major public hospitals providing psychiatric services in Hong Kong. Patients were categorized into early treatment (≤3 years since diagnosis) and chronic (>3 years) groups, and also whether they were receiving polypharmacy (POP).

Results: It was found that patients who were started on early therapy with no POP had the most favourable outcomes. Overall results of the entire cohort, including both early and late treatments, indicate that there was a slight increase in annual in-patient days (IP) per patient and outpatient visit (OP) by 3.18 and 1.87, respectively, and a decrease in emergency room visit (ER) of 0.9 (p?p?p?p?Conclusions: From the 413 patients studied, potential annual savings is higher by early administration of PPIM in patients with NP. Analysis using multivariate linear regression based on generalized estimating equations and sensitivity analysis using a linear mixed model supported the findings.     

Healthcare costs associated with skeletal-related events in breast cancer patients with bone metastases

Background:

Patients with bone metastases secondary to breast cancer are pre-disposed to skeletal-related events (SREs), including spinal cord compression (SCC), pathologic fracture (PF), surgery to bone (SB), and radiotherapy to bone (RT).

Objective:

To document current patterns of healthcare utilization and costs of SREs in patients with breast cancer and bone metastases.

Methods:

This was a retrospective, observational study using the Thomson MedStat MarketScan Commercial Claims and Encounters database from 9/2002 to 6/2011. Study subjects included all persons with claims for breast cancer and for bone metastases, and ≥1 claims for an SRE. Unique SRE episodes were identified based on a gap of at least 90 days without an SRE claim, and classified by treatment setting (inpatient or outpatient) and SRE type (SCC, PF, SB, or RT).

Results:

Of 17,266 patients with breast cancer and bone metastases, 9142 (53%) had one or more SRE episodes. Among 5809 patients who met all other criteria, there were 7617 SRE episodes over mean (SD) follow-up of 17.2 (15.2) months. The percentage of episodes that required inpatient treatment ranged from 11% (RT) to 76% (SB). On average, inpatient SCC episodes (n?=?83 episodes) were most costly; while outpatient PF episodes (n?=?552 episodes) were least costly. Of the total SRE costs (mean [SE] $21,072 [$36,462]/episode), 36% were attributable to outpatient RT (n?=?5265 episodes) and 31% to inpatient PF (n?=?838 episodes).

Limitations:

The administrative claims data used in this study may lack sensitivity and specificity for identification of clinical events and may not be generalizable to other populations. Also, for some SRE episode categories, the number of events was small and cost estimates may lack precision.

Conclusion:

In patients with breast cancer and bone metastases, SREs are associated with high costs and hospitalizations.