Cost-effectiveness analysis on the use of fidaxomicin and vancomycin to treat Clostridium difficile infection in France

Background: Fidaxomicin is a macrocyclic antibiotic with proven efficacy against Clostridium difficile infection (CDI) in adults. It was licensed in France in 2012, but, due to higher acquisition costs compared with existing treatments, healthcare providers require information on its cost/benefit profile.

Objective: To compare healthcare costs and health outcomes of fidaxomicin and vancomycin, as reference treatment for CDI.

Methods: A Markov model was used to simulate the treatment pathway, over 1 year, of adult patients with CDI receiving fidaxomicin or vancomycin. Several patient sub-groups (severe CDI; recurrent CDI; concomitant antibiotics; cancer; renal failure; elderly) were evaluated. Cost-effectiveness was analyzed based on cure and recurrence rates derived from published randomized clinical trials comparing fidaxomicin and vancomycin, and costs calculated from the payer perspective using French hospitalization data and drug cost databases. Model outputs included costs in euros (reference year 2014) and health outcomes (recurrence; sustained cure rates). Alternative scenario and sensitivity analyses were performed using data from other clinical trials in CDI, including one conducted in real-life clinical practice in France.

Results: Drug acquisition costs were €1,692 higher in fidaxomicin-treated patients, but this was offset by the lower hospitalization costs with fidaxomicin, which were reduced by €1,722. The reduction in the cost of hospitalization was driven by the significantly lower number of recurrences in fidaxomicin-treated patients, offsetting the acquisition cost of fidaxomicin in all sub-groups except recurrent CDI and concomitant antibiotics.

Conclusion: This study demonstrated that, despite higher acquisition costs, the lower recurrence rate with fidaxomicin resulted in cost savings or low incremental costs compared with vancomycin.     

Temporal pattern and costs of rehospitalization in atrial fibrillation/atrial flutter patients with one or more additional risk factors

Abstract

Objectives:

The ATHENA study showed that use of dronedarone reduced rates of first cardiovascular (CV) hospitalization in atrial fibrillation/flutter (AF/AFL) patients. AF is associated with high costs to payers, which are driven by high rates of hospitalization. This retrospective cohort study examined readmission patterns and costs to US payers in real-world AF/AFL patients with ≥1 additional risk factor (ARF).

Methods:

Patients hospitalized (January 2005–March 2008) with AF/AFL as primary diagnosis and having ≥1 year of health coverage, before and after their first (index) admission, were identified in the PharMetrics Patient-Centric database. As in the ATHENA study, patients had to be ≥75 years of age or ≥70 years, with ≥1 ARF. Rehospitalization patterns (all-cause, all CV-related [including AF/AFL] and AF/AFL-related alone) were examined over 1 year post-index, and costs of index vs later AF/AFL admissions compared.

Results:

The study included 3498 patients (mean 80 [SD 7.6] years; 42.4% men). Over 1 year, 1389 patients (39.7%) were rehospitalized for any cause (mean 1.7 [SD 1.3] events/patient), with 1223 patients (35.0%) undergoing CV-related (mean 1.6 [SD 1.0] events/patient) and 935 (26.7%) undergoing AF-related rehospitalization (mean 1.4 [SD 0.8] events/patient). Common causes of CV-related readmissions (primary diagnosis) were AF/AFL (47.5%), congestive heart failure (CHF) (9.9%), coronary artery disease (7.4%), and stroke/transient ischemic attack (6.2%). Readmission rates at 3 months were 16.2% (all-cause), 14.3% (all CV-related including AF/AFL), and 10.5% (AF/AFL-related alone). AF/AFL readmissions (primary diagnosis) were longer than initial hospitalizations (mean total 6.9 [SD 12.9] vs 4.3 [SD 5.1] days, p?<?0.0001) and more costly (median $1819 [25th percentile $1066, 75th percentile $5623] vs $1707 [25th percentile $1102, 75th percentile $4749]).

Limitations:

This study excluded patients with pre-existing CHF, did not require electrocardiogram confirmation of AF/AFL diagnosis, and did not distinguish between paroxysmal, persistent, and permanent AF.

Conclusions:

AF/AFL patients with ≥1 ARF have high readmission rates. AF/AFL-related readmissions incur higher costs than the initial AF/AFL admissions.     

Length of stay and hospitalization costs for patients undergoing lung surgery with Progel pleural air leak sealant

Aim: Progel Pleural Air Leak Sealant (Progel) is currently the only sealant approved by the FDA for the treatment of air leaks during lung surgery. This study was performed to determine whether Progel use improves hospital length of stay (LOS) and hospitalization costs compared with other synthetic/fibrin sealants in patients undergoing lung surgery.

Methods: The US Premier hospital database was used to identify lung surgery discharges from January 1, 2010 to June 30, 2015. Eligible discharges were categorized as “Progel Sealant” or “other sealants” using hospital billing data. Propensity score matching (PSM) was performed to control for hospital and patient differences between study groups. Primary outcomes were hospital LOS and all-cause hospitalization costs. Clinical outcomes, hospital re-admissions, and sealant product use were also described.

Results: After PSM, a total of 2,670 discharges were included in each study group; baseline characteristics were balanced between groups. The hospital LOS (mean days?±?standard deviation, median) was significantly shorter for the Progel group (9.9?±?9.6, 7.0) compared with the other sealants group (11.3?±?12.8, 8.0; p?<?.001). Patients receiving Progel incurred significantly lower all-cause hospitalization costs ($31,954?±?$29,696, $23,904) compared with patients receiving other sealants ($36,147?±?$42,888, $24,702; p?<?.001).

Limitations: It is not possible to say that sealant type alone was responsible for the findings of this study, and analysis was restricted to the data available in the Premier database.

Conclusions: Among hospital discharges for lung surgery, Progel use was associated with significantly shorter hospital LOS and lower hospitalization costs compared with other synthetic/fibrin sealants, without compromising clinical outcomes.     

Costs of hospital visits among patients with deep vein thrombosis treated with rivaroxaban and LMWH/warfarin

Background:

For many years, the standard of care for patients diagnosed with deep vein thrombosis (DVT) has been low-molecular-weight heparin (LMWH) bridging to an oral Vitamin-K antagonist (VKA). The availability of new non-VKA oral anticoagulants (NOAC) agents as monotherapy may reduce the likelihood of hospitalization for DVT patients.

Objective:

To compare hospital visit costs of DVT patients treated with rivaroxaban and LMWH/warfarin.

Methods:

A retrospective claim analysis was conducted using the MarketScan Hospital Drug Database for care provided between January 2011 and December 2013. Adult patients using rivaroxaban or LMWH/warfarin with a primary diagnosis of DVT during the first day of a hospital visit were identified (i.e., index hospital visit). Based on propensity-score methods, historical LMWH/warfarin patients (i.e., patients who received LMWH/warfarin before the approval of rivaroxaban) were matched 4:1 to rivaroxaban patients. The hospital-visit cost difference between these groups was evaluated for the index hospital visit, as well as for total hospital-visit costs (i.e., including index and subsequent hospital visit costs).

Results:

All rivaroxaban users (n?=?134) in the database were well-matched with four LMWH/warfarin users (n?=?536). The mean hospital-visit costs were $5257 for the rivaroxaban cohort and $6764 in the matched-cohort of patients using LMWH/warfarin. The $1508 cost difference was statistically significant between cohorts (95% CI?=?[?$2296; ?$580]; p-value?=?0.002). Total hospital-visit costs were lower for rivaroxaban compared to LMWH/warfarin users within 1, 2, 3, and 6 months after index visit (significantly lower within 1 and 3 months, p-values <0.05)

Limitations:

Limitations were inherent to administrative-claims data, completeness of baseline characteristics, adjustments restricted to observational factors, and lastly the sample size of the rivaroxaban cohort.

Conclusion:

The availability of rivaroxaban significantly reduced the costs of hospital visits in patients with DVT treated with rivaroxaban compared to LMWH/warfarin.     

Comparison of hospital length of stay and hospitalization costs among patients with non-valvular atrial fibrillation treated with apixaban or warfarin: An early view

Objective: To quantify and compare hospital length of stay (LOS) and costs between hospitalized non-valvular atrial fibrillation (NVAF) patients treated with either apixaban or warfarin via a large claims database.

Methods: Adult patients hospitalized with AF were selected from the Premier Perspective Claims Database (01JAN2013-31MARCH2014). Patients with evidence of valvular heart disease, valve replacement procedures, or pregnancy during the index hospitalization were excluded. Patients treated with apixaban or warfarin during hospitalization were identified. Propensity score matching (PSM) was performed to control for baseline imbalances between patients treated with apixaban or warfarin. Primary outcomes were hospital LOS (days), post-medication administration LOS, and index hospitalization costs, and were compared using paired t-tests in the matched sample.

Results: Before PSM, 2894 apixaban and 124,174 warfarin patients were identified. Patients treated with warfarin were older and sicker compared to those treated with apixaban. After applying PSM, a total of 2886 patients were included in each cohort, and baseline characteristics were balanced. The mean (standard deviation [SD] and median) hospital LOS was significantly (p?=?0.002) shorter for patients treated with apixaban for 5.1 days (5.7 and 3) compared to warfarin for 5.5 days (4.8 and 4). The trend appeared consistent in the hospital LOS from point of apixaban or warfarin administration to discharge (4.5 vs 4.7 days, p?=?0.051). Patients administered apixaban incurred significantly lower hospitalization costs compared to those administered warfarin ($11,262 vs $12,883; p?<?0.001).

Conclusions: Among NVAF patients, apixaban treatment was associated with significantly shorter hospital LOS and lower costs when compared to warfarin treatment.     

Healthcare resource utilization and costs in working-age patients with high-risk atherosclerotic cardiovascular disease: findings from a multi-employer claims database

Abstract

Objective:

Patients with coronary artery disease with diabetes, a history of acute coronary syndromes, cerebrovascular atherosclerotic disease, or peripheral arterial disease are at particularly high risk for a cardiovascular (CV) event and can be defined as having high-risk atherosclerotic cardiovascular disease (ASCVD). The objective of this study is to examine healthcare resource utilization (HRU) and total healthcare costs (THC) for patients with ASCVD in a commercially insured population.     

Healthcare resource utilization and direct medical costs associated with index and recurrent Clostridioides difficile infection: a real-world data analysis

Abstract

Aims: This study aimed to evaluate all-cause economic outcomes, healthcare resource utilization (HRU), and costs in patients with Clostridioides difficile infection (CDI) and recurrent CDI (rCDI) using commercial claims from a large database representing various healthcare settings.

Materials and methods: A retrospective analysis of commercial claims data from the IQVIA PharMetrics Plus database was conducted for patients aged 18–64 years with CDI episodes requiring inpatient stay with CDI diagnosis code or an outpatient medical claim for CDI plus a CDI treatment. Index CDI episodes occurred between 1 January 2010 and 30 June 2017, including only those where patients were observable 6 months before and 12 months after the index episode. Each CDI episode was followed by a 14-d claim-free period. rCDI was defined as another CDI episode within an 8-week window following the claim-free period. HRU, all-cause direct medical costs and time to rCDI were calculated over 12 months and stratified by number of rCDI episodes.

Results: A total of 46,571 patients with index CDI were included. Mean time from one CDI episode to the next was approximately 1 month. In the 12-month follow-up period, those with no recurrence had 1.4 inpatient visits per person and those with 3 or more recurrences had 5.8. Most patients with 3 or more recurrences had 2 or more hospital admissions. The mean annual, total all-cause direct medical costs per patient were $71,980 for those with no recurrence and $207,733 for those with 3 or more recurrences.

Limitations: The study included individuals 18–64 years only. A stringent definition of rCDI was used, which may have underestimated the incidence of rCDI.

Conclusions: CDI and rCDI are associated with substantial healthcare resource utilization and direct medical costs. Timing of recurrences can be predictable, providing a window of opportunity for interventions. Prevention of multiple rCDI appears essential to reduce healthcare costs.     

Daily costs of hospitalization in non-valvular atrial fibrillation patients treated with anticoagulant therapy

Abstract

Background:

Atrial fibrillation (AF) is the most common cardiac rhythm disturbance in the US, with an estimated prevalence of 2.7–6.1 million persons in 2010.     

Exploring the causal relationship between hospital length of stay and re-hospitalization among Japanese AMI patients

We explore the causal relationship between hospital length of stay (LOS) and re-hospitalization for Acute Myocardial Infarction (AMI) patients in Japan, where the average LOS is the longest among OECD countries. Using chart-based data, we address the endogeneity between LOS and re-hospitalization probability by using an exogenous variation based on Rokuyo (the six basic labels allocated to each day), which is found to be irrelevant to admission day but relevant to discharge day. While we do find a significant and positive association between LOS and re-hospitalization probability in the OLS estimation, we do not find a significant relationship once LOS is instrumented by Rokuyo in various instrumental variable estimations. This implies that additional stay that was induced owing to patient’s choice of preferred Rokuyo at discharge has no effect on re-hospitalization probability.     

Trajectory analysis of healthcare costs for patients with major depressive disorder treated with high doses of duloxetine

Abstract

Objective:

To examine healthcare cost patterns prior to and following duloxetine initiation in patients with major depressive disorder (MDD), focusing on patients initiated at or titrated to high doses.

Research design and methods:

Retrospective analysis of 10,987 outpatients, aged 18–64 years, who were enrolled in health insurance for 6 months preceding and 12 months following duloxetine initiation.

Outcome measures:

Repeated measures and pre–post analyses were used to examine healthcare cost trajectories before and after initiation of low- (<60?mg/day), standard- (60?mg/day), and high-dose (>60?mg/day) duloxetine therapy. Decision tree analysis was used to identify patient characteristics that might explain heterogeneity in economic outcomes following titration to high-dose therapy.

Results:

Low-, standard-, and high-dose duloxetine were initiated for 29.6%, 60.9%, and 9.5% of patients, respectively. Within 6 months, 13.7% of patients had dose increases to >?60?mg/day. Regardless of dose, total costs increased prior to and decreased following initiation of treatment. The High Initial Dose Cohort had higher costs both prior to and throughout treatment compared to the other two cohorts. Following escalation to >?60?mg/day, higher medication costs were balanced by lower inpatient costs. Titration to high-dose therapy was cost-beneficial for patients with histories of a mental disorder in addition to MDD and higher prior medical costs.

Limitations:

Conclusions are limited by a lack of supporting clinical information and may not apply to patients who are not privately insured.

Conclusions:

In data taken from insured patients with MDD who were started on duloxetine in a clinical setting, healthcare costs increased prior to and decreased following initiation of therapy. Compared to patients initiated at low- and standard-doses, costs were greater prior to and following initiation for patients initiated at high doses. Increases in pharmacy costs associated with escalation to high-dose therapy were offset by reduced inpatient expenses.     

Healthcare utilization among patients with depression before and after initiating duloxetine in the United Kingdom

Abstract

Objective:

Duloxetine is indicated for treatment of major depressive disorders in the UK. While clinical trials have documented its clinical effectiveness, little is known regarding the relationship between duloxetine use and healthcare utilization in community practice. This study quantifies the impact of treatment with duloxetine on healthcare utilization among patients with depression and those with depression and co-existing pain.

Methods

Depressed adults initiating duloxetine during 1/1/2006–9/30/2007 were identified from the General Practice Research Database (GPRD). All-cause hospitalization, accident/emergency visits, specialist referrals, and analgesic use in the 12 months before (pre-period) and after (post-period) duloxetine initiation were compared. Generalized Estimating Equation models evaluated the pre–post change in the odds of hospitalization.

Results:

Nine hundred and nine patients were identified, 413 had pre-period unexplained pain (UPain). Rates of hospitalization declined from the pre- to the post-period. Fewer UPain patients received analgesics post-duloxetine initiation. Multivariate analyses confirmed that the odds of hospitalization were lower after duloxetine initiation. UPain patients with pre-period anticonvulsant use had lower odds of hospitalization in the post-period and the reduction in odds was significantly larger than that of patients without pre-period anticonvulsants. While patients with pre-period anxiolytic use, alcohol/drug dependence, or sleep disorders did not show statistically significant pre–post change in the odds of hospitalization, these changes were significantly different from patients without these conditions.

Limitations:

The study did not include a comparison group of patients who were non-users of duloxetine. Prevalence of chronic conditions might be under-estimated due to coding in the GPRD. Medications were assumed to be taken as prescribed. Study results are not generalizable beyond the population covered by the UK’s primary care system.

Conclusions:

All-cause hospitalization rates lowered among depressed patients and fewer UPain patients received analgesics post-duloxetine initiation. The reduction in the odds of hospitalization was most pronounced among UPain patients receiving pre-period anticonvulsants.     

Healthcare utilization and costs of veterans health administration patients with schizophrenia treated with paliperidone palmitate long-acting injection or oral atypical antipsychotics

Abstract

Objective:

This study aimed to compare real world healthcare costs and resource utilization between patients with schizophrenia treated with paliperidone palmitate long-acting injection (PP) and oral atypical antipsychotics (OAT).     

Impact of treatment with liposomal bupivacaine on hospital costs,length of stay,and discharge status in patients undergoing total knee arthroplasty at high-use institutions

Aims: Post-surgical pain experienced by patients undergoing total knee arthroplasty (TKA) can be severe. Enhanced recovery after surgery programs incorporating multimodal analgesic regimens have evolved in an attempt to improve patient care while lowering overall costs. This study examined clinical and economic outcomes in hospitals using liposomal bupivacaine (LB) for pain control following TKA.

Methods: This retrospective observational study utilized hospital chargemaster data from the Premier Healthcare Database from January 2011 through April 2017 for the 10 hospitals with the highest number of primary TKA procedures using LB. Within these hospitals, patients undergoing TKA who received LB were propensity-score matched in a 1:1 ratio to a control group not receiving LB. Outcomes included hospital length of stay (LOS), discharge status, 30-day same-hospital readmissions, total hospitalization costs, and opioid consumption; only patients with Medicare or commercial insurance as the primary payer for TKA were considered.

Results: The study population included 20,907 Medicare-insured patients (LB?=?10,411; control =10,496) and 12,505 patients with commercial insurance (LB?=?6,242; control?=?6,263). Overall, LOS was 0.6?days shorter with LB (p?p?P?p?p?Limitations: Costs were estimated using Premier charge-to-cost ratios and limited to goods and services recorded in the chargemaster. Findings from these 10 hospitals may not be representative of other US hospitals.

Conclusions: In a sub-set of 10?US hospitals with the highest use of LB for TKA, LB use was associated with shorter hospital LOS, increased home discharge, lower total hospitalization costs, and decreased opioid use after TKA.     

Impact on health outcome and costs of influenza treatment with oseltamivir in elderly and high-risk patients

Summary

The main objective of this study was to evaluate health outcomes and costs to the healthcare payer of treating influenza with oseltamivir in a high-risk population. Data from published literature, clinical trials and public sources were used to develop a decision-analytic model simulating a high-risk population in the UK. The underlying clinical pathway predicts morbidity and mortality due to influenza, and its specified complications for the two influenza treatment strategies—oseltamivir and usual care. Health outcomes (quality-adjusted life years [QALYs], days to return to normal activity) and costs were estimated for events in the model. Robustness of the results was tested by probabilistic, univariate and multivariate sensitivity analyses.

Treatment with oseltamivir within 48 hours results in reduced morbidity, which translates into faster recovery and return to normal activity. Economic evaluation showed that treatment with oseltamivir in a high-risk population in the UK is a cost-effective strategy in all analysed scenarios with cost-utility ratios between £225 and £17,900 per QALY gained.

Treatment with oseltamivir is effective in terms of health outcome and cost for high-risk patients from the perspectives of the individual patient and healthcare payer.     

Burden of illness for super-refractory status epilepticus patients

Objective: To provide an estimate of the annual number of super-refractory status epilepticus (SRSE) cases in the US and to evaluate utilization of hospital resources by these patients.

Methods: The Premier Hospital Database was utilized to estimate the number of SRSE cases based on hospital discharges during 2012. Discharges were classified as SRSE cases based on an algorithm using seizure-related International Classification of Diseases-9 (ICD-9) codes, Intensive Care Unit (ICU) length of stay (LOS), and treatment protocols (e.g. benzodiazepines, anti-epileptic drugs (AEDs), and ventilator use). Secondary analyses were conducted using more restrictive algorithms for SRSE.

Results: A total of 6,325 hospital discharges were classified as SRSE cases from a total of 5,300,000 hospital discharges. Applying a weighting based on hospital characteristics and 2012?US demographics, this projected to an estimated 41,156 cases of SRSE in the US during 2012, an estimated incidence rate of ～13/100,000 annually for SRSE in the US. Secondary analyses using stricter SRSE algorithms resulted in estimated incidence rates of ～11/100,000 and 8/100,000 annually. The mean LOS for SRSE hospitalizations was 16.5 days (median =11; interquartile range [IQR]?=?6–20), and the mean ICU LOS was 9.3 days (median =6; IQR =3–12). The mean cost of an SRSE hospitalization was $51,247 (median = $33,294; 95% CI = $49,634–$52,861).

Limitations: The analysis uses ICD-9 diagnostic codes and claims information, and there are inherent limitations in any methodology based on treatment protocol, which created challenges in distinguishing with complete accuracy between SRSE, RSE, and SE on the basis of care patterns in the database.

Conclusion: SRSE is associated with high mortality and morbidity, which place a high burden on healthcare resources. Projections based upon the findings of this study suggest an estimated 25,821–41,959 cases of SRSE may occur in the US each year, but more in-depth studies are required.