Budget impact model of tobramycin inhalation solution for treatment of Pseudomonas aeruginosa in cystic fibrosis patients

Abstract

Background:

Pseudomonas aeruginosa (PA) is the most common airway pathogen in cystic fibrosis (CF) patients. The objective of this analysis was to determine the costs of managing PA infection in CF patients with a chronic regimen of tobramycin inhalation solution (TIS).

Methods:

A budget impact model of CF patients was developed to evaluate the costs of TIS from a US managed-care organization (MCO) perspective. The Microsoft Excel model compared TIS treatment plus standard care with standard care alone over a 4-year time horizon and included the cost of drugs, medical care, and annual probabilities of hospitalization and IV anti-pseudomonal (anti-PA) antibiotics administration.

Results:

For an MCO with 5,000,000 members, 389 members 6 years of age or older were estimated to have CF, and 218 (56%) had PA infection. Assuming that use of TIS increased from 20% to 25%, the 1-year budget increased $231,251 or from $0.049 to $0.053 per member per month (PMPM). The net drug budget increase was $243,919, while medical costs associated with exacerbation management decreased $12,669 over the first year. Increasing utilization of TIS, from 20% to 40% over 4 years resulted in an incremental overall budget increase of $925,002, a 3% decrease in hospitalizations, and a 4% decrease in administrations of IV anti-PA antibiotics. These reductions translated to a medical care cost saving of $50,676 over 4 years. Limitations of this study include that the clinical data for the model are from clinical trials conducted in 1996 and the estimation of TIS use for CF patients with chronic PA infections can be impacted by TIS adherence.

Conclusion:

Model results suggest that increasing the use of TIS decreases medical care costs due to decreased hospital admissions and the use of IV anti-PA antibiotics at the expense of higher drug costs.     

Patterns of relapse and associated cost burden in schizophrenia patients receiving atypical antipsychotics

Abstract

Objective:

To identify relapse in schizophrenia and the main cost drivers of relapse using a cost-based algorithm.

Methods:

Multi-state Medicaid data (1997–2010) were used to identify adults with schizophrenia receiving atypical antipsychotics (AP). The first schizophrenia diagnosis following AP initiation was defined as the index date. Relapse episodes were identified based on (1) weeks during the ≥2 years post-index associated with high cost increase from baseline (12 months before the index date) and (2) high absolute weekly cost. A compound score was then calculated based on these two metrics, where the 54% of patients associated with higher cost increase from baseline and higher absolute weekly cost were considered relapsers. Resource use and costs of relapsers during baseline and relapse episodes were compared using incidence rate ratios (IRRs) and bootstrap methods.

Results:

In total, 9793 relapsers were identified with a mean of nine relapse episodes per patient. Duration of relapse episodes decreased over time (mean [median]; first episode: 34 [4] weeks; remaining episodes: 8 [1] weeks). Compared with baseline, resource utilization during relapse episodes was significantly greater in pharmacy, outpatient, and institutional visits (hospitalizations, emergency department visits), with IRRs ranging from 1.9–2.4 (all p?<?0.0001). Correspondingly, relapse was associated with a mean (95% CI) incremental cost increase of $2459 ($2384–$2539) per week, with institutional visits representing 53% of the increase.

Limitations:

Relapsers and relapse episodes were identified using a cost-based algorithm, as opposed to a more clinical definition of relapse. In addition, their identification was based on the assumption from literature that ～54% of schizophrenia patients will experience at least one relapse episode over a 2-year period.

Conclusions:

Significant cost increases were observed with relapse in schizophrenia, driven mainly by institutional visits.     

Economic burden of skeletal-related events in patients with multiple myeloma: analysis of US commercial claims database

Aims: To estimate incremental healthcare resource utilization (HRU) and costs associated with skeletal-related events (SREs) secondary to multiple myeloma (MM), and HRU and cost differences in patients with one vs multiple SREs.

Methods: Adults with MM diagnosis between January 1, 2010–December 31, 2014, with benefits coverage ≥12 months pre- and ≥6 months post-diagnosis were followed to last coverage date or December 31, 2015, excluding patients with prior anti-myeloma treatment or cancers. SREs were identified by diagnosis or procedure codes (pathological fracture, spinal cord compression, radiation, or surgery to the bone). SRE patients (index?=?first post-diagnosis SRE) were propensity score matched 1:1 to patients without SRE (assigned pseudo-index) using baseline characteristics, and ≥1 month of continuous enrollment after index/pseudo-index date was required. Per-patient-per year (PPPY) HRU and costs (2016?US$) were determined for inpatient, outpatient, emergency department (ED), and outpatient pharmacy services during follow-up. Wilcoxon signed rank for means and McNemar’s tests for proportions were used to assess differences. Negative binomial regression and generalized linear regression analyses estimated differences in HRU and costs, respectively, for the comparison of single vs multiple SREs.

Results: Each cohort included 848 patients (mean age?=?61 – 62 years, 57% male) with no significant differences in pre-index demographic or clinical characteristics between matched cohorts. Versus non-SRE patients, SRE patients had significantly higher PPPY use (p?<?.0001) of inpatient hospitalizations, ED visits, outpatient pharmacy, and higher direct medical costs ($188,723 vs $108,160, p?<?.0001). Adjusted PPPY total costs were $209,820 in patients with multiple SREs; $159,797 in patients with one SRE.

Limitations: SRE misclassification and residual confounding are possible.

Conclusions: Among patients with MM, average annual costs were substantially higher in patients with SRE compared with matched non-SRE patients. The economic burden of SRE increased further with multiple events.     

Healthcare resource utilization among patients diagnosed with idiopathic pulmonary fibrosis in the United States

Abstract

Objectives:

Few studies have characterized healthcare resource utilization among patients with idiopathic pulmonary fibrosis. The objective of this study is to assess healthcare resource utilization among patients with idiopathic pulmonary fibrosis as compared to members without this condition.

Methods:

Patients newly diagnosed with idiopathic pulmonary fibrosis were identified from a national administrative claims database (2006–2011) as having ≥2 claims with idiopathic fibrosing alveolitis, or ≥1 claim with idiopathic fibrosing alveolitis and ≥1 claim with post-inflammatory pulmonary fibrosis (earliest claim with idiopathic fibrosing alveolitis denoted the index date), a procedure of lung biopsy or high-resolution computed tomography within ±90 days of the index date, 12-month pre-index continuous enrollment, plus ≥2 confirmatory idiopathic fibrosing alveolitis diagnoses after the procedure. For each idiopathic pulmonary fibrosis patient, three members without the condition were matched by age/gender/region/payer type. Demographic/clinical characteristics were measured during the 1-year pre-index period. Healthcare resource utilization was assessed by quarter during 1-year pre- and post-index periods. Generalized estimating equation models controlling for patient characteristics were constructed to estimate adjusted post-index healthcare resource utilization.

Results:

In total, 1735 patients with idiopathic pulmonary fibrosis and 5205 without (mean age?=?71.5 years; 46.1% female) were included. Adjusted results revealed idiopathic pulmonary fibrosis patients were more likely to use healthcare resources than members without the condition 1-year post-index (number of hospitalizations, emergency room visits, and outpatients visits: 0.63 vs 0.31, 0.62 vs 0.48, and 5.7 vs 3.1 per person-year, respectively).

Conclusions:

Healthcare resource utilization is considerably higher among patients with idiopathic pulmonary fibrosis than members without the condition. Effective treatments for patients with idiopathic pulmonary fibrosis are needed to help reduce burden of healthcare resource use.     

Healthcare utilization and costs in patients with tuberous sclerosiscomplex-related renal angiomyolipoma

Objective: To quantify healthcare utilization and costs in patients with tuberous sclerosis complex (TSC) and renal angiomyolipoma (AML) in a matched cohort of patients without TSC or AML.

Methods: Administrative data from the MarketScan Research Databases were used to select patients with TSC and renal AML during January 1, 2000–March 31, 2013 from the Commercial database and January 1, 2000–June 30, 2012 from the Medicaid database. Patients were required to have at least 30 days of follow-up from initiation into the study, and were followed until inpatient death, end of insurance coverage, or the end of study. Age, calendar year, and payer-matched controls that had no TSC and no AML were selected. All-cause annualized healthcare utilization and costs were calculated by service category.

Results: A total of 218 patients under 18 years and 377 patients 18 years and older with TSC-renal AML were selected from the Commercial database, and matched to 654 and 1,131 controls, respectively. Thirty-eight patients under 18 years and 110 patients 18 years or older with TSC-renal AML were selected from the Medicaid database, and matched to 54 and 212 controls, respectively. Within the Commercial cohort, and across both age groups, TSC-renal AML patients utilized more healthcare services than their matched controls. Within the Medicaid cohort, in both age groups, utilization was higher in TSC-renal AML patients vs control patients for inpatient admissions, emergency room visits, physician office visits, and hospital-based outpatient visits. Across age groups and in both the Commercial and Medicaid cohorts, the annual average total costs were significantly higher in TSC-renal AML patients compared to control patients (p?Conclusions: Compared to controls, TSC-renal AML patients incurred substantially higher annual healthcare utilization and costs.     

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.     

Healthcare resource utilization among patients with relapsed multiple myeloma in the UK,France, and Italy

Aims: To assess the real-world healthcare resource utilization (HRU) and costs associated with different treatment regimens used in the management of patients with relapsed multiple myeloma in the UK, France, and Italy.

Methods: Retrospective medical chart review of characteristics, time to progression, level of response, HRU during treatment, and adverse events (AEs). Data collection started on June 1, 2015 and was completed on July 15, 2015. In the 3 months before record abstraction, eligible patients had either disease progression after receiving one of their country’s most commonly prescribed regimens or had received the best supportive care and died. Costs were calculated based on HRU and country-specific diagnosis-related group and/or unit reference costs, amongst other standard resources.

Results: Physicians provided data for 1,282 patients (387 in the UK, 502 in France, 393 in Italy) who met the inclusion criteria. Mean [median] total healthcare costs associated with a single line of treatment were €51,717 [35,951] in the UK, €37,009 [32,538] for France, and €34,496 [42,342] for Italy, driven largely by anti-myeloma medications costs (contributing 95.0%, 90.0%, and 94.2% of total cost, respectively). During active treatment, the highest costs were associated with lenalidomide- and pomalidomide-based regimens. Mean cost per month was lowest for patients achieving a very good partial response or better. Unscheduled events (i.e. not considered part of routine management, whether or not related to multiple myeloma, such as unscheduled hospitalization, AEs, fractures) accounted for 1–9% of total costs and were highest for bendamustine.

Limitations: The use of retrospective data means that clinical practice (e.g. use of medical procedures, evaluation of treatment response) is not standardized across participating countries/centers, and some data (e.g. low-grade AEs) may be incomplete or differently adjudicated/reported. The centers involved may not be fully representative of national practice.

Conclusions: Drug costs are the main contributor to total HRU costs associated with multiple myeloma. The duration of active treatment may influence the average total costs, as well as response, associated with a single line of therapy. Improved treatment outcomes, and reductions in unscheduled events and concomitant medication use may, therefore, reduce the overall HRU and related costs of care in multiple myeloma.     

Economic burden and healthcare utilization associated with castration-resistant prostate cancer in a commercial and Medicare Advantage US patient population

Objective: Prostate cancer is a leading cause of cancer death in men in the US. Castration-resistant prostate cancer (CRPC) is an advanced form of the disease and has a poor prognosis and limited treatment options. The objective of this study was to identify patients with CRPC from a medical claims database, and determine the prostate cancer-related economic burden and healthcare utilization of these patients.

Methods: This was a retrospective study using claims and enrollment information from a large US database linkable to laboratory data. Male patients aged 40 or older who were diagnosed with prostate cancer and received surgical or medical castration between July 1, 2001 and December 1, 2007 were considered for study inclusion. Patients with CRPC were initially identified based on at least two increases in prostrate-specific antigen (PSA) values. Due to the small number of patients with available PSA results data, logistic regression modeling using characteristics of patients with known CRPC was used to identify a larger set of patients with likely CRPC. Per-patient per-month healthcare utilization and costs were determined using medical and pharmacy claims data.

Results: The final sample of patients with likely CRPC as determined by regression modeling included 349 patients with known CRPC identified from the database on the basis of PSA results and an additional 2391 with likely CRPC. Within this final sample of 2740 CRPC patients, there was a per-patient per-month average of 1.43 prostate cancer-related ambulatory visits, 0.04 prostate cancer-related inpatient stays, and 0.01 prostate cancer-related ER visits. Average per-patient per-month prostate cancer-related costs were $1152 (SD = $2073) for ambulatory visits, $559 (SD = $2383) for inpatient stays, $72 (SD = $229) for pharmacy costs, and $1 (SD = $14) for ER visits. Total per-patient per-month prostate cancer-related costs were on average $1799 (SD = $3505), and these costs comprised about half of the all-cause healthcare costs for these patients.

Conclusions: CRPC is a costly disease, with ambulatory visits and inpatient care accounting for a substantial proportion of the economic burden. Limitations related to the use of retrospective claims data should be considered when interpreting these results.     

The economic burden of brain metastasis among lung cancer patients in the United States

Objective:

Brain metastases among lung cancer patients can impair cognitive and functional ability, complicate care, and reduce survival. This study focuses on the economic burden of brain metastasis in lung cancer—direct healthcare costs to payers and indirect costs to patients, payers, and employers—in the US.

Methods:

Retrospective study using claims data from over 60 self-insured Fortune 500 companies across all US census regions (January 1999–March 2013). Adult, non-elderly lung cancer patients with brain metastasis were evaluated over two study periods: (1) pre-diagnosis (≤30 days prior to first observed lung cancer diagnosis to ≤30 days prior to first-observed brain metastasis diagnosis) and (2) post-diagnosis (≤30 days prior to first observed brain metastasis diagnosis to end of continuous eligibility or observation).

Outcome measures:

Healthcare costs to payers and resource utilization, salary loss to patients, disability payouts for payers, and productivity loss to employers.

Results:

A total of 132 patients were followed for a median of 8.4 and 6.6 months in the pre- and post-diagnosis periods, respectively. At diagnosis of brain metastasis, 21.2% of patients were on leave of absence and 6.1% on long-term disability leave. Substantial differences were observed in the pre- vs post-diagnosis periods. Specifically, patients incurred much greater healthcare utilization in the post-diagnosis period, resulting in $25,579 higher medical costs per-patient-per-6-months (PPP6M). During this period, patients missed significantly more work days, generating an incremental burden of $2853 PPP6M in salary loss for patients, $2557 PPP6M in disability payments for payers, and $4570 PPP6M in productivity loss for employers.

Limitations:

Type of primary lung cancer and extent of brain metastasis could not be assessed in the data. The analysis was also limited to patients with comprehensive disability coverage.

Conclusions:

Development of brain metastasis among lung cancer patients is associated with a substantial economic burden to payers, patients, and employers.     

Economic impact of using inhaled corticosteroids without prior exacerbation among elderly patients with chronic obstructive pulmonary disorder

Abstract

Objective:

To assess the economic impact of initiating inhaled corticosteroids (ICS) without evidence of prior exacerbation among elderly patients with chronic obstructive pulmonary disease (COPD) in the US.

Methods:

This retrospective study used administrative claims to identify newly diagnosed COPD patients between 1/1/2005 and 6/30/2006 who were dispensed ICS. The dispense date of the first ICS was set as the index date. Patients with prior diagnoses for asthma, cystic fibrosis, or lung cancer were excluded. Cohorts were constructed based on whether ICS therapy was concordant with recommended guidelines of having prior COPD exacerbation. Each COPD patient with prior exacerbation was matched to four patients without exacerbation based on age, gender, Charlson Comorbidity Index, and whether COPD diagnosis code was not elsewhere specified (i.e., 496). Multivariate regressions were estimated to assess the association between use of ICS therapy without prior exacerbation and total healthcare costs, controlling for demographics and clinical characteristics.

Results:

The study included 3650 patients: 730 with prior exacerbation and 2920 without prior exacerbation. Patients were 76 years of age and 54% were male. Those with prior exacerbation were more likely to have inpatient stays both prior to (74.4 vs. 44.1%, p?<?0.05) and following (37.0 vs. 33.1%, p?<?0.05) the index date. Controlling for patient characteristics, patients who were dispensed ICS without prior exacerbation had $1859 higher in total costs (p?<?0.05) compared to patients with prior exacerbation during the 12 months following ICS initiation.

Limitations:

The retrospective design of this study limits the interpretation of findings as association and not causality. This study is subject to selection bias due to unobservable confounders.

Conclusions:

Among COPD patients, initiation of ICS without prior exacerbation appears to be associated with increased healthcare costs. These findings suggest that ICS initiation without evidence of exacerbation as consistent with guidelines is associated with adverse economic consequences.     

Economic burden of venous thromboembolism: a systematic review

Abstract

Objective:

Deep vein thrombosis and pulmonary embolism – together referred to as venous thromboembolism (VTE) – result in a major burden on healthcare systems. However, to the authors’ knowledge no comprehensive review of the economic burden of VTE has so far been published.

Methods:

A literature search was carried out to identify references published in English since 1997 using Medline, the Cochrane Library and the Health Economic Evaluations Database. The primary outcomes of interest were ‘all-cause’ VTE and VTE after major orthopedic surgery.

Results:

A total of 1,037 full research articles and abstracts were screened for inclusion in the review. Of these, ten cost-of-illness studies were identified that met the inclusion criteria and are included in the current review. The results of large US database analyses vary, indicating costs of the initial VTE of approximately US$3,000–9,500. The total costs related to VTE over 3 months (US$5,000), 6 months (US$10,000) and 1 year (US$33,000) were considerable. Studies conducted in the European Union indicate lower additional inpatient costs after VTE of €1,800 after 3 months and €3,200 after 1 year, which still represent a considerable impact on healthcare systems. Complications after VTE can be very expensive, with estimates of the additional cost of treating the post-thrombotic syndrome ranging from $426 to $11,700 and heparin-induced thrombocytopenia from $3,118 to $41,133. A limitation of studies using older data is that recent changes in the treatment of VTE may affect the generalizability of these findings.

Conclusions:

Complications associated with VTE are frequent and costly. In particular, the cost of complications resulting from prophylaxis and treatment of VTE, such as post-thrombotic syndrome and heparin-induced thrombocytopenia, had a considerable economic impact.     

Economic outcomes with prasugrel versus clopidogrel in acute coronary syndrome patients: observations from prasugrel users and matched clopidogrel users

Abstract

Objective:

To compare healthcare costs between clopidogrel and prasugrel over 30-day and 365-day periods after discharge from the hospital or emergency room (ER) in patients treated with prasugrel who were hospitalized or had an ER visit for an acute coronary syndrome (ACS) event.     

Adherence to iron chelation therapy and associated healthcare resource utilization and costs in Medicaid patients with sickle cell disease and thalassemia

Background:

Sub-optimal patient adherence to iron chelation therapy (ICT) may impact patient outcomes and increase cost of care. This study evaluated the economic burden of ICT non-adherence in patients with sickle cell disease (SCD) or thalassemia.

Methods:

Patients with SCD or thalassemia were identified from six state Medicaid programs (1997–2013). Adherence was estimated using the medication possession ratio (MPR) of ≥0.80. All-cause and disease-specific resource utilization per-patient-per-month (PPPM) was assessed and compared between adherent and non-adherent patients using adjusted incidence rate ratios (aIRR). All-cause and disease-specific healthcare costs were computed using mean cost PPPM. Regression models adjusting for baseline characteristics were used to compare adherent and non-adherent patients.

Results:

A total of 728 eligible patients treated with ICT in the SCD cohort, 461 (63%) adherent, and 218 in the thalassemia cohort, 137 (63%) adherent, were included in this study. In SCD patients, the adjusted rate of all-cause outpatient visits PPPM was higher in adherent patients vs non-adherent patients (aIRR [95% CI]: 1.05 [1.01–1.08], p?<?0.0001). Conversely, adherent patients incurred fewer all-cause inpatients visits (0.87 [0.81–0.94], p?<?0.001) and ER visits (0.86 [0.78–0.93], p?<?0.001). Similar trends were observed in SCD-related resource utilization rates and in thalassemia patients. Total all-cause costs were similar between adherent and non-adherent patients, but inpatient costs (adjusted cost difference?=??$1530 PPPM, p?=?0.0360) were lower in adherent patients.

Conclusion:

Patients adherent to ICT had less acute care need and lower inpatient costs than non-adherent patients, although they had more outpatient visits. Improved adherence may be linked to better disease monitoring and has the potential to avoid important downstream costs associated with acute care visits and reduce the financial burden on health programs and managed care plans treating SCD and thalassemia patients.     

Switching of biologic disease modifying anti-rheumatic drugs in patients with rheumatoid arthritis in a real world setting

Objectives:

This study examined total healthcare costs and rates of patients with rheumatoid arthritis (RA) who switch biologic disease-modifying anti-rheumatic drug (bDMARD) therapy in a real world setting.

Methods:

A retrospective longitudinal analysis was conducted in patients with RA using IMS PharMetrics Plus database from 1/1/2004 to 3/31/2010. The first-line cohort included patients newly initiated on abatacept or the tumor necrosis factor-alpha inhibitors (anti-TNFs) adalimumab, etanercept, or infliximab, with 12 months of continuous follow-up. The second-line cohort included patients initiating a bDMARD with evidence of a different bDMARD within the previous 2 years and with 12 months of continuous follow-up. Switching was defined as a different bDMARD claim within a 200% gap in days supply from the previous bDMARD claim. Non-switchers stayed on their bDMARD in the follow-up period. Monthly total healthcare costs for switchers and non-switchers and rates of bDMARD switching were examined. Switch rates for each bDMARD were also compared.

Results:

First-line switchers had significantly higher monthly total healthcare costs after the switch than non-switchers ($3759 vs $2343; p?p?Limitations:

There are no clinical data available in this database and, therefore, this study did not examine the clinical drivers of healthcare costs and switch rates.

Conclusions:

Monthly total healthcare costs were higher for bDMARD switchers following the switch compared to non-switchers. Patients on abatacept switched less frequently than patients on anti-TNFs. This study highlights the need to identify patients who are likely to switch in order to ensure they receive the appropriate therapy which may improve outcomes and decrease healthcare costs.