Retrospective evaluation of the clinical benefit of long-term continuous use of zoledronic acid in patients with lung cancer and bone metastases

Abstract

Background:

For patients with bone metastases, skeletal-related events including fracture are common, can cause considerable morbidity, and may reduce overall survival (OS). This retrospective analysis assessed the effect of Zometa (zoledronic acid, ZOL), an intravenous bisphosphonate (IV-BP), on fracture risk and OS in patients with bone metastases from lung cancer (LC). (Zometa is a registered trademark of Novartis Pharmaceuticals Corporation, USA.)

Methods:

A claims-based analysis using commercial and Medicare Advantage data from >45 US managed-care plans was used to evaluate the association between fracture risk and treatment persistency (31–90, 91–180, 181–365, and ≥366 days) and follow-up duration in LC patients diagnosed with bone metastases between 01/01/2001 and 12/31/2006 and treated with ZOL or without (no IV-BP). Persistency was defined as the absence of a >45-day gap between ZOL treatments. Analysis of variance tests were used to compare follow-up duration, a proxy for OS, between ZOL persistency groups. The effect of time to treatment with ZOL was also assessed.

Results:

In 9874 LC patients with bone metastases (n?=?1090 ZOL; n?=?8784 no IV-BP) the unadjusted relative fracture risk was reduced by 40% with ZOL vs no IV-BP; fracture risk decreased consistently with increasing duration of ZOL treatment. Even short-term (31–90 days) ZOL significantly reduced fracture risk (47%) vs no IV-BP (p?=?0.005) with adjustment for differences in demographic and clinical characteristics. Delaying ZOL until after bone metastases were diagnosed significantly increased fracture risk (p?=?0.0017). For a sub-set of patients included in a survival analysis (n?=?550 ZOL; n?=?4512 no IV-BP), mortality was significantly lower (mean, 38.6 vs 46.8 deaths/100 person-years; p?=?0.038) in those treated with ZOL vs no IV-BP.

Limitations:

Interpretation of this claims-based analysis must be tempered by the inherent limitations of observational data, such as limited clinical information and the ability to control for prognostic factors.

Conclusions:

This retrospective analysis demonstrates that LC patients with bone metastases receiving ZOL had significantly reduced risk of fracture (p?=?0.005) and death (p?<?0.038) vs patients receiving no IV-BP. Longer ZOL persistency consistently yielded better outcomes, with ≥12 months’ treatment producing the greatest benefit.     

Assessment of zoledronic acid treatment patterns and clinical outcomes in patients with bone metastases from genitourinary cancers

Abstract

Background:

Patients with bone metastases secondary to genitourinary (GU) cancer are at risk for skeletal-related events (SREs), including bone pain requiring palliative radiotherapy, fractures or surgery to bone, spinal cord compression, and hypercalcemia of malignancy. These SREs can be debilitating and potentially life-limiting. This study examined treatment practices and the association of treatment patterns with Zometa (zoledronic acid, ZOL), an intravenous bisphosphonate (IV-BP), with SREs and fractures. (Zometa is a registered trademark of Novartis Pharmaceuticals Corporation, USA.)

Methods:

Retrospective analysis of commercial and Medicare Advantage enrollment and medical claims data was performed to evaluate IV-BP use and SRE patterns in adult patients with GU cancers. Criteria included diagnosis of ≥1 bone metastasis and prostate cancer (PC), renal cell carcinoma (RCC), or bladder cancer (BlC) between January 2001 and December 2006; continuous healthcare plan enrollment for ≥6 months before the index date; and no evidence of prior IV-BP use. Patients were followed until disenrollment from the healthcare plan or December 2007.

Results:

Of 6347 patients (PC, n?=?4976; RCC, n?=?941; BlC, n?=?430; mean [standard deviation] age: 68.9 [11.1] years), only ～23% received ZOL. The mean time between diagnosis of bone metastasis and ZOL initiation was ～108 days. Among patients with PC, fracture risk was significantly smaller for ZOL vs no IV-BP (incidence rate ratio?=?0.70; p?<?0.001), and 2-year survival was significantly longer for ZOL-treated vs no IV-BP patients (p?=?0.007). Patients with longer persistency on ZOL had a smaller fracture risk than patients with shorter persistency. Sub-set analyses were not performed for RCC and BIC because the proportion of patients treated was too low.

Limitations:

Interpretation of this claims-based analysis must be tempered by the inherent limitations of observational data, such as limited and accurate available information, and unavailable information including clinical or disease-specific parameters.

Conclusions:

Intravenous BP therapy is not always received in patients with bone metastases secondary to GU cancers, and, when used, there are typically long time periods before treatment initiation. Without IV-BPs, PC patients have significantly larger risks of fracture and death compared with ZOL-treated patients, and benefits appear to be larger with increasing persistency on ZOL.     

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.     

Cost of skeletal complications from bone metastases in six European countries

Objective Patients with bone metastases or lesions secondary to solid tumors or multiple myeloma often experience bone complications (skeletal-related events [SREs]—radiation to bone, pathologic fracture, surgery to bone, and spinal cord compression); however, recent data that can be used to assess the value of treatments to prevent SREs across European countries are limited. This study aimed to provide estimates of health resource utilization (HRU) and cost associated with all SRE types in Europe. HRU data were reported previously; cost data are reported herein.

Methods Eligible patients from 49 centers across Austria (n?=?57), the Czech Republic (n?=?59), Finland (n?=?60), Greece (n?=?59), Portugal (n?=?59), and Sweden (n?=?62) had bone metastases or lesions secondary to breast, lung, or prostate cancer, or multiple myeloma, and ≥1 index SRE (a SRE preceded by a SRE-free period of ≥?6.5 months). SRE-related costs were estimated from a payer perspective using health resource utilization data from patient charts (before and after the index SRE diagnosis). Country-specific unit costs were from 2010 and local currencies were converted to 2010 euros.

Results The mean costs across countries were €7043, €5242, €11,101, and €11,509 per radiation to bone, pathologic fracture, surgery to bone, and spinal cord compression event, respectively. Purchasing power parity (PPP)-adjusted mean cost ratios were similar in most countries, with the exception of radiation to bone.

Limitations The overall burden of SREs may have been under-estimated owing to home visits and evaluations outside the hospital setting not being reported here.

Conclusions All SREs were associated with substantial costs. Variation in SRE-associated costs between countries was most likely driven by differences in treatment practices and unit costs.     

Cost effectiveness of zoledronic acid in the management of skeletal metastases in hormone-refractory prostate cancer patients in France,Germany, Portugal,and the Netherlands

Abstract

Objective:

Zoledronic acid (ZOL) reduces the risk of skeletal related events (SREs) in hormone-refractory prostate cancer (HRPC) patients with bone metastases. This study assessed the cost effectiveness of ZOL for SRE management in French, German, Portuguese, and Dutch HRPC patients.

Methods:

This analysis was based on the results of a randomized phase III clinical trial wherein HRPC patients received up to 15 months of ZOL (n?=?214) or placebo (n?=?208). Clinical inputs were obtained from the trial. Costs were estimated using hospital tariffs, published, and internet sources. Quality adjusted life-years (QALYs) gained were estimated from a separate analysis of EQ-5D scores reported in the trial. Uncertainty surrounding outcomes was addressed via univariate sensitivity analyses.

Results:

ZOL patients experienced an estimated 0.759 fewer SREs and gained an estimated 0.03566 QALYs versus placebo patients. ZOL was associated with reduced SRE-related costs [net costs] (?€2396 [€1284] in France, ?€2606 [€841] in Germany, ?€3326 [€309] in Portugal and ?€3617 [€87] in the Netherlands). Costs per QALY ranged from €2430 (Netherlands) to €36,007 (France).

Conclusions:

This analysis is subject to the limitations of most cost-effectiveness analyses: it combines data from multiple sources. Nevertheless, the results strongly suggest that ZOL is cost effective versus placebo in French, German, Portuguese, and Dutch HRPC patients.     

Cost-effectiveness of denosumab vs zoledronic acid for prevention of skeletal-related events in patients with solid tumors and bone metastases in the United States

Abstract

Objective:

With increasing healthcare resource constraints, it has become important to understand the incremental cost-effectiveness of new medicines. Subcutaneous denosumab is superior to intravenous zoledronic acid (ZA) for the prevention of skeletal-related events (SREs) in patients with advanced solid tumors and bone metastases. This study sought to determine the lifetime cost-effectiveness of denosumab vs ZA in this setting, from a US managed-care perspective.

Methods:

A lifetime Markov model was developed, with relative rate reductions in SREs for denosumab vs ZA derived from three pivotal Phase 3 trials involving patients with castration-resistant prostate cancer (CRPC), breast cancer, and non-small-cell lung cancer (NSCLC), and bone metastases. The real-world SRE rates in ZA-treated patients were derived from a large commercial database. SRE and treatment administration quality-adjusted life year (QALY) decrements were estimated with time-trade-off studies. SRE costs were estimated from a nationally representative commercial claims database. Drug, drug administration, and renal monitoring costs were included. Costs and QALYs were discounted at 3% annually. One-way and probabilistic sensitivity analyses were conducted.

Results:

Across tumor types, denosumab was associated with a reduced number of SREs, increased QALYs, and increased lifetime total costs vs ZA. The costs per QALY gained for denosumab vs ZA in CRPC, breast cancer, and NSCLC were $49,405, $78,915, and $67,931, respectively, commonly considered good value in the US. Costs per SRE avoided were $8567, $13,557, and $10,513, respectively. Results were sensitive to drug costs and SRE rates.

Limitations:

Differences in pain severity and analgesic use favoring denosumab over ZA were not captured. Mortality was extrapolated from fitted generalized gamma function beyond the trial duration.

Conclusion:

Denosumab is a cost-effective treatment option for the prevention of SREs in patients with advanced solid tumors and bone metastases compared to ZA. The overall value of denosumab is based on superior efficacy, favorable safety, and more efficient administration.     

Short-term disability in solid tumor patients with bone metastases and skeletal-related events

Abstract

Objective:

The skeleton is a common site of metastasis in patients with solid tumors. These patients often experience pain and reduced quality-of-life. This analysis evaluated the time and costs associated with short-term disability use among solid tumor patients with bone metastases (BM) and skeletal-related events (SREs).

Methods:

Data from patients 18–64 years old with solid tumors and BM, eligible for short-term disability benefits between January 1, 2002 and December 31, 2010, were extracted from MarketScan Research Databases. Short-term disability hours and costs associated with BM and SREs were evaluated.

Results:

Overall, 1098 patients met the criteria. For all patients with BM, the monthly mean short-term disability hours were 17.7?h pre-BM diagnosis and increased to 60.2?h post-BM diagnosis (p?<?0.001). The corresponding mean monthly short-term disability costs were $277 and $963 in the pre- and post-BM diagnosis periods, respectively (p?<?0.001). Monthly mean short-term disability hours were higher for the cohort of patients with SREs (21.2?h pre-SRE diagnosis and 67.4?h post-SRE diagnosis) than for those without an SRE (8.6?h pre-SRE diagnosis and 14.4?h post-SRE diagnosis) (p?<?0.001). Similarly, the corresponding monthly mean short-term disability costs were higher for patients with SREs ($625 and $1259 pre- and post-SRE diagnosis, respectively) than for patients without an SRE ($452 and $612 pre- and post-SRE diagnosis, respectively) (p?<?0.001). Results of a multivariate analysis indicated that SREs were associated with an additional 39.4 short-term disability hours and $613 in short-term disability costs per month (p?<?0.001).

>Conclusion:

Short-term disability hours and costs increased significantly when patients with solid tumors developed BM and SRE.     

Cost of skeletal-related events in European patients with solid tumours and bone metastases: data from a prospective multinational observational study

Abstract

Objectives:

Patients with bone metastases often experience skeletal-related events (SREs: radiation or surgery to bone, pathologic fracture, and spinal cord compression). This study examined health resource utilization and costs associated with SREs.

Methods:

Data presented are from the European cohort (Germany, Italy, Spain, and the UK) of patients with solid tumours enrolled in a multi-national, prospective, observational study in patients with solid tumours or multiple myeloma. Patients with Eastern Cooperative Oncology Group score 0–2 and life expectancy ≥6 months, who experienced an SRE up to 97 days before enrolment, were eligible. Health resource utilization associated with SREs (including number/length of inpatient stays, numbers of procedures and outpatient visits) were collected through chart review for up to 97 days before enrolment and prospectively during follow-up. Country-specific cost calculations were performed.

Results:

In total, 478 eligible patients contributed 893 SREs to this analysis. Radiation to bone occurred most frequently (66% of total). Spinal cord compression (7%) and surgery to bone (10%) were the least common events, but most likely to require inpatient stays. The most costly SREs were also spinal cord compression (mean per SRE across countries, €4884–€12,082) and surgery to bone (€3348–€9407). Inpatient stays were the main cost drivers.

Limitations:

Health resource utilization used to calculate the costs associated with SREs may have been under-estimated as a result of exclusion of patients with low performance status or life expectancy; unavailable information and exclusion of resource consumption associated with pain. Thus, the estimate of associated costs is likely to be conservative.

Conclusions:

SREs result in considerable health resource utilization, imposing a substantial financial burden driven by inpatient stays. Treatments that prevent/delay SREs may help ease this burden, thereby providing cost savings across European healthcare systems.     

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.     

Cost-effectiveness of zoledronic acid vs clodronic acid for newly-diagnosed multiple myeloma from the United Kingdom healthcare system perspective

Abstract

Objective:

In the Medical Research Council Myeloma IX Study (MMIX), zoledronic acid (ZOL) 4?mg 3–4/week reduced the incidence of skeletal-related events (SREs), increased progression free survival (PFS), and prolonged overall survival (OS), compared with clodronic acid (CLO) 1600?mg daily, in 1970 patients with newly-diagnosed multiple myeloma (MM).

Methods:

An economic model was used to project PFS, OS, the incidence of SREs and adverse events and expected lifetime healthcare costs for patients with newly-diagnosed MM who are alternatively assumed to receive ZOL or CLO. The incremental cost-effectiveness ratio [ICER] of ZOL vs CLO was calculated as the ratio of the difference in cost to the difference in quality-adjusted life years (QALYs). Model inputs were based on results of MMIX and published sources.

Results:

Compared with CLO, treatment with ZOL increases QALYs by 0.30 at an additional cost of £1653, yielding an ICER of £5443 per QALY gained. If the threshold ICER is £20,000 per QALY, the estimated probability that ZOL is cost-effective is 90%.

Limitations:

The main limitation of this study is the lack of data on the effects of zoledronic acid on survival beyond the end of follow-up in the MMIX trial. However, cost-effectiveness was favourable even under the highly conservative scenario in which the timeframe of the model was limited to 5 years.

Conclusions:

Compared with clodronic acid, zoledronic acid represents a cost-effective treatment alternative in patients with multiple myeloma.     

Cost-effectiveness of denosumab versus zoledronic acid for preventing skeletal-related events in the Czech Republic

Aims: This study assessed the cost-effectiveness of the subcutaneous RANKL inhibitor, denosumab, vs the intravenous bisphosphonate, zoledronic acid, for the prevention of skeletal-related events (SREs) in patients with prostate cancer, breast cancer, and other solid tumors (OST) in the Czech Republic.

Materials and methods: A lifetime Markov model was developed to compare the effects of denosumab and zoledronic acid on costs (including drug costs and administration, patient management, SREs, and adverse events), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios from a national payer perspective. Different discount rates, time horizons, SRE rates, distributions, and nature (asymptomatic vs all SREs), and the inclusion of treatment discontinuation were considered in scenario analyses. The robustness of the model was tested using deterministic and probabilistic sensitivity analyses.

Results: Across tumor types, denosumab was associated with fewer SREs, improved QALYs, and higher total costs over a lifetime. The incremental cost per QALY gained for denosumab vs zoledronic acid was 382,673 CZK for prostate cancer, 408,450 CZK for breast cancer, and 608,133 CZK for OST. Incremental costs per SRE avoided for the same tumor type were 54,007 CZK, 51,765 CZK, and 94,426 CZK, respectively. In scenario analyses, the results remained similar to baseline, when different discount rates and time horizons were considered. At a non-official willingness-to-pay threshold of 1.2 million CZK, the probabilities of denosumab being cost-effective vs zoledronic acid were 0.64, 0.67, and 0.49 for prostate cancer, breast cancer, and OST, respectively.

Limitations: The SRE rates used were obtained from clinical trials; studies suggest rates may be higher in clinical practice. Additional evidence on real-world SRE rates could further improve the accuracy of the modeling.

Conclusions: Compared with zoledronic acid, denosumab provides a cost-effective treatment option for the prevention of SREs in patients with prostate cancer, breast cancer, and OST in the Czech Republic.     

Corroboration of claims algorithm for second-line costs of metastatic colorectal cancer treatment with targeted agents

Abstract

Objective:

To refine a claims algorithm for identifying second-line systemic regimens for metastatic colorectal cancer (mCRC) based on clinical evidence and to compare costs during second-line treatment by targeted therapy administered.

Methods:

This retrospective analysis of a large US managed care database identified patients diagnosed with mCRC during 1 July 2007–30 June 2011. A claims-based algorithm was developed to identify patients with at least two lines of therapy (LOT) and the second LOT contained one targeted agent: bevacizumab or any anti-epidermal growth factor receptor (EGFR). Medical chart data from 92 patients were used to corroborate and refine the LOT algorithm. The positive predictive value (PPV) of the initial algorithm and refined algorithm for identification of second LOT are presented. The final algorithm was applied to claims data and two mutually exclusive second-line cohorts were examined: patients with bevacizumab- or cetuximab-containing regimens. Second-line healthcare costs were analyzed with generalized linear models adjusted for demographic and clinical characteristics.

Results:

The PPV increased from 50.0% (95% CI?=?39.4–60.6) for the initial algorithm to 72.1% (95% CI?=?59.2–82.9) for the final algorithm. Mean age in the cohorts (n?=?569) was 61 years; 58% were men. Days of therapy were similar for the bevacizumab (n?=?450) vs cetuximab (n?=?119) cohorts, respectively: 131 vs 148 in first LOT and 123 (both cohorts) in second LOT (p?≥?0.27). Total costs during second-line treatment in the bevacizumab cohort were lower by $12,318 (p?=?0.02) and medical costs were lower by $13,809 (p?=?0.01). Monthly total and medical costs were lower by $2728 (p?=?0.03) and $3133 (p?=?0.01), respectively. Results are based on commercially or Medicare-insured patients and may not be generalizable to Medicaid or uninsured patients.

Conclusions:

Corroboration of claim-based algorithms with medical chart data improved algorithm performance. Second-line total and medical costs were lower for mCRC patients treated with bevacizumab compared with cetuximab.     

Real-world utilization of molecular diagnostic testing and matched drug therapies in the treatment of metastatic cancers

Aims: To assess the frequency of biopsies and molecular diagnostic testing (human DNA/RNA analysis), anti-cancer drug use (genomically-matched targeted therapy [GMTT], unmatched targeted therapy [UTT], endocrine therapy [ET], and chemotherapy [CT]), and medical service costs among adults with metastatic cancer.

Methods: Adults diagnosed with metastatic breast, non-small cell lung (NSCLC), colorectal, head and neck, ovarian, and uterine cancer (2010Q1–2015Q1) were identified in the OptumHealth Care Solutions claims database and followed from first metastatic diagnosis for ≥1 month and until the end of data availability. Utilization was assessed for each cancer cohort (all and patients aged ≥65 years); per-patient-per-month (PPPM) medical service costs were assessed for all patients. Testing frequency estimates were applied to Surveillance, Epidemiology, and End Results Program data to estimate the number of untested patients (2010–2014).

Results: Patients with metastatic cancer (n?=?8,193; breast [n?=?3,414], NSCLC [n?=?2,231], colorectal [n?=?1,611], head and neck [n?=?511], ovarian [n?=?275], and uterine [n?=?151]) were 63 years old (mean), with 11.1–22.2 months of observation. Biopsy and molecular diagnostic testing frequencies ranged from 7% (uterine) to 73% (ovarian), and from 34% (head and neck) to 52% (breast), respectively. Few were treated with GMTT (breast, 11%; NSCLC, 9%; colorectal, 6%). Treatment with UTT ranged from 0.7% (uterine) to 21% (colorectal). Biopsy, diagnostic testing, and anti-cancer drug therapy were less frequent for those ≥65 years. Medical service costs (PPPM, mean) ranged from $6,618 (head and neck) to $9,940 (ovarian). The estimated number of untested new patients with metastatic cancer was 636,369 (all) and 341,397 (≥65).

Limitations: In addition to the limitations of claims analyses, diagnostic testing frequency may be under-estimated if patients underwent testing prior to study inclusion.

Conclusions: The low frequency of molecular diagnostic testing suggests there are opportunities to better inform management of patients with advanced cancer, particularly decisions to treat with GMTT.     

A cost-effectiveness analysis of denosumab for the prevention of skeletal-related events in patients with multiple myeloma in the United States of America

Objective: A large, pivotal, phase 3 trial in patients with newly diagnosed multiple myeloma (MM) demonstrated that denosumab, compared with zoledronic acid, was non-inferior for the prevention of skeletal-related events (SREs), extended the observed median progression-free survival (PFS) by 10.7 months, and showed significantly less renal toxicity. The cost-effectiveness of denosumab vs zoledronic acid in MM in the US was assessed from societal and payer perspectives.

Methods: The XGEVA Global Economic Model was developed by integrating data from the phase 3 trial comparing the efficacy of denosumab with zoledronic acid for the prevention of SREs in MM. SRE rates were adjusted to reflect the real-world incidence. The model included utility decrements for SREs, administration, serious adverse events (SAEs), and disease progression. Drug, administration, SRE management, SAEs, and anti-MM treatment costs were based on data from published studies. For the societal perspective, the model additionally included SRE-related direct non-medical costs and indirect costs. The net monetary benefit (NMB) was calculated using a willingness-to-pay threshold of US$150,000. One-way deterministic and probabilistic sensitivity analyses were conducted.

Results: From a societal perspective, compared with zoledronic acid, the use of denosumab resulted in an incremental cost of US$26,329 and an incremental quality-adjusted life-year (QALY) of 0.2439, translating into a cost per QALY gained of US$107,939 and a NMB of US$10,259 in favor of denosumab. Results were sensitive to SRE rates and PFS parameters.

Limitations: Costs were estimated from multiple sources, which varied by tumor type, patient population, country, and other parameters. PFS and overall survival were extrapolated beyond the follow-up of the primary analysis using fitted parametric curves.

Conclusion: Denosumab’s efficacy in delaying or preventing SREs, potential to improve PFS, and lack of renal toxicity make it a cost-effective option for the prevention of SREs in MM compared with zoledronic acid.     

Indirect costs associated with metastatic breast cancer

Abstract

Objective:

To compare the indirect costs of productivity loss between metastatic breast cancer (MBC) and early stage breast cancer (EBC) patients, as well as their respective family members.

Methods:

The MarketScan® Health and Productivity Management database (2005–2009) was used. Adult BC patients eligible for employee benefits of sick leave and/or short-term disability were identified with ICD-9 codes. Difference in sick leave and short-term disability days was calculated between MBC patients and their propensity score matched EBC cohort and general population (controls) during a 12-month follow-up period. Generalized linear models were used to examine the impact of MBC on indirect costs to patients and their families.

Results:

A total of 139 MBC, 432 EBC, and 820 controls were eligible for sick leave and 432 MBC, 1552 EBC, and 4682 controls were eligible for short-term disability (not mutually exclusive). After matching, no statistical difference was found in sick leave days and the associated costs between MBC and EBC cohorts. However, MBC patients had significantly higher short-term disability costs than EBC patients and controls (MBC: $6166?±?$9194 vs EBC: $3690?±?$6673 vs Controls: $558?±?$2487, both p?<?0.001). MBC patients had more sick leave cost than controls ($2383?±?$5539 vs $1282?±?$2083, p?<?0.05). Controlling for covariates, MBC patients incurred 47% more short-term disability costs vs EBC patients (p?=?0.009). Older patients (p?=?0.002), non-HMO payers (p?<?0.05), or patients not receiving chemotherapy during follow-up (p?<?0.001) were associated with lower short-term disability costs. MBC patients’ families incurred 39.7% (p?=?0.06) higher indirect costs compared to EBC patients’ families after controlling for key covariates.

Conclusion:

Productivity loss and associated costs in MBC patients are substantially higher than EBC patients or the general population. These findings underscore the economic burden of MBC from a US societal perspective. Various treatment regimens should be evaluated to identify opportunities to reduce the disease burden from the societal perspective.     

Medical chart validation of an algorithm for identifying multiple sclerosis relapse in healthcare claims

Abstract

Objective:

Relapse is a common measure of disease activity in relapsing-remitting multiple sclerosis (MS). The objective of this study was to test the content validity of an operational algorithm for detecting relapse in claims data.

Methods:

A claims-based relapse detection algorithm was tested by comparing its detection rate over a 1-year period with relapses identified based on medical chart review. According to the algorithm, MS patients in a US healthcare claims database who had either (1) a primary claim for MS during hospitalization or (2) a corticosteroid claim following a MS-related outpatient visit were designated as having a relapse. Patient charts were examined for explicit indication of relapse or care suggestive of relapse. Positive and negative predictive values were calculated.

Results:

Medical charts were reviewed for 300 MS patients, half of whom had a relapse according to the algorithm. The claims-based criteria correctly classified 67.3% of patients with relapses (positive predictive value) and 70.0% of patients without relapses (negative predictive value; kappa 0.373: p?<?0.001). Alternative algorithms did not improve on the predictive value of the operational algorithm. Limitations of the algorithm include lack of differentiation between relapsing-remitting MS and other types, and that it does not incorporate measures of function and disability.

Conclusions:

The claims-based algorithm appeared to successfully detect moderate-to-severe MS relapse. This validated definition can be applied to future claims-based MS studies.