Cost-Utility Analysis of Platinum-Based Chemotherapy versus Taxane and Other Regimens for Ovarian Cancer

ObjectivesMost economic evaluations of chemotherapies for ovarian cancer patients have used hypothetical cohorts or randomized control trials, but evidence integrating real-world survival, cost, and utility data is limited.MethodsA propensity score–matched cohort of 6856 elderly (≥65 years) ovarian cancer patients diagnosed from 1991 to 2005 from the Surveillance, Epidemiology, and End Results-Medicare data cohort were included. Treatment regimens (i.e., no chemotherapy, platinum-based only, platinum plus taxane, and other nonplatinum) were identified in the 6 months postdiagnosis. Patients were followed until death or end of study (December 2006). Effectiveness was measured in quality-adjusted life-years (QALYs), and total health care costs were measured by using a payer’s perspective (2009 US dollars). Methodological and statistical uncertainties were accounted by including alternative scenarios (for utility values) and net monetary benefit approach. Incremental cost-effectiveness ratios (ICERs) were calculated, and stratified analyses were performed by tumor stages and age groups.ResultsOn comparing the platinum-based group versus no chemotherapy, we found that the ICER was $30,073/QALY and $58,151/QALY for early- and late-stage disease, respectively, while other nonplatinum and platinum plus taxane groups were dominated (less effective and more costly). Similar results were found across alternative scenarios and age groups. For patients 85 years or older, platinum plus taxane, however, was not dominated by the platinum-based group, with an ICER of $133,892/QALY.ConclusionsFollowing elderly ovarian cancer patients over a lifetime using real-world longitudinal data and adjusting for quality of life, we found that treatment with platinum-based regimen was the most cost-effective treatment alternative.     

Cost-Effectiveness and Value of Information of Erlotinib,Afatinib, and Cisplatin-Pemetrexed for First-Line Treatment of Advanced EGFR Mutation-Positive Non-Small-Cell Lung Cancer in the United States

ObjectivesTo determine the cost-effectiveness of tyrosine kinase inhibitors erlotinib or afatinib, or chemotherapy cisplatin-pemetrexed, for first-line treatment of advanced epithelial growth factor receptor mutation-positive non–small-cell lung cancer in the United States. We also assessed the expected benefit of further research to reduce uncertainty regarding which treatment is optimal.MethodsWe developed a Markov model to compare the cost-effectiveness of erlotinib, afatinib, and cisplatin-pemetrexed. Model transition and adverse-effect probabilities were from two published phase III trials: EURTAC (Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer) and LUX-Lung (Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma) 3. EURTAC survival estimates were corrected for patients entering the trial with more severe disease, compared with LUX-Lung 3. Health utilities and costs were from national estimates or the published literature. Inputs were modeled as distributions for probabilistic sensitivity analysis and expected value of perfect information (EVPI) analysis to estimate the expected benefit of reducing uncertainty regarding the decision of optimal treatment.ResultsIn the base case, both tyrosine kinase inhibitors were more cost-effective than cisplatin-pemetrexed. Erlotinib had an incremental cost-effectiveness ratio of $61,809/quality-adjusted life-year (QALY) compared with afatinib. The acceptability curve showed that erlotinib was the optimal treatment at a willingness-to-pay threshold of $100,000/QALY (10-year population EVPI = $85.9 million). At a willingness-to-pay threshold of $50,000/QALY to $70,000/QALY (EVPI = $211.5 million–$261.8 million), however, there was considerable uncertainty whether erlotinib or afatinib was the optimal treatment.ConclusionsOur analysis suggests that erlotinib is the preferred first-line treatment for advanced epithelial growth factor receptor mutation-positive non–small-cell lung cancer. Further research comparing erlotinib and afatinib is potentially justified, although accurate data are needed on the required cost and sample size of the trial.     

Cost-Effectiveness of Neoadjuvant Chemotherapy versus Primary Surgery in Elderly Patients with Advanced Ovarian Cancer

BackgroundThe use of neoadjuvant chemotherapy (NAC) in the treatment of advanced ovarian cancer has increased in recent years. There is uncertainty about NAC’s effectiveness and no study of its cost-effectiveness compared with that of standard primary debulking surgery (PDS).ObjectivesTo seek answers to three important questions: 1) What is the lifetime cost of treating elderly patients with advanced ovarian cancer, based on the primary treatment received? 2) Are the extra costs expended by the NAC group worth any extra survival advantage? 3) Would NAC potentially benefit a particular subgroup and serve as a cost-effective first-line treatment approach?MethodsA cohort of elderly women (≥65 years) with stage III/IV ovarian cancer was identified from the Surveillance, Epidemiology and End Results-Medicare linked database from January 1, 2000, to December 31, 2009. Cost analysis was conducted from a payer perspective, and direct medical costs incurred by Medicare were integrated for each patient. Cumulative treatment costs were estimated with a phase-of-care approach, and effectiveness was measured as years of survival. Incremental cost-effectiveness ratio (ICER) and propensity-score–adjusted net monetary benefit regression was used to estimate the cost-effectiveness of NAC per life-year gained. Analyses were further stratified by risk group categorization on the basis of tumor stage, patient age, and comorbidity score.ResultsAverage lifetime cost for treatment with NAC was $17,417 more than with PDS. With only 0.1 incremental life-year gained, the ICER estimate was $174,173. Stratification, however, helped to delineate the treatment effect. Patients in the high-risk subgroup incurred $34,390 and 0.8 life-years more than did patients in the PDS subgroup, with a corresponding ICER of $42,987. In the non–high-risk subgroup, NAC use was dominated by PDS (more costly, less effective).ConclusionsAdministering NAC before surgery to patients in the high-risk subgroup was cost-effective at “normal” levels of willingness to pay, but not for the overall sample or for patients in the non–high-risk subgroup.     

Cost-Effectiveness of Chemotherapy for Breast Cancer and Age Effect in Older Women

BackgroundPrevious economic evaluations compared specific chemotherapy agents using input parameters from clinical trials and resource utilization costs. Cost-effectiveness of treatment groups (drug classes) using community-level effectiveness and cost data, however, has not been assessed for elderly patients with breast cancer.ObjectiveTo assess the cost-effectiveness of chemotherapy regimens by age and disease stage under “real-world” conditions for patients with breast cancer.MethodsThe Surveillance Epidemiology and End Results-Medicare data were used to identify patients with breast cancer with American Joint Committee on Cancer stage I/II/IIIa, hormone receptor–negative (estrogen receptor–negative and progesterone receptor–negative) patients from 1992 to 2009. Patients were categorized into three adjuvant treatment groups: 1) no chemotherapy, 2) anthracycline, and 3) non–anthracycline-based chemotherapy. Median life-years and quality-adjusted life-years (QALYs) were measured using Kaplan-Meier analysis and were evaluated against average total health care costs (2013 US dollars).ResultsA total of 4575 patients (propensity score–matched) were included for the primary analysis. The anthracycline group experienced 12.05 QALYs and mean total health care costs of $119,055, resulting in an incremental cost-effectiveness ratio of $7,688 per QALY gained as compared with the no chemotherapy group (QALYs 7.81; average health care cost $86,383). The non–anthracycline-based group was dominated by the anthracycline group with lower QALYs (9.56) and higher health care costs ($122,791). Base-case results were found to be consistent with the best-case and worst-case scenarios for utility assignments. Incremental cost-effectiveness ratios varied by age group (range $3,790–$90,405 per QALY gained).ConclusionsAnthracycline-based chemotherapy was found cost-effective for elderly patients with early stage (stage I, II, IIIa) breast cancer considering the US threshold of $100,000 per QALY. Further research may be needed to characterize differential effects across age groups.     

Cost-Effectiveness of Gene-Expression Profiling for Tumor-Site Origin

ObjectivesGene-expression profiling (GEP) reliably supplements traditional clinicopathological information on the tissue of origin (TOO) in metastatic or poorly differentiated cancer. A cost-effectiveness analysis of GEP TOO testing versus usual care was conducted from a US third-party payer perspective.MethodsData on recommendation changes for chemotherapy, surgery, radiation therapy, blood tests, imaging investigations, and hospice care were obtained from a retrospective, observational study of patients whose physicians received GEP TOO test results. The effects of chemotherapy recommendation changes on survival were based on the results of trials cited in National Comprehensive Cancer Network and UpToDate guidelines. Drug and administration costs were based on average doses reported in National Comprehensive Cancer Network guidelines. Other unit costs came from Centers for Medicare & Medicaid Services fee schedules. Quality-of-life weights were obtained from literature. Bootstrap analysis estimated sample variability; probabilistic sensitivity analysis addressed parameter uncertainty.ResultsChemotherapy regimen recommendations consistent with guidelines for final tumor-site diagnoses increased significantly from 42% to 65% (net difference 23%; P<0.001). Projected overall survival increased from 15.9 to 19.5 months (mean difference 3.6 months; two-sided 95% confidence interval [CI] 3.2–3.9). The average increase in quality-adjusted life-months was 2.7 months (95% CI 1.5–4.3), and average third-party payer costs per patient increased by $10,360 (95% CI $2,982–$19,192). The cost per quality-adjusted life-year gained was $46,858 (95% CI $13,351–$104,269).ConclusionsGEP TOO testing significantly altered clinical practice patterns and is projected to increase overall survival, quality-adjusted life-years, and costs, resulting in an expected cost per quality-adjusted life-year of less than $50,000.     

Spotlight on Paclitaxel in Non-Small Cell Lung Cancer

A number of first-line chemotherapy options for patients with advanced non-small cell lung cancer (NSCLC) are advocated in treatment guidelines and/or by various clinical investigators. Platinum-based chemotherapy has clearly demonstrated efficacy in patients with advanced NSCLC and is generally recommended as first-line therapy, although there is increasing interest in the use of non-platinum chemotherapy regimens. Among the platinum-based combinations currently used in clinical practice are regimens such as cisplatin or carboplatin combined with paclitaxel, vinorelbine, gemcitabine, docetaxel or irinotecan. The particular combinations employed may vary between institutions and geographic regions.Several pharmacoeconomic analyses have been conducted on paclitaxel in NSCLC and most have focused on its use in combination with cisplatin. In terms of clinical efficacy, paclitaxel-cisplatin combinations achieved significantly higher response rates than teniposide plus cisplatin or etoposide plus cisplatin (previously thought to be among the more effective regimens available) in two large randomized trials. One of these studies showed a survival advantage for paclitaxel plus cisplatin [with or without a granulocyte colony-stimulating factor (G-CSF)] compared with etoposide plus cisplatin.A Canadian cost-effectiveness analysis incorporated data from one of the large randomized comparative trials and showed that the incremental cost per life-year saved for outpatient administration of paclitaxel plus cisplatin versus etoposide plus cisplatin was $US22 181 (30 619 Canadian dollars; $Can) [1997 costs]. A European analysis incorporated data from the other large randomized study and showed slightly higher costs per responder for paclitaxel plus cisplatin than for teniposide plus cisplatin in The Netherlands ($US30 769 vs $US29 592) and Spain ($US19 923 vs $US19 724) but lower costs per responder in Belgium ($US22 852 vs $US25 000) and France ($US28 080 vs $US34 747) [1995/96 costs].In other cost-effectiveness analyses, paclitaxel plus cisplatin was associated with a cost per life-year saved relative to best supportive care of approximately $US10 000 in a US study (year of costing not reported) or $US11 200 in a Canadian analysis ($Can15 400; 1995 costs). Results were less favorable when combining paclitaxel with carboplatin instead of cisplatin and particularly when G-CSF was added to paclitaxel plus cisplatin. The Canadian study incorporated the concept of extended dominance in a threshold analysis and ranked paclitaxel plus cisplatin first among several comparator regimens (including vinorelbine plus cisplatin) when the threshold level was $Can75 000 ($US54 526) per life-year saved or per quality-adjusted life-year gained (1995 values). Conclusions: Current treatment guidelines for advanced NSCLC recognize paclitaxel-platinum combinations as one of the first-line chemotherapy treatment options. In two large head-to-head comparative clinical trials, paclitaxel plus cisplatin was associated with significantly greater response rates than cisplatin in combination with either teniposide or etoposide, and a survival advantage was shown for paclitaxel plus cisplatin (with or without G-CSF) over etoposide plus cisplatin. There are limitations to the currently available pharmacoeconomic data and further economic analyses of paclitaxel-carboplatin regimens are warranted, as this combination is widely used in NSCLC and appears to have some clinical advantages over paclitaxel plus cisplatin in terms of ease of administration and effects on platelets. Nevertheless, results of various cost-effectiveness studies support the use of paclitaxel-platinum combinations, particularly paclitaxel plus cisplatin, as a first-line chemotherapy treatment option in patients with advanced NSCLC.     

Cost-Effectiveness of the 21-Gene Assay for Guiding Adjuvant Chemotherapy Decisions in Early Breast Cancer

ObjectivesAdjuvant chemotherapy decisions in early breast cancer are complex. The 21-gene assay can potentially aid such decisions, but costs US $4175 per patient. Adjuvant! Online is a freely available decision aid. We evaluate the cost-effectiveness of using the 21-gene assay in conjunction with Adjuvant! Online, and of providing adjuvant chemotherapy conditional upon risk classification.MethodsA probabilistic Markov decision model simulated risk classification, treatment, and the natural history of breast cancer in a hypothetical cohort of 50-year-old women with lymph node–negative, estrogen receptor– and/or progesterone receptor–positive, human epidermal growth factor receptor 2/neu–negative early breast cancer. Cost-effectiveness was considered from an Ontario public-payer perspective by deriving the lifetime incremental cost (2012 Canadian dollars) per quality-adjusted life-year (QALY) for each strategy, and the probability each strategy is cost-effective, assuming a willingness-to-pay of $50,000 per QALY.ResultsThe 21-gene assay has an incremental cost per QALY in patients at low, intermediate, or high Adjuvant Online! risk of $22,440 (probability cost-effective 78.46%), $2,526 (99.40%), or $1,111 (99.82%), respectively. In patients at low (high) 21-gene assay risk, adjuvant chemotherapy increases (reduces) costs and worsens (improves) health outcomes. For patients at intermediate 21-gene assay risk and low, intermediate, or high Adjuvant! Online risk, chemotherapy has an incremental cost per QALY of $44,088 (50.59%), $1,776 (77.65%), or $1,778 (82.31%), respectively.ConclusionsThe 21-gene assay appears cost-effective, regardless of Adjuvant! Online risk. Adjuvant chemotherapy appears cost-effective for patients at intermediate or high 21-gene assay risk, although this finding is uncertain in patients at intermediate 21-gene assay and low Adjuvant! Online risk.     

CDX2 Biomarker Testing and Adjuvant Therapy for Stage II Colon Cancer: An Exploratory Cost-Effectiveness Analysis

ObjectivesAdjuvant chemotherapy is not recommended for patients with average-risk stage II (T3N0) colon cancer. Nevertheless, a subgroup of these patients who are CDX2-negative might benefit from adjuvant chemotherapy. We evaluated the cost-effectiveness of testing for the absence of CDX2 expression followed by adjuvant chemotherapy (fluorouracil combined with oxaliplatin [FOLFOX]) for patients with stage II colon cancer.MethodsWe developed a decision model to simulate a hypothetical cohort of 65-year-old patients with average-risk stage II colon cancer with 7.2% of these patients being CDX2-negative under 2 different interventions: (1) test for the absence of CDX2 expression followed by adjuvant chemotherapy for CDX2-negative patients and (2) no CDX2 testing and no adjuvant chemotherapy for any patient. We derived disease progression parameters, adjuvant chemotherapy effectiveness and utilities from published analyses, and cancer care costs from the Surveillance, Epidemiology, and End Results (SEER)-Medicare data. Sensitivity analyses were conducted.ResultsTesting for CDX2 followed by FOLFOX for CDX2-negative patients had an incremental cost-effectiveness ratio of $5500/quality-adjusted life-years (QALYs) compared with no CDX2 testing and no FOLFOX (6.874 vs 6.838 discounted QALYs and $89 991 vs $89 797 discounted US dollar lifetime costs). In sensitivity analyses, considering a cost-effectiveness threshold of $100 000/QALY, testing for CDX2 followed by FOLFOX on CDX2-negative patients remains cost-effective for hazard ratios of <0.975 of the effectiveness of FOLFOX in CDX2-negative patients in reducing the rate of developing a metastatic recurrence.ConclusionsTesting tumors of patients with stage II colon cancer for CDX2 and administration of adjuvant treatment to the subgroup found CDX2-negative is a cost-effective and high-value management strategy across a broad range of plausible assumptions.     

Upper Body Lipomas in an HIV-Infected Man

Abstract

Purpose: To calculate and compare the direct medical costs of guideline-recommended prophylaxis with prophylaxis that does not fully adhere with guideline recommendations in a large, real-world population. Methods: Discharge records were retrieved from the US Premier Perspective? database (January 2003–December 2003) for patients aged ≥ 40 years with a primary diagnosis of cancer, chronic heart failure, lung disease, or severe infectious disease who received some form of thromboprophylaxis. Univariate analysis and multivariate regression modeling were performed to compare direct medical costs between discharges who received appropriate prophylaxis (correct type, dose, and duration based on sixth edition American College of Chest Physicians [ACCP] recommendations) and partial prophylaxis (not in full accordance with ACCP recommendations). Market segmentation analysis was used to compare costs stratified by hospital and patient characteristics. Results: Of the 683 005 discharges included, 148 171 (21.7%) received appropriate prophylaxis and 534 834 (78.3%) received partial prophylaxis. The total direct unadjusted costs were $15 439 in the appropriate prophylaxis group and $17 763 in the partial prophylaxis group. After adjustment, mean adjusted total costs per discharge were lower for those receiving appropriate prophylaxis ($11 713; 95% confidence interval [CI], $11 675–$11 753) compared with partial prophylaxis ($13 369; 95% CI, $13 332–$13 406; P < 0.01). Appropriate prophylaxis appeared to be associated with numerically lower unadjusted costs than partial prophylaxis, regardless of hospital size, rural/urban location, teaching status, and patient age and gender. Conclusion: This large, real-world analysis suggests that appropriate prophylaxis, in adherence with ACCP guidelines, is potentially cost-saving compared with partial prophylaxis in at-risk medical patients.     

Cost-Effectiveness of Ivacaftor Therapy for Treatment of Cystic Fibrosis Patients With the G551D Gating Mutation

ObjectivesCystic fibrosis (CF) is a rare genetic disease with no cure. Until recently, treatment has targeted symptoms of the disease and not the disease-causing genetic defect. Ivacaftor is included in a new class of breakthrough drugs targeting the genetic defects of CF. We sought to estimate the long-term cost-effectiveness of ivacaftor from a US payer perspective.MethodsWe developed an individual-level microsimulation model that followed a cohort of heterogeneous US CF patients over a lifetime. The primary outcome of interest was quality-adjusted life years (QALYs). We also compared unadjusted life years, count of acute pulmonary exacerbations, and count of lung transplants over a lifetime between patients treated with ivacaftor plus best supportive care and patients treated with best supportive care alone. We conducted one-way and probabilistic sensitivity analyses to test the impact of various model inputs and uncertainties.ResultsWe found a substantial increase in QALYs, life years, and treatment costs over a lifetime for patients treated with ivacaftor plus best supportive care versus best supportive care alone. Discounted results for ivacaftor were 22.92 QALYs and $8 797 840 in total lifetime costs compared to 16.12 QALYs and $2 336 366 lifetime costs for best supportive care alone. The incremental cost-effectiveness ratios (ICERs) were $950 217 per QALY. Results from the probabilistic sensitivity analysis indicated a 0% chance that ivacaftor was cost-effective at a willingness-to-pay (WTP) threshold of $500 000 per QALY.ConclusionsTreatment with ivacaftor plus best supportive care versus best supportive care alone is not cost-effective at or near commonly accepted WTP thresholds.     

Discrete Choice Experiment to Estimate Breast Cancer Patients’ Preferences and Willingness to Pay for Prophylactic Granulocyte Colony-Stimulating Factors

ObjectivesRising out-of-pocket costs for cancer patients have increased shared decision making. Clinical guidelines recommend prophylactic granulocyte colony-stimulating factor (G-CSF) for patients receiving chemotherapy with a 20% or greater risk of febrile neutropenia. A discrete choice experiment was conducted to explore breast cancer patients’ preferences and willingness to pay (WTP) for prophylactic G-CSF to decrease the risk of chemotherapy-induced febrile neutropenia.MethodsAn online discrete choice experiment questionnaire survey of a national US convenience sample of self-reported breast cancer patients with prior chemotherapy treatment was conducted. Sixteen paired G-CSF treatment scenarios, each with four attributes (risk of disruption to chemotherapy schedule due to low white blood cell counts, risk of developing an infection requiring hospitalization, frequency of administration, and total out-of-pocket cost) were presented with a follow-up “no treatment” option. Participant preferences and WTP out of pocket were estimated by logistic regression.ResultsParticipants (n = 296) preferred G-CSF regimens with lower out-of-pocket costs, lower risk of chemotherapy disruption, lower risk of infection, and greater convenience (one G-CSF injection per chemotherapy cycle). Participants’ WTP was $1076 out of pocket per cycle to reduce the risk (high to low) of disrupting their chemotherapy schedule, $884 per cycle to reduce the risk (24% [high] to 7% [low]) of infection, and $851 per cycle to decrease the number of G-CSF injections (11 to 1) per cycle.ConclusionsParticipants highly valued specific features of prophylactic G-CSF treatment including maintaining their chemotherapy schedule, lowering their risk of infection, and reducing the number of injections. Physicians should consider patient preferences to inform the best treatment choices for individual patients.     

Comparing Medical Cost of Care for Patients with Metastatic Breast Cancer Receiving Taxane Therapy: Claims Analysis

Background

It has been estimated that more than $8 billion is spent annually on the management of breast cancer in the United States. The taxane chemotherapeutic agents are cornerstones in the treatment of breast cancer, yet no study has assessed whether the choice of a taxane affects the economic outcomes of metastatic breast cancer treatment.

Objective

To determine if differences exist in the medical cost of care in patients receiving taxane-based chemotherapy for metastatic breast cancer, and to compare the use of ancillary medications (for neutropenia, anemia, and nausea and vomiting) and their associated costs among taxanes.

Method

We identified women with metastatic breast cancer based on diagnosis codes and the women''s previous adjuvant chemotherapeutic regimens. Paid medical insurance claims were captured for the 24-month study period, from January 1, 2006, through December 31, 2007. The groups were determined according to the specific taxane administered. Total medical costs were captured from the date of first taxane administration to the end of data availability. Outpatient pharmacy costs were not available. A multivariate analysis was used to evaluate the total medical costs in each group. Median total medical costs per patient per month during the study period were adjusted using a multiple regression analysis. Utilization and cost of medications administered in the office or hospital for chemotherapy-induced adverse effects were captured and adjusted with Tobit models.

Results

Of the 2245 study participants, 1035 received docetaxel, 997 received generic paclitaxel, and 213 received nab-paclitaxel. On average, patients in the nab-paclitaxel group received more doses (9.6) than those in the generic paclitaxel (6.0) or docetaxel (4.8) groups. The multivariate analysis was robust, explaining 72% of the variability in total medical costs across the 3 taxane groups. Median per-patient per-month total medical costs for study participants were within approximately $800 of each other among the groups. Generic paclitaxel had the lowest total medical costs. The total costs for docetaxel and nab-paclitaxel were not significantly different. Nab-paclitaxel had the lowest utilization and lowest costs associated with colony-stimulating factors. The proportion of patients receiving erythropoiesis-stimulating agents was not significantly different among the 3 drugs, but the costs for these agents were significantly lower in patients receiving nab-paclitaxel than in those receiving docetaxel. Antiemetic use was highest in the docetaxel group, but the costs for antiemetics were not different among the 3 taxane groups.

Conclusion

The differences in total medical costs among the 3 taxanes were modest. Total medical costs were lowest for patients receiving generic paclitaxel and comparable between the docetaxel and nab-paclitaxel groups. Patients taking nab-paclitaxel received more doses than patients taking the other taxanes. Nab-paclitaxel was associated with lower utilization and costs for colony-stimulating factors compared with generic paclitaxel and docetaxel.Breast cancer is the most frequently diagnosed cancer in US women, and ranks second among cancer-related deaths in women, after lung cancer.1 It is estimated that $8.1 billion (in 2004 $US) in total healthcare costs are spent annually on breast cancer diagnosis and treatment in the United States.2 Chemotherapeutic agents represent a significant portion of the cost of breast cancer treatment, and health plans are managing these costs with care pathways and other utilization management strategies.     

Understanding the Costs of Care for Cystic Fibrosis: An Analysis by Age and Health State

ObjectivesCystic fibrosis (CF) is an inherited disease that requires more intensive treatments as the disease progresses. Recent medical advancements have improved survival but have also increased costs. Our lack of understanding on the relationship between disease severity and lifetime health care costs is a major impediment to the timely economic assessment of new treatments.MethodsUsing data from three waves of the Australian Cystic Fibrosis Australia Data Registry, we estimate the annual costs of CF care by age and health state. We define health states on the basis of annual lung-function scores and patient’s organ transplant status. We exploit the longitudinal nature of the data to model disease progression, and we use this to estimate lifetime health care costs.ResultsThe mean annual health care cost for treating CF is US $15,571. Costs for patients with mild, moderate, and severe disease are US $10,151, US $25,647, and US $33,691, respectively. Lifetime health care costs are approximately US $306,332 (3.5% discount rate). The majority of costs are accounted for by hospital inpatients (58%), followed by pharmaceuticals (29%), medical services (10%), complications (2%), and diagnostic tests (1%).ConclusionsOur study is the first of its kind using the Australian Cystic Fibrosis Data Registry, and demonstrates the utility of longitudinal registry data for the purpose of economic analysis. Our results can be used as an input to future economic evaluations by providing analysts with a better understanding of the long-term cost impact when new treatments are developed.     

Estimated Life-Years Saved in Women with HER2-Positive Metastatic Breast Cancer Receiving First-Line Trastuzumab and Pertuzumab in the United States

BackgroundHER2 positive (HER2+) metastatic breast cancer (MBC) is associated with high mortality. Trastuzumab was approved for use in 1998, but the life-years saved from first-line use are unknown, as are the potential US population benefits from adding pertuzumab.ObjectivesThe first aim was to estimate the number of life-years saved by using first-line trastuzumab between 1999 and 2013 in HER2+ women with MBC. In addition, based on these estimates, the second aim was to project the life-years that could be saved by adding pertuzumab to trastuzumab in first-line therapy.MethodsWe constructed a simulation model accounting for incidence, testing rates, therapy utilization, and overall survival. The model was run for 1999 to 2013 (15 years) to estimate the life-years saved from using trastuzumab plus chemotherapy instead of chemotherapy alone. The model was also run from 2013 to 2027 (15 years) to project the life-years that might be saved by adding pertuzumab. Uncertainty was incorporated using Monte-Carlo methods.ResultsThe estimated number of women with HER2+ MBC varied over time, with the peak of 9700 in 2005 and the low of 7700 in 2018. The cumulative incremental life-years saved because of first-line trastuzumab use from 1999 to 2013 was estimated to be 156,413 (95% simulation interval 114,840–195,201). The projection for pertuzumab from 2013 to 2027 was 137,959 (95% simulation interval 56,011–225,069). Exploratory analyses of value showed that pertuzumab, trastuzumab, and chemotherapy is associated with a $1.10 billion gain compared with chemotherapy alone, and adding pertuzumab is associated with a $0.06 billion gain compared with trastuzumab with chemotherapy.ConclusionsThis simulation model suggests that substantial progress has been made in treating HER2+ women over the past 15 years, and the future may witness similar gains with the introduction of pertuzumab.     

An Evaluation of the Cost-Effectiveness of Rituximab in Combination with Chemotherapy for the First-Line Treatment of Follicular Non-Hodgkin's Lymphoma in the UK

ObjectivesIn this study, the cost-effectiveness of rituximab was evaluated in comparison with commonly used chemotherapy regimens for patients with advanced follicular lymphoma (FL), from the perspective of the UK National Health Service (NHS).MethodsResults from four randomized controlled trials comparing the addition of rituximab to chemotherapy regimens: mitoxantrone, chlorambucil, and prednisolone (MCP); cyclophosphamide, vincristine, and prednisolone (CVP); cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP); or cyclophosphamide, etoposide, doxorubicin, prednisolone, and interferon alpha (CHVP + IFNα) versus chemotherapy alone were used to develop a Markov model. The rates of disease progression and the duration of treatment effect were obtained from the trial data. Treatments were compared in two ways: 1) an individual comparison of rituximab + chemotherapy versus chemotherapy and 2) a multiple treatment comparison using league tables. Economic and clinical outcomes (quality-adjusted life-years (QALYs)) were estimated over patient lifetimes and discounted at 3.5% per annum.ResultsIn the individual comparison, the addition of rituximab increased QALYs by (mean, 95% confidence interval) 1.174 (1.02–1.30), 0.909 (0.79–1.01), 0.823 (0.71–0.91), and 0.453 (0.40–0.50) for MCP, CVP, CHOP, and CHVP, respectively, compared with chemotherapy alone. The incremental costs per QALY gained were £7474, £8621, £10,732, and £8551, respectively. Sensitivity analyses indicated that rituximab plus chemotherapy was a cost-effective treatment option, with incremental cost-effectiveness ratios below a threshold of £30,000 per QALY gained. When compared across the chemotherapy regimens, rituximab plus MCP appeared to be the single most cost-effective treatment option, but further randomized trials are required to substantiate this.ConclusionsThe addition of rituximab to chemotherapy in advanced FL was found to be highly cost-effective in the UK.     

Cost-Effectiveness of Switching to Exemestane after 2 to 3 Years of Therapy with Tamoxifen in Postmenopausal Women with Early-Stage Breast Cancer

OBJECTIVES: Data from the Intergroup Exemestane Study (IES) suggest that switching to the aromatase inhibitor, exemestane, after 2 to 3 years of tamoxifen therapy prolongs disease-free survival versus continuing on tamoxifen therapy. We sought to evaluate the cost-effectiveness of this management strategy. METHODS: A Markov model was developed to predict patients' transitions across various health states based on treatment strategy (continuing tamoxifen vs. switching to exemestane), breast cancer status (no recurrence, local or distant recurrence, contralateral breast cancer), and other related health events (osteoporosis, endometrial cancer, death). Rates of disease-related events (recurrence and contralateral breast cancer) were estimated using data from the IES. Survival and lifetime medical-care costs by type of disease-related event were estimated using SEER-Medicare data. The model was used to estimate direct costs (in 2004 US dollars), life expectancy, quality-adjusted life-years (QALYs), and incremental cost-effectiveness. RESULTS: Switching to exemestane versus continuing tamoxifen therapy was associated with increased disease-free survival (181 vs. 172 months), QALYs (12.21 vs. 11.89), and net discounted lifetime costs of cancer care ($12,124 vs. $7724 per patient). The incremental cost-effectiveness ratio of exemestane was $20,100 per QALY gained (95% confidence interval: $12,100, $59,000). Sensitivity analyses showed that results were robust to plausible variations in recurrence rates, costs, and utilities. CONCLUSIONS: Switching postmenopausal early-stage breast cancer patients to exemestane after 2 to 3 years of tamoxifen appears to be a cost-effective treatment strategy versus completing a 5-year course of tamoxifen.     

Real-World Cost of Care for Commercially Insured versus Medicare Patients with Metastatic Pancreatic Cancer Who Received Guideline-Recommended Therapies

BackgroundMuch of the literature about the costs of metastatic pancreatic cancer is focused on the Medicare population, but the cost in the commercially insured population is not well-documented. Differences in treatment patterns between commercially insured and Medicare patients with metastatic pancreatic cancer can provide insights into healthcare utilization and the total cost of care.ObjectiveTo compare the total cost of care for commercially insured versus Medicare patients with metastatic pancreatic cancer who are receiving National Comprehensive Cancer Network (NCCN)-recommended treatment regimens.MethodsWe identified 3904 patients (mean age at diagnosis, 56 years) with metastatic pancreatic cancer using International Classification of Diseases, Ninth/Tenth Revision diagnosis codes in claims data in the 2014–2018 MarketScan commercial database and 28,063 patients (mean age at diagnosis, 73 years) with metastatic pancreatic cancer in the 2014–2017 Medicare Parts A, B, and D 100% research identifiable data files. We calculated the total cost of care and resource utilization by NCCN-recommended (category 1) treatment regimen, including 5-fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFIRINOX); gemcitabine plus nab-paclitaxel; gemcitabine monotherapy; and liposomal irinotecan. All patients had ≥2 claims with a pancreatic cancer diagnosis more than 30 days apart and ≥1 subsequent claims with a secondary malignancy diagnosis for metastatic disease.ResultsThe mean total cost of care was 186% higher in the commercially insured cohort than in the Medicare cohort. Excluding gemcitabine monotherapy, the total cost of care for patients with metastatic pancreatic cancer was similar between the regimens used in each cohort, ranging from $95,426 to $116,325 in the commercial insurance group and from $39,777 to $40,390 in the Medicare group. The components of hospital-based inpatient and outpatient costs varied between similar regimens in both cohorts. The inpatient admission patterns of patients'' regimens were consistent across the 2 cohorts, with patients receiving gemcitabine monotherapy or liposomal irinotecan having the lowest overall number of admissions in each cohort.ConclusionsThe treatment patterns varied across the regimens but were largely consistent between the commercially insured and the Medicare patients who received the same regimen for metastatic pancreatic cancer; the ratio of total cost of care was 3:1 (commercially insured to Medicare). The total costs of care were similar across the regimens in each cohort, but the components of the total cost varied. These results can inform clinical guidelines and pathways for pancreatic cancer therapy as new evidence and treatment options emerge, and in the context of increasing value-based care models.     

Cost-Effectiveness of Cemiplimab Versus Standard of Care in the United States for First-Line Treatment of Advanced Non-small Cell Lung Cancer With Programmed Death-Ligand 1 Expression ≥50%

ObjectivesThis study aimed to evaluate the cost-effectiveness, from a US commercial payer perspective, of cemiplimab versus other first-line treatments for advanced non-small cell lung cancer with programmed death-ligand 1 expression ≥50%.MethodsA 30-year “partitioned survival” model was constructed. Overall survival and progression-free survival were estimated by applying time-varying hazard ratios from a network meta-analysis of randomized clinical trials. Overall survival and progression-free survival were estimated from EMPOWER-Lung 1 (cemiplimab monotherapy vs chemotherapy) and KEYNOTE-024 and KEYNOTE-042 (pembrolizumab monotherapy vs chemotherapy). Drug acquisition costs were based on published 2020 US list prices. A 3% discount rate was applied to life-years, quality-adjusted life-years (QALYs), and costs. A deterministic analysis was performed on the base case; 1-way sensitivity and probabilistic sensitivity analyses assessed model and parameter uncertainties.ResultsCemiplimab was associated with increased time in the “preprogression” (13.08 vs 7.90 and 6.08 months) and “postprogression” (47.30 vs 29.49 and 14.78 months) health states versus pembrolizumab and chemotherapy, respectively. Compared with pembrolizumab and chemotherapy, cemiplimab generated 1.00 (95% CI ?0.266 to 2.440) and 1.78 (95% CI 0.607-3.20) incremental QALYs, respectively, with incremental cost-effectiveness ratios of $68 254 and $89 219 per QALY for cemiplimab versus pembrolizumab and cemiplimab versus chemotherapy, respectively. The probability of cemiplimab being cost-effective at a willingness-to-pay threshold of $100 000 to $150 000 per QALY was 62% to 76% versus pembrolizumab and 56% to 84% versus chemotherapy.ConclusionsFindings suggest that cemiplimab, versus pembrolizumab or versus chemotherapy, is a cost-effective first-line treatment option for advanced non-small cell lung cancer with programmed death-ligand 1 expression ≥50%.     

Japanese encephalitis vaccination in the Philippines: A cost-effectiveness analysis comparing alternative delivery strategies

IntroductionJapanese encephalitis (JE) is a mosquito-borne viral infection of the brain that can cause permanent brain damage and death. In the Philippines, efforts are underway to deliver a live attenuated JE vaccine (CD-JEV) to children under five years of age (YOA), who are disproportionately infected. Multiple vaccination strategies are being considered.MethodsWe conducted a cost-effectiveness analysis comparing three vaccination strategies to the current state of no vaccination from the societal and government perspectives: (1) national routine vaccination only, (2) sub-national campaign followed by national routine, and (3) national campaign followed by national routine. We developed a Markov model to estimate impact of vaccination or no vaccination over the child’s lifetime horizon, assuming an annual incidence of 10.6 cases per 100,000.Costs of illness ($859/case), vaccine ($0.50/dose), routine vaccination ($0.95/dose), and campaign vaccination ($0.98/dose) were based on hospital financial records, expert opinion and literature. The societal perspective included transportation and opportunity costs of caregiver time, in addition to costs incurred by the health system.ResultsJE vaccination via national campaign followed by national routine delivery was the most cost-effective strategy modeled with a cost per disability adjusted life year (DALY) averted of $233 and $29 from the government and societal perspectives, respectively. Results were similar for other delivery strategies with cost/DALY ranging from $233 to $265 from the government perspective and $29–$57 from the societal perspective. JE vaccination was projected to prevent 27,856–37,277 cases, 5571–7455 deaths, and 173,233–230,704 DALYs among children under five over 20 consecutive birth cohorts. Total incremental costs of vaccination versus no vaccination over 20 birth cohorts were $6.6–$9.8 million from the societal perspective ($230 K–$440 K annually) and $45.9–$53.9 million ($2.2 M–$2.7 M annually) from the governmental perspective.ConclusionVaccination with CD-JEV in the Philippines is projected to be cost-effective, reducing long-term costs associated with JE illness and improving health outcomes compared to no vaccination.     

Cost-Effectiveness Analysis of Pertuzumab With Trastuzumab and Chemotherapy Compared to Trastuzumab and Chemotherapy in the Adjuvant Treatment of HER2-Positive Breast Cancer in the United States

Objective

The APHINITY trial assessed the effectiveness and the safety of adding pertuzumab to trastuzumab and chemotherapy (THP) compared to trastuzumab and chemotherapy (TH) in the adjuvant management of human epidermal growth factor 2-positive (HER2+) breast cancer. We performed a study to project the potential cost-effectiveness of THP vs. TH.