Economic burden of multiple myeloma among patients in successive lines of therapy in the United States.

This study characterized the costs of multiple myeloma (MM) during first-line (1L), second-line (2L) and third-line (3L) treatment from the US payer perspective. Patients with ≥2 outpatient or ≥1 inpatient claims with a primary MM diagnosis and 12 months continuous enrollment post index were identified in a retrospective claims database between 1 July 2006 and 30 June 2013. A cost per-patient per-month (PPPM) metric was used to calculate total all-cause and anti-MM pharmacy costs in 1L, 2L, and 3L treatment. Of 5704 patients included, 3626 initiated 1L treatment, 1797 initiated 2L and 817 initiated 3L. Average total all-cause PPPM costs were $22,527 in 1L, $35,266 in 2L and $47,417 in 3L. Anti-MM pharmacy costs represented 22%, 29% and 29% of total all-cause costs PPPM in 1L, 2L and 3L, respectively. Study results suggest that delaying 2L and/or 3L treatment initiation may result in lower treatment costs for patients with MM.

The relationship between adherence and total spending among Medicare beneficiaries with type 2 diabetes.

OBJECTIVES: This study examined the relationship between medication adherence, cost sharing measured as out-of-pocket spending, and total annual spending in Medicare beneficiaries with type 2 diabetes (T2D) to evaluate whether pharmacy cost-sharing programs have the potential to decrease adherence. These programs may unintentionally increase the risk of medical complications and may result in higher spending overall. STUDY DESIGN: This retrospective study used 2006 to 2009 Medicare claims data. The sample included patients 65 years or older with T2D (at least 1 claim with International Classification of Diseases, 9th Revision, Clinical Modification codes 250.x0 and 250.x2 and at least 1 antidiabetes drug claim). METHODS: Medication adherence was measured as proportion of days covered over the first 12 months of observation. Spending and adherence outcomes were defined in deciles. RESULTS: The sample included 12,305 patient-year observations. Pharmacy spending for patients in the most adherent (10th) decile was 59% higher than that for patients in the least adherent (1st) decile ($4839 vs $3046). Yet, patients in the 10th decile had 49% lower total ($12,531 vs $24,468) and 64% lower medical spending ($7692 vs $21,421) than patients in the 1st decile. Greater out-of-pocket spending was correlated with lower adherence and higher total and medical spending. CONCLUSIONS: This study describes a widespread variation in medication adherence, pharmacy cost sharing, and medical spending in a sample of Medicare beneficiaries with T2D. We found that lower adherence was correlated with higher cost sharing in the Medicare population, perhaps because of unobserved confounding factors. However, the existing literature on patients with employer-sponsored insurance suggests some of this correlation may be indicative of causal relationships.

The value of survival gains in myelodysplastic syndromes.

OBJECTIVES: To measure the value of survival gains attributable to the introduction of 3 novel therapies for myelodysplastic syndromes (MDS). STUDY DESIGN: Retrospective study of patients diagnosed with MDS in the Surveillance, Epidemiology and End Results Program (SEER) registry, clinical trial evidence for MDS therapies, and claims data. METHODS: We used multivariate Cox proportional hazards models to estimate the increase in survival associated with the introduction of the 3 new therapies for patients diagnosed with MDS from 2001 to 2011 in the SEER cancer registry. Increases in survival associated with the 3 novel therapies were estimated using retrospective survival analyses and published clinical trial evidence. MDS treatment costs were estimated using Ingenix claims data and used to calculate the share of the value of survival gains retained by patients. RESULTS: We estimated that the introduction of these 3 therapies is associated with a hazard ratio of 0.901 (P <.10), and a 73% increase in median survival from 33 to 57 months. We estimated that for current and future MDS patients, these 3 therapies will generate over $193 billion in cumulative value through extensions in patient survival. CONCLUSIONS: This study demonstrates that the value of recently approved innovative therapies in MDS is large and that the value of survival gains in MDS far outweighs their costs.

The Value of Survival Gains in Pancreatic Cancer from Novel Treatment Regimens.

BACKGROUND: Metastatic pancreatic cancer (mPC) is associated with low survival, with less than 10% of patients surviving 5 years. Recent therapies improve survival outcomes where few alternative therapies exist, but few economic analyses measure the value of survival gains attributable to new therapies. OBJECTIVE: To estimate the value of survival gains in advanced or mPC attributable to the introduction of novel treatment regimens. METHODS: Multivariate Cox proportional hazards models were used to estimate real-world survival gains associated with the introduction of gemcitabine (GEM) for patients diagnosed with stage IV or unstaged mPC in the Surveillance, Epidemiology, and End Results Program cancer registries. Then, evidence from clinical trials was used to evaluate the survival gains associated with nab-paclitaxel + gemcitabine (nP +GEM) and FOLFIRINOX (FFX) relative to GEM. The survival estimates and clinical trial evidence were used to calibrate an economic model and assess the cumulative value of survival gains in mPC to patients. Costs of treatment were calculated based on published cost-effectiveness studies. RESULTS: We estimated that the introduction of GEM in 1996 was associated with a hazard ratio of 0.920 (P < 0.05) and an increase in median survival from 3.1 to 4.5 months. Results suggested that the value of survival gains attributable to GEM equaled about $71,000 per patient, while the value attributable to nP + GEM was an additional $56,700. Estimates for the value of survival gains per patient, net of total incremental lifetime treatment costs (drugs, adverse events, and other costs), were $50,294 for GEM and an additional $31,900 for nP + GEM. Clinical trials and cost-effectiveness studies reported an overall survival gain from FFX that was larger than, but statistically similar to, nP + GEM and had greater risk of adverse events and total incremental costs. We estimated that the total value of survival gains to mPC patients, net of total costs, associated with GEM was up to $47.6 billion, and the additional values attributable to nP+GEM and FFX were up to $39.0 billion and $26.3 billion, respectively. CONCLUSIONS: Historically, mPC patients have faced high disease burden and had few treatment options. Treatments introduced since 1996 have led to improved survival, with varying costs associated with treatment and adverse events. Accounting for total incremental costs, the majority of the value of survival gains from GEM and nP+GEM was retained by mPC patients, highlighting the value of innovation in settings where survival is low and few alternative therapies exist. DISCLOSURES: Support for this research was provided by Celgene. Precision Health Economics was compensated by Celgene for work on this study. MacEwan is an employee of, and Yin is a consultant to, Precision Health Economics. Kaura and Khan are employees of Celgene. Study concept and design were contributed primarily by Yin and MacEwan, along with Kaura and Khan. MacEwan collected the data, and data interpretation was performed primarily by MacEwan and Yin, along with Kaura and Khan. The manuscript was written and revised by MacEwan, Yin, Kaura, and Khan.

Evaluating cost benefits of combination therapies for advanced melanoma.

BACKGROUND: Although a number of monoimmunotherapies and targeted therapies are available to treat BRAF+ advanced melanoma, response rates remain relatively low in the range of 22-53% with progression-free survival (PFS) in the range of 4.8-8.8 months. Recently, combination targeted therapies have improved response rates to about 66-69%, PFS to 11.0-12.6 months and overall survival (OS) to 25.1-25.6 months. While combination immunotherapies have improved response rates of 67 compared with 19-29% with monotherapies and improved PFS of 11.7 compared with 4.4-5.8 months with monotherapies, the OS benefit is yet to be established in phase 3 trials. As healthcare costs continue to rise, US payers have a predominant interest in assessing the value of available treatments. Therefore, a cost-benefit model was developed to evaluate the value of treating BRAF+ advanced melanoma with two combination therapies: nivolumab + ipilimumab (N+I) and dabrafenib + trametinib (D+T). SCOPE: The model was used to estimate total costs, total costs by expenditure category, cost per month of PFS and cost per responder for the payer, and societal perspectives of treating advanced melanoma patients with the BRAF V600 mutation using combination targeted therapy (D+T) or combination immunotherapy (N+I). The model followed patients from initiation of treatment to the point of progression or death. Deterministic and probabilistic sensitivity analyses were conducted to evaluate the robustness of the results and to understand the dispersion of simulated results. FINDINGS: Based on a hypothetical payer with one million covered lives, it was expected that fourteen metastatic melanoma patients with the BRAF V600 mutation would be treated each year. Cost-benefit with N+I and D+T was simulated from the payer perspective. The cost per month of PFS for N+I was $22,162, while that for D+T was $17,716 (-$4,446 cost difference); the cost per responder for N+I was $388,746 and that for D+T was $282,429 (-$106,316 cost difference). The cost per month of PFS and per responder from the societal perspective resembled the patterns observed from the payer's perspective: the cost per month of PFS for N+I was $22,843, while that for D+T was $18,283 (-$4,560 cost difference). The cost per responder for N+I was $400,695 and that for D+T was $291,473 (-$109,222 cost difference). The totals of travel and treatment time for N+I and D+T were 58 hours and 3.9 hours per patient, respectively, of which total infusion time for N+I accounted for a majority - 59% - of the 58 hours. Sensitivity analyses indicated that results were most sensitive to model inputs for median PFS, body weight, and drug cost. Moreover, D+T is likely associated with a lower cost per month of PFS and cost per responder than N+I, except at low body weights (less than 57 kg). CONCLUSION: The model presented in this study was used to analyze the clinical and economic benefit of using combination therapies in advanced melanoma patients with the BRAF V600 mutation. This analysis suggests D+T therapy is associated with less patient time and lower costs relative to N+I to gain similar PFS and overall response rate (ORR) benefits.