Clinical outcomes and healthcare utilization in patients with sickle cell disease: a nationwide cohort study of Medicaid beneficiaries.

To add to the limited existing evidence on clinical outcomes and healthcare use in sickle cell disease (SCD) among beneficiaries of the US Medicaid program, we conducted a cohort study using nationwide Medicaid claims data (2000-2013). Patients were included based on HbSS SCD diagnosis and followed until Medicaid disenrollment, death, bone marrow transplant, or end of data availability to assess vasoocclusive crises (VOC), emergency room (ER) visits, hospitalizations, outpatient visits, and blood transfusions. Annualized event rates (with 95% confidence intervals [CI]) were reported. The impact of VOCs on the risk of mortality was analyzed using a multivariable Cox model with VOC modeled as time-varying and updated annually. In a total of 44,033 SCD patients included with a mean (SD) age of 15.7 (13.6) years, the VOC rate (95% CI) was 3.71 (3.70-3.72) per person-year, with highest rate among patients 19-35 years who had ≥ 5 VOCs at baseline (13.20 [13.15-13.26]). Event rates (95% CI) per person per year for other outcomes were 2.97 (2.97-2.98) ER visits, 2.39 (2.38-2.40) hospitalizations, 5.80 (5.79-5.81) outpatient visits, and 0.91 (0.90-0.91) blood transfusions. A higher VOC burden in the preceding year was associated with an increased risk of mortality, with a hazard ratio (95% CI) of 1.26 (1.14-1.40) for 2-4 VOC vs. < 2 and 1.57 (1.41-1.74) for ≥ 5 VOC vs < 2. In conclusion, we documented a substantial burden of SCD in US Medicaid enrollees, especially during early adulthood and noted that ongoing burden of VOC is associated with mortality in these patients.

Economic Impact of Next-Generation Sequencing Versus Single-Gene Testing to Detect Genomic Alterations in Metastatic Non-Small-Cell Lung Cancer Using a Decision Analytic Model.

PURPOSE: The aim of the current study was to assess the economic impact of using next-generation sequencing (NGS) versus single-gene testing strategies among patients with metastatic non-small-cell lung cancer (mNSCLC) from the perspective of the Centers for Medicare & Medicaid Services (CMS) and US commercial payers. METHODS: A decision analytic model considered patients who were newly diagnosed with mNSCLC who received programmed death ligand 1 and genomic alteration tests-EGFR, ALK, ROS1, BRAF, MET, HER2, RET, and NTRK1-using upfront NGS (all alterations tested simultaneously plus KRAS), sequential testing (sequence of single-gene tests), exclusionary testing (KRAS plus sequential testing), and hotspot panels (EGFR, ALK, ROS1, and BRAF tested simultaneously plus single-gene tests or NGS for MET, HER2, RET, and NTRK1). Model outcomes for each strategy were time-to-test results, the proportion of patients identified harboring alterations with or without US Food and Drug Administration-approved therapies, and total testing costs. A budget impact analysis assessed the economic effects of increasing the proportion of NGS-tested patients. RESULTS: In a hypothetical 1,000,000-member health plan, 2,066 Medicare-insured patients and 156 commercially insured patients were estimated to have mNSCLC and to be eligible for testing. Time-to-test results were 2.0 weeks for NGS and the hotspot panel, faster than exclusionary and sequential testing by 2.7 and 2.8 weeks, respectively. NGS was associated with cost savings for both CMS ($1,393,678; $1,530,869; and $2,140,795 less than exclusionary, sequential testing, and hotspot panels, respectively) and commercial payers ($3,809; $127,402; and $250,842 less than exclusionary, sequential testing, and hotspot panels, respectively). Increasing the proportion of NGS-tested patients translated into substantial cost savings for both CMS and commercial payers. CONCLUSION: Use of upfront NGS testing in patients with mNSCLC was associated with substantial cost savings and shorter time-to-test results for both CMS and commercial payers.

Two-year adherence and costs for biologic therapy for rheumatoid arthritis.

OBJECTIVES: To evaluate adherence to newly initiated biologic disease-modifying antirheumatic drugs (bDMARDs) in effectively treated patients with rheumatoid arthritis (RA). STUDY DESIGN: Retrospective cohort study of administrative claims data (IMS PharMetrics Plus) for services incurred from July 1, 2008, to December 31, 2014. METHODS: Data from patients with RA aged 18 to 64 years with continuous enrollment for at least 30 months and initiating abatacept, adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab were analyzed. Treatment effectiveness was determined using a validated algorithm. Outcomes included adherence rates (proportion of days covered ≥80%) for 1 year and 2 years, year 2 adherence among patients effectively and noneffectively treated in year 1, year 2 adherence predictors, and year 2 costs and cost predictors. RESULTS: Across 10,374 patients, adherence rates were 46% for year 1 and 34% for 2 years; rates were lowest for golimumab and highest for infliximab. In year 1, 3076 (29.7%) patients were considered effectively treated. Year 2 adherence was 59% in effectively treated patients, 32% in patients who failed any effectiveness criteria, and 12% in patients who failed only the adherence criterion. Intravenous bDMARDs, older age, male sex, Northeast region, commercial payer, prior DMARD use, index year 2010 or later, and lower preindex all-cause costs each predicted better adherence. Adjusted year 2 all-cause and RA-related costs were $39,425 and $22,123, respectively, for effectively treated patients and $25,313 and $9250 for noneffectively treated patients. Cost predictors included effective treatment, region, payer, and index year. CONCLUSIONS: Adherence to the first bDMARD was suboptimal even in effectively treated patients, suggesting opportunities to improve adherence in patients with RA initiating biologics.

Cost of biologic treatment persistence or switching in rheumatoid arthritis.

OBJECTIVES: To estimate total costs among patients with rheumatoid arthritis (RA) who persisted on or switched from newly initiated biologic therapy. STUDY DESIGN: A retrospective claims database analysis. METHODS: This analysis included adults in the HealthCore Integrated Research Database with RA who initiated treatment with a biologic for RA (abatacept, adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, rituximab, or tocilizumab) between January 2009 and November 2014. Total healthcare costs (plan- and patient-paid) were estimated for 1 year post index. Treatment persistence was defined as no discontinuation (ie, no refill gap >45 days) and no biologic switch. RESULTS: Of 7468 patients, 45.2% persisted on the index biologic for at least 1 year without a refill gap and 16.7% switched to another biologic in the first year; other patients discontinued the index biologic (23.2%) or restarted after a refill gap (15.0%). Mean 1-year total healthcare costs per patient were $41,901 (95% CI, $40,855-$42,947) among persistent patients and $44,244 (95% CI, $40,820-$47,668) among switchers. In a multivariable analysis of all patients, switchers had 5% higher postindex costs on average than persistent patients (exp(ß) = 1.05; 95% CI, 1.01-1.08), and etanercept had the lowest postindex costs (exp(ß) ranged from 1.03 to 1.51 for other biologics relative to etanercept). CONCLUSIONS: Patients with RA who switched biologic therapy incurred higher 1-year total postswitch healthcare costs compared with patients who were persistent on the index biologic. Healthcare costs were lowest for patients who started on etanercept, particularly those who persisted on etanercept.

Treatment patterns, clinical and economic outcomes of patients with anaplastic lymphoma kinase-positive non-small cell lung cancer receiving ceritinib: a retrospective observational claims analysis.

Objective: To describe patient characteristics, treatment patterns, healthcare resource utilization (HRU), and costs among patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) receiving ceritinib in second or later line of therapy. Methods: Adult patients with NSCLC receiving ceritinib were identified from two large US claims databases (2006-2015). Patient characteristics, comorbidity profile, treatment patterns prior to ceritinib, and ceritinib dosing patterns were described. All-cause, HRU, and costs incurred during the observation period after ceritinib initiation were reported per patient per six months. Results: One hundred sixty-four patients were included (mean age 54.2 years, 57.3% female); the majority had metastatic disease (94.5%) and the average Charlson Comorbidity Index was 7.6. 150 (91.5%) patients received crizotinib prior to ceritinib - average crizotinib duration was 10.2 months and time between crizotinib discontinuation and ceritinib initiation was 2.1 months (median= 0; 25th-75th percentile= 0-0.8). Most patients (73.8%) initiated ceritinib on the recommended dose (750 mg) and maintained the dose until the end of the observation period (mean of 7.4 months) or ceritinib discontinuation; 61 (37.2%) patients discontinued ceritinib during the observation period. A total of 76 (46.3%) patients had at least one inpatient admission during the observation period after ceritinib initiation. Mean total healthcare cost per patient per six months was $111,468. Conclusions: Patients with ALK-positive NSCLC receiving ceritinib had a high comorbidity burden and generally started ceritinib on the recommended dose quickly after crizotinib discontinuation. Medical costs accounted for nearly a half of the total healthcare costs.

Economic analysis of BRAF gene mutation testing in real world practice using claims data: costs of single gene versus panel tests in patients with lung cancer.

AIMS: To assess the time to BRAF testing, compare the characteristics of tested vs not-tested patients, and describe the costs for sequential vs next-generation sequencing (NGS) BRAF testing. METHODS: Patients diagnosed with lung cancer after December 1, 2013 were identified from two US claims databases; their characteristics were assessed during the 12 months before diagnosis (index date). Testing modalities were analyzed from the index date to end of continuous health plan enrollment or data availability (December 2015), based on combinations of Current Procedural Terminology (CPT) procedure codes. Time to BRAF testing was assessed using Kaplan-Meier analysis. Costs were analyzed from a payer's perspective. RESULTS: A total of 28,011 patients newly-diagnosed with lung cancer were identified. Of them, 1,260 (4.5%) were tested for BRAF: 3.2% and 4.2% were tested at 6 and 12 months, respectively, after the index date. Compared to non-tested patients, tested patients were younger (58.3 vs 65.3 years; p < .001), had a lower Charlson Comorbidity Index (2.8 vs 2.9; p = .005), and a higher proportion had metastases (70.9% vs 43.4%; p < .001). In 76.0% of cases, BRAF was tested along with KRAS. BRAF was tested using NGS in 6.6% of cases. The average reimbursed amounts for the 10 most common CPT code combinations were $207-$2,074. Using the average costs of individual mutation tests, the total cost of sequential testing comprising KRAS, EGFR, ALK, ROS1, and BRAF tests was $3,763 ($464, $696, $1,070, $1,127, and $406, respectively), that of NGS was $2,860. LIMITATIONS: Claims data did not include BRAF test results. CONCLUSIONS: Among patients newly-diagnosed with lung cancer, 4.5% were tested for BRAF. Tested patients were younger and had a lower comorbidity burden, but more advanced disease. While reimbursed amounts varied greatly based on combinations of testing procedures, NGS testing was associated with cost savings compared to sequential testing of individual mutations.

Cost-effectiveness of ceritinib in previously untreated anaplastic lymphoma kinase-positive metastatic non-small cell lung cancer in the United States.

AIMS: To assess the cost-effectiveness of first-line ceritinib vs crizotinib and platinum doublet chemotherapy for anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) from a US third-party payer's perspective. MATERIALS AND METHODS: A partitioned survival model with three health states (stable disease, progressive disease, death) was developed over a 20-year time horizon. Ceritinib's efficacy inputs (progression-free and overall survival) were estimated from ASCEND-4; parametric survival models extrapolated data beyond the trial period. The relative efficacy of ceritinib vs chemotherapy was obtained from ASCEND-4, the relative efficacy of ceritinib vs crizotinib was estimated using a matching-adjusted indirect comparison based on ASCEND-4 and PROFILE 1014. Drug acquisition, treatment administration, adverse event management, and medical costs were obtained from publicly available databases and the literature, and inflated to 2016 US dollars. Treatment-specific stable-state utilities were derived from trials and progressive-state utility from the literature. Incremental costs per quality-adjusted life year (QALY) were estimated for ceritinib vs each comparator. Cost-effectiveness was assessed based on US willingness-to-pay thresholds. Deterministic and probabilistic sensitivity analyses were performed to test model robustness. RESULTS: In the base case, first-line ceritinib was associated with total direct costs of $299,777 and 3.28 QALYs (from 4.61 life years gained [LYG]) over 20 years. First-line crizotinib and chemotherapy were associated with 2.73 and 2.41 QALYs, 3.92 and 3.53 LYG, and $263,172 and $228,184 total direct costs, respectively. The incremental cost per QALY gained was $66,064 for ceritinib vs crizotinib and $81,645 for ceritinib vs chemotherapy. In the first 2 years following treatment initiation, ceritinib dominated crizotinib by conferring greater health benefits at reduced total costs. Results were robust to deterministic and probabilistic sensitivity analyses. LIMITATIONS: In the absence of head-to-head trials, an indirect comparison method was used. CONCLUSIONS: Ceritinib is cost-effective compared to crizotinib and chemotherapy in the treatment of previously untreated ALK-positive metastatic NCSLC in the US.

Cost-effectiveness of sequenced treatment of rheumatoid arthritis with targeted immune modulators.

AIMS: To determine the cost-effectiveness of treatment sequences of biologic disease-modifying anti-rheumatic drugs or Janus kinase/STAT pathway inhibitors (collectively referred to as bDMARDs) vs conventional DMARDs (cDMARDs) from the US societal perspective for treatment of patients with moderately to severely active rheumatoid arthritis (RA) with inadequate responses to cDMARDs. MATERIALS AND METHODS: An individual patient simulation model was developed that assesses the impact of treatments on disease based on clinical trial data and real-world evidence. Treatment strategies included sequences starting with etanercept, adalimumab, certolizumab, or abatacept. Each of these treatment strategies was compared with cDMARDs. Incremental cost, incremental quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated for each treatment sequence relative to cDMARDs. The cost-effectiveness of each strategy was determined using a US willingness-to-pay (WTP) threshold of $150,000/QALY. RESULTS: For the base-case scenario, bDMARD treatment sequences were associated with greater treatment benefit (i.e. more QALYs), lower lost productivity costs, and greater treatment-related costs than cDMARDs. The expected ICERs for bDMARD sequences ranged from ∼$126,000 to $140,000 per QALY gained, which is below the US-specific WTP. Alternative scenarios examining the effects of homogeneous patients, dose increases, increased costs of hospitalization for severely physically impaired patients, and a lower baseline Health Assessment Questionnaire (HAQ) Disability Index score resulted in similar ICERs. CONCLUSIONS: bDMARD treatment sequences are cost-effective from a US societal perspective.

Interpretation of verbal descriptors for response options commonly used in verbal rating scales in patient-reported outcome instruments.

PURPOSE: To assess the variation in the interpretation of common verbal descriptors (VDs) used in response scales and examine factors associated with those interpretations. METHODS: Subjects were recruited through MediGuard and they assigned interpretation scores (11-point scale; 0 = lowest possible, 10 = highest possible) to five common sets of VDs: set one (none, mild, moderate, severe, very severe); set two (never, rarely, sometimes, often, always); set three (poor, fair, good, very good, excellent); set four (not at all, a little bit, moderately, quite a bit, extremely); and set five (not at all, a little bit, somewhat, quite a bit, very much). One-sample test for proportions and T-tests examined equality of proportions (anchors) and means scores (non-anchors) with the fixed intervals (0.0, 2.5, 5.0, 7.5, and 10.0). Ordinal regression examined adjusted associations between demographic/clinical factors and VD scores. RESULTS: Of the 350 subjects, 68 % were females and mean (SD) age was 56.9 (12.1). Two sets had two VDs with mean (95 % CI) scores not different than the fixed intervals. Set one had mild = 2.50 (2.33; 2.66) and moderate = 5.01 (4.89; 5.13) with 98.8 % (97.3 %; 100 %) assigning none = 0. Set five had a little bit = 2.35 (2.17; 2.53) and quite a bit = 7.65 (7.43; 7.87) with 95.0 % (95 % CI 91.7; 98.2) assigning not at all = 0. Significant associations (p ≤ 0.05) included age and education with somewhat and income and comorbidities with very severe. Age, sex, and education showed associations with other VDs albeit in nonsignificant models. CONCLUSIONS: Sets one and five yielded data closest to the fixed intervals. Demographic and clinical factors are associated with the interpretation of some VDs and should be adjusted for in analyses of non-randomized data.