Cost-effectiveness of large-panel next-generation sequencing in guiding first-line treatment decisions for patients with nonsquamous advanced non-small cell lung cancer.

BACKGROUND: Clinical practice guidelines recommend broad-panel genomic profiling to identify actionable genomic alterations for patients with advanced non-small cell lung cancer (aNSCLC). OBJECTIVE: To assess the cost-effectiveness of large-panel next-generation sequencing (LP-NGS) compared with current empirical single-gene test (SGT) patterns to inform first-line treatment decisions for patients with aNSCLC from a US commercial payer perspective, accounting for the effect of testing turnaround time and time to treatment initiation. METHODS: We developed a discrete-event simulation model to estimate the impact of LP-NGS vs SGT for patients with nonsquamous aNSCLC. Discrete events and timing included testing patterns, receipt of the initial test result, treatment initiation (targeted vs nontargeted therapies), switching, retesting, rebiopsies, clinical trial participation, progression on therapy, and death. LP-NGS and SGT cohorts each comprised 100,000 adults with aNSCLC simulated over a 5-year postdiagnosis period, assumed to have the same distribution of genomic alterations. The model predicted the proportion of patients receiving appropriate first-line therapy according to clinical practice guidelines. Economic outcomes included expected life-years gained, quality-adjusted life-years, and the total costs of care over 5 years. Sensitivity and scenario analyses explored the robustness of the base-case model results. RESULTS: In the base-case model, LP-NGS was likely to identify more alterations than SGT. Total 5-year costs per patient were $539,658 for LP-NGS and $544,550 for SGT (net difference, $4,892 lower costs per patient for LP-NGS), which is likely to be cost-effective 95.1% of the time. The most influential model parameters on the 5-year total costs of care were preprogression nondrug medical costs on nontargeted therapy, NGS turnaround time, and clinical trial participation. CONCLUSIONS: This study suggests that LP-NGS to guide first-line treatment decisions is clinically more appropriate (more likely to identify alterations and subsequently allocate patients to clinically appropriate therapy) and provides a dominant cost-effectiveness treatment strategy over 5 years for patients with newly diagnosed aNSCLC in the United States.

The Association of Retinal Disease with Vision Impairment and Functional Status in Medicare Patients.

Background: The association of neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), and retinal vein occlusion (RVO) with functional status in the general Medicare population are not well established. Objectives: This study examined patient-reported survey data linked with Medicare claims to describe the burden of these vision-threatening retinal diseases (VTRDs) among Medicare beneficiaries. Methods: Medicare Current Beneficiary Survey data linked with Medicare Fee-for-Service claims data from 2006 to 2018 were used in a nationally representative retrospective pooled cross-sectional population-based comparison study. Outcomes between community-dwelling beneficiaries with nAMD (n = 1228), DME (n = 101), or RVO (n = 251) were compared with community-dwelling beneficiaries without any VTRDs (n = 104 088), controlling for baseline demographic and clinical differences. Beneficiaries with a diagnosis of nAMD, DME, or RVO during the data year were included; those with other VTRDs were excluded. Outcomes included vision function and loss, overall functioning as assessed by difficulties with activities of daily living (ADLs) and instrumental ADLs (iADLs), anxiety/depression, falls, and fractures. Results: In patient cohorts with nAMD, DME, and RVO, approximately one-third (34.2%-38.3%) reported "a little trouble seeing" (vs 28.3% for controls), and 26%, 17%, and 9%, respectively, reported "a lot of trouble seeing/blindness" (vs 5% of controls). Difficulty walking and doing heavy housework were the most reported ADLs and iADLs, respectively. Compared with those without VTRDs, beneficiaries with nAMD had higher odds of diagnosed vision loss (odds ratio [OR], 5.39; 95% confidence interval, 4.06-7.16; P < .001) and difficulties with iADLs (odds ratio, 1.41; 95% confidence interval, 1.11-1.80; P = .005); no differences were observed for DME or RVO vs control. After adjusting for age, sex, race/ethnicity, poverty status, comorbidities, and other relevant covariates, nAMD, DME, and RVO were not significantly associated with anxiety/depression, falls, or fractures. Discussion: Patients with nAMD or DME were more likely to report severe visual impairment than those without VTRDs, although only those with nAMD were more likely to be diagnosed with vision loss. Conclusions: Patients with nAMD continue to experience more vision impairment and worse functional status compared with a similar population of Medicare beneficiaries despite availability of therapies like antivascular endothelial growth factor to treat retinal disease.

Healthcare resource utilization and cost among individuals with late-onset versus adult-onset Huntington's disease: a claims­based retrospective cohort study.

AIMS: Quantify healthcare resource utilization (HRU) and costs for individuals with late-onset Huntington's disease (LoHD) and compare these with adult-onset HD (AoHD) and non-HD controls. METHODS: This retrospective cohort study used US healthcare claims data from the IBM MarketScan Commercial and Medicare Supplemental Databases. Individuals newly diagnosed with HD between 1/1/2009 and 12/31/2017 were selected (index date was first HD claim). Individuals ≥60 years of age at the index date were categorized as having LoHD while individuals 21-59 years of age were categorized as having AoHD. Non­HD controls were exact matched 2:1 to LoHD and AoHD cohorts. Individuals were required to have continuous enrollment for ≥12 months pre- and post-index. Twelve-month all-cause HRU and healthcare costs were assessed for each cohort. RESULTS: In total, 763 individuals with LoHD and 1,073 individuals with AoHD were matched with 3,762 non-HD controls. Unadjusted all-cause HRU in the 12 months post-index was higher for individuals with LoHD and AoHD compared with non-HD controls across most service categories. Adjusted all-cause HRU for the LoHD cohort was significantly higher compared with non-HD controls across all service categories. In the 12 months post-index, mean total costs for the LoHD cohort ($29,055) were significantly higher than for non-HD controls (≥60 years old: $17,286; 21-59 years old: $12,688; p <.001) and similar to total costs in the AoHD cohort ($31,701; p =.47). LIMITATIONS: It was not possible to control for differences in HD stage but regression models were adjusted for baseline HRU. Evaluations of costs did not include indirect costs, which are known to be significant components of the wider HD burden. CONCLUSIONS: This study provides the first analysis of HRU and costs in LoHD, demonstrating that individuals with LoHD experience a significantly higher healthcare burden compared with non-HD controls and a similarly high burden compared with individuals with AoHD.

Huntington's disease (HD) usually develops between the ages of 30­50 but can develop earlier/later. This study looked at healthcare use in people who developed HD at age 60 or later in the United States. Researchers found that people who develop HD at age 60 or later have similar health needs to people with adult-onset HD. Furthermore, they have much greater health needs than people of a similar age who do not have HD.

Trends in Healthcare Resource Use Preceding Diagnosis of Alzheimer's Disease Dementia.

Introduction: An Alzheimer's disease (AD) dementia diagnosis is often preceded by an extended period of cognitive decline. Few studies have examined healthcare resource use (HRU) during an extended period before AD dementia diagnosis. Methods: In a historical claims-based cohort study, propensity score-matched cohorts of patients with and without AD dementia were observed for a 5-year prediagnosis period and a 1-year postdiagnosis period. Demographics, clinical characteristics, and HRU were compared between groups. Results: Individuals in the AD dementia group displayed a greater level of medical complexity in the year before diagnosis of AD dementia relative to those in the matched cohort. Both all-cause and AD dementia complication-related HRU increased gradually, with a marked spike at the time of initial AD dementia diagnosis. Discussion. Further research into the natural history of patients with AD dementia is necessary to improve identification of early AD and to better understand its broader impact.

Health care resource utilization and costs among individuals with vs without Huntington disease in a US population.

BACKGROUND: Quantifying the extent of health care resource utilization (HCRU) and costs associated with Huntington disease (HD) is vital for providers, decisionmakers, and payers to understand unmet treatment needs and to ensure limited resources can be used to benefit the maximum number of people with HD. OBJECTIVE: To quantify HCRU and costs for people with HD, overall and by disease stage, and compare these with non-HD controls. METHODS: This was a retrospective cohort study using administrative claims data from the IBM MarketScan Commercial, Multi-State Medicaid, and Medicare Supplemental Databases from January 1, 2009, to December 31, 2018. People with an HD claim between January 1, 2010, and December 31, 2017, were selected for this analysis and matched with non-HD controls for comparison. The HD cohort and the non-HD controls were exact matched on their follow-up duration and propensity score matched 1:4 to create the final analytical cohort. Index date was the first HD diagnosis for the HD cohort (proxy index date assigned to controls), and all individuals were required to have continuous enrollment for 12 or more months pre-index (baseline) and 3 or more months post-index. Proportions of all-cause HCRU (ie, outpatient visits, inpatient visits, emergency department visits, pharmacy fills, radiology visits, and physical/occupational therapy visits) in the 6-months post-index and HCRU counts and costs per patient per month (PPPM) over the entire follow-up were calculated for each cohort. RESULTS: A total of 2,473 individuals with HD and 9,522 matched non-HD controls were identified. HCRU in 6 months post-index was significantly greater in people with HD compared with non-HD controls for all health care service categories; P < 0.0001. The mean number of HCRU PPPM for all measured healthcare services was significantly higher in people with HD compared with non-HD controls (P < 0.001). Mean total costs (2018 USD PPPM) for the HD cohort ($2,260 [SD = $4,682]) were twice the total costs in the non-HD cohort ($1,056 [SD = $3,078]) (P < 0.0001) and were highest across all disease stages. CONCLUSIONS: This study provides current comprehensive HCRU and cost estimates in individuals with HD relative to those without the disease, thus demonstrating the high economic burden imposed by HD. DISCLOSURES: Dr Ta: Employment with Genentech (at time of study) and stock options with Roche; Dr To: Employment and stock options/dividends with Genentech; Dr Patel: Employment and stock options with Roche/Genentech; Dr Fuller: Employment with CHDI Management/CHDI Foundation; Mr Surinach: Employment with Genesis Research (which receives consulting fees from Genentech/Roche); Dr Abbass: Employment and stock options with Genentech; Dr Exuzides: Employment and stock options with Roche/Genentech; and Ms Luo: Employment with CHDI Management/CHDI Foundation. This study was funded by Genentech Inc. The authors thank Greg Rowe of Chrysalis Medical Communications for providing medical writing support, which was funded by F. Hoffmann-La Roche Ltd, in accordance with Good Publication Practice (GPP3) guidelines (http://www.ismpp.org/gpp3).

Healthcare resource utilization and costs in individuals with Huntington's disease by disease stage in a US population.

AIMS: To quantify healthcare resource utilization (HRU) and costs by disease stage in individuals with Huntington's disease (HD) in a US population. MATERIALS AND METHODS: This retrospective cohort study used administrative claims data from the IBM MarketScan Commercial, Multi-State Medicaid, and Medicare Supplemental Databases between 1 January 2009 and 31 December 2018. Individuals with an HD claim between 1 January 2010 and 31 December 2017 were selected. Index date was the date of first HD diagnosis. Individuals were required to have continuous enrollment for ≥ 12 months pre-index, 3 months post-index, and have no pre-index HD claims. All-cause HRU and costs per patient per month (PPPM) (overall and stratified by disease stage) were assessed for individuals with HD. RESULTS: A total of 2,669 individuals with HD were identified. Of these, 1,432 (53.7%), 689 (25.8%), and 548 (20.5%) had early-, middle-, and late-stage HD at baseline, respectively. Mean HRU PPPM by post-index HD stage increased with disease stage for outpatient visits, pharmacy claims, and HD-related pharmacy claims (p < 0.05 for all). Mean inpatient visits and emergency room visits PPPM were highest in individuals with middle-stage HD (p <0.05 for all). Mean total all-cause healthcare cost PPPM for individuals with HD was $2,889, and it was significantly higher in middle-stage individuals, at $7,988, compared with early- and late-stage individuals, at $3,726 and $5,125, respectively; p <0.0001. LIMITATIONS: In the absence of disease staging information in administrative claims data, staging was based on the presence of clinical markers in claims. Our evaluations didn't include the indirect costs of HD, which may be substantial as HD typically affects people at their peak earning potential. CONCLUSIONS: HRU and costs of care are high among individuals with HD, particularly among those with middle- and late-stage disease. This indicates that the disease burden in HD increases with disease stage, highlighting the need for interventions that can slow or prevent disease progression.

Healthcare Resource Use and Burden Associated with Influenza Transmission Among Household Members with a Primary Infection: Commercial Claims Data Analysis.

PURPOSE: To assess the burden of influenza transmission and care-seeking patterns over 3 influenza seasons among commercially insured households with a primary influenza infection. PATIENTS AND METHODS: This retrospective cohort study used commercial claims data from the US MarketScan® Commercial and Medicare Supplemental databases for the 2014, 2015, and 2016 influenza seasons. Patients with a billed diagnosis of influenza and with coverage for at least 1 household member under the same health plan policy were included. A secondary diagnosed case was defined as a diagnosis of influenza in a second household member occurring within 14 days of the index case in a household. RESULTS: Among 1,224,808 households with ≥2 members and a primary case of influenza, a secondary case of influenza was reported in 119,883 households (9.8%). A secondary diagnosed case of influenza occurred within 4 days of the primary diagnosis in 93,883 (78.3%) of those households. Both primary and secondary diagnosed influenza cases occurred most often among children (~60%). Household size was positively correlated to both the risk of a second case (6.4% of households with 2 or 3 members versus 12.6% of households with ≥4 members, P < 0.001) and the time to diagnosis of a second case (Spearman rank correlation coefficient = 0.09; P < 0.001). CONCLUSION: Claims data for 3 influenza seasons (2014, 2015, 2016) showed that intrahousehold transmission of influenza occurs in approximately 10% of households with a primary case and poses a higher burden on larger households. Intrahousehold transmission of influenza represents a large healthcare resource use burden, with an unmet need for interventions that limit transmission.

Risk of Blindness Among Patients With Diabetes and Newly Diagnosed Diabetic Retinopathy.

OBJECTIVE: To evaluate the association between initial diabetic retinopathy (DR) severity/risk of blindness in patients with newly diagnosed DR/good vision in the U.S. RESEARCH DESIGN AND METHODS: This retrospective cohort study evaluated adult patients with good vision (20/40 or better) and newly diagnosed DR between 1 January 2013 and 31 December 2017 (index date) in the American Academy of Ophthalmology's Intelligent Research in Sight (IRIS) Registry. The primary exposure of interest was DR severity at index: mild nonproliferative DR (NPDR), moderate NPDR, severe NPDR, and proliferative DR (PDR). The main outcome measure was development of sustained blindness (SB), defined as study eyes with Snellen visual acuity readings of 20/200 or worse at two separate visits ≥3 months apart that did not improve beyond 20/100. RESULTS: Among 53,535 eligible eyes (mean follow-up 662.5 days), 678 (1.3%) eyes developed SB. Eyes with PDR at index represented 10.5% (5,629 of 53,535) of the analysis population but made up 26.5% (180 of 678) of eyes that developed SB. Kaplan-Meier analysis revealed that eyes with moderate NPDR, severe NPDR, and PDR at index were 2.6, 3.6, and 4.0 times more likely, respectively, to develop SB after 2 years of DR diagnosis versus eyes with mild DR at index. In a Cox proportional hazards model adjusted for index characteristics/development of ocular conditions during follow-up, eyes with PDR had an increased risk of developing SB versus eyes with mild NPDR at index (hazard ratio 2.26 [95% CI 2.09-2.45]). CONCLUSIONS: In this longitudinal ophthalmologic registry population involving eyes with good vision, more advanced DR at first diagnosis was a significant risk factor for developing SB.

Work Productivity Outcomes Associated with Ocrelizumab Compared with Other Disease-Modifying Therapies for Multiple Sclerosis.

OBJECTIVE: This study evaluated work and activity impairment in patients with multiple sclerosis (MS) treated with ocrelizumab (OCR) versus other disease-modifying therapies (DMTs). METHODS: Data were obtained from the Adelphi Real World Disease Specific Programme for Multiple Sclerosis. Patients with relapsing-remitting or secondary progressive MS who completed surveys in 2018 and 2019 and received ≥ 6 months of an eligible therapy, including OCR, injectable therapy, and oral therapy, were included. Outcomes were assessed using the patient-reported Work Productivity and Activity Impairment questionnaire. Doubly robust estimation, which combined propensity score weighting and regression modeling, was used to compare treatments, controlling for baseline clinical and demographic characteristics. RESULTS: This study included 630 patients (OCR, n = 90; injectable DMT, n = 224; oral DMT, n = 316) with a mean (standard deviation) age of 42 (11) years. A greater proportion of OCR-treated patients had an Expanded Disability Status Scale score of ≥ 3 at treatment initiation compared with those receiving oral and injectable DMTs (51 vs. 15% and 15%, respectively), and a smaller proportion of OCR-treated patients received treatment for ≥ 1 year (43 vs. 90% and 92%, respectively). OCR-treated patients had higher odds of employment [odds ratio (95% confidence interval) 3.4 (1.5-7.7) vs. oral DMT, 5.6 (2.6-12.0) vs. injectable DMT], lower overall work productivity loss [difference (95% confidence interval) - 10.0% (- 6.1 to - 15.0%) vs. oral DMT, - 13.0% (- 8.5 to - 17.0%) vs. injectable DMT] and lower activity impairment [difference (95% confidence interval) - 11% (- 7.1 to - 16.0%) vs. oral DMT, - 9.7% (- 5.0 to - 14.0%) vs. injectable DMT]. CONCLUSION: This real-world evidence suggests that patients with MS treated with OCR experience lower work and activity impairment than patients treated with other DMTs.

Multiple sclerosis (MS) is the most common progressive neurological disease in young adults. It typically starts between the ages of 20 and 40 years­arguably some of the most productive years of an individual's life­and it has a large impact on many aspects of everyday life for the rest of a person's life. The reduction in the ability to do routine activities, including working, results in a large economic burden. Disease-modifying treatments (DMTs) available for MS, particularly high-efficacy DMTs, have been shown to improve work productivity. This study looked at work and activity impairment using the Work Productivity and Activity Impairment Questionnaire in patients with MS who were treated with ocrelizumab (OCR) or other DMTs for ≥ 6 months. A total of 630 patients with relapsing­remitting MS (RRMS) or secondary progressive MS (SPMS) from the Adelphi Real World Disease Specific Programme for Multiple Sclerosis were included in the study, including 90, 316 and 224 patients who completed ≥ 6 months of treatment with OCR, oral or injectable therapy. Compared with patients receiving oral or injectable DMTs, those receiving OCR had higher odds of employment [odds ratio (OR) vs. oral DMT 3.4; OR vs. injectable DMT 5.6], lower overall work productivity impairment (difference vs. oral DMT − 10%; difference vs. injectable DMT − 13%) and lower activity impairment (difference vs. oral DMT − 11%; difference vs. injectable DMT − 9.7%). These findings in patients with RRMS or SPMS being treated in the real world suggest that OCR may reduce the impact of MS disease on work productivity more than other DMTs.

Five-Year Patterns of Diabetic Retinopathy Progression in US Clinical Practice.

PURPOSE: To characterize the natural course of diabetic retinopathy (DR) in contemporary clinical practice. PATIENTS AND METHODS: This was a retrospective analysis of US claims data collected between January 1, 2006, and April 30, 2017. Patients aged ≥18 years with continuous medical and prescription insurance coverage for 18 months before DR diagnosis (index date) and for a follow-up period of 5 years were included (N=14,490). The time and risk of progressing to severe nonproliferative DR (NPDR) or proliferative DR (PDR) and of developing diabetic macular edema (DME) were evaluated over 5 years in patients stratified by DR severity at initial diagnosis. RESULTS: The estimated probability of progressing to severe NPDR or PDR within 5 years of diagnosis was 17.6% for patients with moderate NPDR versus 5.8% for mild NPDR. The probability of developing DME within 5 years was 62.6%, 44.6%, and 28.4% for patients diagnosed with severe NPDR, moderate NPDR, and PDR, respectively, versus 15.6% for mild NPDR. Among those observed to progress, median time to severe NPDR or PDR was approximately 2.0 years in patients with moderate NPDR, whereas median time to DME was approximately 0.5 years in patients with severe NPDR, 1.3 years in moderate NPDR, and 1.6 years in PDR. Relative to mild NPDR, adjusted hazard ratios (95% confidence interval) for progression to severe NPDR or PDR within 5 years were 3.12 (2.61-3.72) in patients with moderate NPDR, and for incident DME were 5.92 (5.13-6.82), 3.54 (3.22-3.91), and 1.96 (1.80-2.14) in patients with severe NPDR, moderate NPDR, and PDR, respectively. CONCLUSION: The risk of DR progression and DME over 5 years was highest among patients diagnosed with moderate and severe NPDR, respectively. Our findings reinforce the importance of close monitoring for these patients to avoid unobserved disease progression toward PDR and/or DME.

Real-World Persistence with Tocilizumab Compared to Other Subcutaneous Biologic Disease-Modifying Antirheumatic Drugs Among Patients with Rheumatoid Arthritis Switching from Another Biologic.

INTRODUCTION: In patients with rheumatoid arthritis (RA) who have an inadequate response to or intolerance of their first biologic disease-modifying antirheumatic drug (bDMARD), guidelines recommend switching to a different biologic class. The objective of this study was to compare persistence with subcutaneous (SC) tocilizumab to persistence with other SC bDMARDs when these drugs are used as subsequent-line therapy in RA patients who previously received ≥ 1 bDMARD. METHODS: RA patients in a US administrative claims database who initiated a second- or subsequent-line SC bDMARD between January 1, 2012 and June 30, 2017 (initiation date = index date) were included. Persistence was defined as the number of days between the bDMARD initiation date and (1) the last supplied day of medication fill (primary) or (2) the day on which the patient switched or there was a gap in treatment of > 90 days (secondary). Parametric survival models utilizing an exponential distribution with a robust variance estimator were used to compare persistence with tocilizumab to persistence with other bDMARDs. RESULTS: A total of 10,301 patients with 12,704 bDMARD episodes were included. Patients receiving tocilizumab had a significantly higher adjusted median (95% CI) number of days of primary persistence [333 (311-356)] than those receiving adalimumab [280 (268-293); P < 0.001], certolizumab [262 (241-284); P < 0.001], and etanercept [289 (274-304); P = 0.001], and a similar persistence to those receiving abatacept [320 (305-335); P = 0.327] and golimumab [304 (274-333); P = 0.122]. CONCLUSION: Among patients with RA who had previously received ≥ 1 bDMARD, tocilizumab-treated patients exhibited a similar or significantly better biologic persistence than those receiving other bDMARDs.

Impact of Coexisting Overactive Bladder in Medicare Patients With Dementia on Clinical and Economic Outcomes.

BACKGROUND: Patients with dementia commonly suffer from symptoms of overactive bladder (OAB); however, limited research exists on the clinical impact of coexisting OAB among patients with dementia. As such, the objective of this study was to examine the impact of OAB on clinical outcomes, health-care resource use, and associated costs among patients with dementia. METHODS: We conducted a retrospective cohort analysis of patients with dementia using 3861 matched pairs of patients with and without OAB. Analyses were based on administrative claims data from January 1, 2007, to September 30, 2015, and compared clinical outcomes, health services use, and associated costs. RESULTS: Patients with dementia and OAB were more likely than those without OAB to have least one fall (incidence rate ratio [IRR]: 1.43, 95% confidence interval [CI], 1.22-1.68, P < .001), fracture (IRR: 1.23, 95% CI, 1.05-1.44, P = .008), combined fall/fracture (IRR: 1.25, 95% CI, 1.11-1.42, P < .001), or urinary tract infection (IRR: 2.75, 95% CI, 2.55-2.96, P < .001). Patients with dementia and OAB demonstrated greater utilization of all-cause encounter types compared to similar patients without coexisting OAB (P < .01). All-cause and dementia-related total health-care costs were approximately 23% (95% CI, 0.19-0.28, P < .001) and 13% (95% CI, 0.05-0.20, P = .001), respectively, greater than similar patients without coexisting OAB. CONCLUSION: Coexisting OAB was associated with impacts on clinical outcomes, health-care resource utilization, and costs in patients with dementia.

Comparison of real-world outcomes in patients with nonvalvular atrial fibrillation treated with direct oral anticoagulant agents or warfarin.

PURPOSE: To compare patients with atrial fibrillation (AF) initiating direct oral anticoagulants (DOACs) versus warfarin on clinical outcomes including stroke, systemic embolism (SE), bleeding events, and cost of care. METHODS: This retrospective observational study used Medicare Advantage Prescription Drug and fully insured commercial claims from the Humana Research Database. Patients with AF who initiated a DOAC or warfarin from January 1, 2012, through September 30, 2015, were included. Date of the first prescription of DOAC or warfarin was the index date. Patients in the DOAC and warfarin groups were matched on propensity scores. Patients were censored at end of enrollment or study period, discontinuation, or switch of index medication. Clinical outcomes were compared in the matched groups using Cox proportional hazards models. Annualized costs and costs adjusted for censoring using Lin's interval method were also compared between the two cohorts. RESULTS: Patients on DOACs had a significantly lower risk of ischemic stroke (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.79-0.98), hemorrhagic stroke (HR, 0.65; CI, 0.46-0.92), SE (HR, 0.53; 95% CI, 0.43-0.65), and composite outcome of stroke or SE (HR, 0.78; 95% CI, 0.71-0.86) compared with patients on warfarin. Bleeding risk was not statistically significant (HR, 0.85; 95% CI, 0.71-1.01). While annualized pharmacy costs were higher, annualized medical and total costs were lower in the DOAC group compared with the warfarin group. CONCLUSION: The results of the study indicated that patients on DOACs had lower rates of ischemic stroke, hemorrhagic stroke, SE, and composite outcome of stroke or SE compared with patients on warfarin. No significant differences in bleeding rates between the DOAC and warfarin groups were observed, while total cost of care was lower in the DOAC group.

Healthcare Costs of Potential Glucocorticoid-Associated Adverse Events in Patients with Giant Cell Arteritis.

OBJECTIVE: To quantify the healthcare expenditures associated with potential oral glucocorticoid (OGC)-related adverse events (AEs) in patients with giant cell arteritis (GCA). METHODS: Patients with GCA and ≥ 1 OGC prescription fill between 2009 and 2014 were identified from the MarketScan Commercial and Medicare Supplemental claims databases. Patients were stratified into four groups based on cumulative OGC dose (> 0 to ≤ 2607 mg, > 2607 to ≤ 4800 mg, > 4800 to ≤ 7200 mg, and > 7200 mg) during the 1-year follow-up period; incidence of potential AEs and AE-related direct healthcare costs in USD were assessed. Association between the log of cumulative OGC dose and AE-related direct healthcare costs was evaluated, adjusting for baseline characteristics. RESULTS: Of 1602 patients with GCA included, 69% were women; the mean age was 73 years. The mean cumulative OGC dose was 5806 mg during the 1-year follow-up; most exposure occurred in the first 6 months. The proportion of patients with potential OGC-related AEs was 36.5% overall and increased as cumulative dose increased (30.7%-45.3% across dose groups). Unadjusted mean AE-related costs for patients with an AE was USD $12,818. In the multivariable model including all patients, increasing OGC dose was associated with increasing AE-related healthcare costs (cost ratio, 1.38 [95% CI, 1.16-1.64] per 1-unit increase in log of cumulative OGC dose [P < 0.001]). Mean (median)-predicted AE costs for the dose groups were USD $4389 ($2749) for > 0 to ≤ 2607 mg, USD $5176 ($3009) for > 2607 to ≤ 4800 mg, USD $5576 ($3633) for > 4800 to ≤ 7200 mg, and USD $6609 ($4447) for > 7200 mg. CONCLUSION: In patients with GCA, OGC-related AEs increased with increasing cumulative OGC dose, resulting in increased healthcare costs. These results highlight the need for efficacious therapies that reduce the exposure to and potential risks associated with OGCs.

Impact of coexisting overactive bladder in Medicare patients with osteoporosis.

BACKGROUND: Osteoporosis and overactive bladder (OAB) are prevalent conditions in older adults and are independent risk factors for falls and fractures. A paucity of evidence exists examining the impact of coexisting OAB in patients with osteoporosis. OBJECTIVE: To examine the impact of OAB on healthcare resource utilization (HRU), clinical outcomes, and healthcare costs among older adult patients with osteoporosis. METHODS: This retrospective analysis compared patients with osteoporosis with and without OAB. Patients with an osteoporosis diagnosis, enrolled in a Medicare Advantage plan, and aged 65-89 inclusive were eligible. Incident OAB among patients with prevalent osteoporosis was identified. A comparison group of patients with osteoporosis but no evidence of OAB was propensity score matched on baseline characteristics. Fall and/or fracture outcomes, HRU and healthcare costs were evaluated during 12 months of follow-up. Bivariate comparisons of outcomes were conducted. Ordinary least squared regression was used to examine the relationship between OAB and total healthcare costs. RESULTS: After matching, 5,526 patients in each group were included. Patients with osteoporosis and OAB demonstrated greater all-cause HRU across all encounter types compared to patients without OAB (all P values<0.001). Patients with osteoporosis and OAB had a greater frequency of any fall/fracture (17.7% vs. 14.9%, P<0.001). Patients with osteoporosis and OAB had 35% greater all-cause total healthcare costs than patients without OAB (P<0.001). CONCLUSIONS: Patients with OAB and osteoporosis had significantly greater all-cause HRU and costs. Falls and fractures were significantly more common in patients with osteoporosis and OAB compared to patients with osteoporosis without OAB.

Predictors of all-cause 30 day readmission among Medicare patients with type 2 diabetes.

OBJECTIVE: Readmission is costly among patients with type 2 diabetes (T2DM) in Medicare Advantage Prescription Drug Plans; identifying high-risk patients is necessary for targeting reduction programs. The objective of this study was to develop a claims-based algorithm to predict all-cause 30 day readmission among patients with T2DM. METHODS: This study used administrative data from 1 January 2012 through 31 January 2014. The cohort included hospitalized T2DM patients, aged 18-90 with ≥12 months' continuous enrollment before an unplanned hospital admission and ≥1 month of enrollment post-discharge, excluding patients in long-term care >30 days pre-index. Multivariate logistic regression predicted the likelihood of readmission following hospitalization in 2013. The analytic file was randomly split into training and test datasets to build and validate the model. Candidate variables included physician and patient demographics, baseline clinical conditions, and healthcare utilization metrics. Clinical conditions were classified using the Healthcare Cost and Utilization Project clinical classification system for ICD-9-CM. RESULTS: Of 63,237 individuals, 17.1% experienced a readmission. Of nearly 200 candidate variables, 14 were predictors of readmission, including total cumulative number of days for inpatient stays and the number of emergency department visits in the baseline period. Male gender, older age, and certain comorbidities were associated with higher likelihood of readmission. The final model demonstrated good discriminant ability (c-statistic = 0.82). CONCLUSIONS: This study provided evidence that certain patient characteristics and healthcare utilization are predictive of readmission. An algorithm with good discriminant ability was developed which could be used to target readmission reduction programs. Physician gender, specialty, and ownership status did not appear to influence the likelihood of readmission.

Medication Nonadherence: The Role of Cost, Community, and Individual Factors.

OBJECTIVE: To explain the association of out-of-pocket (OOP) cost, community-level factors, and individual characteristics on statin therapy nonadherence. DATA SOURCES: BlueCross BlueShield of Texas claims data for the period of 2008-2011. STUDY DESIGN: A retrospective cohort of 49,176 insured patients, aged 18-64 years, with at least one statin refill during 2008-2011 was analyzed. Using a weighted proportion of days covered ratio, differences between adherent and nonadherent groups are assessed using chi-squared tests, t-tests, and a clustered generalized linear model with logit link function. PRINCIPAL FINDINGS: Statin therapy adherence, measured at 48 percent, is associated with neighborhood-level socioeconomic factors, including race/ethnicity, educational attainment, and poverty level. Individual characteristics influencing adherence include OOP medication cost, gender, age, comorbid conditions, and total health care utilization. CONCLUSIONS: This study signifies the importance of OOP costs as a determinant of adherence to medications, but more interestingly, the results suggest that other socioeconomic factors, as measured by neighborhood-level variables, have a greater association on the likelihood of adherence. The results may be of interest to policy makers, benefit designers, self-insured employers, and provider organizations.

Impact of Overactive Bladder Step Therapy Policies on Medication Utilization and Expenditures Among Treated Medicare Members.

BACKGROUND: The impact of formulary management strategies on utilization and expenditures in overactive bladder (OAB) treatment has not been extensively investigated. In 2013, step therapy (ST) policies for 2 branded OAB treatments, mirabegron and fesoterodine, were removed from Humana Medicare Advantage Prescription Drug (MAPD) plans and Medicare prescription drug plans (PDP), allowing for an examination of the effect of ST policies on OAB medication use patterns and costs. OBJECTIVE: To assess the impact of removal of formulary restriction policies for mirabegron and fesoterodine on medication utilization patterns and costs associated with OAB treatment in Medicare patients. METHODS: A retrospective cross-sectional study design was utilized. Subjects included individuals enrolled in Humana MAPD plans or PDPs, aged ≥ 65 years, with ≥ 1 prescription for an OAB medication in 2013. Patient demographic characteristics, OAB medication utilization, and pharmacy cost trends in 2013 were described. OAB medication use was calculated as the number of 30-day-supply equivalent medication claims and reported as a percentage of the total number of 30-day-supply equivalent claims across all OAB products. OAB medication expenditures were calculated as a percentage of the sum of pharmacy costs for OAB medications and reported separately for each month and drug during 2013. Temporal trends of OAB medication utilization and expenditures in 2013 were calculated using ordinary least squares regression. RESULTS: Of 194,511 patients, trends in utilization of OAB medications indicated that on average, there was a statistically significant monthly increase in utilization of mirabegron (regression coefficient [B] = 274; P < 0.001; 95% CI: 218, 330), fesoterodine (B = 167; P < 0.001; 95% CI = 129, 205), oxybutynin extended release (ER; B = 357; P = 0.011; 95% CI = 99, 614), and trospium ER (B = 33; P = 0.001; 95% CI = 17, 50) and statistically significant decreases in utilization of solifenacin (B = -202; P = 0.048; 95% CI = -402, -2), tolterodine ER (B = -287; P = 0.002; 95% CI = -437, -137), darifenacin (B = -94; P < 0.001; 95% CI = -128, -61), and trospium immediate release (IR; B = -22; P = 0.001; 95% CI = -32, -12). Total OAB medication expenditures significantly increased an average of 0.12% for each month during the course of 2013 (B = 0.12; P = 0.026; 95% CI = 0.017, -0.223). While monthly oxybutynin IR utilization did not change significantly throughout 2013 (B = 228; P = 0.169; 95% CI = -114, -570), it demonstrated the largest average monthly expenditure increase (B = 0.082; P < 0.001; 95% CI = 0.056, 0.108). When removing oxybutynin IR costs from the total OAB medication costs, the trend in total OAB medication average monthly expenditures was not significant (B = 0.038; P = 0.365; 95% CI = -0.051, -0.126). An over 4-fold per-unit-cost increase for oxybutynin IR was noted. CONCLUSIONS: Utilization of 2 branded OAB products increased in the months after ST removal with minimal cost impact. One of the possible reasons total OAB expenditures increased may have been due to the increased cost of the largest-volume generic product, oxybutynin IR. DISCLOSURES: This research was funded by Astellas Pharma Global Development and was conducted as part of the Astellas-Humana Research Collaboration. Ng, Kristy, Schermer, and Bradt are employees of Astellas. Astellas manufactures mirabegron (Myrbetriq) and solifenacin (VESIcare). Abbass, Caplan, Collins, and Suehs are employees of Comprehensive Health Insights, a subsidiary of Humana, which received funding from Astellas for this study. Suehs owns stock in Humana. Chan is an employee of Humana Pharmacy Solutions. Portions of this study were presented as a poster at Academy of Managed Care Pharmacy Nexus 2015; October 26-29, 2015; Orlando, Florida. Study concept and design were contributed by Ng, Chan, Suehs, and Abbass, along with Collins. Abbass took the lead in data collection, along with Collins and with assistance from Caplan, Chan, and Suehs. Data interpretation was provided by Kristy and Bradt, along with Abbass, Caplan, Ng, Suehs, Collins, and Chan. The manuscript was written primarily by Caplan, along with Schermer, Suehs, and Abbass, and revised by Caplan, Schermer, and Ng, along with the other authors.

Revisiting the economic efficiencies of observation units.

BACKGROUND: Recent studies cast doubt about the economic efficiency of observation units (OUs). OBJECTIVE: We aimed to reexamine the cost savings of OUs compared with inpatient care. METHODS: Claims for 15,851 patients who were admitted to inpatient or OUs between January 2009 and December 2012 following emergency room (ER) visits for chest pain were retrospectively examined. The two groups were compared for total cost of episode, length of stay (LOS), and utilization rates of diagnostic procedures, including standard exercise and echocardiography stress tests, myocardial perfusion imaging (MPI), coronary computed tomography angiography (CCTA), and computed tomography (CT) chest scans. Total costs of care and LOS were adjusted for age, gender, risk scores, and comorbidities using quantile regression. RESULTS: More than 37% of the sample was admitted to inpatient units (n = 5,890) vs 62.7% to OUs (n = 9,961). Patients admitted to inpatient units had more comorbidities and longer LOS during their ER visit (median 1.5 adjusted days; 10th percentile = 1, 90th percentile = 3) vs. median 21 adjusted hours for OUs (20, 23). The adjusted median cost of OUs was $5,411 ($4,652, $7,157) vs. $6,946 for inpatient admission ($5,978, $18,683). The estimated adjusted cost saving of OUs was $1,535 (95% CI = $1,206, $1,411) compared with inpatient admission. About 37% of patients admitted to OUs stayed longer than 24 hours. Compared with patients admitted to inpatient units, patients in OUs also received more MPI (35.8% vs. 31.5%), CT scans (13.2% vs. 10.4%), standard exercise test (45.6% vs. 33.8%) and echocardiography stress test (8% vs. 3.4%). CONCLUSION: Despite the increased proportion of patients exceeding the 24-hour LOS and the increased utilization of advanced imaging procedures, OUs are still less costly compared with inpatient admission.