Burden of Parkinson's Disease by Severity: Health Care Costs in the U.S. Medicare Population.

BACKGROUND: Current understanding of the health care costs of Parkinson's disease (PD) and the incremental burden of advanced disease is incomplete. OBJECTIVES: The aim of this study was to assess the direct economic burden associated with advanced versus mild/moderate PD in a prevalent national sample of elderly U.S. Medicare beneficiaries with a PD diagnosis. METHODS: Analyzing 100% fee-for-service Medicare claims from 2013, we defined advanced PD with a medication-based algorithm and calculated all-cause and PD-related costs for the overall sample and by disease severity. We measured primary PD-related costs (based on claims with a primary diagnosis of PD) and any PD-related costs (based on claims with PD in any diagnostic field). Generalized linear models were used to estimate risk-adjusted mean cost differences between the advanced and mild/moderate PD groups for the calendar year. RESULTS: The final sample (N = 144,703) had mean observed all-cause, primary PD-related, and any PD-related costs of $23,041 (SD, $34,045), $3429 (SD, $7431), and $9924 (SD, $22,140), respectively. Twenty percent of patients were classified as advanced PD. Costs varied substantially; any PD-related mean costs were $483 for the lowest patient decile (which included 1% of the advanced group) and $48,145 for the highest decile (which included 15% of the advanced group). Incremental risk-adjusted costs of advanced PD were $5818 (95% confidence interval [CI]: $5411-$6225) for all-cause costs, $3644 (95% CI: $3484-$3806) for primary PD-related costs, and $6088 (95% CI: $5779-$6398) for any PD-related costs. CONCLUSIONS: Elderly Medicare beneficiaries with PD had substantial variation in PD-related costs. Advanced PD was associated with a larger economic burden than mild/moderate PD. © 2020 International Parkinson and Movement Disorder Society.

Adopting Clean Fuels and Technologies on School Buses. Pollution and Health Impacts in Children.

RATIONALE: More than 25 million American children breathe polluted air on diesel school buses. Emission reduction policies exist, but the health impacts to individual children have not been evaluated. METHODS: Using a natural experiment, we characterized the exposures and health of 275 school bus riders before, during, and after the adoption of clean technologies and fuels between 2005 and 2009. Air pollution was measured during 597 trips on 188 school buses. Repeated measures of exhaled nitric oxide (FeNO), lung function (FEV1, FVC), and absenteeism were also collected monthly (1,768 visits). Mixed-effects models longitudinally related the adoption of diesel oxidation catalysts (DOCs), closed crankcase ventilation systems (CCVs), ultralow-sulfur diesel (ULSD), or biodiesel with exposures and health. MEASUREMENTS AND MAIN RESULTS: Fine and ultrafine particle concentrations were 10-50% lower on buses using ULSD, DOCs, and/or CCVs. ULSD adoption was also associated with reduced FeNO (-16% [95% confidence interval (CI), -21 to -10%]), greater changes in FVC and FEV1 (0.02 [95% CI, 0.003 to 0.05] and 0.01 [95% CI, -0.006 to 0.03] L/yr, respectively), and lower absenteeism (-8% [95% CI, -16.0 to -0.7%]), with stronger associations among patients with asthma. DOCs, and to a lesser extent CCVs, also were associated with improved FeNO, FVC growth, and absenteeism, but these findings were primarily restricted to patients with persistent asthma and were often sensitive to control for ULSD. No health benefits were noted for biodiesel. Extrapolating to the U.S. population, changed fuel/technologies likely reduced absenteeism by more than 14 million/yr. CONCLUSIONS: National and local diesel policies appear to have reduced children's exposures and improved health.

Treatment utilization patterns of newly initiated oral anticancer agents in a national sample of Medicare beneficiaries.

BACKGROUND: Few studies have examined oral anticancer treatment utilization patterns among Medicare beneficiaries. OBJECTIVE: To assess treatment utilization patterns of newly initiated oral anticancer agents across national samples of Medicare beneficiaries for 5 cancer types: chronic myeloid leukemia (CML), multiple myeloma (MM), metastatic prostate cancer (mPC), metastatic renal cell carcinoma (mRCC), and metastatic breast cancer (mBC). METHODS: This retrospective claims analysis used 100% Medicare Chronic Condition Data Warehouse (CCW) Parts A, B, and D files from 2011 to 2014 (for CML, MM, mPC, and mRCC patients) and a 5% random fee-for-service sample from 2011 to 2013 (for mBC patients). Outcomes of interest were the number of 30-day supply prescriptions, adherence, and discontinuation of newly initiated (ie, index) oral anticancer agents indicated for each of the cancers. Adherence was calculated with both the "traditional" proportion of days covered (PDC) approach, measured over a fixed 1-year period or until hospice/death, and a "modified" PDC approach, measured over the time between the first and last fill of the index oral anticancer agent. Patients with PDC of at least 0.80 were deemed as being adherent. Discontinuation was defined as the presence of a continuous 90-day gap in the availability of days supply of the index oral anticancer agent. RESULTS: Our study included 1,650, 7,461, 6,998, 2,553, and 79 patients for CML, MM, mPC, mRCC, and mBC, respectively. Patients with mRCC had the highest proportion of patients with only 1 fill of their index anticancer agent (28%) followed by mBC (17%), MM (17%), mPC (12%), and CML (12%). Patients with CML had the highest mean (SD) number of 30-day supply equivalent prescriptions (8.3 [4.6]), followed by patients with mPC (6.5 [4.2]), MM (5.7 [4.1]), mBC (4.7 [3.2]), and mRCC (4.5 [3.9]). Using the modified PDC measured between the first and last fills, approximately three-quarters of patients with CML (74%), mRCC (71%), and mBC (70%) were adherent to the index oral anticancer agent. Adherence was highest for patients with mPC (87%) and lowest for patients with MM (58%). The percentage of patients defined as adherent to the index oral anticancer agent decreased for all cancers when using the traditional PDC measure over a fixed 1-year period: CML (54%), MM (35%), mPC (48%), mRCC (37%), and mBC (22%). Rates of discontinuation for patients in our sample were 32% (CML), 38% (mPC), 42% (mRCC), 48% (MM), and 58% (mBC). CONCLUSIONS: Between 13% and 42% of Medicare patients were nonadherent between the first and last fill of their newly initiated oral anticancer therapies across a range of cancers. This study provides a valuable benchmark for stakeholders seeking to measure and improve adherence to oral anticancer agents in Medicare patients. DISCLOSURES: This study was supported by Humana, Inc. (Louisville, KY). The sponsor played a role in the development of the study protocol, interpretation of results, and revisions of the manuscript. The sponsor was not involved in data analysis. Brown is employed by Humana, Inc., and Ward was employed by Humana, Inc., from research inception through initial drafts. Doshi has served as an advisory board member or consultant for Allergan, Ironwood Pharmaceuticals, Janssen, Kite Pharma, Merck, Otsuka, Regeneron, Sarepta, Sage Therapeutics, Sanofi, and Vertex and has received research funding from AbbVie, Biogen, Humana, Janssen, Novartis, PhRMA, Regeneron, Sanofi, and Valeant. Her spouse holds stock in Merck and Pfizer. All other authors have no financial conflicts of interest to report.

Low Sustainment of High-Dose Oral Medication Regimens for Advanced Parkinson's Disease in Medicare Beneficiaries.

BACKGROUND: Increasing doses of oral antiparkinson medications are indicated in advanced Parkinson's disease (PD), but little is known about sustainment of high-dose regimens. OBJECTIVE: To investigate sustainment of high-dose oral medication regimens in Medicare beneficiaries with incident advanced PD. METHODS: This retrospective cohort study utilized 100%fee-for-service Medicare claims from 2011-2013. We identified advanced PD using a pharmacy claims-based proxy and selected patients who initiated a new high-dose oral medication regimen (daily levodopa equivalent dose [LED] >1000 mg/day for ≥30 days) in 2012. In the following 12 months, we examined: 1) annual proportion of days covered (PDC)≥0.80 and 2) presence of a ≥ 90 day continuous gap at varying dosage thresholds: the initial >1000 mg/day, >800 mg/day, >500 mg/day, or >0 mg/day. RESULTS: We identified 9,405 patients with advanced PD (mean age 77.4 [SD 6.8] years; 53%men). Only 5%maintained a regimen of >1000 mg/day at PDC ≥0.80; 75% had a ≥ 90-day gap in that dosage level. At a dosage threshold of >800 mg/day, 20% had a PDC ≥0.80 and 53% had a ≥ 90-day gap; at >500 mg/day, 56% had a PDC ≥0.80 and 19%had a ≥ 90-day gap; and at >0 mg/day (any dose), 76% had a PDC ≥0.80 and only 10%had a≥90-day gap. CONCLUSION: Few patients with advanced PD sustained a high-dose oral medication regimen in the year following initiation, but most sustained a substantially lower-dose regimen. Strategies to improve advanced PD treatment are needed.

Omalizumab Treatment Patterns Among Patients with Asthma in the US Medicare Population.

BACKGROUND: Asthma in older adults is associated with high rates of morbidity and mortality; similarly, asthma can be severe enough among younger adults to warrant disability benefits. Reasons for poor outcomes in both groups of patients may include discontinuation and lack of adherence to controller therapies. OBJECTIVE: To examine characteristics and treatment patterns of US Medicare patients initiating omalizumab for asthma, and factors associated with its discontinuation and adherence. METHODS: A retrospective claims database analysis of Medicare beneficiaries with asthma initiating omalizumab treatment was carried out. The primary outcomes were omalizumab discontinuation (gap in use ≥90 days) and adherence (proportion of days covered ≥0.8) over a 12-month follow-up. Multivariable regressions were used to examine factors associated with omalizumab discontinuation and adherence. RESULTS: Of the 3058 Medicare patients initiating omalizumab for asthma (mean age, 62.7 years), 36.9% discontinued omalizumab and 60.6% were adherent. Discontinuation rates were 32.7% and 42.8%, and adherence rates were 65.4% and 53.9%, for disabled and older Medicare patients, respectively. Patients aged 65 to 69 years and 70 to 74 years had significantly lower odds of discontinuation (odds ratios [95% CI], 0.66 [0.46-0.93] and 0.62 [0.43-0.89], respectively) and higher odds of adherence than did patients aged 80 years or older. Compared with patients receiving low-income subsidy, patients not receiving low-income subsidy had lower odds of discontinuation (0.66 [0.52-0.83]) and higher odds of adherence (1.52 [1.20-1.93]). Greater numbers of preindex evaluation and management physician visits and comorbid rhinitis were associated with lower odds of discontinuation and higher odds of adherence. CONCLUSIONS: More than 60% of Medicare patients with asthma continued and were adherent to omalizumab over a 12-month follow-up. Patient age, low-income subsidy status, and the numbers of evaluation and management physician visits were among factors associated with treatment adherence and discontinuation.

Use of a medication-based algorithm to identify advanced Parkinson's disease in administrative claims data: Associations with claims-based indicators of disease severity.

INTRODUCTION: Lack of a gold standard definition for advanced Parkinson's Disease (APD), coupled with absence of disease severity information in diagnostic codes, hinders use of large administrative databases for conducting population health and comparative effectiveness studies. METHODS: Using pharmacy claims data, we created an algorithm to identify APD: any 30-day average levodopa equivalent dose (LED) >1000 mg/day. Using 2013 100% U.S. Medicare claims, we applied this algorithm and used multivariate logistic regression to examine associations between assigned APD status and claims-based indicators of PD severity (any deep brain stimulation, fall, hallucinations, walker, wheelchair, specialty bed, dementia diagnosis, skilled nursing facility, hospice), adjusting for sociodemographic, clinical, and treatment characteristics. Levodopa >1000 mg/day, levodopa >800 mg/day and LED >800 mg/day were used in sensitivity analysis. RESULTS: In our sample (N = 144,703), 20% were assigned APD status based on the LED >1000 mg/day cut-off. This group had significantly higher odds of having each claims-based indicator, compared with those assigned mild-moderate PD status. Odds ratios were highest for indicators for any DBS (OR: 2.96; 95% CI:2.75-3.19) and specialty bed (OR:2.15, 95% CI: 1.99-2.32) and lowest for fall (OR:1.27; 95% CI:1.20-1.34) and dementia diagnosis (OR:1.21; 95% CI:1.18-1.25). Results based on alternative approaches were similar. CONCLUSIONS: Medicare patients classified as having APD via a pharmacy claims-based algorithm had higher odds of having claims-based clinical markers of APD, compared with patients categorized as having mild-moderate PD. This proxy strategy could facilitate future claims-based studies and warrants further refinement and validation using medical records or other clinical sources.

Comparative Survival Associated With Use of Targeted vs Nontargeted Therapy in Medicare Patients With Metastatic Renal Cell Carcinoma.

Importance: Targeted therapies for advanced renal cell carcinoma (RCC) have shown increased tolerability and survival advantages over older treatments in clinical trials, but understanding of real-world survival improvements is still emerging. Objective: To compare overall and RCC-specific survival associated with use of targeted vs nontargeted therapy for metastatic RCC. Design, Setting, and Participants: This retrospective cohort study used Surveillance, Epidemiology, and End Results-Medicare data from 2000 to 2013 to examine patients with stage IV (distant) clear cell RCC at the time of diagnosis who received any targeted or nontargeted therapy. A 2-stage residual inclusion model was fitted to estimate the survival advantages of targeted treatments using an instrumental variable approach to account for both measured and unmeasured group differences. Data analyses were conducted from July 24, 2017, to April 4, 2019. Exposures: Targeted therapy (study group) or nontargeted therapy (control group). Main Outcomes and Measures: Overall survival and RCC-specific survival, defined as the interval between the date of first drug treatment and date of death or end of the observation period. Results: The final sample included 1015 patients (mean [SD] age, 71.2 [8.1] years; 392 [39%] women); 374 (37%) received nontargeted therapy and 641 (63%) received targeted therapy. The targeted therapy group had a greater percentage of disabled patients (ie, those <65 years old who were eligible for Medicare because of disability) and older patients (ie, those ≥75 years old) and higher comorbidity index and disability scores compared with the nontargeted therapy group. Unadjusted Kaplan-Meier survival curves showed higher overall survival for targeted vs nontargeted therapy (log-rank test, χ21 = 5.79; P = .02); median survival was not statistically significantly different (8.7 months [95% CI, 7.3-10.2 months] vs 7.2 months [95% CI, 5.8-8.8 months]; P = .14). According to the instrumental variable analysis, the median overall survival advantage was 3.0 months (95% CI, 0.7-5.3 months), and overall survival improvements associated with targeted therapy vs nontargeted therapy were statistically significant: 8% at 1 year (44% [95% CI, 39%-50%] vs 36% [95% CI, 30%-42%]; P = .01), 7% at 2 years (25% [95% CI, 20%-30%] vs 18% [95% CI, 13%-23%]; P = .009), and 5% at 3 years (15% [95% CI, 11%-19%] vs 10% [95% CI, 6%-13%]; P = .01). Receipt of targeted therapy was associated with a lower hazard of death compared with nontargeted therapy (overall survival hazard ratio, 0.78 [95% CI, 0.65-0.94]; RCC-specific survival hazard ratio, 0.77 [95% CI, 0.62-0.96]). Conclusions and Relevance: Targeted therapies were associated with modest survival advantages despite a treatment group with more medical complexity, likely reflecting appropriateness for an expanded population of patients. As advances in cancer treatment continue, rigorous methods that account for unobserved confounders will be needed to evaluate their real-world impact on outcomes.

Association of high cost sharing and targeted therapy initiation among elderly Medicare patients with metastatic renal cell carcinoma.

High out-of-pocket costs may limit access to oral therapies covered by patients' prescription drug benefits. We explored financial barriers to treatment initiation in patients newly diagnosed with metastatic renal cell carcinoma (mRCC) by comparing Medicare Part D patients with low out-of-pocket costs due to receipt of full low-income subsidies (LIS beneficiaries) to their counterparts who were responsible for more than 25% cost sharing during Medicare's initial coverage phase (non-LIS beneficiaries). We used 2011-2013 100% Medicare claims for non-LIS and LIS beneficiaries newly diagnosed with metastases in the liver, lung, or bone to examine targeted therapy treatment initiation rates and time to initiation for (1) oral medications (sorafenib, sunitinib, everolimus, pazopanib, or axitinib) covered under Medicare's prescription drug benefit (Part D); (2) injected or infused medications (temsirolimus or bevacizumab) covered by Medicare's medical benefit (Part B); and (3) any (Part D or Part B) targeted therapy. The final sample included 1721 patients. On average, non-LIS patients were responsible for out-of-pocket costs of ≥$2,800 for their initial oral prescription, as compared to ≤$6.60 for LIS patients. Compared to LIS patients, a lower percentage of non-LIS patients initiated oral therapies (risk-adjusted rates, 20.7% vs. 33.9%; odds ratio [OR] = 0.49, 95% CI: 0.36-0.67, P < 0.001) and any targeted therapies (26.7% vs. 40.4%, OR = 0.52, 95% CI: 0.38-0.71, P < 0.001). Non-LIS patients were also slower to access therapy. High cost sharing was associated with reduced and/or delayed access to targeted therapies under Medicare Part D, suggesting that financial barriers play a role in treatment decisions.

A Collaborative, Network-Based Approach to Advance Women's Depression Research in the United States: Preliminary Findings.

OBJECTIVE: Translation of women's mental health research has yet to impact overall prevalence and burden of Mood Disorders in the United States. The lack of standard measures and methodological coordination across studies has contributed to the slow impact of research on outcomes. The primary aims of this project were to demonstrate the process by which multiple investigators, sites, and settings administered a standard women's mental health questionnaire within a new Women's Depression Network. Information on the prevalence of mental health and service use across sites is provided. METHODS: A standard women's mental health questionnaire was developed and administered across seven different women's health sites in the United States. Validated measures of depression and anxiety were included (Patient Health Questionnaire Depression Scale [PHQ-9] and Generalized Anxiety Disorder Scale [GAD-7]). Administration of the questionnaire was embedded into existing clinical or research activities at each site. RESULTS: Data from 1,316 women were collected from seven sites over 12 months. A total of 14% and 15% of the women scored at or above the cutoff on the PHQ-9 and GAD-7 respectively. Just over half of the women screening positive for either depression or anxiety reported current treatment use. CONCLUSIONS: Findings suggest that coordination and administration of a standard women's mental health questionnaire is feasible across multiple settings and sites. Results highlight a low percentage of treatment use across various settings. The infrastructure developed for this study sets the stage for hypothesis-driven studies that can facilitate coordinated, network-based research that has the potential to accelerate advances in the field.

Changing the Paradigm for the Treatment and Development of New Therapies for FSGS.

Focal segmental glomerulosclerosis (FSGS) is a renal pathology finding that represents a constellation of rare kidney diseases, which manifest as proteinuria, edema nephrotic syndrome, hypertension, and increased risk for kidney failure. Therapeutic options for FSGS are reviewed displaying the expected efficacy from 25 to 69% depending on specific therapy, patient characteristics, cost, and common side effects. This variability in treatment response is likely caused, in part, by the heterogeneity in the etiology and active molecular mechanisms of FSGS. Clinical trials in FSGS have been scant in number and slow to recruit, which may stem, in part, from reliance on classic clinical trial design paradigms. Traditional clinical trial designs based on the "learn and confirm" paradigm may not be appropriate for rare diseases, such as FSGS. Future drug development and testing will require novel approaches to trial designs that have the capacity to enrich study populations and adapt the trial in a planned way to gain efficiencies in trial completion timelines. A clinical trial simulation is provided that compares a classical and more modern design to determine the maximum tolerated dose in FSGS.