Real world comparison of filgrastim to filgrastim-sndz in patients with chemotherapy-induced neutropenia.

INTRODUCTION: There exists some apprehension by prescribers, healthcare providers, and other stakeholders regarding the real-world safety and effectiveness of biosimilars. While some of the apprehension is likely due to clinician knowledge gaps in the biosimilarity exercise, additional data (including those generated from the real-world) regarding safety and efficacy could reduce a clinician's perception of biosimilar uncertainty and can potentially increase biosimilar acceptance and uptake. The published literature is lacking regarding the real-world impact on healthcare costs and clinical outcomes when a single healthcare institution converts from filgrastim to filgrastim-sndz as its short-acting Granulocyte Colony Stimulating Factor (GCSF), especially within diverse populations and indications not explicitly studied through the registration trials. Specifically, both filgrastim and filgrastim-sndz possess FDA-approved indications within patients with hematologic malignancies receiving high-dose chemotherapy and in those undergoing bone marrow transplantation. As a biosimilar to filgrastim, the FDA did not require prospective, randomized controlled trials to obtain these indications for filgrastim-sndz. The purpose of this study is to describe real-world healthcare resource costs, utilization patterns, and clinical outcomes in patients with hematologic malignancies who received filgrastim-sndz or filgrastim to support neutrophil recovery following chemotherapy (i.e., induction or consolidation) or a bone marrow transplant (BMT) at Yale New Haven Hospital (YNHH). METHODS: A total of 148 patients were identified and met the following criteria: at least 18 years old, Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, absence of fever or infection, newly diagnosed acute myeloid leukemia or newly post-bone marrow transplant and received filgrastim-sndz (Zarxio®) or reference filgrastim (Neupogen®). RESULTS: Healthcare resource utilization outcomes were compared between biosimilar and reference filgrastim using descriptive statistics. There were no major differences between either cohort, including duration of hospitalization, the number of overall emergency room visits and additional hospital admissions with a primary diagnosis of febrile neutropenia or neutropenia within 30 days post-discharge from initial hospital admission, time to neutrophil recovery following GCSF support, and the incidence and duration of both fever and febrile neutropenia. The total cost based on treatment of all patients in each arm differed significantly with filgrastim-sndz being the most cost-effective choice. CONCLUSION: filgrastim-sndz significantly reduced healthcare utilization costs compared to reference filgrastim with similar effect on absolute neutrophil count, incidence of fever, and febrile neutropenia.

Using Implementation Mapping to Develop Implementation Strategies for the Delivery of a Cancer Prevention and Control Phone Navigation Program: A Collaboration With 2-1-1.

Cancer prevention and control (CPC) behaviors, such as cancer screening, human papillomavirus vaccination, and smoking cessation, are critical public health issues. Evidence-based interventions have been identified to improve the uptake of CPC behaviors; however, they are often inconsistently implemented, affecting their reach and effectiveness. Patient navigation is an evidence-based approach to increasing CPC behaviors. Nevertheless, there are few navigation programs that use systematically developed implementation strategies to facilitate adoption, implementation, and maintenance, which affects uptake and outcomes. This article describes the development of a multifaceted implementation strategy designed to facilitate delivery of a CPC phone navigation program to increase breast, cervical, and colorectal cancer screening; human papillomavirus vaccination; and smoking cessation among 2-1-1 Texas helpline callers. Using implementation mapping, a systematic approach for developing implementation strategies, we designed a strategy that involved training 2-1-1 information specialists to deliver the program, developed online tracking and quality-monitoring (audit and feedback) systems, and developed and distributed protocols and other materials to support training and implementation. Through this iterative process and our collaboration with 2-1-1 Texas call centers, our project resulted in a comprehensive training program with a robust curriculum of pertinent program content, for which we identified core components and appropriate delivery modes that are culturally relevant to the population. The results of this study can be applied to the development of more systematic, transparent, and replicable processes for designing implementation strategies. The study also demonstrates a process that can be applied to other contexts and other CPC program implementation efforts.

The effect of interhospital transfers, emergency medical services, and distance on ischemic time in a rural ST-elevation myocardial infarction system of care.

BACKGROUND: Regional myocardial infarction systems of care have been shown to improve timely access to primary percutaneous coronary intervention (PCI). However, there is a relatively sparse research on rural "frontier" regions. Arrival mode, high rates of interhospital transfers, long transport times, low population density, and mostly volunteer emergency medical services (EMS) distinguish this region from metropolitan systems of care. We sought to assess the effect of interhospital transfers, distance, and arrival mode on total ischemic times for patients with ST-elevation myocardial infarctions undergoing primary PCI. METHODS: We assessed patient data from our observational cohort of 395 patients with ST-elevation myocardial infarction with PCI as their primary treatment strategy. Data came from the 10 PCI hospitals participating in the Wyoming Mission: Lifeline program from January 2013 to September 2014. We performed both regression and tests of differences. RESULTS: Median total ischemic time was nearly 2.7 times greater in transferred patients than those presenting directly (379 vs 140 minutes). Distance in miles traveled between patient's home and PCI facility was 2.5 times larger in transfer patients (51 vs 20 miles). Emergency medical services arrival was associated with 23% shorter total ischemic times than self-arrival. CONCLUSIONS: Transfer patients from referral hospitals had significantly greater total ischemic time, and use of EMS was associated with significantly lower times. Transport distance was mixed in its effect. These findings suggest a continued focus on improving transitions between referral and receiving centers and enhancing coordination in rural systems of care to reduce the multiplier effect of transfers on total ischemic time.

Adherence and persistence to tafamidis treatment among Medicare beneficiaries in the presence of a patient assistance program.

Tafamidis is the only disease-modifying therapy approved to treat patients in the United States with transthyretin amyloid cardiomyopathy (ATTR-CM), which most commonly affects patients aged ≥ 65 years. The manufacturer operates a patient assistance program (PAP) to support access to tafamidis. This study conducted Privacy Preserving Record Linking (PPRL) using Datavant tokens to match patients across Medicare prescription drug plan (PDP) and PAP databases to evaluate the impact of PAPs on treatment exposure classification, adherence, and persistence determined using Medicare PDP data alone. We found 35% of Medicare PDP patients received tafamidis through the PAP only; 14% through both Medicare PDP and the PAP, and 51% through Medicare PDP only. Adherence and persistence were comparable between these cohorts but underestimated among patients who received ≥ 2 prescriptions through Medicare PDP and ≥ 1 through the PAP when solely using Medicare data versus pooled Medicare and PAP data (modified Medication Possession Ratio: 84% [69% ≥ 80% adherent] vs. 96% [93%]; Proportion of Days Covered: 77% [66% ≥ 80% adherent] vs. 88% [88%]; mean days to discontinuation: 186 vs. 252; total discontinuation: 13% vs. 11%). Cross-database PPRL is a valuable method to build more complete treatment journeys and reduce the risk of exposure misclassification in real-world analyses.

Risk of mortality in older adults with loss of appetite: An analysis of Medicare fee-for-service data.

OBJECTIVES: Prior research suggested that loss of appetite (LOA) among adults with Medicare fee-for-service (FFS) insurance in the United States increased the risk of mortality within 1 year; those findings were not adjusted for risk factors and confounders. The objective of this study was to compare the risk of mortality among Medicare FFS beneficiaries with LOA to a control group without LOA while controlling or adjusting for age, comorbidities, body mass index (BMI), and weight loss. DESIGN: Retrospective and observational analysis of Medicare FFS health insurance claims data from October 1, 2015 to December 31, 2021. SETTING: Claims from all settings (e.g., hospital inpatient/outpatient, office, assisted living facility, skilled nursing facility, hospice, rehabilitation facility, home) were included in these analyses. PARTICIPANTS: The LOA group included all individuals aged 65-115 years with continuous Medicare FFS medical coverage (Parts A and/or B) for at least 12 months before a claim with ICD-10 diagnosis code "R63.0 Anorexia". The control group was drawn from individuals aged 65-115 years with continuous Medicare FFS coverage who did not have a diagnosis of R63.0. Individuals with LOA were matched 1:3 to those in the control group based on age, sex, and race/ethnicity. MEASUREMENTS: Mortality in the LOA group was compared to mortality in the control group using Kaplan-Meier and Cox regression analyses and stratified or adjusted in terms of Charlson Comorbidity Index (CCI), claims-based frailty index (CFI), BMI, and weight loss. RESULTS: The study population of 1,707,031 individuals with LOA and 5,121,093 controls without LOA was 61.7% female and 82.2% White. More individuals with LOA compared with the control group had a CCI score 5+ (52.4% vs. 19.4%), CFI score 5+ (31.6% vs. 6.4%), and BMI < 20 kg/m2 (11.2% vs. 2.1%). Median follow-up was 12 months (individuals with LOA) and 49 months (control group). In a matched population, the risk of mortality was significantly higher (unadjusted hazard ratio 4.40, 95% confidence interval 4.39-4.42) for individuals with LOA than the control group. Median survival time was 4 months (individuals with LOA) and 26 months (control group); differences in survival time remained when stratifying by CCI, BMI, and weight loss. CONCLUSION: Individuals with LOA had a substantially increased risk of death even after matching for age, sex, race/ethnicity, and adjusting for comorbidities. These findings highlight the burden of illness in older adults with LOA and the need for therapies.

Pneumococcal vaccine uptake among Medicare Beneficiaries aged ≥65 years following the shared clinical decision-making recommendation for 13-valent pneumococcal conjugate vaccine in 2019.

BACKGROUND: In November 2019, the US Advisory Committee on Immunization Practices recommended shared clinical decision-making (SCDM) for use of 13-valent pneumococcal conjugate vaccine (PCV13) among immunocompetent elderly adults. The impact of SCDM on PCV13 use in this population, immunocompromised persons, and vulnerable subgroups has not been well documented. METHODS: Using Medicare Research Identifiable Files (01/2018 - 09/2020), monthly uptake of pneumococcal vaccine (PCV13, 23-valent pneumococcal polysaccharide vaccine [PPSV23]) was identified among fee-for-service beneficiaries aged ≥ 65 years with Part B coverage and no evidence of prior PCV13. Uptake was stratified by vaccine, risk profile, and demographics. RESULTS: Among the > 12 M beneficiaries included each month, PCV13 uptake declined from > 70% of pneumococcal vaccinations before SCDM to < 60% after SCDM (02/2020). Reductions in PCV13 uptake were consistent across vulnerable subgroups as well as immunocompromised persons. CONCLUSIONS: PCV13 use decreased among immunocompetent and immunocompromised persons alike, despite continued routine PCV13 recommendation for the latter group.

Temporal Trends in Diagnostic Testing Patterns for Wild-Type Transthyretin Amyloid Cardiomyopathy in the Medicare Fee-for-Service Population.

Wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) is frequently misdiagnosed or diagnosed late in the disease course. ATTRwt-CM can be diagnosed invasively through tissue biopsy, but current diagnostic recommendations indicate technetium-99m pyrophosphate (99mTc-PYP) bone scintigraphy is an acceptable noninvasive alternative. The relative use of these confirmatory diagnostic tests in routine clinical practice is unknown. A retrospective observational study assessed temporal trends in biopsy and 99mTc-PYP scintigraphy and differences in patient characteristics using in/outpatient claims data from the US Medicare fee-for-service database. Claims prevalence for biopsy alone (≥1 claim for cardiac/extracardiac biopsy), imaging alone (≥1 claim for 99mTc-PYP scintigraphy), and both tests and patient demographic, geographic, and clinical characteristics were examined. Of patients (n = 1226) receiving an ATTRwt-CM diagnostic code, 29%, 47%, and 24% were diagnosed by biopsy alone, 99mTc-PYP scintigraphy alone, and both tests, respectively. Patients with claims for 99mTc-PYP scintigraphy alone were older than those with claims for biopsy alone (79.9 vs 76.5; p <0.001). Fewer patients in the southern United States and more patients in the northeastern United States had claims for 99mTc-PYP scintigraphy alone than biopsy alone (p <0.001). There was a temporal trend toward more claims for 99mTc-PYP scintigraphy alone (odds ratio 1.21; p <0.001) and both tests (odds ratio 1.10; p = 0.008) versus biopsy alone. From 2017 to 2019, claims increased for 99mTc-PYP scintigraphy alone. In conclusion, these data suggest a growing preference for the noninvasive imaging technique, which has high sensitivity/specificity, usability, and accessibility and may help facilitate earlier disease diagnosis. United States regional differences in the use of 99mTc-PYP scintigraphy highlight the need for education initiatives.

Suboptimal adherence to prescribed daily growth hormone regimen among medicaid beneficiaries in the United States.

OBJECTIVE: The objective of this retrospective cohort study was to describe the adherence and discontinuation patterns of somatropin over 3 years among children with pGHD insured by Medicaid across the United States. METHODS: Eligible children were aged ≥3 and <16 years with Medicaid coverage, diagnosed with pGHD, and had ≥2 new prescriptions for somatropin between 1 July 2014 and 31 December 2018. Four non-exclusive patient cohorts were constructed (≥3, 12, 24, and 36 months of continuous enrollment after initial prescription). Suboptimal adherence was defined as medication possession ratio <0.80, and discontinuation as a gap of >60 days between somatropin fills. Logistic and proportional hazards regression methods were used to estimate odds of suboptimal adherence and time to discontinuation, respectively. RESULTS: In the 12-month cohort (n = 3623), mean age was 10.5 ± 3.2 years, 70.8% were male, 44.4% White, 29.1% Hispanic, 7.1% Black, and 1.7% Asian. At months 12, 24, and 36, the proportion with suboptimal adherence was 40.9, 50.4, 54.4%, respectively, and 49.2% of patients with ≥3 months of follow-up discontinued therapy. At 12 months, lower age and race/ethnicity (Black vs. White referent) had greater odds of suboptimal adherence. Discontinuation was associated with Black (vs. White referent) race and geographic region. CONCLUSIONS: Sociodemographic characteristics may be risk factors for suboptimal adherence and/or discontinuation of prescribed somatropin therapy. Improving GH regimen adherence among this at-risk population, and specifically among subgroups at highest risk, is warranted to improve clinical outcomes.

Baseline Characteristics and Secondary Medication Adherence Patterns Among Patients Receiving Tafamidis Prescriptions: A Retrospective Analysis Using a National Specialty Pharmacy Dispensing Database.

Introduction: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a serious, underrecognized condition, which leads to heart failure and early mortality if left untreated. Until recently, heart transplantation was the only treatment for ATTR-CM. Regulatory approval of tafamidis transformed treatment for patients. In the phase 3 Transthyretin Amyloidosis Cardiomyopathy Clinical Trial (ATTR-ACT), which established the safety and efficacy of tafamidis, medication adherence was high with 97.2% of patients taking ≥80% of scheduled doses. Evidence of real-world adherence to cardiology drugs demonstrates low adherence and suboptimal outcomes; however, real-world adherence to tafamidis has not been investigated. The main objective of this study was to describe adherence patterns of patients filling tafamidis in the Symphony Health database. Methods: This retrospective analysis of the Symphony Health Solutions claims database used secondary adherence measures, including modified medication possession ratio (MPRm), days between fills adherence rate, and compliance rate, to assess adherence patterns of 2020 patients filling tafamidis free acid 61-mg capsules or tafamidis meglumine 4x20-mg capsules from June 1, 2019 to August 31, 2020. Results: Patients receiving a tafamidis formulation had characteristics consistent with the expected patient population; 71.6% were aged 75-84 years, 83.2% were male, and the highest proportion resided in the Northeast region (30.5%) of the United States. Adherence for tafamidis was high, as 75% to 100% of the patients across subgroups met or exceeded the commonly defined adherence threshold of 80%. Median number of refills ordered and received was six refills per patient. Most patients received refills with no gap (n=1633) or a gap <30 days (n=1267/1317 patients). Adherence was high across follow-up time, sex, and age subgroups. Adherence varied by geographic region, with the Northeast being significantly higher than the Midwest (mean MPRm 94.41% vs 88.21%, p=0.0007). Conclusion: These results provide evidence that real-world adherence to tafamidis in patients with ATTR-CM is high.

Viewpoint and the recognition of people from their movements.

Observers can recognize other people from their movements. What is interesting is that observers are best able to recognize their own movements. Enhanced visual sensitivity to self-generated movement may reflect the contribution of motor planning processes to the visual analysis of human action. An alternative view is that enhanced visual sensitivity to self-motion results from extensive experience seeing one's own limbs move. To investigate this alternative explanation, participants viewed point-light actors from first-person egocentric and third-person allocentric viewpoints. Although observers routinely see their own actions from the first-person view, participants were unable to identify egocentric views of their own actions. Conversely, with little real-world experience seeing themselves from third-person views, participants readily identified their own actions from allocentric views. When viewing allocentric displays, participants accurately identified both front and rear views of their own actions. Because people have little experience observing themselves from behind or from third-person views, these findings suggest that visual learning cannot account for enhanced visual sensitivity to self-generated action.

Cost-Effectiveness Analysis of Brentuximab Vedotin With Chemotherapy in Newly Diagnosed Stage III and IV Hodgkin Lymphoma.

PURPOSE: In a recent randomized, open-label trial (ECHELON-1), brentuximab vedotin (BV) combined with doxorubicin, vinblastine, and dacarbazine (AVD+BV) decreased the risk of progression in adults diagnosed with stage III or IV Hodgkin lymphoma (HL) compared with standard bleomycin-containing chemotherapy (doxorubicin, bleomycin, vinblastine, and dacarbazine [ABVD]). However, the cost effectiveness of incorporating BV (US$6,970 per 50-mg vial) into the first-line setting is unknown. PATIENTS AND METHODS: We constructed a Markov decision-analytic model to measure the costs and clinical outcomes for AVD+BV compared with ABVD as first-line therapy in a cohort of patients with stage III or IV HL. Transition probabilities were estimated from ECHELON-1 by fitting parametric survival distributions. Lifetime direct health care costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated for AVD+BV compared with ABVD from a US payer perspective. Our model was also used to estimate BV price reductions that would achieve more favorable cost effectiveness under indication-specific pricing. RESULTS: AVD+BV was associated with an improvement of 0.56 QALYs compared with treatment with standard ABVD. However, incorporating BV into first-line therapy led to significantly higher lifetime health care costs ($361,137 v $184,291), causing the ICER for AVD+BV to be $317,254 per QALY. If indication-specific pricing were implemented, acquisition costs for BV used in the first-line setting would need to be reduced by 56% to 73% for ICERs of $150,000 to $100,000 per QALY, respectively. CONCLUSION: Substituting BV for bleomycin during first-line therapy for stage III or IV HL is unlikely to be cost effective under current drug pricing. Should indication-specific pricing be implemented, significant price reductions for BV used in the first-line setting would be needed to reduce ICERs to more widely acceptable values.

Recognizing people from their movement.

Human observers demonstrate impressive visual sensitivity to human movement. What defines this sensitivity? If motor experience influences the visual analysis of action, then observers should be most sensitive to their own movements. If view-dependent visual experience determines visual sensitivity to human movement, then observers should be most sensitive to the movements of their friends. To test these predictions, participants viewed sagittal displays of point-light depictions of themselves, their friends, and strangers performing various actions. In actor identification and discrimination tasks, sensitivity to one's own motion was highest. Visual sensitivity to friends', but not strangers', actions was above chance. Performance was action dependent. Control studies yielded chance performance with inverted and static displays, suggesting that form and low-motion cues did not define performance. These results suggest that both motor and visual experience define visual sensitivity to human action.