New Vaccine Platforms-Novel Dimensions of Economic and Societal Value and Their Measurement.

The COVID-19 pandemic's dramatic impact has been a vivid reminder that vaccines-especially in the context of infectious respiratory viruses-provide enormous societal value, well beyond the healthcare system perspective which anchors most Health Technology Assessment (HTA) and National Immunization Technical Advisory Group (NITAG) evaluation frameworks. Furthermore, the development of modified ribonucleic acid-based (mRNA-based) and nanoparticle vaccine technologies has brought into focus several new value drivers previously absent from the discourse on vaccines as public health interventions such as increased vaccine adaptation capabilities, the improved ability to develop combination vaccines, and more efficient vaccine manufacturing and production processes. We review these novel value dimensions and discuss how they might be measured and incorporated within existing value frameworks using existing methods. To realize the full potential of next-generation vaccine platforms and ensure their widespread availability across populations and health systems, it is important that value frameworks utilized by HTAs and NITAGs properly reflect the full range of benefits for population health and well-being and cost efficiencies that these new vaccines platforms provide.

Implications of Delayed Testosterone Recovery in Patients with Prostate Cancer.

To assess the clinical impact of delayed testosterone recovery (TR) following the discontinuation of medical androgen deprivation therapy (ADT), a retrospective, longitudinal analysis was conducted in adult males with prostate cancer using the Optum® de-identified Electronic Health Record data set and Optum® Enriched Oncology Data (2010-2021). Of 3875 patients who initiated and discontinued ADT, 1553 received one or more testosterone-level tests within the 12 mo following discontinuation and were included in this study. These 1553 patients were categorized into two cohorts: 25% as TR (testosterone levels >280 ng/dl at any test within 12 mo following ADT discontinuation) and 75% as non-TR. At baseline, non-TR patients were older, had lower testosterone levels, and were more likely to have diabetes, hyperlipidemia, and hypertension, but less likely to have sexual dysfunction. After adjustment for baseline characteristics, the TR cohort had a lower risk of new-onset diabetes (hazard ratio [HR] 0.47; 95% confidence interval [CI] 0.27-0.79), trended toward a lower risk of new-onset depression (HR 0.58; 95% CI 0.33-1.02), and had a higher likelihood of seeking treatment for sexual dysfunction (HR 1.33; 95% CI 0.99-1.78) versus the non-TR cohort. These findings support monitoring testosterone levels after ADT discontinuation to manage potential long-term comorbidities in patients with prostate cancer. Patient summary: This real-world analysis of males with prostate cancer who were treated with medical androgen deprivation therapy (ADT) found that most patients did not have their testosterone level checked in the 12 mo after stopping ADT. Of those who did, 75% did not achieve normal testosterone levels (>280 ng/dl), and these patients were more likely to experience new-onset diabetes than those who achieved normal testosterone levels. These results suggest that to ensure effective clinical decision-making, physicians should check patients' testosterone levels after stopping ADT.

Cost-Effectiveness Modeling of Prostate-Specific Membrane Antigen Positron Emission Tomography with Piflufolastat F 18 for the Initial Diagnosis of Patients with Prostate Cancer in the United States.

BACKGROUND AND OBJECTIVES: Piflufolastat F 18 is a novel prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) radiotracer that is superior to standard of care (SOC) imaging for the initial staging of prostate cancer and the detection of biochemical recurrence. As piflufolastat F 18 has been approved in the United States (US) for this indication, this modeling study assessed the cost effectiveness of piflufolastat F 18 versus fluciclovine F-18, gallium68-PSMA-11 (PSMA 11), and SOC imaging (a mix of bone scans, computed tomography, and magnetic resonance imaging) for the diagnosis and staging of prostate cancer from a US healthcare system perspective. PERSPECTIVE: A US third-party payer perspective was used, which for this population reflects a mix of commercial and Medicare, considering only direct healthcare costs. SETTING: This study utilized a tertiary healthcare setting. METHODS: A decision tree was used to map the diagnostic/treatment pathway, consisting of the proportion of patients with local, regional, distant, or no disease; prostate-specific antigen (PSA) ≤ 1.0 or > 1.0; and accuracy of imaging modalities. A Markov model predicted the long-term outcomes of disease progression according to treatment decisions. Inputs to the model were informed by data from the OSPREY and CONDOR clinical trials, public data, and the literature. Treatment mix included active surveillance, radiation therapy, prostatectomy, androgen deprivation therapy (ADT), and radiation therapy + ADT, informed by expert opinion. Outcomes included life-years (LY), quality-adjusted life-years (QALY), and the incremental cost-effectiveness ratio (ICER). All costs were reported in 2021 US dollars, using the US Bureau of Labor Statistics Consumer Price Index. A willingness-to-pay (WTP) threshold of $150,000 was considered cost effective, consistent with the upper range used as the standard for price benchmarks by the Institute for Clinical and Economic Review. The robustness of the base-case results was assessed in deterministic and probabilistic sensitivity analyses. RESULTS: Over a lifetime horizon, piflufolastat F 18 had the greatest effectiveness in terms of LYs (6.80) and QALYs (5.33); for the comparators, LYs ranged from 6.58 (SOC) to 6.76 (PSMA 11) and QALYs ranged from 5.12 (SOC) and 5.30 (PSMA 11). Piflufolastat F 18 was more cost effective compared with fluciclovine F 18, PSMA 11, and SOC, with ICERs of $21,122, $55,836, and $124,330 per QALY gained, respectively. Piflufolastat F 18 was associated with the greatest net monetary benefit ($627,918) compared with the other options at a WTP threshold of $150,000. The results of the deterministic and probabilistic sensitivity analyses supported the robustness of the base-case results. CONCLUSIONS: This study suggests that piflufolastat F 18 is a cost-effective diagnostic option for men with prostate cancer in the US, with higher associated LY, QALY, and greater net monetary benefit than fluciclovine F 18, PSMA 11, and SOC imaging.

Costs of pediatric liver transplantation among commercially insured and Medicaid-insured patients with cholestasis in the US.

Children with rare cholestatic liver diseases, such as Alagille syndrome, progressive familial intrahepatic cholestasis, and biliary atresia typically require liver transplantation (LT). The objective of this analysis was to assess the economic burden of LT on these patients. Health care resource utilization and costs associated with pediatric LT were retrospectively assessed using insurance claims data from the US IBM MarketScan Commercial and Medicaid databases collected between October 2015 and December 2019. Inclusion criteria were as follows: ≥1 procedure code for LT, <18 years old at transplant, and ≥6 months of insurance eligibility at baseline. A cholestatic liver disease population who received LT was selected in the absence of specific diagnosis codes by excluding other severe liver conditions (ie, acute liver failure, malignancy) and by excluding severely decompensated individuals requiring ICU admission before LT. Annualized rates were reported. Over a mean study duration of 1.8 years, 53 commercially insured and 100 Medicaid-insured children received LT, with mean (SD) ages at baseline of 6.9 (6.0) and 5.7 (5.4) years, respectively. During this period, commercially insured and Medicaid-insured patients had annualized means of 65.3 and 52.8 medical visits, respectively. Most were outpatient visits, although the burden of inpatient visits was also high, with mean inpatient stays (inclusive of LT stay) of 37.2 and 31.6 days per year, respectively. Commercially insured and Medicaid-insured patients averaged US$512,124 and $211,863 in medical costs and $26,998 and $15,704 in pharmacy costs, respectively. These costs remained substantial throughout the first year after transplant. Overall, pediatric LT resulted in substantial health care resource utilization and cost burden in both commercially- and Medicaid-insured patients. Novel targeted medications that negate the need for pediatric LT could decrease the associated morbidity and costs.

Disease Progression and Longitudinal Clinical Outcomes of Lewy Body Dementia in the NACC Database.

INTRODUCTION: As the identification of Lewy body dementia (LBD) is often confirmed postmortem, there is a paucity of evidence on the progression of disease antemortem. This study aimed to comprehensively assess the course of LBD over time across cognitive, functional, and neuropsychiatric outcomes using real-world data. METHODS: Adults with at least one visit to an Alzheimer's Disease Center with a diagnosis of mild cognitive impairment/dementia (index date), indication of LBD, and at least one follow-up visit were identified in the National Alzheimer's Coordinating Center database (September 2005-June 2020). Participant characteristics, medication use, comorbidities, and changes in outcomes were assessed over a 5-year follow-up period and stratified by disease severity based on the Clinical Dementia Rating (CDR®) Dementia Staging Instrument-Sum of Boxes (CDR-SB) score at index. RESULTS: A total of 2052 participants with LBD (mean age at index 73.4 years) were included (mild, 219; moderate, 988; severe, 845). Mean annualized increase over 5 years was 0.9 points for CDR-Global Score, 5.6 points for CDR-SB, 10.4 points for the Functional Activities Questionnaire, and 2.0 points for the Neuropsychiatric Inventory-Questionnaire. Disease progression was greater among participants with moderate and severe LBD at index compared with those with mild LBD. CONCLUSION: Participants with LBD experienced decline across all outcomes over time, and impairment increased with disease severity. Findings highlight the substantial clinical burden associated with LBD and the importance of earlier diagnosis and effective treatment. Further research is needed to understand the predictors of cognitive and functional decline in LBD which may help inform clinical trials.

Maralixibat Treatment Response in Alagille Syndrome is Associated with Improved Health-Related Quality of Life.

OBJECTIVE: The objective of this study was to assess the impact of treatment response to the ileal bile acid transporter inhibitor maralixibat on health-related quality of life (HRQoL) in children with Alagille syndrome. STUDY DESIGN: This analysis used data from the ICONIC trial, a phase 2 study with a 4-week double-blind, placebo-controlled, randomized drug withdrawal period in children with Alagille syndrome with moderate-to-severe pruritus. Clinically meaningful treatment response to maralixibat was defined a priori as a ≥1-point reduction in the Itch-Reported Outcome (Observer) score, from baseline to week 48. HRQoL was assessed using the Pediatric Quality of Life Inventory Generic Core, Family Impact, and Multidimensional Fatigue scale scores, which were collected via the caregiver. The minimal clinically important difference for HRQoL ranged from 4 to 5 points, depending on the scale. RESULTS: Twenty of the 27 patients (74%) included in this analysis achieved an Itch-Reported Outcome (Observer) treatment response at week 48. The mean (SD) change in Multidimensional Fatigue score was +25.8 (23.0) for responders vs -3.1 (19.8) for nonresponders (P = .03). Smaller and non-statistically significant mean changes were observed for the Pediatric Quality of Life Inventory Generic Core and Family Impact scores. Controlling for baseline Family Impact score, responders' Family Impact scores increased an average of 16.9 points over 48 weeks compared with non-responders (P = .05). Smaller and non-statistically significant point estimates were observed for the Pediatric Quality of Life Inventory Generic Core and Multidimensional Fatigue scores. CONCLUSION: The significant improvements in pruritus seen with maralixibat at week 48 of the ICONIC study are clinically meaningful and are associated with improved HRQoL. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02160782.

Health Care Resource Utilization by Patients with Alagille Syndrome.

OBJECTIVE: To assess and characterize health care resource utilization (HRU) in children with the rare, genetic, multisystem disorder, Alagille syndrome. STUDY DESIGN: This retrospective analysis reviewed commercially insured and Medicaid-insured claims from October 1, 2015 to December 31, 2019 to assess HRU in patients with Alagille syndrome. As there is no specific International Classification ofDiseases-10 code for Alagille syndrome, patients were identified using the following algorithm: ≥1 claim with diagnosis code Q44.7 (other congenital malformations of the liver); <18 years of age, with no history of biliary atresia (International Classification ofDiseases-10 code: Q44.2); and ≥6 months of insurance eligibility prior to diagnosis. HRU was summarized per patient per year over all available claims postdiagnosis. RESULTS: A total of 171 commercially insured and 215 Medicaid-insured patients with Alagille syndrome were available for analysis. Annually, commercially insured and Medicaid-insured patients averaged 31 medical visits (range, 1.5-237) and 48 medical visits (range, 0.7-690), respectively. The most common visits were outpatient with the majority encompassing lab/imaging and primary care visits (commercially insured: 21 [range, 0.0-183]; Medicaid-insured: 26 [range, 0.0-609]). Inpatient visits were the highest driver of costs in both the commercial and Medicaid populations. CONCLUSIONS: Patients with Alagille syndrome have a substantial HRU burden driven largely by numerous outpatient visits and costly inpatient stays. Given the complexity and variability of Alagille syndrome presentation, patients may benefit from multidisciplinary and subspecialized care.

Assessing barriers to access and equity for COVID-19 vaccination in the US.

BACKGROUND: Historical vaccination coverage in economically disadvantaged, ethnic minority, non-affluent white and agricultural populations in the US has lagged coverage in more affluent urban and suburban white populations due to a variety of social and economic factors. In the current COVID-19 pandemic, sociocultural and economic challenges continue to present significant obstacles to achieving equitable uptake of COVID-19 vaccines. The goal of this study was to qualitatively assess perceptions of key US healthcare stakeholders of the most significant barriers to COVID-19 vaccine access and equity to better characterize their expected impact on US communities. METHODS: After conducting a targeted literature review (TLR), we hypothesized 20 high-impact barriers which included structural and logistical barriers, capturing systemic challenges to vaccine accessibility, and attitudinal and informational barriers, affecting patient willingness to pursue vaccination. We developed a qualitative discussion guide, which included both open-ended and closed-ended questions, and interview stimulus material to conduct one-on-one in-depth interviews to assess the expected prevalence, severity, and persistence of these 20 high-impact barriers, which were hypothesized based on TLR. As a part of this qualitative study, we conducted one-on-one in-depth interviews with a diverse set of 15 US healthcare stakeholders who were involved in the COVID-19 vaccine rollout in states with relatively disparate vaccination rates by ethnicity. These stakeholders were selected to reflect an array of roles in the COVID-19 vaccine rollout, including infectious disease specialists, pharmacists, community advocacy representatives, and partners of local governments involved in the COVID-19 vaccine rollout and community education. RESULTS: Respondents identified limited vaccination sites in rural settings and technology-related barriers as the most prevalent and severe structural and logistical barriers in US communities. Respondents assessed COVID-19 vaccine safety concerns and politically motivated skepticism to be the most prevalent and severe attitudinal and informational barriers. Respondents cited proliferation of mobile vaccination clinics and local community messaging to endorse vaccines as the most effective solutions to these top structural and attitudinal barriers. Respondents expected politically motivated skepticism to be the most significant and persistent barrier to broader vaccine uptake in the US. CONCLUSIONS: Our study suggests that attitudinal barriers, particularly politically motivated skepticism, are likely to remain the most persistent challenges to widespread vaccination against COVID-19 in the US.

The Economic Burden of Schizophrenia in the United States.

Aim: The economic burden of schizophrenia in the United States (US) was estimated at $155.7 billion in 2013. Since 2013, the US experienced significant health care reforms and treatment advances. This study analyzed recent data and literature to update the US economic burden estimate for schizophrenia.Methods: Direct and indirect costs associated with schizophrenia were estimated using a prevalence-based approach. Direct health care costs were assessed retrospectively using an exact matched cohort design in the IBM Watson Health MarketScan databases from October 1, 2015, through December 31, 2019. Patients with schizophrenia (identified using ICD-10-CM codes F20 and F25) were exactly matched to controls on demographics, insurance type, and index year. Direct non-health care costs were estimated using published literature and government data. Indirect costs were estimated using a human capital approach and the value of quality-adjusted life-years lost. Cost offsets were estimated to account for basic living costs avoided. Excess costs, comparing costs for individuals with and without schizophrenia, were reported in 2019 USD.Results: The estimated excess economic burden of schizophrenia in the US in 2019 was $343.2 billion, including $251.9 billion in indirect costs (73.4%), $62.3 billion in direct health care costs (18.2%), and $35.0 billion in direct non-health care costs (10.2%). The largest drivers of indirect costs were caregiving ($112.3 billion), premature mortality ($77.9 billion), and unemployment ($54.2 billion). Cost offsets, representing $6.0 billion (1.7%), were subtracted from direct non-health care costs.Conclusions: The estimated burden of schizophrenia in the US doubled between 2013 and 2019 and was $343.2 billion in 2019, highlighting the importance of effective strategies and treatment options to improve the management of this difficult-to-treat patient population.

Physician perceptions of drug utilization management: Results of a national survey.

The use of drug utilization management techniques such as formulary exclusions, prior authorizations, and step edits has risen sharply during the last decade, contributing to the growing burden on physicians and patients. Limited quantitative data exist, however, on physician perceptions of drug utilization management. A national survey was conducted between February 9 and March 30, 2021, targeting office-based physicians working in the United States to assess their perceptions on drug utilization management in their practice. Of the 742 physicians that participated in the study, over 80% reported deciding against prescribing certain treatments in anticipation of drug utilization management at least sometimes (>50% of the time). Despite utilization management having an impact on prescribing decisions, about half of physicians said that the utilization management policies they encounter rarely or never (0-25% of the time) align with clinical evidence.

Real-world treatment, dosing, and discontinuation patterns among patients treated with pegvaliase for phenylketonuria: Evidence from dispensing data.

Background: Phenylketonuria (PKU) is an inborn metabolic error characterized by a deficiency of the enzyme required for the metabolism of phenylalanine, an essential amino acid found in most protein-containing foods. Pegvaliase (Palynziq®) is an enzyme substitution therapy approved for adults with PKU who have inadequate blood phenylalanine control (≥600 µmol/L) on existing management. Objective: To characterize the treatment, discontinuation, and dosing patterns in patients treated with pegvaliase in real-world practice settings in the United States following commercial availability in 2018. Study design: Retrospective cohort study using BioMarin's proprietary drug dispense database associated with the pegvaliase REMS program. Methods: Sample construction identified all patients who properly initiated pegvaliase in real world settings ('full cohort') and a subset of patients ('extended follow-up cohort') with ≥12 months between first dispense of maximum dose and last pegvaliase dispense. Key outcomes were quantified across patients in both cohorts: maximum daily dose; time to maximum daily dose; maximum daily syringes; and dose escalation over time. The overall dose at discontinuation and time to discontinuation were calculated. Patients who subsequently reinitiated therapy were identified. For the extended follow-up cohort, 12-month changes in dose and syringes and dispensing gaps during the 12 months after maximum dose were quantified across all patients and were further stratified by maximum dose. Results: Overall, 1596 patients associated with 33,814 dispenses were reflected in the pegvaliase dispense dataset during the study period from July 9, 2018, through December 31, 2021; 1280 patients associated with 25,973 dispenses met inclusion criteria for the full cohort, with 19.9 dispenses each on average. Of these patients, 483 patients associated with 15,149 dispenses also met the extended follow-up criteria, with an average of 31.4 dispenses.Average treatment duration in the full cohort was 82.2 weeks, including 50.8 weeks after maximum daily dose was achieved. The average maximum daily dose was 30 mg with an average time to maximum dose of 31.8 weeks: 43.0% of patients had a maximum dose of 20 mg, 31.3% a maximum dose of 40 mg, and 12.0% a maximum dose of 60 mg. At data cut-off, 289 patients (22.6%) had discontinued; within this group, 126 patients (43.6%) discontinued within the first 6 months after reaching maximum dose.The overall average treatment duration for patients in the extended follow up cohort at data cut off was 131.2 weeks, including 98.6 weeks after maximum dose was achieved. The average maximum daily dose across the cohort was 32.9 mg: 42.4% of patients had a maximum dose of 20 mg, 41.0% a maximum dose of 40 mg, and 11.2% a maximum dose of 60 mg. At 12 months after achieving maximum dose, 35% of patients had down-dosed, with a 46.8% decrease (on average) from their maximum dose. Conclusions: Real-world use of pegvaliase reflects longer titration periods than in the dosing schedule based on trial experience. Over time, a substantial number of patients are able to reduce their daily dose by titrating down from their maximum dose, a finding of great interest to clinicians and patients alike.

Assessment of the Impact of a Meningitis/Encephalitis Panel on Hospital Length of Stay: A Systematic Review and Meta-Analysis.

Meningitis and encephalitis are central nervous system infections with considerable morbidity and mortality. The BioFire® FilmArray® Meningitis/Encephalitis Panel (multiplex ME panel) can identify pathogens rapidly potentially aiding in targeted therapy and curtail antimicrobial exposure. This systematic review and meta-analysis synthesized the literature on the association between the multiplex ME panel and length of hospital stay (LOS), length of acyclovir therapy, and days with antibiotics. MEDLINE and EMBASE were searched. Only studies presenting novel data were retained. Random-effects meta-analyses were performed to assess the impact of the multiplex ME panel on outcomes. Of 169 retrieved publications, 13 met the criteria for inclusion. Patients tested with the multiplex ME panel had a reduction in the average LOS (mean difference [MD] [95% CI]: -1.20 days [-1.96, -0.44], n = 11 studies). Use of the multiplex ME panel was also associated with a reduction in the length of acyclovir therapy (MD [95% CI]: -1.14 days [-1.78, -0.50], n = 7 studies) and a nonsignificant reduction in the average number of days with antibiotics (MD [95% CI]: -1.01 days [-2.39, 0.37], n = 6 studies). The rapidity of pathogen identification contributes to an overall reduced LOS, reductions in the duration of empiric antiviral utilization, and a nonsignificant reduction in antibiotic therapy.

The Physician and Administrator-Reported Cost of Drug Utilization Management to Physician Practices: A Cross-Sectional Survey.

BACKGROUND: The use of drug utilization management techniques such as formulary exclusions, prior authorizations, and step edits has risen sharply during the last decade, contributing to growing administrative costs for physician practices. However, limited data exist on the extent of these administrative costs, with previous studies relying on data from over a decade ago. OBJECTIVE: The aim of this study was to assess physician and practice administrator experiences with drug utilization management. METHODS: A national survey was conducted between 9 February and 30 March 2021, targeting 925 physicians and administrators working at medical practices in the US. Time spent by physicians and their staff on tasks related to drug utilization management for prescription medications was collected and used to calculate the dollar value of that time. RESULTS: We estimated that physicians spent a median of 4.0 h per week on drug utilization management, while nurses spent 15.0 h and other staff spent between 3.6 and 10.0 h on drug utilization management per physician per week. This time was associated with a calculated median dollar value of $75,927 per physician per year. Extrapolating this estimate to a national scale suggests that time spent annually by physician practices on drug utilization management could be valued at more than $43 billion. CONCLUSIONS: Drug utilization management results in significant time spent by US physician practices, which in turn, results in meaningful costs to these practices. As the prevalence of drug utilization management continues to grow, the impact on physician practices will remain an important topic.

Direct health care costs associated with COVID-19 in the United States.

BACKGROUND: Data on the real-world health care burden of COVID-19 in the United States are limited. OBJECTIVE: To compare health care resource use (HRU), direct health care costs, and long-term COVID-19-related complications between patients with vs patients without COVID-19 diagnoses. METHODS: Using IBM MarketScan Commercial Claims and Encounters and Medicare Supplemental and Coordination of Benefits administrative claims databases (January 1, 2018, to March 1, 2021), this retrospective, matched cohort study compared patients with a recorded COVID-19 diagnosis to control subjects with no recorded diagnosis for COVID-19, personal history of COVID-19, or pneumonia due to COVID-19. To capture typical health care utilization, the control group was analyzed in 2019 (prepandemic); their index date was assigned as 1 year before the index date (first observed COVID-19 diagnosis) of their matched COVID-19 patient. All patients had continuous health plan coverage for at least 6 months pre-index (baseline) and at least 6 months post-index (allowing censoring during month 6). Separately for commercial and Medicare cohorts, COVID-19 and control patients were matched 1:1 using propensity scores, number of followup months, and indicator of age 18 years or older. During each month of the 6-month follow-up, all-cause HRU, health care costs, and COVID-19-related complications were compared between patients with COVID-19 and controls. RESULTS: After matching COVID-19 and control patients 1:1, a total of 150,731 commercial matched pairs and 1,862 Medicare matched pairs were retained; baseline characteristics were similar between patients with COVID-19 and controls. Patients with COVID-19 and controls had mean ages of 38.9 and 39.7 years in the commercial cohort and 74.3 and 75.3 years in the Medicare cohort, respectively. In month 1 of follow-up, patients with COVID-19 relative to controls were significantly more likely to have at least 1 inpatient admission (commercial: 6.9% vs 0.5%; Medicare: 29.1% vs 1.3%; both P < 0.001) and at least 1 emergency department visit (commercial: 37.3% vs 3.4%; Medicare: 26.2% vs 4.1%; both P < 0.001). Total health care costs in month 1 were significantly higher among patients with COVID-19 than controls (mean differences: $3,706 for commercial; $10,595 for Medicare; both P < 0.001), driven by inpatient costs. Though the incremental HRU and cost burden of COVID-19 decreased over time, patients with COVID-19 continued to have significantly higher total costs through month 5 (all P < 0.001 for both commercial and Medicare). During follow-up, patients with COVID-19 had significantly higher rates of complications than controls (commercial: 52.8% vs 29.0% with any; Medicare: 74.5% vs 47.9% with any; both P < 0.001), most commonly cough, dyspnea, and fatigue. CONCLUSIONS: COVID-19 was associated with significant economic and clinical burden, both in the short-term and over 6 months following diagnosis. DISCLOSURES: Jessica K DeMartino is an employee of Janssen Scientific Affairs, LLC. Elyse Swallow, Debbie Goldschmidt, Karen Yang, Marta Viola, Tyler Radtke, and Noam Kirson are employees of Analysis Group, Inc., which has received consulting fees from Janssen Scientific Affairs, LLC. This study was funded by Janssen Scientific Affairs, LLC. The sponsor was involved in the study design, interpretation of the results, manuscript review, and the decision to publish the article.

Epidemiology and economic burden of Lewy body dementia in the United States.

OBJECTIVE: To describe the trends in epidemiology, healthcare resource use (HCRU), and costs associated with Lewy body dementia (LBD), dementia with Lewy bodies (DLB), and Parkinson's disease dementia (PDD) in the United States. METHODS: This retrospective study used administrative claims data for Medicare fee-for-service (2010-2018) and commercially-insured beneficiaries (2010-2017). The annual prevalence and incidence were calculated among the Medicare beneficiaries by dividing the number of prevalent or incident LBD, DLB, and PDD patients by the total eligible population of that calendar year. Baseline patient characteristics, HCRU, and costs over time were described for Medicare and commercially insured patients with continuous health plan enrollment for ≥12 months before and ≥24 months after first cognitive impairment (CI) diagnosis. RESULTS: From 2010 to 2016, the incidence and prevalence rates of LBD among Medicare beneficiaries ranged from 0.21%-0.18% and 0.90%-0.83%, respectively. Of 9019 Medicare patients with LBD who met other inclusion criteria, 4796 (53.2%) had DLB and 4223 (46.8%) had PDD. The mean age was 78 years and the mean Charlson Comorbidity Index score was 1.6. On average, patients with LBD incurred $18,309 in medical costs during the 1-year pre-diagnosis and $29,174 and $22,814 at years 1 and 5 after diagnosis, respectively. The main cost drivers were inpatient and outpatient visits. Similar trends were observed for DLB and PDD as well as for commercially-insured patients. CONCLUSIONS: Our findings highlight the substantial epidemiological and economic burden across the LBD spectrum and underscore a high unmet need for effective treatments to improve patient outcomes.

Indirect comparison of apomorphine sublingual film and levodopa inhalation powder for Parkinson's disease 'OFF' episodes.

Aim: To compare efficacy of apomorphine sublingual film (APL) and levodopa inhalation powder (CVT-301) for 'on-demand' treatment of Parkinson's disease 'OFF' episodes. Patients & methods: Patient-level data from an APL pivotal study were re-weighted to match average baseline characteristics from a CVT-301 study (SPAN-PD). Placebo-adjusted treatments were compared at week 12. Results: Improvements in predose Unified Parkinson's Disease Rating Scale Part III scores were significantly larger for APL versus CVT-301 at 60 min postdose (least squares mean difference-in-difference: -8.82; p = 0.002); difference at 30 min favored APL but was not statistically significant (-4.46; p = 0.103). Total daily 'OFF' time reductions were significantly larger for APL versus CVT-301 (-1.31 h; p = 0.013). Conclusion: Results suggest APL treatment may lead to improved efficacy versus CVT-301.

The societal economic value of COVID-19 vaccines in the United States.

AIMS: The COVID-19 pandemic has claimed the lives of more than 800,000 people in the United States (US) and has been estimated to carry a societal cost of $16 trillion over the next decade. The availability of COVID-19 vaccines has had a profound effect on the trajectory of the pandemic, with wide-ranging benefits. We aimed to estimate the total societal economic value generated in the US from COVID-19 vaccines. METHODS: We developed a population-based economic model informed by existing data and literature to estimate the total societal value generated from COVID-19 vaccines by avoiding COVID-19 infections as well as resuming social and economic activity more quickly. To do this, we separately estimated the value generated from life years saved, healthcare costs avoided, quality of life gained, and US gross domestic product (GDP) gained under a range of plausible assumptions. RESULTS: Findings from our base case analysis suggest that from their launch in December 2020, COVID-19 vaccines were projected to generate $5.0 trillion in societal economic value for the US from avoided COVID-19 infections and resuming unrestricted social and economic activity more quickly. Our scenario analyses suggest that the value could range between $1.8 and $9.9 trillion. Our model indicates that the most substantial sources of value are derived from reduction in prevalence of depression ($1.9 trillion), gains to US GDP ($1.4 trillion), and lives saved from fewer COVID-19 infections ($1.0 trillion). LIMITATIONS: Constructed as a projection from December 2020, our model does not account for the Delta or future variants, nor does it account for improvements in COVID-19 treatment. CONCLUSIONS: The magnitude of economic benefit from vaccination highlights the need for coordinated policy decisions to support continued widespread vaccine uptake in the US.

The experience of a severe hypoglycaemic event from the perspective of people with diabetes and their caregivers: "What am I going to do?"

AIMS: Among people with diabetes using insulin, severe hypoglycaemia (SH) can be a life-threatening complication, if untreated. The personal experiences during an SH event from the perspectives of people with diabetes and their caregivers are not well-characterized. This study assessed the perceptions of the event and the decision making processes of people with diabetes (T1D n = 36; T2D n = 24) and their caregivers during SH events. METHODS: In-depth one-on-one telephone interviews were conducted with dyads of people with diabetes and caregivers in the United States (n = 120). An initial synopsis and inductive codebook schema were used to analyse the data with two independent coders (kappa = 0.87-0.89). Themes were developed from the codes, and codes were re-mapped to the themes. RESULTS: Four themes were formed: (1) Caregivers scramble to do the right thing and support people with diabetes in treating SH; (2) Decision making capacity is impaired during an SH event, often a panicked time; (3) People learn to manage SH events through their own experiences and frequently make lifestyle changes to prevent and treat future events; and (4) Discussion with healthcare providers about SH, and particularly SH treatment, is limited. CONCLUSIONS: SH events are stressful and often evoke emotional reactions that can impair decision making. Thus, advance treatment planning of SH events needs to occur. Much of the knowledge about SH treatment derives from prior experience rather than healthcare provider guidance, suggesting a need for healthcare providers to initiate proactive discussions about SH treatment.

Outcomes and resource use of patients with large hemispheric infarction and cerebral edema: analysis of real-world data.

OBJECTIVE: Large hemispheric infarction (LHI) is associated with a high likelihood of the evolution of life-threatening edema. Few studies have assessed real-world clinical outcomes and management strategies among patients with LHI. The objective of this study was to describe the management, in-hospital outcomes, and direct healthcare resource burden of patients with LHI, as well as those of patients with subsequent cerebral edema. METHODS: This observational, retrospective cohort study analyzed de-identified data from US adult patients using the IBM MarketScan Hospital Drug Database (Q4-2015 to Q4-2017). Patients were included in the "Possible LHI" or the "Other Ischemic Strokes" cohorts using ICD-10 diagnosis codes. Patients with possible LHI were further categorized into "LHI with Edema" and "LHI without Edema" subgroups using diagnosis and procedure codes. Select clinical and economic outcomes were compared between cohorts and subgroups using multivariable regressions. RESULTS: Of 79,201 eligible encounters with ischemic strokes, 11,772 unique patients were assigned to the Possible LHI cohort while 67,429 were assigned to the Other Ischemic Strokes cohort. Among patients with possible LHI, 869 (7%) were assigned to the LHI with Edema subgroup and 10,903 (93%) were assigned to the LHI without Edema subgroup. Patients in the Possible LHI cohort had longer hospital stays (mean difference [MD] [95%CI] = 2.6 [2.4;2.8] days), higher total facility charges (MD [95%CI] = $28,656 [26,794;30,524]), and higher odds of death (odds ratio [95%CI] = 2.2 [2.0;2.4]) than the Other Ischemic Strokes cohort. Among patients with possible LHI, the incremental clinical and resource burden was further exacerbated in the subgroup of patients with edema (hospital days: MD [95%CI] = 5.0 [3.9;6.2] days; total facility charges: MD [95%CI] = $59,585 [50,816;67,583]; mortality: odds ratio [95%CI] = 10.3 [8.5;12.4]). CONCLUSIONS: Among patients with ischemic strokes, LHI was associated with increased clinical management and direct healthcare resource burden in real-world hospital settings. The burden was substantially increased among patients who developed cerebral edema.