Minimizing the burden of cancer in the United States: Goals for a high-performing health care system.

Between 1991 and 2015, the cancer mortality rate declined dramatically in the United States, reflecting improvements in cancer prevention, screening, treatment, and survivorship care. However, cancer outcomes in the United States vary substantially between populations defined by race/ethnicity, socioeconomic status, health insurance coverage, and geographic area of residence. Many potentially preventable cancer deaths occur in individuals who did not receive effective cancer prevention, screening, treatment, or survivorship care. At the same time, cancer care spending is large and growing, straining national, state, health insurance plans, and family budgets. Indeed, one of the most pressing issues in American medicine is how to ensure that all populations, in every community, derive the benefit from scientific research that has already been completed. Addressing these questions from the perspective of health care delivery is necessary to accelerate the decline in cancer mortality that began in the early 1990s. This article, part of the Cancer Control Blueprint series, describes challenges with the provision of care across the cancer control continuum in the United States. It also identifies goals for a high-performing health system that could reduce disparities and the burden of cancer by promoting the adoption of healthy lifestyles; access to a regular source of primary care; timely access to evidence-based care; patient-centeredness, including effective patient-provider communication; enhanced coordination and communication between providers, including primary care and specialty care providers; and affordability for patients, payers, and society.

Increases in Medicare Spending and Use after Private Equity Acquisition of Retina Practices.

PURPOSE: Private equity (PE) firms increasingly are acquiring physician practices in the United States, particularly within procedural-based specialties such as ophthalmology including retina. To date, the potential impact of ophthalmology practice acquisitions remains unknown. We evaluated the association between PE acquisition and Medicare spending and use for common retina services. DESIGN: Retrospective difference-in-differences analysis using the 20% Medicare fee-for-service claims dataset from January 1, 2015, through December 31, 2019. PARTICIPANTS: Eighty-two practices acquired by PE during the study period and matched control practices. METHODS: We used novel data on PE acquisitions of retina practices linked to the 20% sample Medicare claims data. Retina practices acquired by PE between 2016 and 2019 were matched to up to 3 non-PE (control) practices based on characteristics before acquisition. Private equity-acquired practices were compared with matched control practices through 6 quarters after acquisition using a difference-in-differences event study design. Data analyses were performed between August 2022 and April 2023. MAIN OUTCOME MEASURES: Medicare spending and use of common retina services. RESULTS: Relative to control practices, PE-acquired retina practices increased the use of higher-priced anti-vascular endothelial growth factor (VEGF) agents including aflibercept, which differentially increased by 6.5 injections (95% confidence interval, 0.4-12.5; P = 0.03) per practice-quarter, or 22% from baseline. As a result, Medicare spending on aflibercept differentially increased by $13 028 per practice-quarter, or 21%. No statistically significant differences were found in use or spending for evaluation and management visits or diagnostic imaging. CONCLUSIONS: Private equity acquisition of retina practices are associated with modest increases in the use of higher-priced anti-VEGF drugs like aflibercept, leading to higher Medicare spending. This finding highlights the need to monitor the influence of PE firms' financial incentives over clinician decision-making and the appropriateness of care, which could be swayed by strong economic incentives. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Changes in Healthcare Spending Attributable to High Deductible Health Plan Offer Among Enrollees with Comorbid Substance Use Disorder and Cardiovascular Disease.

BACKGROUND: The rise in prevalence of high deductible health plans (HDHPs) in the United States may raise concerns for high-need, high-utilization populations such as those with comorbid chronic conditions. In this study, we examine changes in total and out-of-pocket (OOP) spending attributable to HDHPs for enrollees with comorbid substance use disorder (SUD) and cardiovascular disease (CVD). METHODS: We used de-identified administrative claims data from 2007 to 2017. SUD and CVD were defined using algorithms of ICD 9 and 10 codes and HEDIS guidelines. The main outcome measures of interest were spending measure for all non-SUD/CVD-related services, SUD-specific services, and CVD-specific services, for all services and medications specifically. We assessed both total and OOP spending. We used an intent-to-treat two-part model approach to model spending and computed the marginal effect of HDHP offer as both the dollar change and percent change in spending attributable to HDHP offer. RESULTS: Our sample included 33,684 enrollee-years and was predominantly white and male with a mean age of 53 years. The sample had high demonstrated substantial healthcare utilization with 94% using any non-SUD/CVD services, and 84% and 78% using SUD and CVD services, respectively. HDHP offer was associated with a 17.0% (95% CI = [0.07, 0.27] increase in OOP spending for all non-SUD/CVD services, a 21.1% (95% CI = [0.11, 0.31]) increase in OOP spending for all SUD-specific services, and a 13.1% (95% CI = [0.04, 0.23]) increase in OOP spending for all CVD-specific services. HDHP offer was also associated with a significant increase in OOP spending on non-SUD/CVD-specific medications and SUD-specific medications, but not CVD-specific medications. CONCLUSIONS: This study suggests that while HDHPs do not change overall levels of annual spending among enrollees with comorbid CVD and SUD, they may increase the financial burden of healthcare services by raising OOP costs, which could negatively impact this high-need and high-utilization population.

Experiences and Interest in Value-Based Payment Arrangements for Medical Products Among Medicaid Agencies: An Exploratory Analysis.

Policy Points State Medicaid experience with value-based payment (VBP) arrangements for medical products is still relatively limited, and states face a number of challenges in designing and implementing such arrangements, particularly because of the resource-intensive nature of arrangements and data needed to support measurement of desired outcomes. A number of success factors and opportunities to support VBP arrangement efforts were identified through this study, including leveraging established venues or processes for collaboration with manufacturers, engaging external and internal partners in VBP efforts to bolster capabilities, acquiring access to new data sources, and utilizing annual renegotiation of contracts to allow for adjustments. CONTEXT: To date, uptake of value-based payment (VBP) arrangements for medical products and knowledge of their design and impact have been mainly concentrated among private payers. Interest and activity are expanding to Medicaid; however, their experiences and approaches to VBP arrangements for medical products are not well characterized. METHODS: This study sought to characterize the use of VBP arrangements for medical products among state Medicaid agencies through the use of a two-staged, mixed-methods approach. A survey and semistructured interviews were conducted to gain an understanding of state experiences with VBP arrangements for medical products. The survey and interviews were directed at senior leaders from nine states through the survey, with respondents from seven of these states additionally participating in the semistructured interviews. FINDINGS: Although experience with VBP arrangements for medical products among states varied, there were similarities across their motivations and general processes or phases employed in their design and implementation. States collectively identified a number of significant challenges to VBP arrangements, such as manufacturer engagement, outcomes measurement, and the time, expertise, and resources required to design and implement them. We outline a range of strategies to help address these gaps and make it easier for states to pursue VBP arrangements, including more direct engagement from the Center for Medicare and Medicaid Services, state-to-state peer learning and collaboration, data infrastructure and sharing, and additional research to inform fit-for-purpose VBP arrangement approaches. CONCLUSIONS: Findings from this study suggest that it may be easier for states to pursue VBP arrangements for medical products if there is greater clarity on processes employed that support design and implementation as well as effective strategies to address common challenges associated with contract negotiations. As states gain more experience, it will be important to monitor the design and implementation of common VBP arrangements to assess impact on the Medicaid program and the populations it serves.

Health Care Spending, Use, and Financial Hardship Among Traditional Medicare and Medicare Advantage Enrollees With Mental Health Symptoms.

OBJECTIVE: We examined the differences in health care spending and utilization, and financial hardship between Traditional Medicare (TM) and Medicare Advantage (MA) enrollees with mental health symptoms. DESIGN: Cross-sectional study. PARTICIPANTS: We identified Medicare beneficiaries with mental health symptoms using the Patient Health Questionnaire-2 and the Kessler-6 Psychological Distress Scale in the 2015-2021 Medical Expenditure Panel Survey. MEASUREMENTS: Outcomes included health care spending and utilization (both general and mental health services), and financial hardship. The primary independent variable was MA enrollment. RESULTS: MA enrollees with mental health symptoms were 2.3 percentage points (95% CI: -3.4, -1.2; relative difference: 16.1%) less likely to have specialty mental health visits than TM enrollees with mental health symptoms. There were no significant differences in total health care spending, but annual out-of-pocket spending was $292 (95% CI: 152-432; 18.2%) higher among MA enrollees with mental health symptoms than TM enrollees with mental health symptoms. Additionally, MA enrollees with mental health symptoms were 5.0 (95% CI: 2.9-7.2; 22.3%) and 2.5 percentage points (95% CI: 0.8-4.2; 20.9%) more likely to have difficulty paying medical bills over time and to experience high financial burden than TM enrollees with mental health symptoms. CONCLUSION: Our findings suggest that MA enrollees with mental health symptoms were more likely to experience limited access to mental health services and high financial hardship compared to TM enrollees with mental health symptoms. There is a need to develop policies aimed at improving access to mental health services while reducing financial burden for MA enrollees.

Group sequential designs for clinical trials when the maximum sample size is uncertain.

Motivated by the experience of COVID-19 trials, we consider clinical trials in the setting of an emerging disease in which the uncertainty of natural disease course and potential treatment effects makes advance specification of a sample size challenging. One approach to such a challenge is to use a group sequential design to allow the trial to stop on the basis of interim analysis results as soon as a conclusion regarding the effectiveness of the treatment under investigation can be reached. As such a trial may be halted before a formal stopping boundary is reached, we consider the final analysis under such a scenario, proposing alternative methods for when the decision to halt the trial is made with or without knowledge of interim analysis results. We address the problems of ensuring that the type I error rate neither exceeds nor falls unnecessarily far below the nominal level. We also propose methods in which there is no maximum sample size, the trial continuing either until the stopping boundary is reached or it is decided to halt the trial.

A two-stage group-sequential design for delayed treatment responses with the possibility of trial restart.

Common statistical theory applicable to confirmatory phase III trial designs usually assumes that patients are enrolled simultaneously and there is no time gap between enrollment and outcome observation. However, in practice, patients are enrolled successively and there is a lag between the enrollment of a patient and the measurement of the primary outcome. For single-stage designs, the difference between theory and practice only impacts on the trial duration but not on the statistical analysis and its interpretation. For designs with interim analyses, however, the number of patients already enrolled into the trial and the number of patients with available outcome measurements differ, which can cause issues regarding the statistical analyses of the data. The main issue is that current methodologies either imply that at the time of the interim analysis there are so-called pipeline patients whose data are not used to make a statistical decision (like stopping early for efficacy) or the enrollment into the trial needs to be at least paused for interim analysis to avoid pipeline patients. There are methods for delayed responses available that introduced error-spending stopping boundaries for the enrollment of patients followed by critical values to reject the null hypothesis in case the stopping boundaries have been crossed beforehand. Here, we will discuss other solutions, considering different boundary determination algorithms using conditional power and introducing a design allowing for recruitment restart while keeping the type I error rate controlled.

Surgeon-Dependent Variability in Cost of Gastrointestinal Operations in a Single Cancer Center.

INTRODUCTION: Cancer operations are increasingly utilizing specialized equipment and technology. Related costs are often not known to the responsible surgeon. We seek to evaluate cost aspects of care episodes attributable to the surgeon's management decisions. METHODS: Financial cost data in a tertiary academic cancer center were queried over 3 y. Consecutive patients undergoing gastrointestinal operations followed by inpatient admission of two or more days were included, excluding patients with 40+ d admissions. Analysis of variance, Kruskal-Wallis, and multiple regression statistics were utilized. RESULTS: The study population included 1540 patients: 54% men and 46% women, with a median age of 64 y (range 15-95). Eight surgeons conducted major (82%) and minor (18%) operations, with a minimally invasive surgical approach in 60.4%. Procedures included colorectal (37%), pancreatic (19%), esophagogastric (18%), hepatobiliary (18%), and small bowel resections (8%). Total direct costs differed between surgeons with an analysis of variance coefficient range between -$3265 and +$6163 (P < 0.001). Surgeons' cost differences were observed for central medical supply, operating room (OR) supply, total OR, inpatient room, laboratory, pharmacy, supportive care (P < 0.001), and radiology costs (P < 0.02). OR supply cost was the dominant consistent domain with significant differences between surgeons in all case subcategories. When controlled for case category and minimally invasive surgical approach, multiple regression showed the most significant variations between surgeons in ORs, medical supply, and nutrition costs (P < 0.001), followed by laboratory costs (P < 0.01). Top OR supply costs were staplers and energy devices. CONCLUSIONS: Even in a highly subspecialized surgical environment, surgeons' variable utilization of ORs and medical supplies is strongly linked to variations in care-related costs. Specific queries into supply items should reduce costs and optimize value generated.

Financial Toxicity of Withdrawn Poly (Adenosine Diphosphate Ribose) Polymerase Inhibitor Indications for Ovarian Cancer.

OBJECTIVES: We sought to quantify exposure to and financial impacts of poly (adenosine diphosphate ribose) polymerase inhibitor (PARPi) treatments for eventually withdrawn ovarian cancer indications. METHODS: We identified in Optum's deidentified Clinformatics® Data Mart database 1695 patients with ovarian cancer diagnoses who received olaparib, rucaparib, or niraparib between January 2015 and September 2021. We describe PARPi use and out-of-pocket, total healthcare, and PARPi spending among patients with ovarian cancer with 3 or more previous lines of therapy. RESULTS: Of the 1695 patients who received PARPi, 254 were estimated to have been heavily pretreated and exposed to eventually withdrawn indications. Cumulative total medical and pharmacy costs for these patients were $53 392 184; PARPi costs accounted for 34%. Median PARPi cost per patient was $43 347. Cumulative out-of-pocket costs totaled $533 281. CONCLUSIONS: Potential patient harm, including financial toxicity, might have been mitigated through more stringent drug approval requirements.

Partial Orphan Cancer Drugs: US Food and Drug Administration Approval, Clinical Benefit, Trials, Epidemiology, Price, Beneficiaries, and Spending.

OBJECTIVES: The Orphan Drug Act (ODA) incentivizes drug development for rare diseases with limited sales potential. Partial orphans-drugs used to treat rare and common diseases-frequently turn into multi-billion dollar blockbusters. This study analyzes partial orphan cancer drugs' development, approval, and economics. METHODS: 170 drugs with US Food and Drug Administration approval for 455 cancer indications were identified (2000-2021). 110 full, 22 partial, and 38 non-orphan drugs were compared regarding their approval, benefits, trials, epidemiology, price, beneficiaries, and spending with data from regulatory documents, Global Burden of Disease study, and Medicare and Medicaid. RESULTS: Full orphans, relative to partial and non-orphans, were more frequently monotherapies for hematologic cancers supported by smaller single-arm trials treating diseases with a lower incidence and higher severity. The time from first to second indication approval was 1 year shorter for partial than full orphans. Full orphans offered a greater overall survival (median: 4.0 vs 2.8 vs 2.8 months, P < .001) and progression-free survival benefit (median: 5.1 vs 2.5 vs 3.6 months, P < .001). Monthly prices were higher for full and partial than non-orphan drugs (median: $17 177 vs $13 284 vs $12 457, P < .001). Beneficiaries (8790 vs 4390 vs 1730) and spending ($570 vs $305 vs $156 million) per drug were greater for partial than non-and full orphans. CONCLUSIONS: Although partial orphans' benefits, trials, and economics are more similar to non-than full orphans, they receive all of the ODA's benefits and are swiftly extended to new indications; resulting in greater spending. A maximum ODA revenue/patient threshold could limit expenditure on partial orphans.

Financial protection in health revisited: Is catastrophic health spending underestimated for service- or disease-specific analysis?

Economists originally developed methods to assess financial catastrophe using total or aggregate out-of-pocket health spending. Aggregate out-of-pocket health spending is financially catastrophic when it exceeds a fixed proportion (i.e., threshold) of a household's total income or expenditure in a given period. However, these methods are now applied to assess financial catastrophe in disease- or service-specific rather than aggregate out-of-pocket health spending without using disease- or service-specific thresholds. This paper argues that not using disease- or service-specific thresholds for such assessments is misleading and underestimates the burden of financial catastrophe, especially among households from poorer backgrounds. It then proposed disease- or service-specific catastrophic payment thresholds, applied them to Nigeria and found that financial catastrophe was underestimated for the five service groups considered. The paper stresses the importance of using disease- or service-specific thresholds and avoiding unadjusted thresholds, which may leave poorer households behind as financially protected.

Trends in household out-of-pocket health expenditures and their underlying determinants: explaining variations within African regional economic communities from countries panel data.

BACKGROUND: The persistently high out-of-pocket health spending (OOPHE) in Africa raise significant concern about the prospect of reaching SDG health targets and UHC. The study examines the convergence hypothesis of OOPHE in 40 African countries from 2000 to 2019. METHODS: We exploit the log t , club clustering, and merging methods on a panel of dataset obtained from the World Development Indicators, the World Governance Indicators, and the World Health Organization. Then, we employ the multilevel linear mixed effect model to examine whether countries' macro-level characteristics affect the disparities in OOPHE in the African regional economic communities (RECs). RESULTS: The results show evidence of full panel divergence, indicating persistent disparities in OOPHE over time. However, we found three convergence clubs and a divergent group for the OOPHE per capita and as a share of the total health expenditure. The results also show that convergence does not only occur among countries affiliated with the same regional economic grouping, suggesting disparities within the regional groupings. The findings reveal that countries' improved access to sanitation and quality of governance, increased childhood DPT immunization coverage, increased share of the elderly population, life expectancy at birth, external health expenditure per capita, and ICT (information and communication technology) significantly affect within-regional groupings' disparities in OOPHE per capita. The results also show that an increasing countries' share of elderly and younger populations, access to basic sanitation, ICT, trade GDP per capita, life expectancy at birth, childhood DPT immunization coverage, and antiretroviral therapy coverage have significant impacts on the share of OOPHE to total health expenditure within the regional groupings. CONCLUSION: Therefore, there is a need to develop policies that vary across the convergence clubs. These countries should increase their health services coverage, adopt planned urbanization, and coordinate trade and ICT access policies. Policymakers should consider hidden costs associated with access to childhood immunization services that may lead to catastrophic health spending.

Spending on nucleos(t)ide analogues for hepatitis B in medicaid beneficiaries: 2012-2021.

INTRODUCTION AND OBJECTIVES: Treatment of chronic hepatitis B (CHB) with nucelos(t)ide analogues (NA) can improve outcomes, but NA treatment is expensive for insurance plans. MATERIALS AND METHODS: The Centers for Medicare & Medicaid Services database was assessed from 2012 to 2021 to assess the use of NA for CHB in patients on Medicaid. Data extracted included the number of claims, units, and costs of each agent stratified by originator and generic. RESULTS: Over the study period, 1.9 billion USD was spent on NA, with spending peaking in 2016 at $289 million US, which has subsequently decreased. Lower expenditures since 2016 have been associated with increased use of generics. The use of generic tenofovir or entecavir led to savings of $669 million US over the study period. CONCLUSIONS: Increased generic use has significantly reduced expenditures for NA drugs; policy shifts towards generic drug use may help with sustainability.

Association between nintedanib adherence trajectory and healthcare use among idiopathic pulmonary fibrosis patients.

BACKGROUND: Although inverse associations have been found between medication adherence and healthcare use and spending outcomes in many clinical settings, no studies to date have examined these relationships for patients with idiopathic pulmonary fibrosis (IPF) initiating nintedanib. We build on our prior study that used group-based trajectory modeling (GBTM) to compare inpatient hospitalization and medical care spending outcomes between groups of patients with different nintedanib adherence trajectories. METHODS: This analysis used 100% Medicare data and included beneficiaries with IPF who initiated nintedanib during 10/01/2014-12/31/2018. The sample consisted of community-dwelling older adults (≥ 66 years) with continuous coverage in Medicare Parts A (inpatient care), B (outpatient care) and D (prescription drugs) for one year before (baseline) and after (follow-up) initiating nintedanib. Patients were assigned to the GBTM-derived adherence trajectory group closest to their own nintedanib adherence experience. All-cause and IPF-related hospitalization events and total medical spending were measured during the follow-up period. Unadjusted and adjusted regression models were estimated to compare outcomes between patients in different nintedanib adherence trajectories. RESULTS: Among the 1,798 patients initiating nintedanib, the mean age was 75.4 years, 61.1% were male, and 91.1% were non-Hispanic white. The best-fitting GBTM had five adherence trajectories: high adherence, moderate adherence, high-then-poor adherence, delayed-poor adherence, and early-poor adherence. All-cause hospitalizations and total all-cause medical spending were higher among patients in the high-then-poor, delayed-poor and early-poor adherence trajectories than those in the high adherence trajectory. For example, adjusted total all-cause medical spending was $4,876 (95% CI: $1,470 to $8,282) higher in the high-then-poor adherence trajectory, $3,639 (95% CI: $1,322 to $5,955) higher in the delayed-poor adherence trajectory and $3,907 (95% CI: $1,658 to $6,156) higher in the early-poor adherence trajectory compared with the high adherence trajectory. IPF-related hospitalizations and medical care spending were higher among those in the high-then-poor adherence trajectory compared with those in the high adherence trajectory. CONCLUSIONS: Poor adherence to nintedanib was associated with all-cause hospitalizations and medical costs. Therefore, improved adherence programs, such as support programs, can be implemented to reduce economic burden.

Impact of health spending on hospitalization rates in Baltic countries: a comparative analysis.

INTRODUCTION: This study examines the association between healthcare indicators and hospitalization rates in three high-income European countries, namely Estonia, Latvia, and Lithuania, from 2015 to 2020. METHOD: We used a sex-stratified generalized additive model (GAM) to investigate the impact of select healthcare indicators on hospitalization rates, adjusted by general economic status-i.e., gross domestic product (GDP) per capita. RESULTS: Our findings indicate a consistent decline in hospitalization rates over time for all three countries. The proportion of health expenditure spent on hospitals, the number of physicians and nurses, and hospital beds were not statistically significantly associated with hospitalization rates. However, changes in the number of employed medical doctors per 10,000 population were statistically significantly associated with changes of hospitalization rates in the same direction, with the effect being stronger for males. Additionally, higher GDP per capita was associated with increased hospitalization rates for both males and females in all three countries and in all models. CONCLUSIONS: The relationship between healthcare spending and declining hospitalization rates was not statistically significant, suggesting that the healthcare systems may be shifting towards primary care, outpatient care, and on prevention efforts.

Effectiveness of public health spending: Investigating the moderating role of governance using partial least squares structural equation modelling (PLS-SEM).

BACKGROUND: The link between public health spending (PHS) and population health outcomes (PHO) has been extensively studied. However, in sub-Saharan Africa (SSA), the moderating effects of governance in this relationship are little known. Furthermore, studies have focused on mortality as the main health outcome. This study contributes to this literature by investigating the moderating role of governance in the relationship by simultaneously assessing three dimensions of governance (corruption control, government effectiveness and voice accountability) using disability-adjusted life years (DALYs) as a measure of outcomes. METHODS: The study applies the two-stage moderation approach using partial least squares structural equation modelling (PLS-SEM) to panel data from 43 SSA nations from 2013 to 2019. The study also uses domestic general government health expenditure (DGGHE) as an independent variable and disability-adjusted life years (DALY) as the dependent variable in this relationship. RESULTS: The analysis reveals that DGGHE affects DALY negatively and that governance improves the effect of DGGHE on DALY, with bigger improvements among countries with worse governance. CONCLUSION: These findings provide evidence that good governance is crucial to the effectiveness of PHS in SSA nations. Sub-Saharan Africa (SSA) countries should improve governance to improve population health.

PriTKT: A Blockchain-Enhanced Privacy-Preserving Electronic Ticket System for IoT Devices.

Electronic tickets (e-tickets) are gradually being adopted as a substitute for paper-based tickets to bring convenience to customers, corporations, and governments. However, their adoption faces a number of practical challenges, such as flexibility, privacy, secure storage, and inability to deploy on IoT devices such as smartphones. These concerns motivate the current research on e-ticket systems, which seeks to ensure the unforgeability and authenticity of e-tickets while simultaneously protecting user privacy. Many existing schemes cannot fully satisfy all these requirements. To improve on the current state-of-the-art solutions, this paper constructs a blockchain-enhanced privacy-preserving e-ticket system for IoT devices, dubbed PriTKT, which is based on blockchain, structure-preserving signatures (SPS), unlinkable redactable signatures (URS), and zero-knowledge proofs (ZKP). It supports flexible policy-based ticket purchasing and ensures user unlinkability. According to the data minimization and revealing principle of GDPR, PriTKT empowers users to selectively disclose subsets of (necessary) attributes to sellers as long as the disclosed attributes satisfy ticket purchasing policies. In addition, benefiting from the decentralization and immutability of blockchain, effective detection and efficient tracing of double spending of e-tickets are supported in PriTKT. Considering the impracticality of existing e-tickets schemes with burdensome ZKPs, we replace them with URS/SPS or efficient ZKP to significantly improve the efficiency of ticket issuing and make it suitable for use on smartphones.

Information-based group sequential design for post-market safety monitoring of medical products using real world data.

Real world healthcare data are commonly used in post-market safety monitoring studies to address potential safety issues related to newly approved medical products. Such studies typically involve repeated evaluations of accumulating safety data with respect to pre-defined hypotheses, for which the group sequential design provides a rigorous and flexible statistical framework. A major challenge in designing a group sequential safety monitoring study is the uncertainty associated with product uptake, which makes it difficult to specify the final sample size or maximum duration of the study. To deal with this challenge, we propose an information-based group sequential design which specifies a target amount of information that would produce adequate power for detecting a clinically significant effect size. At each interim analysis, the variance estimate for the treatment effect of interest is used to compute the current information time, and a pre-specified alpha spending function is used to determine the stopping boundary. The proposed design can be applied to regression models that adjust for potential confounders and/or heterogeneous treatment exposure. Simulation results demonstrate that the proposed design performs reasonably well in realistic settings.

Beta spending function based on conditional power in group sequential design.

Conditional power (CP) serves as a widely utilized approach for futility monitoring in group sequential designs. However, adopting the CP methods may lead to inadequate control of the type II error rate at the desired level. In this study, we introduce a flexible beta spending function tailored to regulate the type II error rate while employing CP based on a predetermined standardized effect size for futility monitoring (a so-called CP-beta spending function). This function delineates the expenditure of type II error rate across the entirety of the trial. Unlike other existing beta spending functions, the CP-beta spending function seamlessly incorporates beta spending concept into the CP framework, facilitating precise stagewise control of the type II error rate during futility monitoring. In addition, the stopping boundaries derived from the CP-beta spending function can be calculated via integration akin to other traditional beta spending function methods. Furthermore, the proposed CP-beta spending function accommodates various thresholds on the CP-scale at different stages of the trial, ensuring its adaptability across different information time scenarios. These attributes render the CP-beta spending function competitive among other forms of beta spending functions, making it applicable to any trials in group sequential designs with straightforward implementation. Both simulation study and example from an acute ischemic stroke trial demonstrate that the proposed method accurately captures expected power, even when the initially determined sample size does not consider futility stopping, and exhibits a good performance in maintaining overall type I error rates for evident futility.

2024 Alzheimer's disease facts and figures.

This article describes the public health impact of Alzheimer's disease (AD), including prevalence and incidence, mortality and morbidity, use and costs of care and the ramifications of AD for family caregivers, the dementia workforce and society. The Special Report discusses the larger health care system for older adults with cognitive issues, focusing on the role of caregivers and non-physician health care professionals. An estimated 6.9 million Americans age 65 and older are living with Alzheimer's dementia today. This number could grow to 13.8 million by 2060, barring the development of medical breakthroughs to prevent or cure AD. Official AD death certificates recorded 119,399 deaths from AD in 2021. In 2020 and 2021, when COVID-19 entered the ranks of the top ten causes of death, Alzheimer's was the seventh-leading cause of death in the United States. Official counts for more recent years are still being compiled. Alzheimer's remains the fifth-leading cause of death among Americans age 65 and older. Between 2000 and 2021, deaths from stroke, heart disease and HIV decreased, whereas reported deaths from AD increased more than 140%. More than 11 million family members and other unpaid caregivers provided an estimated 18.4 billion hours of care to people with Alzheimer's or other dementias in 2023. These figures reflect a decline in the number of caregivers compared with a decade earlier, as well as an increase in the amount of care provided by each remaining caregiver. Unpaid dementia caregiving was valued at $346.6 billion in 2023. Its costs, however, extend to unpaid caregivers' increased risk for emotional distress and negative mental and physical health outcomes. Members of the paid health care and broader community-based workforce are involved in diagnosing, treating and caring for people with dementia. However, the United States faces growing shortages across different segments of the dementia care workforce due to a combination of factors, including the absolute increase in the number of people living with dementia. Therefore, targeted programs and care delivery models will be needed to attract, better train and effectively deploy health care and community-based workers to provide dementia care. Average per-person Medicare payments for services to beneficiaries age 65 and older with AD or other dementias are almost three times as great as payments for beneficiaries without these conditions, and Medicaid payments are more than 22 times as great. Total payments in 2024 for health care, long-term care and hospice services for people age 65 and older with dementia are estimated to be $360 billion. The Special Report investigates how caregivers of older adults with cognitive issues interact with the health care system and examines the role non-physician health care professionals play in facilitating clinical care and access to community-based services and supports. It includes surveys of caregivers and health care workers, focusing on their experiences, challenges, awareness and perceptions of dementia care navigation.