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Research and development investment of Chinese chemical pharmaceutical companies under the national pooled procurement: a retrospective panel data analysis, 2013-2022
Objective
To generate evidence about changes in the research and development (R&D) investment of Chinese chemical pharmaceutical companies before and after the implementation of the national pooled procurement, to respond to the concerns that significant price reductions might negatively affect R&D investment, and to facilitate the evidence-based decision-making for improvement of the national pooled procurement.
Methods
This retrospective study employed the fixed-effects models with robust SEs to analyse the changes in R&D investment intensities of 76 A-share listed Chinese chemical pharmaceutical companies before and after the procurement implementation in 2019. The analyses were based on a panel data set between 2013 and 2022. Subgroup analyses were conducted to account for the heterogeneity of the target companies. The bootstrap hypothesis test method was employed to assess potential variations across the different subgroups.
Results
Following the procurement implementation, the R&D investment intensity (RDI) of the target companies increased by 1.9% (p
Abstract 4120515: Impact of 2022 AHA/ACC/HFSA Heart Failure Guideline Value Statement Publication on Medicare Drug Coverage Policies
Circulation, Volume 150, Issue Suppl_1, Page A4120515-A4120515, November 12, 2024. Background:Patients with heart failure (HF) often have difficulty obtaining life-saving medications due to coverage barriers, such as prior authorizations (PA) and high out of pocket (OOP) costs. To promote better insurance coverage of high value therapies, the AHA/ACC/HFSA added Value Statements to HF guidelines to inform policymakers about medication cost effectiveness. We assessed whether these guidelines influenced Medicare drug coverage policies for two life-saving, costly HF medications: angiotensin receptor neprilysin inhibitors (ARNI – guideline “high value”) and sodium glucose cotransporter 2 inhibitors (SGLT2i – guideline “intermediate value”).Methods:We performed an observational study of Medicare drug plans from 4/2020-4/2023 to assess for changes in ARNI and SGLT2i coverage after Value Statement publication (4/2022), and subsequent Medicare plan online update (10/2022). The primary outcome was any barrier to drug coverage (PA, tier ≥ 3 OOP cost-sharing, step therapy, or no coverage). Analysis utilized interrupted time series and difference-in-difference (DiD) approaches. DiD analyses used direct oral anticoagulants as a control due to similar cost and utilization as ARNI and SGLT2i, but with no Value Statement.Results:Among 7,396 Medicare drug plans, 94.3%-97.4% had coverage barriers to ARNI and 93.2%-96.6% to SGLT2i. The majority of barriers were due to tier ≥ 3 OOP cost-sharing requirements (ARNI: 94.3%-95.8%; SGLT2i: 93.2%-95.6%). Coverage barriers remained stable in 4/2022, and declined slightly in 10/2022 (Figure). In DiD analyses, the presence of a Value Statement was associated with a ~1 percentage point decline in coverage barriers for ARNI and SGLT2i.Conclusion:Coverage barriers to ARNI and SGLT2i were common and did not change much in response to Value Statements in HF Guidelines. Increased consideration for Value Statements by Medicare policy-makers is needed to meaningfully improve access to high value therapies.
Abstract 4139309: Rural-Urban Differences in Cardiovascular Mortality in the United States, 2010-2022
Circulation, Volume 150, Issue Suppl_1, Page A4139309-A4139309, November 12, 2024. Background:Between 2011-2017, US rural adults experienced higher cardiovascular (CV) death rates than their urban counterparts, and rural-urban disparities in CV mortality widened. Little is known about these trends have evolved in the wake of the pandemic. In this study, we provide an updated analysis of rural-urban differences in CV mortality.Methods:We used CDC WONDER to obtain national death data from 2010-2022. CV cause of death was identified by ICD-10 codes I00-99. Large metro, small/medium metro, and rural areas were defined using the National Center for Health Statistics Urban-Rural Classification. We calculated age-adjusted mortality rates (AAMRs) per 100,000 population and compared 2022 vs. 2010 using rate differences and two-sample t-tests. We then fit a Poisson regression model to estimate annual percent change (APC), evaluating trends from 2010-2019 and 2019-2022 due to reversal in CV mortality observed after 2019. We included an interaction term to assess differential trends by rurality, and repeated the analysis for younger (age 25-64) and older (age >64) adults.Results:Between 2010-2022, AAMRs were consistently highest in rural areas (Figure 1, Table 1). AAMRs increased in rural areas (rate difference [RD] +3.4 [95% CI 0.4, 6.4]) but declined in urban areas (RD -23.8 [-25.3, -22.2]). This significant differential change was driven by a rise in AAMRs among younger, rural adults (RD +23.2 [21.2, 25.1). In contrast, older adults experienced a decline in AAMRs, though this reduction was greater in urban vs. rural areas (Table 2).From 2010-2019, overall APCs in AAMR decreased for all areas. However, when stratified by age, younger rural adults saw a significant increase (+1.0% [95% CI 0.5, 1.5]), while those in large metro areas did not (-0.2% [-0.5, 0.1]). Older adults saw a significant decrease across all areas.Between 2019-2022, the overall APC in AAMR increased significantly in rural areas (+3.1% [0.4, 6]), but in not large metro areas (+1.2% [-0.4, 2.9]). CV mortality rose in most subgroups, but younger rural adults experienced the largest increase (+4.2% [1.3, 7.1]) (Table 2).Conclusions:Between 2010-2022, CV mortality increased in rural areas and decreased in urban areas. Younger, rural adults experienced the most pronounced rise in CV death, while older, urban adults experienced the steepest decline. These findings highlight an urgent need to address widening rural-urban disparities, particularly among younger adults.
Abstract 4119868: Statin and PCSK9 Inhibitor Utilization and Spending in Medicaid between 2018 to 2022: A National Analysis
Circulation, Volume 150, Issue Suppl_1, Page A4119868-A4119868, November 12, 2024. Introduction:Low-income working-aged adults in the Medicaid program have a high burden of cardiovascular risk factors and disease, but often face barriers accessing necessary therapies. Little is known about contemporary patterns of utilization and spending on lipid-lowering therapies in Medicaid programs.Goal:To evaluate national trends in utilization and spending on statins and proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) in Medicaid.Methods:We performed a serial cross-sectional study using the Medicaid Spending by Drug Database, which contains national-level Medicaid spending data for medications partially or fully reimbursed by Medicaid for the approximately 84 million beneficiaries. We evaluated annual trends in utilization (prescription fills) and total spending for statins and PCSK9i from 2018 to 2022, both overall and by individual drug formulation. Spending was adjusted for inflation and reported in 2022 US dollars.Results:Medicaid beneficiaries filled 20.4 million statin prescriptions in 2018 compared to 20.3 million in 2022, representing a 0.4% decrease. However, Medicaid spending on statins decreased by 7.1%, from $246.2 million to $226.8 million over the same period. Prescription fills for generic Rosuvastatin increased the most (0.79 million to 2.6 million, +224.2%), while fills for brand-name Crestor decreased the most (0.065 million to 0.003 million, -95.2%). Medicaid beneficiaries filled 121,737 prescriptions for PCSK9 inhibitors in 2022 compared to 7,617 in 2018 (+1498%), coinciding with a 640% increase in total spending ($8.9 million to $65.7 million). Repatha Sureclick was the most filled PCSK9i in Medicaid with 80,503 fills in 2022, representing $43.9 million in total Medicaid spending.Conclusions:Despite almost no change in statin utilization between 2018 and 2022, Medicaid spending on statins fell by approximately $20 million, driven by a shift from brand-name to generic formulations. In contrast, spending on PCSK9 inhibitors increased by $57 million as these medications became more widely used. Understanding these trends is critical as Medicaid programs work to ensure access to effective cardiovascular therapies while also identifying opportunities for cost efficiencies nationwide.
Abstract 4147016: Trends in Hypertension-related End-Stage Renal Disease (ESRD) across the United States from 1999-2022: An Analysis of Age, Gender, and Ethnic Disparities
Circulation, Volume 150, Issue Suppl_1, Page A4147016-A4147016, November 12, 2024. Introduction:One of the main causes of renal disease, in which the kidneys are unable to function properly, is hypertension. Over time, uncontrolled hypertension can harm the fragile blood vessels in the kidneys, resulting in chronic kidney disease (CKD) and eventually end-stage renal disease (ESRD). In this study, we examined the trends of hypertension-related ESRD mortality in the United States from 1999 to 2022 and determined the disparities between various epidemiological groups.Methods:Our study conducted an in-depth search of the Centers for Disease Control and Prevention’s Wide- Ranging Online Data for Epidemiological Research (CDC Wonder) database and retrieved data on hypertension-related end-stage renal disease mortality from 1999 to 2022. Age-adjusted mortality rates (AAMR) per 100,000 individuals and associated annual percent changes (APC) for the overall study population were calculated using Joinpoint Regression Analysis. The data was further stratified into epidemiological groups of age, gender, ethnicity, and census region.Results:A total of 938,095 deaths occurred from hypertension-related end-stage renal disease. It was observed that the overall AAMR for hypertension-related ESRD increased from 1999-2022 with a fixed APC of 9.08. The populations with the highest mortality rates were males, African Americans, non-Hispanics, and the age group of over 85 years. Region-wise analysis gave variable trends in the AAMR (Overall APC: Northeast: 8.42, Midwest: 10.29, West: 9.04, and South: 12.80 from 2011-2022).Conclusion:In the US, the mortality rates from hypertension-related ESRD have shown a constant incline. The need for additional research and action is highlighted by persistent differences in mortality that are related to geography and demographics.
Abstract 4142044: The prognostic value of criteria for diagnosis of Immune Checkpoint Inhibitor Related Myocarditis: a comparison of the Bonaca et.al. criteria and European Society of Cardiology (ESC)-International Cardio-Oncology Society (ICOS) guidelines
Circulation, Volume 150, Issue Suppl_1, Page A4142044-A4142044, November 12, 2024. Background:Myocarditis is a dreaded complication of immune-checkpoint inhibitor (ICI) therapy but challenging to diagnose. There are no published data comparing the two leading diagnostic criteria for ICI myocarditis and their association with cardiovascular events.Methods:Patients treated with ICI and cardiac Troponin (cTnT) measurements thereafter at a tertiary institution from 2011 to 2022 were identified. Charts were reviewed for ICI-related myocarditis according to the Bonaca et. al criteria and the ESC-ICOS guideline criteria. A propensity matched control group was identified of patients treated with ICI but without developing myocarditis. Medical records were reviewed for baseline characteristics and long-term outcomes, including cardiac death, MACE (myocardial infarction, TIA/stroke, new heart failure diagnosis), and arrhythmias (V-tach, A-fib, complete heart block).Results:A total of 59 patients were identified as having a diagnosis of ICI-related myocarditis per Bonaca criteria (16 having definite, 13 probable and 30 possible myocarditis), and 47 met the ESC-ICOS guideline criteria. Mean age was 73.1±10.2 years, 60.1% were male, median follow-up was 2.5 years. ICI-related myocarditis as diagnosed by both diagnostic criteria had prognostic value for cardiac death (HR 13.94, 95%CI 1.84-105.64, p=0.011 per Bonaca, HR 6.22, 95%CI 1.77-21.88, p=0.004 per ESC-ICOS), MACE, (HR 3.17, 95%CI 1.34-7.47, p=0.008 per Bonaca, HR 2.97, 95%CI 1.37-6.45, p=0.006 per ESC-ICOS), and arrhythmias (HR 1.93, 95%CI 1.10-3.38, p=0.022 per Bonaca, HR 2.09, 95%CI 1.21-3.60, p
Abstract 4146291: Trends and Disparities in Circulatory Disease Prevalence in U.S. Adults: A National Health Interview Survey Database Analysis (2019-2022)
Circulation, Volume 150, Issue Suppl_1, Page A4146291-A4146291, November 12, 2024. Background:Circulatory diseases represent the primary cause of mortality in the US. Comprehending trends and potential disparities in the prevalence of circulatory conditions, such as angina pectoris (AP), myocardial infarction (MI), hypertension (HTN), and coronary heart disease (CHD), is essential for forming public health strategies.Aim:To investigate trends in the prevalence of circulatory conditions, including AP, MI, HTN, and CHD among US adults from 2019 to 2022.Methods:Prevalence percentages for all available circulatory diseases from the Centers for Disease Control and Prevention’s National Health Interview Survey (NHIS) database were retrieved for patients aged >18 years from 2019 to 2022. Annual Percentage Changes (APCs) along with their respective 95% CIs were calculated using regression analysis with Join point. The data was stratified by year, gender, age, race, nativity, veteran status, social vulnerability, employment status, metropolitan statistical area (MSA) status and census region.Results:Between 2019 and 2022, HTN was steadily the most prevalent, staying relatively constant at 27.0% (95% CI: 26.4, 27.7) in 2019 and 27.2% (95% CI: 26.5, 27.8) in 2022. Males consistently had higher prevalence than females with significant increases noted from 2019 to 2022 (APC: 1.0234). Black or African American had the highest prevalence (34.4% in 2022). The South (30.1% in 2022) and the West (22.5% in 2022) had respectively the highest and lowest rates. The second highest prevalence was seen in CHD increasing from 4.6% (95% CI: 4.3, 4.9) in 2019 to 4.9 (95% CI: 4.7, 5.2) in 2020. Males consistently exhibited a higher prevalence than females, with both genders showing significant increases in recent years (Male APC: 3.1448) (Female APC: 2.0165). For MI, a slight decrease was noted from 3.1% (95% CI:2.9, 3.4) in 2019 to 3.0% (95% CI:2.7, 3.2) in 2022. White individuals exhibited the highest prevalence (3.3% in 2022). AP had the lowest overall prevalence staying relatively consistent (1.7% in 2019 and 1.6% in 2022) (Figure 1).Conclusion:Significant trends (Figure 2) in most common circulatory diseases have been identified. Targeted interventions are imperative, particularly for high-risk demographics such as males, older adults, veterans, and unemployed individuals.
Abstract 4146278: Trends in Obesity-related Cardiovascular Disease Mortality across the United States from 1999-2022: An Analysis of Age, Gender, and Race disparities
Circulation, Volume 150, Issue Suppl_1, Page A4146278-A4146278, November 12, 2024. Background:Cardiovascular disease (CVD) is a leading cause of mortality worldwide and is inextricably linked to obesity, which is a modifiable risk factor for the pathology. In this study, we aimed to analyze the trends of obesity-related cardiovascular disease mortality in the United States from a period of 1999-2022 and also explored the incongruities between various epidemiological groups.Methods:Our study involved accessing multiple cause of mortality records obtained from the Centers for Disease Control and Prevention’s Wide-Ranging Online Data for Epidemiological Research (CDC Wonder) database, specifically focusing on obesity-related cardiovascular mortality, from 1999 to 2022. Age-adjusted mortality rates (AAMR) per 100,000 individuals and associated annual percent changes (APC) for the overall study population were calculated. We further analyzed the data by dividing it into epidemiological groups of age, race, gender, and ethnicity. We further stratified the cardiovascular disease mortality into heart failure, hypertension, ischemic heart disease, and cerebrovascular disease. We used Joinpoint Regression Program to analyze trends in AAMR.Results:A total of 33,359 deaths occurred from obesity-related cardiovascular disease in the US from 1999 to 2022. The overall AAMR for obesity-related cardiovascular mortality increased from 1999-2018 with an APC of 5.26, but following this, almost tripled from 2018-2022 with an APC of 14.69. The populations with the highest mortality rates were those in Males, African Americans, non-Hispanics, and the age group of 65-74 years. Among the stratification for the causes of CVD mortality, the highest increase in obesity-related AAMR was observed in hypertensive diseases (APC of 7.56 from 1999-2018, and 15.91 from 2018-2022).Conclusion:Obesity-related CVD mortality experienced a moderate incline in the United States. However, since COVID-19, there has been a significant increase in mortality. Persistent demographic and geographic disparities in mortality underscore the need for further investigation and intervention.