Modeling impact of inflation reduction act price negotiations on new drug pipeline considering differential contributions of large and small biopharmaceutical companies.

Background/aims: Provisions of the Inflation Reduction Act mandating drug price negotiation by the Centers for Medicare & Medicaid Services have been criticized as a threat to pharmaceutical innovation. This study models potential impacts of the Inflation Reduction Act on drug approvals based on the differential contributions of large pharmaceutical companies and smaller biotechnology firms to clinical trials and the availability of capital.

Methods: This study examined research and development expense, revenue, and new investment (sale of common and preferred stock) by public biopharmaceutical companies and sponsorship of phased clinical trials in ClinicalTrials.

Association between expedited review designations and the US or global burden of disease for drugs approved by the US Food and Drug Administration, 2010-2019: a cross-sectional analysis.

Objectives: Pharmaceutical innovation can contribute to reducing the burden of disease in human populations. This research asks whether products approved by the US Food and Drug Administration (FDA) from 2010 to 2019 and expedited review programmes incentivising development of products for serious disease were aligned with the US or global burden of disease.

Design: Cross-sectional study.

Comparing the economic terms of biotechnology licenses from academic institutions with those between commercial firms.

Licenses of drug-related biotechnologies from academic institutions to commercial firms are intended to promote practical applications of public sector research and a return on government investments in biomedical science. This empirical study compares the economic terms of 239 biotechnology licenses from academic institutions to biotechnology companies with 916 comparable licenses between commercial firms. Academic licenses had lower effective royalty rates (median 3% versus 8%, p<0.

Finding a rhythm: Relating ultra-short-term heart rate variability measures in healthy young adults during rest, exercise, and recovery.

Ultra-short-term (UST; <5 min) heart rate variability (HRV) is increasingly used to indirectly assess autonomic nervous system modulation and physical health. However, UST HRV estimates may vary with measurement technique, physiological state, and data preprocessing. The purpose of this investigation was to assess the information content of UST HRV and its sensitivity to different physiological states and preprocessing techniques.

Efficient interaction selection for clustered data via stagewise generalized estimating equations.

Model selection in the presence of interaction terms is challenging as the final model must maintain a hierarchy between main effects and interaction terms. This work presents two stagewise estimation approaches to appropriately select models with interaction terms that can utilize generalized estimating equations to model clustered data. The first proposed technique is a hierarchical lasso stagewise estimating equations approach, which is shown to directly correspond to the hierarchical lasso penalized regression.

Profitability of Large Pharmaceutical Companies Compared With Other Large Public Companies.

Importance: Understanding the profitability of pharmaceutical companies is essential to formulating evidence-based policies to reduce drug costs while maintaining the industry's ability to innovate and provide essential medicines.

Objective: To compare the profitability of large pharmaceutical companies with other large companies.

Design, Setting, And Participants: This cross-sectional study compared the annual profits of 35 large pharmaceutical companies with 357 companies in the S&P 500 Index from 2000 to 2018 using information from annual financial reports.

Stagewise generalized estimating equations with grouped variables.

Forward stagewise estimation is a revived slow-brewing approach for model building that is particularly attractive in dealing with complex data structures for both its computational efficiency and its intrinsic connections with penalized estimation. Under the framework of generalized estimating equations, we study general stagewise estimation approaches that can handle clustered data and non-Gaussian/non-linear models in the presence of prior variable grouping structure. As the grouping structure is often not ideal in that even the important groups may contain irrelevant variables, the key is to simultaneously conduct group selection and within-group variable selection, that is, bi-level selection.

Spatial, socio-economic, and ecological implications of incorporating minimum size constraints in marine protected area network design.

Marine protected areas (MPAs) are the cornerstone of most marine conservation strategies, but the effectiveness of each one partly depends on its size and distance to other MPAs in a network. Despite this, current recommendations on ideal MPA size and spacing vary widely, and data are lacking on how these constraints might influence the overall spatial characteristics, socio-economic impacts, and connectivity of the resultant MPA networks. To address this problem, we tested the impact of applying different MPA size constraints in English waters.

Abundance and prevalence of Aedes aegypti immatures and relationships with household water storage in rural areas in southern Viet Nam.

Since 2000, the Government of Viet Nam has committed to provide rural communities with increased access to safe water through a variety of household water supply schemes (wells, ferrocement tanks and jars) and piped water schemes. One possible, unintended consequence of these schemes is the concomitant increase in water containers that may serve as habitats for dengue mosquito immatures, principally Aedes aegypti. To assess these possible impacts we undertook detailed household surveys of Ae.

Ionic reaction of halogens with terminal alkenes: the effect of electron-withdrawing fluorine substituents on the bonding of halonium ions.

Ionic reactions of terminal alkenes with chlorine (Cl(2)), bromine (Br(2)), and iodine monochloride (ICl) are sensitive to the alkyl substituents, and the positions and number of vinyl fluorine atoms. These perturbations influence the symmetry of the halonium ion intermediates, which can be determined by the distribution of the Markovnikov to anti-Markovnikov products. A vinyl fluorine on the number-2 carbon favors an unsymmetrical intermediate with greater charge on the number-2 carbon unless the alkyl group is electron withdrawing.