The Price of Progress: Funding and Financing Alzheimer\u27s Disease Drug Development

Introduction Advancing research and treatment for Alzheimer\u27s disease (AD) and the search for effective treatments depend on a complex financial ecosystem involving federal, state, industry, advocacy, venture capital, and philanthropy funding approaches. Methods We conducted an expert review of the literature pertaining to funding and financing of translational research and drug development for AD. Results The federal government is the largest public funder of research in AD. The National Institute on Aging, National Institute of Mental Health, National Institute of General Medical Sciences, and National Center for Advancing Translational Science all fund aspects of research in AD drug development. Non-National Institutes of Health federal funding comes from the National Science Foundation, Veterans Administration, Food and Drug Administration, and the Center for Medicare and Medicaid Services. Academic Medical Centers host much of the federally funded basic science research and are increasingly involved in drug development. Funding of the “Valley of Death” involves philanthropy and federal funding through small business programs and private equity from seed capital, angel investors, and venture capital companies. Advocacy groups fund both basic science and clinical trials. The Alzheimer Association is the advocacy organization with the largest research support portfolio relevant to AD drug development. Pharmaceutical companies are the largest supporters of biomedical research worldwide; companies are most interested in late stage de-risked drugs. Drugs progressing into phase II and III are candidates for pharmaceutical industry support through licensing, mergers and acquisitions, and co-development collaborations. Discussion Together, the funding and financing entities involved in supporting AD drug development comprise a complex, interactive, dynamic financial ecosystem. Funding source interaction is largely unstructured and available funding is insufficient to meet all demands for new therapies. Novel approaches to funding such as mega-funds have been proposed and more integration of component parts would assist in accelerating drug development

Bioinformatics and the politics of innovation in the life sciences: Science and the state in the United Kingdom, China, and India

The governments of China, India, and the United Kingdom are unanimous in their belief that bioinformatics should supply the link between basic life sciences research and its translation into health benefits for the population and the economy. Yet at the same time, as ambitious states vying for position in the future global bioeconomy they differ considerably in the strategies adopted in pursuit of this goal. At the heart of these differences lies the interaction between epistemic change within the scientific community itself and the apparatus of the state. Drawing on desk-based research and thirty-two interviews with scientists and policy makers in the three countries, this article analyzes the politics that shape this interaction. From this analysis emerges an understanding of the variable capacities of different kinds of states and political systems to work with science in harnessing the potential of new epistemic territories in global life sciences innovation

Development of a GPU-based Monte Carlo dose calculation code for coupled electron-photon transport

Monte Carlo simulation is the most accurate method for absorbed dose calculations in radiotherapy. Its efficiency still requires improvement for routine clinical applications, especially for online adaptive radiotherapy. In this paper, we report our recent development on a GPU-based Monte Carlo dose calculation code for coupled electron-photon transport. We have implemented the Dose Planning Method (DPM) Monte Carlo dose calculation package (Sempau et al, Phys. Med. Biol., 45(2000)2263-2291) on GPU architecture under CUDA platform. The implementation has been tested with respect to the original sequential DPM code on CPU in phantoms with water-lung-water or water-bone-water slab geometry. A 20 MeV mono-energetic electron point source or a 6 MV photon point source is used in our validation. The results demonstrate adequate accuracy of our GPU implementation for both electron and photon beams in radiotherapy energy range. Speed up factors of about 5.0 ~ 6.6 times have been observed, using an NVIDIA Tesla C1060 GPU card against a 2.27GHz Intel Xeon CPU processor.Comment: 13 pages, 3 figures, and 1 table. Paper revised. Figures update

Analytic philosophy for biomedical research: the imperative of applying yesterday's timeless messages to today's impasses

The mantra that "the best way to predict the future is to invent it" (attributed to the computer scientist Alan Kay) exemplifies some of the expectations from the technical and innovative sides of biomedical research at present. However, for technical advancements to make real impacts both on patient health and genuine scientific understanding, quite a number of lingering challenges facing the entire spectrum from protein biology all the way to randomized controlled trials should start to be overcome. The proposal in this chapter is that philosophy is essential in this process. By reviewing select examples from the history of science and philosophy, disciplines which were indistinguishable until the mid-nineteenth century, I argue that progress toward the many impasses in biomedicine can be achieved by emphasizing theoretical work (in the true sense of the word 'theory') as a vital foundation for experimental biology. Furthermore, a philosophical biology program that could provide a framework for theoretical investigations is outlined

Group interventions to improve health outcomes : a framework for their design and delivery

Peer reviewedPublisher PD

American Family Cohort, a data resource description

This manuscript is a research resource description and presents a large and novel Electronic Health Records (EHR) data resource, American Family Cohort (AFC). The AFC data is derived from Centers for Medicare and Medicaid Services (CMS) certified American Board of Family Medicine (ABFM) PRIME registry. The PRIME registry is the largest national Qualified Clinical Data Registry (QCDR) for Primary Care. The data is converted to a popular common data model, the Observational Health Data Sciences and Informatics (OHDSI) Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM). The resource presents approximately 90 million encounters for 7.5 million patients. All 100% of the patients present age, gender, and address information, and 73% report race. Nealy 93% of patients have lab data in LOINC, 86% have medication data in RxNorm, 93% have diagnosis in SNOWMED and ICD, 81% have procedures in HCPCS or CPT, and 61% have insurance information. The richness, breadth, and diversity of this research accessible and research ready data is expected to accelerate observational studies in many diverse areas. We expect this resource to facilitate research in many years to come

Integrated trajectories of the maternal metabolome, proteome, and immunome predict labor onset

Estimating the time of delivery is of high clinical importance because pre- and postterm deviations are associated with complications for the mother and her offspring. However, current estimations are inaccurate. As pregnancy progresses toward labor, major transitions occur in fetomaternal immune, metabolic, and endocrine systems that culminate in birth. The comprehensive characterization of maternal biology that precedes labor is key to understanding these physiological transitions and identifying predictive biomarkers of delivery. Here, a longitudinal study was conducted in 63 women who went into labor spontaneously. More than 7000 plasma analytes and peripheral immune cell responses were analyzed using untargeted mass spectrometry, aptamer-based proteomic technology, and single-cell mass cytometry in serial blood samples collected during the last 100 days of pregnancy. The high-dimensional dataset was integrated into a multiomic model that predicted the time to spontaneous labor [R = 0.85, 95% confidence interval (CI) [0.79 to 0.89], P = 1.2 × 10−40, N = 53, training set; R = 0.81, 95% CI [0.61 to 0.91], P = 3.9 × 10−7, N = 10, independent test set]. Coordinated alterations in maternal metabolome, proteome, and immunome marked a molecular shift from pregnancy maintenance to prelabor biology 2 to 4 weeks before delivery. A surge in steroid hormone metabolites and interleukin-1 receptor type 4 that preceded labor coincided with a switch from immune activation to regulation of inflammatory responses. Our study lays the groundwork for developing blood-based methods for predicting the day of labor, anchored in mechanisms shared in preterm and term pregnancies