Frontiers in Precision Medicine II: Cancer, Big Data and the Public

Precision medicine is being developed within a complex landscape of public policy, science, economics, law, and regulation. In these and other policy areas, the goal of developing individually-tailored therapies poses novel challenges for health care research, delivery and policy. In this symposium, a range of experts in genetics, medicine, bioinformatics, intellectual property, health economics and bioethics identified and discussed many of the pressing questions raised by the development and practice of precision medicine. These and other issues will need to be taken into account as precision medicine moves ahead and becomes the standard of medical practice and care in the United States and around the world

Frontiers in Precision Medicine IV: Artificial Intelligence, Assembling Large Cohorts, and the Population Data Revolution

Large cohort studies and more recently electronic medical records (EMR) are being used to collect massive amounts of genetic information. Implementation of artificial intelligence has become increasingly necessary to interpret this data with the goal of augmenting patient care. While it is impossible to predict what the future holds, policy makers are challenged to create guiding principles and responsibly roll out these new technologies. On March 22, 2019, the University of Utah hosted its fourth annual Precision Medicine Symposium focusing on artificial intelligence, assembling large cohorts, and the population data revolution. The symposium brought together experts in medicine, science, law and ethics to discuss and debate these emerging issues

Grand Rounds: Research Reproducibility - Willard Dere, MD (01-23-2018)

Spencer S. Eccles Health Sciences Library Grand Rounds: Research Reproducibility (GRRR). "Improving the Science of Translation and the Role of the Center for Clinical and Translational Science (CCTS)" presented by Willard Dere, M.D., FACP, Professor, Internal Medicine U of U. GRRR is a weekly endeavor to raise awareness about reproducibility issues, showcase Utah researchers' work, and to create an open forum for discussions. Grand Rounds: Research Reproducibility website: http://campusguides.lib.utah.edu

The role of pharmacogenetics and pharmacogenomics in improving translational medicine

The approval of new medicines has slowed significantly over the past years. In order to accelerate the development of new compounds, novel approaches in drug development are required. Translational medicine or research, an emerging discipline on the frontier of basic science and medical practice, has the potential to enhance the speed and efficiency of the drug development process through the utilization of pharmacogenetics and pharmacogenomics. Pharmacogenetics is the study of genetic causes of individual variations in drug response whereas pharmacogenomics deals with the simultaneous impact of multiple mutations in the genome that may determine the patient’s response to drug therapy. The utilization of these methods in the drug development process may therefore identify patient sub-populations that exhibit more effective responses and/or an improved benefit/risk profile upon treatment. The authors provide examples of the use of pharmacogenetics and pharmacogenomics in the fields of cardiovascular, pulmonary, oncological, and bone diseases and also highlight the potential economic value of their development

Frontiers in Precision Medicine II: Cancer, Big Data and the Public

Precision medicine is being developed within a complex landscape of public policy, science, economics, law, and regulation. In these and other policy areas, the goal of developing individually-tailored therapies poses novel challenges for health care research, delivery and policy. In this symposium, a range of experts in genetics, medicine, bioinformatics, intellectual property, health economics and bioethics identified and discussed many of the pressing questions raised by the development and practice of precision medicine. These and other issues will need to be taken into account as precision medicine moves ahead and becomes the standard of medical practice and care in the United States and around the world

A Conceptual Architecture for Reproducible On-demand Data Integration for Complex Diseases

Eosinophilic Esophagitis, which is a complex and emerging condition characterized by poorly defined phenotypes, and associated with both genetic and environmental conditions. Understanding such diseases requires researchers to seamlessly navigate across multiple scales (e.g., metabolome, proteome, genome, phenome, exposome) and models (sources using different stores, formats, and semantics), interrogate existing knowledge bases, and obtain results in formats of choice to answer different types of research questions. All of these would need to be performed to support reproducibility and sharability of methods used for selecting data sources, designing research queries, as well as query execution, understanding results and their quality. We present a higher level of formalizations for building multi-source data platforms on-demand based on the principles of meta-process modeling and provide reproducible and sharable data query and interrogation workflows and artifacts. A framework based on these formalizations consists of a layered abstraction of processes to support administrative and research end users: Top layer (meta-process): An extendable library of computable generic process concepts (PC) stored in a metadata repository1 (MDR) and describe steps/phases in the translational research life cycle. Middle layer (process): Methods to generate on-demand queries by assembling instantiated PC into query processes and rules. Researchers design query processes using PC, and evaluate their feasibility and validity by leveraging metadata content in the MDR. Bottom layer (execution): Interaction with a hyper-generalized federation platform (e.g. OpenFurther1) that performs complex interrogation and integration queries that require consideration of interdependencies and precedence across the selected sources. This framework can be implemented using process exchange formats (e.g., DAX, BPMN); and scientific workflow systems (e.g., Pegasus2, Apache Taverna3). All content (PC, rules, and workflows), assembling, and executing mechanism are sharable. The content, design, and development of the framework is informed by user-centered design methodology and consists of researcher and integration-centric components to provide robust and reproducible workflows. References 1. Gouripeddi R, Facelli JC, et al. FURTHeR: An Infrastructure for Clinical, Translational and Comparative Effectiveness Research. AMIA Annual Fall Symposium. 2013; Wash, DC. 2. Pegasus. The Pegasus Project. 2016; https://pegasus.isi.edu/. 3. Apache Software Foundation. Apache Taverna. 2016; https://taverna.incubator.apache.org/

Frontiers in Precision Medicine IV: Artificial Intelligence, Assembling Large Cohorts, and the Population Data Revolution

Large cohort studies and more recently electronic medical records (EMR) are being used to collect massive amounts of genetic information. Implementation of artificial intelligence has become increasingly necessary to interpret this data with the goal of augmenting patient care. While it is impossible to predict what the future holds, policy makers are challenged to create guiding principles and responsibly roll out these new technologies. On March 22, 2019, the University of Utah hosted its fourth annual Precision Medicine Symposium focusing on artificial intelligence, assembling large cohorts, and the population data revolution. The symposium brought together experts in medicine, science, law and ethics to discuss and debate these emerging issues

Efficacy and Effectiveness Too Trials: Clinical Trial Designs to Generate Evidence on Efficacy and on Effectiveness in Wide Practice

Efficacy trials, designed to gain regulatory marketing approval, evaluate drugs in optimally selected patients under advantageous conditions for relatively short time periods. Effectiveness trials, designed to evaluate use in usual practice, assess treatments among more typical patients in real-world conditions with longer follow-up periods. In “efficacy-to-effectiveness (E2E) trials,” if the initial efficacy trial component is positive, the trial seamlessly transitions to an effectiveness trial component to efficiently yield both types of evidence. Yet more time could be saved by simultaneously addressing efficacy and effectiveness in an “efficacy and effectiveness too (EE2) trial.” Additionally, hybrids of the E2E and EE2 approaches with differing degrees of overlap of the two components could allow flexibility for specific drug development needs. In planning EE2 trials, each stakeholder's current and future needs, incentives, and perspective must be considered. Although challenging, the ultimate benefits to stakeholders, the health system, and the public should justify this effort.National Center for Advancing Translational Sciences (Grant U24TR001609