Dataset Information

Defining Disease, Diagnosis, and Translational Medicine within a Homeostatic Perturbation Paradigm: The National Institutes of Health Undiagnosed Diseases Program Experience.

ABSTRACT: Traditionally, the use of genomic information for personalized medical decisions relies on prior discovery and validation of genotype-phenotype associations. This approach constrains care for patients presenting with undescribed problems. The National Institutes of Health (NIH) Undiagnosed Diseases Program (UDP) hypothesized that defining disease as maladaptation to an ecological niche allows delineation of a logical framework to diagnose and evaluate such patients. Herein, we present the philosophical bases, methodologies, and processes implemented by the NIH UDP. The NIH UDP incorporated use of the Human Phenotype Ontology, developed a genomic alignment strategy cognizant of parental genotypes, pursued agnostic biochemical analyses, implemented functional validation, and established virtual villages of global experts. This systematic approach provided a foundation for the diagnostic or non-diagnostic answers provided to patients and serves as a paradigm for scalable translational research.

SUBMITTER: Gall T

PROVIDER: S-EPMC5445140 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Defining Disease, Diagnosis, and Translational Medicine within a Homeostatic Perturbation Paradigm: The National Institutes of Health Undiagnosed Diseases Program Experience.

Gall Timothy T Valkanas Elise E Bello Christofer C Markello Thomas T Adams Christopher C Bone William P WP Brandt Alexander J AJ Brazill Jennifer M JM Carmichael Lynn L Davids Mariska M Davis Joie J Diaz-Perez Zoraida Z Draper David D Elson Jeremy J Flynn Elise D ED Godfrey Rena R Groden Catherine C Hsieh Cheng-Kang CK Fischer Roxanne R Golas Gretchen A GA Guzman Jessica J Huang Yan Y Kane Megan S MS Lee Elizabeth E Li Chong C Links Amanda E AE Maduro Valerie V Malicdan May Christine V MCV Malik Fayeza S FS Nehrebecky Michele M Park Joun J Pemberton Paul P Schaffer Katherine K Simeonov Dimitre D Sincan Murat M Smedley Damian D Valivullah Zaheer Z Wahl Colleen C Washington Nicole N Wolfe Lynne A LA Xu Karen K Zhu Yi Y Gahl William A WA Tifft Cynthia J CJ Toro Camillo C Adams David R DR He Miao M Robinson Peter N PN Haendel Melissa A MA Zhai R Grace RG Boerkoel Cornelius F CF

Frontiers in medicine 20170526

Traditionally, the use of genomic information for personalized medical decisions relies on prior discovery and validation of genotype-phenotype associations. This approach constrains care for patients presenting with undescribed problems. The National Institutes of Health (NIH) Undiagnosed Diseases Program (UDP) hypothesized that defining disease as maladaptation to an ecological niche allows delineation of a logical framework to diagnose and evaluate such patients. Herein, we present the philos ...[more]

PMID: 28603714

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Project description:BackgroundThe Clinical and Translational Science Award (CTSA) program aims to strengthen and support translational research by accelerating the process of translating laboratory discoveries into treatments for patients, training a new generation of clinical and translational researchers, and engaging communities in clinical research efforts. Yet, little is known about how emergency care researchers have interacted with and utilized the resources of academic institutions with CTSAs.ObjectivesThe purpose of this survey was to describe how emergency care researchers use local CTSA resources, to ascertain what proportion of CTSA consortium members have active emergency care research (ECR) programs, and to solicit participation in a national CTSA-associated emergency care translational research network.MethodsThis study was a survey of all emergency departments affiliated with a CTSA.ResultsOf the 65 CTSA consortium members, three had no ECR program and we obtained responses from 46 of the remaining 62 (74% response rate). The interactions with and resources used by emergency care researchers varied widely. Methodology and biostatistics support was most frequently accessed (77%), followed closely by education and training programs (60%). Several ECR programs (76%) had submitted for funding through CTSAs, with 71% receiving awards. Most CTSA consortium members had an active ECR infrastructure: 21 (46%) had 24/7 availability to recruit and screen for research, and 21 (46%) had less than 24/7 research recruitment. A number of emergency care research programs participated in National Institutes of Health research networks with the Neurological Emergencies Treatment Trials network most highly represented with 23 (59%) sites. Most ECR programs (96%) were interested in participating in a CTSA-based emergency care translational research network.ConclusionsDespite little initial involvement in development of the CTSA program, there has been moderate interaction between CTSAs and emergency care. There is considerable interest in participating in a CTSA consortium-based emergency care translational research network.

Project description:Far too much biomedical research is wasted and ends in the so called "Valley of Death": the gap that exists between biomedical research and its clinical application. While the translational process requires collaboration between many disciplines, current translational medicine focuses on single disciplines. Therefore, educational pathways that integrate clinical and research skills in interdisciplinary and interprofessional contexts are needed. The Eureka institute (http://www.eurekainstitute.org/) was founded to address these issues. The institute organizes an annual 1-week international certificate course to educate professionals in the domains of translational medicine. Study design: This study set out to investigate the impact of the Eureka certificate course on the alumni, focusing on their ability to engage in translational activities and thus become more proficient translational professionals. An explanatory, mixed-methods study was executed. Data collection: A questionnaire was distributed to collect quantitative data on the number of alumni who were able to apply what they learned during the Eureka course and engage in translational activities. Questionnaire data were also used to inform the semi-structured interviews that were conducted subsequently. Results: Fifty-one percent of the alumni reported that participating in the Eureka course played a role in their decision to change to a different job or in the way they were accomplishing their everyday work. Ten conditions for change that either hampered or supported the Eureka alumni's engagement in translational research activities were identified. Further, the learning outcomes of the Eureka course that impacted the alumni's professional activities were explored using Personal Professional Theory (PPT). The insight that alumni gained in the full translational spectrum and stakeholders involved stimulated reflection on their own role within that pathway. Further, according to the alumni, the course provided them with the skills and confidence to pursue a career as translational professional. These learning outcomes, in combination with conditions that supported alumni's engagement in translational activities, such as supportive professional partners, opportunities to network or collaborate, and a translational work environment, contributed to the large number of alumni that were able to engage in translational activities.

Dataset Information

Defining Disease, Diagnosis, and Translational Medicine within a Homeostatic Perturbation Paradigm: The National Institutes of Health Undiagnosed Diseases Program Experience.

Publications

Defining Disease, Diagnosis, and Translational Medicine within a Homeostatic Perturbation Paradigm: The National Institutes of Health Undiagnosed Diseases Program Experience.

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