Clinical And Translational Science Award Research Articles

Research Subject Advocacy

In 2000, the National Center for Research Resources mandated that general research centers create a research subject advocate (RSA) position. In 2008, the Clinical and Translational Science Award (CTSA) consortium endorsed a new advocacy model based on four RSA Best Practice Functions. The authors surveyed CTSA centers to learn about their implementation of programs to fulfill the RSA functions. In 2010, the RSA taskforce developed a two-part online survey to examine leadership, organizational structure, governance, scope, collaboration and integration, and funding and evaluation of RSA activities implemented at CTSA centers. Respondents from 45 RSA programs at 43 CTSA centers completed the survey. Senior university or CTSA officials led all programs. Ninety-six percent (43/45) of programs were funded by a CTSA core. Eighty percent (36/45) designated an individual "RSA." Ninety-eight percent (44/45) provided diverse services either in collaboration with or complementary to other departments, including development of data and safety monitoring plans (16/45; 36%), informed consent observation (10/45; 22%), training responsive to audit findings (12/45; 27%), and direct advocacy services to participants (11/45; 24%). Eighty-six percent (24/28) reported qualitative evaluation methods for these activities. RSA programs conduct both collaborative and unique research protection activities. This survey, an initial step in developing a more robust mechanism for evaluating RSA programs, collected valuable feedback. The authors recommend defining and developing outcome-based evaluation measures that take the heterogeneity of the individual RSA programs into account while advancing their value and effectiveness in protecting human research subject participants.

Creating a Practice-Based Research Network From Scratch: Where Do I Begin?

As of today, 50% of Clinical and Translational Science Award (CTSA)-funded Academic Health Centers are engaging community clinicians through the practice-based research network (PBRN) mechanism, which has been identified as a best practice by the CTSA National Leadership. A PBRN is an organization of community clinicians who work together with researchers to answer meaningful questions that will improve patient care. This paper outlines the steps that were led to success during the University of Texas Health Science Center at San Antonio's journey of developing four PBRNs over 3 years: (1) identifying network directors; (2) deciding who to include; (3) obtaining recruitment lists; (4) sending out mailers; (5) hosting the first PBRN meeting; (6) gaining institutional review board (IRB) approval; (7) launching a simple study; (8) returning the findings; and (9) formalizing the PBRN and moving forward. CTSAs will continue to seek ways to effectively engage community members in the clinical translation process. PBRNs are a promising laboratory for generating research questions directly from clinicians, conducting meaningful research, and then disseminating the findings to the larger community to accelerate positive change.

The Utah Center for Clinical and Translational Science: Transformation through Collaboration

The Intermountain West encompasses a 400,000 square mile area that includes the states of Utah, Idaho, Wyoming, and Montana. Within the region the University of Utah Health Sciences Center (UUHSC) is the only academic health center and Intermountain Healthcare (Intermountain), a not-for profit corporation, is the largest healthcare provider. The UUHSC and Intermountain are competitors for clinical market share in most service lines. Both UUHSC and Intermountain have significant research enterprises and each has different strengths. The University of Utah developed the first Biomedical Informatics Department in the nation, is internationally recognized for research in human genetics, and has robust programs in molecular medicine and other laboratory-based sciences. Intermountain is internationally recognized for health services research and programs in quality improvement. The impetus for collaboration in the research enterprise was however, limited before the national initiative to establish a consortium of academic health centers supported through the National Institutes of Health (NIH) clinical and translational science awards (CTSA). Here we describe the transformation of the clinical research environment in the Intermountain West as a result of the collaborative relationships developed between UUHSC and Intermountain following the establishment of the Utah Center for Clinical and Translational Science (CCTS) through the CTSA consortium. Founded in 1905, the University of Utah School of Medicine, located in Salt Lake City, houses 16 clinical and 6 basic science departments. In collaboration with UUHSC, the faculty and staff of the University of Utah educate and train healthcare professionals, conduct research, and provide medical care for adults and children in Utah and the surrounding Intermountain states. Intermountain Healthcare (Intermountain), founded in 1975, is a not-for-profit, integrated healthcare delivery system based in Salt Lake City, UT. Intermountain is the largest healthcare provider in the Intermountain West, providing healthcare services in southeastern Idaho plus the entire state of Utah and operating 23 inpatient facilities including one tertiary children’s hospital, Primary Children’s Medical Center [PCMC] in Salt Lake City, UT. Over 500 multi-specialty physicians are employed through the Intermountain Medical Group and hundreds of other affiliated providers practice in Intermountain hospitals and clinics. Within the region, competition related to clinical market share decreased the ability of institutions to collaborate. Exceptions included 1) the delivery of inpatient pediatric care at PCMC which is owned and operated by Intermountain and staffed by both UUHSC and Intermountain physicians and 2) the training of physicians to serve several western states in both urban and rural locations which resulted in a well-developed Affiliation Agreement defining teaching programs operated in several Intermountain hospitals for UUHSC trainees. Intermountain and UUHSC operate integrated residency and fellowship programs in medicine, obstetrics and gynecology, pediatrics, radiation therapy, and surgery. In contrast, the collaboration in the research enterprise for the past three decades had been limited to the efforts of individual investigators and there were no institutional policies or infrastructure to systematically support the research efforts across institutions or to share resources. The national competition to join the CTSA consortium provided an opportunity to re-evaluate the research relationship and to and develop and support research collaboration between both institutions. UUHSC and Intermountain joined forces in order to apply for a CTSA and to represent the Intermountain West in the consortium. The Utah Center for Clinical and Translational Science (CCTS) became part of the national CTSA consortium in 2008. Linkages created through the CCTS across both organizations have served to create productive and trusting work relationships, allowing us to provide a shared research infrastructure that takes advantage of our innovative systems and shared intellectual capital of personnel. These linkages have increased collaboration and resulted in significant benefits for both instituions.

CTSA-Enhanced Innovative Device Development

The key objective of the NIH Clinical and Translational Science Award (CTSA) is to more effectively translate basic science discoveries into new human therapies, diagnostics, and practices. Given the societal impression that we are in an unprecedented time of scientific and technologic acceleration in biomedical research, it can be disheartening to learn that it takes up to 15 years for discoveries to translate into treatments and that a large majority of medical research studies never reach the clinical trials or become widely available to patients (1). As part of the CTSA consortium, the University of New Mexico Clinical and Translational Science Center (CTSC) is a catalyst for more rapid translation within the pipeline of therapeutic development by encouraging innovation and high-risk projects, facilitating productive collaborations, assisting with study design, supporting clinical trials, and providing new mechanisms to more rapidly and effectively address regulatory requirements. CTSAs at comparatively smaller universities such as ours immediately transform the research landscape of their institutions, since support mechanisms for clinical and translational research would not otherwise exist. Now in its third year, the UNM CTSC was able to assist in the development of a point-of-care biosensor, which recently received an R&D Magazine Top 100 Technologies Award (2). Our biosensor project demonstrates the efficacy of the CTSA model in translating basic science conducted at universities into devices that will dramatically improve clinical practices.

Preliminary Competencies for Comparative Effectiveness Research

The Clinical and Translational Science Award (CTSA) Workgroup for Comparative Effectiveness Research (CER) Education, Training, and Workforce Development identified a need to delineate the competencies that practitioners and users of CER for patient-centered outcomes research, should acquire. With input from CTSA representatives and collaborators, we began by describing the workforce. We recognize the workforce that conducts CER and the end users who use CER to improve the health of individuals and communities. We generated a preliminary set of competencies and solicited feedback from the CER representatives at each member site of the CTSA consortium. We distinguished applied competencies (i.e., skills needed by individuals who conduct CER) from foundational competencies that are needed by the entire CER workforce, including end users of CER. Key competency categories of relevance to both practitioners and users of CER were: (1) asking relevant research questions; (2) recognizing or designing ideal CER studies; (3) executing or using CER studies; (4) using appropriate statistical analyses for CER; and (5) communicating and disseminating CER study results to improve health. Although CER is particularly broad concept, we anticipate that these preliminary, relatively generic competencies will be used in tailoring curricula to individual learners from a variety of programmatic perspectives.

From the Editors’ Desk: Why NCATS Should Read this Issue of JGIM

From the Editors’ Desk: Why NCATS Should Read this Issue of JGIM

Cervical spinal demyelination with ethidium bromide reversibly impairs phrenic nerve activity in adult rats

Respiratory complications are a major cause of morbidity/mortality in many diseases associated with demyelination. Little is known concerning mechanisms whereby lack of myelin impairs ventilation, or how patients compensate for such changes (compensatory plasticity). We tested the hypothesis that respiratory function is diminished with focal spinal demyelination using unilateral ethidium bromide (EB) injections into C2 bulbospinal tracts. Ventilation (plethysmography) and phrenic nerve activity (neurophysiological recordings) were made 7–21 days post‐EB at baseline and in hypoxia±hypercapnia. EB produced maximal demyelination at day 7 with spontaneous remyelination in 14–21 days (all P<0.05). Ventilation did not differ between groups (all P>0.05). Ipsilateral phrenic nerve voltage was lower than the contralateral voltage 7 days post‐EB during hypoxia and hypoxia/hypercapnia (both P<0.05), as well as the ipsi‐ and contralateral voltage of SHAM and 14 day rats in all conditions (all P<0.05). Average voltage ratios (ipsi:contra) correlated to lesion size at baseline (P<0.05) and were signficantly reduced in 7 day rats (all P<0.05). Our reversible demyelination model provides a powerful tool to study respiratory motor impairment, mechanisms underlying compensatory plasticity/spontaneous recovery, and therapies to reduce demyelination and its associated respiratory motor dysfunction. Support: Supported by grant 1UL1RR025011 from the Clinical and Translational Science Award (CTSA) program of the National Center for Research Resources (NCRR), National Institutes of Health (NIH).

Preparedness of the CTSA's Structural and Scientific Assets to Support the Mission of the National Center for Advancing Translational Sciences (NCATS)

The formation of the National Center for Advancing Translational Sciences (NCATS) brings new promise for moving basic science discoveries to clinical practice, ultimately improving the health of the nation. The Clinical and Translational Science Award (CTSA) sites, now housed with NCATS, are organized and prepared to support in this endeavor. The CTSAs provide a foundation for capitalizing on such promise through provision of a disease-agnostic infrastructure devoted to clinical and translational (C&T) science, maintenance of training programs designed for C&T investigators of the future, by incentivizing institutional reorganization and by cultivating institutional support.

Practices and perspectives on building integrated data repositories: results from a 2010 CTSA survey

Clinical integrated data repositories (IDRs) are poised to become a foundational element of biomedical and translational research by providing the coordinated data sources necessary to conduct retrospective analytic research and to identify and recruit prospective research subjects. The Clinical and Translational Science Award (CTSA) consortium's Informatics IDR Group conducted a survey of 2010 consortium members to evaluate recent trends in IDR implementation and use to support research between 2008 and 2010. A web-based survey based in part on a prior 2008 survey was developed and deployed to 46 national CTSA centers. A total of 35 separate organizations completed the survey (74%), representing 28 CTSAs and the National Institutes of Health Clinical Center. Survey results suggest that individual organizations are progressing in their approaches to the development, management, and use of IDRs as a means to support a broad array of research. We describe the major trends and emerging practices below.

An Unparalleled Engine for Discovery and Clinical Introduction: The Clinical and Translational Science Awards and Gene Therapy

Gene therapy has taken longer than any of us had hoped to come to clinical utility. Its promise is only now beginning to be fulfilled. Improvements in vectors and sufficient duration of follow-up now indicate that for some indications, such as severe combined immune deficiency, Leber congenital amaurosis, and hemophilia B, gene therapy is effective (Thrasher et al., 2006; Silver and Flotte, 2008; Kohn, 2010; Kaiser, 2011; Nathwani et al., 2011; Ponder, 2011; Jacobson et al., 2012). Other diseases, both single gene and multigene, may also yield to this therapeutic approach. But gene therapy is now at the preclinical stage for most indications, or just coming to phase I and phase IIa studies in humans. At this stage, the field will need studies of biomarkers, preclinical animal testing, ethical considerations, and first-in-human studies of the gene therapy reagents compliant with federal regulations, with careful follow-up studies for life. The intensity and lifelong duration of the follow-up studies required, if not the number of subjects necessary for these studies, will require informatics, data capture, and data storage. Development of novel therapeutic approaches and their testing in appropriate patient populations will require the resources now assigned to the Clinical and Translational Science Award (CTSA) program. But is the program ready for this challenge?

A virtual national laboratory for reengineering clinical translational science.

Clinical research is burdened by inefficiencies and complexities, with a poor record of trial completion, none of which is desirable. The Clinical and Translational Science Award (CTSA) Consortium, including more than 60 clinical research institutions, supports a unified national effort to become, in effect, a virtual national laboratory designed to identify, implement, evaluate, and extend process improvements across all parts of clinical research, from conception to completion. If adequately supported by academic health centers, industry, and funding agencies, the Consortium could become a test bed for improvements that can dramatically reduce wasteful complexity, thus increasing the likelihood of clinical trial completion.

Molecular Nutrition, Nutrigenomics and Health Promotion: A Long Road Ahead

Molecular Nutrition, Nutrigenomics and Health Promotion: A Long Road Ahead Advances in “omics”-based fields have produced an explosion of new information, fueling high expectations for improved public and individualized health. Unfortunately, there exists a widening gap between basic biochemistry and omics-based population research, with both disciplines failing to translate their full potential impact to human health applications. In an attempt to address this current situation, the National Institutes of Health (NIH) has made “translational” or “bench-to-bedside” research a priority, forming specialized centers and launching the Clinical and Translational Science Award (CTSA) program in 2006.

ResearchMatch: A National Registry to Recruit Volunteers for Clinical Research

The authors designed ResearchMatch, a disease-neutral, Web-based recruitment registry to help match individuals who wish to participate in clinical research studies with researchers actively searching for volunteers throughout the United States. In this article, they describe ResearchMatch's stakeholders, workflow model, technical infrastructure, and, for the registry's first 19 months of operation, utilization metrics. Having launched volunteer registration tools in November 2009 and researcher registration tools in March 2010, ResearchMatch had, as of June 2011, registered 15,871 volunteer participants from all 50 states. The registry was created as a collaborative project for institutions in the Clinical and Translational Science Awards (CTSA) consortium. Also as of June 2011, a total of 751 researchers from 61 participating CTSA institutions had registered to use the tool to recruit participants into 540 active studies and trials. ResearchMatch has proven successful in connecting volunteers with researchers, and the authors are currently evaluating regulatory and workflow options to open access to researchers at non-CTSA institutions.

Translational Medicine: Are we Ready for the Prime Time?

Translational medicine is an increasingly important field designed to bridge the gap between basic science and clinical care. Academic institutions, industry, and other health organizations commit billions of dollars annually for the development of translational medicine programs and initiatives. In 2006, the National Institutes of Health (NIH) launched the Clinical and Translational Science Award (CTSA) program with the goal of establishing 60 centers of translational research at academic institutes across the country [1]. These efforts are aimed at integrating knowledge gained through basic science research and clinical practice to provide effective and novel strategies for the diagnosis, prevention, and treatment of common diseases.

Identifying and Aligning Expectations in a Mentoring Relationship

The mentoring relationship between a scholar and their primary mentor is a core feature of research training. Anecdotal evidence suggests this relationship is adversely affected when scholar and mentor expectations are not aligned. We examined three questions: (1) What is the value in assuring that the expectations of scholars and mentors are mutually identified and aligned? (2) What types of programmatic interventions facilitate this process? (3) What types of expectations are important to identify and align? We addressed these questions through a systematic literature review, focus group interviews of mentors and scholars, a survey of Clinical and Translational Science Award (CTSA) KL2 program directors, and review of formal programmatic mechanisms used by KL2 programs. We found broad support for the importance of identifying and aligning the expectations of scholars and mentors and evidence that mentoring contracts, agreements, and training programs facilitate this process. These tools focus on aligning expectations with respect to the scholar's research, education, professional development and career advancement as well as support, communication, and personal conduct and interpersonal relations. Research is needed to assess test the efficacy of formal alignment activities.

University of Florida Clinical and Translational Science Institute: Transformation and Translation in Personalized Medicine

We are constantly reflecting on whether and how our efforts are transformational as we work to achieve the ambitious goals articulated for the University of Florida’s Clinical and Translational Science Institute (UF CTSI). As the only Clinical and Translational Science Award (CTSA) recipient in the fourth most populous state, the UF CTSI must aim to support research and improve health care for 19 million Floridians, 6% of the US population. The strong commitment of our university leadership and a team-science approach has enabled us to move swiftly in the context of a very large comprehensive public research university. The UF CTSI involves two major health systems, agricultural extension offices in all 67 counties in Florida, and numerous partners throughout the state. All of UF’s 16 colleges* participate in the CTSI, which supports 140 faculty and staff; 10 programs; 13 clinical research units; five core labs; and six educational programs. As we enter year three of our grant, the UF CTSI is launching a Personalized Medicine Program – a feat made possible by the transformational changes championed by the National Institutes of Health (NIH), its National Center for Research Resources (NCRR) and the CTSA program. We share this as one of many examples unfolding across the country in which CTSA institutions are adding new capacity for translational research, which in turn is leading to new approaches for how we translate scientific discoveries into medical practice – a need around which the NIH is vigorously seeking to catalyze new breakthroughs.1

Barriers to conducting clinical research in reproductive medicine: United States of America

A decrease in National Institute of Health funding and an increase regulations are significant barriers in conducting research in the United States of America.

The end of the beginning: A commentary on ‘Evaluation metrics for biostatistical and epidemiological collaborations’: A rejoinder

Statistics in MedicineVolume 30, Issue 23 p. 2783-2784 Commentary The end of the beginning: A commentary on ‘Evaluation metrics for biostatistical and epidemiological collaborations’: A rejoinder Doris McGartland Rubio, Corresponding Author Doris McGartland Rubio [email protected] School of Medicine, University of Pittsburgh, Pittsburgh, PA, U.S.A. Doris McGartland Rubio, School of Medicine, University of Pittsburgh, Pittsburgh, PA, U.S.A. E-mail: [email protected]Search for more papers by this authorDeborah J. del Junco, Deborah J. del Junco Biostatistics, Epidemiology, and Research Design Core, University of Texas Health Sciences Center, Houston, TX, U.S.A.Search for more papers by this authorRafia Bhore, Rafia Bhore Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX, U.S.A.Search for more papers by this authorChristopher J. Lindsell, Christopher J. Lindsell Center for Clinical and Translational Science and Training, University of Cincinnati, Cincinnati, OH, U.S.A. Department of Emergency Medicine, University of Cincinnati, Cincinnati, OH, U.S.A.Search for more papers by this authorRobert A. Oster, Robert A. Oster Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, U.S.A.Search for more papers by this authorKnut M. Wittkowski, Knut M. Wittkowski Biostatistics, Epidemiology, and Research Design Core, Rockefeller University, New York, NY, U.S.A.Search for more papers by this authorLeah J. Welty, Leah J. Welty Department of Preventive Medicine, Northwestern University, Chicago, IL, U.S.A.Search for more papers by this authorYi-Ju Li, Yi-Ju Li Department of Biostatistics and Bioinformatics, Duke University, Durham, NC, U.S.A.Search for more papers by this authorDave DeMets, Dave DeMets Biostatistics Department, University of Wisconsin—Madison, Madison, WI, U.S.A.Search for more papers by this authorThe Biostatistics, Epidemiology, and Research Design (BERD) Key Function Committee of the Clinical and Translational Science Awards (CTSA) Consortium, The Biostatistics, Epidemiology, and Research Design (BERD) Key Function Committee of the Clinical and Translational Science Awards (CTSA) ConsortiumSearch for more papers by this author Doris McGartland Rubio, Corresponding Author Doris McGartland Rubio [email protected] School of Medicine, University of Pittsburgh, Pittsburgh, PA, U.S.A. Doris McGartland Rubio, School of Medicine, University of Pittsburgh, Pittsburgh, PA, U.S.A. E-mail: [email protected]Search for more papers by this authorDeborah J. del Junco, Deborah J. del Junco Biostatistics, Epidemiology, and Research Design Core, University of Texas Health Sciences Center, Houston, TX, U.S.A.Search for more papers by this authorRafia Bhore, Rafia Bhore Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX, U.S.A.Search for more papers by this authorChristopher J. Lindsell, Christopher J. Lindsell Center for Clinical and Translational Science and Training, University of Cincinnati, Cincinnati, OH, U.S.A. Department of Emergency Medicine, University of Cincinnati, Cincinnati, OH, U.S.A.Search for more papers by this authorRobert A. Oster, Robert A. Oster Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, U.S.A.Search for more papers by this authorKnut M. Wittkowski, Knut M. Wittkowski Biostatistics, Epidemiology, and Research Design Core, Rockefeller University, New York, NY, U.S.A.Search for more papers by this authorLeah J. Welty, Leah J. Welty Department of Preventive Medicine, Northwestern University, Chicago, IL, U.S.A.Search for more papers by this authorYi-Ju Li, Yi-Ju Li Department of Biostatistics and Bioinformatics, Duke University, Durham, NC, U.S.A.Search for more papers by this authorDave DeMets, Dave DeMets Biostatistics Department, University of Wisconsin—Madison, Madison, WI, U.S.A.Search for more papers by this authorThe Biostatistics, Epidemiology, and Research Design (BERD) Key Function Committee of the Clinical and Translational Science Awards (CTSA) Consortium, The Biostatistics, Epidemiology, and Research Design (BERD) Key Function Committee of the Clinical and Translational Science Awards (CTSA) ConsortiumSearch for more papers by this author First published: 23 September 2011 https://doi.org/10.1002/sim.4290Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. Volume30, Issue2315 October 2011Pages 2783-2784 RelatedInformation

The Role of the Clinical and Translational Science Awards Program in Improving the Quality and Efficiency of Clinical Research

Recognizing the need to increase the efficiency and quality of translating basic discovery into treatment and prevention strategies for patients and the public, the National Institutes of Health (NIH) announced the Clinical and Translational Science Awards (CTSAs) in 2006. Academic health centers that competed successfully for these awards agreed to work as a consortium and in cooperation with the NIH to improve the translation process by training the next generation of investigators to work in interdisciplinary teams, developing public-private partnerships in the movement of basic discovery to preclinical and clinical studies and trials, improving clinical research management, and engaging with communities to ensure their involvement in shaping research questions and in implementing research results. The CTSAs have addressed the crucial need to improve the quality and efficiency of clinical research by (1) providing training for clinical investigators and for bench researchers to facilitate their participation in the clinical and translational research environment, (2) developing more systematic approaches to clinical research management, and (3) engaging communities as active participants in the design and conduct of clinical research studies and trials and as leaders in implementing health advances that are of high importance to them. We provide an overview of the CTSA activities with attention to these three areas, which are essential to developing efficient clinical research efforts and effective implementation of research results on a national level.

The Clinical and Translational Science Awards (CTSAs) Are Transforming the Way Academic Medical Institutions Approach Translational Research: The University of Michigan Experience

In 2006 the National Institutes of Health (NIH), guided by the leadership of Elias Zerhouni, launched the Clinical and Translational Science Award (CTSA) program to jump-start transformative change in the nation’s research agenda to emphasize translating discovery from the bench to implementation in the community (1–5). Much of the Funding for the CTSAs was garnered by rolling NIH funding of General Clinical Research Centers (GCRCs), and educational K and T awards. Successful applicants were then asked to utilize these funds to (as stated in the Request for Applications [RFA]) “transform the local, regional and national environments for clinical and translational science and to increase the safety, efficiency and speed of clinical and translational research”(4). Each of the 60 CTSA institutions has approached addressing this transformation in slightly different ways; however, it has become clear over the last 5 years that substantive changes, as a result of CTSA funding at academic institutions, are transforming medical research and the infrastructure that supports it. Each of the CTSA’s is required to address specific Key Functions to advance the consortium goals. These required Key Functions are: (i) expertise in Biomedical Informatics, (ii) a program in Research Education, Training and Career Development, (iii) a program in Community Engagement and Research, (iv) an Evaluation component, (v) Pilot Projects in Translational and Clinical Studies, and (vi) a Regulatory Knowledge and Support component. Optional CTSA Key Functions include: (vii) support of the Development of Novel Clinical and Translational Methodologies, (viii) components or cores to support Research Design, Epidemiology, Biostatistics and Clinical Research Ethics, (ix) Clinical Research Resources and Facilities, and (x) components or cores that develop Translational Technologies and Resources. It is also encouraged for institutions to support research in Child Health. Addressing these Key Functions at the University of Michigan, for example, has led to transformational change in the structure and culture of the institution.