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The recognition that basic discoveries are frequently not translated to human applications (1) and that the process is unnecessarily slow (2) provides the rationale underpinning the current emphasis on translational research. It is apparent that an enormously broad scope of research is required for such translation. At the University of Rochester Medical Center, all externally-sponsored research projects are identified in a biennial Research Resource Inventory and the principal investigators are asked to classify the project as basic science (pre-clinical) or clinical. Investigators also classify the clinical research studies as T1 translation: “Applying basic science results to develop new diagnostic or therapeutic procedures in patients with specific health concerns;” T2 translation: “Testing the safety and efficacy of drugs and devices in specific patient groups;” or T3 translation “Testing drugs, devices, or other interventions in community settings to establish effectiveness and efficiency.” In 2009, investigators classified 1243 sponsored research projects as 41% basic and 59% clinical. Of the clinical research projects, 39% were classified as T1, 30% as T2, and 19% as T3, highlighting a broad scope of research requiring support by the University of Rochester Clinical and Translational Science Institute (UR-CTSI).
Prior to the CTSA Program, the General Clinical Research Center (GCRC) served as a model for clinical research, with dedicated space, skilled professional staff, specialized equipment, and funds available to support all aspects of patient-oriented research and research training. However, the scope of the research typically performed in the GCRC is considerably more narrow than URMC translational research. Nonetheless, the GCRC did provide a model for support of translational research, as a facility with resources to support research directly and as a model for research programs located elsewhere.
Clearly, a new organizational plan was required to support the entire spectrum of research translation. Perceived needs included a unit designed specifically to engage basic scientists. There was also a need to engage other disciplines and professions in the University, including the School of Nursing and the Eastman Institute for Oral Health (Dentistry).
To meet these newly perceived needs, we applied the Clinical Research Center model to four specific areas of translational science, namely Experimental Therapeutics/Drug Development, Patient-Oriented Research, Comparative-Effectiveness/Implementation Research, and Practice/Community-Based and Participatory Research. These areas of science overlap across the translational research spectrum (Figure) and have been linked to key functions by the national CTSA Program. The conceptual model interfaces with basic science programs through T1 research translation. All these areas of science share requirements for expertise in study designs; data collection, management and analysis; ethical issues involving human subjects and patient groups; regulatory issues; and opportunities for didactic and experiential research training. These needs are all met by other CTSI key functions.
Four Centers of Excellence have been established or enhanced at the UR-CTSI, each with a focus of faculty and staff expertise, facilities and equipment, training programs, and other resources. They are: Center for Human Experimental Therapeutics (CHET), Clinical Research Center (CRC), Center for Research Implementation and Translation (CRIT), and Center for Community Health (CCH). Each Center has distinguishing primary roles, expertise, facilities, governance, etc., including different lines of reporting (Table). Each Center is represented by its Director on the Executive Committee of the UR-CTSI.
The Center for Human Experimental Therapeutics (CHET) organizes and conducts early human clinical trials, as well as advising other researchers on the conduct of such trials and on the design of animal experiments that enable human clinical trials. Initial human investigation of novel interventions has not been a traditional focus of academic institutions, driven by a perceived lack of relevant expertise necessary for this important stage of translational research. Such expertise includes an understanding of clinical trial methodology, clinical pharmacology, an ability to create and distribute experimental interventions, and familiarity with regulatory guidelines and requirements.
The overall goals of CHET are to efficiently conduct initial learning phase clinical trials in targeted diseases, drawing on interventions discovered at established URMC translational centers; to form regional, national and global consortia of expert clinical investigators, with URMC investigators serving as the scientific and logistical leaders of early human clinical trials; and to recruit and maintain leaders of research collaborative cores who serve as local and national educators in clinical trial methodology. CHET provides consultation and collaborative guidance regarding clinical trial designs for early human experimentation. The T1 translation key function provides specific biostatistical and research methodology consultation, and collaborative guidance for investigators interested in initial human clinical trials. CHET also provides pharmacokinetic and pharmacodynamic consultation and modeling. Through a strong collaboration with the Center of Excellence for Bioinformatics and Life Sciences at the University at Buffalo (UB), consultation and clinical pharmacology collaborative services are provided for both animal and early human experiments. Finally, CHET provides logistical support to investigators conducting learning phase clinical trials, primarily through the Clinical Trials Coordination Center (CTCC) and the Clinical Materials Services Unit (CMSU). These two collaborative research cores have a long experience in supporting NIH- as well as industry-sponsored trials in an array of diseases.
The Clinical Research Center provides the space and staffing for the Clinical Research Resources and Facilities Key Function and has the overall goal of providing a safe, encouraging and supportive environment for patients and investigators to perform translational research. For the most part, studies performed on the CRC are T2 translational research, involving delineation of normal human physiologic processes or the pathophysiology and natural history of disease states and development and evaluation of new diagnostic and therapeutic modalities. The CRC optimizes the opportunity of investigators to perform translational research. The CRC also contributes to institutional standards for protocol and project development (any and all stages), assessment of scientific integrity (processes), and appropriate identification and utilization of resources. Finally, the CRC provides additional specialized services, including the PEAK Laboratory (Physical Exercise, Activity and Kinesiology); and a Human Behavioral Assessment Unit.
CRIT has been developed as a model for leadership by and integration of Schools of Nursing within Clinical and Translational Science Award Programs. The new CRIT, a multi-disciplinary center housed in the School of Nursing, gives focus to the development, conduct, and evaluation of research implementation and translation (3, 4). Supported by multidisciplinary, NIH funded investigators from the Schools of Nursing and Medicine, CRIT has developed infrastructure, experience, and resource capacity in Comparative Effectiveness Research (CER) and implementation science.
In response to the June 2009 reports from the Institute of Medicine (5) and the Federal Coordinating Council for Comparative Effectiveness Research (FCC) (6), the aims of the CER key function are consistent with IOM and FCC recommendations. CRIT emphasizes capacity, infrastructure, and network building; investigator and systems support; development of innovative methods and approaches to CER; education and training across disciplines and stakeholders; and process and outcomes evaluation across the various centers and other key functions of the UR-CTSI.
Two new research networks were developed by CRIT to support CER: the Morehouse/Rochester Research in Comparative Effectiveness Network and the Supported Living Research Network (SLRN). A supplement to the CTSA award was received in 2009 “to establish, in collaboration with Morehouse School of Medicine (MSM), a practice-based research network which focuses on comparative effectiveness.” The SLRN also was established to develop infrastructure for research in settings in which vulnerable patients with some of the most intractable, costly, and complex problems in health care require timely and judicious management of co-morbidities and exacerbations. The SLRN will include home care agencies, nursing homes, assisted living dwellings, group homes for the developmentally disabled and the mentally ill, and partial hospitalization programs.
The Community Engagement key function of the CTSI is embedded in the CCH, supporting research that addresses translation to community and clinical interventions to improve the health of our community and the nation. The CCH provides resources to support participatory clinical and translational research in the community and in practice settings, and to facilitate genuine partnerships among investigators, health care providers, and community members to assure a continuum from bench to community. Community and provider engagement in the design and conduct of research has increased through community partnerships with oversight by a Community Advisory Council, and the Greater Rochester Practice-Based Research Network (which currently includes 75 practices covering 80% of children and 30% of adults in the local community). The CCH increases community engagement capacity of investigators/students through educational programs, and supports increased diversity in study recruitment. Finally, the CCH includes the Healthy Living Research Center, focused on prevention and health behaviors, integrating community programs, clinical prevention services, and research.
The creation of four centers of research excellence across the spectrum of research translation enhances opportunities to engage investigators in the science of research translation. The development of faculty, staff, and facilities across this spectrum assures that a wide variety of investigators will access these resources and use them as models for their own research programs. Moreover, the opportunity for basic discoveries to be translated across the entire translational spectrum will require such a research infrastructure (3, 4).
This work was supported in part by the Clinical and Translational Science Award Program of the NIH through grants UL1 RR024160, KL2 RR024136 and TL1 RR024135.