Re-engineering the Clinical Research Enterprise

The 21st century is witnessing an increasing need to move research results more quickly to clinical settings. Clinical research is a vital component of progress toward improving America's health. But while clinical research helps assure that new treatments are safe and effective, it is a lengthy and sometimes inefficient process. The current system of clinical research must be re-engineered if it is to respond to these changing scientific and health care needs. Meeting these demands will require new and more efficient approaches to discovery and clinical validation of research results. The initiatives within this theme of the NIH Roadmap for Medical Research aim to contribute to accelerating and strengthening clinical research by adopting a systematic infrastructure that will better serve the evolving field of scientific discovery. The NIH recognizes the complexity of the issues affecting clinical research and is collaborating with other key agencies to address this theme.

Specifically, the initiatives of this theme area include: Clinical Research Networks and NECTAR, Clinical Outcomes Assessment, Clinical Research Training, Clinical Research Policy and Analysis Coordination, and Translational Research.

Clinical Research Networks and NECTAR

Because of the vast number of diagnostic measures, preventive therapies, and treatments that must be evaluated through clinical trials, intervention- and disease-specific clinical research networks have evolved and operate simultaneously, but independently, of each other. As a result, researchers must sometimes duplicate data that already exist because they are either unaware of, or do not have access to, the data. As a result valuable opportunities to evaluate coexisting health conditions in large groups of patients are lost in the process.

Initiatives have been to capture best practices of existing clinical research networks and to test the feasibility of integrating and expanding clinical research networks. Through the NIH Roadmap, NIH is exploring how to enhance and expand existing networks and their interoperability through funding a series of pilot studies. In addition, standardizing data reporting would enable seamless data- and sample-sharing across studies. Ultimately, the goal is to have a common informatics platform that can offer economies of scale and allow complex research programs to benefit from a common infrastructure. These efforts include determining the feasibility of a National Electronic Clinical Trials/Research Network (NECTAR). The following studies have been funded in fiscal year (FY) 2004:

Clinical Research Network Inventory

The overall goal of this effort is to determine best practices in clinical research networks by conducting an inventory of existing networks. This project is examining organizational and management structures of existing networks and will evaluate the types and volume of studies being conducted. Other parameters to be analyzed include network performance, informatics infrastructure, and training procedures.

Integrating Clinical Research Networks

This initiative will test the feasibility of integrating and expanding existing clinical research networks. A particular focus is on assessing the capacity for interoperability among networks. This will broaden the kinds of research questions that can be addressed and will enhance the efficiency of conducting clinical research. The long range goals are to develop networks that are based on common infrastructure elements, such as informatics, governance, common language, and training activities, that conduct research in both academic and clinical care settings. Successful models can be used by other networks and for dissemination to the clinical research community.

Clinical Outcomes Assessment

Currently, assessment of chronic disease outcomes relies heavily on subjective reports of symptoms and health-related quality of life items. Important targets for disease treatment include patients' subjective experiences, which cannot be measured with laboratory tests and x-rays. Despite a proliferation of tools to measure such factors, these instruments do not allow comparisons among clinical studies.

This initiative, entitled Dynamic Assessment of Patient-Reported Chronic Disease Outcomes, supports researchers who will develop and implement a publicly available system of a large item bank and Computerized Adaptive Tests. As members of a network, the Patient-Reported Outcomes Measurement Information System (PROMIS), scientists funded through this FY 2004 initiative are developing a computerized system to measure patient-reported outcomes more efficiently in study participants with a wide range of chronic diseases and demographic characteristics. This effort will lead to more sensitive and efficient testing of major chronic disease symptoms and functioning, such as pain, fatigue, and quality of life. Ultimately, such a system will also be useful in clinical practice to assess patients' treatment responses and to inform them of therapy modifications.

Clinical Research Training

One of the most important factors determining the health and vitality of the clinical research enterprise is the scientific workforce. Through the NIH Roadmap, NIH is finding ways to expand and diversify the clinical research workforce by optimizing training and career development programs for the many necessary players required to conduct successful clinical investigations. These players include physicians, dentists, nurses, dieticians, epidemiologists, biostatisticians, and informatics specialists. Tomorrow's clinician must be trained to work in the interdisciplinary, team-oriented environments that characterize today's emerging research efforts.

The clinical research workforce must be sufficiently large to catalyze the translation of research discoveries to patient care at the community level. Within this set of NIH Roadmap initiatives are the following programs: Multidisciplinary Clinical Research Career Development, National Clinical Research Associates, and the NIH Clinical Research Training Program.

Multidisciplinary Clinical Research Career Development Program

This initiative, funded in FY 2004 and scheduled for re-announcement in FY 2005, will train health professionals from a variety of disciplines or specialties in the knowledge and skills required for the discipline of clinical research. The programs will foster the career development of doctoral-level health professionals to become the next generation of clinical researchers who will conduct clinical research in multidisciplinary, collaborative settings. These individuals, who will be trained in team research settings and will be known as NIH Clinical Research Scholars, will be expected to become leaders in various fields of clinical research that are critical to the NIH mission.

National Clinical Research Associates

The lack of a diverse clinical research workforce comprising both community-based practitioners and academic researchers is a major barrier to clinical research. By assessing the feasibility of developing and training a cadre of community-based practitioners, NIH seeks to enhance the efficiency of clinical research networks and extend the generalizability of the results obtained in these studies. Ultimately, these National Clinical Research Associates (NCRAs) are envisioned to function as clinical investigators by participating in clinical research in a practice setting, in the context of delivering health care. The NCRAs will participate in clinical studies, assist in patient recruitment, administer experimental treatments, report data, and be among the first to integrate new research findings into routine healthcare delivery.

NIH Clinical Research Training Program

This program, on the NIH campus, was established in 1997 to provide medical and dental students an intensive one-to-two year experience in clinical or translational research after completion of their clinical rotations. The size of the program doubled in FY2004 from 15 to 30 students. Through this program, selected medical and dental students obtain stipends and academic and administrative support. The program also hosts an annual Clinical Investigator Student Trainee Forum for medical and dental students in clinical research training programs across the country. Additional information on this program is available at http://www.training.nih.gov/crtp/.

Clinical Research Policy Analysis and Coordination

Currently, clinical research is impeded by multiple and variable requirements for addressing what are fundamentally the same oversight concerns. Considerable variability among and within agencies creates uncertainty about how to comply with regulations and policies, hampering the research enterprise's overall efficiency and effectiveness. The CRpac program thus aims to harmonize federal requirements that pertain to the conduct of clinical research, facilitating compliance with pertinent regulations and policies and ultimately creating a more effective oversight framework.

NIH has established working groups with its sister agencies to make progress in high priority policy areas. Some of the goals of this initiative include the development of clear, effective, and coordinated rules for clinical research; maximally effective human subjects protections; more comprehensive analysis and sharing of research data; and overall enhanced quality and productivity of the research enterprise.

Translational Research

To improve human health, scientific discoveries must be translated into practical applications. Such discoveries typically begin at “the bench” with basic research — in which scientists study disease at a molecular or cellular level — then progress to the clinical level, or the patient's “bedside.”

Scientists are increasingly aware that this bench-to-bedside approach to translational research is really a two-way street. Basic scientists provide clinicians with new tools for use in patients and for assessment of their impact, and clinical researchers make novel observations about the nature and progression of disease that often stimulate basic investigations.

Translational research has proven to be a powerful process that drives the clinical research engine. However, a stronger research infrastructure could strengthen and accelerate this critical part of the clinical research enterprise. The NIH Roadmap attempts to catalyze translational research in various ways.

Enhancing the Discipline of Clinical and Translational Science

Growing barriers between clinical and basic research, along with the ever the increasing complexities involved in conducting clinical research, are making it more difficult to translate new knowledge to the clinic — and back again to the bench. These challenges are limiting professional interest in the field and hampering the clinical research enterprise at a time when it should be expanding.

Through discussions with deans of academic health centers, recommendations from the Institute of Medicine, and meetings with the research community, the NIH recognized that a broad re-engineering effort is needed to create greater opportunity to catalyze the development of a new discipline of clinical and translational science. The outcome, a bolder transforming vision for 21st Century, resulted in the launch of the Clinical and Translational Science Awards (CTSA) Consortium in October 2006.

This new consortium begins with 12 academic health centers located throughout the nation. An additional 52 awardees are receiving planning grants to help them prepare applications to join the consortium. When fully implemented in 2012, about 60 institutions will be linked together to energize the discipline of clinical and translational science.

The purpose of the CTSA Program, which NCRR is leading on behalf of the NIH Roadmap for Medical Research, is to assist institutions to forge a uniquely transformative, novel, and integrative academic home for Clinical and Translational Science that has the consolidated resources to: 1) captivate, advance, and nurture a cadre of well-trained multi- and inter-disciplinary investigators and research teams; 2) create an incubator for innovative research tools and information technologies; and 3) synergize multi-disciplinary and inter-disciplinary clinical and translational research and researchers to catalyze the application of new knowledge and techniques to clinical practice at the front lines of patient care.

The members of the CTSA consortium are expected to serve as a magnet that concentrates basic, translational, and clinical investigators, community clinicians, clinical practices, networks, professional societies, and industry to facilitate the development of new professional interactions, programs, and research projects. It is anticipated that these new institutional arrangements, coupled with innovative advanced degree programs, will foster the nascent development of a new discipline of Clinical and Translational Science that will be much broader and deeper than the classical and separate domains of translational research and clinical investigation.

CTSAweb.org : The CTSA Consortium has developed a Web site to ensure access to CTSA resources, enhance communication, and encourage information sharing. In addition, the current CTSA awardees have agreed to post part of their applications for public viewing.

For additional programmatic information about the CTSA program including the latest Request for Applications and Notices, please visit http://www.ncrr.nih.gov/clinicaldiscipline.asp.

Translational Research Core Services — The NIH-RAID Pilot Program

Promising ideas for novel therapeutic interventions may encounter roadblocks in bench-to-bedside testing. While translation is sometimes facilitated by public-private partnerships, high-risk ideas or therapies for uncommon disorders frequently do not attract private sector investment. Where private sector capacity is limited or not available, public resources can bridge the gap between discovery and clinical testing so that more efficient translation of promising discoveries may take place.

To help address this need, the NIH is establishing a pilot program to make available, on a competitive basis, certain critical resources needed for the development of new small molecule therapeutic agents. The NIH Rapid Access to Interventional Development (RAID) Pilot Program is intended to reduce some of the common barriers between laboratory discoveries and clinical trials for new therapies. Projects in both the early and late stages of pre-clinical development are suitable for NIH-RAID applications. The NIH Pilot will accept requests over a two year period, with four submission dates.

For the complete Notice, please see http://grants.nih.gov/grants/guide/notice-files/NOT-RM-05-004.html.

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