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

In a seminal paper about the NIH Roadmap for Medical Research, former NIH Director Elias Zerhouni laid out his vision for the Clinical and Translational Science Awards (CTSA) program. ¹ He wrote that clinical and translational research faced “increases in costs and complexity, a dearth of information systems and increases in the regulatory burden,” that clinical trials were delayed by “difficulties in the recruitment and retention of human subjects,” and that we could no longer “recruit, mentor and retain a critical mass of clinical and translational scientists.” The CTSA program, launched in 2006 with 12 institutional sites, was proposed to address these critical needs.

The original vision for the CTSAs was clear: They were established to create an academic home for clinical and translational research by reengineering existing capabilities at academic medical centers and by developing some new resources, especially for training, informatics and outreach to communities. Although less prominent in the original charge, the NIH had an even more ambitious vision for the CTSAs that encompassed transforming clinical research across the nation: building a better bridge between preclinical and clinical science; providing networks with shared resources that could reduce the costs, delays and difficulties experienced in clinical trials; and developing partnerships that would result in research that was more fully integrated into the delivery of care.

With the creation of the National Center for Advancing Translational Science (NCATS) in the final days of 2011, the administration of the CTSA program has moved into a new home. Within NCATS, the program will continue to support the highest quality translational research, now as part of a new division, the Division of Clinical Innovation, which should benefit from adjacency to the new Division of Preclinical Innovation (DPI). The DPI includes programs that focus on reengineering the early phases of translation (including assay development, high‐throughput screening, lead optimization and predictive toxicology) as well as the Therapeutics for Rare and Neglected Diseases program.

This organizational change, coming as it does just a little more than five years since the first CTSA awards were made, provides an excellent opportunity to take stock and to consider what we have accomplished and what remains to be done to achieve the broad goals of transforming clinical and translational research throughout the United States and perhaps beyond. The accompanying article, Preparedness of the CTSA’s structural and scientific assets to support the mission of the National Center for Advancing Translational Sciences (NCATS), by the current CTSA principal investigators (PIs), is a welcome invitation to begin a process of assessment. In particular, I appreciate the opportunity to comment on the authors’ vision for a “CTSA 2.0” that builds on the accomplishments of “CTSA 1.0.”

First, it is important to recognize what has already been accomplished with CTSA 1.0. Across 60 academic health centers, we now have a “home” for clinical and translational research that is leveraged with considerable support from their academic institutions and linked in novel ways to a variety of communities, including some that previously were not engaged in research. As noted in the article, the CTSA infrastructure has supported nearly 6,000 unique NIH grants across all disease areas in the most recently reported project period [or year]. Progress has been made in addressing some of the major barriers to clinical research—recruitment of subjects, regulatory delays and lack of information systems—often with innovative solutions that potentially can be used more broadly. The training of the next generation of clinical researchers, which a decade ago was approaching a national crisis, has been an unambiguous success of the CTSA program not only for physician scientists but for allied professionals in the many aspects of translational science. In a recent count, we identified 445 T (predoctoral) trainees and 485 K (young investigator) scholars across the CTSA Consortium. As the CTSA PIs note in the accompanying article, some brilliant successes have been achieved in the adoption or creation of data management tools, and there has been an unprecedented engagement of diverse communities in the research enterprise. Reading this account of what has been accomplished, it is easy to be enthusiastic about the CTSA program.

What’s next? As the CTSA PIs suggest in their article, we now can move beyond the original concept of the CTSAs as homes for translational research to a more ambitious role for them as a national community engaged in the full range of translation, from discovery to community‐engaged research (CeR). While CTSA 1.0 used work groups and conference calls to build multiple consortium activities, the vision for CTSA 2.0 should include the development of a functioning, nimble networking capacity with shared data management, reciprocity of institutional review boards (IRBs), and seamless sharing of information. Imagine a CTSA Consortium that fully exploits local capabilities as it builds upon the strengths of each member institution and deploys such effective linked networking capacity that twice the number of clinical trials could be completed in half the time and at half the costs, with increased safety for the research participants. As described in the paper, the creation of regional nodes is a step toward this goal. Similarly, the development of disease‐specific clusters, such as NeuroNEXT (Network for Excellence in Neuroscience Clinical Trials), which includes 21 CTSA sites studying neurological diseases that have a common IRB and shared data management, may build upon the CTSA infrastructure to be a model for CTSA 2.0.

The CTSA PIs are justifiably proud of their institutions’ broad capabilities for research across the entire translational spectrum. In fact, the 60 research centers they represent constitute much of the clinical research capacity for the nation at this time. The vision for NCATS, spelled out last year by NIH Director Francis Collins, includes this entire spectrum of science, from early discovery to CeR, from biomarkers to therapeutics, from drugs to devices to preventive interventions. ² CTSA 2.0 could give centers the flexibility to pursue a broader range of translational science, recognizing that all will have unique strengths and areas of expertise. The nation needs disruptive innovation from T1 through T4. Imagine a CTSA program that develops new tools for high‐throughput screening and predictive toxicology capabilities at some sites, provides unique phenotyping capabilities for experimental medicine at others (using some of those 625+ inpatient beds and 800+ outpatient facilities available through the CTSAs), and creates innovative opportunities for “citizen science” and community partnerships at yet others. As the accompanying article notes, all of these activities exist today. In CTSA 2.0, they could be part of an integrated strategy to bring new diagnostics and new treatments to the nation.

As a director of an NIH Institute with a categorical disease mission (the National Institute of Mental Health), I look to the CTSAs to make clinical and translational research cheaper, better and faster. I am not alone among Institute directors in facing tough budgetary challenges and continuing unmet public health needs. The CTSAs should help categorical NIH Institutes succeed, where success is defined by the development of new, affordable, effective, and safe biomarkers and treatments. The long‐term success of the CTSA program depends on demonstrating that the investments in “infrastructure” have paid off for patients. As the PIs note, the CTSAs already provide the platform for a broad range of disease‐specific research. Imagine, for example, if the CTSAs were fully integrated with clinical efforts across the NIH Institutes and Centers, cloning the NeuroNEXT effort for 20 more disease‐specific areas, including opportunities for rare diseases. If CTSA 2.0 can integrate more fully in this way with other Institutes and Centers and can demonstrate more clearly how it is transforming research for specific needs, the program can become the flagship for the effective integration of research into improved health care delivery, as was originally proposed.

Finally, as we consider the next generation of the CTSA program, we must ensure that we continue to preserve the many pieces that already are working well. As the accompanying paper demonstrates, we have much to be proud of. We also have a talented pool of national leaders who have committed themselves to making this program successful. As we develop CTSA 2.0, we look forward to engaging this remarkable group of leaders to help us make this outstanding program even better. The unmet health care needs in our nation are urgent; the opportunities for science to make a difference are unprecedented. The CTSAs in NCATS must be the bridge for linking fundamental discoveries in science to reductions in morbidity and mortality. It appears from their article that the CTSA PIs are prepared to build this bridge.