August 21, 2018 – DCRI founder and former U.S. Food and Drug Administration Commissioner Robert Califf, MD, provides some thoughts on the past and future of the DCRI.
The DCRI is currently experiencing its fourth transition in leadership since its founding in 1996. It seems like only yesterday that we were first imagining what could be accomplished if we organized an entity that convened talented staff and faculty leadership within an operational infrastructure—one that was purposefully designed to enable faculty in leading and conducting multisite clinical research in concert with remarkably creative staff professionals.
Early Successes, Early Challenges
Our early experience was shaped by significant success with research done in acute care cardiology and undergirded by the decades of development that went into the Duke Databank for Cardiovascular Disease. Despite this promising foundation, building the DCRI nevertheless entailed substantial risk. We endured many sleepless nights as we tested the capacity of an academic medical center to work with other academic leaders and clinical research sites around the world to generate large volumes of high-quality evidence in conjunction with industry, the National Institutes of Health, and other federal agencies. However, the result of these early efforts was not only a large and productive organization, but also the development of a generation of leaders in clinical and translational research, as highlighted recently in Forbes.
Growth and Transition
Successfully navigating changes in leadership is essential for any institution. After a period of initiation and leadership, I left the DCRI in 2006 to found the Duke Translational Medicine Institute (now the Duke Clinical and Translational Science Institute) when we received our first CTSA grant. At this point Dr. Robert Harrington, a faculty cardiologist, took the reins. During his tenure, he improved upon deficiencies that had evolved during my tenure and moved the DCRI to a new level by focusing on worldwide collaborations in multiple therapeutic areas while building the depth and diversity of quantitative sciences. Stanford University wisely recruited Dr. Harrington from Duke in 2012, doubtless seeking to leverage his considerable administrative and leadership skill, as well as his knowledge of clinical research, to complement its globally prominent discovery science and technology enterprises.
During this interval, the global research enterprise was pivoting toward the use of “real-world evidence” and an approach that blended health services research, quality assessment, and clinical trials. Dr. Eric Peterson, a highly accomplished outcomes research leader who was already an integral part of the DCRI faculty community, was well-suited to take the helm and steer the organization in this new direction. His leadership of key projects for the Databank for Cardiovascular Disease, the Society of Thoracic Surgeons Registry, the precursor to the American College of Cardiology registries, and the American Heart Association’s “Get With The Guidelines” effort paved the way for the current focus on real-world evidence.
The DCRI’s achievements under Eric’s leadership are substantial. Over the 6 years he led the organization, hundreds of clinical trials and other research studies were conducted. In the first 20 years of the DCRI from 1997 to 2017, DCRI faculty and staff published 12,230 peer-reviewed manuscripts and 2,192 of these were published in journals with an impact factor of 10 or higher. Eric’s tenure saw a marked acceleration in the pace of academic productivity, with more than 5,500 manuscripts published; of these, 1,090—20 percent—appeared in journals with an impact factor of 10 or higher. Dozens of fellows have been educated, a program to train fellows at the NIH has continued successfully, almost $1.5 billion in research funding was awarded, and substantial indirect costs have been generated for the institution. More than 130 faculty across multiple therapeutic areas and scientific disciplines have DCRI appointments. The institution is thriving while contributing to new and related efforts in the Department of Population Health Sciences and the Department of Biostatistics and Bioinformatics, and it’s also forging new alliances with the clinical and information technology communities.
Looking Back, Moving Forward
Now, after 6 years as DCRI director, Eric has decided to take a new direction in his career, and Dr. Lesley Curtis has stepped in as interim director. Dr. Curtis is an experienced and able leader, researcher, and administrator, one with a track record as an inspirational pioneer in combining real-world data with novel methods to produce real-world evidence that can guide decisions about health and healthcare. While the institution prepares to undertake a global search preparatory to recruiting a new leader, as the founding director of the DCRI, I find myself reflecting on the job and the characteristics and circumstances that should be considered by the next generation of leaders. What have been the key factors in the DCRI’s success?
First and foremost, the DCRI was built on strong collaboration among clinical investigators, biostatisticians, informaticians, and operational staff. Over time, the array of collaborators expanded to include health services researchers, economists, epidemiologists, and data scientists. Because the DCRI is poised at the interface of industry, government and academia, its relative independence is critically important. This independence encompasses the ability to manage financial issues in ways that allow the DCRI to grow and invest in its own future. The operational and financial needs of multisite research are different than single-site research done internally at Duke; the job titles and responsibilities are complex and sometimes idiosyncratic to the clinical research industry and distinct from other parts of the university. And the regulated information technology environment has required a level of attention to auditable issues that was not present in the rest of the medical center until recently.
Accordingly, the DCRI needed its own human resources, legal, and information technology structures that were part of Duke but were also constituted as independently operating units with decision-making authority. The DCRI’s matrix leadership structure (with scientific leadership on one side, business/operations leadership on the other, woven together in a matrix system of organization), while unusual for an academic medical center, is also central to the institute’s success. The huge educational investments in fellowships and faculty development have greatly aided the creation of a mission-driven culture of research on campus with a size and scope that are hard to match. Substantial effort is needed to produce and sustain operational expertise. Likewise, the development of faculty leaders who are clinical experts but who also devote significant time to research concerning the diseases and problems afflicting the patients they care for gives Duke an edge in the national competition for grants and contracts. More importantly, the research driven by the DCRI has benefitted from the close involvement of researchers with deep, first-hand knowledge of clinical issues, generating the evidence that gives patients and clinicians the knowledge that truly informs practice.
However, the multifarious and sometimes competing priorities of different funders and sponsors across the clinical research enterprise can present challenges for the DCRI. While in some ways the DCRI invented the “technology-enhanced megatrial” with the GUSTO study, the enormous clinical need and large amounts of money involved attracted the interests of business, and for-profit contract research organizations now dominate this arena. At the same time, Duke’s relatively conservative institutional approach to interaction with for-profit entities has made the large amounts of capital in this space used for investment in technology upgrades inaccessible to the DCRI, which is thus highly dependent on its own operating margins for investment in large-scale research infrastructure.
In addition, academic centers continue to grapple with the diverse interests of faculty and an organizational structure that tends to aggregate resources in siloed departments. This in turn leads to friction about the allotment of faculty time and effort and competitive infrastructure investments, pressure that Dean Klotman is now addressing through the “One Duke” effort. Finally, the field of clinical research as an academic endeavor continues to suffer broadly from “Rodney Dangerfield syndrome”—it “don’t get no respect” relative to the perceived primacy of basic science and discovery research.
Despite these challenges, the DCRI is a robust organization that continues to generate high-quality, reliable evidence across the spectrum from early translation to population studies. It also continues to pioneer new methodologic approaches to research, most notably the use of electronic health records, claims data, and wearable devices and sensors in the development of actionable evidence. Its faculty and staff play critical roles in the development of academic and regulatory standards through organizations such as the Clinical Trials Transformation Initiative and the Cardiac Safety Research Consortium. Its pediatrics component has several of the largest most important NICHD long-term grants and contracts for therapeutics (the Pediatric Trials Network) and epidemiology (ECHO), which together account for almost $200 million in funding over 9-10 years. It also serves as the coordinating center for the NIH-funded Health Care Systems Research Collaboratory and the pioneering National Patient-Centered Clinical Research Network (PCORnet), both of which are engaged in critically important proof-of-concept research in the arena of pragmatic clinical trials. And it co-leads the Antibiotic Resistance Leadership Group, a long-term NIH consortium dealing with critical issues in antibiotic resistance. These are only a few of the many areas in which DCRI is setting the pace for future research, filling critical national needs for evidence and conducting complex research with the high-quality operations needed for multisite research.
Evolving Challenges and New Opportunities
Clinical research is changing, and our local environment is complex. Faculty will thrive if they have access to robust infrastructure that can deliver proposals, operations, and data that match the design and analysis that represent the academic “sweet spot” for faculty effort. The transition to a digital information environment has massively expanded access to data that must be organized and approached with appropriate research methods in order to enable a learning health system. We are moving away from a construct oriented around clinical research sites toward one based on clinical research systems. And because large health systems now own most of U.S. clinical research sites, a common infrastructure for operations, contracting, and ethics review is being established.
Our own efforts at Duke should show the way in transforming the fundamental idea of research from a set of activities comprising a “set-aside” distinct from other missions, to a construct in which learning through research is a fundamental attribute of the health system. The power of closer collaboration among the Duke Health System and Duke Office of Clinical Research (DOCR), the DCRI, and the Department of Population Health Sciences, further enabled by the expansion of the quantitative science expertise across campus, could unleash a powerful, higher-quality, and less expensive institutional effort in clinical and population research consistent with Dean Klotman’s vision of “One Duke.”
This period of transition is a perfect time to imagine what is possible if we pull together, take advantage of a successful past that has changed the way clinical research is done, and create a new approach that will bring the clinical care and research worlds into a common learning system. A new leader for DCRI will need to consolidate the successful strategies and infrastructure of the past, “ride the wave” of changes in the new digital learning health environment, and lead the organization with vision while balancing the tensions inherent in the job.
I can see that many people from a diverse array of backgrounds could be up to the task. The ability to navigate a rapidly evolving environment while providing inspiration and leadership to faculty and staff is a more important consideration than is specific research discipline. I am certain that Dr. Curtis will continue to enhance the DCRI as previous leaders have until a permanent successor is chosen. There has never been a more exciting time for clinical research, and I’m confident that the DCRI can lead the transition to a learning health system.
This post originally appeared on Duke Forge.