Craig J. Reist, Tyrus L. Rorick, Lisa G. Berdan, and Renato D. Lopes
The label academic research organization (ARO), used broadly within the clinical and drug development industries, primarily refers to an academic and/or nonprofit institution that performs one or more functions in the conduct of clinical trials. The services that an ARO provides can range from academic leadership to full-service clinical trial management capabilities, including site monitoring, data management, statistical analysis, safety monitoring, and clinical events classification, in addition to clinical expertise.
The concept of an ARO dates back several decades, when researchers recognized the need for large global clinical trials to answer important medical questions. Clinical scientists from several of the world’s leading academic institutions formed teams of like-minded investigators with the goal of developing and conducting global clinical studies to improve patient care. AROs are focused on developing and sharing knowledge with the end goal of improving patient care. They accomplish this goal not only by leading and conducting multinational clinical trials but also by ensuring that the results from these trials are published and presented. These groups also focus on managing major national patient registries designed to collect data and determine best practices, which can then be incorporated into clinical practice guidelines. Education and development of clinical investigators is also a focus, with many of the leading AROs having fellowship programs whose influence extends around the globe.
The concept of the ARO dates back to the late 1980s, when several groups of physician investigators first came together to address unmet clinical needs by organizing and centralizing the operational efforts associated with conducting large multicenter clinical trials, so-called “megatrials.” The first such group, located at the University of Oxford in the United Kingdom, developed in 1975 from a single research team. It began enrollment of the then-largest trial in history—6,027 patients with suspected acute myocardial infarction (MI)—in mid-1981, completed enrollment at the 245 participating coronary care units in 1985, and published the results the next year (1). Similarly, the Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico (GISSI), formed from a collaboration between the Mario Negri Institute and the Associazione Nazionale dei Medici Cardiologi Ospedalieri, began enrolling 11,806 patients with acute MI in 176 Italian intensive care units in 1984. It published the study results 2 years later (2). Both groups have since continued to perform large, important multicenter trials.
Two groups in particular have paved the way for what we now know as AROs. The Thrombolysis In Myocardial Infarction (TIMI) study group, based in Boston, Massachusetts, and affiliated with Brigham and Women’s Hospital and Harvard Medical School, was among the first groups to take on the challenges associated with organizing and implementing global clinical trials (3). The TIMI series of trials began in 1984, initially sponsored by the National Heart, Lung, and Blood Institute (NHLBI). At first, the trials studied thrombolytic and antithrombotic therapies in patients with acute MI and unstable angina, but they now cover many aspects of cardiovascular disease.
Around the same time, other groups of academic investigators were beginning to organize their efforts to address important clinical questions, and thought leaders from around the world formed an alliance to facilitate the conduct of pivotal cardiovascular clinical trials. The VIrtual Coordinating Centre for Global CollabOrative CardiovascUlar Research (VIGOUR) is a working group of global thought leaders in cardiovascular clinical medicine who have achieved academic and industry recognition for performing large multinational clinical trials. The alliance developed from a group of academic investigators participating in the international Global Utilization of Streptokinase and TPA (alteplase) for Occluded Coronary Arteries (GUSTO-1) trial, which began enrollment in 1990 (4). VIGOUR members have since conducted many large international trials, all according to the group’s philosophical perspectives on clinical trial design and methods (5). The VIGOUR organization is committed to improving the practice of cardiovascular medicine and patient outcomes (6).
During the 1990s and into the new millennium, many more now-prominent AROs began to formalize their efforts to lead the development of new therapeutics and shape the future of clinical practice across the globe. Table 3–1 lists some of the major AROs currently leading clinical trials (7), and Figure 3–1 displays their global distribution.
TABLE 3–1 Major academic research organizations
FIGURE 3—1. Global distribution of the academic research organizations listed in Table 3–1.
Although each ARO has unique characteristics, they share some common values and principles. In general, AROs are nonprofit organizations dedicated to quality research based on high standards and scientific integrity. The operational services that these groups perform comply with Good Clinical Practice guidelines and adhere to national and international regulations. The groups strive to ensure that the questions being asked are important clinical questions that will lead to new therapeutics and improved patient care, regardless of the outcome of the trial. Critical to the academic mission of these organizations is the dissemination of new knowledge to the clinical community and patient population being studied (8). Revenue margins are used to fund unfunded or underfunded trials that often address key clinical questions unrelated to commercial development of a drug or device. The results obtained from ARO trials undergo rigorous analyses, and the knowledge gained is incorporated into clinical practice guidelines and supports evidence-based medicine around the globe.
Much of the research being conducted around the world is currently being managed by contract or clinical research organizations (CROs). CROs typically provide trial management services for companies in the pharmaceutical and biotechnology industries. These services can include preclinical research, clinical research, clinical trials management and/or monitoring, data management, and medical writing. CROs range from large (several thousand employees worldwide) to small specialty groups focused on a particular therapeutic area or type of service. CROs market to their clients that they can move a new drug or device from conception to regulatory and marketing approval more efficiently than the company can using its own staff for these services.
A primary difference between CROs and most AROs is that CROs are for-profit companies whose purpose is to provide operational services for their clients, typically pharmaceutical companies, whereas the primary focus of an ARO is knowledge-based, with improving clinical care as the goal. These different perspectives are reflected in the mission and purpose statements available on the Web sites of several of the major CROs and AROs (see Table 3–2). Another difference is a greater emphasis on collaboration among AROs, which is less typical among often-competing CROs (9).
TABLE 3–2
Mission/purpose statements of major academic/contract research organizations
AROs not only believe that they are responsible for the conduct and quality of each trial but also strive to ensure that the products of their research activities result in enhanced knowledge and improved patient care. This is done by ensuring clinical input in the design and operations of trials and by making certain that the results are published for the healthcare community at large.
A primary goal of any academic organization is education and training. AROs pride themselves on being institutions where future investigators can come to learn clinical research methods, leading to responsible research.
The inception of the Duke Clinical Research Institute (DCRI) dates from 1969 with the formation of the Duke Databank for Cardiovascular Disease, a research group within Duke University Medical Center. The Databank was the result of an idea of then-Chairman of Medicine, Eugene A. Stead, Jr., MD, who envisioned it as a “computerized textbook of medicine,” using information gathered by one physician today to help other physicians care for similar patients tomorrow.
Since 1969, data from all patients undergoing invasive cardiac procedures at Duke have been entered into the Databank, which has since been expanded to include noninvasive diagnostic procedures. Patients with a diagnosis of coronary artery disease are followed annually throughout their lives. Follow-up of the >130,000 patients in the Databank continues today and is more than 99% complete. The continuous maintenance of the Databank for nearly 35 years has given DCRI faculty and staff extensive experience with a long-term follow-up system, including ascertainment of hospital records. The Databank is the world’s oldest and largest cardiovascular database.
In the mid-1980s, the research team began to coordinate multicenter clinical trials. The group used its clinical expertise to help design well-crafted protocols and its biostatistics expertise to determine appropriate trial designs and sample sizes to answer the questions addressed in the protocols. The group’s landmark trial began in 1990: GUSTO-1, a 4-arm study of thrombolytic therapies that enrolled 41,021 patients with acute MI in 1081 hospitals in 15 countries (4). As noted above, GUSTO-1 gave rise not only to the VIGOUR collaboration but also to a variety of multinational randomized trials in which global academic leaders played increasingly pivotal roles. Today these academic partners often serve as principal investigators, while the DCRI provides operational expertise in jointly designed clinical research projects.
In addition to designing, managing, and analyzing clinical trials, the DCRI also has extensive capabilities in outcomes research and has incorporated cost-effectiveness and quality-of-life assessments into many megatrials. The DCRI has also become increasingly involved in managing data warehouses and conducting registries and clinical trials in collaboration with professional medical societies and the National Institutes of Health.
To date, the DCRI has completed more than 760 Phase I–IV clinical trials, registries, and economics/outcomes studies comprising more than 1 million subjects from 65 countries (10). The organization employs 1100 faculty and staff and occupies almost 150,000 square feet of space within and around the Duke University Medical Center campus. As an Institute of the Medical Center, it is a fully integrated component of the university, governed by the Duke University Health System Board of Trustees, which in turn reports to the University Board of Trustees.
Clearly, more can be done as we move forward, including closer networking of academic groups, ensuring value to both commercial and academic partners, and ensuring that academic groups commit to and deliver results that rival any large CRO.
The history of the DCRI shows the ability of an ARO to incorporate both new initiatives and new capabilities to meet the needs of an evolving clinical research enterprise. Whether the aim is to know the risks and benefits of a new therapy, to measure the cost-effectiveness of an existing technique, or to integrate the most appropriate patient care into the practice of every physician, AROs such as the DCRI constantly reassess their abilities to respond to the evolving needs of the healthcare system.
1. First International Study of Infarct Survival Collaborative Group. Randomised trial of intravenous atenolol among 16027 cases of suspected acute myocardial infarction: ISIS-1. Lancet. 1986;2(8498):57-66.
2. Gruppo Italiano per lo Studio della Streptochinasi nell’Infarto Miocardico (GISSI). Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Lancet. 1986;1(8478):397-402.
3. TIMI Study Group. About TIMI Study Group. http://www.timi.org/?page_id=97. Accessed April 5, 2012.
4. The GUSTO Investigators. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med. 1993;329(10):673-682.
5. Topol EJ, et al. Perspectives on large-scale cardiovascular clinical trials for the new millennium. The Virtual Coordinating Center for Global Collaborative Cardiovascular Research (VIGOUR) Group. Circulation. 1997;95(4): 1072-1082.
6. Armstrong PW, Kaul P. Charting the course of clinical research: from an inspired past to a promising future. Am Heart J. 2004;148(2):190-192.
7. Harrington RA, et al. Careers for clinician investigators. Circulation. 2009; 119(22):2945-2950.
8. Carayol N, Matt M. Does research organization influence academic production? Laboratory level evidence from a large European university. Res Policy. 2004;33(8):1081-1102.
9. Shuchman M. Commercializing clinical trials–risks and benefits of the CRO boom. N Engl J Med. 2007;357(14):1365-1368.
10. Duke Clinical Research Institute. DCRI Annual Report, 2011. https://dcri.org/about-us/resolveuid/16abf2791474beb759324d47db642ee1. Accessed April 5, 2012.
