By 2001, the Consortium of Rheumatology Researchers of North America, Inc. (CORRONA) was launched and began to enroll its first patients. Today, CORRONA is generally recognized as the largest rheumatologic registry in the world. As of late September, it had enrolled 39,963 patients with rheumatoid arthritis, psoriatic arthritis, and gout. All other forms of spondylarthritis, in addition to psoriatic arthritis, will be added in early 2013; the organization has also gone international, with a total of 10 additional countries. The CORRONA network of 100 affiliated rheumatology practices in 40 states has now reported on more than 250,387 office visits conducted with their patients and over 80,000 patient-years of data. The rich database, run by internal biostatistics and epidemiologist staff members, and directed by esteemed biostatistician George Reed, PhD, associate professor in the division of preventive and behavioral medicine at the University of Massachusetts Medical School in Worcester, handles scores of scientific queries from researchers worldwide.
The Rheumatologist recently spoke with several leading CORRONA officers and investigators about the factors that have contributed to the registry’s exponential growth.
Data Collection and Practice Efficiency
One of Dr. Kremer’s initial premises when establishing the registry was to acknowledge the barriers to participation for private practitioners. “Filling out forms was counterintuitive to physicians,” he explains. “Completing forms has to be workable in the context of their busy day, so we recognized early on that initially they had to be paid for [completing] the forms.” Jeffrey Greenberg, MD, MPH, assistant professor and associate director for clinical translational sciences at NYU’s Hospital for Joint Diseases in New York City, and CORRONA’s chief scientific officer, believes that Dr. Kremer’s recognition of the time factor has been key for attracting participants. “There is a delicate balance for collecting data in a busy clinical practice,” he notes. “Dr. Kremer’s recognition of that is one factor that has allowed CORRONA to grow.”
J. Timothy (Tim) Harrington, MD, a rheumatologist at UW Health, the academic health system for the University of Wisconsin in Madison, became interested in CORRONA “because of the ability to create a ‘laboratory’ for testing standardized data management and its impacts on care and disease outcomes,” he says. His collaborations with Dr. Kremer had their start in 2000 with a discussion during a continuing medical education course in Whistler, B.C. “We shared our dreams,” Dr. Harrington recalls. “His was to build an RA observational registry, which has become CORRONA, and mine was to improve and redesign rheumatology practice in the United States—both rather humble goals,” he quips.
Since that time, Dr. Harrington, a noted quality-improvement researcher and author, has become chief site quality officer for CORRONA. In that capacity, he has overseen refinement of the data questionnaire and incorporation of several practice efficiency elements, such as the Physician Quality and Reporting System and Meaningful Use, into the CORRONA registry for participating practices. He was also the first to do a pilot study implementing the CORRONA data set, and found that by using its standardized data set, he was able to decrease by 40% the amount of time he spent taking the patient’s history and documenting encounters in the medical record. “I used to spend 70% of my time finding out what’s going on with the patient and 30% doing something about it. Now I spend 30% of my finding out what’s going on and 70% of my time doing something about it!” Dr. Harrington says. This process has implications for dealing with workforce issues as well, he notes. “If you standardize the data process within your practice, then you can start to move major amounts of work for coordinating patient care, assessing disease status, and treatment safety from the physician visit into the nurse or [nurse practitioner] encounter,” he maintained. [For more on practice redesign, read “High-Impact Rheumatology Practice Redesign” at www.The-Rheumatologist.org.]
“The CORRONA Virus”
At the outset, Dr. Kremer says, “I insisted on two themes. One was to work with and empower good people, and the other was to be inclusive. We have a horizontal structure, not a vertical one, and that has allowed an environment of mutual respect.” He rejoices about the high level of talent the database has attracted. The company now has a staff of 35 employees, including Chief Operating Officer James Cavan, MS, crack information-technology and project-management teams, and an experienced epidemiological and biostatistician cadre, as well as legal and other support staff.
CORRONA is a virtual enterprise, and its key board members and investigators also run their own full-time academic or private practices, as well as independent research studies. Dr. Kremer notes that the penchant for dedicating time to the venture has been linked to what members have dubbed the “CORRONA virus.” “It’s bizarre and it’s frightening,” Dr. Kremer laughs. “You catch this uncontrollable desire to do good things working with your other collaborators in this company. And as a consequence, nobody works a 40-hour week.”
A Good Fit
Dr. Greenberg first became involved with CORRONA as a rheumatology fellow in 2003, when he was searching for interesting data sets for his own rheumatology research. He has since become the chief scientific officer for the organization, juggling his own research, busy academic practice, and CORRONA participation. “Observational registries, both in the U.S. and Europe, have made substantial contributions to our understanding of long-term biologic drug safety, and they’ll continue to do so,” he says. “CORRONA is a unique resource in the U.S. for rheumatology research.”
Philip J. Mease, MD, director of rheumatology research at Swedish Medical Center and clinical professor at the University of Washington in Seattle, is a member of CORRONA’s board of directors and scientific advisory committee. He joined the venture because he was impressed with the uniqueness of the registry: “It has the computer and biostatistics infrastructure and a broad array of clinics across the country—both private and academic—that is representative of rheumatology in general,” he says. At the Swedish Medical Center, he and his department have been “early adopters” of quantitative measurement, employing the Disease Activity Score-28 and other patient assessments. “It’s been pretty easy for us to slip into efforts like the Treat-to-Target paradigm,” Dr. Mease notes, “because of the fact that we’ve been collecting that quantitative information.” Joining the CORRONA registry was a good fit for his practice and for his patients. “Oftentimes, our patients will track their own quantitative information, and it helps them think through decision making with us. So, [participation in CORRONA] has been a win–win in our setting.”
Nested Trials and Studies
Jeffrey Curtis, MD, MPH, associate professor of medicine, clinical immunology, and rheumatology at the University of Alabama at Birmingham, has been involved with CORRONA for the past five years and was the initial designer of the CERTAIN substudy, a comparative effectiveness study which has now enrolled 2,733 patients with inflammatory arthritis treated with biologics. The study will follow patients for one year after the initiation of a biologic agent for moderate or high disease activity and is designed to supply “real-world data,” mainly on biologic treatment comparative effectiveness and safety, but also on treatment patterns and preferences of U.S. patients with inflammatory arthritis. This is especially needed, says Dr. Curtis, because data on biologic treatments have mostly originated from clinical trials where biologic agents are compared against placebo and not compared head to head. In addition, most other large available observational registries are European; and in those countries, biologic therapies are not allowed in patients with moderate disease activity, as is the case in the U.S. “In terms of maximizing the generalizability of what we learn from registries, it’s important to make sure the registry provides results relevant for the kinds of people, practice settings, and geography of the patients doctors see on a day-to-day basis,” says Dr. Curtis. “In the U.S., I think CORRONA is quite unique in that regard.”
Dimitrios Pappas, MD, MPH, assistant professor of medicine at Columbia University, has been the scientific director for the CERTAIN substudy since July of 2009. He explains that patients in the study will be seen at three-month intervals for one year after initiation of a biologic agent. Biologic agents will be started at the discretion of the treating CORRONA investigator and there will not be any intervention by CORRONA regarding the treatment chosen. Information about disease activity, disease severity, functionality, concurrent medication, and comorbidities will be collected at every visit. Blood samples, to include complete blood count, comprehensive metabolic panel, serologies, immunoglobulin levels, high-sensitivity C-reactive protein, and a lipid panel with a direct low-density lipoprotein, will also be obtained and tested in a central laboratory. In addition DNA, RNA, serum, and plasma will be collected and stored for future research. After completion of their participation in CERTAIN, patients will be followed in the main CORRONA registry, allowing long-term follow-up on safety. “You know, most clinical trials last for a few months and enroll few hundreds of patients, thus possibly not allowing for rare safety signals to be detected,” says Dr. Pappas. “Participation in CERTAIN is followed by regular follow up in the main CORRONA registry and collection of information for adverse events—even the most rare ones. If the patients in our registry have any safety issues, we’ll be able to associate those with the biologic they began at the start of our study.”
Dr. Pappas began his association with CORRONA as an internal medicine resident at Albany Medical College, where Dr. Kremer was his mentor. He started working with the registry in earnest after completing his rheumatology fellowship at Johns Hopkins University in Baltimore in 2009. In addition to directing the CERTAIN substudy, he now heads the International Registry, which started enrolling patients in Asia, Eastern Europe, and Latin America just over a year ago.
The logic for starting the CORRONA International Registry was driven by trends in the pharmaceutical industry, says Dr. Kremer. Due to the dearth of U.S. participants, industry has now been conducting clinical trials in Asia, India, Mexico, and South America. “We have no societal context for these populations,” Dr. Kremer points out. CORRONA has stepped into the vacuum, to supply crucial “real-world data” information about those patients’ comorbidities, malignancies, and disease severity.
The time is now right for initiating another new arm to include the spondylarthritidies, says Dr. Mease, who will be the scientific director of that new nested study, set to roll out in the first quarter of 2013. The broadened criteria set developed by the Assessment of SpondyloArthritis International Society and a parallel interest from pharmaceutical companies to examine the effects of drugs such as adalimumab in the patients with axial and/or peripheral symptoms have set the stage for capturing a broader cohort of patients. “We think that some patients with spondylarthritidies may be ‘hidden’ in primary, orthopedic, or physiatry clinics because their symptoms are not recognized,” he says.
Dr. Kremer reflects on the CORRONA enterprise: “I never set out to do all this. It was just one of those classic situations where one thing led to another: You start collaborating with really good people, your horizons expand, and you recognize that some of the dots can be connected in various domains of our discipline.” Dr. Greenberg echoes that idea: “There is a need for complementary sources of drug safety data for long-term pharmacovigilance,” he notes, “and the potential for new registries, nested clinical trials [such as the CERTAIN or Treat-to-Target (T2T) substudies] is tremendous.”
It looks like the registry is on track to capitalize on its potential. Besides the starts of the spondylarthropathy and gout registries, plans are also in the works for a lupus registry sometime in the next year. “We’ve done good things,” says Dr. Kremer, “but the glass is half full—we still have an awful lot of hard work to do.”
Gretchen Henkel is writing the “Metrics in Rheumatology” series.
