New NHGRI grants focus on using genomic information in patient care
Projects center on the use of family health histories, gene variants associated with kidney disease in African Americans and pharmacogenomics
By Steven Benowitz
Associate Director of Communications, Extramural Research Program
Survey after survey repeatedly shows that most physicians see genomics as crucial to major advances in disease diagnostics, treatment and prevention. But for many of those same physicians, how to best use genomics in taking care of patients remains challenging.
Several newly funded grants from the National Human Genome Research Institute (NHGRI), one of the 27 institutes and centers that make up the National Institutes of Health (NIH), will address these challenges and help find solutions. One project, for example, will examine the use of a person's family health history, which can provide a doctor with key insights into both disease risk and prevention. In another, researchers plan to study the use of a genetic marker that can warn African Americans with high blood pressure that they are at increased risk for developing chronic kidney disease. A third group hopes to find out if a better understanding of an individual's genetic makeup and how it impacts drug response can help doctors customize disease treatments.
This is the first set of grants from the Genomic Medicine Pilot Demonstration Projects (GMPDP) program. These grants are unique in their focus on developing new approaches to incorporating genomic information into patient care, with special attention to the use of increasingly available electronic medical record (EMR) systems and accompanying clinical decision-support programs. The four-year awards total more than $2.6 million in the first year (and if funding remains available, approximately $12.8 million overall).
The four scientists receiving grants include:
Geoffrey Ginsburg, M.D., Ph.D., director of genomic medicine at the Duke Institute for Genome Sciences & Policy and executive director of the Center for Personalized and Precision Medicine at the Duke University Health System
Erwin Bottinger, M.D. , director of the Charles Bronfman Institute for Personalized Medicine at the Icahn School of Medicine at Mount Sinai
Julie Johnson, Pharm.D., Distinguished Professor of Pharmacy and V. Ravi Chandran Professor of Pharmaceutical Sciences at the University of Florida
Stephen Kimmel, M.D., professor of medicine and epidemiology at the University of Pennsylvania (Coordinating Center)
"Groups around the country have begun to explore the use of genomic medicine, and many have been studying new ways to take genomic results and implement them into electronic medical records and clinical care," said Heather Junkins, NHGRI health science analyst. "We're still learning the best ways to do this and putting together a funded consortium of investigators allows people to network, develop best practices and disseminate information."
Electronic medical records and accompanying decision-making guides promise to change patient care with faster access to patient information. "A physician may have a pop-up in the patient's electronic record saying that a certain drug should not be used if the patient has a particular condition because of a variant preventing him from metabolizing the medication," said Ebony Bookman, Ph.D., NHGRI epidemiologist. "A major goal of the projects is the development of clinical decision-support tools to provide physicians useful information so they can make decisions on the spot. We hope these projects will show how genomic medicine will work and will eventually be used in patients."
Exploring the importance of family health histories
According to Dr. Ginsburg, who heads a project focusing on the implementation of electronic family health histories, such histories - while long a staple of medical practice and a source of potentially valuable information about hereditable disease - are seldom collected completely. As a result, physicians may not make appropriate screening recommendations. He and his co-workers at Duke pioneered the development of a family history software tool several years ago to help patients provide their family health history electronically, and to facilitate physician and patient decision-making.
This study will allow them to expand their research into many different clinical settings. They plan to use family histories that patients provide electronically to improve both patients' and health care professionals' understanding of disease risk. The study encompasses five healthcare settings, including academic, rural, underserved and community and family medicine clinics in six states. Some facilities will have experience with using genomic medicine in their patients' health histories and in using electronic medical record systems, while others will not. They plan to recruit at least 7,000 English- or Spanish-speaking adults over three years.
Researchers will test how to best implement a user-friendly system where patients provide family health histories specifically for heart disease, thrombosis and certain cancers. After data collection, the system will transmit the information to a decision-making program and provide a report to both the patient and the physician. The report will provide recommendations for further testing, counseling and prevention measures.
"We want to show the value of taking accurate and adequate family histories that are patient-driven, and develop an instruction book of how to do it universally," said Dr. Ginsburg. "Our aim is to show whether it is feasible and valuable - and translatable - in a number of different environments, and to understand if the use of and outcomes of family history information are different in academic settings compared to practices with rural or underserved patient populations."
Using a genomic marker
At the Icahn School of Medicine at Mount Sinai in New York, Dr. Bottinger, co-principal investigator Carol Horowitz, M.D., M.P.H., associate professor of health evidence and policy, and their co-workers plan to conduct a clinical trial to study the effects of using genomic risk information in the care of African-American patients who have high blood pressure and who are at risk for developing chronic kidney disease. The study - which will be conducted in a network of community health centers and primary care physician offices - will compare outcomes between patients at centers or offices where genomic information is shared between doctors and patients with patients in offices where genomic risk information is not provided.
The 12 participating primary care centers and practices are located in Harlem, the Bronx and at Mount Sinai Medical Center. According to Dr. Bottinger, African Americans who have high blood pressure have a 2-3 times higher risk for chronic kidney disease. Many, however, may not receive the proper care, including diagnostic tests or medication to treat both the disease and high blood pressure.
The trial will examine whether or not care is improved in those offices that have electronic medical record systems and clinical decision support based on genomic information, compared to those systems that do not have such genomic data. The researchers will take advantage of a relatively recent discovery of a gene marker called APOL1. Studies have shown that one in eight African Americans with high blood pressure carry two copies of the disease risk version of the APOL1 gene, and have a four- to five-fold increased risk of developing chronic kidney disease.
"As primary care providers in communities of color, we are anxious to test the implementation of genetic testing as a potentially powerful tool to motivate patients and providers to focus on hypertension as a critical risk factor for kidney disease as well as heart disease and stroke," said Dr. Bottinger. "We are just learning how to use genomic information to benefit patients. We hope our research will create new insights on how to share genomic information with patients, and will show us whether this information can improve primary care and overall health of patients from diverse, underserved communities with common, chronic diseases."
Moving pharmacogenomics into the clinic
According to Dr. Johnson, a better understanding of how a person's genetic makeup affects drug response will continue to fuel a more personalized approach to medicine. However, many clinical practices do not readily use such information in patient care.
Her program is aimed at bringing the clinical use of pharmacogenomics closer to business as usual. Last year, the university implemented a personalized medicine program that included pharmacogenetic testing, and the group wants to expand the program within and beyond UF Health at the University of Florida.
The team currently utilizes "genotype-guided" treatment with clopidogrel, a drug used in treating cardiac patients, and plans to also broaden the program's scope, increasing the number and types of patients and drugs they employ. These studies will include pediatric and adult gastroenterology and pediatric hematology patients.
Dr. Johnson and her team plan to implement the personalized medicine genotyping program involving pharmacogenomic testing and decision support in a large private health system in Orlando, and will also engage smaller community centers affiliated with Florida State University. They will develop training and education courses in pharmacogenomics for students and health care professionals, and educational materials for patients.
There will be challenges in instituting such programs, she said, particularly in helping educate busy doctors and other specialists in the best ways to use pharmacogenomics in their practices.
The final component of the new consortium is the coordinating center at the University of Pennsylvania. A successful coordinating center pulls everything together organizationally. It makes sure the various project groups collaborate, share data and insights, and, in the end, come up with broad, more generalizable results that can be used in a wider application of clinical genomics, said Penn's Stephen Kimmel.
"We'll work together with each of the centers, and collect information that the sites need to answer broader questions about the implementation of genomic medicine," explained Dr. Kimmel. "We want to help establish a framework that can apply to the use of genomics more broadly." He noted that the coordinating center team will also pay special attention to the developing ethical, social and legal implications of implementing genomics into medicine and patient care.
While these genomic medicine demonstration projects are an important place to start, Dr. Bookman said, there is a long road ahead.
"We are just at the beginning of understanding how to best use genomic medicine," she said. "The academic institutions are providing funds to start programs, but clinical practices in the community, for the most part, don't have very much knowledge or experience using genomic medicine in their daily practices. Academic centers increasingly have EMRs in place; it's a mixed bag in the community centers."
"Both patients and clinicians need training and background in understanding the potential uses of genomic medicine," Dr. Bookman said. "We have to learn how to engage clinicians and make them comfortable in ordering new kinds of tests, interpreting the results and talking to patients."
The grant numbers of the new awards include: HG007266, HG007269, HG007278, and HG007282.