Multi-Site Studies
All of Us
The All of Us Research Program is a historic effort to gather data from one million or more people living in the United States to accelerate research and improve health.
PI: Habibul Ahsan, MD
Co-PI: David Meltzer, MD, PhD
Far too many diseases do not have a proven means of prevention, or effective treatment. We must gain better insights into the biological, environmental, and behavioral influences on these diseases to make a difference for the millions of people who suffer from them. Precision medicine is a revolutionary approach for disease prevention and treatment that takes into account individual differences in lifestyle, environment, and biology. While some advances in precision medicine have been made, the practice is not currently in use for most diseases.
The All of Us Research Program is a key element of the Precision Medicine Initiative (PMI). Through advances in research, technology, and policies that empower patients, the PMI will enable a new era of medicine in which researchers, health care providers, and patients work together to develop individualized care.
PMI launched in fiscal year 2016 when $130 million was allocated to NIH to build a national, large-scale research participant group, called a cohort, and $70 million was allocated to the National Cancer Institute to lead efforts in cancer genomics as part of PMI for Oncology.
A set of core values is guiding the development and implementation of the All of Us Research Program:
- Participation is open to all.
- Participants reflect the rich diversity of the U.S.
- Participants are partners.
- Participants have access to their information.
- Data will be accessed broadly for research purposes.
- Security and privacy will be of highest importance.
- The program will be a catalyst for positive change in research.
The All of Us Research Program seeks to extend precision medicine to all diseases by building a national research cohort of one million or more U.S. participants. Many factors have converged to make now the right time to begin a program of this scale and scope.
Americans are engaging in improving their health and participating in health research more than ever before, electronic health records have been widely adopted, genomic analysis costs have dropped significantly, data science has become increasingly sophisticated, and health technologies have become mobile.
All of Us is a participant-engaged, data-driven enterprise supporting research at the intersection of human biology, behavior, genetics, environment, data science, computation and much more to produce new knowledge with the goal of developing more effective ways to treat disease.
For more information on the All of US study, please visit allofus.nih.gov
ACCOuNT
African-American Cardiovascular Pharmacogenetic CONsorTium
Discovery of African-American Specific Genetic Biomarkers That Affect Cardiovascular Drug Phenotypes
Site PI: David Meltzer, MD, PhD
The vast majority of pharmacogenomic association studies, which are the drivers of discovery in the field of precision medicine, have been conducted on exclusively European populations, thereby precluding the discovery of African-American-specific genetic biomarkers that affect drug phenotypes. Without scientific inquiry on the presence and association of these genetic variants to drug response, our ability to deliver precision medicine to all Americans is severely hampered.
African ancestry populations harbor more genetic diversity than any other world population, and hence have a genetic variation that may only be found within this population. In addition, thrombotic diseases disproportionally affect African-Americans and the variation associated with response to therapy in African Americans is still unknown. One notable example in pharmacogenomics is the discovery of novel genetic variants found exclusively in African Americans, which significantly affect warfarin dose response. We and others have shown that because these variants are not present (or in some instances present, yet not predictive), in other racial groups; hence, a more tailored approach to the delivery of pharmacogenomic recommendations are needed. Moreover, many clinical phenotypes that have a robust pharmacogenomic association (e.g. Clopidogrel response) have never been investigated in an African American cohort; therefore, the unique SNPs that may contribute to these phenotypes are completely absent from the scientific literature.
For more information on the ACCOuNT study, please visit: https://precisionmedicine4all.com/
MINT
PI: Jeffrey L. Carsons, MD
Site PI: Tamar Polonsky, MD
Co-PI: David Meltzer, MD, PhD
Co-PI: Micah Prochaska, MD, MS
Accumulating evidence from clinical trials suggests that a restrictive transfusion strategy is safe in most clinical settings. However, a low oxygen carrying capacity from moderate anemia may be deleterious in patients with cardiac ischemia. The potential for harm associated with anemia in patients with acute symptomatic coronary disease is supported by pathophysiological data that maintaining higher hemoglobin levels could benefit the ischemic heart by increasing oxygen delivery. Systematic reviews of clinical trials evaluating transfusion strategies in patients with known ischemic heart disease document the absence of high quality data, which has resulted in an ongoing controversy. The lack of high quality evidence to guide transfusions in patients with acute myocardial infarction has been cited in several major guidelines as well as by an NIH expert panel.
This multicenter trial, the Myocardial Ischemia and Transfusion (MINT) trial, randomly allocates 3500 patients with acute myocardial infarction and a hemoglobin concentration less than 10 g/dL to be treated either according to a liberal or restrictive blood transfusion strategy. Patients assigned to the liberal transfusion strategy receive one unit of packed red blood cells following randomization and enough blood to raise the hemoglobin concentration to 10 g/dL or above any time a concentration less than 10 g/dL is detected. Patients assigned to the restrictive transfusion strategy are permitted to receive a transfusion if the hemoglobin concentration falls below 8 g/dL or if angina symptoms clearly related to the anemia occur and are not controlled with anti-anginal medications. Only enough blood is given to reach a hemoglobin concentration of 8 g/dL or relieve the symptoms. Transfusion is strongly recommended if the hemoglobin concentration falls below 7 g/dL.
The transfusion protocol is followed during the index hospitalization (up to 30 days). Each patient is contacted at 30 days for a comprehensive follow-up for assessment of several relevant clinical outcomes. Patients are contacted again at 180 days to ascertain vital status for assessment of six-month mortality.