Biennial Report of the Director

Overview of NIH Research Portfolio

In pursuit of its mission to seek fundamental knowledge about the nature and behavior of living systems and to apply that knowledge to enhance health, lengthen life, and reduce the burdens of illness and disability, NIH conducts and supports biomedical and behavioral research across a broad spectrum of scientific disciplines and approaches. NIH scientists may have been trained in any number of disciplines, from molecular biology to demography to engineering. Yet, as science and technology have advanced and the complexity of the issues addressed has grown, the disciplinary boundaries that previously defined science have become blurred, such that NIH research is not delineated by scientific discipline, but instead by a continuum of inquiries.

NIH research is predicated on the understanding of ongoing and newly emerging public health needs. As these needs are identified, scientific approaches are brought to bear across a continuum of research designed to understand basic causes and mechanisms of disease, find new ways of identifying and interrupting disease processes based on this understanding, and bring these new interventions into common practice so that all may benefit. The path from basic research to clinical practice (see Figure 2-1) is not a continuum in the strictest sense, because all steps of biomedical and behavioral research, from basic to translational to clinical, can inform other areas. For example, findings in clinical research can provide new areas of inquiry in basic science.

Figure 2-1. NIH Supports the Full Continuum of Biomedical Research

Step 1. The research continuum begins with basic research, the study of the fundamental mechanisms of biology and behavior. Investments in basic biomedical and behavioral research make it possible to understand the causes of disease onset and progression. Basic research is essential to the development of better diagnostics, the design of preventive interventions, and the discovery of new treatments and cures. Thus, basic research is a critical component of the nation’s public investment in research and a central feature of NIH’s research program.

In the past, most basic science projects in biomedicine required investigators to limit the scope of their studies to a single aspect of cell biology or physiology. With the advent of technologies that can automate research techniques at rapid speed (e.g., high throughput technology), the revolution now sweeping the field is the ability to be comprehensive (i.e., the genes of the human or a model organism, the human proteins and their structures, the common variations in the genome, the major pathways for signal transduction in the cell, the patterns of gene expression in the brain, the steps involved in early development, and the components of the immune system). Technologies contributing to these advances, many of which have moved from the development stage to broad use across the research community in the last few years, include DNA sequencing, microarray technology, nanotechnology, new imaging modalities, and computational biology.

Step 2. Realizing the benefits of fundamental biomedical discoveries depends on the translation of knowledge into the development of new diagnostics, therapeutics, and preventive measures. NIH is a key supporter of early (preclinical) translational research—studies that serve as a bridge between basic research and human medicine. The early translational stage applies fundamental laboratory discoveries to the preclinical development of studies in humans. Such early translational investigations often are carried out using animal models, cultures, samples of human or animal cells, or a variety of experimental systems, such as computer-assisted modeling of disease progression and drug therapy.

This is an extraordinarily exciting time to advance translational science and speed the development of new cures. Through the application of genomic research and high throughput technologies, breakthroughs in understanding of the causes of many diseases and the identification of new targets and pathways for the development of new therapeutics are within reach. Coupled with these advances, progress in technology and other fields of biomedical research have advanced the potential for development of new diagnostics and treatments for a wide range of diseases, opening a door of opportunity in translational science.

Step 3. Medical advances arise from rigorous testing of new strategies for recognizing and intervening on disease processes, whether intervention occurs before it manifests (prevention) or after it takes hold (treatment). Clinical research is patient-oriented research that is conducted with human subjects (studies that involve direct interaction between investigators and human subjects or the use of material of human origin, such as tissues, specimens, and data that retain information that would allow the investigator to readily ascertain the identity of the subject). Clinical research includes clinical trials, behavioral and observational studies, and the testing and refinement of new technologies.

Clinical trials, a crucial subset of clinical research, provide the best method to determine whether diagnostics and interventions are safe and effective in people and to assess side effects or other complications. There are many different types of trials that are designed to answer specific research questions about a biomedical or behavioral intervention. For example, treatment trials might test experimental drugs or devices, new combinations of drugs, innovative approaches to surgery or radiation therapy, or behavioral interventions such as exercise training or medication adherence. Prevention trials test the effectiveness of approaches to prevent diseases or other adverse health conditions, or to keep them from recurring. Comparative effectiveness research entails real-world comparisons of known interventions. Screening and diagnostic trials are conducted to find better ways to detect or diagnose diseases or conditions. Finally, quality-of-life trials (or supportive care trials) explore ways to improve people’s comfort and ability to continue the activities of daily life even as they deal with chronic illnesses or approach the end of life.

Additionally, NIH supports clinical and translational studies unlikely to garner substantial investment by other sources because of insufficient financial incentives. For example, studies that address rare diseases are unlikely to be conducted by for-profit entities because of the small number of patients that will make use of new interventions.

Step 4. In order for evidence-based research to have an impact on public health, NIH must ensure that new diagnostics and interventions reach the populations that need them most: patients, families, health care providers, and the broader public health community. The late (postclinical) translational stage takes results from studies in humans and optimizes them to have broad applicability. For example, NIH supports research that will identify factors that enhance access to and implementation of new interventions. Studies in this area include the development and testing of novel models and methods to best implement newly discovered interventions in order to reach diverse groups and populations (e.g., racial/ethnic groups, rural populations). The focus of health services research is on optimizing the health care delivery system to reflect the latest medical advances.

Step 5. As an important part of NIH’s mission, each IC engages in a broad-based effort to ensure that scientific findings are communicated rapidly and clearly to the public. However, simply communicating scientific breakthroughs and the availability of new treatments does not assure that they will be adopted in common medical practice. Nor does simply communicating research results ensure that these results will be used to inform policy making. In addition to its communication efforts, NIH works with many partners to bring the rich evidence base of NIH research into clinical and community practice, both in terms of treatment and prevention, and in policy-making that affects public health. These partnerships include all those engaged in improving health and reducing the burdens of disease, including many federal partners both within HHS (e.g., FDA, CDC) and outside the Department (e.g., Veteran’s Administration, Department of Defense). NIH also partners with non-governmental agencies, scientific organizations, patient advocacy groups, and healthcare delivery systems. These partnerships provide the American public with a healthcare system that will enhance health, lengthen life, and reduce the burdens of illness and disability.

Step 6. As mentioned above, the course of NIH research is not a true continuum, because it does not necessarily progress stepwise, nor does it move in only one direction. All areas of biomedical and behavioral research, from basic to translational to clinical, inform and influence other areas. Basic research scientists provide clinicians with new tools for use with patients, and clinical researchers make new observations about the nature and progression of disease that often produce feedback to stimulate new basic investigations. Research on new outreach approaches and the comparative effectiveness of prevention and treatment strategies not only address the feasibility of the strategies themselves, but in turn inform the development of future interventions.

In the process of translating basic research into clinical practice, NIH supports the development of research technologies, which provide innovative tools that are used at multiple points in the continuum and often provide the means for an exchange of information. With continued advancements in high-throughput methods, computing technologies that rapidly analyze increasing amounts of data, and inter-related bioinformatics platforms, NIH researchers across the spectrum are able to share technologies that were only dreamed of a few years ago.