National Institutes Of Health - Clinical Trial Budget

The National Institutes of Health (NIH) is a biomedical research facility primarily located in Bethesda, Maryland. An agency of the United States Department of Health and Human Services, it is the primary agency of the United States government responsible for biomedical and health-related research. The NIH both conducts its own scientific research through its Intramural Research Program (IRP) and provides major biomedical research funding to non-NIH research facilities through its Extramural Research Program.

With 1,200 principal investigators and more than 4,000 postdoctoral fellows in basic, translational, and clinical research, the IRP is the largest biomedical research institution in the world, while, as of 2003, the extramural arm provided 28% of biomedical research funding spent annually in the U.S., or about US$26.4 billion.

The NIH comprises 27 separate institutes and centers that conduct research in different disciplines of biomedical science. The IRP is responsible for many scientific accomplishments, including the discovery of fluoride to prevent tooth decay, the use of lithium to manage bipolar disorder, and the creation of vaccines against hepatitis, Haemophilus influenzae (HIB) and human papillomavirus (HPV).

History

NIH's roots extend back to a Marine Hospital Service in the late 1790s that provided medical relief to sick and disabled men in the U.S. Navy. By 1870, a network of marine hospitals had developed and was placed under the charge of a medical officer within the Bureau of the Treasury Department. In the late 1870s, Congress allocated funds to investigate the causes of epidemics like cholera and yellow fever, and it created the National Board of Health, making medical research an official government initiative.

In 1887, a laboratory for the study of bacteria, the Hygienic Laboratory, was established at the Marine Hospital in New York. In the early 1900s, Congress began appropriating funds for the Marine Hospital Service. By 1922, this organization changed its name to Public Health Services and established a Special Cancer Investigations laboratory at Harvard Medical School. This marked the beginning of a partnership with universities. In 1930, the Hygienic Laboratory was re-designated as the National Institute of Health by the Ransdell Act and was given $750,000 to construct two NIH buildings. Over the next few decades, Congress would increase its funding tremendously to the NIH, and various institutes and centers within the NIH were created for specific research programs. In 1944, the Public Health Service Act was approved, and National Cancer Institute became a division of NIH. In 1948, the name changed from National Institute of Health to National Institutes of Health.

In 1967, the Division of Regional Medical Programs was created to administer grants for research for heart disease, cancer, and strokes. That same year, the NIH director lobbied the White House for increased federal funding in order to increase research and the speed with which health benefits could be brought to the people. An advisory committee was formed to oversee further development of the NIH and its research programs. By 1971, cancer research was in full force and President Nixon signed the National Cancer Act, initiating a National Cancer Program, President's Cancer Panel, National Cancer Advisory Board, and 15 new research, training, and demonstration centers.

The funding of NIH has often been a source of contention in Congress, serving as a proxy for the political currents of the time. This contention was seen most dramatically during the 1980s, when President Reagan repeatedly tried to cut funding for research, only to see Congress partly restore funding. The political contention over NIH funding slowed the nation's response to the AIDS epidemic; while AIDS was reported in newspaper articles from 1981, no funding was provided for research on the disease. In 1984, National Cancer Institute scientists found implications that "variants of a human cancer virus called HTLV-III are the primary cause of acquired immunodeficiency syndrome (AIDS)," a new epidemic that gripped the nation. But it was not until July 1987, as NIH celebrated its 100th anniversary, that President Reagan announced a committee to research the HIV epidemic.

By the 1990s, the focus of the NIH committee had shifted to DNA research, and the Human Genome Project was launched. In 2009, President Obama reinstated federally funded stem-cell research, revoking the ban imposed by President Bush in 2001.

From logistical restructuring, to funding increases, to research prioritization, to government expansion and political influence, the history of the National Institutes of Health is extensive and full of change. The NIH has grown to encompass nearly 1 percent of the federal government's operating budget. The NIH now controls more than 50 percent of all funding for health research, and 85 percent of all funding for health studies in universities.

5 Common Clinical Trial Budgeting Mistakes to Avoid

NIH Directors

• Joseph J. Kinyoun, served August 1887 - April 30, 1899
• Milton J. Rosenau, served May 1, 1899 â€" September 30, 1909
• John F. Anderson, served October 1, 1909 â€" November 19, 1915
• George W. McCoy, served November 20, 1915 â€" January 31, 1937
• Lewis R. Thompson, served February 1, 1937 â€" January 31, 1942
• Rolla Dyer, served February 1, 1942 â€" September 30, 1950
• William H. Sebrell, Jr, served October 1, 1950 â€" July 31, 1955
• James Augustine Shannon, served August 1, 1955 â€" August 31, 1968
• Robert Q. Marston, served September 1, 1968 â€" January 21, 1973
• Robert Stone, served May 29, 1973 â€" January 31, 1975
• Donald S. Fredrickson, served July 1, 1975 â€" June 30, 1981
• James B. Wyngaarden, served April 29, 1982 â€" July 31, 1989
• Bernadine Healy, served April 9, 1991 â€" June 30, 1993
• Harold E. Varmus, served November 23, 1993 â€" December 31, 1999
• Elias A. Zerhouni, served May 2, 2002 â€" October 31, 2008
• Francis S. Collins, served August 17, 2009 â€" Present

Locations and campuses

Intramural research is primarily conducted at the main campus in Bethesda, Maryland, and the surrounding communities. The National Institute on Aging and the National Institute on Drug Abuse are located in Baltimore, Maryland, and the National Institute of Environmental Health Sciences is located in the Research Triangle region of North Carolina. The National Institute of Allergy and Infectious Diseases maintains its Rocky Mountain Labs in Hamilton, Montana, with an emphasis on BSL3 and BSL4 laboratory work.

Research

NIH devotes 10% of its funding to research within its own facilities (intramural research). The institution gives 80% of its funding in research grants to extramural (outside) researchers. Of this extramural funding, a certain percentage (2.8% in 2014) must be granted to small businesses under the SBIR/STTR program. The extramural funding consists of about 50,000 grants to more than 325,000 researchers at more than 3000 institutions. In FY 2010, NIH spent US$10.7bn (not including temporary funding from the American Recovery and Reinvestment Act of 2009) on clinical research, US$7.4bn on genetics-related research, US$6.0bn on prevention research, US$5.8bn on cancer, and US$5.7bn on biotechnology.

Public Access Policy

In 2008, a Congressional mandate called for investigators funded by the NIH to submit an electronic version of their final manuscripts to the National Library of Medicine's research repository, PubMed Central (PMC), no later than 12 months after the official date of publication. The NIH Public Access Policy was the first public access mandate for a U.S. public funding agency.

NIH Interagency Pain Research Coordinating Committee

February 13, 2012 the National Institutes of Health (NIH) announced a new group of individuals assigned to research pain. This committee is composed of researchers from different organizations and will focus to "coordinate pain research activities across the federal government with the goals of stimulating pain research collaboration… and providing an important avenue for public involvement" ("Members of new," 2012). With a committee such as this research will not be conducted by each individual organization or person but instead a collaborating group which will increase the information available. With this hopefully more pain management will be available including techniques for arthritis sufferers.

NIH Toolbox

In September 2006, a contract for the NIH Toolbox for the Assessment of Neurological and Behavioral Function (www.nihtoolbox.org) was initiated by the NIH Blueprint for Neuroscience Research (www.neuroscienceblueprint.nih.gov) to develop a set of state-of-the-art measurement tools to enhance collection of data in large cohort studies and to advance the biomedical research enterprise. The NIH Toolbox was officially rolled out to the research community on September 10â€"11, 2012 at a public conference "Unveiling the NIH Toolbox" held in Bethesda, Maryland and Washington, D.C. Scientists from more than 100 institutions nationwide contributed to the development of the NIH Toolbox. The construction of NIH Toolbox assessments is based, where possible, on Item Response Theory and adapted for testing by computer.

Economic impact

In 2000, a report from a Joint Economic Committee of Congress outlined the benefits of NIH research. It noted that some econometric studies had given its research, which was funded at $16 billion a year in 2000, a rate of return of 25 to 40 percent per year. It also found that of the 21 drugs with the highest therapeutic impact on society introduced between 1965 and 1992, public funding was "instrumental" for 15.

Funding

To allocate funds, the NIH must first obtain its budget from Congress. This process begins with institute and center (IC) leaders collaborating with scientists to determine the most important and promising research areas within their fields. IC leaders discuss research areas with NIH management who then develops a budget request for continuing projects, new research proposals, and new initiatives from the Director. NIH submits its budget request to the Department of Health and Human Services (HHS), and the HHS considers this request as a portion of its budget. Many adjustments and appeals occur between NIH and HHS before the agency submits NIH's budget request to the Office of Management and Budget (OMB). OMB determines what amounts and research areas are approved for incorporation into the President's final budget. The President then sends NIH's budget request to Congress in February for the next fiscal year's allocations. The House and Senate Appropriations Subcommittees deliberate and by fall, Congress usually appropriates funding. This process takes approximately 18 months before the NIH can allocate any actual funds.

NIH employs five broad decision criteria in its funding policy. First, ensure the highest quality of scientific research by employing an arduous peer review process. Second, seize opportunities that have the greatest potential to yield new knowledge and that will lead to better prevention and treatment of disease. Third, maintain a diverse research portfolio in order to capitalize on major discoveries in a variety of fields such as cell biology, genetics, physics, engineering, and computer science. Fourth, address public health needs according to the disease burden (e.g., prevalence and mortality). And fifth, construct and support the scientific infrastructure (e.g., well-equipped laboratories and safe research facilities) necessary to conduct research.

In 2007 the director of the agency stated "responsibilities for identifying ... FCOIs (financial conflict of interest) must remain with grantee institutions" but institutions that administer grants have no interest to identify grantee's conflicts of interest.

The NIH issued dozens of waivers for NIH's advisory committee members up to 2012. Such waivers exempt a conflicted government employee from ethics laws. Since 2005 the U.S. Office of Government Ethics had documented only three times where the NIH consulted with the office as required by law, and none of the waivers in question had to do with a member of an advisory committee. Advisory committee members advise the Institute on policy and procedures affecting the external research programs and provide a second level of review for all grant and cooperative agreement applications considered by the Institute for funding.

Recent changes

The NIH funding policy has changed in several significant ways over time. First, the amount of money given to the NIH has increased in hard dollars, although in relation to inflation and the increased expense of doing science, the funding levels are currently down. Most scientists know that in the history of the NIH, it is more difficult now to get R01 grant funding than ever before, let alone have them renewed. The scientific community concerns the low funding to be a crisis in America, and wonder how China can busily recruit our scientists who cannot stay funded given the lowered NIH funding levels without American realizing the great cost to this nation of not funding research. R01 Grants scored even in the top 20% are not being funded nowadaysâ€"and that 20% is after fifty percent of the grants are first triaged. So only five percent of grants are getting funded. And grants cannot be submitted more than two times.

However, in hard dollars, the funding appears to have gone up. For example, in 1999, Congress increased the NIH's budget by $2.3 billion. (to $17.2 billion in 2000) In 2009 Congress again increased the NIH budget to $31 billion in 2010. Second, with the creation of the various ICs, the responsibility to allocate funding to researchers has shifted from the OD and Advisory Committee to the individual ICs. Additionally, Congress increasingly sets apart funding for particular causes. In the 1970s, Congress began to earmark funds specifically for cancer research and in the 1980s there was a significant amount allocated for AIDS/HIV research. Congress has continued to play an active role in allotting funds for specified research. These are some of the most significant changes in NIH funding policy over the last century.

A few of the key issues in evaluating NIH funding policy were previously mentioned in the paper as the five criteria the NIH has established. Three of the criteria are particularly relevant. First, is the NIH ensuring the highest quality of research by fairly implementing their peer review process and allocating extramural research funds? Second, is the NIH maximizing opportunities to produce research that yields new knowledge that will lead to better disease prevention and treatment? Next, are public health needs being addressed according to the public disease burden; in other words, are the most important needs of society being met rather than those of special interest groups? These are the most important issues in evaluating NIH funding policy.

When a government shutdown occurs, the NIH continues to treat people who are already enrolled in clinical trials, but does not start any new clinical trials and does not admit new patients who are not already enrolled in a clinical trial, except for the most critically ill, as determined by the NIH Director.

In 2014, it was announced that the NIH is directing scientists to perform their experiments with both female and male animals, or cells derived from females as well as males if they are studying cell cultures, and that the NIH would take the balance of each study design into consideration when awarding grants. However, the announcement also stated that this rule would probably not apply when studying sex-specific diseases (for example, ovarian or testicular cancer).

Grant allocation bias controversy

In 2011, a paper published in Science found that black researchers were 10% less likely to win NIH R01 grants (the oldest and most widely used) than white researchers, after controlling for "educational background, country of origin, training, previous research awards, publication record, and employer characteristics." It also found that black researchers are significantly less likely to resubmit an unapproved grant than white researchers. The study lead and economist Donna Grant said that grant reviewers do not have access to the applicant race, but may infer it from biographies or names. She also speculated that the decreased re-submission rate may be due to lack of mentoring. The study, which was commissioned by the NIH, included in its analysis 83,000 grant applications, made between 2000 and 2006. Dr. Otis W. Brawley, chief medical officer at the American Cancer Society and a black man, commented on the cause of the disparity as one unrelated to racism per se, but rather to the reviewers' unconscious tendency to more likely give the benefit of the doubt to someone they are familiar with, in a scientific world where black researchers tend to keep a lower profile than other groups. The study did not reveal similar difficulties for members of other races and ethnic groups (e.g., Hispanics).

Stakeholders

Many groups are highly invested in NIH funding.

General Public

One of the goals of the NIH is to "expand the base in medical and associated sciences in order to ensure a continued high return on the public investment in research." Taxpayer dollars funding NIH are from the taxpayers, making them the primary beneficiaries of advances in research. Thus, the general public is a key stakeholder in the decisions resulting from the NIH funding policy. Congress theoretically represents the public interest as the NIH Advisory Committee allocates to the NIH, and the funds to the Director. However, many in the general public do not feel their interests are being accurately represented. As a result, individuals have formed patient advocacy groups to represent their own interests. Patient advocacy groups tend to focus on specific aspects of health care or diseases. Advocates get involved in many different areas such as organizing awareness campaigns, promoting patients' rights, and enhancing health policy initiatives. Most importantly, patient advocacy groups are often involved with advisory panels to ensure that current projects and those projects being considered for funding will directly impact patients' lives, improve delivery of care, and provide support for tertiary care. Advocacy groups strive to promote a health care system that is beneficial for all parties involved. Through congressional representation, NIH Advisory Committee efforts, and patient advocacy groups, the public is able to influence funding allocation as well as the policy itself.

Extramural Researchers and Scientists

Other important stakeholders of the NIH funding policy are the researchers and scientists themselves. Extramural researchers differ from intramural researchers in that they are not employed by the NIH but must apply for funding. Throughout the history of the NIH, the amount of funding received has increased, but the proportion to each IC remains relatively constant. The individual ICs then decide who will receive the grant money and how much will be allotted. Research funding is important to extramural researchers for multiple reasons. Without the help of an NIH grant (or a similar type of funding), researchers and scientists are unable to pursue their own research interests but are obliged to follow the agenda of the company or university for which they work. This could potentially hinder discoveries in novel research areas. In 2000, Brian Jacobs and Lars Lefgren researched extensively the impact of NIH grants on basic research and development, and the careers of grant recipients. For the period of 1980â€"2000, they reviewed all postdoctoral research grants and standard research grants for those who received funding and those who did not. Jacobs and Lefgren found that scientists who received postdoctoral research grants were 20 percent more likely to be published within the first five years after receiving the grant. They also found that scientists who received grants were 11 percent more likely to have one publication and 23 percent more likely to have five publications. Due to the 'publish or perish' standard that many researchers face, NIH funding can have a great impact on researchers' careers. Receiving a standard research grant also has a significant impact on researchers. Young scientists who receive a first-time grant (R01) usually produce more than one additional publication in the five-year period after they receive the grant. Those who receive an NIH grant will typically receive $252,000 more in NIH funding in the following six to ten years, and a statistically significant relationship exists between scientists receiving NIH grants and their research productivity throughout their careers.

Policy changes on who receives funding also significantly affect researchers. For example, the NIH has recently attempted to approve more first-time NIH R01 applicants, or the research grant applications of young scientists. To encourage the participation of young scientists who potentially think outside the box, the application process has been shortened and made easier. In addition, first-time applicants are being offered more funding for their research grants than those who have received grants in the past. Although this change provides greater opportunities for young scientists, it also places older, more experienced scientists at a funding disadvantage.

Commercial partnerships

In 2011 and 2012, the Department of Health and Human Services Office of Inspector General published a series of audit reports revealing that throughout the fiscal years 2000â€"2010, institutes under the aegis of the NIH, did not comply with the time and amount requirements specified in appropriations statutes, in awarding federal contracts to commercial partners, committing the federal government to tens of millions of dollars of expenditure ahead of appropriation of funds from Congress.

Institutes and Centers

The NIH is composed of 27 separate institutes and centers (ICs) that conduct and coordinate research across different disciplines of biomedical science. These are:

In addition, the National Center for Research Resources operated from April 13, 1962 to December 23, 2011.