Health-Related Research
A portion of federal income taxes are assigned to a government agency
known as the Department of Health and Human Services. The Appropriations
Committee and sub-committee within the United States House and
Senate, fund this entity. Within this overall organization are several
different sub-agencies - one of which is the National Institutes of
Health (NIH). The NIH conducts basic and applied research which
covers every aspect of human health and any living organisms which may
harm or help human health. Each year, the NIH is funded to maintain
this effort. There are two general kinds of research which are
supported - basic and applied research. Basic research involves
investigations of the biochemical mechanisms of living cells, organ
systems and non-human organisms which are specifically related to human
health. Applied research is research which uses the information obtained
from basic research to come up with ways to apply the information to a
particular procedure and/or treatment.
General Organization of the NIH
There are presently 14 institutes which comprise the National
Institutes of Health. Each institute is organized to provide a specific
focus related to a given aspect of human health research. (You may
wish to take a quick look at the complete list of institutes:
Individual Institutes of the National Institutes
of Health).
The NIH Budget
According to the Division of Research Grants document "trends
'94"
(Please see: NIH Extramural
Awards)
"The total NIH budget was $10.9 billion in Fiscal-Year
1994. The distribution of this amount was as follows: 83 percent to
extramural awards (direct and indirect costs), 11 percent to intramural
research, and 6 percent to management costs, buildings and facilities,
interagency agreements, and other services." The present requested
budget for the next FY is approximately $12 billion. At the end of this
article I will provide some relative perspective for this
seemingly exorbitant amount of money our government spends on this kind of
research.... you may be surprised.... and I hope, at least a little
appreciative. To paraphrase the great Sir Winston Churchill, in my
opinion, never have so few, done so much, for so many, with so little.
A Little History
In Europe, there had been for many years an organized system of institutes
associated with university structures which governments funded for all
kinds of research efforts. Unlike European systems, however, within
the United States prior to the late 1940's there was a very disorganized
effort among scientists to engage in any kind of
basic research. Then, after World War II, the government of the United
States established what is known as the National Institutes of Health
(NIH). This interconnected system of individual institutes was established and
funded to engage in basic and applied research to examine the causes of
human disease, and to provide methodology for treatment of disease based
upon the research findings. The National Institutes of Health are presently
located in Bethesda, Maryland.
A broad-based system was organized to inter-link scientists who worked within each of the institutes to scientists employed at universities across the nation. This structure was established to allow essentially equivalent probability of distribution of money and research effort among the various institute scientists, but more importantly, also among the various states. There was a particular recognition of the importance of providing a mechanism to rapidly disseminate research findings throughout the nation via educational instruction by faculty of undergraduate and graduate students - with these faculty members being the very people who would perform the research. So, unlike the most common European system of research institutes, the vast majority of scientists in our country are located all over the place within the various universities throughout our nation. Because of this arrangement, the entire nation rapidly receives information from all of the work being performed, and students receive new findings almost as soon as the data are accumulated.
To effect such a system, funding power was given to each of the institutes such that individual investigators at each research-oriented university throughout the country could compete for research money through submission of a grant proposal to the institute most suited for the type of research in which an investigator was engaged. Unlike the European system in which funds are provided to an institute and disseminated among the researchers within that same institute, obtaining an award is not automatic within our system. Each investigator who wishes to perform research in our country must compete with many other investigators for any money available; and, the decision as to whether or not to make an award is based entirely upon the perceived scientific merit of the proposal, as judged by accomplished scientists in the field. These scientists - peer reviewers - are selected after they are reviewed at the NIH, on the basis of their individual expertise and scientific accomplishments. These scientists receive very little compensation for this work - only travel, food, and lodging costs to attend formal meetings. There is no compensation for any work done prior to or after any of these meetings which are held several times per year.
The Individual Basic-Research Investigator
I will use, as an example, my own experience. When my university hired
me as an Assistant Professor in the Department of Microbiology, I was
hired under the condition that I would spend a certain percentage of my
time in each of three areas: teaching, performing basic research, and
performing service to my department and the university. At the time I
was hired, I had by then received a B.S. degree (4 years - Forestry), an
M.S. degree (2 years- Plant Physiology) a Ph.D. degree (4 years -
Biochemistry) and had completed 3 additional years of post-doctoral
study in immunochemistry. To establish and maintain an on-going
research program, I submit grant proposals to the NIH because my
choice of research is in the discipline of immunology (study of the
immune system). The particular institute to which I and others who
investigate the immune system submit proposals is the National
Institute of Allergy and Infectious Diseases (NIAID). If a proposal is
submitted by an individual investigator, it is called an RO1 proposal
(submission of proposed research
by an individual investigator outside the NIH
structure - one specific kind of extramural proposal). If the grant is
funded, it is called an RO1 Extramural Award (there are other non-RO1
extramural awards which may go to collections of investigators or
programs). The system works on a peer-review basis, as follows:
The Research Proposal
As Principal Investigator, I am personally responsible for writing the
proposal, the organization of the proposal, the establishment of the
annual budget for each year of the proposal, and, I am required to
assume complete financial and ethical responsibility for the work, data
collection, personnel involved, publications which may occur, and the
use of any funds which may be awarded.
The grant proposal includes: (1) an abstract of the work to be performed; (2) complete budget information for each of the years (usually 3-5) for which funding is sought; (3) complete information on each individual associated with the research, e.g., a complete curriculum vitae which shows education, publications, previous and/or current funded research, and a precise description of individual duties and responsibilities, and a statement that none of the proposed research is already funded by a different source, and a list of all funding sources to which the present proposal may also be submitted; (4) a background/significance section which thoroughly describes completely referenced previous published results of other investigators, which relate these data to the proposed research, and a detailed argument in support of the merit of the proposed research; (5) a preliminary data section which provides detailed information on all related work already accomplished by the person submitting the proposal; (6) a research plan which describes in detail the order and methodology of all of the proposed experiments to be conducted over the entire period - usually 5 years worth of designed experiments - which must include, predicted outcomes, any pitfalls and/or possible difficulties which may be encountered, experiments designed to resolve these difficulties, and their predicted outcomes; and, (7) individual university committee-approved Principal Investigator and Committee Chairperson sign-off documentation attesting to: (a) the proper use of any experimental animals involved - including detailed descriptions of exactly what will be done; (Institutional Animal Care and Use Committee); (b) the proper use of any radioactive materials - including exactly what will be used and how the isotopes will be handled, stored, accounted for (University Radioisotope Committee); (c) the proper use and disposal of any hazardous chemicals (University Biohazard Committee); and, (d) the protocols for any human research involved - including a copy of the consent form and methodology to be used (University Advisory Committee on Human Experimentation).
The Research Proposal Review Process
Once all of these items have been completed, the proposal is
first examined by the chairperson of my department, who signs a document
to the effect that laboratory space, equipment, and departmental support
services are indeed available, and that proper procedures will be
followed with respect to any hazardous materials and/or radioisotopes
involved. The proposal then journeys to the university's Office of
Research Support where administrative personnel with oversight
responsibility for all proposals which originate within the university,
examine the budget in detail, review all of the appropriate committee
approvals, examine all of the personnel noted, check to see if the
chairperson of the unit involved has approved the document, and if all
information is correct, the head of The Office of Research Support signs the
face-page of the document. Then, several copies of the proposal are
mailed to the Division of Research Grants at the NIH in Bethesda,
Maryland. Once received, the Division of Research Grants personnel
examine the proposal and assign the proposal to the appropriate
institute for peer review by one of several review groups
within the institute called "Study Sections."
These study sections are individually organized to examine specific research sub-areas within the overall institute's focus area. Each study section is chaired by an Executive Secretary, who is responsible for all of the documentation of the study section, a panel of reviewers which is comprised of individual scientists who are experts in the field (peers), and a President of the study section selected from the members of the review panel by the NIH. Three to four times per year, each grant proposal received at the NIH during a particular cycle is mailed to these review-panel members several months prior to the meeting of the panel for that given cycle. An individual study section member will be assigned (by the Exec Sec) the proposals which contain research with which the study section member is most familiar. Sometimes, ad hoc "outside" reviewers are also asked to review a particular proposal.
These reviewers write a thorough, detailed review/criticism of each section of the assigned proposal, and an overall review summary of each proposal. Each review panel member will be assigned as either a Primary, Secondary, or Tertiary reviewer of several different proposals. A copy of each critique is given to the Executive Secretary, and the Primary reviewer for a particular proposal will be the first to orally present the review to the entire study section at a formal meeting. Then, each secondary and tertiary reviewer will present their completely independently-derived critiques of the same proposal. After these presentations, any other independent ad hoc reviews will be read to the panel by the Executive Secretary. After each proposal is presented in turn, and after discussion of the proposed work by the entire study section, each member of the study section votes independently by secret ballot as to their estimation of the merit of the proposed work - the scale is 1.00 (perfect) to 5.00 (lousy). The votes are recorded, but no person knows the other's vote. After the meeting, these votes are tabulated, averaged, and the average score ultimately establishes the relative priority of each of the proposals reviewed at the meeting (there are several such meetings throughout each year). As mentioned above, the scores may range within 0.1 points between 1.00 and 5.00.
The Funding Process
After all of the scores for all of the grants reviewed by
all of the study sections are summarized for the particular
submission date, these scores and critiques of each proposal are
individually examined at a higher level by a Council composed of
investigators and NIH administrators. Any perceived discrepancies, as
for example, a very good score but a lousy summary critique, or, a very
poor score and an excellent summary critique may call for yet another
independent review of a particular proposal. After all of these efforts
are made, funds are distributed from top score down until the money runs
out for that particular time-period for that particular institute. The
worst priority score which is funded establishes the "cut-off"
point - the minimum score - necessary for funding for that particular
go-'round.
Because of the vagaries of human decision-making and estimations of quality, the individual scores for all of the grants reviewed among all of the institutes are cross-compared, normalized, and a percentile ranking is assigned. This treatment of the scoring data helps to normalize the scoring distribution within and among study sections for all institutes. Therefore, if a particular study section on average tends to give lower numbers (better rating) routinely, this tendency is somewhat balanced by consideration of the tendency for a different study section to give higher numbers (worse rating). Consequently, each investigator, regardless of study section scoring tendencies, has an even chance for comparison. Too, each study section member's scores are averaged and a record kept of the scoring tendency of this particular study section member. All of these efforts are attempts to, as closely as possible, assure a fair and equitable review, and a fair and equitable probability of funding the proposal. Presently, the NIAID "cut-off" percentile ranking is around the 90th percentile - meaning - the proposal must rank in the top 10% to have a chance for funding. This percentile ranking approximately equates to a priority score of less than 1.20 - remember, a perfect grant would be 1.00. So - it's pretty competitive... <grin>.
What Happens to the Money if the Proposal is Funded?
In my experience, there are significant misconceptions about where the
money goes and how the money is used if a research proposal is funded.
One misconception is that awarded monies can be used to paint my
house, or used by me to buy a new car, or used by me to
increase my salary compensation... Nothing could be further
from the truth...
If funded, the money is not awarded to me per se, but rather in my name to the institution at which I am employed. While the use of any awarded funds is restricted - meaning that I am the only person who has the authority to spend the money, I am not allowed to use any of the money whatsoever for personal use, with the exception that my salary may be paid from grant funds if the university does not pay such a salary while I am working on the research involved. For example, The University of Kansas pays on the basis of a 9-month academic year. Non-administrative staff (like me) are not paid during the 3 summer months; therefore, any work on the proposed research during the summer can be supported by salary requested as a line-item within the proposal. The amount of salary requested, however, cannot exceed my University's normal, monthly pay rate to me. Too, the awarding of such PI salary funds as a part of the proposal's overall budget, is not automatic.
The funds which may be requested in a proposal are listed in very specific categories - called lines (line items within the overall budget - any of which may be "vetoed" <grin>. Such as:
1. Personnel - may include the PI's summer salary, and any co-investigator salary (summer), will include a research technician salary (12 month), graduate students' salaries (12 month), and any post-doctoral students' salaries (12 months). Included in the salary is money for fringe benefits (health insurance, social security, and the like). Every single person must be justified with respect to the duties, responsibilities, and individual contribution to the proposed work.
2. Equipment - each piece of equipment must be itemized, the cost provided, and a complete justification for the need for each piece of equipment.
3. Consumable Supplies - all glassware, plasticware, reagents, radioisotopes, disposable gloves, serum, cells, cell-culture reagents, filters, gel reagents, chromatography reagents (gel, molecular sieve, and ion-exchange), x-ray film, enzymes, and everything else expendable, must each be listed with the estimated annual costs itemized.
4. Experimental animal costs - the annual cost of all animals (if any) which are to be housed, fed, and medically cared for must be listed and justified as to the need in the research.
5. Consultant - a request for monetary compensation for any person who contributes to the proposed research by intellectual contributions, reagent contributions, etc., is allowed.
6. Professional Travel - a request may be made for a sum of money to cover the annual cost of one domestic meeting (within the United States) for the PI, Co-Investigator and other professional personnel (graduate student, post-doc) to present research findings.
The majority of funds requested is usually for equipment, supplies, and graduate student salaries. Some PI's do not request summer salary, even though it is allowed, but instead request graduate student support. None of the money in non-salary lines may be converted to a salary line. Money in salary lines may be, with approval from the NIH, converted to non-salary items if justification is thoroughly and adequately provided - as in the case of someone leaving in mid-year due to an emergency, or by choice, etc., and the use of the funds for equipment and/or supplies for experiments can be justified. Therefore, as there should be, there are very strict regulations with respect to the use of these funds.
A Perspective
You may not realize that the entire NIH-funded extramural research
effort to maintain our population's health and welfare, is performed by
only about 30,000 investigators, and only 35,000 awarded grants! These
grants are spread here and there across the nation at any given time.
There are 270,000,000 people in the US - which means that only one-tenth of one
percent of the population is doing this work - BUT, there are only about
6,500 RO1 new and competitive NIH renewals awarded per year (a competitive
renewal means an initial multi-year award, but at the end of the
next-to-last year, one must "pass muster" again in order to
receive additional years of support requested). Therefore, 6,500/270,000,000
means that only 2-thousandths of one percent of the entire nation's
population in any given year is receiving new funds to do the work
which helps us to stay alive in this old world! - work over only the
past 50 years which has significantly increased the longevity of
human life in this country, which has significantly increased the
longevity of many cancer patients, significantly decreased the risk of
death due to heart disease, led to extraordinary advances in infectious
disease therapy and prevention, the elimination of smallpox from the
entire planet, the apparent elimination of polio from North, Central and
South America (not one case of polio in the past 4 years), the ability to
save lives by routinely performing organ transplantation, the
development of several new vaccines which prevent birth defects, and
which save children as well as adults from terrible harm - all of
these wonderful things. Remember that the first use of
antibiotics was only 50 years ago! And, the structure of DNA and the
function of genes was not even remotely understood until about 40
years ago! Also, even as late as the 1930's women were accused of causing
birth defects because of "bad thoughts!" There has been
astonishing progress over a very short period of time, because of all
of the efforts of these relatively few scientists. Please see:
The National Institutes of
Health, and please scroll to the paragraph: "WHAT IMPACT HAS THE
NIH HAD ON THE HEALTH OF THE NATION?"
A Relative Comparison
Now, here is one way to look at the NIH budget - the budget which is
paying for research on maintaining your health, your family's health, and
your friends' health. Remember, there are 14 different institutes, with
a total budget among them of approximately $11 billion. Wow! - you may
say. Well, take a gander at this: Eighty-three percent of the
approximately $11 billion was for all Extramural Awards
($9.1 billion)... and, RO1 (individual investigator awards) accounted
for 44% of this amount = $4 billion. Now, let's pretend that this
$4 billion was equally distributed among the 14 institutes; therefore,
$4 billion divided by 14 = $0.286 billion (less-than 1/3 of $1 billion
per institute). And, let's also pretend that the 30,000 investigators
are equally distributed among these institutes - therefore, 30,000/14 =
approx 2,143 investigators/institute. Therefore, $0.286 billion/2,143 =
$133,457 per investigator - this sum includes around, say, 33% due to
what are called indirect costs - additional money above the amount
the investigator requested, which is paid to the institution to aid in
administration of the research - things such as electricity, water, and
the like. These indirect costs then, are provided to the university to
prevent any cost to the university for the research; the investigator is
not allowed to use this money directly. So, the investigator is
allowed approximately $100,000/year to do this work. For your
information, one centrifuge may cost $15,000.00; and, 500 milliliters
(ml), which is approximately one pint, of serum for cell-culture may cost
$350.00.
Now, please take a look at the following comparison - keeping in mind that our example investigator will be receiving $100,000 per year for research.
The cost of a single B-2 Stealth bomber (several are on order) is
$2.2-billion - yep - $2.2 billion for only one such airplane. For
some idea of what $2.2 billion represents, our example investigator could
receive that $100,000 per year
And, you will please note that the entire NIH budget is
only 5-fold greater than the cost of only one of these airplanes.
Further, the nation's federal budget proposed spending for 1995 was:
So, as I said above, "in my opinion, never have so few, done so much, for so many, with so little." Heck, it was only about 1,000 years ago that the Viking leader, "Eric the Red" was still tooling around looking for a place to hide and exclaiming all the while to his son, Lief, that Vinland was surely somewhere to be found! And I will guarantee that old Eric had no idea about the use of ß-blockers, stem cell transplantation, or the DPT (diphtheria, pertussis, and tetanus) vaccination for infant Lief <grin>.
Individual Institutes of the National Institutes of Health
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
National Institute on Aging (NIA)
National Institute of Allergy & Infectious Diseases (NIAID)
National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS)
National Institute on Drug Abuse (NIDA)
National Institute on Deafness and Other Communication Disorders (NIDCD)
National Institute of Dental Research (NIDR)
National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK)
National Institute of Environmental Health Sciences (NIEHS)
National Eye Institute (NEI)
National Institute of General Medical Sciences (NIGMS)
National Institute of Child Health & Human Development (NICHD)
National Heart, Lung & Blood Institute (NHLBI)
National Institute of Mental Health (NIMH)
National Institute for Nursing Research (NINR)
National Institute of Neurological Disorders & Stroke (NINDS)
National Cancer Institute (NCI)
Book: Don't Touch That Doorknob!