This Program Announcement expires on October 1, 2004 unless reissued.

CHROMIUM AS ADJUVANT THERAPY FOR TYPE 2 DIABETES AND IMPAIRED GLUCOSE TOLERANCE

Release Date:  July 2, 2001

PA NUMBER:  PA-01-114

Office of Dietary Supplements
 (http://dietary-supplements.info.nih.gov/)
National Center for Complementary and Alternative Medicine
 (http://nccam.nih.gov/)
National Institute of Diabetes and Digestive and Kidney Diseases
 (http://www.niddk.nih.gov/)

THIS PA USES THE "MODULAR GRANT" AND "JUST-IN-TIME" CONCEPTS. IT INCLUDES 
DETAILED MODIFICATIONS TO STANDARD APPLICATION INSTRUCTIONS THAT MUST BE USED 
WHEN PREPARING APPLICATIONS IN RESPONSE TO THIS PA.

PURPOSE

The Office of Dietary Supplements (ODS), the National Center for 
Complementary and Alternative Medicine (NCCAM), and the National Institute of 
Diabetes and Digestive and Kidney Diseases (NIDDK) invite basic and clinical 
applications to study the role of chromium as adjuvant therapy in type 2 
diabetes and/or impaired glucose tolerance. 

The use of chromium supplements among individuals with diabetes is not an 
uncommon practice and the accumulating evidence from small, non-controlled 
clinical trials suggests that chromium supplementation may alleviate symptoms 
associated with diabetes and reduce the need for extraneous insulin in 
patients with type 2 diabetes. The results of a systematic review together 
with the findings from a scientific workshop conducted by the ODS have 
provided convincing reasons to support the conduct of small-scale, focused 
clinical studies. The potential mechanism of action of chromium in enhancing 
insulin secretion or action is not known. 

The purpose of this Program Announcement (PA) is to encourage 1) basic 
studies of chromium action on insulin secretory and signaling pathways and 2) 
clinical studies to assess the safety and efficacy of chromium as an adjuvant 
treatment of type 2 diabetes and/or impaired glucose tolerance.

HEALTHY PEOPLE 2010

The Public Health Service (PHS) is committed to achieving the health 
promotion and disease prevention objectives of "Healthy People 2010," a 
PHS-led national activity for setting priority areas. This Program 
Announcement, Chromium as Adjuvant Therapy for Type 2 Diabetes and Impaired 
Glucose Tolerance, is related to one or more of the priority areas. Potential 
applicants may obtain a copy of "Healthy People 2010" at 
http://www.health.gov/healthypeople/.

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic and foreign, for-profit and 
non-profit organizations, public and private, such as universities, colleges, 
hospitals, laboratories, units of State and local governments, and eligible 
agencies of the Federal government. Racial/ethnic minority individuals, 
women, and persons with disabilities are encouraged to apply as principal 
investigators.

MECHANISM OF SUPPORT

This PA will use the National Institutes of Health (NIH) Research Project 
Grant (R01) and Exploratory/Developmental Research Grant (R21) award 
mechanisms. Responsibility for the planning, direction, and execution of the 
proposed project will be solely that of the applicant. The total project 
period for an R01 application submitted in response to this PA may not exceed 
five years.

The R21 awards are to demonstrate feasibility and to obtain preliminary data 
testing innovative ideas that represent clear departure from ongoing research 
interests. These grants are intended to 1) provide initial support for new 
investigators; 2) allow exploration of possible innovative new directions for 
established investigators; and 3) stimulate investigators from other areas to 
lend their expertise to research within the scope of this announcement. 
Applicants for the R21 must limit their requests to $125,000 direct costs per 
year for a two-year period. These R21 grants are not renewable and may not be 
used to supplement an ongoing project. Applicants who anticipate submitting 
an R21 application should review the NCCAM web site at 
http://nccam.nih.gov/research/instructions/r21/index.htm
 
Continuation of projects developed under this program may be through the 
regular research grant (R01) program. Additional information on this 
mechanism may be obtained from the NIH web site (Research Grants, Application 
Guidelines) at http://grants.nih.gov/grants/forms.htm.
 
RESEARCH OBJECTIVES

Background

Diabetes is common, affecting 16 million people or 6.9% of the US adult 
population; 800,000 new cases are diagnosed each year. The Diabetes Control 
and Complications Trial (DCCT), for type 1 diabetes, and the United Kingdom 
Prospective Diabetes Study (UKDPS), for type 2 diabetes, established the 
importance of intensive diabetes control in dramatically reducing the 
devastating complications that result from poorly controlled diabetes.  Both 
the DCCT and the UKPDS demonstrated the efficacy of intensive glucose control 
in reducing the risk for the microvascular complications of diabetes, such as 
retinopathy, neuropathy, and nephropathy. In addition, results from the UKPDS 
suggested that strokes may be reduced in patients with type 2 diabetes 
through a combined regimen of intensive blood pressure and glycemic control.

Unfortunately, the advances of these studies have not been successfully 
incorporated into general health care practice. Prevention and treatment of 
long-term micro- and macrovascular complications remain critical problems in 
the management of type 1 and type 2 diabetes mellitus. In the United States, 
diabetes is the leading cause of new blindness in working-age adults, of new 
cases of end-stage renal disease and of non-traumatic lower leg amputations. 
In addition, cardiovascular complications are now the leading cause of 
diabetes-related morbidity and mortality, particularly among women and the 
elderly.  In adult patients with diabetes, the risk of cardiovascular disease 
(CVD) is three-to-five fold greater than in the general population. Diabetes 
is the seventh leading cause of death in the United States and costs the 
American economy approximately $98 billion annually. 

Type 2 diabetes is treated with diet, exercise and medication. However, for 
many patients, achievement of tight glucose control is difficult with current 
regimens. Given the enormous public health cost of diabetes, the prospect of 
being able to use a relatively low-cost dietary supplement, such as chromium, 
as an adjuvant therapy to help in achieving euglycemia merits further study. 
Despite the large gaps in our knowledge regarding chromium, the US public 
uses chromium supplements for the treatment of diabetes and its 
complications. This widespread use warrants extensive testing of its efficacy 
and monitoring of its safety for long-term use.

Chromium

Chromium remains the only essential transition metal whose mechanism of 
action is not known. Chromium is thought to play a role in normal 
carbohydrate metabolism by potentiating the action of insulin. Chromium may 
increase insulin binding to cells and insulin receptor number, as well as 
activate insulin receptor kinase, leading to increased insulin sensitivity.

Chromium exists in several valence states, the most prevalent oxidation 
states being hexavalent chromium (which is associated with industrial 
exposure and toxicity) and trivalent chromium (which is stable and the 
biologically active form). Chromium supplements are available as trivalent 
chromium in the chloride or picolinate salt form. Trivalent chromium also 
occurs in organic complexes with nicotinic acid. For purposes of this 
document, chromium will refer to trivalent chromium unless otherwise noted. 

The concentration of chromium in foods varies widely; there is also 
considerable variation between batches or lots of the same foods. Therefore, 
chromium intakes cannot be accurately predicted from dietary information. 
Survey data exist for a small number of isolated groups; however, no 
comprehensive studies exist determining intakes of individual subgroups.  No 
national survey data are available. Estimates of chromium intake from diet in 
the United States are roughly 25 ug for women and 33 ug for men, which are 
thought to be reflective of an adequate intake for the population. 

 The frequency of actual chromium deficiency in the general population is 
unknown; however, an intake level of 5 ug /1,000 kcal has been shown to 
deplete subjects in well-controlled studies.  Clinically, chromium deficiency 
has been well characterized in three patients who did not receive chromium in 
total parenteral nutrition solutions. Reliable measures for assessing 
chromium status in humans are limited. Chromium is present in biological 
tissues and fluids at extremely low levels, so many of the problems 
associated with finding a measure of status have been analytical in nature. 
Only three analytical techniques have the required sensitivity to make these 
measurements; however, neutron activation analysis and mass spectrometry are 
not widely available, and graphite furnace atomic absorption spectrometry is 
the one most susceptible to interference from the sample matrix. Collecting 
samples without contaminating them and generating sufficiently low analytical 
and reagent blanks is extremely difficult. Therefore, plasma chromium is 
unlikely to be a viable clinical indicator because it is easily contaminated. 
Additional investigation of urinary chromium in response to very low levels 
of intake is needed.

A putative chromium deficiency, as induced by feeding a chromium-deficient 
diet, has been reported in mammals and centers on disturbances involving 
insulin insensitivity.  The signs and symptoms of chromium deficiency in 
mammals include impaired glucose tolerance, elevated circulating insulin 
concentration, glycosuria, fasting hyperglycemia, impaired growth, 
hypoglycemia, elevated circulating cholesterol and triglyceride 
concentrations, neuropathy, decreased insulin binding, decreased insulin 
receptor number and impaired humoral immune response. 

Chromium Supplementation  in Diabetes

Several studies have suggested that chromium supplementation might be 
beneficial in individuals with glucose intolerance, type 2 diabetes, 
gestational diabetes or steroid-induced diabetes, as evidenced by decreased 
blood glucose values or decreased insulin requirements. However, randomized 
trials of chromium supplementation in diabetes have not been definitive. Many 
studies have not been blinded, have used inappropriate glucose metabolism 
assessment parameters, or have included heterogeneous and not well-
characterized patient populations. In addition, studies are difficult to 
compare because they have used different doses (ranging from 200 ug to 1000 
ug) and formulations of chromium (such as chromium rich yeast, chromium 
chloride, chromium picolinate and chromium nicotinate), and have been short 
in duration. More rigorous, blinded and well-controlled studies are needed to 
fully assess the efficacy and mechanism of action of chromium supplementation 
as an adjuvant therapy for type 2 diabetes and impaired glucose tolerance. 

Trivalent chromium, the form found in foods and dietary supplements, is 
believed to be safe. The Environmental Protection Agency established a 
reference dose (an estimate of daily exposure that is likely to be without 
appreciable risk of deleterious effect over a lifetime) for chromium that is 
350 times the estimated safe and adequate daily dietary intake.  Because of 
the widespread use of supplementation, more research is needed to assess the 
safety of high-dose chromium.  

Most reports of adverse events to the Food and Drug Administration involved 
chromium taken in conjunction with various herbal preparations or other 
pharmacological agents, which may have been responsible for the adverse 
events. In a recent review of 19 randomized controlled trials in which 
individuals received between 175 and 1,000 ug /day chromium for duration of 
between 6 and 64 weeks, there was no evidence of any toxic effects. However, 
there are data to suggest that individuals with preexisting renal and liver 
disease may be particularly susceptible to adverse effects from excess 
chromium intake.  There have been only a few confirmed case reports of 
toxicity attributed to chromium chloride and picolinate, including induced 
rhabdomyolysis and acute renal failure due to interstitial nephritis.  

In vivo genotoxicity assays for chromium and most studies of genotoxicity in 
cellular systems have been negative. Chromium picolinate is extremely stable, 
but concern has been expressed that reduction of chromium picolinate within 
cells could lead to the generation of hydroxyl radicals and potential DNA 
lipid damage.  In fact, a few studies suggest that chromium picolinate and 
tri-picolinate may cause DNA damage. Therefore, there is a need to consider 
the genotoxicities of a variety of chromium complexes particularly when high 
doses are administered.  

There are no human studies that report reproductive toxicity or fetotoxic 
effects with chromium supplementation, but animal studies suggest reduced 
fertility in male mice, a reduction in the number of implantation sites and 
the number of viable fetuses, and delayed sexual maturity.

In November 1999, the Office of Dietary Supplements (ODS) sponsored a 
workshop on Chromium and Diabetes 
(http://ods.od.nih.gov/news/conferences/chromium_diabetes.html),
to review studies of chromium supplementation in diabetes and identify 
priority research areas. Workshop members reached consensus that small-scale, 
focused clinical studies might be warranted in certain population groups. In 
addition, in a recent report, the Institute of Medicine (IOM) of the National 
Academy of Sciences also recommended the need for research related to 
chromium and diabetes. Research initiatives should be directed at 
investigating the possible relationships between chromium status and insulin 
resistance, impaired glucose tolerance, and type 2 diabetes; monitoring any 
adverse effects of self-supplementation; and design of controlled studies to 
assess potential beneficial, as well as, adverse effects of high-dose 
chromium supplementation (IOM, 2001).

As a follow-up to the workshop and prior to initiating clinical studies,  the 
ODS sponsored a systematic review and meta-analysis of published clinical 
trial reports evaluating the role of chromium in individuals with glucose 
intolerance or type 2 diabetes. The report concluded “there was strong 
evidence that chromium has no effect on glucose control in healthy subjects.”   
However, the data for patients with diabetes were found to be equivocal and 
pointed to the need for small, focused, clinical trials in glucose-intolerant 
and diabetic subjects.  These studies would further explore the efficacy of 
chromium as an adjunct treatment in type 2 diabetes and impaired glucose 
tolerance and determine the effective dose and formulation of chromium 
supplementation. In addition, they would provide additional information on 
the long-term safety of chromium supplementation.

Scope and Objectives

The purpose of this PA is to encourage 1) basic studies of chromium action on 
insulin secretory and signaling pathways and 2) clinical studies to assess 
the safety and efficacy of chromium as an adjuvant treatment of type 2 
diabetes and/or impaired glucose tolerance.

It is not the intent of this PA to support phase III clinical trials, as 
developmental studies are needed. The main objective of a full-scale, 
definitive phase III trial is to determine whether the intervention is more 
effective than that used in a control (or comparison) group. Also, this PA 
does not have as its primary focus case-control studies; health services 
studies, surveys or epidemiological studies. 

Appropriate topics for investigation under this PA include, but are not 
limited to:

o Studies to determine what form of chromium is present in the tissues, 
blood, and urine;

o Studies to determine factors that impact on chromium bioavailability;

o Studies to develop tests or biomarkers of chromium toxicity, both 
systemically and at the tissue 
level;

o Dose-response studies to delineate physiological versus pharmacological 
doses and responses to chromium supplementation;

o Studies to develop improved techniques for the analysis of chromium in 
biological fluids;

o Studies to develop tests or biomarkers that can be used to measure and 
monitor chromium status;

o Small, focused phase I and phase II clinical trials to determine the safe 
and effective dose and formulation of chromium supplementation in individuals 
with type 2 diabetes or impaired glucose tolerance; 

o Studies to establish clinically relevant biomarkers for assessing the 
efficacy of chromium supplementation in individuals with type 2 diabetes or 
impaired glucose tolerance; 

o Studies to elucidate the mechanisms by which chromium enhances insulin 
secretion or action;

o Studies to determine factors that predict response to chromium 
supplementation in individuals with type 2 diabetes or impaired glucose 
tolerance (e.g., diet, degree of insulin resistance or secretion, duration of 
diabetes);

o Studies to evaluate the effects of long-term use of chromium on iron 
status.

SPECIAL REQUIREMENTS

Phase I or II clinical trials must include provisions for assessment of 
patient eligibility and status, rigorous data management, quality assurance, 
and auditing procedures. Patient eligibility is limited to US residents since 
chromium status may vary by culture and geographic location. In addition, it 
is NIH policy that all clinical trials require data and safety monitoring, 
with the method and degree of monitoring being commensurate with the risks 
(NIH Policy for Data Safety and Monitoring, NIH Guide for Grants and 
Contracts, June 12, 1998: 
http://grants.nih.gov/grants/guide/notice-files/not98-084.html). 
The NIH has also released “Further Guidance on a Data 
and Safety Monitoring for Phase I and Phase II Trials, NIH Guide, June 5, 
2000: http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-038.html. In 
addition, NCCAM requires that all masked clinical trials, regardless of size, 
establish an independent data and safety monitoring board. The NCCAM Data 
Safety and Monitoring Guidelines for clinical trials are available at: 
http://nccam.nih.gov/research/policies/datasafety/index.htm Funds should be 
budgeted for these activities. They should not duplicate internal review and 
monitoring systems that are already in place at the institution.

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of the NIH that women and members of minority groups and 
their sub-populations must be included in all NIH-supported biomedical and 
behavioral research projects involving human subjects, unless a clear and 
compelling rationale and justification are provided indicating that inclusion 
is inappropriate with respect to the health of the subjects or the purpose of 
the research. This policy results from the NIH Revitalization Act of 1993 
(Section 492B of Public Law 103-43).

All investigators proposing research involving human subjects should read the 
UPDATED "NIH Guidelines for Inclusion of Women and Minorities as Subjects in 
Clinical Research," published in the NIH Guide for Grants and Contracts on 
August 2, 2000 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-048.html); 
a complete copy of the updated Guidelines is available at 
http://grants.nih.gov/grants/funding/women_min/guidelines_update.htm: The 
revisions relate to NIH defined Phase III clinical trials and require: a) all 
applications or proposals and/or protocols to provide a description of plans 
to conduct analyses, as appropriate, to address differences by sex/gender 
and/or racial/ethnic groups, including subgroups if applicable; and b) all 
investigators to report accrual, and to conduct and report analyses, as 
appropriate, by sex/gender and/or racial/ethnic group differences.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of NIH that children (i.e., individuals under the age of 21) 
must be included in all human subjects research, conducted or supported by 
the NIH, unless there are scientific and ethical reasons not to include them. 
This policy applies to all initial (Type 1) applications submitted for 
receipt dates after October 1, 1998.

All investigators proposing research involving human subjects should read the 
"NIH Policy and Guidelines" on the Inclusion of Children as Participants in 
Research Involving Human Subjects” that was published in the NIH Guide for 
Grants and Contracts, March 6, 1998, and is available at the following URL 
address: http://grants.nih.gov/grants/guide/notice-files/not98-024.html
  
Investigators also may obtain copies of these policies from the program staff 
listed under INQUIRIES. Program staff may also provide additional relevant 
information concerning the policy.

REQUIRED EDUCATION IN THE PROTECTION OF HUMAN RESEARCH PARTICIPANTS

All investigators proposing research involving human subjects should read the 
policy that was published in the NIH Guide for Grants an Contracts, June 5, 
2000 (Revised August 25, 2000), available at:  
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html. 

URLS IN NIH GRANT APPLICATIONS OR APPENDICES

All applications and proposals for NIH funding must be self-contained within 
specified page limitations. Unless otherwise specified in an NIH 
solicitation, internet addresses (URLs) should not be used to provide 
information necessary to the review because reviewers are under no obligation 
to view the Internet sites. Reviewers are cautioned that their anonymity may 
be compromised when they directly access an internet site.

PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT

The Office of Management and Budget (OMB) Circular A-110 has been revised to 
provide public access to research data through the Freedom of Information Act 
(FOIA) under some circumstances.  Data that are (1) first produced in a 
project that is supported in whole or in part with Federal funds and (2) 
cited publicly and officially by a Federal agency in support of an action 
that has the force and effect of law (i.e., a regulation) may be accessed 
through FOIA. It is important for applicants to understand the basic scope of 
this amendment. NIH has provided guidance at: 
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.

Applicants may wish to place data collected under this PA in a public 
archive, which can provide protections for the data and manage the 
distribution for an indefinite period of time. If so, the application should 
include a description of the archiving plan in the study design and include 
information about this in the budget justification section of the 
application. In addition, applicants should think about how to structure 
informed consent statements and other human subjects procedures given the 
potential for wider use of data collected under this award.

APPLICATION PROCEDURES

The research grant application form PHS 398 (rev. 4/98) at: 
http://grants.nih.gov/grants/funding/phs398/phs398.html  is to be used in 
applying for these grants and will be accepted at the standard application 
deadlines (http://grants.nih.gov/grants/dates.htm) as indicated in the 
application kit. Application kits are available at most institutional offices 
of sponsored research and from the Division of Extramural Outreach and 
Information Resources, National Institutes of Health, 6701 Rockledge Drive, 
MSC 7910, Bethesda, MD 20892-7910, telephone 301/435-0714, email: 
GrantsInfo@nih.gov.

Applicants planning to submit an investigator-initiated new (type 1), 
competing continuation (type 2), competing supplement, or any amended/revised 
version of the preceding grant application types requesting $500,000 or more 
in direct costs for any year are advised that he or she must contact the 
appropriate Institute’s program staff (see below, “Inquiries”) before 
submitting the application, i.e., as plans for the study are being developed.  
Furthermore, the applicant must obtain agreement from the staff that the 
Institute will accept the application for consideration for award.  Finally, 
the applicant must identify, in a cover letter sent with the application, the 
staff member and Institute who agreed to accept assignment of the 
application.

This policy requires an applicant to obtain agreement for acceptance of both 
any such application and any such subsequent amendment.  Refer to the NIH 
Guide for Grants and Contracts, March 20, 1998 at 
http://grants.nih.gov/grants/guide/notice-files/not98-030.html. 

R21 APPLICATION GUIDELINES  

o The R21 mechanism is specifically intended to support innovative ideas 
where preliminary data as evidence of feasibility are sparse or do not exist. 
These grants are not intended for large-scale undertakings or to support or 
supplement ongoing research. Rather, R21-supported projects are intended to 
serve as a basis for planning and strengthening future investigator-initiated 
research project grant applications (R01). It is important to note that, 
while originality of approach and potential significance of the proposed 
research are major considerations in evaluation for funding R21 grants, the 
applicant is also responsible for presenting the background literature that 
provides some basis for the approach and developing a rigorous research plan.

o For R21 applications, direct costs are limited to a maximum of $125,000 per 
year for a maximum of two years.  Direct costs requested for the proposed 
period may not exceed $250,000.  Direct costs should be requested in 
increments of $25,000. Total costs should equal the modular direct costs plus 
Facilities and Administrative (F&A) costs. The award is nonrenewable and may 
not be used to supplement an ongoing project.

o Do not exceed a total of 15 pages for Items a-d in the Research Plan. 
Tables and figures are included in the page limitation.  Applications that 
exceed the page limitation or NIH requirements for type size and margins 
(refer to PHS 398 application for details) will be returned to the applicant 
without further consideration.  The 15-page limitation does not include Items 
e-l (Human Subjects, Vertebrate Animals, Literature Cited, Consortia, and 
Consultants).

SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS 

The modular grant concept establishes specific modules in which direct costs 
may be requested as well as a maximum level for requested budgets. Only 
limited budgetary information is required under this approach. The just-in-
time concept allows applicants to submit certain information only when there 
is a possibility for an award. It is anticipated that these changes will 
reduce the administrative burden for the applicants, reviewers and Institute 
staff. The research grant application form PHS 398 (rev. 4/98) at 
http://grants.nih.gov/grants/funding/phs398/phs398.html  is to be used in 
applying for these grants, with the modifications noted below.

BUDGET INSTRUCTIONS

PHS 398

o FACE PAGE: Items 7a and 7b should be completed, indicating Direct Costs (in 
$25,000 increments up to a maximum of $250,000) and Total Costs [Modular 
Total Direct plus Facilities and Administrative (F&A) costs] for the initial 
budget period.  Items 8a and 8b should be completed indicating the Direct and 
Total Costs for the entire proposed period of support.

o DETAILED BUDGET FOR THE INITIAL BUDGET PERIOD - Do not complete Form Page 4 
of the PHS 398. It is not required and will not be accepted with the 
application.

o BUDGET FOR THE ENTIRE PROPOSED PERIOD OF SUPPORT - Do not complete the 
categorical budget table on Form Page 5 of the PHS 398. It is not required 
and will not be accepted with the application.

o NARRATIVE BUDGET JUSTIFICATION - Prepare a Modular Grant Budget Narrative 
page. (See http://grants.nih.gov/grants/funding/modular/modular.htm for 
sample pages.) At the top of the page, enter the total direct costs requested 
for each year. This is not a Form page.

o Under Personnel, list all project personnel, including their names, percent 
of effort, and roles on the project. No individual salary information should 
be provided. However, the applicant should use the NIH appropriation language 
salary cap and the NIH policy for graduate student compensation in developing 
the budget request.

For Consortium/Contractual costs, provide an estimate of total costs (direct 
plus facilities and administrative) for each year, each rounded to the 
nearest $1,000. List the individuals/organizations with whom consortium or 
contractual arrangements have been made, the percent effort of all personnel, 
and the role on the project. Indicate whether the collaborating institution 
is foreign or domestic. The total cost for a consortium/contractual 
arrangement is included in the overall requested modular direct cost amount. 
Include the Letter of Intent to establish a consortium.

Provide an additional narrative budget justification for any variation in the 
number of modules requested.

o BIOGRAPHICAL SKETCH - The Biographical Sketch provides information used by 
reviewers in the assessment of each individual's qualifications for a 
specific role in the proposed project, as well as to evaluate the overall 
qualifications of the research team. A biographical
sketch is required for all key personnel, following the instructions below. 
No more than three pages may be used for each person. A sample biographical 
sketch may be viewed at: 
http://grants.nih.gov/grants/funding/modular/modular.htm

- Complete the educational block at the top of the form page;
- List position(s) and any honors;
- Provide information, including overall goals and responsibilities, on 
research projects ongoing or completed during the last three years.
- List selected peer-reviewed publications, with full citations;

o CHECKLIST - This page should be completed and submitted with the 
application. If the F&A rate agreement has been established, indicate the 
type of agreement and the date. All appropriate exclusions must be applied in 
the calculation of the F&A costs for the initial budget period and all future 
budget years.

o The applicant should provide the name and phone number of the individual to 
contact concerning fiscal and administrative issues if additional information 
is necessary following the initial review.

Submit a signed, typewritten original of the application, including the 
Checklist, and five signed, photocopies, in one package to:

CENTER FOR SCIENTIFIC REVIEW
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040, MSC 7710
BETHESDA, MD 20892-7710
BETHESDA, MD 20817 (for express/courier service)

Applications will be accepted on the standard application receipt dates for 
investigator-initiated research as indicated in the PHS 398 directions. The 
Center for Scientific Review (CSR) will not accept any application in 
response to this PA that is essentially the same as one currently pending 
initial review, unless the applicant withdraws the pending application. The 
CSR will not accept any application that is essentially the same as one 
already reviewed. This does not preclude the submission of substantial 
revisions of applications already reviewed, but such applications must 
include an introduction addressing the previous critique.

Applications will be assigned on the basis of established PHS referral 
guidelines.  Applications will be evaluated for scientific and technical 
merit by an appropriate peer review group convened by in accordance with the 
standard NIH peer review procedures. As part of the initial merit review, all 
applications will receive a written critique and undergo a process in which 
only those applications deemed to have the highest scientific merit, 
generally the top half of the applications under review, will be discussed, 
assigned a priority score, and receive a second level review by the 
appropriate national advisory council or board.

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed for completeness by CSR staff. 
Incomplete applications will be returned to applicants without further 
consideration. Applications that are complete will be evaluated for 
scientific and technical merit in accordance with the standard NIH peer 
review procedures. 

The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health. In 
the written comments reviewers will be asked to discuss the following aspects 
of the application in order to judge the likelihood that the proposed 
research will have a substantial impact on the pursuit of these goals. Each 
of these criteria will be addressed and considered in assigning the overall 
score, weighting them as appropriate for each application. Note that the 
application does not need to be strong in all categories to be judged likely 
to have major scientific impact and thus deserve a high priority score. For 
example, an investigator may propose to carry out important work that by its 
nature is not innovative but is essential to move a field forward.

Review Criteria

(1) Significance: Does this study address an important problem? If the aims 
of the application are achieved, how will scientific knowledge be advanced? 
What will be the effect of these studies on the concepts or methods that 
drive this field?

(2) Approach: Are the conceptual framework, design, methods, and analyses 
adequately developed, well-integrated, and appropriate to the aims of the 
project? Does the applicant acknowledge potential problem areas and consider 
alternative tactics?

(3) Innovation: Does the project employ novel concepts, approaches or method? 
Are the aims original and innovative? Does the project challenge existing 
paradigms or develop new methodologies or technologies?

(4) Investigator: Is the investigator appropriately trained and well suited 
to carry out this work? Is the work proposed appropriate to the experience 
level of the principal investigator and other researchers (if any)?

(5) Environment: Does the scientific environment in which the work will be 
done contribute to the probability of success? Do the proposed experiments 
take advantage of unique features of the scientific environment or employ 
useful collaborative arrangements? Is there evidence of institutional 
support?

In addition to the above criteria, in accordance with NIH policy, all 
applications will also be reviewed with respect to the following:

o  The adequacy of plans to include genders, minorities and their subgroups, 
and children as appropriate for the scientific goals of the research. Plans 
for the recruitment and retention of subjects will also be evaluated.

o  The reasonableness of the proposed budget and duration in relation to the 
proposed research.

o  The adequacy of the proposed protection for humans, animals or the 
environment, to the extent they may be adversely affected by the project 
proposed in the application.

o  The adequacy of the proposed plan to share data, if appropriate.

AWARD CRITERIA

Award criteria that will be used to make award decisions include:

o scientific merit (as determined by peer review)
o availability of funds
o programmatic priorities

Applications will compete for available funds with all other recommended 
applications. The following will be considered in making funding decisions: 
Quality of the proposed project as determined by peer review, availability of 
funds, and program priority.

INQUIRIES

Inquiries concerning this PA are encouraged. The opportunity to clarify any 
issues or answer questions from potential applicants is welcome.

Direct inquiries regarding programmatic issues to:

Rebecca B. Costello, PhD
Office of Dietary Supplements
Office of Disease Prevention, Office of the Director
BuiLding 31, 1B29 
Bethesda, MD 20892
Telephone: (301) 435-2920 
FAX: 301-480-1845
Email: CostellB@od.nih.gov

Marguerite Evans, MS, RD
National Center for Complementary and Alternative Medicine
6707 Democracy Blvd.
Democracy 2, Suite 106
Bethesda, MD 20892-5475
Telephone: 301-402-5860
FAX: 301-480-3621
Email: me16o@nih.gov

Barbara Linder, MD, PhD 
Division of Diabetes, Endocrinology and Metabolic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Rm. 699
Bethesda, MD 20892-5460
Telephone: 301-594-0021
FAX: 301-480-3503
Email: linderb@extra.niddk.nih.gov

Direct inquiries regarding fiscal matters to:

Victoria C. Carper, MPA 
Chief, Grants Management Officer, 
National Center for Complementary and Alternative Medicine 
6707 Democracy Boulevard 
Democracy Two, Room 106 
Bethesda, Maryland 20892 
Direct: (301) 594-9102 
Office: (301) 496-4792 
Fax: (301) 480-3621 
Email: vp8g@nih.gov

Charlette Kenley
Division of Extramural Activities 
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Rm. 640 MSC 54444456
Bethesda, MD 20892-5456
Telephone:  (301) 594-8847 
FAX:  (301) 480-3504
E-mail: kenleyc@extra.niddk.nih.gov

AUTHORITY AND REGULATIONS

The Office of Dietary Supplements (ODS) was mandated by Congress in 1994 and 
established within the Office of the Director, National Institutes of Health 
(NIH). The Dietary Supplement Health and Education Act (DSHEA) [Public Law 
103-417, Section 3.a] amended the Federal Food, Drug, and Cosmetic Act “to 
establish standards with respect to dietary supplements.” This law authorized 
the establishment of the ODS.

This program is described in the Catalog of Federal Domestic Assistance No. 
93.213 and 93.847. Awards are made under authorization of Sections 301 and 
405 of the Public Health Service Act as amended (42 USC 241 and 284) and 
administered under NIH grants policies and Federal Regulations 42 CFR 52 and 
45 CFR Parts 74 and 92. This program is not subject to the intergovernmental 
review requirements of Executive Order 12372 or Health Systems Agency review.

The PHS strongly encourages all grant recipients to provide a smoke-free 
workplace and promote the non-use of all tobacco products. In addition, 
Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in 
certain facilities (or in some cases, any portion of a facility) in which 
regular or routine education, library, day care, health care, or early 
childhood development services are provided to children. This is consistent 
with the PHS mission to protect and advance the physical and mental health of 
the American people.


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