This Program Announcement expires on February 1, 2004 unless reissued.
BIOMARKERS AND CLINICAL ENDPOINTS IN PEDIATRIC CLINICAL TRIALS
Release Date: January 18, 2001
PA NUMBER: PA-01-043
National Institute of Child Health and Human Development
(http://www.nichd.nih.gov/)
National Institute of Diabetes and Digestive and Kidney Diseases
(http://www.niddk.nih.gov/)
National Institute of Mental Health
(http://www.nimh.nih.gov/)
National Institute of Neurological Disorders and Stroke
(http://www.ninds.nih.gov/)
THIS PA USES “MODULAR GRANT” AND “JUST-IN-TIME” CONCEPTS. IT INCLUDES
DETAILED MODIFICATIONS TO STANDARD APPLICTION INSTRUCTIONS THAT MUST BE USED
WHEN PREPARING AN APPLICATION IN RESPONSE TO THIS PA.
PURPOSE
The overall goal of this initiative is to invite qualified researchers to
submit new research grant applications to conduct mechanistic studies using
patients, patient materials or information from multi-site pediatric drug
trials sponsored by the National Institute of Child Health and Human
Development (NICHD), National Institute of Diabetes and Digestive and Kidney
Diseases (NIDDK), National Institute of Mental Health (NIMH), and the
National Institute of Neurological Disorders and Stroke (NINDS).
Applications in response to this announcement should propose ancillary
mechanistic studies of disease pathogenesis and/or of results of therapeutic
intervention, determination of biomarkers or surrogate endpoints, and
development and validation of clinical endpoints in infants and older
children. These ancillary studies must not interfere with the objectives and
the conduct of clinical trials. These studies can be performed in clinical
trials supported by any source (industry, public and private). Current
participation in a trial as a Principal Investigator, co-investigator, or
clinical site investigator is not a prerequisite for submission of an
ancillary study application.
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
(PA) 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, and 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 the interactive research project grants (IRPG) award
mechanisms. The Interactive Research Project Grant (IRPG)
(http://grants.nih.gov/grants/guide/pa-files/PA-96-001.html) provides support
for formal, investigator-initiated, collaborative relationships. An IRPG group
consists of the coordinated submission of two or more applications for related
research project grants (R01). Although the applications must describe both
the objectives and the scientific importance of the collaboration, each
project could be accomplished independently. Principal Investigators may be
from separate institutions. Applications will be reviewed independently for
scientific and technical merit with those judged to have significant and
substantial merit considered for funding both as an independent award and as
a component of the proposed IRPG group. Responsibility for the planning,
direction, and execution of the proposed project will be solely that of the
applicant.
For all competing applications requesting up to $250,000 direct costs per
year, specific application instructions have been modified to reflect
"MODULAR GRANT" and "JUST-IN-TIME" streamlining efforts being examined by
NIH. Complete and detailed instructions and information on Modular Grant
applications can be found at:
http://grants.nih.gov/grants/funding/modular/modular.htm. Applications that
request more than $250,000 in any year must use the standard PHS 398 (rev.
4/98) application instructions.
RESEARCH OBJECTIVES
Background
In the last three years, major drug legislative and regulatory events have
occurred that will profoundly affect pediatric drug development in the
future: 1) the enactment of the pediatric provisions of the Food and Drug
Administration Modernization Act (FDAMA) of 1997, and 2) the adoption by the
Food and Drug Administration (FDA) of the Final Rule of 1998. The former
provides for a six-month exclusivity for marketed drugs with remaining patent
or any kind of exclusivity. The Final Rule of 1998 became effective in April
1999 and mandates pediatric studies on new drugs that can benefit children.
An unprecedented surge in the number of pediatric drug trials has occurred as
a result of these regulatory changes.
The marked increase in the number of drug studies that occurred after the
implementation of FDAMA has brought to light the problem of finding enough
children to conduct efficacy trials. This situation occurs despite the fact
that a typical pediatric drug trial involves a relatively small number of
patients compared to efficacy trials in adults. Regulatory requirements
allow for extrapolation to children of the results of efficacy trials
performed in adults if the response to therapy and the natural history of the
disease is sufficiently similar in children and adults. For a number of
conditions, the disease process is dissimilar or the comparison of the
natural history of the disease in children and adults has not been
undertaken.
Another identified problem is the difficulty in establishing efficacy and
safety for drugs used in the treatment of chronic childhood conditions
because of the lack of adequate markers to establish disease severity,
recurrence, and response to therapy.
The need to shorten duration and cost of clinical trials in adults has
stimulated interest in the development of biomarkers and surrogate endpoints
that may substitute for clinical endpoints.
This initiative follows the definitions of biomarkers and surrogate endpoints
developed by the Definition Working Group NIH-FDA
(http://www1.od.nih.gov/osp/ospp/biomarkers/biomarkers.htm).
Diagnostic biomarkers or biomarkers of disease severity permit stratification
of patients in more homogeneous groups and allow for a decrease in the needed
sample size. Biomarkers can also be used to estimate the efficacy of drugs
(efficacy biomarkers). These biomarkers must correlate with the clinical
outcome, be mechanistically linked to the disease process, and must
significantly capture the treatment effect of a drug. The pre-treatment
variability of an efficacy biomarker must be small compared to the changes in
the biomarker concentration or activity produced by therapy. The effect of
drug on a proposed efficacy biomarker must be sustained to allow
determination of efficacy.
Currently, the majority of biomarkers proposed or developed in pediatrics
have been for use in practice and not in clinical trials. A number of
examples follow:
Biologic substances measured in lung lavage aspirates have been proposed to
determine the severity or course of asthma in children. These biomarkers are
related to the activation of inflammatory cells and their mediators.
Eosinophilic cationic protein, nitric oxide, S-Nitrosothiols, and bcl-2, an
apoptosis marker in sputum eosinophils, have been proposed as biomarkers of
disease severity. A non-invasive approach--measuring products of inflammatory
cell activation in the urine (e.g., leukotriene E4, 9-alpha 11-beta
prostaglandin F2)--has also been proposed as biomarkers to estimate activity
of the asthmatic process.
Biomarkers of disease activity have also been proposed in cystic fibrosis, a
disease characterized by chronic inflammation and infection of the lungs and
airways. Measurements of elastin degradation products in urine, lipocalcin
concentration in serum, and markers of inflammation in sputum have all been
suggested, but have not been systematically studied.
CD4 counts and viral load determinations has been well studied as surrogate
endpoints in children with human immunodeficiency virus (HIV)infections.
Clonal markers have been developed to quantify cells in acute lymphoblastic
leukemia of childhood. This technology allows for the determination of
minimal residual disease. Clonal markers may be used as prognostic biomarkers
in acute lymphoblastic leukemia of childhood.
Current research into the pathophysiology of diabetes and other endocrine and
metabolic diseases has identified candidates for surrogate markers. Examples
in type 1 diabetes include the biochemical islet cell antibody markers of
GAD65, ICA512/IA2, and IAA; these markers and combinations of these markers
need further refinement as to their correlation and specificity to type 1
diabetes, and how they vary by age and ethnicity. New measures which need
more extensive research include markers of T cell reactivity to islet cell
components, cytokines, the use of MHC-class II tetramers for identifying
antigen-specific T cells, and imaging of B-cell inflammation and mass. Such
markers may also be useful for distinguishing between type 1 and type 2
diabetes in children, as this is sometimes difficult using clinical criteria
alone. Also needed are surrogate markers to predict the development and
track the progression of diabetic complications.
The identification and development of biomarkers for neurological disorders
in children is necessary for the ascertainment of natural history and effect
of treatment. A number of gene discoveries have been made on pediatric
neurogenetic diseases that cause progressive and/or life- long disability.
In addition, there are a number of acquired conditions, such as injury to the
developing brain, for which there is a growing understanding of the
pathological mechanisms. Great excitement exists in translational research
involving experimental therapeutics for these once thought to be untreatable
neurological conditions. It is paramount that biomarkers reflective of
disease state, progression or complications be established to assess
potential therapeutic manipulations.
Imaging technology can also be used for the development of diagnostic or
mechanistic biomarkers for estimating treatment effects of drug action at the
tissue level.
Neuroimaging technology, including MR spectroscopy, diffusion tensor imaging,
functional magnetic imaging, cranial neonatal ultrasound, and near infrared
spectroscopy, can also provide important assessments of the treatment effects
of a variety of therapeutic agents in treating acquired, metabolic, and
genetic brain disorders of children, and/or monitoring potential
complications of the disease or treatment side effects.
Ultrasound technology has been used sparingly for the development of
biomarkers in pediatrics. For example, high resolution ultrasound monitoring
can detect atheromatous plaque formation in young children.
The majority of markers proposed or developed in pediatrics have not been
subjected to the rigorous validation process needed for their use in clinical
trials that lead to drug labeling. In fact most biomarkers have been
suggested on the basis of a small number of patients, often without controls
and without knowledge of the variability and time course in untreated
patients.
There are a number of factors that may affect the usefulness of potential
biomarkers and surrogate endpoints in pediatrics. The marked difference in
the natural history of several diseases when children are compared with
adults must be taken into account when biomarkers developed for the adult
population are used in pediatrics. Developmental issues are also important.
The concentration or activity of many biomarkers used in pediatrics varies
according to age. Examples of biomarkers that vary with age include
glycosylated hemoglobin, prealbumin, beta-2 microglobulin, adhesion molecules
and host immunologic markers. The importance of variation with age has been
clearly demonstrated when CD4 counts have been used as prognostic biomarkers
in children with AIDS. In normal children, CD4 counts change with age, and
in young infants the biologic variability can be quite large. These
developmental characteristics must be taken into account when using this
laboratory measurement as a biomarker.
Ethical considerations may limit the application of biomarkers. The use of
controls for validation purposes, invasive procedures, or the use of
radioactive materials as biomarkers may lead to the classification of studies
as non-beneficial research in normal children.
The small sample size characteristic of pediatric drug trials may also
prevent the validation of surrogate endpoints and, for certain conditions
such as hypertension and hyperlipidemias, the time to endpoint is too long.
Clinical endpoints are considered the gold standard for determining efficacy.
In the past, drug trials in pediatrics were limited to a few therapeutic
categories (e.g., antibiotics, analgesics).
The incentives created by FDAMA resulted in the study of a wide range of
therapeutic categories not previously studied in children.
The establishment of efficacy for a number of drugs is based on clinical
endpoints that have not been validated. For example, pain scales in young
infants are based on behavioral studies and not specifically designed to test
the efficacy of analgesics, and parent’s diaries to establish efficacy of
bronchodilators are a poor substitute for measurements of bronchial function.
Also diagnosis of certain conditions (e.g., asthma) may be difficult in young
infants.
Research Scope
The following are examples of topics that might be proposed for study in
response to this announcement. However, these are only examples and are not
meant to be limiting. (Please note that Institutes’ interest in these topics
does not guarantee approval by a trial’s organization leadership).
o Identification, development, validation, and/or extrapolation from adult
trials of biomarkers of diagnosis, prognosis, and of disease activity.
o Identification, development, validation, and/or extrapolation from adult
trials of biomarkers of efficacy or toxicity.
o Study of treatment effects on additional outcome variables not included in
the parent trial.
o Use of non-invasive measures of organ function (e.g., functional MRI,
magnetic resonance spectroscopy, ultrasound, PET) to identify, characterize,
and validate diagnostic biomarkers, intermediate surrogate endpoints, and
prognostic biomarkers.
o Development of genetic biomarkers and genetic databases using samples and
data from trial subjects.
o Study and validation of biomarkers used in clinical practice, including
markers of disease severity that reflect underlying pathogenesis.
o Application of cDNA microarray technology for the development of
biomarkers in pediatrics.
o Identification and validation of natural history biomarkers that may
predict clinical outcome in the absence of therapy.
o Estimation of the magnitude of treatment effect on validated adult
biomarkers that reflect underlying pathogenesis.
o Characterization of the effect of developmental stages in the
concentration, activity or other quantifiable measurement of a biomarker.
o Development of statistical methodology to establish the validity of
surrogate endpoints in pediatrics.
o Study of related biomarkers (e.g., biomarkers of inflammation) to
determine the most specific and valid measurement of or ascertain whether a
composite marker provides a more accurate estimate of underlying pathogenic
mechanisms than the individual biomarkers.
o Identification and development of biomarkers that can be used in
combination with or substitute for severity of illness scoring systems that
are inadequate for stratification of patients according to disease severity
or for estimation of a treatment effect.
o Linking of pharmacokinetics and pharmacodynamic methods to biomarker
applications in pediatrics.
o Identification and/or validation of osteopenia biomarkers in relation to
child development and their correlation to drug effects.
o Biomarkers to assess immunoresponsiveness in children at different
developmental stages.
o Development of biomarkers for pain assessment in young infants that are
more sensitive and specific than current pain scales and can be used to
determine drug effects accurately.
o Applications in pediatrics of echocardiographic and ultrasonographic
biomarkers including brachial artery flow mediated dilatation.
o Applications in pediatrics of neuroimaging and neurophysiological
biomarkers to monitor disease progression, effects of therapeutic
interventions, or complications
o Development of biomarkers that reflect appropriate neurodevelopmental
status from infancy through adolescence with respect to any domain of the
developmental process: motor, sensory, cognitive, and behavioral assessment.
Research Focus
This PA does not seek applications that propose research that merely
identifies associations or the development of methodology or instrumentation.
The major emphasis of this PA is on mechanistic studies using ongoing
pediatric clinical trials at the participating Institutes. Studies needed to
develop biomarkers or clinical endpoints such as development of
instrumentation should be integrated into the proposed research program.
Proposed biomarkers or surrogate endpoints must be biologically plausible,
specific with limited interpatient variability, and exhibit significant
changes in activity, concentration or other appropriate quantitative
measurement in response to treatment (effectiveness biomarkers) or in
relation to severity and/or recurrence of a disease.
Proposed new clinical endpoints must also be validated in relation to
clinical outcome and must be compared to clinical endpoints currently in use.
The distinguishing feature of the ancillary studies sought in response to
this PA is the requirement for the resources of a clinical trial.
Prospective applicants for this PA may or may not be investigators of the
parent clinical trial(s) whose data and/or materials and/or subjects they
propose to use. It is expected that applicant Principal Investigators who
are not parent study investigators will work together with the parent study
investigators in developing their applications. All ancillary study
applications MUST include a letter or statement documenting that the
patients, samples, data, and/or materials are available from the parent
clinical trial and that the proposed ancillary study has the approval of the
parent study’s organization/leadership. Applicants must submit a time line in
their application demonstrating that the ancillary study can be completed
within a reasonable time.
INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECT
It is the policy of the NIH that women and members of minority groups and
their subpopulations 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 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 are 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,”
published in the NIH Guide for Grants and Contracts, March 6, 1998, and
available at: 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.
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.
APPLICATION PROCEDURES
Applicants are strongly encouraged to contact program staff listed in
INQUIRES, below, with any questions regarding their proposed projects.
Applications are to be submitted on the grant application form PHS 398 (rev.
4/98) and will be accepted at the standard application deadlines as indicated
in the application kit. Application kits are available at most institutional
offices of sponsored research and may be obtained 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. Applications are also available on the
Internet at http://grants.nih.gov/grants/funding/phs398/phs398.html.
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
Institute program staff before submitting the application, i.e., as plans for
the study are being developed. Furthermore, the application must obtain
agreement from the Institute 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.
Application Instructions
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 NIH
staff. The research grant application form PHS 398 (rev. 4/98) is to be used
in applying for these grants, with the modifications noted below.
Modular Grant applications will request direct costs in $25,000 modules, up
to a total direct cost request of $250,000 per year. (Applications that
request more than $250,000 direct costs in any year must follow the
traditional PHS398 application instructions.) The total direct costs must be
requested in accordance with the program guidelines and the modifications
made to the standard PHS 398 application instructions described below:
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 F & A) 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 telephone number of the
individual to contact concerning fiscal and administrative issues if
additional information is necessary following the initial review.
Submission Instructions
The title and number of the PA must be typed on line 2 of the face page of
the application form and the YES box must be marked.
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)
REVIEW CONSIDERATIONS
Applications will be assigned on the basis of established PHS referral
guidelines. Applications will be reviewed for completeness by the Center for
Scientific Review (CSR). Applications that are complete will be evaluated
for scientific and technical merit by an appropriate peer review group
convened in accordance with 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 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 Criteria
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.
o 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?
o 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?
o 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?
o 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)?
o 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 both 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 or the environment, to
the extent they may be adversely affected by the project proposed in the
application.
AWARD CRITERIA
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. Written documentation of approval from a
trial’s Principal Investigator and the parent’s study organization/leadership
must be provided prior to funding.
INQUIRIES
Inquiries are encouraged. The opportunity to clarify any issues or questions
from potential applicants is welcome. Direct inquiries regarding programmatic
issues to:
George P. Giacoia, M.D.
Endocrinology, Nutrition and Growth Branch
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 4B11B, MSC 7510
Bethesda, MD 20892-7510
Telephone: (301) 496-5589
FAX: (301) 480-9791
E-mail: gg65m@nih.gov
Catherine C. Cowie, Ph.D.
Division of Diabetes, Endocrinology and Metabolic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Blvd, Room 691, MSC 5460
Bethesda, MD 20892-5460
Telephone: (301) 594-8804
FAX: (301) 480-3503
E-mail: cowiec@extra.niddk.nih.gov
Barbara Linder, M.D., Ph.D.
Division of Diabetes, Endocrinology and Metabolic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Blvd, Room 699, MSC 5460
Bethesda, MD 20892-5460
Telephone: (301) 594-0021
FAX: (301) 480-3503
E-mail: linderb@extra.niddk.nih.gov
Judith M. Rumsey, M.D.
Division of Neuroscience and Basic Behavioral Science
National Institute of Mental Health
6001 Executive Boulevard, Room 7175, MSC 9643
Bethesda, MD 20892-9643
Telephone: (301) 443-1692
FAX: (301) 402-4740
E-mail: jrumsey@box-j.nih.gov
Giovanna M. Spinella, M.D.
Neurogenetics and Development
National Institute of Neurological Disorders and Stroke
6001 Executive Boulevard, Room 2132, MSC 9527
Rockville, MD 20892-9527
Telephone: (301) 496-5745
FAX: (301) 402-1501
E-mail: gs41b@nih.gov
Direct inquiries regarding fiscal matters to:
Mary E. Daley
Grants Management Branch
National Institute of Child Health and Human Development
Building, Room 8A 17
Bethesda, MD 20892- 7510
Telephone: (301) 496-1305
FAX: (301) 402-0915
E-mail: md74u@nih.gov
Diana S. Trunnell
Grants Management Branch
National Institute of Mental Health
6001 Executive Boulevard, Room 6115, MSC 9605
Bethesda, MD 20892-9605
Telephone: (301) 443-6885
E-mail: dt21a@NIH.GOV
Karen Shields
Grants Management Branch
National Institute of Neurological Disorders and Stroke
6001 Executive Boulevard, Room 3625
Rockville, MD 20892-9527
E-mail: ks26n@NIH.GOV
AUTHORITY AND REGULATIONS
This program is described in the Catalog of Federal Domestic Assistance Nos.
93.865, 93.848, 93.242, and 93.853. 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 and contract 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, and 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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