NIH GUIDE, Volume 21, Number 42, November 20, 1992

PA:  PA-93-22

P.T. 34







National Institute on Aging

National Institute of Mental Health


Recently, a geriatric syndrome termed "failure to thrive" has been

described, consisting of weight loss, decreased appetite, poor

nutrition, and inactivity, often accompanied by dehydration, depressive

symptoms, impaired immune function, and low serum cholesterol.  Failure

to thrive occurs in both acute and chronic forms, leading to impaired

functional status, morbidity from infection, pressure sores, and

increased mortality.  This syndrome has been identified as an aging

research priority in the Institute of Medicine's report:  Extending

Life, Enhancing Life.  A National Research Agenda on Aging.  (Institute

of Medicine; National Academy Press, Washington, 1991.)  The

relationships between nutritional, metabolic and other pathophysiologic

factors in failure to thrive and their effects on clinical outcomes

remain to be clarified.  While there is evidence that psychiatric

conditions (major and subsyndromal depression and cognitive decline)

are frequently associated with failure to thrive, the nature of this

association needs to be clarified.

"Failure to thrive" in older persons may not be a single process.  It

may be caused by several different pathophysiologic processes.  Thus

there is a strong need for descriptive information on the progression

of failure to thrive in various specific groups of older persons with

different chronic diseases and disabilities, to elucidate potential

differences and commonalities in pathophysiologic mechanisms and

clinical course.

The relationship between nutritional, metabolic and other

pathophysiologic mechanisms in failure to thrive, and their effects on

clinical outcomes, remains to be clarified.  Numerous studies have

documented the extent of protein-calorie malnutrition among nursing

home residents and other specific older populations.  In addition, it

has been suggested that micronutrient deficiencies may play a larger

role in chronic debilitating changes in older persons than is currently

appreciated.  Alterations in endocrine factors affecting metabolism,

inflammatory mediators, and depressive changes in affect have also been

suggested to play a major role in failure to thrive.  The contribution

of specific chronic disease processes and acute conditions to failure

to thrive has yet to be explored fully.  The effectiveness of

interventions against failure to thrive and loss of appetite in older

persons has not been rigorously tested.


The Public Health Service (PHS) is committed to achieving the health

promotion and disease prevention objectives of "Healthy People 2000,"

a PHS-led national activity for setting priority areas.  This Program

Announcement (PA), "Failure to Thrive" Syndrome Among Older Persons, is

related to the priority area of aging.  Potential applicants may obtain

a copy of "Healthy People 2000" (Full Report:  Stock No.

017-001-00474-0) or "Healthy People 2000" (Summary Report:  Stock No.

017-00473-1) through the superintendent of Documents, Government

Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238).


Applications may be submitted by foreign and domestic, for-profit and

non-profit organizations, public and private, such as universities,

colleges, hospitals, laboratories, unit of state and local governments,

and eligible agencies of the Federal government.  Applications from

minority individuals and women are encouraged.  Foreign institutions

are not eligible for First Independent Research Support and Transition

(FIRST) awards (R29) or for the Career Awards (K01, K04, K07, K08, K11,

K20, K21).


Awards will be administered under PHS grants policy as stated in the

Public Health Service Grants policy statement, DHHS Publication No.

(OASH) 90-50,000, revised October 1, 1990.  The National Institute on

Aging (NIA) intends to commit $1.8 million in Fiscal Year 1994 for this

research area.  This funding level is dependent on the receipt of a

sufficient number of applications of high scientific merit.

Applications in response to this announcement assigned to the NIA may

not request funding over $175,000 (direct and indirect costs) for the

first year, and may not request more than four percent per year above

$200,000 for subsequent years.  Additionally, the National Institute of

Mental Health (NIMH) anticipates supporting approximately 4-6 awards

under this announcement.  The Principal Investigators will meet

annually with NIA and NIMH staff in Bethesda, Maryland to review the

progress of their studies.  Funds for such travel must be requested in


The mechanisms for support are:

o  Research Grant (RO1)

o  FIRST award  (R29)

o  Career awards, which include:  Special Emphasis Research Career

Awards (K01) in Nutritional

and Metabolic Factors in Aging, Research Career Development Award

(K04), Clinical Mental Health Academic Award (K07), Clinical

Investigator Award (K08), Physician Scientist Award (K11), Scientist

Development Award for Clinicians (K20), and Scientist Development Award



The NIA seeks applications for support of research to clarify

pathophysiological features of the "failure to thrive" syndrome in

older persons and research into its causes, prevention, and treatment.

Topics of interest include:

o  Risk factors, natural history, clinical, and functional features of

failure to thrive in various high-risk older subpopulations.  Though

large scale primary epidemiologic studies are outside the scope of this

PA, ancillary studies to existing population studies are appropriate

and encouraged.

o  Primary endocrine, metabolic, cellular and related pathophysiologic

mechanisms contributing to failure to thrive in older persons.

o  Relationship between nutritional deficiencies, or impairments in

nutrient disposition or metabolism, as causes or results of the various

pathophysiological abnormalities described in "failure to thrive" in

older persons.

o  Interactions and interrelationships among the different components

of failure to thrive, e.g. hypocholesterolemia, specific abnormalities

in immunologic and inflammatory factors, infection, depression.

o  Metabolic responses and alterations in nutritional needs of older

persons associated with acute conditions that may provoke failure to

thrive, e.g., infections, trauma, or surgery.

o  Factors modulating control of appetite as a cause or consequence of

failure to thrive.

o  Pathophysiologic effects of coexisting chronic diseases and/or

comorbid processes of aging contributing to failure to thrive.

o  The role of psychosocial and cultural factors, (e.g., social

supports, social stressors, bereavement, depression, mood and affect,

cultural preferences) in failure to thrive syndrome.

o  Development and use of appropriate animal models for studying

failure to thrive in older persons.

o  Neural interactions with physiological processes underlying failure

to thrive syndrome.

o  Efficacy of interventions in preventing, arresting, or reversing

failure to thrive.  Applicants may choose to study specific populations

and conditions, e.g., post-surgical or trauma patients, infections, or

depression.  Attention to physiologic factors or comorbid conditions

modulating efficacy of interventions in these conditions is

particularly encouraged.

o  Delineation of psychiatric conditions of failure to thrive

(including the range of clinically significant affective symptoms) and

the elucidation of the interrelationship among psychiatric status,

physiological measures, and behavior.

For any of the above topics, attention to the heterogeneity and

frequent multiple morbidity within the geriatric population is

encouraged in the design of research projects.


It is NIH policy that women and minorities must be included in clinical

study populations unless there is a good reason to exclude them.  The

study design must seek to identify any pertinent gender or minority

population differences.




NIH policy is that, as appropriate, applicants for NIH grants,

cooperative agreements, and contracts will be required to include

minorities and women in study populations so that research findings can

be of benefit to all persons at risk of the diseases, disorders, or

conditions under study; special emphasis should be placed on the need

for inclusion of minorities and women in studies of diseases,

disorders, and conditions that disproportionately affect them.  This

policy is intended to apply to males as well as females of all ages.

If women or minorities are excluded or inadequately represented in

clinical research, particularly in proposed population-based studies,

a clear compelling rationale for exception to the policy must be


The composition of the proposed study population must be described in

terms of gender and racial/ethnic groups, together with a rationale for

its choice.  In addition, gender and racial/ethnic issues should be

addressed in developing a research design and sample size appropriate

for the scientific objectives of the study.  This information should be

included in the form PHS 398 (rev. 9/91) in Sections 1-4 of the

Research Plan AND summarized in Section 5, Human Subjects.

Applicants are urged to assess carefully the feasibility of including

the broadest possible representation of minority groups.  However, NIH

recognizes that it may not be feasible or appropriate in all research

projects to include representation of the full array of United States

racial/ethnic minority populations (i.e., Native Americans (including

American Indians or Alaskan Natives, Asian/Pacific Islanders, Blacks,

Hispanics).  The rationale for studies on single minority populations

should be provided.  For the purpose of this policy, clinical research

includes human biomedical and behavioral studies of etiology,

diagnosis, or treatment of diseases, disorders or conditions, including

but not limited to clinical trials.

The usual NIH policies concerning research on human subjects also

apply.  Basic research or clinical studies in which human tissues

cannot be identified or linked to individuals are exempt.  However,

every effort should be made to include human tissues from women and

racial/ethnic minorities when it is important to apply the results of

the study broadly, and this should be addressed by applicants.  For

foreign awards, the policy on inclusion of women applies fully; since

the definition of minority differs in other countries, the applicant

must discuss the relevance of research involving foreign population

groups to the United States' populations, including minorities.

If the required information is not contained within the application,

the application will be returned without review.

Peer reviewers will address specifically whether the research plan in

the application conforms to these policies.  If the representation of

women or minorities in a study is inadequate to answer the scientific

questions(s) addressed and the justification for the selected study

population is inadequate, it will be considered a scientific weakness

or deficiency in the study design and will be reflected in assigning

the priority score to the application.  All applications for clinical

research submitted to NIH are required to address these policies.  NIH

funding components will not award grants or cooperative agreements that

do not comply with these policies.


Applications are to be submitted on the application form PHS 398 (rev.

9/91) available at most institutional offices of sponsored research and

from the Office of Grants Inquiries, Division of Research Grants,

National Institutes of Health, 5333 Westbard Avenue, Room 449,

Bethesda, Maryland 20892, telephone 301/496-7441.  Applications will be

accepted on the standard application receipt dates as indicated in the

application kit.  The program announcement title and number must be

typed on line 2a of the face page.

The completed original application and five legible copies must be sent

or delivered to:

Application Receipt Office

Division of Research Grants

National Institutes of Health

Westwood Building, Room 240

Bethesda, MD  20892**


Applications will be reviewed by the NIH Division of Research Grants

(DRG).  The review criteria are the traditional considerations

underlying scientific merit.  Applications will be reviewed by standard

NIH review procedures in accordance with the usual NIH peer review

procedures, based on scientific merit.  Following study section review,

the applications will be evaluated by the appropriate national advisory


The review criteria for each mechanism may be obtained from the program

contact listed below.


Applications will compete for available funds on the basis of

scientific merit with other applications.  The following will be

considered in making funding decisions:

o  Quality of the proposed project as determined by peer review

o  Availability of funds

o  Program balance among research areas of the announcement


The opportunity to clarify any issues and questions from potential

applicants is welcome.

Direct inquiries regarding programmatic issues to:

Pamela Starke-Reed, Ph.D., Geriatrics Program, Suite 3E327

Telephone:  (301) 496 6761

Huber Warner, Ph.D., Biology of Aging Program, Suite 2C231

Telephone:  (301) 496-6402

Marcia Ory, Ph.D., M.P.H., Behavioral and Social Research Program,

Suite 2C234

Telephone:  (301) 496-3136

Andrew Monjan, Ph.D., Neuroscience and Neuropsychology of Aging

Program, Suite 3C307

Telephone:  (301) 496-9350

All are at the NIA with the following address:

National Institute on Aging

Gateway Building

Bethesda, MD  20892


Rick Martinez, M.D.  or  Enid Light, Ph.D.

Mental Disorders of the Aging Research Branch

National Institute of Mental Health

5600 Fishers Lane, Room 7-103

Rockville, MD  20857

Telephone:  (301) 443-1185

Direct inquiries regarding fiscal matters to:

Barbara Cunningham

Grants and Contracts Management Office

National Institute on Aging

Gateway Building, Room 2N212

Bethesda, MD  20892

Telephone:  (301) 496-1472


This program is described in the Catalog of Federal Domestic Assistance

No. 93.866.  Awards are made under authorization of the Public Health

Service Act, Title IV, Part A (Public Law 78-410), as amended by Public

Law 99-158, 42 USC 241 and 285) and administered under PHS grants

policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74.  This

program is not subject to the intergovernmental review requirements of

Executive Order 12372 or Health Systems Agency review.


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