MANAGEMENT OF SYMPTOMS AT THE END OF LIFE

NIH GUIDE, Volume 26, Number 40, December 19, 1997

PA NUMBER: PA-98-019

P.T.

National Institute of Nursing Research
National Cancer Institute
National Institute of Allergy and Infectious Diseases
National Institute of Mental Health
Office of Alternative Medicine

PURPOSE

The National Institute of Nursing Research (NINR), National Cancer Institute
(NCI), National Institute of Allergy and Infectious Diseases (NIAID), National
Institute of Mental Health (NIMH), and Office of Alternative Medicine (OAM)
seek research grant applications concerning the clinical management of
symptoms and syndromes that are associated with life-limiting illness, such as
pain, dyspnea, delirium, cachexia, nausea, fatigue, and depression.  The
purpose of this initiative is to stimulate research that will lead to improved
quality of life for those at the end of life and decreased distress for their
caregivers.

HEALTHY PEOPLE 2000

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),
Management of Symptoms at the End of Life, is related to the priority areas of
heart disease and stroke, cancer, diabetes and chronic disabling conditions,
and HIV infection.  Potential applicants may obtain a copy of "Healthy People
2000" (Full Report:  Stock No. 017-001-00474-0 or Summary Report:  Stock No.
017-001-00473-1) through the Superintendent of Documents, Government Printing
Office, Washington, DC 20402-9325 (telephone 202-512-1800).

ELIGIBILITY REQUIREMENTS

Research 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

The mechanisms of support will be the National Institutes of Health (NIH)
research project grants (R01).  Responsibility for the planning, direction,
and execution of the proposed project will be solely that of the applicant.

RESEARCH OBJECTIVES

Background

Patients at the end of life experience many of the same symptoms, regardless
of their underlying medical condition.  Pain is the most obvious example, but
others are dyspnea, nausea, fatigue, depression, and the symptoms associated
with delirium and cachexia.  Taken together, these symptoms add significantly
to the suffering of patients and their families, and to the costs and burden
of their medical care.  Yet in many cases the symptoms could be treated or
prevented.

There is widespread dissatisfaction in the United States with care at the end
of life.  A recent investigation, the "Study to Understand Prognoses and
Preferences for Outcomes and Risks of Treatments" (SUPPORT) documented many
problems with the delivery of palliative care.  Forty percent of the dying
patients studied were treated aggressively in intensive care units; pain was
common; there were discrepancies between patient desires and actual treatment;
and almost half of the physicians in the study did not know that their
patients' preference was not to be resuscitated.  Broad public interest in and
support for physician-assisted suicide is widely viewed as another indicator
of major public dissatisfaction with treatment of the terminally ill.  In the
recommendations made at the conclusion of its study "Approaching Death:
Improving Care at the End of Life", the Institute of Medicine recognized the
need for action on the part of clinicians, educators, researchers, policy
makers and the public.

There has been substantial response.  Many of the major health professional
organizations now have initiatives to improve health care provider education,
quality of care of the terminally ill, and public perceptions of palliative
care.  Several major foundations have established multi-million dollar
initiatives in various aspects of palliative care.  This effort is much needed
to implement current knowledge to improve care.  However, there are also
important gaps in understanding of the process of dying, including the best
way to manage diverse but interrelated symptoms in order to optimize comfort
and alertness for those experiencing life-limiting illnesses.  The IOM
recommendations included encouragement of the nation's research establishment
to strengthen the knowledge base of the end-of-life and specifically to
advance basic and clinical research on the physiological mechanisms and
treatment of commonly experienced symptoms.

The end of life is recognized as an important phase of life, one in which
individuals have the right to expect quality of life and the opportunity to
address key personal issues. When symptoms are well controlled, people with
life-threatening illnesses can focus on important personal concerns. Good
symptom control is an essential component of quality care at the end of life.

Significant advances have been made in recent years in the knowledge necessary
for adequate pain control.  Important lessons have been learned in the study
of this symptom that will inform research on other symptoms associated with
life-limiting illness.  However, significant challenges remain. With respect
to pain management, health providers still need better assessment tools for
diverse settings and special populations, as well as more selective and
individualized therapies.  Moreover, most patients with advanced disease
experience multiple symptoms, requiring that their care be based on an
understanding of the complex interactions of multiple pathologies and
therapies.

A Research Workshop, "Symptoms in Terminal Illness," was convened by the
National Institutes of Health (NIH) in September 1997.  The workshop had three
principal goals:  (1) to summarize the current state of knowledge concerning
the most common symptoms associated with terminal illness; (2) to identify
important needs and opportunities for research that would be appropriate for
NIH funding; and (3) to initiate a process for enhancing interdisciplinary
collaboration and interagency collaboration in research in palliative care. 
The report of this workshop is available at www.nih.gov/ninr.

Consistent with the recommendations made by that panel, this initiative seeks
to stimulate integrative, multidisciplinary research that brings basic and
clinical investigators together to address the constellation of symptoms at
the end of life across disease conditions.

Objectives

Specific areas of interest include, but are not limited to, the following
topics:

o  studies comparing the incidence and combinations of symptoms that are
experienced at the end of life in specific populations, such as persons with
cancer, AIDS, end-stage heart disease, etc.

o  research on the mechanisms and interactions of these symptoms, including
biochemical, neurological, endocrine, and immune approaches.

o  studies of the efficacy of combination therapies to address clusters of
symptoms with multiple determinants

o  small scale studies to develop and test instruments that are sensitive to
the distress associated with symptoms at the end of life and useful for
monitoring the effectiveness of interventions, especially for culturally
diverse populations and disadvantaged groups, such as the cognitively impaired

o  research on the impact of depression and anxiety and of their treatment on
patient status and management at the end of life

o  research on the ethical issues associated with research at the end of life,
including the needs and expectations of dying persons and their families

Projects may be descriptive or experimental.  The ultimate goal is clinical
intervention, but descriptive data is important to enhance the development of
targeted interventions.  Where appropriate, interventions that are designed to
reduce the severity, frequency, duration or distress of symptoms should be
evaluated for efficacy under conditions that will permit comprehensive
analysis of appropriate outcome measures. Interventions should also have the
potential for implementation in routine clinical practice, particularly in the
home or hospice setting.

Because of the complex interaction of clinical symptoms and the associated
subjective responses, a multidisciplinary research approach is recommended.
Expertise from health-related disciplines should be included as appropriate
for both the target symptom and the clinical population. The participating NIH
agencies anticipate collaborating to fund meritorious applications that
address multiple institutes' missions.

Applicants are encouraged to make use of ongoing research efforts where
feasible. Applications from institutions that have a General Clinical Research
Center (GCRC) may wish to identify these programs as a resource for conducting
the proposed research.  If so, a letter of agreement from the program director
or the Principal Investigator should be included with the application.

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 subpopulations must be included in all NIH supported biomedical and
behavioral research projects involving human subjects, unless a clear and
compelling rationale and justification is provided that inclusion is
inappropriate with respect to the health of the subjects or the purpose of the
research.  This new 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
"NIH Guidelines For Inclusion of Women and Minorities as Subjects in Clinical
Research," which have been published in the Federal Register of March 28, 1994
(FR 59 14508-14513) and in the NIH Guide for Grants and Contracts, Volume 23,
Number 11, March 18, 1994. Investigators also may obtain copies of the policy
from the program staff listed under INQUIRIES. Program staff may also provide
additional relevant information concerning the policy.

APPLICATION PROCEDURES

Applications are to be submitted on grant application form PHS 398 (rev. 5/95)
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 301/710-0267,
email: [email protected].  The title and number of the program announcement
must be typed in Section 2 on the face page of the application.

The complete original application and five legible copies must be sent or
delivered to:

CENTER FOR SCIENTIFIC REVIEW (formerly Division of Research Grants)
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 that are complete will be evaluated for scientific
and technical merit by an appropriate peer review group convened in accordance
with the standard NIH peer review procedures.  As part of the initial merit
review, all applications will receive a written critique.  Applications will
also undergo a process in which only those 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, when applicable.

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 review, comments on the following aspects of the application will
be made 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 the assignment of the overall score:

(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 methods?  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, the adequacy of plans to include both genders and minorities and
their subgroups as appropriate for the scientific goals of the research will
be reviewed.  Plans for the recruitment and retention of subjects will also be
evaluated.

The initial review group will also examine the provisions for the protection
of human and animal subjects, the safety of the research environment, and
conformance with the NIH Guidelines for the Inclusion of Women and Minorities
as Subjects in Clinical Research.

AWARD CRITERIA

Applications will compete for available funds with all other approved
applications assigned to that institute or center. 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 are encouraged.  We welcome the opportunity to clarify any issues or
questions from potential applicants.

Direct inquiries regarding programmatic issues to:

June R. Lunney, PhD, RN
Division of Extramural Activities
National Institute of Nursing Research
Building 45, Room 3AN-12
Bethesda, MD  20892-6300
Telephone:  (301) 594-6908
FAX:  (301) 480-8260
Email:  [email protected]

Claudette G. Varricchio DSN, RN, FAAN
Division of Cancer Prevention and Control
National Cancer Institute
Executive Plaza North, Room 300
Bethesda, MD  20892-7340
Telephone:  (301) 496-8541
FAX:  (301) 496 8667
Email:  [email protected]

Dr. Fred Batzold
Division of AIDS
National Institute of Allergy and Infectious Diseases
6003 Executive Boulevard, Room 2B27
Bethesda, MD  20892-7640
Telephone:  (301) 402-0143
FAX:  (301) 402-3171
Email:  [email protected]

Benedetto Vitiello, M.D.
Office on AIDS
National Institute of Mental Health
Parklawn Building, Room 18/103
Bethesda, MD 20892-8030
Telephone:  (301) 443-7281
FAX: (301) 443-9719
Email:  [email protected]

Richard L. Nahin, M.P.H., Ph.D.
Office of Alternative Medicine
National Institutes of Health
Building 31, Room 5B-36
Bethesda, MD  20892-2182
Telephone:  (301) 496-4792
FAX:  (301) 480-3519
Email:  [email protected]

Direct inquiries regarding fiscal matters to:

Jeff Carow
Grants Management Office
National Institute of Nursing Research
6300 Center Drive, Room 3AN-12 - MSC 6301
Bethesda, MD  20892-6301
Telephone:  (301) 594-6869
FAX:  (301) 480-8260
Email:  [email protected]

William T. Wells
Grants Administration Branch
National Cancer Institute
6120 Executive Boulevard, Room 243
Bethesda, MD  20892
Telephone:  (301) 496-7800, ext. 250
FAX:  (301) 496-8601
Email:  [email protected]

Mary Kirker
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
6003 Executive Boulevard, Room 4B21
Bethesda, MD  20892-7610
Telephone:  (301) 402-6400
FAX:  (301) 480-3780
Email:  [email protected]

Diana S. Trunnell
Grant Management Branch
National Institute of Mental Health
Parklawn Building, Room 7C-08
Rockville, MD  20892-8030
Telephone:  (301) 443-2805
FAX:  (301) 443-6885
Email:  [email protected]

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance Nos.
93.361, 93.399, 93.855, 93.856, 93.242, and 93.213.  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.

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, 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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