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Note: This grant announcement amplifies a request for applications (RFA) that was originally published in the NIH Guide for Grants and Contracts on January 22, 1999.

Release Date: January 22, 1999

National Institute of Nursing Research
Agency for Health Care Policy and Research
National Cancer Institute
National Center for Complementary and Alternative Medicine
National Institute of Allergy and Infectious Diseases
National Institute of Dental and Craniofacial Research
National Institute of Mental Health
National Institute on Aging
National Institute of Neurological Disorders and Stroke

RFA: NR-99-004

Letter of Intent Receipt Date: April 30, 1999
Application Receipt Date: May 21, 1999

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Purpose

The National Institute of Nursing Research (NINR), the Agency for Health Care Policy and Research (AHCPR), the National Cancer Institute (NCI), the National Center for Complementary and Alternative Medicine (NCCAM), the National Institute of Allergy and Infectious Diseases (NIAID), the National Institute of Dental and Craniofacial Research (NIDCR), the National Institute of Mental Health (NIMH), and the National Institute on Aging (NIA) seek research grant applications that will generate scientific knowledge to lead to improved care for those at the end of life. Research applications may include basic, clinical or health care studies focused on the clinical management of physical and psychological symptoms, patient-provider and patient-family communication, ethics and clinical decisionmaking, caregiver support, or the context of care delivery for those facing life-limiting illnesses. The purpose of this initiative is to generate research that will improve the quality of dying for Americans and decrease the 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 request for applications (RFA), "Research on Care at the End of Life," is related to the areas of heart disease and stroke, cancer, diabetes and chronic disabling conditions, and HIV infection. Potential applicants may obtain a print 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

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. AHCPR cannot, by law, make grants to for-profit organizations. However, for-profit organizations may participate as subcontractors or members of consortia. Organizations described in section 501(c)4 of the Internal Revenue Code that engage in lobbying are not eligible. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as Principal Investigators.

Mechanism of Support

This RFA will use the National Institutes of Health (NIH) research project grant (R01) award mechanism and the exploratory/developmental grant (R21) mechanism. Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. This RFA is a one-time solicitation. The anticipated award date is September 30, 1999.

R01 Applications. R01 awards will vary in size and duration reflecting the nature and scope of the research proposed. Future unsolicited competing continuation applications will compete with all investigator-initiated applications and be reviewed according to customary peer review.

R21 Applications. The objective of the exploratory/developmental mechanism (R21) is to encourage applications from individuals who are interested in testing innovative or conceptually creative ideas that are scientifically sound and may advance our understanding of dying. Another objective is to encourage necessary initial development to provide a basis for future research project applications.

Exploratory/developmental studies are not intended for large-scale undertakings, nor to support or supplement ongoing research. Instead, investigators are encouraged to explore the feasibility of an innovative research question or approach which may not yet be sufficiently justified through existing research to compete as a standard research project grant (e.g., R01), and to develop a research basis for a subsequent application through other mechanisms.

Exploratory/developmental (R21) grants, may not exceed $75,000 per year in direct costs, not including indirect costs for collaborating institutions, if any. The total project period for an R21 application submitted in response to this RFA may not exceed 3 years. These grants are non-renewable and continuation of projects developed under the R21 program will be through the traditional unsolicited (R01 or P01) grant programs.

Funds Available

The NINR, AHCPR, NCI, NCCAM, NIAID, NIDCR, NIMH, NIA, and NINDS collectively intend to commit at least $2.7 million in FY 1999 to fund 10-12 new grants in response to this RFA. Additional projects will be considered on a case-by-case basis. Because the nature and scope of the research proposed may vary, it is anticipated that the size of awards will also vary. Although the financial plans of the participating institutes provide support for this program, awards pursuant to this RFA are contingent upon the availability of funds and the receipt of a sufficient number of applications of outstanding scientific and technical merit. At this time, it is not known if competing renewal applications will be accepted and/or if this RFA will be re-issued.

Research Objectives

Background

During the past several decades, biomedical advances have changed the way Americans die. The dying process now tends to be more extended, in part because medical treatments can manage pneumonia, infections, kidney failure, and other immediate causes of death. Many deaths involve a difficult period of decisionmaking between the patient's family and the clinical team about how much aggressive treatment to try and when to stop. Because it is often difficult to recognize futility, many patients experience burdensome diagnostic procedures and therapies that are exhausting, expensive, demoralizing, and of no ultimate benefit. Conversely, there is widespread fear that the only alternative to aggressive treatment is abandonment and suffering.

The healthcare system is primarily oriented to the cure of patients with acute medical conditions and injuries. It does not recognize that the medical needs of the dying patient are fundamentally different and require the integration of both medical and social service interventions. There is little infrastructure coordination between care service organizations. For most dying Americans end-of-life care is fragmented, painful, and emotionally distressing, with unnecessary transitions between medical care institutions.

In response to these fears and concerns, there are many national initiatives underway to improve care of the dying. Significant efforts are being made to better train health professionals and to encourage public awareness of the issues. Yet important gaps in knowledge limit the evidence base for care of the dying. From the cellular to the social level, much remains to be learned about how people die and how reliably excellent and compassionate care can be achieved (IOM, 1997). Research is needed to better understand the circumstances under which treatment is likely not to succeed, to facilitate communication and decisionmaking among those involved in end-of-life decisions, to support the development of a well integrated health care system and to provide better palliative care when comfort becomes the primary objective.

A research workshop, convened by the National Institutes of Health in September 1997, focused on "Symptoms in Terminal Illness." The report from that workshop is available at http://www.nih.gov/ninr/wnew/end-of-life.html. A subsequent program announcement was published in December 1997, PA-98-019, "Management of Symptoms at the End of Life" at http://grants.nih.gov/grants/guide/pa-files/PA-98-019.html. The research objectives from that program announcement are subsumed within the expanded focus of this request for applications.

In addition to basic biomedical research into the epidemiology and pathophysiology of symptoms and the mechanisms of symptom relief, the foundation for improved care at the end of life requires social, behavioral, and health services research. More needs to be understood about the emotional, social, cultural, and spiritual experiences of people who are dying and about the attitudinal, organizational, legal, cultural, and other factors which influence the care of those persons.

Currently, issues related to research methods play an important role in constraining inquiry into dying. There are pressing needs to better define key concepts, identify and test appropriate measures, develop strategies to minimize subject burden, and devise methods for complex data analysis. Advances in the scientific knowledge base for end-of-life care can only occur if resources are committed to these fundamental requirements.

Deficiencies in basic scientific knowledge about dying affect, at some point, the care of every individual. Biomedical, behavioral, social, and health services research is needed to provide the scientific foundation to support public and professional efforts to improve care at the end of life.

Objectives

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

Symptom management

• Epidemiology, pathogenesis, and clinical management of symptoms common at the end of life.
• Improved prevention and reduction of secondary side effects of drugs (including dysguesia and oral stomatitis).
• Better targeted drugs.
• Improved techniques for drug delivery.
• More precise assessment strategies for complex clinical problems.
• Identification of prognostic factors that help guide strategies to prevent or ease symptoms.
• Studies of the outcomes and quality of end-of-life care, including development of outcomes and quality measures.
• Additional descriptive data of symptom patterns and physiological changes surrounding the death event to enhance clinical management and information sharing with family members.
• Research on the management/treatment of pain at the end of life.

Communication

• Patterns of communication between patients and caregivers and processes which facilitate open discussion, discernment of patient and family wishes and concerns, and respect for diverse decisionmaking styles.
• Strategies to activate patients and families to expect and negotiate high quality care at the end of life.

Ethics and clinical decisionmaking

• Sources of information that assist providers, patients, and families to assess the situation-specific value of health care interventions.
• Autonomy issues for dying persons who are cognitively impaired.
• Strategies to better incorporate patients' values and preferences into advance care planning.
• Cultural variations influencing patient and family preferences.
• Interventions to enhance the psychological, social or spiritual well-being of persons facing life-limiting illness.

Caregiver support

• Strategies to assist professional caregivers to maintain the integrity of the patient-family dyad.
• Interventions which enhance existential meaningfulness, social support, and perception of professional availability for those caring for dying persons.
• Efficacy and appropriateness of therapies for grieving survivors.

Context of care delivery

• Collaborative investigations that combine community and social service organizations with medical care institutions in the care of chronically ill patients at the end of life.
• Innovative structures and processes to help patients and families to make transitions among care settings.
• Clinical information systems that capture data important to care at the end of life.
• Medical demographic studies in this and other countries of trends in the use of life-sustaining devices such as respirators.
• Investigations of the economic aspects of care at the end of life, including studies of the costs and avoidable costs of end-of-life care.
• Models of palliative care that are appropriate for dying persons with no primary caregiver.
• Identification of contextual factors that foster or deter a "good" death.
• Models of palliative care appropriate for nontraditional settings or special populations.

Research applications may be descriptive or correlational, but where possible should be hypothesis-driven. New knowledge should be anticipated that can be generalized beyond the program being studied. Applicants may propose secondary analyses of existing data, provided that new questions will be answered. Applications addressing the methodologic issues that constrain research into the care of the dying would also be appropriate.

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 and AHCPR 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 "NIH Guidelines on the Inclusion of Women and Minorities as Subjects in Clinical Research," published in the Federal Register of March 28, 1994 (FR 59 14508-14513), and printed in the NIH Guide for Grants and Contracts of March 18, 1994. AHCPR follows these guidelines, as applicable.

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 subject research conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them. 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: http://www.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.

Letter of Intent

Prospective applicants are asked to submit a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, the identities of other key personnel and participating institutions, and the number and title of the RFA in response to which the application may be submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows staff to estimate the potential review workload and avoid conflict of interest in the review.

The letter of intent is to be sent to:

Robin L. Gruber, M.P.S.
National Institute of Nursing Research
Building 45, Room 3AN-12, MSC 6300
Bethesda, MD 20857-6300
Telephone: (301) 594-2736
Fax: (301) 480-8260
E-mail: robin_gruber@nih.gov

Application Procedures

The research grant application form PHS 398 (rev. 4/98) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research and from:

Division of Extramural Outreach and Information Resources
National Institutes of Health
6701 Rockledge Drive, MSC 7910
Bethesda, MD 20857-7910
Telephone: (301) 435-0714
E-mail: GrantsInfo@nih.gov

The RFA label available in the PHS 398 (rev. 4/98) application form must be affixed to the bottom of the face page of the application. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number 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 20857-7710
Bethesda, MD 20817 (for express/courier service)

At the time of submission, please also send one additional copy of the application to:

Robin L. Gruber, M.P.S.
National Institute of Nursing Research
Building 45, Room Number 3AN-12, MSC 6300
Bethesda, MD 20857-6300

Applications must be received by the application receipt date listed in the heading of this RFA. If an application is received after that date, it will be returned to the applicant without review.

The Center for Scientific Review (CSR) will not accept any application in response to this RFA 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.

Review Considerations

Upon receipt, applications will be reviewed for completeness by the CSR and for responsiveness by the participating institutes. Incomplete and/or non-responsive applications will be returned to the applicant without further consideration. Applications that are complete and responsive to the RFA will be evaluated for scientific and technical merit by an appropriate peer review group convened by the CSR in accordance with the review criteria stated below. As part of the initial merit review, a process will be used by the initial review group in which applications 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 may receive a second-level review by the institutes' National Advisory Councils or Boards.

Review Criteria

The goals of the supported research are to advance our understanding of biologic systems, improve the control of disease, improve health care services, 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.

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

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

The initial review group will also examine the provisions for the protection of human subjects and the safety of the research environment.

Schedule

Letter of Intent Receipt Date: April 30, 1999
Application Receipt Date: May 21, 1999
Peer Review Date: July 1999
Council Review: September 1999
Earliest Anticipated Start Date: September 30, 1999

Award Criteria

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

• Scientific merit (as determined by peer review).
• Availability of funds.
• Programmatic priorities.

Inquiries

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

Direct inquiries regarding general programmatic issues to:

Dr. June Lunney
Division of Extramural Activities
National Institute of Nursing Research
Building 45, Room Number 3AN-12, MSC 6300
Bethesda, MD 20857-6300
Telephone: (301) 594-6908
Fax: (301) 480-8260
E-mail: June_Lunney@nih.gov

Dr. Claudette G. Varricchio
Division of Cancer Prevention
National Cancer Institute
Executive Plaza North, Room 300
Bethesda, MD 20857-7340
Telephone: (301) 496-8541
Fax: (301) 496-8667
E-mail: CV9H@nih.gov

Dr. Richard L. Nahin
National Center for Complementary and Alternative Medicine
Division for Research, Training, and Review
Building 31, Room 5B-36
Bethesda, MD 20857-2182
Telephone: (301) 496-4792
Fax: (301) 594-6757
E-mail: NahinR@od.nih.gov

Dr. Frederick Batzold
Division of AIDS
National Institute of Allergy and Infectious Diseases
6003 Executive Blvd., Room 2B27
Bethesda, MD 20857-7640
Telephone: (301) 402-0143
Fax: (301) 480-4582
E-mail: fb10c@nih.gov

Dr. Patricia Bryant
Division of Extramural Research
National Institute of Dental and Craniofacial Research
Building 45, Room 4AN-24E
Bethesda, MD 20857-6500
Telephone: (301) 594-2095
Fax: (301) 480-8318
E-mail: BryantP@DE45.nidr.nih.gov

Dr. David M. Stoff
Office on AIDS Research
National Institute of Mental Health
Parklawn Building, Room 18-101
Rockville MD 20847
Telephone: (301) 443-4625
Fax: (301) 443-9719
E-mail: dstoff@nih.gov

Dr. Sidney M. Stahl
Behavioral and Social Research Program
National Institute on Aging
7201 Wisconsin Avenue, Room 533
Bethesda, MD 20895-9205
Telephone: (301) 402-4156
Fax: (301) 402-0051
E-mail: Sidney_Stahl@nih.gov

Dr. Cheryl A. Kitt
Division of Convulsive, Infectious, and Immune Disorders
National Institute of Neurological Disorders and Stroke
7550 Wisconsin Avenue, Room 504
Bethesda, MD 20857
Telephone: (301) 496-1431
Fax: (301) 402-2060
E-mail: kittc@ninds.nih.gov

An application in response to this RFA may be of interest to the National Heart, Lung, and Blood Institute (NHLBI). Possible assignment to that institute will be considered on a case-by-case basis depending on the objectives of the study. For inquiries regarding NHLBI programmatic issues, contact:

Dr. Gail G. Weinmann
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Suite 10018
Bethesda, MD 20857
Telephone: (301) 435-0202
Fax: (301) 480-3557
E-mail: weinmang@gwgate.NHLBI.NIH.gov

Direct inquiries regarding fiscal matters to:

Jeff Carow
Grants and Contracts Management Office
National Institute of Nursing Research
Building 45, 3AN-12, MSC 6300
Bethesda, MD 20857-6300
Telephone: (301) 594-6869
Fax: (301) 480-8260
E-mail: jeff_carow@nih.gov

Mable L. Lam
Grants Management Office
Agency for Health Care Policy and Research
540 Gaither Road, Suite 4000
Rockville, MD 20850
Telephone: (301) 427-1448
E-mail: MLam@ahrq.gov

William T. Wells
Grants Administration Branch
National Cancer Institute
6120 Executive Boulevard, Room 243
Bethesda, MD 20857
Telephone: (301) 496-7800, ext. 250
Fax: (301) 496-8601
E-mail: William_Wells@nih.gov

Suzanne White
Division of Extramural Affairs
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 7156, MSC 7926
Bethesda, MD 20857-7926
Telephone: (301) 435-0171
Fax: (301) 480-3310
E-mail: sw52h@nih.gov

Mary Kirker
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
6003 Executive Blvd., Room 4B21
Bethesda, MD 20857-7610
Telephone: (301) 402-6400
Fax: (301) 480-3780
E-mail: mk35h@nih.gov

Martin Rubenstein
Division of Extramural Research
National Institute of Dental and Craniofacial Research
Building 45, Room 4AN-44A
Bethesda, MD 20857-6402
Telephone: (301) 594-4800
Fax: (301) 480-8301
E-mail: Rubenstein@DE45.nidr.nih.gov

Diana S. Trunnell
Grant Management Branch
National Institute of Mental Health
Parklawn Bldg., Room 7C-08
Rockville, MD 20847
Telephone: (301) 443-2805
Fax: (301) 443-6885
E-mail: Diana_Trunnell@nih.gov

Crystal Ferguson
Grants and Contracts Management Office
National Institute on Aging
7201 Wisconsin Avenue, 2N212
Bethesda, MD 20857
Telephone: (301) 496-1472
Fax: (301) 402-3672
E-mail: Crystal_Ferguson@nih.gov

Karen D. Shields
Grants Management Branch
National Institute of Neurological Disorders and Stroke
Federal Building, Room 1004
Bethesda, MD 20857
Telephone: (301) 496-9231
E-mail: s26n@nih.gov

Authority and Regulations

This program is described in the Catalog of Federal Domestic Assistance, No. 93.361 (Nursing Research), No. 93.226 (AHCPR), No. 93.399 (Cancer Control), 93.213 (Alternative Medicine), No. 93.855 (Immunology, Allergy, and Transplantation Research), No. 93.856 (Microbiology and Infectious Disease Research), No. 93.121 (Dental), No. 93.242 (Mental Health), No. 93.866 (Aging), and No. 93.854 (Neurology). 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 Title IX (42 USC 299-299c-6). Awards are administered under PHS grants policies and Federal Regulations 42 CFR 52 and 67, subpart A, 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 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.

AHCPR Publication No. 99-R034
Current as of January 22, 1999