REDUCING BARRIERS TO SYMPTOM MANAGEMENT AND PALLIATIVE CARE
RELEASE DATE: May 26, 2004
RFA Number: RFA-CA-05-013
EXPIRATION DATE: September 27, 2004
Department of Health and Human Services (DHHS)
National Institutes of Health (NIH)
COMPONENTS OF PARTICIPATING ORGANIZATION:
National Cancer Institute (NCI)
National Institute of Nursing Research (NINR)
Office of Research on Women’s Health (ORWH)
CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S): 93.399 (NCI); 93.361 (NINR)
LETTER OF INTENT RECEIPT DATE: August 24, 2004
APPLICATION RECEIPT DATE: September 24, 2004
THIS RFA CONTAINS THE FOLLOWING INFORMATION
o Purpose of this RFA
o Research Objectives
o Mechanisms of Support
o Funds Available
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Special Requirements
o Where to Send Inquiries
o Letter of Intent
o Submitting an Application
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations
PURPOSE OF THIS RFA
The purpose of this RFA is to solicit grant applications for research
directed at developing and testing interventions to reduce or overcome
barriers to the delivery of appropriate symptom management and
palliative care to patients suffering from disease and/or treatment-
related sequelae. Historically, the cancer symptom management research
community has focused largely on describing symptom prevalence and
testing new interventions to ameliorate one or more symptoms. Many of
these studies have shown efficacy, yet, because of a number of patient,
clinician, and health system-related barriers, the larger cancer
community is not adopting these findings. Research is needed to
discover new or innovative way to implement evidenced based practices
into routine clinical care. We must expand and accelerate our potential
to address the problems of inadequate symptom management and palliative
care among diverse populations in the United States. Given NCI’s
challenge goal of eliminating the suffering and death due to cancer by
2015, efforts must be directed to improving the delivery of treatments
to prevent or ameliorate the adverse physical and psychosocial
consequences associated with the diagnosis and treatment of cancer.
As a result of advances in the early detection, prevention, and
treatment of cancer, the population of individuals living with,
through, and beyond a cancer diagnosis in this country is growing.
Currently, an estimated 9.6 million Americans are living with a history
of malignancy. At one time almost uniformly fatal for most, cancer has
now become a chronic condition for many. Success in achieving this
goal, however, has not been without cost. None of our current cancer
therapies is symptom-free. Side effects may range from mild and
transient (e.g., alopecia, nausea, neutropenia), to chronic (e.g
fatigue, sexual dysfunction, lymphedema), to late and potentially life-
threatening (e.g., second cancers, cardiomyopathy). While prevalence
estimates vary widely, a substantial number of patients and survivors
experience cancer- and treatment-related physical and psychosocial
impairments. Pain, depression, and fatigue, alone or in combination,
are the most frequently cited symptoms that occur along the trajectory
of the cancer experience. Cancer patients may also suffer from
anorexia, cachexia, gastrointestinal problems, cognitive impairments,
dyspnea, and anxiety at various stages of their illness. Although the
chronicity of cancer-associated conditions mandates symptom management
and palliative care throughout the course of the disease, many cancer
patients fail to receive such care and continue to suffer needlessly.
The prevalence of a number of cancer-related symptoms, most notably
pain, depression, and fatigue, has been unacceptably high for more than
two decades and there is little indication that it is decreasing. Of
the 29 epidemiological studies reporting on the prevalence and/or
incidence of cancer-related pain between 1982 and 2001, no single
survey identified a pain prevalence rate below 14 percent of the
patients surveyed. One recent study reported a pain prevalence rate of
52 percent among 240 Veterans diagnosed with both solid tumors and
hematological cancers. For both the clinician and the cancer patient,
depression is often viewed as a natural symptom or outcome of the
disease. To the contrary, cancer patients are three times more likely
than the general population and almost two times more likely than other
medically hospitalized patients to develop depression. A number of
studies have shown that depressed cancer patients are more likely to
request euthanasia or physician-assisted suicide and are more likely to
commit suicide. The prevalence of depression is higher in cancer
patients with the greatest disability and distressing physical
symptoms, such as pain. Similar to cancer-related pain and depression,
the prevalence of cancer-related fatigue is high and often variable.
Three studies, conducted on a total of 1,796 cancer patients diagnosed
with a variety of cancer types and stages, reported prevalence rates
ranging from 26 percent to as high as 58 percent.
The variability in the prevalence of specific cancer related symptoms
could be attributed to a variety of factors, which include: disease
characteristics, patient demographics, clinician and health system
characteristics, and methodological issues, such as lack of consensus
on the best measures of symptoms. For example, stage of disease is
frequently cited as an important predictor of symptom incidence and
severity. Cleeland and colleagues, surveying 54 treatment locations
affiliated with the Eastern Cooperative Oncology Group (ECOG),
estimated that 67 percent of metastatic cancer patients (871 of 1308)
had pain. Vuorinen, on the other hand, found a much lower prevalence
of pain, 28 percent, in 240 newly diagnosed cancer patients.
We believe that a number of advances have been made in the
understanding and treatment of cancer-related symptoms, but these
advances have not translated into standard-of-care practices in the
cancer setting. Many cancer patients report that they are not
routinely asked about their symptoms, are reluctant or afraid to report
symptoms, are unaware of available symptom management treatments, do
not adhere to symptom treatments when provided, and at times are not
offered any treatment even when they do report problematic symptoms.
In the same study conducted by Cleeland and colleagues, 42 percent of
those with pain were inadequately managed. Clearly, the prevalence of
one or more symptoms would be much lower and overall quality of life
improved if patients were asked about their symptoms, were offered
treatments, and were assisted in adhering to the treatment plan.
Special populations, such as children, the elderly, minority, and
individuals of lower socio-economic status are at higher risk for
receiving inadequate or no treatment for their cancer-related symptoms.
Barriers unique to vulnerable and medically underserved populations
include pharmacies that do not stock opiods or have inadequate supplies
of these drugs and individuals lacking knowledge of federal, state, and
local benefits that may assist them in accessing hospice and end of
Pain management has been well-studied, resulting in the publication and
wide dissemination of clinical practice guidelines through multiple
channels and organizations, including requirements through the Joint
Commission on Accreditation of Healthcare Organizations (JCAHO).
Despite the long publication history of these guidelines, cancer
patients continue to suffer from inadequate relief of their pain. The
identification and treatment of psychiatric disorders and psychosocial
distress have also greatly improved, but in patients with cancer, they
continue to be under diagnosed and under treated, especially in those
with advanced cancer. The American Society of Clinical Oncology
conducted a survey in 1998 of more than 3,200 oncologists and found
that one of their top educational needs was to improve their ability to
diagnose and treat depression and psychosocial distress in cancer
patients, especially those nearing the end-of-life (Ezekial Emmanuel,
personal communication, 2003). Interventions must be developed that
reduce the barriers to patients receiving optimal relief of their
symptoms, not only to eliminate suffering, but also to ensure adherence
to cancer treatment when cancer can be cured or controlled.
Physician-related barriers to delivering symptom management are most
often related to inadequate skills and knowledge in the areas of
communication, assessment, and treatment. The physician, for example,
may not remember or think to ask a patient about symptoms, while the
patient may not feel comfortable raising issues beyond immediate cancer
care. There are often difficulties in communication, notably in
children, the elderly, and across cultures. The physician may hesitate
to prescribe narcotics for pain control for fear of potential addiction
or side effects. In treating patients who are on multiple medications
for co-morbidities, which are common to many older cancer patients, the
physician may be unsure how best to manage additional medications.
Lack of adequate time and staff may also compromise a physician’s
ability to treat symptoms appropriately. Further exacerbating the
problem is the fragmentation of follow-up care of cancer survivors.
Oncologists, which can include medical, surgical, and radiation
oncologists, as well as primary care providers, mental health
specialists, and other subspecialties may all be involved in the care
of cancer patients and survivors, yet there may not be a point person
coordinating the logistics of these many specialties. Communication
between and among all the health care providers caring for a cancer
patient can be difficult, particularly if they are in different
locations, without a common database for medical records.
A number of health system factors can potentially hinder the delivery
of symptom management. They can range from environmental, legal and
regulatory restrictions to the macro (hospital policies and
pharmacies, information systems) and micro (shared practice cultures
and processes) within health care systems. The legal and regulatory
restrictions compound the problem because they often vary from state to
state and reimbursement policies can vary among private health
insurance and public programs. All such factors can affect safety,
effectiveness, patient-centeredness, timeliness, efficiency, and
equity. For example, problems related to the larger healthcare system
include inadequate reimbursement, restrictive regulation of controlled
substances, and problems of availability of opioids in the patient’s
Effective delivery of palliative care within a health care environment
depends on the timely coordinated response to patient needs. Examples
of problems include inadequate information systems to learn about
patient symptoms and to provide resources both to clinicians and
patients to address them. Examples of challenges at the level of the
office or clinic include organizing care processes to anticipate need,
to respond to individual patient preferences and to problems when they
are most needed, to address capacity and patient flow, to gather
information about patterns of care for use in designing processes and
improving care, and to develop effective multidisciplinary teams that
use the skills and knowledge of all members. Addressing these
challenges might go beyond a focus on the patient visit to include
other forms of communicating with patients and providing care using a
variety of telecommunication platforms. Any proposal, however, needs
to be evaluated in relation to its effect on patient care and outcomes.
In addition to system and provider barriers, patients and their family
members or caregivers may also contribute to problems in the delivery
of optimal symptom management. Among the most common recipient barriers
is lack of awareness of need. For example, many patients, like their
providers, may simply assume that symptoms of depression or anxiety are
expected when the diagnosis is cancer. The adverse impact on patients
functioning of insomnia and fatigue, among the more common symptoms
experienced in those in active treatment, is often underappreciated.
The frequently parallel belief that there is nothing to be done when a
symptom occurs is a further barrier to receipt of appropriate help.
Reluctance to appear weak or foolish or unable to cope additionally can
contribute to failure to report symptoms when they do occur, even when
these are troublesome to patients. For example, a woman undergoing
chemotherapy may be very upset by her hair loss but fail to mention
this to her treating team because she feels her preoccupation is a
vain concern in the context of the seriousness of her illness.
The perceived stigma associated with needing or having to ask for help
itself can be a potent barrier to accessing care. This may be
particularly true among different ethnocultural groups where a premium
is placed on stoicism. In other cases, concern about taking up limited
clinic time or physician visits to discuss what may seem to be
unrelated or seemingly non-medical issues (e.g., anxiety, social
isolation) may cause patients to avoid these important topics in
discussions with their doctors or clinic staff. Patients may also wait
for a physician to introduce a topic before expressing their concerns.
At times, embarrassment can keep a patient from discussing a bothersome
symptom. This is especially true when the symptom affects bowel,
bladder, or sexual functioning domains. Finally, even when effective
help is offered, patients may be resistant to use the interventions
that are recommended. This may be due to fear of an intervention’s
consequences. A classic example is the often expressed concern that
narcotic use for pain will lead to subsequent addiction. Alternatively,
they may be overwhelmed with the challenge of self-medicating and
adjusting dosage to maximize benefits. Reluctance to seek help (e.g.,
counseling or rehabilitation services) may also be driven by lack of
insurance or financial resources to pay for these services.
Cancer and treatment-related symptoms among survivors may pose an
additional set of problems. These post-treatment symptoms may be
interpreted as potential disease recurrence and result in fear and a
reluctance to acknowledge them. Alternatively survivors may believe
that chronic symptoms (e.g., pain, fatigue, lymphedema) are simply
something with which they must learn to live. Because research
documenting the types and frequency of long-term and late effects of
cancer is only now beginning to appear, it is difficult to know how
common some symptoms are in the growing population of both young and
older Americans living with a history of cancer.
For their part, both family and non-family caregivers often share
concerns and reservations similar to those experienced by patients
themselves. They may fail to recognize that the patient’s symptom
warrants further workup or care, may want to believe the individual for
whom they are caring is coping well, may think there is little to be
done for a given problem, may worry about addicting a patient or
inducing undesirable side effects by providing medication, or may
believe they or others in the home or external care setting can provide
all the support or intervention required to meet a patient’s symptom
In summary, there is compelling evidence that cancer patients do not
receive adequate symptom management or palliative care throughout the
course of their disease. We need to be able to identify who is at risk
for cancer-related symptoms and test methods that will ensure the
routine delivery of interventions across the continuum of cancer care.
Results of research related to this RFA should (1) generate knowledge
about how to reduce barriers to the delivery of symptom management and
palliative care, (2) address barriers for vulnerable, medically
underserved, and special populations to access and receive palliative
care, and (3) encourage research collaborations across disciplines and
cancer care delivery systems (i.e., academic centers, community
hospitals, HMOs, doctor practices, hospices) and public-private
Objectives and Scope
The goals of this research initiative are to develop and test
interventions to overcome barriers to the delivery of symptom
management and palliative care, thereby decreasing the suffering and
improving the health and quality of life of persons living with cancer.
Program staff at the NCI and other NIH Institutes and Centers that are
participating in this RFA conceptualize symptom management as one
component of the care delivered to cancer patients at risk for or
experiencing disease-and treatment-related symptoms. Other components,
as defined by the World Health Organization, include communication,
decision-making, management of complications of treatment, psychosocial
care of patient and family, and care of the dying. To address the
complex and interdependent physical, social, psychological, and
existential needs of patients and their families requires a
multidisciplinary team approach. Ideally, palliative care begins at
the diagnosis of cancer or other illness and is given in conjunction
with disease directed therapies, such as chemotherapy or radiation
therapy. Accordingly, the focus of this initiative is broad and
includes cancer patients across the disease trajectory. Settings where
interventions could be tested include, but are not limited to, acute
care facilities, the home, skilled nursing facilities, outpatient
clinics, and hospices. Given the significant number of cancer patients
being treated in community settings, we are particularly interested in
applications that would access this type of setting or would develop
interventions that are generalizable to the broader community setting.
For example, the unique research infrastructures of the Community
Clinical Oncology Program
(http://www3.cancer.gov/prevention/ccop/aboutccop.html) and the HMO
Cancer Research Network (http://hmoresearchnetwork.org/) make them
particularly suitable for implementing these types of interventional
Common strategies to disseminate evidenced based practice guidelines,
e.g., scientific publications, direct mailings, electronic
dissemination, etc., have been found to be insufficient to change or
improve clinical practice. New methods are needed to implement
(sometimes referred to as translate) what is known to be effective or
appropriate symptom management into routine cancer care. The focus of
this RFA is to solicit applications in this emerging field of
The proposed interventions should build on current knowledge and
research findings in the area of patient, family/informal caregiver,
clinician, and/or health care system barriers. We anticipate that most
projects will meet the following NIH operational definition of a
clinical trial, a prospective biomedical or behavioral research study
of human subjects that is designed to answer specific questions about
biomedical or behavioral interventions. Please note, clinical trials
that are testing agents or drug delivery systems to improve one or more
symptoms will not be considered responsive to this RFA. In addition,
projects that are primarily descriptive or observational will not be
considered responsive to this RFA.
The following list of research topics are for illustrative purposes.
Applications on topics not explicitly listed below, but which fall
within the objective described above, are also welcome.
A) Research Related to Patient, Family, or Informal Caregiver
o Examine the effects of patient concerns, patient choices, decision-
making strategies, and caregiver values on adhering to symptom
management or palliative care strategies.
o Test interventions that will promote patients and caregivers
understanding and use of medications for symptom relief.
o Test whether interventions to improve patient’s and caregiver’s
ability to report onset, severity, and duration of symptoms at any
point along the cancer continuum will improve patient reported
o Test interventions targeted to specific age groups that experience
challenges to optimal symptom management due to developmental stage,
such as young children, adolescents and young adults, or the elderly.
Include both patients and caregivers wherever appropriate.
B) Research Related to Health Care Providers:
o Determine if systematic use of clinical practice guidelines improves
o Examine the effect of knowledge of ethical and legal codes on the
quality of symptom management.
o Test whether interventions that incorporate the routine use of a
brief, validated symptom assessment tool would improve symptoms.
o Test whether interventions to increase clinician referral to and/or
recommendation for the use of support groups would improve patient
o Test interventions to improve clinician’s communication, assessment
and management of symptoms or problems that are under reported or
difficult to discuss, i.e., end of life issues, sexual dysfunction.
o Test interventions to reduce communication barriers between provider
and patients and/or caregivers that impede symptom relief and HRQOL
throughout the cancer trajectory.
C) Health Care System
o Assess the efficacy of and cost effectiveness of new ways for
patients and families to report distressing symptoms to their health
o Examine the impact of novel technologies to enhance patients and
their families abilities to report distressing symptoms.
o Examine the impact of a feedback mechanism that would routinely
describe practice patterns for assessing and managing symptoms.
o Test novel strategies that improve delivery of symptom management to
medically underserved and vulnerable cancer populations.
o Test innovative models of care coordination within health care
systems that will improve communication and quality of care for
patients transitioning between care delivery systems, i.e., acute care
o Examine the effect of standardizing elements of palliative care
within clinical information systems.
o Examine the impact of shared formularies when patients move to
another site of care.
The cultural, ethnic, and developmental aspects of the population
targeted for study must be considered in designing interventions.
Validation of established assessment guides in low literacy and non-
English speaking populations should be considered as part of a broader
intervention where appropriate. Biological and behavioral variables
should be included as appropriate to the research question.
Collaboration across disciplines and the inclusion of community and
primary care givers on the research team are considered essential
elements to the success of the project.
MECHANISMS OF SUPPORT
This RFA will use NIH R01 (research project grant) and R21
(exploratory/developmental grant) award mechanisms. As an applicant
you will be solely responsible for planning, directing, and executing
the proposed project. This RFA is a one-time solicitation. Future
unsolicited, competing-continuation applications based on this project
will compete with all investigator-initiated applications and will be
reviewed according to the customary peer review procedures. The
anticipated award date is July, 2005. Applications that are not funded
in the competition described in this RFA may be resubmitted as NEW
investigator-initiated applications using the standard receipt dates
for NEW applications described in the instructions to the PHS 398
For R21 submissions, an applicant may request a project period of up to
2 years and submit budgets up to $100,000 direct cost (four budget
modules) per year unless the application includes consortium costs, in
which case the limit is $125,000 direct costs (five budget modules) per
year. These grants are non-renewable and continuation of projects
developed under this RFA will be through the traditional unsolicited
investigator initiated grant program.
For R01 submissions, an applicant may request a project period of up to
5 years and is strongly encouraged to submit budgets that do not exceed
$500,000 in direct costs in any year of the project.
(Please note that facilities and administrative [F&A] costs requested
by any consortium participants are excluded from the direct cost limit
per NIH Guide Notice NOT-OD-04-040.)
This RFA uses just-in-time concepts. It also uses the modular as well
as the non-modular budgeting formats (see
Specifically, if you are submitting an application with direct costs in
each year of $250,000 or less, use the modular format. Otherwise
follow the instructions for non-modular research grant applications.
This program does not require cost sharing as defined in the current
NIH Grants Policy Statement at
The participating ICs intend to commit $5,200,000 in FY 2005 to fund
ten to fifteen new and/or competitive continuation grants in response
to this RFA. Because the nature and scope of the proposed research
will vary from application to application, it is anticipated that the
size and duration of each award will also vary. Although the financial
plans of the ICs 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 meritorious applications. At this time, it is
not known if this RFA will be reissued.
You may submit (an) application(s) if your institution has any of the
o For-profit or non-profit organizations;
o Public or private institutions, such as universities, colleges,
hospitals, and laboratories;
o Units of state and local governments;
o Eligible agencies of the Federal government;
o Domestic or foreign institutions/organizations; and
o Faith-based or community-based organizations.
INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS
Any individual with the skills, knowledge, and resources necessary to
carry out the proposed research is invited to work with their
institution to develop an application for support. Individuals from
underrepresented racial and ethnic groups as well as individuals with
disabilities are always encouraged to apply for NIH programs.
Data Safety and Monitoring: applicants should describe the
organizational structures and procedures they will employ to ensure the
safety of participants and the validity and integrity of the data.
Annual Meetings: Applicants funded under this RFA will be required to
attend meetings in which study plans, findings, and issues of common
interest and concern will be shared and discussed. All R01 applicants
should include in their budgets funds for attending an initial kick-
off meeting at or near the time of the award, and annual meetings
thereafter through the end of the requested term of award. All R21
applicants should include in their budgets funds for 1 meeting in the
second year of the grant. For budgeting purposes, applicants should
assume that the meetings will be held in Bethesda, Maryland at the
National Institutes of Health and require the attendance of at least
the Principal Investigator (PI). Travel and lodging costs should be
Final Report: at the completion of the project, the Principal
Investigator (PI) must provide a detailed report to the Program
Director that addresses:
o overall aims / goals of the proposal,
o the extent to which the aims were accomplished,
o the challenges encountered,
o the detailed results of the study and of interim analyses,
o detailed list of presentations, abstracts, and papers (accepted, in
o hard copies of publications (accepted, in press, published), and
o copies of any products developed as part of the research (e.g.
measurement tools, educational materials, intervention manuals, etc).
WHERE TO SEND INQUIRIES
We encourage inquiries concerning this RFA and welcome the opportunity
to answer questions from potential applicants. Inquiries may fall into
three areas: scientific/research, peer review, and financial or grants
o Direct your questions about scientific/research issues to:
Ann O Mara, Ph.D., M.P.H., R.N.
Community Oncology and Prevention Trials Research Group
Division of Cancer Prevention
National Cancer Institute
6130 Executive Blvd., EPN Room 2012
Bethesda, MD 20892-8329
Rockville, MD 20854 (for express/courier service)
Telephone: (301) 496-8541
Martha L. Hare, Ph.D., R.N
NIH/National Institute of Nursing Research
6701 Democracy Boulevard
One Democracy Plaza, Room 710
Bethesda, MD 20892-4870 (Courier: 20817)
Lisa Begg, Ph.D.
Director of Research Programs
1 Center Drive
Bethesda, MD 20892
o Direct your questions about peer review issues to:
National Cancer Institute
Division of Extramural Activities
6116 Executive Boulevard, Room 8041, MSC 8329
Bethesda, MD 20892-8329
Telephone: (301) 496-3428
FAX: (301) 402-0275
o Direct your questions about financial or grants management matters
Grants Administration Branch
National Cancer Institute
6120 Executive Boulevard, EPS Room 243
Bethesda, MD 20892-7150
Rockville, MD 20852 (for express/courier service)
Telephone: (301) 846-1014
FAX: (301) 846-5720
LETTER OF INTENT
Prospective applicants are asked to submit a letter of intent that
includes the following information:
o Descriptive title of the proposed research
o Name, address, and telephone number of the Principal Investigator
o Names of other key personnel
o Participating institutions
o Number and title of this RFA
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 NCI staff to estimate the potential review
workload and plan the review.
The letter of intent is to be sent by the date listed at the beginning
of this document. The letter of intent should be sent to:
Ann O Mara, Ph.D., M.P.H., R.N.
Community Oncology and Prevention Trials Research Group
Division of Cancer Prevention
National Cancer Institute
6130 Executive Blvd., EPN 2012
Bethesda, MD 20892-7150
Rockville, MD 20852 (for express/courier service)
Telephone: (301) 496-8541
Prospective applicants are strongly encouraged to contact the program
director listed above at their earliest convenience.
SUBMITTING AN APPLICATION
Applications must be prepared using the PHS 398 research grant
application instructions and forms (rev. 5/2001). Applications must
have a Dun and Bradstreet (D&B) Data Universal Numbering System (DUNS)
number as the Universal Identifier when applying for Federal grants or
cooperative agreements. The DUNS number can be obtained by calling
(866) 705-5711 or through the web site at
http://www.dunandbradstreet.com/. The DUNS number should be entered on
line 11 of the face page of the PHS 398 form. The PHS 398 document is
available at http://grants.nih.gov/grants/funding/phs398/phs398.html in
an interactive format. For further assistance, contact GrantsInfo,
Telephone: (301) 710-0267, Email: GrantsInfo@nih.gov.
SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS: Applications
requesting up to $250,000 per year in direct costs must be submitted in
a modular grant format. The modular grant format simplifies the
preparation of the budget in these applications by limiting the level
of budgetary detail. Applicants request direct costs in $25,000
modules. Section C of the research grant application instructions for
the PHS 398 (rev. 5/2001) at
http://grants.nih.gov/grants/funding/phs398/phs398.html includes step-
by-step guidance for preparing modular grants. Additional information
on modular grants is available at
USING THE RFA LABEL: The RFA label available in the PHS 398 (rev.
5/2001) application form must be affixed to the bottom of the face page
of the application. Type the RFA number on the label. 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. The RFA
label is also available at:
SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten
original of the application, including the Checklist, and three 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)
At the time of submission, two additional copies of the application and
all five copies of the appendices must be sent to:
Division of Extramural Activities
National Cancer Institute
6116 Executive Blvd., Room 8041, MSC-8329
Rockville, MD 20852 (express courier)
Bethesda MD 20892-8329
Appendices should be comprised of single-sided, unbound materials, with
separators between documents.
APPLICATIONS HAND-DELIVERED BY INDIVIDUALS TO THE NATIONAL CANCER
INSTITUTE WILL NO LONGER BE ACCEPTED. This policy does not apply to
courier deliveries (i.e., FEDEX, UPS, DHL, etc.)
This policy is similar to and consistent with the policy for
applications addressed to Centers for Scientific Review as published in
the NIH Guide Notice
APPLICATION PROCESSING: Applications must be received on or before 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.
Although there is no immediate acknowledgement of the receipt of an
application, applicants are generally notified of the review and
funding assignment within 8 weeks.
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. However, when a previously unfunded application,
originally submitted as an investigator-initiated application, is to be
submitted in response to an RFA, it is to be prepared as a NEW
application. That is the application for the RFA must not include an
Introduction describing the changes and improvements made, and the text
must not be marked to indicate the changes from the previous unfunded
version of the application.
PEER REVIEW PROCESS
Upon receipt, applications will be reviewed for completeness by the CSR
and responsiveness by the NCI. Incomplete and/or non-responsive
applications will not be reviewed.
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 Division of Extramural Activities of the
NCI in accordance with the review criteria stated below. As part of
the initial merit review, all applications will:
o 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 and assigned a priority score
o Receive a written critique
o Receive a second level review by an appropriate national advisory
council or board.
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 evaluate the
application in order to judge the likelihood that the proposed research
will have a substantial impact on the pursuit of these goals. The
scientific review group will address and consider each of these
criteria in assigning the application’s overall score, weighting them
as appropriate for each application.
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.
SIGNIFICANCE: Does this study address an important problem in barriers
to delivering symptom management and palliative care? 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?
APPROACH: Are the conceptual framework, design, methods, and analyses
adequately developed, well-integrated, and appropriate to the aims of
the project? Is there a well-designed evaluation plan of the effect of
the intervention on patient outcomes? Does the applicant acknowledge
potential problem areas and consider alternative tactics? Does this
intervention carry the potential to be incorporated in routine cancer
care? Is it likely to be sustainable after research funding has ended?
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
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
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?
ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, the
following items will be considered in the determination of scientific
merit and the priority score.
PROTECTION OF HUMAN SUBJECTS FROM RESEARCH RISK: The involvement of
human subjects and protections from research risk relating to their
participation in the proposed research will be assessed. (See criteria
included in the section on Federal Citations, below).
INCLUSION OF WOMEN, MINORITIES AND CHILDREN IN RESEARCH: The adequacy
of plans to include subjects from both genders, all racial and ethnic
groups (and subgroups), and children as appropriate for the scientific
goals of the research. Plans for the recruitment and retention of
subjects will also be evaluated. (See Inclusion Criteria in the
sections on Federal Citations, below).
ADDITIONAL REVIEW CONSIDERATIONS
Sharing Research Data
Applicants requesting more than $500,000 in direct costs in any year of
the proposed research must include a data sharing plan in their
application. The reasonableness of the data sharing plan or the
rationale for not sharing research data will be assessed by the
reviewers. However, reviewers will not factor the proposed data sharing
plan into the determination of scientific merit or priority score.
BUDGET: The reasonableness of the proposed budget and the requested
period of support in relation to the proposed research.
RECEIPT AND REVIEW SCHEDULE
Letter of Intent Receipt Date: August 24, 2004
Application Receipt Date: September 24, 2004
Peer Review Date: February 200
Council Review: June 2005
Earliest Anticipated Start Date: July 2005
Award criteria that will be used to make award decisions include:
o Scientific merit (as determined by peer review)
o Availability of funds
o Programmatic priorities.
REQUIRED FEDERAL CITATIONS
HUMAN SUBJECTS PROTECTION: Federal regulations (45CFR46) require that
applications and proposals involving human subjects must be evaluated
with reference to the risks to the subjects, the adequacy of protection
against these risks, the potential benefits of the research to the
subjects and others, and the importance of the knowledge gained or to
be gained. See
DATA AND SAFETY MONITORING PLAN: Data and safety monitoring is
required for all types of clinical trials, including physiologic,
toxicity, and dose-finding studies (phase I); efficacy studies (phase
II); efficacy, effectiveness and comparative trials (phase III). The
establishment of data and safety monitoring boards (DSMBs) is required
for multi-site clinical trials involving interventions that entail
potential risk to the participants. (See NIH Policy for Data and Safety
Monitoring, NIH Guide for Grants and Contracts, June 12, 1998 at
SHARING RESEARCH DATA: Investigators submitting an NIH application
seeking $500,000 or more in direct costs in any single year are
expected to include a plan for data sharing
(http://grants.nih.gov/grants/policy/data_sharing) or state why this is
not possible. Investigators should seek guidance from their
institutions, on issues related to institutional policies, local IRB
rules, as well as local, state and Federal laws and regulations,
including the Privacy Rule. Reviewers will consider the data sharing
plan but will not factor the plan into the determination of the
scientific merit or the priority score.
Clinical trials supported or performed by NCI require special
considerations. The method and degree of monitoring should be
commensurate with the degree of risk involved in participation and the
size and complexity of the clinical trial. Monitoring exists on a
continuum from monitoring by the principal investigator/project manager
or NCI program staff or a Data and Safety Monitoring Board (DSMB).
These monitoring activities are distinct from the requirement for study
review and approval by an Institutional review Board (IRB). For
details about the Policy for the NCI for Data and Safety Monitoring of
Clinical trials see
http://deainfo.nci.nih.gov/grantspolicies/datasafety.htm. For Phase I
and II clinical trials, investigators must submit a general description
of the data and safety monitoring plan as part of the research
application. For additional information, see NIH Guide Notice on
Further Guidance on a Data and Safety Monitoring for Phase I and II
Trials at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-038.html
. Information concerning essential elements of data safety
monitoring plans for clinical trials funded by the NCI is available at
INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH: It is the
policy of the NIH that women and members of minority groups and their
sub-populations must be included in all NIH-supported clinical research
projects unless a clear and compelling justification is provided
indicating that inclusion is inappropriate with respect to the health
of the subjects or the purpose of the research. This policy results
from the NIH Revitalization Act of 1993 (Section 492B of Public Law
All investigators proposing clinical research should read the "NIH
Guidelines for Inclusion of Women and Minorities as Subjects in
Clinical Research - Amended, October, 2001," published in the NIH Guide
for Grants and Contracts on October 9, 2001
a complete copy of the updated Guidelines are available at
The amended policy incorporates: the use of an NIH definition
of clinical research; updated racial and ethnic categories in
compliance with the new OMB standards; clarification of language
governing NIH-defined Phase III clinical trials consistent with the new
PHS Form 398; and updated roles and responsibilities of NIH staff and
the extramural community. The policy continues to require for all NIH-
defined Phase III clinical trials that: a) all applications or
proposals and/or protocols must 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)
investigators must report annual accrual and progress in conducting
analyses, as appropriate, by sex/gender and/or racial/ethnic group
INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN
SUBJECTS: The NIH maintains a policy 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.
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 is available at
REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS: NIH
policy requires education on the protection of human subject
participants for all investigators submitting NIH proposals for
research involving human subjects. You will find this policy
announcement in the NIH Guide for Grants and Contracts Announcement,
dated June 5, 2000, at
A continuing education program in the protection of human participants
in research is available online at: http://cme.nci.nih.gov/.
HUMAN EMBRYONIC STEM CELLS (hESC): . Criteria for federal funding of
research on hESCs can be found at http://stemcells.nih.gov/index.asp
and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html.
Only research using hESC lines that are registered in the NIH Human
Embryonic Stem Cell Registry will be eligible for Federal funding
(see http://escr.nih.gov). It is the responsibility of the
applicant to provide, in the project description and elsewhere in the
application as appropriate, the official NIH identifier(s) for the hESC
line(s) to be used in the proposed research. Applications that do not
provide this information will be returned without review.
PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT:
The Office of Management and Budget (OMB) Circular A-110 has been
revised to provide public access to research data through the Freedom
of Information Act (FOIA) under some circumstances. Data that are (1)
first produced in a project that is supported in whole or in part with
Federal funds and (2) cited publicly and officially by a Federal agency
in support of an action that has the force and effect of law (i.e., a
regulation) may be accessed through FOIA. It is important for
applicants to understand the basic scope of this amendment. NIH has
provided guidance at
Applicants may wish to place data collected under this RFA in a public
archive, which can provide protections for the data and manage the
distribution for an indefinite period of time. If so, the application
should include a description of the archiving plan in the study design
and include information about this in the budget justification section
of the application. In addition, applicants should think about how to
structure informed consent statements and other human subjects
procedures given the potential for wider use of data collected under
STANDARDS FOR PRIVACY OF INDIVIDUALLY IDENTIFIABLE HEALTH INFORMATION:
The Department of Health and Human Services (DHHS) issued final
modification to the Standards for Privacy of Individually Identifiable
Health Information , the Privacy Rule, on August 14, 2002. The
Privacy Rule is a federal regulation under the Health Insurance
Portability and Accountability Act (HIPAA) of 1996 that governs the
protection of individually identifiable health information, and is
administered and enforced by the DHHS Office for Civil Rights (OCR).
Decisions about applicability and implementation of the Privacy Rule
reside with the researcher and his/her institution. The OCR website
(http://www.hhs.gov/ocr/) provides information on the Privacy Rule,
including a complete Regulation Text and a set of decision tools on Am
I a covered entity? Information on the impact of the HIPAA Privacy
Rule on NIH processes involving the review, funding, and progress
monitoring of grants, cooperative agreements, and research contracts
can be found at
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. Furthermore, we caution reviewers that their
anonymity may be compromised when they directly access an Internet
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 RFA is related to one or more of the priority areas.
Potential applicants may obtain a copy of "Healthy People 2010" at
AUTHORITY AND REGULATIONS: This program is described in the Catalog of
Federal Domestic Assistance at http://www.cfda.gov/ and is not subject
to the intergovernmental review requirements of Executive Order 12372
or Health Systems Agency review. Awards are made under the
authorization of Sections 301 and 405 of the Public Health Service Act
as amended (42 USC 241 and 284 and under Federal Regulations 42 CFR 52
and 45 CFR Parts 74 and 92. All awards are subject to the terms and
conditions, cost principles, and other considerations described in the
NIH Grants Policy Statement. The NIH Grants Policy Statement can be
found at http://grants.nih.gov/grants/policy/policy.htm.
The PHS strongly encourages all grant recipients to provide a smoke-
free workplace and discourage the 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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