CANCER SURVIVORSHIP STUDIES IN ESTABLISHED EPIDEMIOLOGIC COHORTS

Release Date:  February 18, 1998

PA NUMBER:  PA-98-027

P.T.

National Cancer Institute

PURPOSE

The Division of Cancer Control and Population Sciences (DCCPS) of the National
Cancer Institute (NCI) invites investigator-initiated grant applications (R01s)
and applications for competing supplements to existing NIH-funded research
project grants (R01s, P01s) or cooperative agreements (U01s) for innovative,
interdisciplinary research using existing epidemiologic study populations to
address issues related to long-term survivorship of cancer, particularly in the
areas of specific health or lifestyle outcomes and their modulation by common
risk factors or other exposures.

During the past decades, the National Cancer Institute and other Institutes and
Centers at NIH have sponsored many epidemiologic studies which now present
special opportunities for research in long-term cancer survivorship. Since many
of these studies were implemented, new methodology has been developed for
computerized linkage to augment original data sets and for follow-up of study
participants, and advances in cellular biology have made it possible to evaluate
risk and prognostic factors at the molecular level and to more accurately
identify precursors of invasive disease.  This initiative seeks to build on
existing resources from previous epidemiologic studies through the application
of these new technologies, to enhance knowledge and understanding of long-term
cancer survivorship.

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), "Cancer
Survivorship Studies in Established Epidemiological Cohorts," is related to the
priority area of cancer.  Potential applicants may obtain a copy of "Healthy
People 2000" (Full Report: Stock No. 017-001-00474-0 or Stock No.
017-001-10473-1) 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 or local government, 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 mechanism of support will be the individual research project grant (R01) and
competing supplements to existing NIH-funded research project grants and
cooperative agreements.  R01 applications may be based on cohorts from grants or
cooperative agreements previously funded by NCI or other Institutes and Centers
at NIH.  Applications may be submitted for competing supplements to ongoing
grants or cooperative agreements supported by NCI or other Institutes  and
Centers at NIH for innovative, interdisciplinary research using existing
epidemiologic study populations to address issues related to long-term
survivorship of cancer, particularly in the areas of specific health or lifestyle
outcomes and their modulation by common risk factors or other exposures. 
Responsibility for the planning, direction, and execution of the proposed project
will be solely that of the applicant. 

The total requested project period for an application submitted in response to
this PA may not exceed five years.  Competing supplements may not extend beyond
the funding period of the parent grant; the parent grant must have at least one
year remaining in its project period after award of the supplement.

RESEARCH OBJECTIVES

Background

Scientific advances in cancer prevention, early detection, and treatment have
changed the course of cancer from an acute terminal illness to a more chronic
disease process which, for many, includes prolonged remission or cure.  Currently
in the United States, there are over 10 million persons who have survived a
diagnosis of cancer; approximately 8 million of whom have survived five or more
years.  However, despite the broad impact of survivorship throughout the lives
of patients and their families and caregivers, relatively little research has
been directed at problems of survivorship beyond the immediate post-treatment
phase.

The NCI Office of Cancer Survivorship was established in 1996 to articulate the
opportunities and challenges of survivorship research and to provide a focus for
programmatic research to address questions posed by the scientific and survivor
communities.  The Office held a meeting on "Unresolved Issues in Cancer
Survivorship" in November 1996 at which panels of researchers and survivors
explored the need for research in areas including quality of life, physiologic
outcomes, reproduction and sexuality, second malignancies, and economic impact
of cancer survival.  Conference participants concluded that current support for
research dealing with issues of concern to survivors is inadequate and that
additional research directed toward outcomes is necessary to determine
appropriate long-term medical care and psychosocial needs and to identify
interventions which are likely to improve the quality of life for long-term
survivors.  Participants recognized the importance of considering risk factors
for second cancers and other chronic diseases in health outcomes and, for all
areas of study, encouraged the use of existing data resources for cohort
identification.

During the past decades, the National Cancer Institute has sponsored many
epidemiologic studies in cancer etiology and epidemiology which now present
special opportunities for research in long-term survivorship.  Utilization of
these existing study populations for survivorship research by prospective or
historical follow-up of the original study participants offers unique advantages
in study design and implementation:

--Cancer cases and controls have already been identified, diagnoses have been
confirmed, and an initial contact has been established with each participant as
part of the original study.

--Risk factor and exposure information has been collected as part of the original
study, so that these data are complete and are available even for participants
who are now deceased.

--The existence of cohorts established at the time of cancer diagnosis allows
description of the survivorship experience over time, including an overview of
who survives and which characteristics contribute to survival and other outcomes.

--The existence of an established control group allows direct comparisons of risk
factors, exposure data, and outcomes.

--For selected studies, serum banks or specimen repositories may allow inclusion
of physiologic or molecular variables as covariates, or of changes in physiologic
function as outcome variables.

Additional advantages include the ability to :

Incorporate recently adopted epidemiologic techniques.  New methods for tracking
individual participants (e.g., credit bureau locators), computerized matching and
merging records from diverse sources (e.g., cancer registry data, vital
statistics files, health care billing codes), and new approaches to ascertainment
of health outcomes (e.g., quality of life/health status measures, comorbidity
scores) may provide additional dimensions to traditional approaches for
participant follow-up and outcomes assessment.

Include newly recognized molecular markers for risk factors and disease outcomes. 
The use of molecular markers for disease predisposition and/or diagnosis of
preneoplastic changes, and consideration of genetic polymorphisms which
potentially modulate exposure effects, allow exploration of interactions between
genetic and environmental risk factors.

Promote collaboration between epidemiologists and clinicians experienced in
survivorship research.  This approach links expertise from scientific backgrounds
in cancer epidemiology and clinical oncology, assuring optimal use of existing
and new data bases for study purposes.

While prospective studies of patients currently completing cancer therapy can
eventually provide detailed information on survivorship issues, particularly
about physiologic outcomes and quality of life, late events associated with
survivorship may not be recognized for many years.  There is an immediate need
for information about health consequences late in the survivorship experience,
to assure appropriately targeted surveillance and quality medical care for long
term-survivors and to enable them to achieve and maintain the highest possible
quality of life.  Building survivorship research on a foundation of existing and
relevant resources such as established epidemiologic cohorts and case-control
study populations provides the opportunity to expand our knowledge and
understanding of long-term problems of survivorship in a timely and efficient
manner and enhances our understanding of survival determinants in the context of
documented etiologic/risk factors.

Research Scope and Goals

This goal of this PA is to foster effective and efficient research in issues
related to long-term cancer survivorship through the use of existing
epidemiologic study populations, particularly in the areas of specific health or
lifestyle outcomes (e.g., general health outcomes, reproductive patterns, second
cancers, comorbid diseases)  and their modulation by common risk factors and
other exposures.  Its major objective is to expand the scope of existing
epidemiologic data sets to more comprehensively address survivorship issues
through the use of innovative epidemiologic and molecular approaches. 

The PA requests R01 applications and competing supplements to existing grants or
cooperative agreements for survivorship research which are based on established
epidemiologic study populations from NIH-supported research projects.  In
contrast to RFA CA-97-018 "Long-Term Cancer Survivors: Research Initiatives,"
this PA encourages applications exploring differences between cancer survivors
and non-survivors that may be linked to mechanisms of disease development or
progression, including genetic predisposition and modulating factors.

The original project may be a retrospective epidemiologic study (e.g., case-
control study of etiologic or risk factors) or a prospective study or
demonstration project in which incident cancer cases have been identified.  For
either approach, the number of cases and duration of potential follow-up must be
sufficient to provide a clear picture of the survivorship experience from time
of diagnosis and to address specific questions about late effects and long-term
consequences in cases surviving more than two years from completion of therapy.

Applications should address specific issues in any of the following areas:

1)  Physiologic function and/or medical diagnoses, including but not limited to:
competing causes of mortality; comorbid medical conditions, modulation of medical
outcomes by epidemiologic or molecular risk factors.

2)  Reproduction and sexuality, including but not limited to: post-treatment
fertility, complications of pregnancy, occurrence and consequences of early
menopause, medical/surgical interventions for sexual dysfunction.

3)  Second cancers, including premalignant and predisposing conditions.

4)  Other areas: psychosocial issues (including quality of life); career,
employment, and economic impact.

To address these questions, investigators are encouraged to use innovative and
efficient approaches toward augmenting original study data and collecting cancer
treatment information and follow-up.  These may include:

1) To provide follow-up and/or expand outcome information on participants in the
parent study; 

2) To add new data variables (e.g., risk factors, confounding variables,
prognostic indicators, outcome variables) by computerized data linkage with other
information systems; 

3) To incorporate routinely-collected clinical data not usually considered in
survivorship studies (e.g., performance status scores, physiologic measurements
during treatment); and

4) For projects with existing tissue or serum banks, or for cancer cohorts with
tissue blocks from primary cancer diagnosis (and/or second cancer diagnosis, as
applicable), to include molecular variables as indicators of exposure,
physiologic risk factors, or prognostic indicators.  

Whenever possible, study designs should incorporate risk factor and other
epidemiologic information from the original study as secondary study hypotheses
or as potential confounders of primary study questions.  

Investigators are also encouraged to integrate methodologic approaches from
social science research and health services research to address diverse, non-
medical outcomes and to include collaborators and consultants with experience in
these areas on the investigative team.  Expertise in other medical/surgical
subspecialties, rehabilitation medicine, psychosocial sciences, outcomes
assessment, medical informatics and data management, and statistical analysis
should be included in the study team as needed.

Applications submitted in response to the Program Announcement should represent
collaborative efforts between investigators skilled in clinical and/or preventive
oncology and colleagues with expertise in cancer epidemiology.  R01 applications
based on completed epidemiologic studies should, if possible, include the
Principal Investigator of the original epidemiologic studies as a collaborator
in the proposed research.  If the Principal Investigator of the original study
is not included in the research team, assurance of access to the original study
population, epidemiologic data, and repository specimens must be provided. 

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 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 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, Vol. 23, No.
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 the grant application form PHS 398 (rev.
9/95) 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, E-mail:
[email protected].  The title and number of the program announcement must be
typed in Item 2 on the face page of the application and the "YES" box marked.

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

CENTER FOR SCIENTIFIC REVIEW
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040, MSC 7710
BETHESDA, MD 20892-7710
BETHESDA, MD, 20817 (for courier/overnight 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 and undergo a process in which
only those applications deemed to have the highest scientific merit, generally
the top half of applications under review, will be discussed, assigned a priority
score, and receive a second level review by the appropriate national advisory
council or board.

Review Criteria

The goals of NIH-supported research are to advance our understanding of
biological systems, improve the control of disease, and enhance health.  The
reviewers will comment on the following aspects of the application in their
written critiques 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 by the reviewers 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 a 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 the study address an important problem?  If the aims of
the application are achieved, how will scientific knowledge be advanced?  What
will be the effects 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?

The initial review group will also examine: the appropriateness of proposed
project budget and duration; the adequacy of plans to include both genders and
minorities and their subgroups as appropriate for the scientific goals of the
research and plans for recruitment and retention of subjects;  the provisions for
the protection of human and animal subjects;  and the safety of the research
environment.

AWARD CRITERIA

Applications will compete for available funds.  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, particularly during the planning phase of the grant
applications.  The opportunity to clarify any issues or questions from potential
applicants is welcome.

Direct inquiries regarding programmatic issues to:

Dr. Susan G. Nayfield
Division of Cancer Control and Population Sciences
National Cancer Institute
6130 Executive Boulevard, Suite 535, MSC 7395
Bethesda, MD  20892-7395
Telephone:  (301) 594-7344
FAX:  (301) 435-5477
Email:  [email protected]

Direct inquiries regarding fiscal matters to:

Mr. Bill Wells
Grants Administration Branch
National Cancer Institute
Executive Plaza South
6120 Executive Boulevard, Suite 243, MSC 7150
Bethesda, MD  20892-7150
Telephone:  (301) 496-7800, EXT. 250
FAX:  (301) 496-8601

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance No.
93.393 and No. 93.856.  Awards are made under authorization of the Public Health
Service Act, Title IV, Part A (Public Law 78-140, as amended by Public Law
99.158, 42 USC 241 and 285) and administered under DHHS policies and grant
regulations.  This program is not subject to the intergovernmental review
requirements of Executive Order 12372 or Health Systems Agency review.

The Public Health Service (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.

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