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

RFA:  CA-98-002


National Cancer Institute
National Institute of Child Health and Human Development
National Institute on Drug Abuse
National Institute of Dental Research
National Institute of Mental Health

Letter of Intent Receipt Date:  Feb 19, 1998
Application Receipt Date:  March 27, 1998


The National Cancer Institute (NCI), National Institute of Child Health and
Human Development (NICHD), National Institute on Drug Abuse (NIDA), National
Institute of Dental Research (NIDR), National Institute of Mental Health
(NIMH), and the National Institute of Nursing Research (NINR) seek grant
applications for innovative research that have clear implications for the
immediate and significant reduction of tobacco use by children and youth in
the United States.


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),
Prevention and Cessation of Tobacco Use by Children and Youth in the U.S., 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 Summary
Report:  Stock No. 017 001-00473-1) through the Superintendent of Documents,
U.S. Government Printing Office, Washington, DC 20402-9325 (telephone 202


Applicants 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, health boards, public
health departments, territorial health departments (including the District of
Columbia), volunteer organizations, clinics, coalitions, and consortia.  Teams
of applicants are encouraged.  Among a team of applicants, one must be
designated as the lead applicant and assume responsibility for conduct of the
project, which includes assembly and submission of the application, overall
management of project, and disbursement of funds.  Applications from domestic
organizations may include international components, if the research proposed
by these organizations has direct and immediate implications for reduction of
tobacco use by youth in the U.S.  Women and minority individuals and persons
with disabilities are encouraged to apply as principal investigators.


This RFA will use the National Institutes of Health (NIH) individual research
project grant (R01).  Responsibility for the planning, direction, and
execution of the proposed project will be solely that of the applicant.  The
total project period for an application submitted in response to this RFA may
not exceed four years.

This RFA is a one-time solicitation for FY 98. Future unsolicited competing
continuation applications will compete with all investigator-initiated
applications and be reviewed according to customary peer review procedures
unless additional re-issuances are required.  The total (direct and indirect)
costs for any application in any one-year budget period may not exceed
$500,000.  The anticipated award date for this solicitation is September

Awards and level of support depend on receipt of a sufficient number of
applications of high scientific merit.  Although this program is provided for
in the financial plans of the sponsoring institutes, the award of grants
pursuant to this RFA is contingent upon the continuing availability of funds
for this purpose.


Approximately $5.6 million per year in total costs for four years will be
committed to fund applications that are submitted in response to this RFA.  It
is anticipated that 12 to 18 new individual awards will be made through this



Efforts to control tobacco use and tobacco-related morbidity and mortality in
the United States have met with reasonable success, at least through the early
1990s.  In the thirty-two years since the publication of the first Surgeon
General's Report on Tobacco and Health, adult smoking rates in the U.S. have
been reduced by nearly 34%, with reductions among males accounting for much of
this success (1).  Other indices of success, such as changing attitudes toward
tobacco use in public places, widespread perception of tobacco use as a health
hazard, and increasing numbers of laws restricting tobacco use have also  been

Controlling tobacco use among U.S. youth, however, has not been as successful.
Although there was considerable success in reducing adolescent tobacco use in
the late 1970's and early 1980's, tobacco use among high school seniors - for
whom data with the longest time trends are available - have remained
essentially stable for more than a decade, with just under 20% of seniors
reporting daily smoking (3). Furthermore, high school dropouts smoke at an
alarmingly high rate. One study in Minnesota found that 77% of both male and
female 16-year old dropouts smoked on a daily basis (4); a similar study in
Ontario, Canada, found a nearly 68% smoking rate among high school dropouts
(5). When the high school senior tobacco use prevalence rates are considered
in tandem with the dropout smoking rates, the smoking prevalence rate among
U.S. adolescents nearly equals that among adults, i.e., about 25%. Smokeless
tobacco use - spit tobacco - among youth, especially among males, also
continues to rise (6). If these trends continue, the prospect for further
reductions in national tobacco use prevalence rates, and accompanying tobacco-
related disease rates and economic costs, is unlikely to change substantially
in the foreseeable future.

Research Goals

Although a great deal has been learned about tobacco use by children and youth
- as demonstrated by several recent reviews of this issue (e.g., 7-10) - there
is also a great need to learn more and, especially, to apply broadly and
systematically what has already been learned.

Research alone, however, will certainly not solve this society-wide and well-
entrenched problem, public awareness campaigns, policy change, revenue
restructuring, agricultural reform and other measures are essential, as well.
In fact, there is little doubt that it is the combination of effort from many
channels, including public awareness and commitment, policy change and
research, as demonstrated through the NCI's and American Cancer Society's
ASSIST (American Stop Smoking Intervention Study) program, that will likely
have the greatest effect on reducing tobacco use among children and youth.

Therefore, the research arm of this multi-pronged effort, if it has as its
clear purpose the immediate and significant reduction of tobacco use by
children and youth and, particularly, if it is innovative, extends and does
not merely replicate existing research, and is conducted with the broad
application of relevant results as one of its primary goals, can make an
enormous contribution.  Accordingly, among the research issues that may be
considered in response to this solicitation, include, but are not limited to
the following:

o  What are the characteristics, pharmacological, physiological, and
psychological, of nicotine dependence in its early stages and, especially,
during the transition between experimental and dependent use? Are there
differences in individual susceptibility to nicotine dependence among youth?
What is the relationship between the characteristics of different tobacco
products and early nicotine dependence? Are there pharmacological treatments
from which nicotine dependent children and youth will benefit? What are the
characteristics of successful nicotine dependence cessation programs for youth
under age 18? How can these programs be adopted on a large scale?

o  What are the factors influencing the decline in, or relative lack of
involvement in, tobacco use among particular ethnic, social, religious, or
racial groups in the U.S., e.g. African-American youth? How can these factors
be applied to the larger population of U.S. youth? Conversely, is there need
for prevention programs aimed at youth subpopulations at high risk for tobacco
use? Can such programs be successfully developed, evaluated, and adopted on a
large scale?

o  What are the factors that influence youths' responses to advertising,
promotional, mass media, and warning messages aimed at discouraging tobacco
use? What are factors that influence youth's responses to advertising,
promotional, and mass media messages aimed at encouraging tobacco use? What
are the ethnic, gender, and social class differences which influence these
responses? What are the characteristics of failed and successful advertising
and mass media campaigns aimed at discouraging tobacco use by children and

o  How do tobacco price increases, especially through higher taxes, affect
youth tobacco use in comparison to the effect of prices increases on adult
tobacco use, i.e. are youth more, less, or equally price-sensitive to tobacco
prices than adults?

o  What is the optimal age, and circumstances, at which programs aimed at
discouraging tobacco use by children and youth should begin? Is it better to
focus on tobacco use alone in these programs or to include other youth-
relevant health issues such as diet and exercise? What is the role of the
family in discouraging tobacco use among children and youth? What is the role
of the health care community, ranging from practitioners (e.g. nurses,
pediatricians, dentists, OB-GYNs, family physicians), professional
organizations, and health-care delivery and reimbursement systems?

o  What is the role of stress and anxiety in tolerance and dependence to
nicotine, relapse to nicotine use, as well as optimal stress reduction
strategies within treatment settings?  For example, stress corticosteroids
have been found to reduce sensitivity to nicotine, potentially leading youth
who are under stress to smoke more to overcome a blunted subjective effect. 
Studies in animal models have shown that stress can directly cause relapse to
nicotine self-administration after a period of abstinence. We also know that
following stressful episodes, adult smokers take longer to regain emotional
equilibrium if they have been abstaining from smoking. Few such questions have
been extended to youth.

o  What are the dysphoric or aversive effects of smoking abstinence? For
example, chronic adult smokers deprived of cigarettes for a day have been
shown to have increased anger, hostility, aggression, and loss of social
cooperation.  During periods of abstinence and/or craving smokers have shown
impairment across a wide range of psychomotor and cognitive functions. 
Additional studies can better characterize the intense dysphoria and
functional impairment that youthful smokers may experience when they stop
smoking, potentially a primary factor in relapse.

o  What are the behavioral and neurobiological underpinnings of craving for
nicotine by youth, as well as development of new medications to treat cravings
such as nicotine antagonists?  Brain imaging studies during exposure to
nicotine or during exposure to cues that signal the availability of nicotine
will help to map sites that are importantly involved  in nicotine urges and

o  Are oral effects of tobacco use (e.g., mouth odor, tooth discoloration,
increased risk of periodontal diseases, increased risk of early tooth loss)
salient to children or youth?  At what age and under what circumstances can
the effectiveness of preventive interventions, preventive messages, or
cessation programs be enhanced by integrating  oral factors? Is use of oral
biomarkers (e.g., salivary cotinine) practical in settings in which youth or
children receive interventions? Does use of oral biomarkers substantially
enhance assessing regularity of tobacco use, improving the  targeting of
interventions to reduce tobacco use, or monitoring intervention outcomes with
children or youth?

o  Are alternative activities and recreational options effective in reducing
youth cigarette use, as has been shown with other drugs? For example, in a
laboratory study cigarette smokers reduced cigarette consumption when they
engaged in "simulated employment" or recreational activities.

o  Studies on decision making, risk taking and impulsivity are needed to
determine the conditions under which youth begin to experiment with smoking,
particularly in group settings. Additionally, psychosocial, mood, and
temperament factors likely play important roles in early experimentation with
tobacco products; theory-driven research in this area is especially needed.
Treatment studies that promote impulse control as well as conduct-based
intervention strategies are also encouraged.

o  Some studies have suggested an increased use of tobacco among adolescents
with attention deficit disorder, depression, and eating disorders.  Others
have suggested that smoking may be self-medicating for adolescents with
attention deficit disorders and that nicotine may have some therapeutic
effects on attentional dysfunction in addition to its toxic effects on health.
What is the incidence of early tobacco use among children and adolescents with
neuropsychiatric disorders, including (but not limited to) attention deficit
disorders, depression, and eating disorders? Do the effects of nicotine mimic
those of certain psychostimulants and antidepressants? What are the
implications for the pharmacologic treatment of these disorders? Are there
other implications of these disorders for cognitive-behavioral and/or other
psychosocial approaches to smoking cessation interventions for these

o  What is the optimal way to disseminate and implement successful youth and
children tobacco prevention/cessation programs on a large scale?

Other Requirements

Several requirements should be observed in preparing an application in
response to this RFA:

(1) The term "Children and Youth" refers to males and females under the age of

(2) The term "Tobacco Use" includes smoking and smokeless (chewing) tobacco.

(3) The term "Innovative Research" refers to studies that address the problem
of tobacco use by children and youth from a new perspective and do not merely
add to the scientific literature in areas where considerable research has
already been conducted and where the needs and challenges are more clearly in
the realm of how the programs developed through previous research can be
adopted on a broad scale, e.g., school-based interventions to prevent tobacco

(4) Where scientifically reasonable, possible, and defensible, such
investigative devices as secondary data analysis and meta-analyses are
encouraged in lieu of primary data collection.

(5) All applications should include a detailed discussion of (a) why the
results of the research being proposed, if disseminated and adopted on a large
scale, could have an immediate and significant effect on the reduction of
tobacco use by children and youth in the U.S. and (b) how the results of the
research being proposed can, either immediately or in the near-term, be
disseminated and adopted on a large scale.


Applications responding to this RFA should include one round trip, two-day
meeting to Bethesda, MD in the budget.


It is the policy of the NIH that women and members of minority groups and
their subpopulations must be included in all NIH supported biomedical and
behavioral research projects involving human subjects, unless a clear and
compelling rationale and justification is provided that inclusion is
inappropriate with respect to the health of the subjects or the purpose of the
research.  This policy results from the NIH Revitalization Act of 1993
(Section 492B of Public Law 103-43).

All investigators proposing research involving human subjects should read the
"NIH Guidelines For Inclusion of Women and Minorities as Subjects in Clinical
Research," which have been published in the Federal Register of March 28, 1994
(FR 59 14508-14513) and in the NIH Guide for Grants and Contracts, Volume 23,
Number 11, March 18, 1994.

Investigators also may obtain copies of the policy from the program staff
listed under INQUIRIES.  Program staff may also provide additional relevant
information concerning the policy.


Prospective applicants are asked to submit, by February 19, 1998 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 subsequent applications, the information that it
contains allows NIH staff to estimate the potential review workload and to
avoid conflict of interest in the review.

The letter of intent is to be sent to:

Ms. Veronica Chollette
Division of Cancer Control and Population Sciences
National Cancer Institute
6130 Executive Boulevard, Room 232  MSC 7330
Bethesda, MD  20892-7330
Rockville, MD  20852 (for express/courier service)
Telephone:  (301) 496-8520
FAX:  (301) 496-8675 or 480-6637


Applications are to be submitted on the research grant application form PHS
398 (rev. 5/95).  These forms are available at most institutional offices of
sponsored research; from the Division of Extramural Outreach and Information
Resources, National Institutes of Health, 6701 Rockledge Drive MSC 7910,
Bethesda, MD 20892-7910; telephone 301/710-0267, email:; and
from the program administrator listed under INQUIRIES.

The RFA label available in the PHS 398 (rev. 5/95) 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 in Section 2 of the face page of the application form
and the YES box must be marked.

All requirements with regard to type, size, page limitations, appendix
material, etc. must be followed or applications will be returned without
review. Submit a signed, typewritten original of the application, including
the Checklist, and three signed, photocopies, in one package to:

CENTER FOR SCIENTIFIC REVIEW (formerly Division of Research Grants)
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 must also
be sent to:

Mrs. Toby Friedberg
Division of Extramural Activities
National Cancer Institute
6130 Executive Boulevard, Room 636
Bethesda, MD  20892
Rockville, MD  20852 (for express/courier service)

Applications must be received by March 27, 1998.  If an application is
received after the application receipt 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 previously reviewed, but
such applications must include an introduction addressing the previous


Upon receipt, applications will be reviewed for completeness by CSR and
responsiveness by the NCI.  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 NCI in
accordance with the peer criteria stated below.  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

(1) Significance:  Does this study address an important problem? If the aims
of the application are achieved, how will scientific, technical and medical
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?

For applications involving primary data collection appropriateness and
adequacy of the experimental design and methodology, including appropriateness
of control and comparison groups, reliability and validity of instruments to
assess key variables, methods to identify and minimize biases and threats to
validity, and specification of statistical power and sample sizes; and, for
applications involving secondary data analysis or meta-analysis, clearly
stated inclusionary criteria and appropriate methods of data selection and

(3) Innovation:  Does the project employ novel concepts, approaches or method?
Are the aims original and innovative? Does the project challenge existing
paradigms or develop new methodologies or technologies?  Can the research
results be applied on a large scale to the immediate and significant reduction
of tobacco use by children and youth?

(4) Investigator:  Is the investigator appropriately trained and well suited
to carry out this work?  Does the investigator provide evidence of familiarity
with and understanding of relevant research literature as it relates to
tobacco use prevention and control and youth? Is the work proposed appropriate
to the experience level of the principal investigator and other researchers
(if any)? What qualifications and relevant research experience does the
Principal Investigator and collaborating scientists, including the senior
collaborator have in this particularly area of research?

(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 review group will critically examine the submitted budget and will
recommend an appropriate budget and period of support for each application
recommended for support.


Applications found to have significant and substantial merit will be
considered for funding by using the following criteria:

o  priority score
o  availability of funds
o  programmatic priorities


Letter of Intent Receipt Date:  February 19, 1998
Application Receipt Date:       March 27, 1998
Review by NCAB Advisory Board:  September 1998
Anticipated Award Date:         September 30, 1998


Written, telephone and, especially, email inquiries concerning this RFA are
encouraged. The opportunity to clarify any issues or questions from potential
applicants is welcome.

Direct inquiries regarding programmatic issues to:

Sherry Mills, M.D., M.P.H.
Division of Cancer Control and Population Sciences
National Cancer Institute
6130 Executive Boulevard, Room 232
Bethesda, MD  20892-7330
Rockville, MD  20852 (for express/courier service)
Telephone:  (301) 496-8520
FAX:  (301) 480-6637

Norman Krasnegor, Ph.D.
Center for Research for Mothers and Children
National Institute of Child and Human Development
6100 Executive Boulevard, Room 4B05
Rockville, MD  20852
Telephone:  (301) 496-6591
FAX:  (301) 480-7773

Jaylan S Turkkan, Ph.D.
Division of Basic Research
National Institute of Drug Abuse
5600 Fishers Lane, Room 10A-20
Rockville, MD  20857
Telephone:  (301) 443-1263
FAX:  (301) 594-6043

Patricia S. Bryant, Ph. D.
Behavior, Health Promotion and Environment
National Institute of Dental Research
45 Center Drive, Room 4AN 18A - MSC 6402
Bethesda, MD  20892-6402
Telephone:  (301) 594-2095

Judy Rumsey, Ph.D.
National Institute of Mental Health
Parklawn Building, Room 18C-17
Rockville, MD  20857
Telephone:  (301) 443-9264
FAX:  301-480-4415

The National Institute of Nursing Research (NINR) has an interest in research
on prevention of tobacco use among youth.
Applications that are of mutual interest may be given assignment to NINR in
accordance with the NIH referral guidelines.  Contact:

Dr. Carole Hudgings
Division of Extramural Activities
National Institute of Nursing Research
Building 45, Room 3AN-12
Bethesda, MD  20892-6300
Telephone:  (301) 594-5976

Direct inquiries regarding fiscal matters to:

Barbara A. Fisher
Grants Administration Branch
National Cancer Institute
6120 Executive Boulevard, Room 243
Bethesda, MD  20892
Telephone: (301) 496-7800, ext. 229

Doug Shawver
Grants Management Officer
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 8A,17-F
Bethesda, MD  20892
Telephone:  (301) 496-1303

Martin R. Rubinstein
Grants Management Office
National Institute of Dental Research
45 Center Drive, Room 4AN 44A - MSC 6402
Bethesda, MD  20892-6402
Telephone:  (301) 594-4800

Gary P. Fleming, J.D., M.A.
Grants Management Office
National Institute of Drug Abuse
5600 Fishers Lane, Room 10A-42
Rockville, MD  20857
Telephone:  (301) 443-6710
FAX:  (301) 594-6847


This program is described in the Catalog of Federal Domestic Assistance No.
93.399, Cancer Control.  Awards are made under authorization of the Public
Health Services Act, Title IV, Part A (Public Law 78-410, as amended by Public
Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and
Federal Regulations 42 CFR 52 and 45 CFR Part 74 and Part 92. This program is
not subject to the intergovernmental review requirements of Executive Order
12372 or Health Systems Agency review.

The PHS strongly encourages all grant and contract recipients to provide a
smoke-free workplace and promote the non-use of all tobacco products. In
addition, Public Law 103- 227, the Pro-Children Act of 1994, prohibits smoking
in certain facilities (or in some cases, any portion of a facility) in which
regular or routine education, library, day care, health care or early
childhood development services are provided to children.  This is consistent
with the PHS mission to protect and advance the physical and mental health of
the American people.


1) Centers for Disease Control and Prevention. Cigarette smoking among
adults - United States, 1993. Morbidity and Mortality Weekly Report, 1994,
43(50), 925-930.

2) U.S. Department of Health and Human Services. Reducing the Health
Consequences of Smoking: 25 Years of Progress. A Report of the Surgeon
General. DHHS Publication No. (CDC) 89-8411, 1989. Washington, DC: U.S.
Government Printing Office, 1989.

3) Johnston, L.D., O'Malley, P.M., and Bachman, J.G. National Survey Results
on Drug Use from the Monitoring the Future Study, 1975- 1995. Rockville, MD:
U.S. National Institute on Drug Abuse, 1996.

4) Pirie, P.L., Murray, D.M., and Luepker, R.V. Smoking prevalence in a cohort
of adolescents, including absentees, dropouts, and transfers. American Journal
of Public Health, 1988, 78, 176-178.

5) Flay, B.R. et al. Six-year followup of the first Waterloo school smoking
prevention trial. American Journal of Public Health, 1989, 79, 1371-1376.

6) Boyd, G.M. and Darby, C.A. Smokeless Tobacco Use in the United States.
National Cancer Institute Monograph, 1989, 81, 1-105.

7) Glynn, T.J., Greenwald, P., Mills, S.M., and Manley, M.W. Youth tobacco use
in the United States - Problems, progress, goals, and potential solutions.
Preventive Medicine, 1993, 22, 568-575.

8) Reid, D.J., McNeill, A.D., and Glynn, T.J. Reducing the prevalence of
smoking in youth in Western countries: An international review. Tobacco
Control, 1995, 4, 266-277.

9) U.S. Department of Health and Human Services. Preventing Tobacco Use Among
Young People: A Report of the Surgeon General. Atlanta, GA: Centers for
Disease Control and Prevention, Office on Smoking and Health, 1994.

10) Lynch, B.S. and Bonnie, R.J. (eds) Growing Up Tobacco Free - Preventing
Nicotine Addiction in Children and Youths: A Report of the Institute of
Medicine. Washington, DC: National Academy Press, 1994.

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