Full Text CA-95-013

PHARMACO-BEHAVIORAL TREATMENT OF NICOTINE DEPENDENCE

NIH GUIDE, Volume 24, Number 24, June 30, 1995

RFA:  CA-95-013
      (previously CA/DA-95-013)

P.T. 34

Keywords: 
  Addiction 
  Pharmacology 
  Behavioral/Experimental Psychology 


National Cancer Institute
National Institute on Drug Abuse

Letter of Intent Receipt Date:  August 11, 1995
Application Receipt Date:  September 21, 1995

PURPOSE

The Division of Cancer Prevention and Control (DCPC) of the National
Cancer Institute (NCI) and the Division of Clinical and Services
Research at the National Institute on Drug Abuse (NIDA) seek
applications for controlled, randomized trials to determine the most
effective, generalizable, cost-efficient, and durable adjuvant
behavioral therapies to support the pharmacological treatment of
nicotine dependence.

HEALTHY PEOPLE 2000

The Public Health Service (PHS) is committed to achieving the health
promotion and disease prevention objectives of "Healthy People 2000,"
a PHS-led national activity for setting priority areas.  This Request
for Applications (RFA), Pharmaco-Behavioral Treatment of Nicotine
Dependence, is related to the priority area of cancer prevention and
control.  Potential applicants may obtain a copy of "Healthy People
2000" (Full Report:  Stock No. 017-001-00474-0 or Summary Report:
Stock No. 017-001-00473-1) through the Superintendent of Documents,
Government Printing Office, Washington, DC 20402-9325 (telephone
202-783-3238).

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic and foreign, for-profit and
non-profit organizations, public and private, such as universities,
colleges, hospitals, laboratories, units of State and local
governments, and eligible agencies of the Federal government.
Racial/ethnic minority individuals, women, and persons with
disabilities are encouraged to apply as Principal Investigators.

MECHANISM OF SUPPORT

This RFA will use the National Institutes of Health (NIH) research
project grant (R01) award mechanism.  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.  The anticipated award date is April 1, 1996.  This RFA is
one-time solicitation.  Future unsolicited competing continuation
applications will compete with all investigator-initiated
applications and be reviewed according to the customary peer review
procedures.

FUNDS AVAILABLE

Approximately $1.2 million in total costs per year for four years
will be committed by the NCI to specifically fund three to five
applications submitted in response to this RFA.  In addition,
$800,000 per year in total costs will be committed by the NIDA to
fund two to four applications.  This funding level is dependent on
the receipt of a sufficient number of applications of high scientific
merit.  Because the nature and scope of the research proposed in
response to this RFA may vary, it is anticipated that the size of the
awards will also vary.  The expected number of awards is five to
nine.  Although this RFA is provided for in the financial plans of
the NCI and NIDA, the award of grants pursuant to it is contingent
upon the availability of funds for this purpose.

RESEARCH OBJECTIVES

Background

Tobacco use, although slowly declining in most of the industrialized
world, remains a significant public health problem.  In the U.S., for
example, while the prevalence of smoking has been reduced to
approximately 25 percent of the adult population, 46 million adults
remain current smokers (MMWR, 1994), accounting for more than 400,000
deaths per year.  Worldwide, tobacco smoking accounts for more than
three million deaths per year (Peto et al., 1994).  Yet, despite such
mortality, smoking not only continues in the industrialized
countries, but is increasing in the developing world.  There is wide
agreement (DHHS, 1988; Benowitz, 1988) that nicotine dependence is
the primary cause of the maintenance of this behavior.

In 1987, the American Psychiatric Association, in the Diagnostic and
Statistical Manual of Mental Disorders (DSM-III-R), classified
"nicotine dependence" as a psychoactive substance dependence disorder
(American Psychiatric Association, 1987).  Although a wide variety of
approaches to reducing nicotine dependence have been used (e.g.,
Lichtenstein and Glasgow, 1992; Orleans and Slade, 1993; Richmond,
1994), the most common medical treatment in the U.S. over the past
decade (i.e., more than six million users) has been pharmacotherapy -
i.e., almost exclusively, either nicotine polacrilex (nicotine-
containing gum, or NG) or transdermal nicotine patch (or TNP).  The
effectiveness of both NG and TNP as treatment aids in smoking
cessation has been established in a wide range of research (e.g.,
Imperial Cancer Research Fund General Practice Research Group, 1993;
Silagy et al., 1994; Foulds, 1994; Fiore et al., 1994).  An important
aspect of this treatment about which there is a lack of clarity,
however, is the role of adjuvant counseling or behavioral therapy
(defined here as any advice, counseling, or program - whether
delivered in person, in print, or through other media - which employs
basic behavior change principles in its delivery).  As noted by Fiore
et al. (1994), many insurers require that smokers who are prescribed
NG or TNP participate in an adjuvant behavioral smoking cessation
program.  The manufacturers themselves encourage such participation
(both in package inserts and, in some cases, by providing self-help
cessation guides), and the U.S. Food and Drug Administration (FDA)
requires that NG and TNP only be prescribed as "part of a
comprehensive behavioral smoking cessation program".  Yet, there is
no consensus about the effectiveness, or the specific, necessary
elements, of adjuvant behavioral therapy for smoking cessation
(Hajek, in press).  There is a great need to establish both the
effectiveness and the specific required elements and necessary level
of intensity of behavioral therapy when it is provided as an adjuvant
to pharmacotherapy aimed at smoking cessation.  The importance of
smoking cessation as a public health problem, the millions of smokers
who are prescribed NG or TNP, the implications for insurers and
health care reform efforts, and the need for providers to be able to
offer the most effective, cost-efficient, and durable treatment
possible requires that this question be addressed.

Research Goals

The primary goal of the research being solicited is to determine the
most effective, generalizable, cost-efficient, and durable adjuvant
behavioral therapy in the pharmacological treatment of nicotine
dependence.  There appears to be general agreement that as the
intensity of adjuvant behavioral therapy increases, so also does
success in the pharmacological treatment of nicotine dependence
(e.g., Fiore et al., 1994).  It is not realistic, however, to assume
that sufficient intensity for universal effectiveness will be
achievable, due to fiscal, time, and/or personnel constraints.
Therefore, controlled, randomized studies are sought that will
address such questions as:  Is there a behavioral therapy that offers
the best balance among the four core aims of efficacy,
generalizability, cost-efficiency, and durability?  Is behavioral
therapy a necessary adjuvant to pharmacological treatment of nicotine
dependence?  What is the minimal behavioral therapy needed to achieve
a 10%/25%/etc. difference between control and treatment groups
prescribed NG or TNP?  Since NG and TNP are physician/dentist-
prescribed in the U.S., can physicians and/or dentists, particularly
in a primary care setting, deliver a sufficiently effective
behavioral therapy to address the four core aims above?  What role
should other primary care staff, especially nurses, play in the
delivery of adjuvant behavioral therapy?  Are there elements in
adjuvant behavioral therapy that appear to be essential to reduction
of nicotine dependence?  What components of a primary care
intervention could increase rates of patient participation in more
intensive adjuvant therapies (which are presumably more effective,
but limited by low participation rates)?

Other Requirements

Several requirements should be observed in preparing applications in
response to this RFA:  (1) "Pharmaco-therapy" and "pharmacological
treatment of nicotine dependence" is defined as treatment with FDA-
approved nicotine polacrilex (nicotine gum) and transdermal nicotine
patch (subsequent solicitations may focus on other pharmacological
treatment approaches); (2) Definitions of the four "core aims" cited
above are:  (a) efficacy = tobacco use cessation rate; (b)
generalizability = ability of the intervention being tested to be
adapted to, and used routinely and effectively in, a non-research
setting; (c) cost-efficiency = cost comparisons, per successful
quitter, of different adjuvant therapies (note: investigators may
suggest alternative definitions of cost-efficiency in their
proposals); and (d) durability = cessation for at least 6 months; (3)
At least one adjuvant behavioral therapy to be tested in any study
must be conducted in, or be readily adaptable to, primary care
medical or dental settings and all adjuvant therapies should be
adaptable to a variety of population characteristics (e.g., women,
ethnic minorities, heavy smokers); (4) Minimum patient follow-up
should be six months; and (5) At least one measure of treatment
"success" shall be continuous non-smoking at all measurement points
between the end of treatment (or other measurement point, if the
investigator views treatment as an ongoing process) and the final
follow-up.

SPECIAL REQUIREMENTS

Investigators should budget for two, two-day meetings in Bethesda for
the PI and one other key staff in Years 1 and 4 and one meeting per
year in Years 2 and 3.  Additionally, investigators should be
prepared to discuss the adoption of data elements and outcome
measures common to all studies funded through this RFA.

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN
SUBJECTS

It is the policy of the NIH that women and members of minority groups
and their subpopulations must be included in all NIH supported
biomedical and behavioral research projects involving human subjects,
unless a clear and compelling rationale and justification is provided
that inclusion is inappropriate with respect to the health of the
subjects or the purpose of the research.  This new policy results
from the NIH Revitalization Act of 1993 (Section 492B of Public Law
103-43) and supersedes and strengthens the previous policies
(Concerning the Inclusion of Women in Study Populations, and
Concerning the Inclusion of Minorities in Study Populations), which
have been in effect since 1990.  The new policy contains some
provisions that are substantially different from the 1990 policies.

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 reprinted
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.

LETTER OF INTENT

Prospective applicants are asked to submit, by August 11, 1995, a
letter of intent that includes a descriptive title of the proposed
research, the name, address, and telephone number of the Principal
Investigator, the identities of other key personnel and participating
institutions, and the number and title of the RFA in response to
which the application may be submitted.  Although a letter of intent
is not required, is not binding, and does not enter into the review
of a subsequent application, the information that it contains allows
NCI staff to estimate the potential review workload and avoid
conflict of interest in the review.

The letter of intent is to be sent to Dr. Thomas J. Glynn at the
address listed under INQUIRIES.

APPLICATION PROCEDURES

The research grant application form PHS 398 (rev. 5/95) is to be used
in applying for these grants.  These forms are available at most
institutional offices of sponsored research; from the Office of
Grants Information, Division of Research Grants, National Institutes
of Health, 6701 Rockledge Drive, Room 3032, Bethesda, MD 20892-7762,
telephone 301/435-0714; 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 on
line 2a of the face page of the application form and the YES box must
be marked.  Submit a signed typewritten original of the application,
including the Checklist, and three signed photocopies in one package
to:

DIVISION OF RESEARCH GRANTS
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710
BETHESDA, MD  20892-7710
BETHESDA, MD  20817 (for express/courier service)

At the time of submission, two additional copies of the application
must be sent to:

Ms. Toby Friedberg
Division of Extramural Activities
National Cancer Institute
Executive Plaza North, Room 636
6130 Executive Boulevard
Bethesda, MD  20892
Rockville, MD  20852 (for express mail)

Applications must be received by September 21, 1995.  If an
application is received after that date, it will be returned to the
applicant without review.  The Division of Research Grants (DRG) 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 DRG will not
accept any application that is essentially the same as one already
reviewed.  This does not preclude the submission of substantial
revisions of applications already reviewed, but such applications
must include an introduction addressing the previous critique.

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed for completeness by DRG
and responsiveness by the NCI and NIDA.  Incomplete applications will
be returned to the applicant without further consideration.  If the
application is not responsive to the RFA, DRG staff may contact the
applicant to determine whether to return the application to the
applicant or submit it for review in competition with unsolicited
applications at the next review cycle.  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 review criteria stated below.  As
part of the initial merit review, all applications will receive a
written critique and may undergo a process in which only those
applications deemed to have the highest scientific merit will be
discussed, assigned a priority score, and receive a second level
review by the appropriate national advisory council or board.

Review Criteria

o  scientific, technical, or medical significance and originality of
proposed research;

o  appropriateness and adequacy of the experimental approach and
methodology proposed to carry out the research;

o  qualifications and research experience of the Principal
Investigator and staff, particularly, but not exclusively, in the
area of the proposed research;

o  availability of the resources necessary to perform the research;

o  appropriateness of the proposed budget and duration in relation to
the proposed research;

o  Adequacy of plans to include both genders and minorities and their
subgroups as appropriate for the scientific goals of the research.
Plans for the recruitment and retention of subjects will also be
evaluated.

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

AWARD CRITERIA

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

o  Quality of the proposed study as determined by peer review;

o  Availability of funds; and

o  Responsiveness to the goals and requirements of the RFA.

INQUIRIES

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:

Thomas J. Glynn, Ph.D.
Division of Cancer Prevention and Control
National Cancer Institute
Executive Plaza North, Room 320
6130 Executive Boulevard
Bethesda, MD  20892
Telephone:  (301) 496-8520
FAX:  (301) 496-8675
Email:  glynnt@dcpcepn.nci.nih.gov

Debra Grossman, M.A.
Division of Clinical and Services Research
National Institute on Drug Abuse
5600 Fishers Lane, Room 10-A-10
Rockville, MD  20857
Telephone:  (301) 443-0107
FAX:  (301) 443-8674
Email:  dgrossma@aoada.ssw.dhhs.gov

Direct inquiries regarding fiscal matters to:

Victoria Price
Grants Administration Branch
National Cancer Institute
Executive Plaza South, Room 243
Bethesda, MD  20892
Telephone:  (301) 496-7800, ext. 252
FAX:  (301) 496-8601
Email:  PriceV@GAB.NCI.NIH.GOV

Gary Fleming, J.D., M.A.
Grants Management Branch
National Institute on Drug Abuse
5600 Fishers Lane, Room 8A54
Rockville, MD  20857
Telephone:  (301) 443-6710
FAX:  (301) 594-6847
Email:  gfleming@aoada2.ssw.dhhs.gov

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic
Assistance No. 93.399.  Awards are made under authorization of the
Public Health Service Act, Title IV, Part A (Public Law 78-410, as
amended by Public Law 99-158, 42 USC 241 and 285) and administered
under PHS grants policies and Federal Regulations 42 CFR 52 and 45
CFR Part 74 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 routing 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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