kristoff@GENBANK.BIO.NET (Dave Kristofferson) (04/12/91)
$$XID NIHGUIDE 19910412 V20N15 P2O2 ************************************
community data and epidemiological studies, applicants should consult
BSR staff for advice.
V. INCLUSION OF MINORITIES AND WOMEN
NIH and ADAMHA policy is that applicants for NIH/ADAMHA clinical
research grants and cooperative agreements will be required to include
minorities and women in study populations so that research findings can
be of benefit to all persons at risk of the disease, disorder or
condition under study; special emphasis should be placed on the need for
inclusion of minorities and women in studies of diseases, disorders and
conditions which disproportionately affect them. This policy is
intended to apply to males and females of all ages. If women or
minorities are excluded or inadequately represented in clinical
research, particularly in proposed population-based studies, a clear
compelling rationale should be provided.
The composition of the proposed study population must be described in
terms of gender and racial/ethnic group, together with a rationale for
its choice. In addition, gender and racial/ethnic issues should be
addressed in developing a research design and sample size appropriate
for the scientific objectives of the study. This information should be
included in the form PHS 398 in Section 2, A-D of the Research Plan AND
summarized in Section 2, E, Human Subjects.
Applicants/offerors are urged to assess carefully the feasibility of
including the broadest possible representation of minority groups.
However, NIH recognize that it may not be feasible or appropriate in all
research projects to include representation of the full array of United
States racial/ethnic minority populations (i.e., Native Americans
(including American Indians or Alaskan Natives), Asian/Pacific
Islanders, Blacks, Hispanics). The rationale or studies on single
minority population groups should be provided.
For the purpose of this policy, clinical research includes human
biomedical and behavioral studies of etiology, epidemiology, prevention
(and preventive strategies), diagnosis, or treatment of diseases,
disorders or conditions, including but not limited to clinical trials.
The usual NIH policies concerning research on human subjects also apply.
Basic research or clinical studies in which human tissues cannot be
identified or linked to individuals are excluded. However, every effort
should be made to include human tissues from women and racial/ethnic
minorities when it is important to apply the results of the study
broadly, and this should be addressed by applicants.
For foreign awards, the policy on inclusion of women applies fully;
since the definition of minority differs in other countries, the
applicant must discuss the relevance of research involving foreign
population groups to the United States' populations, including
minorities.
If the required information is not contained within the application, the
review will be deferred until the information is provided.
Peer reviewers will address specifically whether the research plan in
the application conforms to these policies. If the representation of
women or minorities in a study design is inadequate to answer the
scientific question(s) addressed AND the justification for the selected
study population is inadequate, it will be considered a scientific
weakness or deficiency in the study design and will be reflected in
assigning the priority score to the application.
All applications for clinical research submitted to NIH are required to
address these policies. NIH funding components will not award grants or
cooperative agreements that do not comply with these policies.
VI. ELIGIBILITY
Applications for research grants may be made by public or private,
for-profit or non-profit organizations, such as universities, colleges,
hospitals, or laboratories. Women and minority investigators, in
particular, are encouraged to apply.
VII. MECHANISMS OF SUPPORT
The primary mechanisms for support of this initiative are the research
project grant (R01), program project (P01), FIRST award (R29),
institutional training grant (T32), individual fellowships (F32, F33),
and research career development awards (K04).
VIII. REVIEW CRITERIA AND APPLICATION PROCEDURES
R01, R29, F32, F33 and K04 applications will be reviewed for scientific
and technical merit by an appropriate Initial Review Group of the
Division of Research Grants. All other applications will be reviewed by
an appropriate Institute review group. Secondary review will be by the
corresponding National Advisory Council. Applications compete on the
basis of scientific merit.
Although it is not required, potential applicants are encouraged to
contact NIA staff in advance of formal submission. This may be
accomplished by calling the program office listed below. Requests for
additional information should be addressed to:
Richard Suzman, Ph.D.
Behavioral and Social Research Program
National Institute on Aging
Building 31, Room 5C32
Bethesda, MD 20892
Telephone: (301) 496-3136
For fiscal and administrative matters, contact:
Joe Ellis
Grants and Contracts Management Office
National Institute on Aging
Building 31, Room 5C07
Bethesda, MD 20892
Telephone: (301) 496-1472
Applicants must use the research project application form (PHS 398,
revised 10/88, reprinted 9/89) that is available at the applicant's
institutional research office and from the Office of Grants Inquiries,
Division of Research Grants, NIH (301-496-7441). Individual fellowship
applicants must use PHS 416-1 (revised 7/88). In order to expedite the
application's routing, please check the box on the application face
sheet indicating that your proposal is in response to this announcement
and type (next to the box) "Economics of Aging, Health and Retirement,
PA-91-41."
The application (with six copies) must be mailed to:
Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD 20892**
If applying for an F32, the application and only two copies need to be
sent to the above address.
Receipt dates for Research Project Grant, Career Development Award, and
FIRST Award applications are February 1, June 1, and October 1 of each
year. Those for the individual fellowships (F32, F33) and institutional
training grants (T32) applications are January 10, May 10, and September
10.
This program is described in the Catalog of Federal Domestic Assistance
No. 93.866. Agency Research Awards will be made under the authority of
the Public Health Service Act, Title III, Section 301 (Public Law
78-410, as amended; 42 USC 241 and 41 USC 289) and be subject to PHS
Grant Policies and Federal Regulations 42 CFR Part 52 and 45 CFR Part
74. This program is not subject to Health Systems Agency review.
$$P2 END ***************************************************************
$$P3 BEGIN *************************************************************
CLINICAL CANCER THERAPY RESEARCH
PA: PA-91-42
P.T. 34; K.W. 0715035, 0740020, 0745005, 0755025, 0785140
National Cancer Institute
Application Receipt Dates: June 1, October 1, February 1
I. PURPOSE
The National Cancer Institute (NCI) seeks grant applications
to conduct clinical therapeutic studies of neoplastic diseases in
human subjects. Clinical research, by definition, involves a
clinician/patient-subject interaction with a therapeutic intent.
This Program Announcement (PA) encompasses a full range of
therapeutic studies and clinical trials employing drugs,
biologics, radiation, or surgery. The intent of the announcement
is to encourage clinical researchers to translate insights in
cancer biology and the development of new agents into innovative
cancer therapeutic studies.
This type of grant solicitation (Program Announcement) is
utilized when it is desired to encourage investigator-initiated
research projects in areas of special importance to the National
Cancer Institute. Applicants who will be funded under this PA
will be supported through the customary National Institutes of Health
(NIH) grant-in-aid (R01, R29).
The 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 PA, Clinical Cancer Therapy Research, 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 "Healthy People 2000"
(Summary Report: Stock No. 017-001-00473-1) through the
Superintendent of Documents, Government Printing Office,
Washington, D.C. 20402-9325 (telephone 202-783-3238).
II. BACKGROUND INFORMATION
In the past several years, the research effort into understanding
the basic biology of the cancer cell has been highly productive.
Recent discoveries concerning the role of growth factors, genes
that promote and suppress neoplasia, mechanisms of treatment
sensitivity and resistance, and the biology of the immune systems
have provided the basis for the development of novel and improved
cancer treatments. The rate of progress in the treatment of
cancer will depend upon the translation of these basic and
preclinical discoveries into clinical cancer therapies.
The NCI supports an extensive network of clinical and laboratory
research studies related to cancer therapy through contracts,
grants, and cooperative agreements. At present, the traditional
research grant mechanism (R01, R29) is underutilized by clinical
investigators for the support of clinical research. The Cancer
Therapy Evaluation Program (CTEP), Division of Cancer Treatment,
NCI, the program primarily responsible for the promotion and
translation of new basic and preclinical research into
therapeutic advances, receives relatively few research grant
applications. Whereas a Request for Applications (RFA)
represents a single solicitation, a
PA provides the opportunity for the receipt of
new applications on an indefinite basis. NCI encourages clinical
investigators to submit clinical therapeutic studies and is
committed to moving advances in basic biology and drug
development into the clinical setting.
III. RESEARCH GOALS AND SCOPE
The Division of Cancer Treatment (DCT) is requesting qualified
investigators to develop research grant applications (R01,
R29) involving clinical therapeutic studies of neoplastic
diseases. Clinical studies must involve human subjects and be
designed to ultimately improve cancer treatment. The
applications may include single or multi-institutional (e.g.,
consortia, cooperative groups) research studies with appropriate
biological correlates linked to these studies. New clinical
therapeutic studies may employ drugs, biologics, radiation, or
surgery used as single agents/modalities or in combination.
Biological correlative studies that have clinical relevance to
cancer therapies and are aimed at improving cancer treatment are
also appropriate.
Some examples of clinical therapeutic studies include:
1) therapies based on novel mechanisms of action; 2) mechanism of
action and metabolic studies of antitumor agents; 3) studies of
mechanisms of hormone-, drug- or radiation-resistance and
reversal; 4) mechanism of action of biological response modifiers
in the treatment of cancer, e.g., cancer immunotherapy
(monoclonal antibodies, cytokines, antisense, and vaccines) alone or
in combination with chemotherapeutic agents; 5) mechanism of
action of new growth factor targeted therapies; 6) new radiation
therapies or radiation modifiers to enhance cell kill or protect
normal tissue; 7) surgical therapies in combination with
therapeutic agents.
Some examples of biological correlative studies include:
1) phenotypic or genotypic alterations that appear to correlate
with the development of drug-, hormone-, or radiation-resistance;
2) oncogenes, growth factors, and specific antigen expression on
tumor cells; 3) pharmacokinetic and pharmacodynamic measurements;
4) biochemical pharmacologic parameters; 5) imaging studies to
assess efficacy of treatment.
Investigators are not limited to the above areas of potential
studies. Clinical research, by definition, must involve a
clinician/patient-subject interaction with a therapeutic intent.
Applicants from institutions that have a General Clinical
Research Center (GCRC) funded by the NIH National Center for
Research Resources are requested to identify the GCRC as a resource
for conducting the proposed research.
IV. MECHANISM OF SUPPORT
Support of this program will be through the research project (R01
and R29) NIH grant-in-aid. Applicants will be responsible for
the planning, direction, and execution of the proposed project.
All PHS and NIH grants policies will apply to applications
received in response to this announcement. Domestic applicants
may request no more than five years of support, and foreign
applicants may request no more than three years. Applications
submitted in response to this PA will compete for funds with all
other investigator-initiated applications. The award of grants
in response to this PA is also contingent upon the availability
of funds.
V. ELIGIBILITY REQUIREMENTS
Non-profit organizations and institutions, governments and their
agencies, and occasionally individuals are eligible to apply.
For-profit organizations are also eligible unless specifically
excluded by legislation. Both domestic and foreign applicants
may apply. Applications may be submitted from a single
institution or may include arrangements with multiple
institutions (e.g., consortia, clinical cooperative group) if
appropriate. Applications from minority individuals and women
are encouraged.
VI. REVIEW PROCEDURES AND CRITERIA
A. REVIEW PROCEDURE
Upon receipt, applications will be reviewed initially by the
Division of Research Grants (DRG) for completeness. Incomplete
applications will be returned to the applicant without further
consideration. Applications will be assigned on the basis of
established Public Health Service referral guidelines.
Applications will be reviewed for scientific and technical merit
by appropriate peer review groups.
Following peer review, the applications
will receive a second-level review by the appropriate national
advisory council/board.
B. SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF
NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN
CLINICAL RESEARCH STUDY POPULATIONS
NIH and ADAMHA policy is that applicants for NIH/ADAMHA clinical
research grants and cooperative agreements will be required to
include minorities and women in study populations so that
research findings can be of benefit to all persons at risk of the
disease, disorder or condition under study; special emphasis
should be placed on the need for inclusion of minorities and
women in studies of diseases, disorders and conditions which
disproportionately affect them. This policy is intended to apply
to males and females of all ages. If women or minorities are
excluded or inadequately represented in clinical research,
particularly in proposed population-based studies, a clear
compelling rationale should be provided.
The composition of the proposed study population must be
described in terms of gender and racial/ethnic group, together
with a rationale for its choice. In addition, gender and
racial/ethnic issues should be addressed in developing a research
design and sample size appropriate for the scientific objectives
of the study. This information should be included in the form
PHS 398 in Section 2, A-D of the Research Plan AND summarized in
Section 2, E, Human Subjects.
Applicants are urged to assess carefully the feasibility of
including the broadest possible representation of minority
groups. However, NIH recognizes that it may not be feasible or
appropriate in all research projects to include representation of
the full array of United States racial/ethnic minority
populations (i.e., Native Americans (including American Indians
or Alaskan Natives), Asian/Pacific Islanders, Blacks, Hispanics).
The rationale for studies on single minority population groups
should be provided.
For the purpose of this policy, clinical research includes human
biomedical and behavioral studies of etiology, epidemiology,
prevention (and preventive strategies), diagnosis, or treatment
of diseases, disorders or conditions, including not but limited
to clinical trials.
The usual NIH policies concerning research on human subjects also
apply. Basic research or clinical studies in which human tissues
cannot be identified or linked to individuals are excluded.
However, every effort should be made to include human tissues
from women and racial/ethnic minorities when it is important to
apply the results of the study broadly, and this should be
addressed by applicants.
For foreign awards, the policy on inclusion of women applies
fully; since the definition of minority differs in other
countries, the applicant must discuss the relevance of research
involving foreign population groups to the United States'
populations, including minorities.
If the required information is not contained within the
application, the review will be deferred until the information is
provided.
Peer reviewers will address specifically whether the research
plan in the application conforms to these policies. If the
representation of women or minorities in a study design is
inadequate to answer the scientific question(s) addressed AND the
justification for the selected study population is inadequate, it
will be considered a scientific weakness or deficiency in the
study design and will be reflected in assigning the priority
score to the application.
All applications for clinical research submitted to NIH are
required to address these policies. NIH funding components will
not award grants or cooperative agreements that do not comply
with these policies.
VII. METHOD OF APPLYING
The research grant
application form PHS 398 (revised 10/88) must be used in applying
for these grants and will be accepted at the regular application
deadlines. These forms are available at most institutional
business offices; from the Office of Grants Inquiries, Division
of Research Grants, National Institutes of Health, Room 449,
Westwood Building, Bethesda, MD 20892; or from the NCI Program
Director named below. The title and number of this announcement
must be typed in line 2 on the face page of the application.
The original application and six (6) signed exact photocopies
must be submitted or delivered to:
Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD 20892**
IX. INQUIRIES
Written or telephone inquiries concerning the objectives and
scope of this PA and inquiries about whether or not specified
proposed research would be responsive are encouraged and should
be directed to the Program Directors, Ms. Diane Bronzert and Dr.
Roy Wu, at the address below. The Program Directors welcome the
opportunity to clarify any issues or questions from potential
applicants.
For Technical Information: For Business Information:
Ms. Diane A. Bronzert or Ms. Donna Shields
Dr. Roy S. Wu Grants Management Specialist
Program Directors National Cancer Institute
Cancer Therapy Evaluation Program EPS, Room 242
Division of Cancer Treatment Bethesda, MD 20892
National Cancer Institute Telephone: (301) 496-7800
EPN, Room 734
Bethesda, MD 20892
Telephone: (301) 496-8866
FAX #: (301) 480-4663
This program is described in the Catalog of Federal Domestic
Assistance No 93.395, Cancer Treatment Research. Awards are made
under the authorization of the Public Health Service Act,
Sections 301, 410, and 411 (Public Law 78-410, 42 USC 241 as
amended, Public Law 99-158, 42 USC 285a) and administered under
PHS grant policies and Federal Regulations at 42 CFR Part 52 and
45 CFR Part 74. This program is not subject to the
intergovernmental review requirements of Executive Order 12372 or
Health Systems Agency review.
$$P3 END ***************************************************************
**THE MAILING ADDRESS GIVEN FOR SENDING APPLICATIONS TO THE DIVISION OF
RESEARCH GRANTS OR CONTACTING PROGRAM STAFF IN THE WESTWOOD BUILDING IS
THE CENTRAL MAILING ADDRESS FOR THE NATIONAL INSTITUTES OF HEALTH.
APPLICANTS WHO USE EXPRESS MAIL OR A COURIER SERVICE ARE ADVISED TO
FOLLOW THE CARRIER'S REQUIREMENTS FOR SHOWING A STREET ADDRESS. THE
ADDRESS FOR THE WESTWOOD BUILDING IS:
5333 Westbard Avenue
Bethesda, Maryland 20816
FULL TEXT OF RFAs FOR ONLINE ACCESS
$$XID RFA MH9110 MH-91-10 P1O1 *****************************************
INSTITUTIONAL CLINICAL TRAINING GRANTS:
PROFESSIONAL TRAINING ADDRESSING SEVERE MENTAL DISORDERS
RFA: MH-91-10
P.T. 44; K.W. 0720005, 0715129, 0715177, 0715180
National Institute of Mental Health
Application Receipt Date: June 12, 1991
Catalog of Federal Domestic Assistance 93.244
Under the authority of Section 303, Public Health Service
Act, 42 U.S.C. 242a; 42 CFR Part 64a, the National
Institute of Mental Health will accept applications in
response to this request under the single receipt date
of June 12, 1991.
Darrel A. Regier, M.D., M.P.H.
Director
Division of Clinical Research
Alan I. Leshner, Ph.D.
Acting Director
National Institute of Mental Health
PURPOSE
The purpose of the National Institute of Mental Health
(NIMH) clinical training program is to enhance the
quality and effectiveness of services to persons with
major mental disorders. Insufficient numbers of well-
trained mental health professionals are available to
serve (1) severely and persistently mentally ill adults,
e.g., adults with schizophrenic disorders or mood
disorders, including homeless persons with these
disorders; (2) seriously emotionally disturbed children
and adolescents; (3) elderly persons with mental
disorders; (4) individuals with mental disorders in
rural areas; (5) racial/ethnic minorities with mental
disorders.
This program is designed to recruit and prepare mental
health professionals in the core mental health
disciplines of social work, psychiatric nursing,
psychology, psychiatry, and marriage and family therapy
who are well trained and experienced in modern mental
health diagnostic, treatment, and rehabilitation
techniques, research methodologies and findings, and the
delivery of care within community-based systems.
TRAINING ISSUES
Applicants under this Request for Applications (RFA) must
focus in depth on one or
more of the priority populations described below.
Programs must demonstrate that they incorporate the
latest diagnostic and treatment procedures, as well as
the latest relevant research findings.
The priority service populations for this RFA are:
o Severely and Persistently Mentally Ill Adults
This priority population includes, but is not limited to,
adults with schizophrenic disorders, major mood
disorders, including homeless persons with these
disorders, and persons with co-morbidity, i.e., the
mentally ill who are also alcohol and/or drug abusers.
o Children and Adolescents with Mental Disorders
Mental disorders of children and adolescents include, but
are not limited to, serious emotional disturbances;
childhood psychoses; major mood disorders; disruptive
behavior and personality disorders; and serious
developmental disorders or alcohol and/or drug abuse when
combined with other mental disorders.
o Elderly with Mental Disorders
Mental disorders of the aging include Alzheimer's disease
and other dementias; affective disorders with their
associated medical, behavioral, cognitive, social, and
emotional aspects; as well as anxiety disorders, late-
onset schizophrenia, and personality disorders.
o Mentally Ill in Rural Areas
This population includes individuals with severe and
persistent mental and emotional disorders living in rural
areas, especially those areas--rural towns and
communities--with low population density and limited
access to health, mental health, and social services.
Applicant institutions selecting this priority must
include a strategy for the recruitment of students from
rural areas and the development of curriculum addressing
rural mental health issues.
o Racial/Ethnic Minorities with Mental Disorders
While minority persons are represented among the priority
service populations listed above, developing and
implementing targeted, culturally appropriate mental
health services for minorities within these groups (i.e.,
severely ill minority adults, minority children and
adolescents, minority elderly, and minorities in rural
areas) are a complex and challenging priority. Applicant
institutions selecting this priority must, therefore,
demonstrate a capacity to develop and implement a
focused, culturally appropriate clinical training program
with curriculum and clinical experiences based on
culturally relevant concepts and the latest scientific
findings. (The term "minority" in this announcement
refers to Blacks or African Americans, Hispanics or Latin
Americans, Asian/Pacific Island Americans (including
Native Hawaiians and Samoans), and American
Indians/Alaskan Natives.)
Additional cross-cutting priorities are linkages between
academic programs and State/community service systems,
i.e., public-academic linkages (PAL) and linkages with
clinical researchers and research trainers. Therefore,
training institutions are strongly encouraged to
collaborate with State and local Mental Health and State
and local Alcohol and Drug Abuse service systems in order
to make training sites available in public facilities and
to ensure that trainees receive high-quality relevant
clinical experiences in these settings. Similarly,
intra-institution collaboration with ongoing clinical
research components is also encouraged.
All programs must also show evidence that curriculum
content addresses ethnic and cultural issues. Programs
must ensure that, in the clinical field experience,
significant numbers of minority clients or patients are
seen by all trainees.
ELIGIBILITY
Accredited and/or approved departments/divisions in the
mental health disciplines of psychiatric nursing,
psychiatry, psychology, social work, and marriage and
family therapy in colleges or universities of the United
States, including territories and possessions, are
eligible to apply. Multidisciplinary applications are
encouraged. Applications may be for predoctoral and/or
postdoctoral training in any of these fields. Requests
for support of trainees at multiple levels, e.g.,
master's, post-master's, doctoral, postdoctoral, that
are consistent with the disciplines' educational
patterns, may be incorporated into single applications,
if appropriate. The disciplines and eligible
institutional units are:
o an accredited college or university school of
nursing that offers a graduate program in psychiatric
nursing
o a department of psychiatry, a division of child
psychiatry, or a division of geriatric psychiatry having
an accredited training program for general and/or child
psychiatry residents in an accredited medical school or
a free-standing institution
o a department of psychology, a school of professional
psychology, or an internship program, each with
appropriate accreditation for training in clinical,
counseling, or school psychology
o a school or department of social work offering
accredited master's/doctoral programs; accredited
baccalaureate programs in States having no graduate
program; and postmaster's and postdoctoral training
programs
o a college or university-based accredited graduate
program in marriage and family therapy and accredited
postmaster's and postdoctoral training programs
Important Note: A grantee eligible for a noncompeting
continuation award in fiscal year 1991 may not apply for
a new award in the same priority area.
One clinical training grant may be applied for in each
of the core disciplines under this
RFA. However, NIMH encourages
multidisciplinary training programs whenever appropriate.
APPLICATION CHARACTERISTICS
Applications must include a brief description of the
applicant educational institution and, where appropriate,
associated service and clinical research settings,
including background, history, programmatic focus,
organization, resources, personnel, and record of
educational/service/research linkage achievements. Any
existing mental health or substance abuse clinical or
research training activities in the priority area(s)
addressed by an application must be described. A
carefully organized plan for teaching the mental health
skills necessary must be presented. Of particular
interest are linkages of ongoing or proposed clinical
training activities with clinical research or research
training at the applicant institution.
Each application must include descriptions of the:
o goals and objectives of the program and specify one
or more of the priority populations
o key faculty members and clinical supervisors or
field instructors, including their assignment of
responsibility to the program, and other qualifications,
experience, and roles
o history and current structure of the proposed
education/training program, with an overall
characterization of principles and conceptual framework
around which the program is organized
o differences between the proposed program and ongoing
general mental health training at the institution
highlighting how the proposed program enhances ongoing
training particularly in the focused priority area
o educational and training components of the proposed
program, highlighting courses and clinical experiences
that are proposed but not yet implemented:
- a didactic component that is designed to make
available to the student the latest scientific
knowledge regarding the designated priority population,
including minority content where appropriate
- an experiential component that involves direct
service to priority population patients or clients,
including minorities whenever practicable, as well as
exposure to issues of services delivery
o evidence of training directed to promoting an
understanding of research methodologies, and the
incorporation of research findings into clinical practice
o documentation of support for the proposed program
by the educational/training institution and the related
State/community service systems
o documentation of linkages between the academic
institution and public mental health service systems
o documentation of linkages between clinical
researchers and research and clinical trainers within the
institution
o professional activities of all trainees who have
completed this specialty program in the last five years,
indicating minority students, and specifying effects of
previous NIMH grant support, if any
o documentation of numbers of students currently
enrolled in the program receiving training in working
with the designated priority service populations,
indicating the number of minority students so enrolled
o specific steps taken for the recruitment, retention,
and graduation of minority trainees.
o review of the pool from which trainees will be
recruited, recruitment strategies, selection criteria,
and numbers of minority students to be enrolled, as well
as the total number of trainees, including those who
would not receive a stipend but who would benefit
directly and indirectly from the supported training
o an evaluation plan that addresses all aspects of the
training program, including formative and summative
evaluations to provide feedback for program improvement
TERMS AND CONDITIONS OF SUPPORT
In fiscal year 1991, approximately $1.2 million will be available to
fund approximately 15 to 20 three-year awards under this RFA. However,
since the program is proposed in the FY 1991 President's budget for
phase down over three years, no guarantee can be provided for funding
beyond the first year. The objectives and activities of the first year
should be designed to be significant in themselves. Awards will be
limited to a maximum of $80,000 (total costs) per year, with the
exception of multidisciplinary awards which may be funded up to $120,000
(total costs) per year.
Direct Costs
Support under this program is primarily to provide for
trainee stipends, and stipend requests must be included
in all applications.
Awards are made directly to eligible applicant
institutions. Funds may be used only for those expenses
that are directly related to and necessary for carrying
out the project and must be expended in conformance with
DHHS cost principles, the Public Health Service (PHS)
Grants Policy Statement (Public Health Service Grants
Policy Statement, DHHS Publication No. (OASH) 90-50,000
(rev. October 1, 1990), and conditions set forth in this
document.
Grantees are expected to be familiar and comply with
applicable cost policies.
Trainee Stipends
Trainee stipends are intended to assist students in
meeting subsistence expenses and to enable them to pursue
education on a full-time basis. No part-time stipends
are allowed. The amount of the stipend is determined by
the academic status of the appointee. Stipends for full-
time trainees enrolled in educational programs leading
to or based on a degree are as follows:
Prebaccalaureate - These stipends are at a level of
$6,504 for a 12-month program, prorated according to
actual length of support.
Postbaccalaureate-predoctoral - These stipends will be
paid at an annual (12 months) rate of $8,800, prorated
according to the length of the training program.
Postdoctoral - Postdoctoral stipends range from $18,600
to $32,300 per year, depending upon the level of relevant
experience of the students at the time of appointment.
These amounts must be prorated according to actual length
of support.
Years of Relevant Experience Stipend
0 $18,600
1 $19,700
2 $25,600
3 $26,900
4 $28,200
5 $29,500
6 $30,800
7 or more $32,300
Relevant experience is considered to include activities
beyond the doctoral degree such as internship, residency,
teaching, or providing services in the specific area of
training. For trainees who receive a stipend for the
first time in a second or later year in the NIMH training
program, the level of support shall be determined by
relevant experience before entry into the program plus
full-time years in the program without a stipend.
Stipends for full-time trainees enrolled in postdoctoral
programs that are not degree related may be paid
commensurate with the trainee's career status and
experience in accordance with the above schedule.
Maximum support is $32,300, prorated according to the
length of the program.
Allowances are available for medical students to engage
in not-for-credit supervised clinical experience and/or
related special studies/projects in any of the NIMH-
supported programs in psychiatry.
Teaching and Associated Costs
Direct cost items are allowable for teaching costs
associated with these projects. Direct cost items
include personnel, consultants, supplies, travel,
reproduction and printing costs, rental equipment, minor
equipment items, and other items that are directly
related to the proposed clinical training program and are
otherwise unavailable from the institution. It is
expected that the educational institutions will fund a
substantial part of the support for personnel costs.
Teaching costs may be requested up to a ceiling of $1,500
per predoctoral stipend and $2,500 per postdoctoral
stipend. No teaching costs are permitted except in
association with stipends.
Other Trainee Costs
In addition to stipends, the institution may request
funds for tuition, fees, and trainee travel. Trainee
travel costs are allowable only between the institutional
and field training sites or in the special cases
indicated on pages
7-16 of the PHS Grants Policy Statement. Requests for
tuition must not exceed $8,000 per stipend.
Indirect Costs
All grants under this RFA will be reimbursed at 8 percent
of total allowable direct costs or actual indirect costs,
whichever is less.
Payback Provisions
Any trainee who receives a clinical traineeship in
psychology, psychiatry, psychiatric nursing, social work,
or marriage and family therapy, in an established
training program, designed to be for a period of 180 days
or more under an NIMH clinical training grant, must pay
back a period of obligated service equal to the length
of the traineeship. The period of support need not be
continuous. Any support received for any period of time
under previous NIMH clinical training grants, if the
stipend and/or other allowances were awarded on or after
September 1, 1981, will be added to the total length of
service required. The conditions of the obligated
service requirement are set forth in 42 Code of Federal
Regulations Part 64a and include a triple damages
repayment provision for the failure to fulfill the
obligated service. No trainee may receive a stipend or
other allowance from the grant until he/she has signed
and submitted a Payback Agreement form, a Statement of
Appointment of Trainee form (PHS 2271), and a
certification of Non-Delinquency on Federal Debt.
Additional information on payback requirements and fiscal and
administrative issues is available from:
Mr. Stephen Hudak
Chief, Grants Management Section
Grants Management Branch
National Institute of Mental Health
5600 Fishers Lane, Room 7C-26
Rockville, MD 20857
Telephone: (301) 443-4456
APPLICATION PROCEDURES
Prospective applicants are encouraged to consult NIMH
Educational and Training staff for
assistance in developing applications. Prospective
applicants are also encouraged to notify appropriate NIMH
staff of their intent to apply. Applications kits (PHS
398, rev. 10/88) containing the necessary forms and
Special Instructions must be obtained by contacting the
Education and Training Branch staff. Applicants must use
the Special Instructions included in the application kit
specifically designed for this NIMH Institutional
Clinical Training Grant program.
Applications must be complete and contain all information
needed for initial and Advisory Council review. No
addenda will be accepted later unless specifically
requested by the Executive Secretary of the review
committee. No site visits will be made.
The applicant must include a project abstract that cannot
exceed the space provided in the application.
The narrative section of the application may not exceed
20 pages. Appendices may be used but not to expand the
narrative section. Applications exceeding this
limitation will be returned without review. The original
and five (5) copies of the application must be
submitted to:
Division of Research Grants
Westwood Building, Room 240
5333 Westbard Avenue
Bethesda, MD 20892**
Complete line 2 of the application by typing in the RFA number and
title. The RFA label (found in the 10/88 revision of application form
PHS 398) must be affixed to the bottom of the face page of the original
copy of the application. Failure to use this label could result in
delayed processing of your application such that it will not reach the
review committee in time for review.
Because of the very short time available for initial and
Council reviews, it is requested that one additional copy
of the application be sent directly to:
NIMH Division of Extramural Activities
Room 9C-23, 5600 Fishers Lane
Rockville, MD 20857
Attention: Ms. Edna Hardy-Hill
REVIEW OF APPLICATIONS
A dual review system is used to ensure expert, objective
review of the quality of applications. The first step,
peer review for educational and technical merit, is by
primarily non-Federal experts comprising Initial Review
Groups. Notification of the review recommendations will
be sent to the applicant after the initial review. The
final review is by the National Advisory Mental Health
Council. Only applications recommended for approval by
the Council may be considered for funding.
Each grant application is evaluated on its own merits.
The following criteria are used in the initial review:
(1) Quality of education/training program
o clarity of the goals of the proposed
educational/training program and their consonance with
the purposes and requirements of this RFA
o relevance, feasibility, and specificity of the
content, methods, and organization of the training
program in relation to specified project goals and
objectives, including minority content whenever appropriate
o subpopulations adequately addressed
o soundness of the plan for providing balanced
didactic and experiential educational content, including
existing and/or new and innovative curricular offerings
and teaching methods oriented to the priority
population(s), including minority content where
appropriate
o inclusion in the curriculum of up-to-date research
findings and scientific knowledge about diagnostic and
treatment services for the priority population(s),
including minority content where appropriate
o inclusion of research methods and evaluation
o appropriateness of plans for evaluating the proposed
program
(2) Budget
o adequacy of the budget projections and other
resources for carrying out the project activities
(3) Quality of public-academic linkages
o degree to which the educational plan has been
developed and will be implemented in conjunction with
public mental health systems and services, and commitment
of key personnel and institutions to public-academic
linkages
o availability and extent of trainee experience in
publicly funded (including private non-profit) clinical
programs
(4) Quality of faculty
o expertise with the priority population(s), including
national leadership and publications
o clinical qualifications of faculty, including
appropriateness as role models
(5) Quality of students/trainees
o feasibility of the plan to recruit from a high-
quality pool of potential students and to retain and
graduate competent students, including minority students
o degree to which students who do not receive stipends
will also have appropriate exposure to special content
and skills development relevant to the priority
populations
(5) Training record
o evidence of applicant's history and commitment to
educate professionals for publicly funded service to the
identified priority population(s), as documented in the
career patterns of graduates of this specialty program
in the last five years
o evidence of successful use of previous NIMH grants,
if any, to train professionals for service in the
priority areas, including minority and disadvantaged
professionals
RECEIPT AND REVIEW SCHEDULE
National Advisory
Receipt of Initial Mental Health Earliest
Application Review Council Review Award
Date
June 12, 1991 July September September 1991
Applications received after the above receipt date will
not be reviewed and will be returned to the applicant.
AWARD OF GRANTS
Awards will be made on the basis of the following
criteria:
o quality of proposed education/training programs as
determined by the review process
o balance among programs directed to the priority
populations, among the disciplines and, if
appropriate, among geographic, especially rural,
locations
o availability of funds
STAFF CONSULTATION
Staff consultation on clinical training grants is
available from the following:
General Information Lemuel B. Clark, M.D., Chief
Education and Training Branch
(301) 443-5850
Social Work and Neilson F. Smith, D.S.W., Chief,
Marriage and Family Social Work Education Program
Therapy (301) 443-5850
Psychiatry Melvyn R. Haas, M.D., Chief
Psychiatry Education Program
(301) 443-2120
Psychology Paul Wohlford, Ph.D., Chief
Psychology Education Program
(301) 443-5850
Psychiatric Nursing Carol Bush, Ph.D., R.N., Chief
Psychiatric Nursing
Education Program
(301) 443-5850
The mailing address for all the above is:
Education and Training Branch
Division of Clinical Research
National Institute of Mental Health
5600 Fishers Lane, Room 7C02
Rockville, MD 20857
Applications submitted in response to this announcement
are not subject to the intergovernmental review
requirements of Executive Order 12372 as implemented
through HHS regulations at 45 CFR Part 100, and are not
subject to Health Systems Agency review.
$$XID RFA AR9104 AR-91-04 P1O1 *****************************************
REQUEST FOR APPLICATIONS
RFA: AR-91-04
DIAGNOSIS AND TREATMENT OF LYME DISEASE
P.T. 34; K.W. 0715125, 1002032, 0745020, 0745070
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Letter of Intent Receipt Date: May 1, 1991
Application Receipt Date: June 17, 1991
PURPOSE
The National Institute of Arthritis and Musculoskeletal and
Skin Diseases (NIAMS) invites applications for grants to
conduct research on the diagnosis and treatment of Lyme
disease.
BACKGROUND
Lyme disease is a spirochetal disease, usually transmitted
by the bite of a tick, most often by a nymphal Ixodes
dammini, when this species is prevalent in the Spring.
Subsequent to its first description in 1975, Lyme disease
has become the most common tick-borne illness in the United
States, with approximately 8,800 new cases reported in 1990.
Endemic areas in the United States include the northeast,
north central, and western regions.
The spectrum of manifestations resulting from Lyme disease
ranges from the initial skin lesion, erythema migrans, in
approximately 60 percent of all cases, to chronic arthritic
and neurologic disability. Symptoms of different organ
systems (skin, heart, nervous system, eye, and joints) are
often combined.
Some researchers have distinguished three separate disease
stages: Stage I, characterized primarily by erythema migrans
and flu-like symptoms; Stage II, differentiated by
dermatologic, ophthalmologic, neurologic, and cardiac
disorders; and Stage III, with chronic arthritis,
psychiatric disorders, and a chronic fatigue syndrome.
Efficacy of staging is limited, however, because of the
inconsistency of clinical manifestations among patients.
Further, stages may overlap with a mixture of both acute and
chronic facets of the disease.
Lyme disease remains difficult to diagnose, in part because
the causative agent, Borrelia burgdorferi, is usually not
easily cultured or directly observable from patients'
specimens. Currently available standard laboratory tests
are not fully satisfactory in that they lack sensitivity and
specificity and are not well standardized.
Underdiagnosis has proven to be a problem in parts of the
country where it is not endemic or is relatively uncommon.
Lyme disease can present with a wide variety of signs and
symptoms, making it difficult for physicians who have little
or no experience with it to make a correct diagnosis. On
the other hand, in parts of the country where Lyme disease
is well established and where there has been extensive
publicity, patients with signs and symptoms suggestive of
Lyme disease may be diagnosed inappropriately as having the
disease when in fact they have some other disease resembling
it.
Both aspects of this problem could be addressed by more
sensitive, accurate, and inexpensive diagnostic tests. In
general, serologic tests currently available do not detect
some cases of early Lyme disease; conversely, in the later
stages of the disease, tests are often too sensitive and
less specific.
Once diagnosed, the manifestations of Lyme disease appear to
be potentially treatable with a variety of antibiotics. The
optimal regimen, including choice of drug, dose, route of
administration, and length of therapy, has yet to be
determined. Further clarification is also needed to
determine the best method of treating disease sequelae at
both early and late stages of Lyme disease.
Recent studies seem to indicate that tetracyclines or
ceftriaxone may be superior to penicillin. Oral
tetracycline administration is typically effective in
treating early erythema migrans, but once arthritis or
neurologic manifestations have developed, high-dose
parenteral treatment is recommended, although the effect on
neurologic symptoms has not yet been proven. In the absence
of long-term observations, it is not clear that oral
administration of drugs alone can effect a cure, prevent
further complications, or forestall evolution to a chronic
disease state.
RESEARCH GOALS AND SCOPE
The goal of this Request for Applications (RFA) is to
stimulate research to effect
better diagnosis and treatment of Lyme disease.
Applications submitted in response to this RFA are expected
to concentrate upon: developing and testing methods of
diagnosis that are more reliable, accurate, and sensitive
than current techniques to detect Lyme disease in patients;
and/or developing and testing improved ways to treat all
aspects (arthritic, cardiac, neurologic, and so forth) and
stages of the disease.
Specific issues that may be addressed include, but are not
limited to:
Diagnosis:
o Classification and validation of clinical criteria;
o Proper identification of erythema migrans (in contrast to
non-tick insect bites);
o Whether diagnostic criteria differ in children and
adults;
o Optimal methods for serodiagnosis;
o The effect of therapy on serodiagnosis;
o The utility of various biological fluids and tissue for
diagnosis;
o The best and most sensitive methods to detect spirochetal
antigens;
o Differential diagnosis strategies.
Treatment:
o Drugs to be used in treating erythema migrans;
o Optimal treatments for arthritic, neurologic, cardiac, and
other later manifestations of Lyme disease;
o Appropriate treatment of Lyme disease in children;
o Appropriate treatment of Lyme disease in pregnant women;
o Appropriate treatment of congenital Lyme disease;
o Utility of prophylactic antibiotics in exposed
individuals from endemic areas.
MECHANISM OF SUPPORT
Applications considered appropriate responses to this RFA
are the traditional research project grants (R01).
Approximately $1,500,000 in total costs per year for 3 to 5
years will be committed by the
NIAMS
specifically to fund applications that are submitted in
response to this RFA.
Approximately seven awards are expected to be made for this RFA.
The funding level for this RFA is dependent on the receipt
of a sufficient number of applications of high scientific
merit. The total project period for applications submitted
may not exceed five (5) years. The earliest possible
start date for the initial awards will be September 30,
1991. Although there are provisions for this program in the
financial plans of the NIAMS, award of grants pursuant to
this RFA is contingent upon the availability of funds for
this purpose. Applications may receive secondary
assignment, when appropriate, to other institutes of the
NIH. Non-profit and for-profit institutions, as well as
foreign and domestic institutions, are eligible to apply.
This RFA is a one-time solicitation. Future
unsolicited competing renewal applications that result from
this current RFA will compete as research project
applications with all other investigator-initiated
applications and be reviewed by a standing Division of
Research Grants study section.
In order to facilitate program planning and development, and
to promote research interactions, the NIAMS
intends to organize annual meetings of Principal
Investigators and other key staff members of NIAMS-supported
Lyme disease research projects. Funds for travel to these
meetings (in Bethesda, Maryland) must be included in each
year of the budget.
SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF
NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN
CLINICAL RESEARCH STUDY POPULATIONS
NIH and ADAMHA policy is that applicants for NIH/ADAMHA clinical
research grants and cooperative agreements will be required to
include minorities and women in study populations so that
research findings can be of benefit to all persons at risk of the
disease, disorder or condition under study; special emphasis
should be placed on the need for inclusion of minorities and
women in studies of diseases, disorders and conditions which
disproportionately affect them. This policy is intended to apply
to males and females of all ages. If women or minorities are
excluded or inadequately represented in clinical research,
particularly in proposed population-based studies, a clear
compelling rationale should be provided.
The composition of the proposed study population must be
described in terms of gender and racial/ethnic group. In
addition, gender and racial/ethnic issues should be addressed in
developing a research design and sample size appropriate for the
scientific objectives of the study. This information should be
included in the form PHS 398 in Section 2, A-D of the Research
Plan AND summarized in Section 2, E, Human Subjects.
Applicants/offerors are urged to assess carefully the feasibility
of including the broadest possible representation of minority
groups. However, NIH recognizes that it may not be feasible or
appropriate in all research projects to include representation of
the full array of United States racial/ethnic minority
populations (i.e., Native Americans (including American Indians
or Alaskan Natives), Asian/Pacific Islanders, Blacks, Hispanics).
The rationale for studies on single minority population groups
should be provided.
For the purpose of this policy, clinical research includes human
biomedical and behavioral studies of etiology, epidemiology,
prevention (and preventive strategies), diagnosis, or treatment
of diseases, disorders or conditions, including but not limited to
clinical trials.
The usual NIH policies concerning research on human subjects also
apply. Basic research or clinical studies in which human tissues
cannot be identified or linked to individuals are excluded.
However, every effort should be made to include human tissues
from women and racial/ethnic minorities when it is important to
apply the results of the study broadly, and this should be
addressed by applicants.
For foreign awards, the policy on inclusion of women applies
fully; since the definition of minority differs in other
countries, the applicant must discuss the relevance of research
involving foreign population groups to the United States'
populations, including minorities.
If the required information is not contained within the
application, the application will be returned.
Peer reviewers will address specifically whether the research
plan in the application conforms to these policies. If the
representation of women or minorities in a study design is
inadequate to answer the scientific question(s) addressed AND the
justification for the selected study population is inadequate, it
will be considered a scientific weakness or deficiency in the
study design and will be reflected in assigning the priority
score to the application.
All applications for clinical research submitted to NIH are
required to address these policies. NIH funding components will
not award grants or cooperative agreements that do not comply
with these policies.
REVIEW PROCEDURES AND CRITERIA
REVIEW PROCEDURES
Applications will be reviewed initially by the Division of
Research Grants for completeness and will be assigned to a
special NIAMS review group. Evaluation for responsiveness
to the RFA is an NIAMS program staff function. Applications
that are judged non-responsive will be returned to the
applicant but may be submitted as investigator-initiated
applications at the next receipt date.
If the number of applications submitted is large
compared to the number of awards to be made, the NIH will
conduct an administrative review (triage) to eliminate
those that are clearly not competitive. The NIH will
withdraw from further competition those applications judged
to be noncompetitive and notify the applicant and
institutional business official.
Those applications judged to be both responsive and
competitive will be evaluated in accordance with the
criteria stated below for scientific/technical merit by an
appropriate initial review group convened by the NIAMS
Review Branch. The second level of review will be conducted
by the National Arthritis and Musculoskeletal and Skin
Diseases Advisory Council.
REVIEW CRITERIA
Applications responsive to this competitive solicitation will
be reviewed in accordance with the following criteria:
1. Extent of relevance of the proposed research to the aims
of the RFA.
2. Scientific merit of the proposed approach, including the
accuracy and quality of the methodological approach and
the research design. Familiarity with the proposed
techniques should be demonstrated, e.g., by presentation
of preliminary data.
3. Expertise and qualifications of the Principal
Investigator and proposed staff and/or collaborators to
perform the proposed research.
4. Documentation of the adequacy of the facilities and
resources.
The review group will critically examine the proposed budget
and recommend an appropriate budget for each approved
application.
APPLICATION PROCEDURES
The research grant application form PHS 398 (revised 10/88)
must be used in applying for these grants. This form is
available at most institutional business offices and from
the Office of Grants Inquiries, Division of Research Grants,
National Institutes of Health, Room 449, Westwood Building,
5333 Westbard Avenue, Bethesda, MD 20892.
The RFA label available in the 10/88 revision of form PHS
398 must be affixed to the bottom of the face page. 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 title of the RFA and
the RFA number must be typed on line 2 of the face page of
the application form.
Submit a signed, typewritten original of the application,
including the Checklist, and four (4) signed, exact
photocopies, in one package to the Division of Research
Grants at the address below. The photocopies must be clear
and single-sided.
DIVISION OF RESEARCH GRANTS
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD 20892**
At the time of submission, two (2) additional copies of the
application must also be sent to:
REFERRAL OFFICER
Extramural Program
National Institute of Arthritis and Musculoskeletal and Skin
Diseases
Westwood Building, Room 5A-07
5333 Westbard Avenue
Bethesda, MD 20892
Applications must be received by June 17, 1991. If an
application is received after that date it will be returned
to the applicant.
If the application submitted in response to this RFA is
substantially similar to a research grant application already
submitted to the NIH for review, but has not yet been reviewed,
the applicant will be asked to withdraw either the pending
application or the new one. Simultaneous submission of identical
applications will not be allowed, nor will essentially identical
applications be reviewed by different review committees.
Therefore, an application cannot be submitted in response to this
RFA that is essentially identical to one that has already been
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.
LETTER OF INTENT
Prospective applicants are asked to submit a letter of
intent by May 1, 1991. This letter should
include the name of the institution, any other
participating institutions, the Principal
Investigator and other key investigators, and a
descriptive title. Such a letter of intent is not binding
and will not enter into the review of any application
subsequently submitted, nor is it a necessary requirement
for application. Letters of intent are requested solely for
review planning purposes. They allow NIAMS staff to
estimate the potential review workload and to avoid possible
conflict of interest in the review. NIAMS staff will not
provide responses to such letters.
Letters of Intent are to be submitted to:
Dr. Tommy L. Broadwater
Chief, Grants Review Branch
Extramural Program
National Institute of Arthritis and Musculoskeletal and Skin
Diseases
Westwood Building, Room 5A-05A
Bethesda, MD 20892
Telephone: (301) 496-0754
INQUIRIES
Written and telephone inquiries concerning the objective and
scope of this RFA and inquiries about whether specific
proposed research would be responsive are encouraged and
should be directed to:
Dr. Lawrence Petrucelli
Arthritis Program Director
National Institute of Arthritis and Musculoskeletal and Skin
Diseases
5333 Westbard Avenue
Westwood Building, Room 405
Bethesda, MD 20892
Telephone: (301) 496-7326
For fiscal and administrative matters, contact:
Diane M. Watson
Grans Management Officer
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Westwood Building, Room 407-A
Bethesda, MD 20892
Telephone: (301) 496-7495
This program is described in the Catalog of Federal Domestic
Assistance No. 93.846, Arthritis, Musculoskeletal and Skin
Diseases Research. Awards will be made under authorization
of the Public Health Service Act, Title III, Section 301 (c)
(Public Law 78-410, as amended; 42 USC 241) and administered
under PHS grant policies and Federal Regulations 42 CFR Part
52 and 45 CFR Part 74. This program is not subject to the
intergovernmental review requirements of Executive Order
12372 or Health Systems Agency review.
Letters of Intent are to be submitted to:
Dr. Tommy L. Broadwater
Chief, Grants Review Branch
Extramural Program
National Institute of Arthritis and Musculoskeletal and Skin
Diseases
Westwood Building, Room 5A-05A
Bethesda, MD 20892
Telephone: (301) 496-0754
INQUIRIES
Written and telephone inquiries concerning the objective and
scope of this RFA and inquiries about whether specific
proposed research would be responsive are encouraged and
should be directed to:
Dr. Lawrence Petrucelli
Arthritis Program Director
National Institute of Arthritis and Musculoskeletal and Skin
Diseases
$$XID RFA AR9104 AR-91-04 P1O1 *****************************************
REQUEST FOR APPLICATIONS
RFA: AR-91-04
DIAGNOSIS AND TREATMENT OF LYME DISEASE
P.T. 34; K.W. 0715125, 1002032, 0745020, 0745070
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Letter of Intent Receipt Date: May 1, 1991
Application Receipt Date: June 17, 1991
PURPOSE
The National Institute of Arthritis and Musculoskeletal and
Skin Diseases (NIAMS) invites applications for grants to
conduct research on the diagnosis and treatment of Lyme
disease.
BACKGROUND
Lyme disease is a spirochetal disease, usually transmitted
by the bite of a tick, most often by a nymphal Ixodes
dammini, when this species is prevalent in the Spring.
Subsequent to its first description in 1975, Lyme disease
has become the most common tick-borne illness in the United
States, with approximately 8,800 new cases reported in 1990.
Endemic areas in the United States include the northeast,
north central, and western regions.
The spectrum of manifestations resulting from Lyme disease
ranges from the initial skin lesion, erythema migrans, in
approximately 60 percent of all cases, to chronic arthritic
and neurologic disability. Symptoms of different organ
systems (skin, heart, nervous system, eye, and joints) are
often combined.
Some researchers have distinguished three separate disease
stages: Stage I, characterized primarily by erythema migrans
and flu-like symptoms; Stage II, differentiated by
dermatologic, ophthalmologic, neurologic, and cardiac
disorders; and Stage III, with chronic arthritis,
psychiatric disorders, and a chronic fatigue syndrome.
Efficacy of staging is limited, however, because of the
inconsistency of clinical manifestations among patients.
Further, stages may overlap with a mixture of both acute and
chronic facets of the disease.
Lyme disease remains difficult to diagnose, in part because
the causative agent, Borrelia burgdorferi, is usually not
easily cultured or directly observable from patients'
specimens. Currently available standard laboratory tests
are not fully satisfactory in that they lack sensitivity and
specificity and are not well standardized.
Underdiagnosis has proven to be a problem in parts of the
country where it is not endemic or is relatively uncommon.
Lyme disease can present with a wide variety of signs and
symptoms, making it difficult for physicians who have little
or no experience with it to make a correct diagnosis. On
the other hand, in parts of the country where Lyme disease
is well established and where there has been extensive
publicity, patients with signs and symptoms suggestive of
Lyme disease may be diagnosed inappropriately as having the
disease when in fact they have some other disease resembling
it.
Both aspects of this problem could be addressed by more
sensitive, accurate, and inexpensive diagnostic tests. In
general, serologic tests currently available do not detect
some cases of early Lyme disease; conversely, in the later
stages of the disease, tests are often too sensitive and
less specific.
Once diagnosed, the manifestations of Lyme disease appear to
be potentially treatable with a variety of antibiotics. The
optimal regimen, including choice of drug, dose, route of
administration, and length of therapy, has yet to be
determined. Further clarification is also needed to
determine the best method of treating disease sequelae at
both early and late stages of Lyme disease.
Recent studies seem to indicate that tetracyclines or
ceftriaxone may be superior to penicillin. Oral
tetracycline administration is typically effective in
treating early erythema migrans, but once arthritis or
neurologic manifestations have developed, high-dose
parenteral treatment is recommended, although the effect on
neurologic symptoms has not yet been proven. In the absence
of long-term observations, it is not clear that oral
administration of drugs alone can effect a cure, prevent
further complications, or forestall evolution to a chronic
disease state.
RESEARCH GOALS AND SCOPE
The goal of this Request for Applications (RFA) is to
stimulate research to effect
better diagnosis and treatment of Lyme disease.
Applications submitted in response to this RFA are expected
to concentrate upon: developing and testing methods of
diagnosis that are more reliable, accurate, and sensitive
than current techniques to detect Lyme disease in patients;
and/or developing and testing improved ways to treat all
aspects (arthritic, cardiac, neurologic, and so forth) and
stages of the disease.
Specific issues that may be addressed include, but are not
limited to:
Diagnosis:
o Classification and validation of clinical criteria;
o Proper identification of erythema migrans (in contrast to
non-tick insect bites);
o Whether diagnostic criteria differ in children and
adults;
o Optimal methods for serodiagnosis;
o The effect of therapy on serodiagnosis;
o The utility of various biological fluids and tissue for
diagnosis;
o The best and most sensitive methods to detect spirochetal
antigens;
o Differential diagnosis strategies.
Treatment:
o Drugs to be used in treating erythema migrans;
o Optimal treatments for arthritic, neurologic, cardiac, and
other later manifestations of Lyme disease;
o Appropriate treatment of Lyme disease in children;
o Appropriate treatment of Lyme disease in pregnant women;
o Appropriate treatment of congenital Lyme disease;
o Utility of prophylactic antibiotics in exposed
individuals from endemic areas.
MECHANISM OF SUPPORT
Applications considered appropriate responses to this RFA
are the traditional research project grants (R01).
Approximately $1,500,000 in total costs per year for 3 to 5
years will be committed by the
NIAMS
specifically to fund applications that are submitted in
response to this RFA.
Approximately seven awards are expected to be made for this RFA.
The funding level for this RFA is dependent on the receipt
of a sufficient number of applications of high scientific
merit. The total project period for applications submitted
may not exceed five (5) years. The earliest possible
start date for the initial awards will be September 30,
1991. Although there are provisions for this program in the
financial plans of the NIAMS, award of grants pursuant to
this RFA is contingent upon the availability of funds for
this purpose. Applications may receive secondary
assignment, when appropriate, to other institutes of the
NIH. Non-profit and for-profit institutions, as well as
foreign and domestic institutions, are eligible to apply.
This RFA is a one-time solicitation. Future
unsolicited competing renewal applications that result from
this current RFA will compete as research project
applications with all other investigator-initiated
applications and be reviewed by a standing Division of
Research Grants study section.
In order to facilitate program planning and development, and
to promote research interactions, the NIAMS
intends to organize annual meetings of Principal
Investigators and other key staff members of NIAMS-supported
Lyme disease research projects. Funds for travel to these
meetings (in Bethesda, Maryland) must be included in each
year of the budget.
SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF
NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN
CLINICAL RESEARCH STUDY POPULATIONS
NIH and ADAMHA policy is that applicants for NIH/ADAMHA clinical
research grants and cooperative agreements will be required to
include minorities and women in study populations so that
research findings can be of benefit to all persons at risk of the
disease, disorder or condition under study; special emphasis
should be placed on the need for inclusion of minorities and
women in studies of diseases, disorders and conditions which
disproportionately affect them. This policy is intended to apply
to males and females of all ages. If women or minorities are
excluded or inadequately represented in clinical research,
particularly in proposed population-based studies, a clear
compelling rationale should be provided.
The composition of the proposed study population must be
described in terms of gender and racial/ethnic group. In
addition, gender and racial/ethnic issues should be addressed in
developing a research design and sample size appropriate for the
scientific objectives of the study. This information should be
included in the form PHS 398 in Section 2, A-D of the Research
Plan AND summarized in Section 2, E, Human Subjects.
Applicants/offerors are urged to assess carefully the feasibility
of including the broadest possible representation of minority
groups. However, NIH recognizes that it may not be feasible or
appropriate in all research projects to include representation of
the full array of United States racial/ethnic minority
populations (i.e., Native Americans (including American Indians
or Alaskan Natives), Asian/Pacific Islanders, Blacks, Hispanics).
The rationale for studies on single minority population groups
should be provided.
For the purpose of this policy, clinical research includes human
biomedical and behavioral studies of etiology, epidemiology,
prevention (and preventive strategies), diagnosis, or treatment
of diseases, disorders or conditions, including but not limited to
clinical trials.
The usual NIH policies concerning research on human subjects also
apply. Basic research or clinical studies in which human tissues
cannot be identified or linked to individuals are excluded.
However, every effort should be made to include human tissues
from women and racial/ethnic minorities when it is important to
apply the results of the study broadly, and this should be
addressed by applicants.
For foreign awards, the policy on inclusion of women applies
fully; since the definition of minority differs in other
countries, the applicant must discuss the relevance of research
involving foreign population groups to the United States'
populations, including minorities.
If the required information is not contained within the
application, the application will be returned.
Peer reviewers will address specifically whether the research
plan in the application conforms to these policies. If the
representation of women or minorities in a study design is
inadequate to answer the scientific question(s) addressed AND the
justification for the selected study population is inadequate, it
will be considered a scientific weakness or deficiency in the
study design and will be reflected in assigning the priority
score to the application.
All applications for clinical research submitted to NIH are
required to address these policies. NIH funding components will
not award grants or cooperative agreements that do not comply
with these policies.
REVIEW PROCEDURES AND CRITERIA
REVIEW PROCEDURES
Applications will be reviewed initially by the Division of
Research Grants for completeness and will be assigned to a
special NIAMS review group. Evaluation for responsiveness
to the RFA is an NIAMS program staff function. Applications
that are judged non-responsive will be returned to the
applicant but may be submitted as investigator-initiated
applications at the next receipt date.
If the number of applications submitted is large
compared to the number of awards to be made, the NIH will
conduct an administrative review (triage) to eliminate
those that are clearly not competitive. The NIH will
withdraw from further competition those applications judged
to be noncompetitive and notify the applicant and
institutional business official.
Those applications judged to be both responsive and
competitive will be evaluated in accordance with the
criteria stated below for scientific/technical merit by an
appropriate initial review group convened by the NIAMS
Review Branch. The second level of review will be conducted
by the National Arthritis and Musculoskeletal and Skin
Diseases Advisory Council.
REVIEW CRITERIA
Applications responsive to this competitive solicitation will
be reviewed in accordance with the following criteria:
1. Extent of relevance of the proposed research to the aims
of the RFA.
2. Scientific merit of the proposed approach, including the
accuracy and quality of the methodological approach and
the research design. Familiarity with the proposed
techniques should be demonstrated, e.g., by presentation
of preliminary data.
3. Expertise and qualifications of the Principal
Investigator and proposed staff and/or collaborators to
perform the proposed research.
4. Documentation of the adequacy of the facilities and
resources.
The review group will critically examine the proposed budget
and recommend an appropriate budget for each approved
application.
APPLICATION PROCEDURES
The research grant application form PHS 398 (revised 10/88)
must be used in applying for these grants. This form is
available at most institutional business offices and from
the Office of Grants Inquiries, Division of Research Grants,
National Institutes of Health, Room 449, Westwood Building,
5333 Westbard Avenue, Bethesda, MD 20892.
The RFA label available in the 10/88 revision of form PHS
398 must be affixed to the bottom of the face page. 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 title of the RFA and
the RFA number must be typed on line 2 of the face page of
the application form.
Submit a signed, typewritten original of the application,
including the Checklist, and four (4) signed, exact
photocopies, in one package to the Division of Research
Grants at the address below. The photocopies must be clear
and single-sided.
DIVISION OF RESEARCH GRANTS
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD 20892**
At the time of submission, two (2) additional copies of the
application must also be sent to:
REFERRAL OFFICER
Extramural Program
National Institute of Arthritis and Musculoskeletal and Skin
Diseases
Westwood Building, Room 5A-07
5333 Westbard Avenue
Bethesda, MD 20892
Applications must be received by June 17, 1991. If an
application is received after that date it will be returned
to the applicant.
If the application submitted in response to this RFA is
substantially similar to a research grant application already
submitted to the NIH for review, but has not yet been reviewed,
the applicant will be asked to withdraw either the pending
application or the new one. Simultaneous submission of identical
applications will not be allowed, nor will essentially identical
applications be reviewed by different review committees.
Therefore, an application cannot be submitted in response to this
RFA that is essentially identical to one that has already been
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.
LETTER OF INTENT
Prospective applicants are asked to submit a letter of
intent by May 1, 1991. This letter should
include the name of the institution, any other
participating institutions, the Principal
Investigator and other key investigators, and a
descriptive title. Such a letter of intent is not binding
and will not enter into the review of any application
subsequently submitted, nor is it a necessary requirement
for application. Letters of intent are requested solely for
review planning purposes. They allow NIAMS staff to
estimate the potential review workload and to avoid possible
conflict of interest in the review. NIAMS staff will not
provide responses to such letters.
Letters of Intent are to be submitted to:
Dr. Tommy L. Broadwater
Chief, Grants Review Branch
Extramural Program
National Institute of Arthritis and Musculoskeletal and Skin
Diseases
Westwood Building, Room 5A-05A
Bethesda, MD 20892
Telephone: (301) 496-0754
INQUIRIES
Written and telephone inquiries concerning the objective and
scope of this RFA and inquiries about whether specific
proposed research would be responsive are encouraged and
should be directed to:
Dr. Lawrence Petrucelli
Arthritis Program Director
National Institute of Arthritis and Musculoskeletal and Skin
Diseases
5333 Westbard Avenue
Westwood Building, Room 405
Bethesda, MD 20892
Telephone: (301) 496-7326
For fiscal and administrative matters, contact:
Diane M. Watson
Grans Management Officer
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Westwood Building, Room 407-A
Bethesda, MD 20892
Telephone: (301) 496-7495
This program is described in the Catalog of Federal Domestic
Assistance No. 93.846, Arthritis, Musculoskeletal and Skin
Diseases Research. Awards will be made under authorization
of the Public Health Service Act, Title III, Section 301 (c)
(Public Law 78-410, as amended; 42 USC 241) and administered
under PHS grant policies and Federal Regulations 42 CFR Part
52 and 45 CFR Part 74. This program is not subject to the
intergovernmental review requirements of Executive Order
12372 or Health Systems Agency review.