Subject: RFA AR-9l-04 4/l2/9l NIH Guide
From: Dot Baker <[email-masked]>
To: [email-masked]
Date: Wed, 10 Apr 91 14:07 EST

Hi Paul,
   Please post this to the NIH Listserver as:
       RFAAR-91-04.910412
                         Dottie
 ---------------------------- Text of forwarded message -----------------------
 
$$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
Received: from NIHCU.BITNET by JHUVM.BITNET (Mailer R2.07) with BSMTP id 5868;
 Wed, 10 Apr 91 11:28:11 EST
To:       NIHGDE-L@JHUVM, SPR001@TTUHSC
From:     Q2C@NIHCU
Date:     Wed, 10 Apr 91  11:26:36 EDT
Subject:  NIH GUIDE - Vol. 20, No. 15, April 12, 1991 - RFA AR9104
          AR-91-04
 
$$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.