Full Text AR-95-003

CLINICAL STUDIES:  SKIN DISEASES IN HIV/AIDS

NIH GUIDE, Volume 24, Number 1, January 13, 1995

RFA:  AR-95-003

P.T. 34

Keywords: 
  AIDS 
  Skin Diseases 
  Treatment, Medical+ 


National Institute of Arthritis and Musculoskeletal and Skin Diseases

Letter of Intent Receipt Date:  March 15, 1995
Application Receipt Date:  April 21, 1995

PURPOSE

The National Institute of Arthritis and Musculoskeletal and Skin
Diseases (NIAMS) invites applications for clinical studies on the
treatment of skin diseases associated with HIV infection, including
AIDS.  These studies are designed primarily to evaluate innovative or
new treatments and/or combination therapy in the treatment of any of
the skin diseases seen in association with HIV infection, including
AIDS, and compare them to more standard therapeutic approaches for
these diseases, particularly in relation to efficacy, side effects
and costs.  It is not intended that large scale multicenter clinical
trials be supported in response to this RFA, but rather that clinical
studies be designed that may, once validated, form the basis for
subsequent clinical trials.

HEALTHY PEOPLE 2000

The Public Health Service (PHS) is committed to achieving the health
promotion and disease prevention objectives of "Healthy People 2000,"
a PHS-led national activity for setting priority areas.  This Request
for Applications (RFA),  Clinical Studies in Skin Diseases Associated
with HIV/AIDS, is related to the priority area of chronic disabling
conditions.  Potential applicants may obtain a copy of "Healthy
People 2000" (Summary 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,
DC 20402-9325 (telephone 202-783-3238).

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic and foreign, for-profit and
non-profit organizations, public and private, such as universities,
colleges, hospitals, laboratories, units of State and local
governments, and eligible agencies of the Federal government.
Foreign institutions are not eligible for First Independent Research
Support and Transition (FIRST) (R29) awards.  Racial/ethnic minority
individuals, women, and persons with disabilities are encouraged to
apply as Principal Investigators.

MECHANISM OF SUPPORT

This RFA will use the National Institutes of Health (NIH) individual
research project grant (R01), FIRST (R29) awards, and interactive
research project grant (IRPG) mechanisms.  The IRPG mechanism is
described in PA-94-086, NIH Guide, Vol. 23, No. 28, July 29, 1994.
Responsibility for the planning, direction, and execution of the
proposed project will be solely that of the applicant.  The total
project period for applications submitted in response to the present
RFA may not exceed three years.  The anticipated award date is
September 15, 1995.  Because the nature and scope of the research
proposed in response to this RFA may vary, it is anticipated that the
size of an award will vary also.  This RFA is a one time
solicitation.  Future unsolicited competing continuation applications
will compete with all investigator-initiated applications and be
reviewed according to the customary peer review procedures.

FUNDS AVAILABLE

The estimated funds (total costs) available for the first year of
support for the entire program is anticipated to be 1.5 million
dollars.  The anticipated number of new awards is four to five.

RESEARCH OBJECTIVES

Background

Previously supported studies of the natural history of HIV infection,
including AIDS, focusing on the incidence and prevalence of skin
disease, have indicated that essentially all individuals infected
with HIV manifest skin diseases at some time during their infection.
These diseases may be similar in nature to those seen in the non-HIV
infected population, but are often more chronic and resistant to
treatment.  These diseases include, but are not limited to seborrheic
dermatitis, psoriasis, verruca vulgaris, molluscum contagiosum,
superficial fungal infections, folliculitis, both bacterial and of
other etiologies, and pruritus.  Other skin manifestations associated
with HIV infection are more specific to individuals infected with
HIV.  Malignancies associated with HIV infection are not within the
scope of this RFA.  Although many of these diseases respond
reasonably well to standard dermatologic therapy, many of them
eventually become resistant to therapy and necessitate either
combination treatment or innovative therapies (utilization of
medications for non-FDA approved indications).  These approaches have
been anecdotally reported and discussed in clinical dermatologic
circles, but there are no controlled clinical studies to determine
the efficacy, side effects, or cost attendant with these approaches.
As individuals with HIV live longer, it becomes even more likely that
they will suffer significant skin manifestations potentially
requiring the use of innovative therapeutic approaches.  This RFA is
designed to initiate studies that have the long term potential of
indicating whether novel agents or therapeutic combinations are
likely to be effective for these diseases.

Applications in response to this RFA are not expected to be for large
scale multicenter clinical trials.  Rather, it is expected that
applications will be for clinical studies designed to develop and
test protocols that have the potential for providing statistically
valid information concerning efficacy, side effects and cost of
innovative approaches to these diseases.  These studies should have
reproducible and quantifiable end points and appropriate control
groups.  Outcome measures or endpoints taking into account meaningful
clinical improvement are preferred.  Consideration should be given to
the level of improvement (for example 20, 30, or 50 percent) that
would be accepted as meaningful to clinicians or subjects.  The
validity of outcome measures or endpoints should be addressed.  It is
strongly recommended that applicants have or enlist individuals with
clinical trial and biostatistical expertise and training in order to
ensure proper design of these clinical investigations.  The NIAMS
strongly supports the provision of training or experience in
biostatistics and clinical trials for individuals interested in
careers in these disciplines within dermatology as a component of
projects submitted in response to this RFA.  The sample size
considerations for the pilot study should be addressed.  The
application should include a plan for data management and analysis.
A plan for data safety monitoring is strongly recommended,
particularly for studies incorporating larger numbers of subjects or
testing interventions with potentially significant adverse effects.
It is also expected that there will be a discussion of the size of
subsequent studies that would have sufficient power to prove the
hypothesis once the clinical studies have demonstrated the validity
of the approach to be taken.  Therefore, the clinical studies
supported under this RFA are expected to be of three years duration
to allow enough time for study design, development of the protocol,
and field testing and evaluation.  These studies are not to be
designed to be definitive tests of therapeutic interventions that
typically would require larger multicenter approaches and budgets
well in excess of those expected in responses to this RFA.

The specific disease or diseases to be investigated, the
interventions to be tested, and the control groups, are to be
proposed by the applicant.  These should be adequately justified by
literature citations and/or clinical experience, which may be
anecdotal.

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN
SUBJECTS

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

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

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

Applicants from institutions that have a General Clinical Research
Center (GCRC) funded by the NIH National Center for Research
Resources may wish to identify the GCRC as a resource for conducting
the proposed research.  If so, a letter of agreement from either the
GCRC program director or Principal Investigator should be included
with the application.

LETTER OF INTENT

Prospective applicants are asked to submit, by March 15, 1995, a
letter of intent that includes a descriptive title of the proposed
research, the name, address, and telephone number of the Principal
Investigator, the identities of other key personnel and participating
institutions, and the number and title of the RFA in response to
which the application may be submitted.

Although a letter of intent is not required, is not binding, and does
not enter into the review of subsequent applications, the information
that it contains allows NIAMS staff to estimate the potential review
workload and to avoid conflict of interest in the review.

The letter of intent is to be sent to Dr. Alan N. Moshell at the
address listed under INQUIRIES.

APPLICATION PROCEDURES

The research grant application form PHS 398 (rev. 9/91) is to be used
in applying for these grants.  These forms are available at most
institutional offices of sponsored research; from the Office of
Grants Information, Division of Research Grants, National Institutes
of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892,
telephone 301/435-0714; and from the program administrator listed
under INQUIRIES.

The RFA label available in the PHS 398 (rev. 9/91) application form
must be affixed to the bottom of the face page of the application.
Failure to use this label could result in delayed processing of the
application such that it may not reach the review committee in time
for review.  In addition, the RFA title and number must be typed on
line 2a of the face page of the application form and the YES box must
be marked.

Applications for the FIRST Award (R29) must include at least three
sealed letters of reference attached to the face page of the original
application.  FIRST Award (R29) applications submitted without the
required number of reference letters will be considered incomplete
and will be returned without review.

Submit a signed, typewritten original of the application, including
the Checklist, and three signed, photocopies, in one package to:

Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD  20892**

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

Tommy L. Broadwater, Ph.D.
Chief, Grants Review Branch
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Natcher Building, Room 5AS-25U
45 Center Drive, MSC 6500
Bethesda, MD  20892-6500

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

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed for completeness by DRG
and responsiveness by the NIAMS.  Incomplete applications will be
returned to the applicant without further consideration. If the
application is not responsive to the RFA, NIAMS staff will contact
the applicant to determine whether to return the application to the
applicant or submit it for review in competition with unsolicited
applications at the next review cycle.

Applications that are complete and responsive to the RFA will be
evaluated for scientific and technical merit by an appropriate peer
review group convened by the (ICD) in accordance with the review
criteria stated below.  As part of the initial merit review, a
process (triage) may be used by the initial review group in which
applications will be determined to be competitive or non-competitive
based on their scientific merit relative to other applications
received in response to the RFA.  Applications judged to be
competitive will be discussed and be assigned a priority score.
Applications determined to be non-competitive will be withdrawn from
further consideration and the Principal Investigator and the official
signing for the applicant organization will be notified.  The second
level of review will be provided by the National Advisory ICD
Council/Board.

Review criteria for this RFA are generally the same as those for
unsolicited research grant applications.

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

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

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

o  availability of the resources necessary to perform the research;

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

o  adequacy of plans to include both genders and minorities and their
subgroups as appropriate for the scientific goals of the research.
Plans for the recruitment and retention of subjects will also be
evaluated.  The initial review group will also examine the provisions
for the protection of human and animal subjects, the safety of the
research environment, and conformance with the NIH Guidelines for the
Inclusion of Women and Minorities as Subjects in Clinical Research.

AWARD CRITERIA

The anticipated date of award is September 15, 1995.  Awards will be
based upon the following criteria:

o  priority score
o  availability of funds
o  programmatic priorities of the funding ICD

INQUIRIES

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

Direct inquiries regarding programmatic issues to:

Alan N. Moshell, M.D.
Skin Diseases Program Director
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Natcher Building, Room 5AS-25L
45 Center Drive
Bethesda, MD  20892-6500
Telephone:  (301) 594-5017
FAX:  (301) 480-4543
Email:  moshella@ep.niams.nih.gov

Direct inquiries regarding fiscal matters to:

Mary  L. Graham
Grants Management Officer
National Institute of Arthritis, Musculoskeletal and Skin Diseases
Natcher Building, Room 5AS-49A
Bethesda, MD  20892-6500
Telephone:  (301) 594-3504
FAX:  (301) 480-5450
email:  Grahamm@ep.niams.nih.gov

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic
Assistance No. 93.361.  Awards are made under authorization of the
Public Health Service Act, Title IV, Part A (Public Law 78-410, as
amended by Public Law 99-158, 42 USC 241 and 285) and administered
under PHS grants policies and Federal Regulations 42 CFR 52 and 45
CFR Part 74.  This program is not subject to the intergovernmental
review requirements of Executive Order 12372 or Health Systems Agency
review.

The Public Health Service (PHS) strongly encourages all grant
recipients to provide a smoke free workplace and promote the non-use
of all tobacco products.  This is consistent with the PHS mission to
protect and advance the physical and mental health of the American
people.

.

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