Full Text AR-94-003

PROGRAM OF EXCELLENCE IN ORTHOPAEDIC BIOMATERIALS

NIH GUIDE, Volume 22, Number 38, October 22, 1993

RFA:  AR-94-003

P.T. 34

Keywords: 
  Biomaterials 
  Orthopedics 
  Prosthetic Device, Limbs 


National Institute of Arthritis and Musculoskeletal and Skin Diseases

Letter of Intent Receipt Date:  February 16, 1994
Application Receipt Date:  March 16, 1994

PURPOSE

The National Institute of Arthritis and Musculoskeletal and Skin
Diseases (NIAMS) invites investigators to submit interactive grant
applications for a Program of Excellence in Orthopaedic Biomaterials.
The several related projects should have a common theme or focus on a
specific type of device or on an important research issue common to
several types of devices.  There should be a demonstrated positive
interaction among the investigators and the projects.  Individual
projects may include basic, applied, or clinical research.  The long
range objective should be the development of improved and longer
lasting orthopaedic devices.

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), Program of Excellence in Orthopaedic
Biomaterials, is related to the priority area of chronic disabling
conditions.  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,
DC 20402-9325 (telephone 202-783-3238).

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic 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.  Applications from
minority individuals and women are encouraged.  Foreign institutions
are not eligible for First Independent Research Support and
Transition (FIRST) (R29) awards.

MECHANISM OF SUPPORT

This RFA will use the National Institutes of Health (NIH) Interactive
Research Project Grant (IRPG) mechanism.  The IRPG mechanism
encourages interaction and collaboration among scientists with common
goals.  It is intended to bring together research projects from
investigators who wish to collaborate, but who do not require
extensive shared resources.  There should be constructive interchange
of ideas, data, and/or materials.  A minimum of two independent
investigators are encouraged to submit concurrent, collaborative,
cross-referenced individual research project grants (R01) or FIRST
(R29) award applications.  Applicants may be from one or several
institutions.  Detailed information about this mechanism of support
is available in the NIH Program Announcement PA-93-078, NIH Guide for
Grants and Contracts, Volume 22, Number 16, April 23, 1993.  The
total project period for applications submitted in response to the
present RFA may not exceed four years for R01s.

Responsibility for the planning, direction, and execution of the
proposed project will be solely that of the applicants.  The
anticipated award date is September 30, 1994.  In addition to the
requirements stated in this RFA, awards will be administered under
PHS grants policy as stated in the Public Health Service Grants
Policy Statement, DHHS Publication No. (OASH) 90-50-000, revised
October 1, 1991.

This RFA is a one-time solicitation.  Future unsolicited competing
continuation applications will compete with all
investigator-initiated applications and be reviewed according to
customary peer review procedures.

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 resources for conducting
the proposed research.  If so, a letter of agreement from either the
GCRC program director or Principal Investigator could be included
within the application.

FUNDS AVAILABLE

It is anticipated that the group of applications funded will result
in one IRPG award made for a "Program of Excellence in Orthopaedic
Biomaterials."  The estimated funds available for the first year of
support for this program are $700,000 in total costs.  Actual funding
is dependent on the receipt of a sufficient number of applications of
high scientific merit.  Funding beyond the first and subsequent years
of the grant will be contingent upon satisfactory progress during the
preceding years and the availability of funds.

This project is part of the NIH Advanced Material and Processing
Program (AMPP) of the Federal Coordination Council for Science and
Engineering Technology (FCCSET).

RESEARCH OBJECTIVES

Orthopaedic implants are commonly used in the treatment of
musculoskeletal diseases and injuries.  One major class of
orthopaedic devices is used for fixation and includes pins, screws,
wires, plates and rods.  The other large class consists of joint
replacement devices (e.g., total knee and total hip replacement
systems).  In 1992, there were an estimated 400,000 arthroplasties
performed on knees or hips.  Based on cross-sectional data gathered
in 1988, it is estimated that approximately 5,000,000 people in the
U.S. currently have an orthopaedic device implanted.

While these orthopaedic devices have had great general success in
reducing the morbidity and disability that may result from
musculoskeletal disorders, the long-term outcomes are not fully
satisfactory; some devices require surgical replacement.  As an
example, failure of total hip devices may occur because of factors
such as remodelling due to stress shielding, biological response to
wear products, infection, other host/implant biological responses, or
failure of any of the component devices or cement.  Revision surgery
is costly to perform and less likely to be successful than the
original procedure.  Public health cost savings could be greatly
increased from orthopaedic devices that have an improved longevity.

The Program of Excellence in Orthopaedic Biomaterials will be a
multidisciplinary effort combining advances in material and
mechanical, science with recent progress in biological areas
including immunology, molecular and cellular biology.  The ultimate
goal of this coordinated effort is fundamental, applied, or clinical
knowledge that would lead to more effective long-term orthopaedic
implants and improve the quality of life of the recipient patients.

The research investigators should have expertise in areas such as
orthopaedic surgery, biomaterials, biomechanics, and biology.  Each
IRPG application should have a central theme or focus that serves to
interconnect the component projects.  There should be a demonstrated
positive interaction among the investigators and the projects.
Although clinical studies may be proposed, this RFA is not intended
to support large clinical trials.

Appropriate research areas include, but are not limited to:

o  Study of implant/host interface at molecular and cellular levels;

o  Study of mechanisms of wear particle release from metals,
ceramics, plastics, etc, and the host response to these particles in
their natural and subsequent forms;

o  Study of long-term response of bone to stress deprivation and
develop approaches to minimize this effect;

o  Investigation of underlying immune response to the large foreign
body orthopaedic device;

o  Investigation of origins and microcolonization of orthopaedic
implants with infectious agents and optimal prevention and treatment
of infections;

o  Understanding of fundamental and clinical response to porous
coatings and ingrowth enhancing coatings;

o  Establishment of the potential role for stimulating bone growth
into and around the implant with growth factors, angiogenic factors,
and other modifiers of bone metabolism;

o  Development of new biomaterials or innovative approaches to design
or surgical implantation procedures;

o  Establishment of innovative, accelerated procedures to assess the
likely long-term response of biomaterials or devices;

o  Exploration of production technologies and their influence on the
final product that may lead to enhanced practical orthopaedic
devices.

STUDY POPULATIONS

SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH
POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL
RESEARCH STUDY POPULATIONS

NIH policy is that applicants for NIH clinical research grants and
cooperative agreements are 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 must 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 must 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 must be addressed in developing a research
design and sample size appropriate for the scientific objectives of
the study.  This information must be included in the form PHS 398
(rev. 9/91) in Sections 1-4 of the Research Plan AND summarized in
Section 5, 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 is defined as 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.

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 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.

LETTER OF INTENT

Prospective applicants are asked to submit, by February 16, 1994, 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. Tommy Broadwater
Review Branch, Extramural Program
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Westwood Building, Room 406
Bethesda, MD  20892
Telephone:  (301) 594-9979
FAX:  (301) 594-9673

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 301/710-0267; and from the NIH program administrator named
below.  Additional instructions for IRPG applications are in PA-93-
038.

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 (Program of Excellence in
Orthopaedic Biomaterials) and number must be typed on line 2a of the
face page of the application form and the YES box must be marked.

Submit a signed, typewritten original of the applications, including
the cover letter, checklist, and three signed, photocopies, in one
package, whether or not the applications arise from the same
institution, to:

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

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.

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

Dr. Tommy Broadwater
Review Branch, Extramural Program
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Westwood Building, Room 406
Bethesda, MD  20892
Telephone:  (301) 594-9979
FAX:  (301) 594-9673

Applications must be received by March 16, 1994.  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 announcement 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 may be triaged by an NIAMS peer review group on the
basis of relative competitiveness.  The NIH will withdraw from
further competition those applications judged to be non-competitive
for award and notify the applicant Principal Investigator and
institutional official.  Those applications judged to be competitive
will undergo further scientific merit review.  Those applications
that are complete and responsive will be evaluated in accordance with
the criteria stated below for scientific/technical merit by an
appropriate peer review group convened by the NIAMS.  The second
level of review will be provided by the National Advisory Arthritis
and Musculoskeletal and Skin Diseases Council.

Review criteria for RFAs are generally the same as those for
unsolicited research grant applications:

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

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

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

o  availability of the resources necessary to perform the research;

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

The special value of the cooperative and interactive nature of the
individual research applications and applicants comprising the IRPG
should be emphasized in each application.

AWARD CRITERIA

The anticipated date of award is September 30, 1994.

Applications will compete for available funds with all other
applications responsive to this RFA.  The following items will be
considered in making funding decisions:

o  quality of the proposed program project grants as determined by
peer review;
o  availability of funds; and
o  programmatic priorities.

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:

Dr. Stephen L. Gordon
Musculoskeletal Diseases Branch
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Westwood Building, Room 407
Bethesda, MD  20892
Telephone:  (301) 594-9951
FAX:  (301) 594-9673

Direct inquiries regarding fiscal matters to:

Ms. Diane M. Watson
Grants Management Branch
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Westwood Building, Room 732A
Bethesda, MD  20892
Telephone:  (301) 594-9955
FAX:  (301) 594-9673

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic
Assistance No. 93.846, Arthritis, Musculoskeletal, and Skin Diseases.
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.

.

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