Subject: RFAAG-91-04 January l8, l990 NIH Guide
From: Dot Baker <[email-masked]>
To: [email-masked]
Date: Wed, 16 Jan 91 14:30 EST

Hi,
  This is the third of six:  Please post this one as:
     RFAAG91-04
     Thanks.   dottie
 ---------------------------- Text of forwarded message -----------------------
 
SITES TESTING OSTEOPOROSIS PREVENTION/INTERVENTION TREATMENTS
 
RFA AVAILABLE:  AG-91-04
 
P.T. 34; K.W. 0705050, 0745027, 0755015, 0710010
 
National Institute on Aging
 
Letter of Intent Receipt Date:  March 15, 1991
Application Receipt Date:  April 29, 1991
 
The National Institute on Aging (NIA) invites applications for
cooperative agreements to develop and test interventions to
lessen, prevent, or reverse loss of bone strength in the hip
to reduce risk of hip fractures in older persons.
 
I.  BACKGROUND
 
The enormous public health impact of osteoporosis continues
to grow.  This burden is concentrated heavily among persons
65 years old and older.  In particular, the vast majority of
hip fractures occur in this age range causing
hospitalization and temporary disability for more than
215,000 persons per year and long-term loss of independence
for a significant fraction of these.
 
Understanding of the causes of osteoporosis has progressed
significantly in recent years, and several clinical trials of
interventions have reported promising results.  However, most
trials have included relatively few subjects over age 65, few
trials have studied effects on bone density in the hip, and
no trials have had adequate statistical power to determine
the effect of interventions on hip fractures in this
population.  This Request for Applications (RFA) seeks to fill the
above gaps in
knowledge.
 
II.  RESEARCH GOALS, SCOPE, AND ELIGIBILITY REQUIREMENTS
 
The RFA solicits projects that will test the efficacy of
interventions (or combinations of interventions) against
osteoporosis of the hip in persons aged 65 or older. All
proposed studies must measure effects in the hip but may
also include measures of effects at additional skeletal
sites. Studies may also measure effects of osteoporosis
treatment on fractures of the hip and other skeletal sites.
Subjects for inclusion in proposed trials must be age 65 or
over.
 
To achieve the required number of subjects for a study,
applicants may require performance sites at more than one
institution. Applicants considering this approach should
contact program staff listed below regarding
administrative options.
 
Applicants are encouraged to consider designs that will
permit determination of intervention efficacy in different
age groups and sexes within the population over age 65, in
older subjects with low bone mass compared to the average for
their age, and in subjects whose rates of bone loss are
faster than the average for their age, or at high risk for
such accelerated loss. Such designs are, however, not
required.
 
A pilot phase for safety and feasibility testing and protocol
refinement may be proposed.
 
NIA anticipates that bone mass and/or bone density will be a
primary outcome variable in most, if not all, proposed
studies.  However, because development of interventions that
will increase bone strength is the goal of this RFA,
applicants are encouraged also to include studies that will
provide information on the effects of their interventions on
bone strength.
 
Because comorbidity and use of multiple medications are
extremely common among persons over age 65, the ability to
screen, characterize, and monitor study subjects regarding
diseases and medications is essential in these studies.
Similarly, study designs should address potential confounding
issues posed by the presence of concurrent diseases and
medication use.   Applicants may find it useful to include
staff with geriatric research expertise to address the above
considerations.
 
All proposed intervention studies should be blinded to the
maximum extent feasible.
 
The Principal Investigators and key staff of STOP/IT
(Sites Testing Osteoporosis Prevention/Intervention Treatments)
projects, under the terms of the awards, will meet with the
NIA Program Administrator every six months to review the
progress of their studies. Funds for such travel will be
included in awards.
 
A maximum of $550,000 first year total (direct plus indirect)
costs may be requested per application and a total of no more
than $3.1 million may be requested per application for the
entire project duration.  This RFA is a one-time
solicitation.  Up to $2.1 million (total cost) for first-year
expenses and additional approved expenses for up to five
years will be committed in Fiscal Year 1991 to fund
applications submitted in response to this RFA.  It is
anticipated that up to four awards will be made in FY 1991.
This funding level is dependent on the receipt of a
sufficient number of applications of high scientific merit.
In addition to FY 1991 awards, other proposals responding to
this RFA may be funded in Fiscal Year 1992, depending on
quality of proposals and availability of funds.  Issuance of
awards pursuant to this RFA is contingent on the availability
of funds for this purpose.
 
Generally, future competing continuation
applications will compete with all investigator-initiated
applications and be reviewed by the Division of Research
Grants (DRG).  However, should the NIA determine that there
is a sufficient continuing program need, the RFA will be
reissued.  The earliest feasible start date for the initial
awards will be  September 30, 1991.
 
COMPANION STUDIES ON OSTEOPOROSIS IN ADVANCED AGE.  Screening
and recruitment of subjects age 65 and older in these studies
will provide opportunities for studies on the pathophysiology
of osteoporosis in advanced age, and the mechanisms affecting
response to treatment in older persons.  Hence, applicants are
encouraged to submit concurrent proposals on these topics in
response to NIA's accompanying RFA (AG-91-08) for companion
research project grants (R01s) on these topics. Such
proposed studies should in no way compromise the proposed
clinical trials.
 
III.  MECHANISM OF SUPPORT
 
Support of this program will be through Cooperative
Agreements (UO1) between each awardee and NIA.  Under the terms of
these cooperative agreements, the awardee defines the design
and details of the project under the terms of this RFA,
retains primary responsibility for performance of the
research and for analyzing and publishing results, and agrees
to accept assistance from the NIA Program Administrator in
the following:
 
o     Participation in the monitoring of intervention study
      issues relating to recruitment, treatment, follow-up,
      quality control, and adherence to protocol.
 
o     Consideration of refinements and adjustments of
      intervention study designs and protocols.
 
o     Assistance in analysis and reporting of intervention
      study results.
 
The rationale for the above types of participation by the NIA
Program Administrator results from the fact that this RFA has
the objective of determining the efficacy of osteoporosis
interventions in older populations with a complex
variety of medical conditions and lifestyle factors that can
affect responses to treatment and compliance with protocols.
These interactions cannot always be foreseen before the start
of intervention studies.  Even after scientific merit,
personnel, and resources of projects have been assessed by
peer review, needs for protocol modifications and additional
data analyses may arise during the course of the award.
There is need for the Program Administrator to work
cooperatively with awardees in considering these needs and
options for modifications and additions to ensure that they
permit achieving the goals of this RFA.
 
The NIA Program Administrator may provide advice on staffing,
statistical requirements, and implementation of intervention
studies, and will cooperate with awardees in considering
protocol adjustments.  In instances where there has been
significant involvement in study design and analysis by
the NIA Program Administrator, he/she may cooperate with
awardees as co-authors in preparing manuscripts that report
results from these intervention studies.
 
Cooperative Agreements are subject to the same administrative
requirements as grants.  Projects will be supported by the
Cooperative Agreement (U01) mechanism.  The regulations (Code
of Federal Regulations, Title 42, Part 52 and Title 45, Part
74) and policies that govern the research grant programs of
the PHS will prevail.  The awarding of funds pursuant to this
RFA is contingent on availability  of funds.  All pertinent
DHHS, PHS, and NIH grant regulations, policies, and procedures
are applicable.  Business management aspects of the awards
will be administered in accordance with DHHS and PHS grant
administration requirements by the NIH, as stated in the
Public Health Service Grants policy statement, DHHS
Publication No. (OASH) 82-50,000, revised October 1, 1990.
 
IV.  REVIEW PROCEDURES AND CRITERIA
 
Applications will be received by the NIH Division of Research
Grants and will be assigned to the NIA.  Responsive
applications will be assigned to a special review group
organized by NIA.  Proposals judged by the NIA Program
Adminstrator to be non-responsive (those not directed at the
goals of this RFA) will be returned to the applicant without
review.  Proposals may first receive a preliminary review
by a subcommittee of the NIA review panel to establish those
applications deemed to be competitive.  Those proposals judged
non-competitive will be so designated, and an abbreviated
summary statement noting the major areas of concern will be
sent to the Principal Investigator.  Applications judged to
be competitive will be given full review.  Following review
by the initial review group, the applications will be
considered by the National Advisory Council on Aging.
 
Listed below are the major review criteria to be used in the
evaluation of the applications received in response to this
RFA:
 
o     scientific merit of the research proposed.
 
o     significance of the research project to the goals
      of the RFA, i.e., the ability to obtain information
      on the effects of the intervention(s) being tested
      on bone loss in the hip in persons age 65 or older.
 
o     qualifications, experience, and commitment of the
      investigators (particularly regarding osteoporosis
      research, clinical trials, and research involving
      older persons), and their ability to devote the
      required time and effort to the project.
 
o     appropriateness of the total budget and budgetary
      requests.
 
o     institutional commitment to the requirements of the
      project.
 
o     plans for assurance and monitoring of safety of human
      subjects.
 
o     plans to implement special program requirements under
      this RFA, including cooperation
      with the Program Administrator concerning transmission
      and review of data on recruitment, treatment, follow-up,
      quality control, and adherence to protocol in the
      proposed study.
 
o     issues relating to inclusion of women and minorities
      (see following special instructions).
 
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 and offerors for NIH grants,
cooperative agreements, and contracts 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 diseases, disorders, or conditions under study; special
emphasis should be placed on the need for inclusion of
minorities and women in studies of diseases, disorders, and
conditions that disproportionately affect them.  This policy
is intended to apply to males as well as females of all ages.
If women and minorities are excluded or inadequately
represented in clinical research, particularly in proposed
population-based studies, a clear compelling rationale for
exception to the policy should be provided.
 
The composition of the proposed study population must be
described in terms of gender and racial/ethnic groups,
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.
 
Applicant/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 populations should be provided. For the
purpose of this policy, clinical research includes human
biomedical and behavioral studies of etiology, 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 definitions of minority differs in other
countries, the applicant must discuss the relevance of
research involving foreign population groups to the United
States' population, 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 is
inadequate to answer the scientific questions(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.
 
V.  METHOD OF APPLYING
 
A letter of intent to submit an application, while not required, is
requested.  This letter should be sent to the staff contact listed below
(see VI below) by March 15, 1991.  The letter of intent should include a
descriptive title, the name and address of the principal investigator
and other key investigators as well as identification of any other
participating institutions.  Applications should be submitted on the
standard PHS 398 application form (revised October 1988, reprinted
9/89), available at most institutional business offices and from the
Division of Research Grants, NIH, telephone (301) 496-7441.  The
deadline for receipt of applications is April 29, 1991.  On item 2 of
the face page of the application, applicants should enter:  NIA
RFA--Sites Testing Osteoporosis Prevention/Intervention Treatments
(STOP/IT), AG-91-04.  The RFA label available in the 10/88 revision of
the Application Form PHS 398 must be affixed to the bottom of the face
page and placed on the top of the entire package.  Failure to use this
label could result in delayed processing of the application and prevent
it from reaching the review committee in time for review.
 
The completed application and four copies must be sent to:
 
Application Receipt Office
Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD  20892**
 
When the application is submitted to the Division
of Research grants, two
copies of the application should be sent to:
 
Chief, Scientific Review Office
National Institute on Aging
Building 31, Room 5C12
9000 Rockville Pike
Bethesda, MD  20892
 
Failure of these copies to be received by the deadline may
prevent the application from being reviewed under this
announcement in time to be considered for an award.
 
VI.  STAFF CONTACT
 
Potential applicants interested in obtaining further
information may write or call:
 
Stanley L. Slater, M.D.
Geriatrics Program
National Institute on Aging
Room 5C27, Building 31
National Institutes of Health
Bethesda, MD  20892
Telephone:  (301) 496-6761
 
This program is described in the Catalog of Federal
Domestic Assistance,  Number 93.866.  Awards are made
under the authority of the Public Health Service Act,
Section 301 (42 USC 241) and administered under PHS
grant policies and Federal Regulations, most
specifically at 42 CFR Part 52 and 45 CFR Part 74.
Special Terms of Awards applying to projects funded in
response to this RFA are in addition to, and not in lieu
of, otherwise applicable OMB administrative guidelines,
HHS grant administrative regulations at 45 CFR Part 74,
and other HHS, PHS, and NIH grant administration
policies. Awardees will maintain custody of and primary
rights to their data developed under their awards,
subject to Government rights of access, consistent with
current HHS, PHS, and NIH policies. This program is not
subject to the intergovernmental review requirements of
Executive Order 12372 or Health Systems Agency review.