Full Text OD-97-006
 
ACUPUNCTURE TREATMENT FOR OSTEOARTHRITIS
 
NIH GUIDE, Volume 26, Number 24, July 25, 1997
 
RFA:  OD-97-006
 
P.T.


Keywords: 

 
Office of Alternative Medicine
National Institute of Arthritis and Musculoskeletal and Skin Diseases
 
Letter of Intent Receipt Date:  August 17, 1997
Application Receipt Date:  September 19, 1997
 
PURPOSE
 
The Office of Alternative Medicine (OAM) was mandated by Congress in
1991 and permanently established within the Office of the Director,
National Institutes of Health (NIH), through the National Institutes
of Health Revitalization Act of 1993 (Public Law 103-43, Section
209).  The mission of the OAM is to encourage and support the
investigation of complementary and alternative medical (CAM)
practices, with the ultimate goal of integrating validated
alternative medical practices into health and medical care.
 
The OAM and the National Institute of Arthritis and Musculoskeletal
and Skin Diseases (NIAMS) seeks, with this RFA, to initiate a
clinical trial of acupuncture for the treatment of osteoarthritis
(OA) of the knee by experienced investigators who have the unique
technical capabilities to study acupuncture in a clinical setting.
This proposal has the potential to address the efficacy of
acupuncture for the treatment of OA.
 
HEALTHY PEOPLE 2000
 
The Public Health Service is committed to achieving the health
promotion and disease prevention objectives of  "Healthy People
2000," an initiative for setting national health policy and
priorities.  Although Healthy People 2000 does not currently specify
a CAM or acupuncture  objective, this RFA involves priority areas
within the Healthy People 2000 objectives, such as the area of
chronic disabling conditions.  Applicants may obtain a copy of
"Healthy People 2000" (Full Report:  Stock No. 017-001-00474-0 or
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).
 
ELIGIBILITY REQUIREMENTS
Applications may be submitted only by domestic and foreign for-profit
and not-for-profit organizations, public and private organizations
such as universities, colleges, hospitals, laboratories, units of
State or local governments, Federally recognized Indian Tribal
organizations, and eligible agencies of the Federal government.
Applications from minority and women investigators and persons with
disabilities are encouraged.
 
MECHANISM OF SUPPORT
 
This RFA will use the cooperative agreement (U01) mechanism.  The
cooperative agreement is an assistance mechanism in which it is
anticipated that the NIH will have substantial involvement with the
recipient during the performance of the planned activity.  The nature
of the NIH's involvement is described under the "Terms and
Conditions" of the award.  Responsibility for the planning,
direction, and execution of the proposed project will be solely that
of the applicant/awardee.
 
The total project period for applications submitted in response to
the present RFA may not exceed five years, although a three to four
year study is anticipated.  The anticipated award date is April 1,
1998.  This RFA is a one-time solicitation.  Future unsolicited
competitive continuation applications will compete with all other
investigator-initiated research applications and be peer-reviewed by
a study section in the Division of Research Grants (DRG), NIH.
 
FUNDS AVAILABLE
 
Depending upon the scope of work, up to $500,000 (total costs) per
year is available to support this RFA.  It is expected that one award
will be made.  Because the nature and scope of the research proposed
in response to this RFA may vary, it is anticipated that the size of
the award will vary also.  Although this program is provided for in
the financial plans of the OAM and the NIAMS, awards made pursuant to
this RFA will be contingent on the continued availability of funds
for this purpose.
 
RESEARCH OBJECTIVES
 
Background
 
Osteoarthritis (OA) is a common, costly and potentially disabling
disease of joints that affects more than 16 million Americans at an
economic cost in excess of $8 billion, annually.  Pain and limitation
of motion are its major manifestations.  Since OA cannot be cured,
management of OA is dependent on adequate pain control and
maintaining or improving mobility.  The analgesics and anti-
inflammatory medications commonly prescribed to treat OA pain may not
be effective for all individuals and sometimes produce side effects.
A variety of surgical procedures may be recommended depending upon
disease severity and patient complaints.
 
Since its reintroduction to the West in 1972, acupuncture has been
subject to scientific investigation resulting in a substantial body
of literature.  Some of this literature suggests that acupuncture may
provide substantial pain relief for OA without producing the side
effects associated with conventional medications.  Unfortunately, the
few studies that have specifically examined the efficacy of
acupuncture for the treatment of OA have produced contradictory
results.  Part of the discrepancy in these studies has been the
difficulty in designing adequate control groups, differences in the
length and mode of the acupuncture treatment, inadequate endpoints
and insufficient sample sizes.
 
Purpose of Proposed Research
 
The purpose of the proposed study is to initiate a clinical efficacy
trial of acupuncture for OA of the knee.  Also examined will be the
safety and acceptability of acupuncture.  Research activities will be
conducted by clinical investigators skilled in acupuncture and
knowledgeable about the diagnosis, staging and clinical management of
OA.  The ultimate goal is to determine the efficacy of acupuncture
for OA and extend knowledge about its utility for this condition.
 
Research Plan
 
Objectives of the RFA will be met through the initiation of a full-
scale, randomized, controlled trial to test the efficacy of
acupuncture for the treatment of OA of the knee.  It is expected that
the trial will compare acupuncture needling to sham needling (placebo
control).  Additional treatment comparisons may be added if it/they
are solidly supported by the research literature and/or compelling
preliminary data.  Potential applicants should understand that
additional treatment comparisons will add to the cost of the overall
study and enhance problems with patient recruitment and project
management.  All applicants should demonstrate their ability to
manage a complex trial, and provide a detailed patient recruitment
plan, a detailed data management plan, and sample size and power
calculations.  These criteria are particularly important for those
applicants who propose to expand the trial beyond two arms.  In
addition, it is important to evaluate any side effects or
complications of treatment.  The appropriate acupuncture needling
treatment, placebo control and other treatment comparisons will be
chosen based on review of the literature and standards of practice.
 
The rationale for the proposed patient population should include
disease severity and other inclusion/exclusion criteria.  It is
recommended that the study population include both men and women with
either unilateral and bilateral knee OA of at least mild severity.
Subjects who have previously used acupuncture for any illness,
including OA, may be included in the study; however those subjects
who have failed acupuncture treatment for OA should be excluded from
the study.  Plans for patient follow-up and choices of outcome
measures (primary and secondary) should be well-defined and clearly
justified.  Outcome measures could include, but are not limited to:
1) pain assessment; 2) functional status; 3) health status/quality-
of-life indicators and 4) side effects 5) health care utilization
(e.g., increased or decreased use of non-steroidal anti-inflammatory
drugs or office visits).  Selected outcome measures and criteria for
meaningful clinical improvement must be specifically addressed in the
application.
 
The study should consist of four phases:  1) an initial phase during
which the protocol is finalized (e.g., study procedure, data
collection manuals, data management, training, establishment of the
DSMC, etc.) after consultation with the NIAMS Program Officer and the
OAM Project Consultant; 2) a recruitment period; 3) a period of
intervention and follow-up; and 4) data analysis and dissemination.
Applicants must demonstrate the ability to recruit and randomize the
required number of study participants, be able to implement the
various study procedures, and maintain high rates of follow-up during
the course of the trial.  It will be particularly important to
minimize the number of self-medicating patients.  Applicants should
pay special attention to the choice of an appropriate placebo, the
issue of masking, and subject inclusion and exclusion criteria.  If
preliminary data are not available, the proposal should include a
pilot phase to validate these items.
 
To assure adequate statistical power, the clinical trial design
should include an adequate number of participants and should be of
sufficient duration to address the study questions of efficacy,
safety and
acceptability, as well as any other secondary research questions.  To
this end, biostatistics and clinical trial design expertise should be
included during the planning and design of the study.  Study size and
duration will vary according to specific study hypotheses, target
population and endpoints; as such, the study size and duration should
reflect both the choice of outcome measures and the predicted effect
sizes.
 
Any secondary objectives and scientific approaches included by the
applicant should reflect the creativity and capability of the
investigators.  This RFA provides an opportunity for clinical
investigators within an institution or consortia of institutions to
initiate or expand a program on acupuncture research.
 
All costs required for these studies must be included in the
application and must be fully justified.  These costs include quality
control, data management and data analysis, study monitoring, and
travel.
 
Applications funded under this RFA will be supported through the
cooperative agreement (U01) mechanism.  An assistance relationship
will exist between the NIH and the awardees to accomplish the
research objectives.  As described more fully below, the recipients
will have primary responsibility for the development and performance
of the activity.
 
SPECIAL REQUIREMENTS
 
Definitions
 
NIAMS Program Officer:  the NIAMS Program Staff official having
responsibility for the stewardship and monitoring of the award.  In
addition, the NIAMS Program Officer will participate as a Project
Scientist in cooperation with the OAM Project Consultant.
 
OAM Project Consultant:  the OAM Project Consultant will provide
scientific/programmatic assistance to the Awardee as noted in the
terms and conditions of the award, and will provide input to the
NIAMS Program Officer concerning normal stewardship functions.
 
Data Safety and Monitoring Committee:  the committee composed of
external, nonparticipating scientists appointed by the Principal
Investigator to monitor patient safety, conduct data audits, and
document progress to the NIAMS Program Officer and the OAM Project
Consultant.
 
General Issues
 
An independent Data and Safety Monitoring Committee (DSMC) will be a
required component of the study.  The DSMC will monitor response data
to ensure patient safety.  Assessment of the adequacy of the DSMC
will be an important review criterion.  Applicants should not name
DSMC members until an award is made; however, within the application,
they should specify the process by which DSMC members will be
identified.  Although identified by the applicant after consultation
with the NIAMS Program Officer and the OAM Project Consultant, the
DSMC will be appointed by the applicant's institution and report to
the Director of NIAMS through the NIAMS Program Officer.  An
operating budget for the DSMC shall be specified and justified in the
application.
 
The Awardee(s) will be required to submit semiannual progress reports
to NIAMS.  These reports should include recruitment data, indices of
quality control, reports of significant side effects or morbidity and
changes in the protocol.  Such reports are in addition to the annual
awardee noncompeting continuation progress report.  The Data Safety
and Monitoring Committee may require additional information.  The
Awardee(s) also will be requested to present a final oral report to
the Advisory Councils of both the OAM and the NIAMS.
 
The Awardee(s) will be expected to disseminate the research findings
in a timely manner through peer-reviewed publications.
 
TERMS AND CONDITIONS OF THE AWARD
 
These special Terms and Conditions of Award are in addition to and
not in lieu of otherwise applicable OMB administrative guidelines,
HHS grant administration regulations in 45 CFR part 74 and 92, and
other HHS, PHS and NIH grant administration policy statements.
 
The administrative and funding instrument used shall be a cooperative
agreement, an "assistance" mechanism (rather than an "acquisition"
mechanism) in which substantial NIAMS and OAM scientific and/or
programmatic involvement with the Awardee is anticipated during
performance of the activity.  Under the cooperative agreement, the
purpose of the NIAMS and the OAM is to support and/or stimulate the
recipient's activity by involvement in and otherwise working jointly
with the award recipient in a partner role, but it is not to assume
direction, prime responsibility, or a dominant role in the activity.
 
Consistent with the above concept, the dominant role and prime
responsibility for the activity reside with the awardee(s) for the
project as a whole, although specific tasks and activities in
carrying out the studies will be shared among the awardees, the NIAMS
Program Officer and the OAM Project Consultant.
 
Under the cooperative agreement, a relationship will exist between
the recipient of these awards, the NIAMS and the OAM, in which the
performers of the activities are responsible for the requirements and
conditions described below, and agree to accept program assistance
from the NIAMS Program Officer and OAM Project Consultant.
 
A.  Awardee(s) Rights and Responsibilities.
 
The Awardee(s) is responsible for:
 
1.  Research design and protocol development, including definition of
objectives and approaches, planning, implementation, participant
recruitment and follow-up, data collection, quality control, interim
data and safety monitoring, final data analysis and interpretation,
and publication of results.
 
2.  Establishing an external Data Safety and Monitoring Committee to
review data.  The Principal Investigator, after consultation with the
NIAMS Program Officer and the OAM Project Consultant, will name
external, nonparticipating investigators to serve as members on a
Data Safety and Monitoring Committee and schedule meetings
periodically.  The NIAMS Program Officer and OAM Project Consultant
will be non-voting members.
 
3.  Functioning as the scientific coordinator for the protocol and
assuming responsibility for developing and monitoring the protocol.
All proposed protocol modifications will be submitted by the
Principal Investigator to the NIAMS  Program Officer and OAM Project
Consultant, for review and approval, subject to negotiation with  the
Awardee(s).
 
4.  Implementing the data collection method and strategy.
 
5.  Establishing mechanisms for quality control and monitoring.
Awardees are responsible for ensuring accurate and timely assessment
of the progress of their study, including development of procedures
to ensure that data collection and management are:  (1) adequate for
quality control and analysis; (2) for clinical trials, as simple as
appropriate in order to encourage maximum participation of physicians
and patients and to avoid unnecessary expense; and (3) sufficiently
staffed.
 
6.  Establishing procedures to comply with the requirements of 45 CFR
Part 46 for the protection of human subjects.  The Principal
Investigator is responsible for obtaining approval from the
Institutional Review Board (IRB) prior to enrolling patients, and,
once enrollment has commenced, from the IRB, the NIAMS Program
Officer and the OAM Project Consultant prior to changing the
protocol.
 
7.  The Awardee(s) will retain custody of and have primary rights to
the data developed under these awards, subject to Government rights
of access consistent with current DHHS, PHS and NIH policies.
 
B. NIH Staff Responsibilities
 
It is expected that the dominant role and prime responsibility for
the activity will reside with the awardee(s) for the project as a
whole, although specific tasks and activities in carrying out the
studies will be shared among the awardee(s), the NIAMS Program
Officer and the OAM Project Consultant concerning specific scientific
and/or analytic issues as described below.  However, the NIAMS
Program Officer will retain overall administrative responsibility for
the award and will be the contact point for all facets of
interactions with the awardee(s) concerning such issues.
 
NIH Program Staff responsibilities will include:
 
1.  The NIAMS Program Officer and OAM Project Consultant will attend
meetings of the Data Safety and Monitoring Committee as non-voting
members.  The NIAMS and OAM retain, as an option, the right to
conduct periodic external review of progress.
 
2.  The NIAMS Project Officer will provide scientific/technical
assistance primarily on issues concerning osteoarthritis and other
items indicated in this section.  The OAM Project Consultant will
provide scientific/technical assistance primarily on issues
concerning acupuncture and other items indicated in this section.
 
3.  If applicable, the NIAMS Program Officer and OAM Project
Consultant will serve as a resource with respect to other ongoing
NIAMS and OAM activities that may be relevant to the protocol to
facilitate compatibility and avoid unnecessary duplication of effort.
 
4.  The NIAMS Program Officer and OAM Project Consultant will assist
in the design and coordination of research activities for Awardees as
elaborated below:
 
a.  Assist by providing advice in the management and technical
performance of the investigations.
 
b.  Assist through participation in meetings/correspondence with the
research team.  With the agreement of the Principal Investigator, the
NIAMS Program Officer and OAM Project Consultant may assist in the
design, development, and coordination of the research or clinical
protocol, in the statistical evaluations of data, in the preparation
of questionnaires and other data recording forms, and in the
publication of results.
 
c.  Assist with the review and approval of protocols to ensure they
are within the scope of peer review and also for safety
considerations, as required by Federal regulations.  The NIAMS
Program Officer and OAM Project Consultant will monitor protocol
progress, and may request that a protocol study be closed to accrual
for reasons including:  a) an accrual rate insufficient to complete
study in a timely fashion; b) accrual goals met early; c) poor
protocol performance; d) patient safety and regulatory concerns; e)
study results that are already conclusive; and f) emergence of new
information that diminishes the scientific importance of the study
question.
 
d.  Review and provide advice regarding the establishment of
mechanisms for quality control and study monitoring.
 
5.  The NIAMS Program Officer, in conjunction with, or upon
recommendations of, the OAM Project Consultant, reserves the right to
curtail or terminate the study and award in the event of:
 
a)  failure to implement the collaborative protocol in a timely
fashion;
 
b)  substantial shortfall in patient recruitment, follow-up, data
reporting, quality control, or other major breech of the protocol;
 
c)  substantive changes in the agreed upon protocol with which the
NIAMS and the OAM do not concur;
 
d)  reaching a major study end point substantially before schedule
with persuasive statistical significance; or
 
e)  human subject ethical issues that dictate premature termination.
 
6.  Reporting of the study findings.  The NIAMS and OAM will have
access to and may periodically review all data generated under an
award.  NIH policies governing possible co-authorship of publications
with NIH staff will apply in all cases.  In general, to warrant  co-
authorship, NIH staff must have contributed to the following areas:
(a) design of the concepts or experiments being tested; (b)
performance of significant portions of the activity; and preparation
and authorship of pertinent manuscripts.
 
C.  Collaborative Responsibilities
 
In addition to the interactions defined above, the NIAMS Program
Officer, OAM Project Consultant and Awardees shall share
responsibility for the following activity:
 
Data Safety and Monitoring Committee.
 
This committee is organized by the Principal Investigator, the NIAMS
Program Officer and the OAM Project Consultant and is the main
oversight body of the clinical trial.  The Data Safety and Monitoring
Committee has primary responsibility to review progress, monitor
patient accrual, data management, and patient safety, and cooperate
on the publication of results.  The Data Safety and Monitoring
Committee will document progress in written reports to the Director
of NIAMS through the NIAMS Program Officer, and will provide periodic
supplementary reports to designated NIH staff upon request.
 
The Data Safety and Monitoring Committee will be composed of
external, nonparticipating peer Investigators, including those of
data coordinating/statistical centers, if any, and the NIAMS Program
Officer and OAM Project Consultant.  An initial meeting of the Data
Safety and Monitoring Committee will be convened by the Principal
Investigator early after an award is made.  The final structure and
membership of the Data Safety and Monitoring Committee will be
established at the first meeting.  The Principal Investigator will
not be a member or routine attendee of the Committee after the first
meeting of the Committee.  The NIAMS Program Officer and OAM Project
Consultant will have nonvoting membership on the Committee, and as
appropriate, its subcommittees.  Such a Committee usually will meet
at least yearly.
 
A Chairperson, other than the NIH representatives, will be selected
by a vote of the members.  The Chairperson is responsible for
coordinating the Committee activities, for preparing meeting agendas,
and for scheduling and chairing meetings.
 
E.  Arbitration
 
Any disagreement that may arise on scientific/programmatic matters
(within the scope of the award), between award recipients and the NIH
may be brought to arbitration.  An arbitration panel will be composed
of three members -- one selected by the awardee, a second member
selected by NIAMS and OAM, and the third member selected by the two
prior selected members.  These special arbitration procedures in no
way affect the awardee's right to appeal an adverse action that is
otherwise appealable in accordance with PHS regulations at 42 CFR
Part 50, Subpart D, and HHS regulations at 45 CFR Part 16.
 
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 new
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 9, 1994 (CFR 59 11146-11151), and reprinted
in the NIH GUIDE FOR GRANTS AND CONTRACTS of March 18, 1994, Volume
23, Number 11.
 
Investigators may obtain copies from these sources or from the
program staff or contact person listed below.  Program staff may also
provide additional relevant information concerning the policy.
 
LETTER OF INTENT
 
Prospective applicants are asked to submit, by August 17, 1997, 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 title ACUPUNCTURE TREATMENT FOR OSTEOARTHRITIS
and the RFA number: OD-97-06.
 
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 OAM and 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
Extramural Program
NIAMS
Natcher Building, Room 5AS-25U
45 Center Drive MSC 6500
Bethesda, MD 20892-6500
Telephone: (301) 594-4952
FAX: (301) 480-4543
 
APPLICATION PROCEDURES
 
To apply for this RFA, a research grant application form, PHS Form
398 (rev. 5/95) must be used.  Forms are available at most
institutional offices of sponsored research, from the NIAMS and OAM
program administrators named below or from the World Wide Web at:
https://grants.nih.gov/grants/funding/funding.htm.
 
Prior to writing the application, applicants should carefully read
the instructions provided with PHS Form 398 and this RFA.
 
The RFA label available in the PHS 398 application package 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.  In addition, the RFA title and number must be typed on
line two of the face page of the application form and the YES box
must be marked.
 
Submit a typewritten, signed original of the application, three
signed photocopies, and the completed checklist in one package to:
 
DIVISION OF RESEARCH GRANTS
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710
BETHESDA, MD  20892-7710
BETHESDA, MD  20817 (for express/courier service)
 
At the time of submission, it is also required to mail one additional
complete, signed copy of the application to each of the following RFA
program administrators:
 
Richard L. Nahin, Ph.D., M.P.H.
NIH Office of Alternative Medicine
9000 Rockville Pike
Bldg. 31, Room 5B-38
Bethesda, MD  20892-2182
 
James Panagis, M.D., M.P.H.
Medical Officer
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Natcher Building Room 5AS-37K - MSC 6500
Bethesda, MD  20892-6500
Tel:  301-594-3513
Fax:  301-480-4543
E-mail: panagis@ep.niams.nih.gov
 
Applications must be received by September 19, 1997.  If an
application is received after the 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 a substantial
revision of an application already reviewed, but such an application
must follow the guidance in the PHS Form 398 application instructions
for the preparation of revised applications, including an
introduction addressing the previous critique.
 
Preparation of the Application
 
The general instructions provided in PHS-398 for the preparation of
applications must be used.  Because the "Terms and Conditions of
Award" will be included in all awards issued as a result of this RFA,
it is critical that each applicant provides specific plans for
responding to the terms and conditions of award and requirements
stated in the RFA.  Plans must take into account NIH staff
involvement, as well as how all the responsibilities of Awardees will
be fulfilled.
 
The following items apply to all applications:
1.  Clinical trial designs should include an adequate number of
participants and should be of sufficient duration to assure
statistical power to address the study questions of efficacy, long-
term safety and acceptability.  To this end, biostatistics and
clinical trial design expertise should be included from the first
efforts in study planning and design.
 
2.  A rationale for selection of the target patient cohort and an
estimate of the number of participants required to complete the
clinical study should be provided.  Criteria and calculations used to
estimate sample size should be included.  The patient cohort should
be described and its selection justified.  The cohort should be
defined, as appropriate, by age, sex, race, education, geographic
location, occupation, etc.  An accrual rate should be estimated.  If
multiple institutions are involved, the proposal should include
verification of the co-investigators' willingness to participate, and
pertinent additional information regarding the cooperating
institutions' staff qualifications, resources, research plans,
including patient availability and data flow, as well as
corresponding budget requirements.
 
3.  In addition, if multiple institutions will be involved, a
description of how implementation of the trial will be standardized
across
participating centers.  Items that should be addressed include, but
are not limited to:  a) training to standardize the diagnosis,
enrollment (inclusion/exclusion criteria) and treatment of subjects;
b) programs to standardize data management and confidentiality; and
c) procedures to ensure patient safety.  If preliminary data are not
available, the proposal should include a pilot phase to validate
these items.
 
4.  Any known or potential complications should be described, along
with the techniques and procedures to monitor any adverse events.
 
5.  A willingness to work cooperatively with the NIAMS and OAM staff
in the implementation and conduct of the study should be indicated.
 
6.  Applicants from institutions which 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.  In such a case, a letter of agreement from
either the GCRC Program Director or Principal Investigator could be
included with the application.
 
REVIEW CONSIDERATIONS
 
General Considerations
 
Upon receipt, applications will be reviewed for completeness by the
DRG and responsiveness by the OAM and NIAMS.  Incomplete applications
will be returned to the applicant without further consideration.  If
the application is not responsive to the RFA, OAM and NIAMS staff
will return the application to the applicant.
 
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 NIAMS in accordance with the NIH peer
review procedures.  As part of the initial merit review, all
applications will receive a written critique and undergo a process in
which only those applications deemed to have the highest scientific
merit, generally the top half of applications under review, will be
discussed, assigned a priority score, and receive a second level
review by the National Advisory Council for NIAMS.
 
Review Criteria
 
All applications submitted in response to this RFA will be reviewed
according to an explicitly-stated set of five review criteria
recently adapted by the NIH:  significance, approach, innovation,
investigator (qualifications) and environment.  Reviewers will
consider these criteria when assigning a single overall score to each
application.  A detail description of these criteria can be accessed
on the World Wide Web at:
https://grants.nih.gov/grants/peer/rgacriteria.htm.
 
In addition, reviewers will consider the following issues, which are
specific to this RFA:
 
o  Appropriateness of the proposed budget and duration in
   relation to the proposed research;
o  Overall feasibility and the likelihood of achieving the
   clinical trial goals and the potential for a successful
   trial.
o  Pilot phase experience including evidence of patient
   accession and retention.
o  Adequacy of the statistical features of the study
   including sample size projections and power estimates,
   methods of analysis, and the use of sequential analyses
  of data.
o  Logistical aspects of the project including plans for
   patient recruitment, quality control of data, proper
   randomization and masking procedures, data collection,
   data management and, reporting and plans for defining
   access and restriction to data.  If preliminary data are
   not available, the proposal should include a pilot phase
   to validate these items.
o  Availability of suitable subjects for the clinical trial
   and the likelihood of participation through to completion of the
follow-up.
o  Adequacy of ethical and human safety issues, including
   current Institutional Review Board (IRB) human subjects
   approval(s).
o  Adequacy of plans to include subjects from both genders,
   and from minority groups and subgroups as appropriate
   for the scientific goals of the proposed research.
   Plans for the recruitment and retention of subjects also
   will be evaluated.
 
In order to ensure patient safety, the independence, proposed
composition (in general terms, not specific individuals), and
procedures of the DSMC will be considered among the review criteria.
In addition, the initial review group will evaluate the proposed
gender and minority composition of the study population in relation
to the scientific issues being addressed during scientific and
technical merit reviews.
 
For the initial review of the individual institutions participating
in a multicenter clinical trial as a participating center, the review
criteria will include:
o  Commitment of the institution and staff to a
   collaborative protocol and to the success of the study.
   The inclusion of letters of agreement from collaborating
   investigators, countersigned by the appropriate
   institutional official is necessary.
o  Qualifications and the experience of the investigators
   and the availability of suitable subjects for the trial
   and the likelihood of full participation.
o  Adequacy of the facilities including technical resources
   and space.
o  Appropriateness of the local organization and
   administration.
o  Appropriateness of the budget.
o  Adequacy of methods for data collection and reporting
   from each institution
o  Adequacy of ethical and human safety issues, including
   current Institutional Review Board (IRB) human subjects
   approval(s).
 
AWARD CRITERIA
 
The anticipated date of award is April 1, 1998
 
Award criteria are:
o  responsiveness to goals and objectives of RFA
o  priority score
o  availability of funds
 
Award of funds for the approved future years of the grant will
require submission of a noncompeting continuation application, PHS
form 2590, to NIAMS at least two months prior to the anniversary date
of the award.  Failure to supply the PHS form 2590 in a timely manner
will impede release of outyear funding.
 
Letter of Intent Due:  August 17, 1997
Application Receipt Date:  September 19, 1997
Review by Initial Review Group:  November-December, 1997
Review by Advisory Council:  February 5-6, 1998
Anticipated Award Date:  April 1, 1998
 
INQUIRIES
 
Inquiries concerning this RFA are encouraged.  The opportunity to
clarify any issues or questions from potential applicants is welcome.
 
Direct inquires regarding programmatic issues to:
 
Richard L. Nahin, Ph.D., M.P.H.
Program Officer
NIH Office of Alternative Medicine
9000 Rockville Pike
Bldg. 31, Room 5B-38
Bethesda, MD  20892-2182
Tel:  301-496-4792
Fax:  301-480-3519
E-mail: NahinR@OD31EM1.OD.NIH.GOV
 
and
 
James Panagis, M.D., M.P.H.
Program Officer
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Natcher Building Room 5AS-37K - MSC 6500
Bethesda, MD  20892-6500
Tel:  301-594-5055
Fax:  301-480-4543
E-mail: panagisj@ep.niams.nih.gov
 
Direct inquiries regarding fiscal matters to:
Vicki L. Mauer
Grants Management Specialist
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Natcher Building Room 5AS.49A - MSC 6500
Bethesda, MD  20892-6500
Tel: 301-594-3504
FAX: 301-480-5450
E-mail: maurerv@ep.niams.nih.gov
 
AUTHORITY AND REGULATIONS
 
This program is described in the Catalog of Federal Domestic
Assistance Nos. 93.213 (OAM) and 93.846 (NIAMS).  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 Parts 52 and 45 CFR Part 74 [and Part 92 when
applicable for State and Local governments].  This program is not
subject to the intergovernmental review requirements of Executive
Order 12372 or Health Systems Agency review.
 
The PHS strongly encourages all grant and contract recipients to
provide a smoke-free workplace and promote the non-use of all tobacco
products.  In addition, Public Law 103-227, the Pro-Children Act of
1994, prohibits smoking in certain facilities (or in some cases, any
portion of a facility) in which regular or routine education,
library, day care, health care or early childhood development
services are provided to children.  This is consistent with the PHS
mission to protect and advance the physical and mental health of the
American people.
 
.

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	Office of Extramural Research (OER)			National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892			Department of Health and Human Services (HHS)
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