CLINICAL TRIAL PLANNING GRANT

Release Date:  October 1, 2001

RFA:  RFA-AR-02-001

National Institute of Arthritis and Musculoskeletal and Skin Diseases
 (http://www.nih.gov/niams/)

Letter of Intent Receipt Date:  February 22, 2002
Application Receipt Date:       March 22, 2002

THIS RFA USES "MODULAR GRANT" AND "JUST-IN-TIME" CONCEPTS.  MODULAR 
INSTRUCTIONS MUST BE USED FOR RESEARCH GRANT APPLICATIONS REQUESTING 
LESS THAN $250,000 PER YEAR IN ALL YEARS. MODULAR BUDGET INSTRUCTIONS 
ARE PROVIDED IN SECTION C OF THE PHS 398 (REVISION 5/2001) AVAILABLE AT 
http://grants.nih.gov/grants/funding/phs398/phs398.html.

PURPOSE

The purpose of the NIAMS Clinical Trial Planning Grant is to provide 
support for the organization of activities critical for the successful 
implementation of clinical trials in areas within the NIAMS mission.  
The planning grant is intended to (a) allow for early peer review of 
the rationale and design for high risk, complex, or large-scale 
clinical trials; (b) provide support for the development of a detailed 
clinical trial research plan, including a manual of operations and 
procedures, as a means of decreasing the long start-up time often 
needed for initiating large trials after award; and (c) provide support 
to refine critical components of a clinical trial, such as experimental 
design, analytical techniques, recruitment strategies, data management, 
and collaborative arrangements.  The purpose of the NIAMS planning 
grant is not to obtain preliminary data nor to conduct studies to 
support the rationale for the clinical trial.

Applicants should be aware that the award of a planning grant does not 
guarantee NIAMS acceptance of the full-scale clinical trial for peer 
review, nor subsequent funding of the trial following peer review.  
However, it is expected that the applicant will develop a full-scale 
clinical trial for submission to a public or private agency if the 
Clinical Trial Planning Grant is approved for funding.

HEALTHY PEOPLE 2010

The Public Health Service (PHS) is committed to achieving the health 
promotion and disease prevention objectives of "Healthy People 2010," a 
PHS-led national activity for setting priority areas.  This Request for 
Applications (RFA), Clinical Trial Planning Grant, is related to one or 
more of the priority areas.  Potential applicants may obtain a copy of 
"Healthy People 2010" at http://www.health.gov/healthypeople/.

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.  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) R21 award 
mechanism.  Responsibility for the planning, direction, and execution 
of the proposed project will be solely that of the applicant.  
Applicants can request direct costs in $25,000 modules, up to a total 
direct cost request of $100,000.  This is a one-year award.  For the 
purposes of this solicitation the research plan for the application 
must be limited to 15 pages and appendix material will not be accepted. 
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

It is estimated that $600,000 total costs will be available for support 
of this initiative.  Direct costs will be awarded in modules of 
$25,000, less any overlap or other necessary administrative 
adjustments.  Facilities and Administrative costs will be awarded based 
on the negotiated rates.  Awards are contingent on the availability of 
funds and the receipt of highly meritorious applications.

RESEARCH OBJECTIVES

Background

Complex, high risk, or large-scale clinical trials require extensive 
planning.  The NIAMS Clinical Trial Planning Grant supports the 
development of specific elements essential to the conduct of a 
successful clinical trial.  Examples of these elements include adequate 
plans for recruitment and retention of patients, experimental design 
and protocols, data management, analytical techniques, identification 
of facilities, administrative procedures, and collaborative 
arrangements.  Detailed information regarding the rationale of the 
clinical trial, based on adequate, preclinical science and preliminary 
clinical research, must be developed prior to submission and included 
in the application for a Clinical Trial Planning Grant.  The purpose of 
the planning grant is not to obtain preliminary data or to conduct 
studies to support the rationale for the clinical trial. The expected 
product of the Clinical Trial Planning Grant is a detailed clinical 
trial research plan including a complete manual of operations and 
procedures (MOP).  The NIAMS Clinical Trial Planning Grant is intended 
to help support this and other related activities necessary for a 
successful clinical trial.

For some diseases of interest to the NIAMS the design and 
implementation of successful clinical trials has been hampered by the 
lack of refined outcome measures, difficulties with recruitment of 
patients with rare diseases, and lack of information about 
standardization of procedures among participating clinics.  The NIAMS 
Clinical Trial Planning Grant also provides an opportunity to support 
these activities.
Examples of Research Objectives for the Planning Period

The actual activities performed during the planning period will depend 
upon the nature of the trial, and the degree to which the investigators 
have already developed their trial.  The planning activities should be 
such that they would enable imminent commencement of the actual 
clinical trial.  A few examples are:

o  Testing recruitment strategies

o  Developing subject retention strategies

o  Conducting meetings to address issues such as trial design, 
methodologies, etc.

o  Preparing a Manual of Operations and Procedures (MOP), a specific 
safety plan, etc.

Other

Detailed information regarding the rationale of the clinical trial, 
based on adequate preclinical science and preliminary clinical 
research, must be developed prior to submission and included in the 
Clinical Trial Planning Grant application.  The purpose of the planning 
grant is not to support activities of a pilot trial or to conduct 
studies to support the rationale for the clinical trial.  Examples of 
expected products of the planning grant are a complete Manual of 
Operations and Procedures, validated outcome measures, or proven 
feasibility of a new recruitment plan.

Any disease area that is within the NIAMS mission is appropriate for 
consideration under this RFA.

SPECIAL REQUIREMENTS

The Research Plan should be presented in two parts as described below.  
Applicants are encouraged to address issues listed in “Review Criteria” 
and “Specific Review Criteria” in this RFA.

PART 1 - FUTURE CLINICAL TRIAL  (Approximately 2-5 pages)

This part may or may not be written using the standard headings of PHS 
form 398 (Specific Aims, Background and Significance, Preliminary 
Studies, Research Design and Methods, and Human Subjects) but should 
clearly describe the following items: 

o  Specific Aims, including a clear statement of any hypotheses that 
the clinical trial would address.

o  Background/Rationale - Provide rationale for the trial.  The 
rationale must be supported by existing data/information.  The planning 
grant is not to be used to conduct studies  in order to rationalize the 
clinical trial.
o  Significance - Give information documenting significance and the 
need to perform the clinical trial.  Describe the potential impact of 
the clinical trial on health care: What is the need for new therapy?  
What are the potential advantages and disadvantages of competitive 
therapies? 

o Research Design and Methods - No details are required, but enough 
information should be provided to evaluate how the trial would be 
conducted.  Pertinent information must be included on: (a) 
Intervention(s) to be used, reasons for the selection of 
intervention(s), and mode(s) of delivery; (b) study design, treatment 
group(s), trial size, and inclusion/exclusion criteria (if not 
developed yet, please state so, and you may include it as a part of 
your planning grant part 2); (c) control group(s) if applicable; (d) 
outcome measures; and (e) data analysis plan if applicable.

o  Proposed Clinical Sites and Investigators-provide a list.  Letters 
of commitment are not required at this stage.

o  Gender, Minorities & Children Issues - Proposed population 
description in terms of gender, minorities and children; justification 
for excluding any gender, minority groups or children; plans for 
recruitment outreach, as appropriate.

o  Human Subjects Issues - Ethical considerations for placebo/control 
groups, risk/benefit for the participants; availability of the 
requisite eligible patient pool.

PART 2 - PLANNING GRANT (Approximately 10-13 pages)

This part must be written using the PHS form 398 headings, and should 
include:

a.  Specific Aims for the planning period (examples include: “We will 
prepare a Manual of Operations and Procedures”; “We will conduct 
meetings to address the following issues:”; “We will test recruitment 
strategies”; “We will organize essential safety committees”; etc.).

b.  Background and Significance, including rationale for planning 
period;  Why is the planning period needed?  Why not start the trial 
now?

c.  Preliminary Studies - Not required, but if any preliminary work 
already completed is included, it should be relevant to the work 
proposed in the planning period, and to the trial proposed in Part 1.

d.  Research Design and Methods - Detailed approach for each Specific 
Aim of the planning period.  Highlight any innovations applicable to 
the planning period.

e.  Human Subjects - Address all the required items on human subjects 
for anticipated issues arising in the planning phase.  If no human 
subjects issues are involved during the planning period, state so.

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 sub-populations  must be included in all NIH-supported 
biomedical and behavioral research projects involving human subjects, 
unless a clear and compelling rationale and justification are provided 
indicating that inclusion is inappropriate with respect to the health 
of the subjects or the purpose of the research.  This policy results 
from the NIH Revitalization Act of 1993 (Section 492B of Public Law 
103-43).

All investigators proposing research involving human subjects should 
read the UPDATED "NIH Guidelines for Inclusion of Women and Minorities 
as Subjects in Clinical Research," published in the NIH Guide for 
Grants and Contracts on August 2, 2000 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-048.html); a 
complete copy of the updated Guidelines is available at 
http://grants.nih.gov/grants/funding/women_min/guidelines_update.htm: 
The revisions relate to NIH defined Phase III clinical trials and 
require: a) all applications or proposals and/or protocols to provide a 
description of plans to conduct analyses, as appropriate, to address 
differences by sex/gender and/or racial/ethnic groups, including 
subgroups if applicable; and b) all investigators to report accrual, 
and to conduct and report analyses, as appropriate, by sex/gender 
and/or racial/ethnic group differences.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of the NIH that children (i.e., individuals under the 
age of 21) must be included in all human subjects research conducted or 
supported by the NIH unless there are scientific or ethical reasons not 
to include them.  This policy applies to all initial (Type 1) 
applications submitted for receipt dates after October 1, 1998.  

All investigators proposing research involving human subjects should 
read the "NIH Policy and Guidelines" on the Inclusion of Children as 
Participants in Research Involving Human Subjects that was published in 
the NIH Guide for Grants and Contracts, March 6, 1998, and is available 
at the following URL address: 
http://grants.nih.gov/grants/guide/notice-files/not98-024.html.

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

URLS IN NIH GRANT APPLICATIONS OR APPENDICES

All applications and proposals for NIH funding must be self-contained 
within specified page limitations.  Unless otherwise specified in an 
NIH solicitation, internet addresses (URLs) should not be used to 
provide information necessary to the review because reviewers are under 
no obligation to view the Internet sites.  Reviewers are cautioned that 
their anonymity may be compromised when they directly access an 
Internet site.

REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS

NIH policy requires education on the protection of human subject 
participants for all investigators submitting NIH proposals for 
research involving human subjects.  This policy announcement is found 
in the NIH Guide for Grants and Contracts Announcement dated June 5, 
2000, at the following website:  
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT

The Office of Management and Budget (OMB) Circular A-110 has been 
revised to provide public access to research data through the Freedom 
of Information Act (FOIA) under some circumstances.  Data that are (1) 
first produced in a project that is supported in whole or in part with 
Federal funds and (2) cited publicly and officially by a Federal agency 
in support of an action that has the force and effect of law (i.e., a 
regulation) may be accessed through FOIA.  It is important for 
applicants to understand the basic scope of this amendment.  NIH has 
provided guidance at:  
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm

Applicants may wish to place data collected under this RFA in a public 
archive, which can provide protections for the data and manage the 
distribution for an indefinite period of time.  If so, the application 
should include a description of the archiving plan in the study design 
and include information about this in the budget justification section 
of the application. In addition, applicants should think about how to 
structure informed consent statements and other human subjects 
procedures given the potential for wider use of data collected under 
this award.

LETTER OF INTENT

Prospective applicants are asked to submit, by February 22, 2002, 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 this RFA in response to which 
the application would be submitted.  

Although a letter of intent is not required, is not binding, and does 
not enter into the review of a subsequent application, the information 
that it contains allows NIAMS staff to estimate the potential review 
workload and plan the review.  The letter of intent is to be sent to 
Tommy L. Broadwater, Ph.D. at the address listed under INQUIRIES by 
February 22, 2002.

APPLICATION PROCEDURES

The PHS 398 research grant application instructions and forms (rev. 
5/2001) at http://grants.nih.gov/grants/funding/phs398/phs398.html must 
be used in applying for these grants. This version of the PHS 398 is 
available in an interactive, searchable PDF format.  For further 
assistance contact GrantsInfo, Telephone 301/435-0714, Email: 
GrantsInfo@nih.gov.

SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS

The modular grant concept establishes specific modules in which direct 
costs may be requested as well as a maximum level for requested 
budgets. Only limited budgetary information is required under this 
approach.  The just-in-time concept allows applicants to submit certain 
information only when there is a possibility for an award. It is 
anticipated that these changes will reduce the administrative burden 
for the applicants, reviewers and NIH staff.  The research grant 
application form PHS 398 (rev. 5/2001) at 
http://grants.nih.gov/grants/funding/phs398/phs398.html is to be used 
in applying for these grants, with modular budget instructions provided 
in Section C of the application instructions.  Applicants are 
permitted, however, to use the 4/1998 revision of the PHS 398 for 
scheduled application receipt dates until January 9, 2002.  If you are 
preparing an application using the 4/1998 version, please refer to the 
step-by-step instructions for Modular Grants available at 
http://grants.nih.gov/grants/funding/modular/modular.htm.  Additional 
information about Modular Grants is also available on this site.

The RFA label available in the PHS 398 (rev. 5/2001) application form 
must be affixed to the bottom of the face page of the application.  
Type the RFA number on the label.  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 2 of the face page of the 
application form and the YES box must be marked. The RFA label is also 
available at: http://grants.nih.gov/grants/funding/phs398/label-bk.pdf.

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

CENTER FOR SCIENTIFIC REVIEW
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, three additional copies of the application 
must be sent to:

Dr. Tommy L. Broadwater
Extramural Program
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Building 45, Room 5AS.25U
Bethesda, MD  20892-6500
Telephone:  (301) 594-4952
FAX:  (301)-402-2406
Email:  broadwat@mail.nih.gov

Applications must be received by the application receipt date listed in 
the heading of this RFA.  If an application is received after that 
date, it will be returned to the applicant without review.

The Center for Scientific Review (CSR) 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 CSR 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 that 
addresses the previous critique.  

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed for completeness by CSR and 
responsiveness by NIAMS staff.  Incomplete and/or non-responsive 
applications will be returned to the applicant without further 
consideration.

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 review 
criteria stated below.  As part of the initial merit review, all 
applications will receive a written critique.  Applications may undergo 
a process in which only those applications deemed to have the highest 
scientific merit, generally the top half of the applications under 
review, are discussed, assigned a priority score, and receive a second 
level review by the National Arthritis and Musculoskeletal and Skin 
Diseases Advisory Council.

REVIEW CRITERIA

The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  
In the written comments reviewers will be asked to discuss the 
following aspects of the application in order to judge the likelihood 
that the proposed research will have a substantial impact on the 
pursuit of these goals.  Each of these criteria will be addressed and 
considered in assigning the overall score, weighting them as  
appropriate for each application.  Note that the application does not 
need to be strong in all categories to be judged likely to have major 
scientific impact and thus deserve a high priority score.  For example, 
an investigator may propose to carry out important work that by its 
nature is not innovative but is essential to move a field forward.  

Please note that there may be high enthusiasm for the future trial 
(part 1) but little enthusiasm for the planning (part 2), or vice 
versa, or high enthusiasm for both, etc.  Review committees should 
indicate their enthusiasm for the two sections separately (with only 
one priority score for the overall application). 

SPECIFIC REVIEW CRITERIA

The criteria used to evaluate Clinical Trial Planning Grant 
applications are based on the "Specific Requirements," as spelled out 
in an earlier section of the RFA.  The reviewers will provide a two-
part critique on the application.

o  PART 1 - This will be a brief critique of the future clinical trial, 
and will be based upon the items requested under part 1 of “Special 
Requirements” of this RFA.  General enthusiasm (low, medium, high) 
about the proposed trial should be based on the following:

(1) Significance:  Would the future clinical trial address an important 
problem?  Would conduct of the trial influence standard of care, 
develop a new therapy, or provide a better understanding of the 
disease?  Is there convincing rationale to conduct the trial?

(2) Investigator:  Is the investigative team qualified to conduct the 
clinical trial?

(3) Feasibility: Do the research design and methods appear appropriate 
and reasonable for the successful conduct of the proposed trial?  
(Please note that detailed research design and methods are NOT 
required.)

(4) Human Subjects:  Only major ethical concerns surrounding human 
subjects should be noted.

o  PART 2 - This will be a detailed critique of the planning period 
activities, and will be based upon the items requested under part 2 of 
“Special Requirements” of this RFA.

(1)  Significance:  Will the proposed planning process address major 
barriers in conducting the future clinical trial?  Is the planning 
period necessary?

(2) Approach:  Are the conceptual framework, design, methods, and 
analyses adequately developed, well-integrated, and appropriate to the 
aims of the project?  Does the applicant acknowledge potential problem 
areas and consider alternative tactics?

(3) Innovation:  Does the project employ novel concepts, approaches or 
methods?  Are the aims original and innovative?  Does the project 
challenge existing paradigms or develop new methodologies or 
technologies? 

(4) Investigator:  Is the investigator appropriately trained and well 
suited to carry out this work?  Is the work proposed appropriate to the 
experience level of the principal investigator and other researchers 
(if any)?

(5) Environment:  Does the environment in which the work will be done 
contribute to the probability of success?  Do the proposed Aims take 
advantage of unique features of the environment or employ useful 
collaborative arrangements?  Is there evidence of institutional 
support? 

(6) Gender, Minorities, and Children: (Applicable only if human subject 
issues are involved in the planning period.)  The adequacy of plans to 
include both genders, minorities, and children as appropriate for the 
scientific goals of the research will be evaluated.  

(7) Human Subjects: (Applicable only if human subject issues are 
involved in the planning period)  Ethical issues surrounding human 
subjects will also be evaluated.

SCHEDULE

Letter of Intent Receipt Date:    February 22, 2002
Application Receipt Date:         March 22, 2002
Peer Review Date:                 TBA
Council Review:                   September 26, 2002
Earliest Anticipated Start Date:  September 30, 2002

AWARD CRITERIA

Award criteria that will be used to make award decisions include:

o  scientific merit (as determined by peer review)
o  availability of funds
o  programmatic priorities.

INQUIRIES

Inquiries concerning this RFA are encouraged.  The opportunity to 
clarify any issues or answer questions from potential applicants is 
welcome.

Direct inquiries regarding programmatic issues to one of the following 
persons, according to scientific area: 

Dr. Joan McGowan
Bone Diseases
45 Center Drive, Room 5AS-43E
Bethesda, MD  20892-6500
Telephone:  (301) 594-5055
FAX:  (301) 480-4543
Email:  mcgowanj@mail.nih.gov

Dr. Alan N. Moshell
Skin Diseases
45 Center Drive, Room 5AS-25L
Bethesda, MD  20892-6500
Telephone:  (301) 594-5017
FAX:  (301) 480-4543
Email:  moshella@mail.nih.gov

Dr. James S. Panagis
Orthopaedics
45 Center Drive, Room 5AS-37K
Bethesda, MD  20892-6500
Telephone:  (301) 594-5055
FAX:  (301) 594-4543
Email:  panagisj@mail.nih.gov

Dr. Susana A. Serrate-Sztein
Rheumatic Diseases
45 Center Drive, Room 5AS-37G
Bethesda, MD  20892-6500
Telephone:  (301) 594-5032
FAX:  (301) 480-4543
Email:  szteins@mail.nih.gov

Direct inquiries regarding review issues to:

Tommy L. Broadwater, Ph.D.
Scientific 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
Telephone:  (301) 594-4952
FAX:  (301) 480-4543
Email:  broadwat@mail.nih.gov

Direct inquiries regarding fiscal matters to: 

Melinda Nelson
Grants Management Office
National Institute of Arthritis and Musculoskeletal and Skin Diseases
45 Center Drive, Room 5AS-49F, MSC 6500
Bethesda, MD  20892-6500
Telephone:  (301) 594-3535
FAX:  (301) 480-5450
Email:  nelsonm@mail.nih.gov

AUTHORITY AND REGULATIONS
 
This program is described in the Catalog of Federal Domestic Assistance 
No. 93.846.  Awards are made under authorization of Sections 301 and 
405 of the Public Health Service Act as amended (42 USC 241 and 284) 
and administered under NIH grants policies and Federal Regulations 42 
CFR 52 and 45 CFR Parts 74 and 92.  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 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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