CLINICAL TRIAL PLANNING GRANT

Release Date:  October 5, 2000

RFA:  AR-00-010

National Institute of Arthritis and Musculoskeletal and Skin Diseases

Letter of Intent Receipt Date:  February 8, 2001
Application Receipt Date:       March 19, 2001

THIS RFA USES THE "MODULAR GRANT" AND "JUST-IN-TIME" CONCEPTS.  IT INCLUDES 
DETAILED MODIFICATIONS TO STANDARD APPLICATION INSTRUCTIONS THAT MUST BE USED 
WHEN PREPARING APPLICATIONS IN RESPONSE TO THIS RFA.

PURPOSE

The goal of the NIAMS Clinical Trial Planning Grant is to provide support for 
planning activities critical for the successful implementation of clinical 
trials in areas of interest to the NIAMS.  In addition, the Planning Grant is 
intended to (a) allow for early peer review of the rationale and design for 
complex or large-scale clinical trials and studies in those areas that are in 
the NIAMS mission; (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 protocol, such as outcome measures, recruitment 
strategies, inclusion and exclusion criteria, etc.

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 
funded

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 R21 award mechanism.  Applicants can request direct 
costs in $25,000 modules, up to a total direct cost request of $75,000.  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. 

FUNDS AVAILABLE

It is estimated that $500,000 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 or large-scale clinical trials and studies require extensive planning. 
 A clinical trial requires detailed information on the study design, protocols 
and procedures, analytical techniques, identification of facilities, and 
organization of an effective group of investigators with an effective 
administrative plan.  The clinical trial research plan is best presented in a 
well-documented Manual of Operations and Procedures (MOP) that is submitted as 
part of the application/proposal for the clinical trial.  However, preparation 
of a MOP is a time-consuming and expensive activity.  The NIAMS Clinical Trial 
Planning Grant can help support this activity as well as other administrative 
aspects of planning a 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, or Phase I 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, Minority & Children Issues - Proposed population description in 
terms of gender, minorities and children; justification for excluding any 
gender, minority 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.

Appendix material will be limited to color/glossy copies of text figures.

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.

Appendix material will be limited to color/glossy copies of text figures.

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.

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 are 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 the policy.

LETTER OF INTENT

Prospective applicants are asked to submit, by February 08, 2001, 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 08, 2001.

APPLICATION PROCEDURES

The research grant application form PHS 398 (rev. 4/98) is to be used in 
applying for these grants.  These forms are available at most institutional 
offices of sponsored research and from the Division of Extramural Outreach and 
Information Resources, National Institutes of Health, 6701 Rockledge Drive, 
MSC 7910, Bethesda, MD 20892-7910, telephone 301/435-0714, email: 
GrantsInfo@nih.gov.

BUDGET INSTRUCTIONS

Only budget for the planning period (part 2) should be presented. Direct costs 
may be requested in $25,000 modules, up to a total direct cost request of 
$75,000. ONLY ONE YEAR OF SUPPORT MAY BE REQUESTED.  The total direct costs 
must be requested in accordance with the  program guidelines and the 
modifications made to the standard PHS 398 application  instructions described 
below:

APPLICATION FORM PHS 398

o FACE PAGE: Items 7a and 7b should be completed, indicating Direct Costs (in 
$25,000 increments up to a maximum of $75,000) and Total Costs [Modular Total 
Direct plus Facilities and Administrative (F&A) costs] for the initial budget 
period.  Items 8a and 8b should be completed indicating the Direct and Total 
Costs for the entire proposed period of support.

o DETAILED BUDGET FOR THE INITIAL BUDGET PERIOD - Do not complete Form Page 4 
of the PHS 398. It is not required and will not be accepted with the 
application.

o BUDGET FOR THE ENTIRE PROPOSED PERIOD OF SUPPORT - Do not complete the 
categorical budget table on Form Page 5 of the PHS 398. It is not required and 
will not be accepted with the application.

o NARRATIVE BUDGET JUSTIFICATION - Prepare a Modular Grant Budget Narrative 
page. (See http://grants.nih.gov/grants/funding/modular/modular.htm for sample 
pages.) At the top of the page, enter the total direct costs requested.  This 
is not a Form page.

o Under Personnel, list all project personnel involved in the planning period 
(part 2), including their names, percent of effort, and roles on the project. 
No individual salary information should be provided. However, the applicant 
should use the NIH appropriation language salary cap and the NIH policy for 
graduate student compensation in developing the budget request.

For Consortium/Contractual costs, provide an estimate of total costs (direct 
plus facilities and administrative), each rounded to the nearest $1,000. List 
the individuals/organizations with whom consortium or contractual arrangements 
have been made, the percent effort of key personnel, and the role on the 
project. Indicate whether the collaborating institution is foreign or 
domestic. The total cost for a consortium/contractual arrangement is included 
in the overall requested modular direct cost amount.  Include the Letter of 
Intent to establish a consortium.

o BIOGRAPHICAL SKETCH - The Biographical Sketch provides information used by  
reviewers in the assessment of each individual's qualifications for a specific 
role in the proposed project, as well as to evaluate the overall 
qualifications of the research team. A biographical sketch is required for all 
key personnel, following the instructions below. No more than three pages may 
be used for each person. A sample biographical sketch may be viewed at:  
http://grants.nih.gov/grants/funding/modular/modular.htm

- Complete the educational block at the top of the form page;
- List position(s) and any honors;
- Provide information, including overall goals and responsibilities, on 
research projects ongoing or completed during the last three years.
- List selected peer-reviewed publications, with full citations;

o CHECKLIST - This page should be completed and submitted with the 
application.  If the F&A rate agreement has been established, indicate the 
type of agreement and the date.  All appropriate exclusions must be applied  
in the calculation of the F&A costs for the initial budget period and all 
future budget years.

o The applicant should provide the name and phone number of the individual to 
contact concerning fiscal and administrative issues if additional information 
is necessary following the initial review. 

The RFA label available in the PHS 398 (rev. 4/98) 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 (NIAMS Clinical Trial Planning 
Grant) and number (RFA-AR-00-010) must be typed on line 2 of the face page of 
the application form and the YES box must be marked.

The sample RFA label available at: 
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf has been modified to 
allow for this change.  Please note this is in pdf format.

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, two 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@exchange.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 low 
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 8, 2001
Application Receipt Date:         March 19, 2001
Peer Review Date:                 TBA (June/July 2001)
Council Review:                   September 24, 2001
Earliest Anticipated Start Date:  December 1, 2001

AWARD CRITERIA

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

o  scientific merit 
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: Joan_Mcgowan@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: Alan_N_Moshell@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: James_Panagis@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: Susana_Serrate-Sztein@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:  Tommy_Broadwater@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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