CLINICAL TRIAL PLANNING GRANT
RELEASE DATE: July 1, 2002
PA NUMBER: PAR-02-119
EXPIRATION DATE: October 24, 2003, unless reissued.
National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIAMS,
(http://www.niams.nih.gov/)
Application Receipt Dates: October 24, 2002, June 24, 2003, and October 24,
2003.
THIS PA CONTAINS THE FOLLOWING INFORMATION
o Purpose of the PA
o Research Objectives
o Mechanism(s) of Support
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Special Requirements
o Where to Send Inquiries
o Submitting an Application
o Peer Review Process
o Review Criteria
o Award Criteria
o Required Federal Citations
PURPOSE OF THIS PA
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,
or 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 recommended for funding.
RESEARCH OBJECTIVES
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.
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 Evaluating 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.
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 PA.
MECHANISM(S) OF SUPPORT
This PA will use the NIH R21 award mechanism. As an applicant, you will be
solely responsible for planning, directing, and executing the proposed
project.
This PA uses just-in-time concepts. It also uses the modular budgeting
format. (see https://grants.nih.gov/grants/funding/modular/modular.htm). This
is a one-year award, for up to a total direct cost request of $100,000.
ELIGIBLE INSTITUTIONS
You may submit (an) application(s) if your institution has any of the
following characteristics:
o For-profit or non-profit organizations
o Public or private institutions, such as universities, colleges, hospitals,
and laboratories
o Units of State and local governments
o Eligible agencies of the Federal government
o Domestic or foreign
o Faith-based organizations
INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS
Any individual with the skills, knowledge, and resources necessary to carry
out the proposed research is invited to work with their institution to
develop an application for support. Individuals from underrepresented racial
and ethnic groups as well as individuals with disabilities are always
encouraged to apply for NIH programs.
Also, new investigators are encouraged to apply. They may wish to develop
small, focused research projects that provide initial findings for larger
research proposals in the future. It would be expected that such applications
also would have smaller budgets reflecting the scope of the research
proposed.
SPECIAL REQUIREMENTS
The Research Plan should be presented in two parts as described below, and
must be limited to 15 pages. Appendix material, with the exception of color
glossy photographs, will not be accepted. Applicants are encouraged to
address issues listed in "Review Criteria" and "Other Review Criteria" in
this PA.
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.
Discussion of the below two topics are not subject to page limits.
o Gender, Minorities and 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.
Discussion of the below topic is not subject to page limits.
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.
WHERE TO SEND INQUIRIES
We encourage your inquiries concerning this PA and welcome the opportunity to
answer questions from potential applicants.
o Direct your questions about scientific/research issues to:
Dr. Deborah Ader
Behavioral & Prevention Research
NIH, NIAMS, EP
One Democracy Plaza
6701 Democracy Blvd., Suite 800
Bethesda, MD 20892-4872
Telephone: (301) 594-5032
FAX: (301) 480-4543
Email: aderd@mail.nih.gov
Dr. Gayle Lester
Osteoarthritis Initiative & Diagnostic Imaging
NIH, NIAMS, EP
One Democracy Plaza
6701 Democracy Blvd., Suite 800
Bethesda, MD 20892-4872
Telephone: (301) 594-5055
FAX: (301) 480-4543
Email: lester1@mail.nih.gov
Dr. Joan McGowan
Bone Diseases
NIH, NIAMS, EP
One Democracy Plaza
6701 Democracy Blvd., Suite 800
Bethesda, MD 20892-4872
Telephone: (301) 594-5055
FAX: (301) 480-4543
Email: mcgowanj@mail.nih.gov
Dr. Alan N. Moshell
Skin Diseases
NIH, NIAMS, EP
One Democracy Plaza
6701 Democracy Blvd., Suite 800
Bethesda, MD 20892-4872
Telephone: (301) 594-5017
FAX: (301) 480-4543
Email: moshella@mail.nih.gov
Dr. James S. Panagis
Orthopaedics
NIH, NIAMS, EP
One Democracy Plaza
6701 Democracy Blvd., Suite 800
Bethesda, MD 20892-4872
Telephone: (301) 594-5055
FAX: (301) 594-4543
Email: panagisj@mail.nih.gov
Dr. Susana A. Serrate-Sztein
Rheumatic Diseases
NIH, NIAMS, EP
One Democracy Plaza
6701 Democracy Blvd., Suite 800
Bethesda, MD 20892-4872
Telephone: (301) 594-5032
FAX: (301) 480-4543
Email: szteins@mail.nih.gov
o Direct your questions about peer review issues to:
John Lymangrover, Ph.D.
Scientific Review Branch
NIH, NIAMS, EP
One Democracy Plaza
6701 Democracy Blvd., Suite 800
Bethesda, MD 20892-4872
Telephone: (301) 594-4952
FAX: (301) 480-4543
Email: broadwat@mail.nih.gov
o Direct your questions about financial or grants management matters to:
Melinda Nelson
Grants Management Office
NIH, NIAMS, EP
One Democracy Plaza
6701 Democracy Blvd., Suite 800
Bethesda, MD 20892-4872
Telephone: (301) 594-3535
FAX: (301) 480-5450
Email: nelsonm@mail.nih.gov
SUBMITTING AN APPLICATION
Applications must be prepared using the PHS 398 research grant application
instructions and forms (rev. 5/2001). The PHS 398 is available at
https://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive
format. For further assistance contact GrantsInfo, Telephone (301) 710-0267,
Email: GrantsInfo@nih.gov.
SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS: Because the CTPG
applications are limited to $100,000 per year in direct costs, they must be
submitted in a modular grant format. The modular grant format simplifies the
preparation of the budget in these applications by limiting the level of
budgetary detail. Applicants request direct costs in $25,000 modules.
Section C of the research grant application instructions for the PHS 398
(rev. 5/2001) at https://grants.nih.gov/grants/funding/phs398/phs398.html
includes step-by-step guidance for preparing modular grants. Additional
information on modular grants is available at
https://grants.nih.gov/grants/funding/modular/modular.htm.
SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten original of
the application, including the checklist, and five 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)
APPLICATION PROCESSING: Applications must be received by or mailed on or
before the receipt dates described at
https://grants.nih.gov/grants/funding/submissionschedule.htm. The CSR will
not accept any application in response to this PA 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 a substantial revision of an application already reviewed, but
such application must include an Introduction addressing the previous
critique.
PEER REVIEW PROCESS
Applications submitted for this PA will be assigned on the basis of
established PHS referral guidelines. An appropriate scientific review group
convened by NIAMS in accordance with the standard NIH peer review procedures
(http://www.csr.nih.gov/refrev.htm) will evaluate applications for scientific
and technical merit.
As part of the initial merit review, all applications will:
o Receive a written critique
o Undergo a selection process in which only those applications deemed to have
the highest scientific merit, generally the top half of applications under
review, will be discussed and assigned a priority score
o Receive a second level review by the appropriate national advisory council
or board
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 your application in order to judge the likelihood that the
proposed research will have a substantial impact on the pursuit of these
goals:
o Significance
o Approach
o Innovation
o Investigator
o Environment
The scientific review group will address and consider each of these criteria
in assigning your application"s overall score, weighting them as appropriate
for each application. Your 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, you may propose to carry out
important work that by its nature is not innovative but is essential to move
a field forward.
(1) SIGNIFICANCE: Does your study address an important problem? If the aims
of your application are achieved, how do they advance scientific knowledge?
What will be the effect of these studies on the concepts or methods that
drive this field?
(2) APPROACH: Are the conceptual framework, design, methods, and analyses
adequately developed, well integrated, and appropriate to the aims of the
project? Do you acknowledge potential problem areas and consider alternative
tactics?
(3) INNOVATION: Does your project employ novel concepts, approaches or
methods? Are the aims original and innovative? Does your project challenge
existing paradigms or develop new methodologies or technologies?
(4) INVESTIGATOR: Are you appropriately trained and well suited to carry out
this work? Is the work proposed appropriate to your experience level as the
principal investigator and to that of other researchers (if any)?
(5) ENVIRONMENT: Does the scientific environment in which your work will be
done contribute to the probability of success? Do the proposed experiments
take advantage of unique features of the scientific environment or employ
useful collaborative arrangements? Is there evidence of institutional
support?
ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, your
application will also be reviewed with respect to the following:
PROTECTIONS: The adequacy of the proposed protection for humans or the
environment, to the extent they may be adversely affected by the project
proposed in the application.
INCLUSION: The adequacy of plans to include subjects from both genders, all
racial and ethnic groups (and subgroups), and children as appropriate for the
scientific goals of the research. Plans for the recruitment and retention of
subjects will also be evaluated. (See Inclusion Criteria included in the
section on Federal Citations, below)
BUDGET: The reasonableness of the proposed budget and the requested period
of support in relation to the proposed research.
OTHER 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
this PA. The reviewers will provide a two-part critique on the application.
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).
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 PA. 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: Any concerns involving the participation of human
subjects will 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 PA.
(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.
AWARD CRITERIA
Applications submitted in response to a PA will compete for available funds
with all other recommended applications. The following will be considered in
making funding decisions:
o Scientific merit of the proposed project as determined by peer review
o Availability of funds
o Relevance to program priorities
REQUIRED FEDERAL CITATIONS
INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH: 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 clinical research projects unless a
clear and compelling justification is 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 clinical research should read the AMENDMENT "NIH
Guidelines for Inclusion of Women and Minorities as Subjects in Clinical
Research - Amended, October, 2001," published in the NIH Guide for Grants and
Contracts on October 9, 2001
(https://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html), a complete
copy of the updated Guidelines is available at
https://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.
The amended policy incorporates: the use of an NIH definition of clinical
research, updated racial and ethnic categories in compliance with the new OMB
standards, clarification of language governing NIH-defined Phase III clinical
trials consistent with the new PHS Form 398, and updated roles and
responsibilities of NIH staff and the extramural community. The policy
continues to require for all NIH-defined Phase III clinical trials that: a)
all applications or proposals and/or protocols must 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) investigators must report annual accrual and progress in conducting
analyses, as appropriate, by sex/gender and/or racial/ethnic group
differences.
INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS:
The NIH maintains a policy 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 and 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 is available at
https://grants.nih.gov/grants/funding/children/children.htm.
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. You will find this policy announcement in the NIH Guide for Grants
and Contracts Announcement, dated June 5, 2000, at
https://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
https://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.
Applicants may wish to place data collected under this PA 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.
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. Furthermore,
we caution reviewers that their anonymity may be compromised when they
directly access an Internet site.
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 PA
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.
AUTHORITY AND REGULATIONS: This program is described in the Catalog of
Federal Domestic Assistance No. 93.846, and is not subject to the
intergovernmental review requirements of Executive Order 12372 or Health
Systems Agency review. 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 described at
https://grants.nih.gov/grants/policy/policy.htm and under Federal Regulations
42 CFR 52 and 45 CFR Parts 74 and 92.
The PHS strongly encourages all grant recipients to provide a smoke-free
workplace and discourage the 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.
https://grants.nih.gov/grants/guide/pa-files/PA-02-015.html.