NINDS CLINICAL TRIAL PLANNING GRANT

RELEASE DATE:  January 7, 2003

PA NUMBER: PAR-03-051 (see correction NOT-NS-04-010)

March 2, 2006 (NOT-OD-06-046) – Effective with the June 1, 2006 submission date, 
all R03, R21, R33 and R34 applications must be submitted through Grants.gov using 
the electronic SF424 (R&R) application. A replacement R34 (PAR-06-460) funding 
opportunity announcement has been issued for the submission dates after June 1, 2006.

EXPIRATION DATE:  Dec 16, 2005, unless reissued. 

APPLICATION RECEIPT DATES:  April 15, August 15, and December 15

National Institute of Neurological Disorders and Stroke (NINDS)
 (http://www.ninds.nih.gov)

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  

This PA replaces PAR-01-118

The NINDS seeks to fund high quality clinical trials to evaluate treatments 
for neurological disorders.  The purpose of the NINDS Clinical Trial Planning 
Grant is to provide support for the organization of activities critical for 
the successful implementation of high-risk, complex, or large-scale clinical 
trials.  The planning grant is intended to (a) allow for early peer review 
for the rationale and design of the proposed clinical trial; (b) provide 
support for the development of a detailed manual of operations and 
procedures; and (c) provide support to develop essential elements of a 
clinical trial, such as adequate plans for recruitment of patients, 
experimental design and protocols, data management, analytical techniques, 
facilities, administrative procedures, obtaining IND/IDE, and collaborative 
arrangements.  The purpose of the NINDS planning grant is not to obtain 
preliminary data or to conduct pilot studies to support the rationale for the 
clinical trial.

RESEARCH OBJECTIVES

The NINDS encourages clinical research to evaluate interventions to treat and 
prevent neurological disease.  The NINDS has established the Clinical Trial 
Planning Grant because extensive efforts are required to develop a detailed 
study protocol and to organize an effective research group.  After the basic 
design and rationale for a neurological treatment trial has been reviewed, 
the NINDS Clinical Trial Planning Grant supports the development of specific 
elements which will be essential to conducting a successful full-scale 
clinical trial, including adequate plans for recruitment of patients, 
experimental design and protocols, data management, analytical techniques, 
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 pilot studies to support the rationale for the 
clinical trial.  The expected product of the planning grant is a detailed 
clinical trial research plan including a complete manual of operations and 
procedures.  Included in the planning grant application must be a completed 
study protocol and projected direct costs for the future phase III trial.  
This estimate, broken down by year, should be included in the research plan 
of the application.

MECHANISM(S) OF SUPPORT 

This PA will use the NIH Developmental Planning Grant (R21) award mechanism.  
(Note: NIH is planning to issue a generic announcement for clinical trial 
planning grants, which will then supercede this specific announcement).  As 
an applicant, you will be solely responsible for planning, directing, and 
executing the proposed project.  This grant mechanism provides up to $150,000 
in direct costs for a single year.  The award cannot be renewed.

This PA uses just-in-time concepts.  It also uses the modular as well as the 
non-modular budgeting formats (see 
http://grants.nih.gov/grants/funding/modular/modular.htm).  Specifically, if 
you are submitting an application with direct costs in each year of $250,000 
or less, use the modular format.  Otherwise follow the instructions for non-
modular research grant applications.

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

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.

SPECIAL REQUIREMENTS

The Research Plan of the application must contain the following four elements 
described below.  For details of these four elements, see the REVIEW CRITERIA 
section of this PAR.

o Rationale/Significance – Provide the rationale for the future clinical 
trial and give information documenting significance and need to perform the 
clinical trial.  The application should also include the specific aims for 
the planning period.  The projected direct costs, broken down by year, must 
be included with the rational for the future trial.

o Experimental Design – The application for the planning grant must include a 
full protocol for the future clinical trial, including such elements as the 
following: (a) intervention(s) and mode(s) of delivery; (b) study design, 
treatment group(s), trial size, and inclusion/exclusion criteria; (c) control 
group(s) if applicable; (d) outcome measures; and (e) data 
analysis/management plan.  A full descriptive template for a study protocol 
submitted for a NINDS planning grant can be seen at the following URL: 
http://www.ninds.nih.gov/funding/research/clinical_research/protocoltemplate.htm 

o Plans to Address Patient Recruitment/Retention – The application must 
address the availability and population description of the requisite patient 
population (including gender, minorities, and children) and plans for 
recruitment outreach and follow-up.

o Investigators – The application must include a description of the 
leadership and proposed organization of the clinical trial, including 
proposed clinical sited (letters of commitment are not required at this 
stage). 

WHERE TO SEND INQUIRIES

We encourage your inquiries concerning this PA and welcome the opportunity to 
answer questions from potential applicants.  Inquiries may fall into three 
areas:  scientific/research, peer review, and financial or grants management 
issues:

o Direct your questions about scientific/research issues to:

John R. Marler, M.D.
Associate Director for Clinical Trials
National Institute of Neurological Disorders and Stroke
6001 Executive Blvd., Room 2216
Bethesda, MD 20892-9520
Telephone:  (301) 496-9135
Fax:  (301) 480-1080
Email:  jm137f@nih.gov

Scott Janis, Ph.D.,
Clinical Trials Program Analyst
National Institute of Neurological Disorders and Stroke
6001 Executive Blvd., Room 2210
Bethesda, MD 20892-9520
Telephone:  (301) 496-9135
Fax:  (301) 480-1080
Email: sj151t@nih.gov

o Direct your questions about peer review issues to:

Katherine Woodbury-Harris, Ph.D.
SRA, Scientific Review Branch
NSC/NINDS/NIH
6001 Executive Boulevard
Bethesda, MD 20892-9529
Telephone:  (301) 496-5980
Fax:  (301) 402-0182
E-mail:  kw47o@nih.gov

o Direct your questions about financial or grants management matters to:

Gladys Melendez
Senior Grants Management Specialist
NIH/NINDS/GMB/Suite 3290
6001 Executive Blvd.
Rockville, MD 20892
Telephone: (301) 496-9231
Fax:  (301) 402-0219
Email:  bohlerg@ninds.nih.gov

LETTER OF INTENT
 
Prospective applicants are asked to submit a letter of intent that includes 
the following information:

o Descriptive title of the proposed research
o Name, address, and telephone number of the Principal Investigator
o Names of other key personnel 
o Participating institutions
o Number and title of this RFA 

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 IC staff to estimate the potential review workload and plan 
the review.
 
The letter of intent is to be sent 6 weeks prior to the intended submission 
date.  The letter of intent should be sent to (e-mail is acceptable):

Scott Janis, Ph.D.,
Clinical Trials Program Analyst
National Institute of Neurological Disorders and Stroke
6001 Executive Blvd., Room 2210
Bethesda, MD 20892-9520
Telephone:  (301) 496-9135
Fax:  (301) 480-1080
Email: sj151t@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 
http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive 
format.  For further assistance contact GrantsInfo, Telephone (301) 435-0714, 
Email: GrantsInfo@nih.gov.

SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS:  Applications 
requesting up to $250,000 per year in direct costs 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 
http://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 
http://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 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)

The title, NINDS CLINICAL TRIAL PLANNING GRANT, and the number of this 
announcement must be typed on line 2 of the face page of the application form 
and the YES box must be checked.

At the same time of submission, mail two additional copies of the application 
to:

Alan Willard, Ph.D.
Chief, Scientific Review Branch
Division of Extramural Research
National Institute of Neurological Disorders & Stroke
6001 Executive Boulevard, Room 3208
Bethesda, MD 20892-9529
Rockville, MD 20852 (Courier service only)
Telephone:  (301) 496-9223
Fax:  (301) 402-0182
E-mail:  AlanW@ninds.nih.gov

The submission, review, and award schedule is:

Submission deadline     NINDS Review    Council Earliest Funding
April 15            Jun/Jul     Sept/Oct         Dec 1
August 15           Oct/Nov     Jan/Feb          Apr 1
December 15         Feb/Mar     May/Jun          Jul 1

APPLICATION PROCESSING: Applications must be received by or mailed on or 
before the receipt dates listed on the face page of the PA.  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

Complete applications for this PAR will be assigned to evaluated for 
scientific and technical merit by the NINDS clinical trials special emphasis 
study group (NSD-K) in accordance with the standard NIH peer review procedures 
(http://www.csr.nih.gov/refrev.htm.)

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 National Neurological Disorders and 
Stroke Advisory Council 

REVIEW CRITERIA

Under the scope of the NINDS planning grant, the scientific review group will 
address and consider the research project using the four criteria listed 
below.  Each of these criteria will be addressed and considered by the 
reviewers in assigning your application's overall score.  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 may have an important health impact in clinical practice.  
Each of the following criteria will be addressed and considered in the 
assignment of the overall scientific merit rating.

(1) RATIONALE/SIGNIFICANCE:  

o Is there adequate information to determine the significance and need to 
perform a future full-scale randomized clinical trial (RCT)?  
o Are adequate reasons presented for selection of intervention and mode of 
delivery, and for selecting particular doses or procedures?  
o Is there adequate information provided regarding the biological mechanisms 
and clinical data that support conducting an RCT?  
o Did the applicant present a compelling case for a need to proceed with an 
RCT as soon as possible?  
o Did the applicant adequately explain the impact of the future RCT on health 
care?  
o Was there adequate discussion included of advantages and disadvantages of 
competitive therapies?  
o Is the discussion of the ethical issues surrounding an RCT and the disease 
under study complete and thorough, and are there adequate safeguards in place 
to protect the welfare of human subjects?
o Did the applicant provide the estimated direct costs of the future Trial?  

(2) EXPERIMENTAL DESIGN:  

o Are the conceptual framework, design, methods, and analyses adequately 
developed and appropriate for the aim of the future RCT?  
o In evaluating the experimental design, the reviewers will consider the 
adequacy of the following: 
1) translation of the clinical question into a statistical hypothesis; sample 
size and duration of the RCT; 
2) selection of endpoint(s) and data to be collected; 
3) randomization and masking; and inclusion/exclusion criteria;
4) strengths and weaknesses of the proposed methods, and possible 
alternatives; 
5) ancillary therapies; 
6) capability to develop methods for standardization of procedures for data 
management and quality control.
 
(3) PLANS TO ADDRESS PATIENT RECRUITMENT/RETENTION: 

o Are there adequate plans for documenting the availability of the requisite 
eligible patient pool and for including women, children, and minority 
individuals, (as appropriate) as trial participants?  
o Has the applicant provided adequate plans for recruitment outreach, as 
appropriate, and for follow-up procedures to ensure collection of data at 
stated intervals?

(4) INVESTIGATORS:  

o Is there a clear statement of the leadership and proposed organization of 
the RCT, including: identification of a principal investigator, and for 
multi-center trials, a core of potential center investigators?  
o Is there evidence of professional training and experience of the RCT 
organizers in such areas as the clinical problem under study, administration 
of complex projects, and study design?  
o Are there plans for inclusion of statisticians, data managers and study 
coordinators? 
o Has the applicant developed plans to add or drop centers?  
o Are there adequate plans for essential committee structure, i.e., Planning, 
Steering, and Executive committees?

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, animals, 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)

DATA SHARING:  The adequacy of the proposed plan to share data.

BUDGET:  The reasonableness of the proposed budget and the requested period 
of support in relation to the proposed research.

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 

MONITORING PLAN AND DATA SAFETY AND MONITORING BOARD:  Research components 
involving Phase I and II clinical trials must include provisions for 
assessment of patient eligibility and status, rigorous data management, 
quality assurance, and auditing procedures.  In addition, it is NIH policy 
that all clinical trials require data and safety monitoring, with the method 
and degree of monitoring being commensurate with the risks (NIH Policy for 
Data Safety and Monitoring, NIH Guide for Grants and Contracts, June 12, 
1998: http://grants.nih.gov/grants/guide/notice-files/not98-084.html).  

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
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html);
a complete copy of the updated Guidelines are available at 
http://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 
http://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 
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 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. 93.853, 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 
http://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.

Weekly TOC for this Announcement
NIH Funding Opportunities and Notices

	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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