This Program Announcement expires on July 31, 2004, unless reissued.

PILOT STUDIES FOR CLINICAL TRIALS IN NEUROLOGICAL DISORDERS

Release Date:  July 25, 2001 (see replacement PAR-03-174)

PA NUMBER:  PAR-01-119

National Institute of Neurological Disorders and Stroke

THIS PAR USES "MODULAR GRANT" AND "JUST-IN-TIME" CONCEPTS.  MODULAR INSTRUCTIONS 
MUST BE USED FOR RESEARCH GRANT APPLICATIONS UP TO $250,000 PER YEAR. 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 NINDS is committed to identifying effective treatments for neurological 
disorders by supporting well-executed clinical trials. Before proceeding to a 
full-scale clinical trial, pilot clinical studies are often required.  The NINDS 
announces its interest in supporting pilot studies required to obtain necessary 
information to clearly establish the clinical basis for proceeding to a full-
scale trial.  The purpose of PILOT STUDIES FOR CLINICAL TRIALS IN NEUROLOGICAL 
DISORDERS grant (for brevity referred to as NINDS Pilot Studies grant) is to 
obtain preliminary data and conduct studies to support the rationale for a 
subsequent full-scale clinical trial of an intervention to treat or prevent 
neurological disease.
 
RESEARCH OBJECTIVES
 
The research project should directly address how the pilot study will advance 
the design of a subsequent full-scale clinical trial.  The application should 
also address the intrinsic scientific merit of the study conducted under the 
NINDS Pilot Studies Grant, whether or not a full-scale trial is performed.
 
Examples of relevant research include, but are not limited to, the following:

1.  Studies to refine the intervention strategy (dosage, duration, delivery 
system).

2.  Studies to define and refine the target population.
 
3.  Collection of preliminary data for establishing measures of efficacy and 
safety.

In preparing for the definitive clinical trial, a pilot study will address 
questions that are formulated to optimize the design of the eventual trial 
rather than address the clinical question with lower power.
 
The objective of the NINDS Pilot Studies Grant is to increase the quality of 
clinical research to evaluate interventions for the treatment or prevention of 
neurological disease.  To meet this objective the proposed pilot study must 
successfully incorporate creative and realistic solutions to difficult problems 
in clinical neurological research for the particular intervention being 
evaluated.



MECHANISM OF SUPPORT
 
This PAR will use the National Institutes of Health (NIH) R01 award mechanism.  
Responsibility for the planning, direction, and execution of the proposed 
project will be solely that of the applicant.  The total project period for an 
application submitted in response to this PA may not exceed 3 years.
 
ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic and foreign 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.

INQUIRIES

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

Direct inquiries regarding programmatic 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

Barbara Radziszewska, Ph.D., M.P.H.
Clinical Research Project Manager
National Institute of Neurological Disorders and Stroke
6001 Executive Blvd., Room 2216
Bethesda, MD 20892-9520
Telephone:  (301) 496-2076
Fax:  (301) 480-1080
Email: br94h@nih.gov

Direct inquiries regarding review issues to:

Lillian Pubols, Ph.D.
Chief, Scientific Review Branch
NSC/NINDS/NIH
6001 Executive Boulevard
Bethesda, MD 20892-9529
Telephone:  (301) 496-5324
Fax:  (301) 402-0182
E-mail:  lp28e@nih.gov

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

Direct inquiries regarding fiscal matters to:

Gladys Melendez-Bohler
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

APPLICATION PROCEDURES

The PHS 398 research grant application instructions and forms (rev. 5/2001) at 
http://grants.nih.gov/grants/funding/phs398/phs398.html are to be used in 
applying for these grants and will be accepted at the standard application 
deadlines (http://grants.nih.gov/grants/dates.htm) as indicated in the 
application kit.  This version of the PHS 398 is available in an interactive, 
searchable PDF format. Although applicants are encouraged to begin using the 
5/2001 revision of the PHS 398 as soon as possible, the NIH will continue to 
accept applications prepared using the 4/1998 revision until January 9, 2002. 
Beginning January 10, 2002, however, the NIH will return applications that are 
not submitted on the 5/2001 version.  For further assistance contact GrantsInfo, 
Telephone 301/435-0714, Email: GrantsInfo@nih.gov.

Applicants planning to submit an investigator-initiated new (type 1), competing 
continuation (type 2), competing supplement, or any amended/revised version of 
the preceding grant application types requesting $500,000 or more in direct 
costs for any year are advised that he or she must contact the Institute or 
Center (IC) program staff before submitting the application, i.e., as plans for 
the study are being developed.  Furthermore, the application must obtain 
agreement from the IC staff that the IC will accept the application for 
consideration for award.  Finally, the applicant must identify, in a cover 
letter sent with the application, the staff member and Institute or Center who 
agreed to accept assignment of the application.  

This policy requires an applicant to obtain agreement for acceptance of the 
original application as well as any subsequent revisions.  Refer to the NIH 
Guide for Grants and Contracts, March 20, 1998 at 
http://grants.nih.gov/grants/guide/notice-files/not98-030.html. 

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 title and number of the program announcement must be typed on line 2 of the 
face page of the application form and the YES box must be marked.

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 mail or courier service)

In order to facilitate the review of applications assigned to the
NINDS, the applicant should, at the same time, mail or deliver two
copies of the application to:
 
Dr. Lillian Pubols
Chief, Scientific Review Branch
NINDS, NIH
6001 Executive Boulevard
Bethesda, MD 20892-9529
Rockville, MD 20852 (Courier service only)
EMAIL:  lp28e@nih.gov

Applicants from institutions that have a General Clinical Research Center 
(GCRC) funded by the NIH National Center for Research Resources may wish to 
identify the GCRC as a resource for conducting the proposed research.  If so, 
a letter of agreement from either the GCRC Program Director or Principal 
Investigator should be included with the application.

REVIEW CONSIDERATIONS  

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

Applications that are complete and responsive to the PAR will be evaluated for 
scientific and technical merit by an appropriate peer review group convened by 
the NINDS in accordance with the review criteria stated below.  As part of the 
initial merit review, all applications will receive a written critique and 
undergo a process in which only those applications deemed to have the highest 
scientific merit, generally the top half of the applications under review, will 
be discussed, assigned a priority score, and receive a second level review by 
the NINDS National 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.

(1) Significance:  Does this study address an important problem?  If the aims of 
the application are achieved, how will scientific knowledge be advanced?  
What will be the effect of these studies on the concepts or methods that 
drive this field? 

In evaluating significance, the reviewers should also consider the state of 
equipoise in the medical and patient communities and the potential impact of the 
proposed intervention on health care and quality of life.

(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? 
In addition to the standard evaluation criteria described above, applications 
will also be reviewed with respect to the following: 

The adequacy of plans for sequence of clinical studies, including the proposed 
pilot study, that will produce a definitive clinical trial;  The scientific 
soundness of the proposed methodology, such as translation of the clinical 
question into statistical hypotheses, selection of outcome measure(s), inclusion 
and exclusion criteria, plans for randomization and masking, secondary questions 
(including capacity for post hoc analyses);  The completeness and quality of the 
protocol and standardized procedures that will be used for this pilot study;  
The ethical aspects of the study and the appropriateness of subject safety 
protections;  And the adequacy of quality control procedures.
  
Reviewers will also evaluate plans for data management and analyses.  However, 
sophisticated data management procedures are not required for a pilot study, 
although this study may be used to test these procedures.  Likewise, description 
of specific methods to be used for data analyses is not required; it is assumed 
that in most cases, pilot studies will provide mostly descriptive statistics.  
Reviewers will evaluate plans for demographic subgroup analyses, if applicable. 

In evaluating plans for the sample size for the pilot, the reviewers should take 
into account that pilot studies need not be oriented toward detecting treatment 
differences; however, the data from this study should provide a basis for 
reliable sample size estimates for future trials.

 (3) Innovation:  Does the project employ novel concepts, approaches or method?  
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)? The 
reviewers should consider training and expertise in the clinical problem and the 
proposed intervention, and training and expertise in clinical trials. 

(5) Environment:  Does the scientific environment in which the 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? 

 In addition to the above criteria, in accordance with NIH policy, all 
applications will also be reviewed with respect to the following:

o  The adequacy of plans to include both genders, minorities and their 
subgroups, and children as appropriate for the scientific goals of the research.  
Plans for the recruitment and retention of subjects will also be evaluated.

o  The reasonableness of the proposed budget and duration in relation to the 
proposed research

o  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.

AWARD CRITERIA

Applications will compete for available funds with all other recommended 
applications. The following will be considered in making funding decisions:  
Quality of the proposed project as determined by peer review, availability of 
funds, program priority, and program balance.

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 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 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 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.

DATA AND SAFETY MONITORING PLAN

For phase I and II clinical trials, investigators must submit a general 
description of the data and safety monitoring plan as part of the research 
application.  For further information, see 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-038.html

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.

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 a 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.

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 (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.

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, “PILOT STUDIES FOR 
CLINICAL TRIALS IN NEUROLOGICAL DISORDERS”, is related to the priority area of 
chronic disabling conditions.  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.  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 and contract recipients to provide a 
smoke-free workplace and promote the non-use of all tobacco products.  In 
addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in 
certain facilities (or in some cases, 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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