NIH CLINICAL TRIAL PLANNING GRANT (R34) PROGRAM

RELEASE DATE:  October 16, 2003

PA NUMBER:  PA-04-008

EXPIRATION DATE:  November 15, 2006, unless reissued.

Department of Health and Human Services (DHHS)

PARTICIPATING ORGANIZATIONS:  
National Institutes of Health (NIH)
 (http://www.nih.gov)

COMPONENTS OF PARTICIPATING ORGANIZATIONS:
National Institute on Aging (NIA)
 (http://www.nia.nih.gov/) 
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
 (http://www.niaaa.nih.gov/) 
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
 (http://www.niams.nih.gov/) 
National Institute of Child Health and Human Development (NICHD)
 (http://www.nichd.nih.gov/) 
National Center for Complementary and Alternative Medicine (NCCAM)
 (http://www.nccam.nih.gov/) 
National Institute on Deafness and Other Communication Disorders (NIDCD)
 (http://www.nidcd.nih.gov/) 
National Institute on Drug Abuse (NIDA)
 (http://www.nida.nih.gov/) 
National Institute of Neurological Disorders and Stroke (NINDS)
 (http://www.ninds.nih.gov/) 
Office of Research on Women's Health (ORWH)
 (http://www4.od.nih.gov/orwh/index.html)
Office of Behavioral and Social Sciences Research (OBSSR)
 (http://obssr.od.nih.gov/)
Office of Rare Diseases (ORD)
 (http://rarediseases.info.nih.gov/)
Office of Dietary Supplements (ODS)
 (http://dietary-supplements.info.nih.gov/)

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S):  93.173, 93.209, 93.213, 
93.271, 93.272, 93.273, 93.277, 93.278, 93.279, 93.846, 93.853, 93.864, 
93.865, 93.866, 93.891

THIS PA CONTAINS THE FOLLOWING INFORMATION

o Purpose of the PA
o Research Objectives
o Mechanism 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 NIH Clinical Trial Planning Grant (R34) is to provide 
support for the development of a Phase III clinical trial, including the 
establishment of the research team, the development of tools for data 
management and oversight of the research, the definition of recruitment 
strategies, and the finalization of the protocol and other essential elements 
of the study included in a manual of operations/procedures.  The Clinical 
Trial Planning Grant is not designed for the collection of preliminary data 
or the conduct of pilot studies to support the rationale for a clinical 
trial.

An NIH-defined Phase III clinical trial is a broadly based prospective 
clinical investigation, usually involving several hundred or more human 
subjects, for the purpose of evaluating an experimental intervention in 
comparison with a standard or control intervention or comparing two or more 
existing treatments.  Often, the aim of such investigation is to provide 
evidence leading to a scientific basis for consideration of a change in 
health policy or standard of care.  The definition includes pharmacologic, 
non-pharmacologic, and behavioral interventions for disease prevention, 
prophylaxis, diagnosis or therapy.  Community- and other population-based 
intervention trials also are included. 

The planning grant is designed to permit early peer review of the rationale 
and design of the proposed clinical trial and to provide support for the 
development of a detailed Manual of Procedures (MOP) including all elements 
essential to the launching of a trial.

Investigators wishing to apply for an R34 grant should be aware that 
individual ICs may have specific requirements for this funding mechanism and, 
therefore, should consult IC staff to determine if an application is 
appropriate. NIH Offices that participate in this PA (ORWH, OBSSR, ORD, ODS) 
are listed but do not have funding authority and must work through an 
Institute or Center.

RESEARCH OBJECTIVES

Background

At the time of submission, applications requesting support for Phase III 
clinical trials are expected to provide detailed information regarding the 
study's rationale, design, analytic techniques, protocols and procedures, 
facilities and environment, organizational structure, and collaborative 
arrangements.  This information is best conveyed in a well-documented Manual 
of Procedures (MOP), the development of which typically represents a costly 
and time-consuming activity.  Delay of the trial caused by the need to 
develop a MOP reduces the time available to carry out the trial itself.  The 
R34 has been established to allow for the planning and organizational 
activities necessary to implement a Phase III clinical trial to take place 
well in advance of funding of the actual trial.

Scope 

The planning grant is designed to:  (1) permit early peer review of the 
rationale for the proposed clinical trial; (2) permit assessment of the 
design/protocol of the proposed trial in its current, early form; (3) provide 
support for the development of a detailed MOP; and (4) support the 
development of other essential elements of a clinical trial as defined by the 
individual participating ICs.  

Activities supported by the R34 may include, but are not limited to, the 
following examples: 

o developing/finalizing the Manual of Operations; basic elements in the MOP 
should include identification of the patient population; inclusion and 
exclusion criteria; adequate plans for recruitment and retention of 
participants; experimental design and protocols; clear definition of the 
research hypothesis and outcome measures; quality control/assurance 
procedures; data management and analytical techniques; sample size estimates 
with justification; administrative procedures (including regulatory approvals 
if necessary); collaborative arrangements; duties and responsibilities of 
study chairperson, clinical sites, coordinating center, and other central 
resources such as a central laboratory; and monitoring plans to assure 
patient protection and data integrity; 

o finalizing plans for addressing Federal and NIH gender/minority inclusion 
and human subjects protection requirements; 

o establishing collaborative arrangements; 

o instituting means to assure standardization of procedures across sites and 
among staff; 

o developing tools needed for data collection and data management; 

o developing/finalizing safety and monitoring plans; in the application, do  
not name individuals for the Data and Safety Monitoring Board (DSMB), but  
include areas of expertise that will be tapped in forming the DSMB; contact 
the relevant IC for specific DSMB policies; 

o developing plans for any training that may be required to carry out the 
proposed trial, including, for example, training of data collectors and 
individuals who will carry out the planned intervention.

Please note that an IC may support any or all of these activities; see 
http://grants.nih.gov/grants/funding/r34.htm for contact information and 
specific IC requirements regarding the content and format of a MOP.

The Clinical Trial Planning Grant is not designed for the collection of 
preliminary data or the conduct of pilot studies to support the rationale for 
a clinical trial.  Consider other funding mechanisms to support pilot or 
feasibility studies; IC staff should be consulted for guidance.

It is expected that receipt of an R34 grant will lead to the timely 
submission of an application for support of the full-scale trial, 
incorporating the elements developed under the planning grant.  Prospective 
applicants should note that funding of a Clinical Trial Planning Grant does 
not guarantee or imply funding for a subsequent application.

MECHANISM OF SUPPORT 

This PA will use the NIH Clinical Trial Planning Grant (R34) award mechanism.  
As an applicant, you will be solely responsible for planning, directing, and 
executing the proposed project. 

You may request a project period of one year and a budget for direct costs of 
up to four $25,000 modules or $100,000 per year.
 
This PA uses just-in-time concepts.  It also uses the modular budgeting 
format (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.  This program does not 
require cost sharing as defined in the current NIH Grants Policy Statement at 
http://grants.nih.gov/grants/policy/nihgps_2001/part_i_1.htm.  

Planning Grant support is for new projects only; competing continuation 
applications will not be accepted.  

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 institutions/organizations
o Faith-based or community-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.

SPECIAL REQUIREMENTS 

Minimum Application Requirements

Future Clinical Trial:

o Rationale/Significance - Provide the rationale for the future clinical 
trial, documenting the significance and need to perform the trial.  Describe 
the potential impact of the clinical trial on health care, policy or 
practice.  

o Research Design and Methods - Enough information should be provided to 
allow reviewers to evaluate how the trial would be conducted.  

o Inclusion and Human Subjects Issues – The application must address the 
availability and population description of the requisite patient population  
and plans for recruitment outreach and follow-up.  In addition, plans for 
addressing issues and challenges regarding adherence to the proposed 
intervention protocol should be included.
Planning Period Activities:

o Justification for the Planning Grant – Explain the need for the planning 
grant.  Describe the anticipated advantages to beginning the proposed RCT 
after planning period support as contrasted to beginning the trial without 
such support.

o Investigators - The application must include a description of the 
leadership and proposed organization of the clinical trial, including 
proposed clinical sites (letters of commitment are not required at this 
stage).  This includes the ability of the Principal Investigator to bring 
together the necessary trial network.  Describe the mechanism for 
identification and selection of additional collaborators.  Describe the 
participants in the planning process, their roles in the development of the 
plan, and their experience in related studies.   

o Planning Activities - Specify how the planning period will be used.  The 
application should include the specific aims and rationale for the planning 
period, and descriptions of the activities to be carried out.  

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.  Because the participating ICs may have specific programmatic 
interests in their use of the Planning Grant, you are encouraged to contact 
relevant staff prior to submitting an application.  A listing of NIH contacts 
for the Clinical Trial Planning Grant (R34) program may be found at:  
http://grants.nih.gov/grants/funding/r34.htm. 

SUBMITTING AN APPLICATION

Applications must be prepared using the PHS 398 research grant application 
instructions and forms (rev. 5/2001).  Applications must have a Dun and 
Bradstreet (D&B;) Data Universal Numbering System (DUNS) number as the 
Universal Identifier when applying for Federal grants or cooperative 
agreements.  The DUNS number can be obtained by calling (866) 705-5711 or 
through the web site at http://www.dunandbradstreet.com/.  The DUNS number 
should be entered on line 11 of the face page of the PHS 398 form.  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.

The title , “NIH Clinical Trial Planning Grant (R34) Program,” and number of 
the program announcement (PA-04-008) must be typed on line 2 of the face page 
of the application form and the YES box must be marked

APPLICATION RECEIPT DATES:  Applications submitted in response to this 
program announcement will be accepted at the standard application deadlines, 
which are available at http://grants.nih.gov/grants/dates.htm.  Application 
deadlines are also indicated in the PHS 398 application kit.

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.

For the NIH Clinical Trial Planning Grant (R34), you may request direct costs 
in $25,000 modules, up to a total direct cost request of $100,000 for one 
year.  

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 mailed on or before the receipt 
dates described at 
http://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.  

Although there is no immediate acknowledgement of the receipt of an 
application, applicants are generally notified of the review and funding 
assignment within eight weeks.

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  in accordance with the standard NIH peer review procedures 
(http://www.csr.nih.gov/refrev.htm) will evaluate applications for scientific 
and technical merit.  In general, continuity will be maintained between the 
review of the planning grant application and the review of the eventual 
application for the proposed clinical trial.

As part of the initial merit review, all applications will:

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 written critique
o Receive a second level review by the appropriate national advisory council 
or board.

REVIEW CRITERIA

The NIH R34 is designed to support planning activities in preparation for a 
full-scale Phase III clinical trial.  These activities are primarily 
logistical, conceptual, and/or technical in nature.  They do not involve the 
collection of data typical of research-related activities supported by the 
traditional NIH research project grant.  As such, the evaluation of R34 
applications will focus on the justification of or need for the proposed 
trial along with the appropriateness of the proposed planning activities. 

The Future Clinical Trial:

(1) RATIONALE/SIGNIFICANCE

Are the significance and need to perform a future full-scale randomized 
clinical trial (RCT) adequately justified?  Would the results of the proposed 
trial be likely to affect health care policy or practice?  

(2) APPROACH

Are the conceptual framework, design, methods, and analyses, as currently 
developed, appropriate for the aim of the future RCT?  

The reviewers should consider the appropriateness of the intervention(s), 
selection of endpoints, study population (inclusion/exclusion criteria), 
randomization schemes, data management, statistical analysis, recruitment and 
retention plans, and capacity to generalize results.

(3) INVESTIGATORS  

Is the investigator appropriately trained and suited to carry out the 
proposed trial?  Is the work proposed appropriate to the experience level of 
the Principal Investigator and the research team?  Is there clear evidence of 
leadership?  Is there evidence documenting the investigators’ ability to 
organize and manage complex projects?

(4) ENVIRONMENT

Does the scientific environment in which the proposed clinical will be 
carried out contribute to the probability of success?  Will the proposed 
clinical trial take advantage of the unique features of the scientific 
environment or employ useful collaborative arrangements?  Is there evidence 
of institutional support? 

The Planning Period Activities:

(1) RATIONALE/SIGNIFICANCE

Is the planning period necessary?  Will the activities planned enhance the 
development of the future clinical trial?  Will the proposed planning period 
address major barriers to the future clinical trial? 

(2) APPROACH

Evaluate the adequacy of the activities proposed for the planning period. 
Will these activities contribute to the likelihood of timely and successful 
trial implementation?  Can these activities be accomplished in the proposed 
time period?  These activities may include, but are not limited to:  (a) 
developing/finalizing the MOP; (b) finalizing plans for addressing 
gender/minority inclusion and human subjects protection requirements; (c) 
establishing collaborative arrangements; (d) developing tools needed for data 
collection and data management; (e) developing/finalizing safety and 
monitoring plans (applicants are asked not to name individuals for the DSMB 
but only to include areas of expertise that will be tapped in forming the 
DSMB); (f) developing plans for Certification Training.

(3) INVESTIGATORS  

Is the investigator appropriately trained and suited to carry out the 
proposed planning activities?  Is the work proposed appropriate to the 
experience level of the Principal Investigator and the research team?  Is 
there clear evidence of leadership?  Is there evidence documenting the 
investigators’ ability to plan, organize, and manage complex projects?

(4) ENVIRONMENT/ORGANIZATION

Does the scientific environment in which the planning activities will take 
place contribute to the probability of success?  Are there adequate plans for 
the development of an effective organizational structure for carrying out the 
proposed trial?  Are there adequate plans for the development of an essential 
committee structure, e.g., Steering, Executive, Planning, Data and Safety 
Committees?  Does the application appropriately address issues such as the 
flow of information to and from the Coordinating Center, to the enrolling 
centers, and to the appropriate committees?

ADDITIONAL CONSIDERATIONS 

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

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 

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 at http://www.cfda.gov/ and is not subject to the 
intergovernmental review requirements of Executive Order 12372 or Health 
Systems Agency review.  Awards are made under the authorization of Sections 
301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) 
and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92.  All 
awards are subject to the terms and conditions, cost principles, and other 
considerations described in the NIH Grants Policy Statement.  The NIH Grants 
Policy Statement can be found at 
http://grants.nih.gov/grants/policy/policy.htm.

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

Department of Health and Human Services

National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892