RELEASE DATE:  April 6, 2004

PA NUMBER:  PAR-04-087

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 using 
the electronic SF424 (R&R) application. Accordingly, this funding opportunity 
expires on the date indicated below. A replacement R21 (PAR-06-090) funding 
opportunity announcement has been issued for the submission date of June 1, 2006 
and submission dates thereafter.

See NOT-OD-06-048 for information on May 1, 2006 Submission Date for AIDS and 
AIDS-related R03 and R21 Applications. 

EXPIRATION DATE:  March 2, 2006

Department of Health and Human Services (DHHS)

National Institutes of Health (NIH) 

National Center for Complementary and Alternative Medicine (NCCAM)



o Purpose of the PAR
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 Supplementary Instructions
o Peer Review Process
o Review Criteria
o Award Criteria
o Required Federal Citations


The 80 General Clinical Research Centers (GCRC’s) supported by the 
National Center for Research Resources (NCRR) are described by Congress 
as "critical" resources for providing optimal venues and essential 
infrastructure for patient-oriented research.  The GCRC’s are expected 
to be a driving force for future biomedical research, technologies and 
resources, and are in the forefront of clinical research training.  
They may also play a prominent part in implementation of the NIH 
Roadmap on translational research.

Historically, some of the first complementary and alternative medicine 
(CAM) clinical research supported by NIH was through GCRC’s in the 
1970s and 1980s.  Such support has continued to the present day.  
However, the support is limited both in the number of projects funded 
(out of the thousands of GCRC projects funded) and the numbers of 
GCRC’s involved.

The purpose of this PAR, General Clinical Research Center Complementary 
and Alternative Medicine Research Program, is to solicit projects from 
investigators poised to use GCRC resources to pursue clinical research 
investigating CAM.  As used by the U.S. public, CAM is made up of many 
heterogeneous systems of medicine as well as numerous stand-alone 
therapies (for examples, see 
Research on the entire range of CAM is encouraged by this PAR.  It will 
be important for each applicant to consider how the development of a 
CAM research program will impact on their communities, placing special 
emphasis, when possible, on minority and underserved populations in the 


The primary goal of this PAR is to stimulate submission of high 
quality, preliminary studies of CAM at GCRC’s nation-wide.  These 
studies will provide solid foundation and justification for larger 
clinical studies.  In addition, this initiative is expected to 
facilitate and expand the evaluation of CAM treatments for the wide 
array of diseases and conditions currently being evaluated at GCRC’s, 
as well as to explore mechanisms of action of promising CAM therapies. 

Other goals are to attract GCRC investigators to the field of CAM 
research and to provide a stable scientific environment where CAM 
practitioners can actively participate in rigorous research.

Examples of types of investigations appropriate for this  program 
announcement include, but are not limited to the following:

o Feasibility studies to test and optimize parameters such as accrual 
rates, acceptance of randomization, adherence, delivery of the 
intervention, appropriate inclusion/exclusion criteria, and 
optimization of the overall protocol design for planned clinical trials 
of CAM interventions.

o Studies to develop and validate biological and behavioral outcome 
measures in humans for use in CAM clinical research.  Examples include 
optimization of imaging methods and enzymatic assays; development and 
validation of behavioral assessment tools to be used in clinical 
trials; development and validation of self-report questionnaires and 
survey instruments, including the use of new computerized interview 
assessment technologies (e.g., ACASI), to be used in CAM 
epidemiological and health services research.  

o Studies to determine if the effect sizes described in the literature 
or clinically significant effect sizes can be achieved in CAM research.

o Small clinical trials to determine safety, toxicity, 
pharmacokinetics, pharmacodynamics, and the optimal dosage of 
biologically-based interventions, as well as the optimal dose for 
mind/body and other CAM interventions as a prelude to a larger efficacy 

o Studies that explore mechanisms of action of CAM interventions, such 
as investigations of the immunomodulatory, neurophysiological, 
neuroendocrinological, and/or biochemical pathways that may mediate CAM 

o Qualitative research, such as detailed case studies and patient and 
health care provider interviews or ethnographic/ethnobotanical studies, 
to describe diagnostic and treatment approaches; to explore patient and 
health-care provider preferences, beliefs and attitudes; and to 
investigate the relevance of those approaches to future clinical 

Preliminary data are not required as a prerequisite for submission in 
response to this announcement, because part of the goal of this program 
announcement is to produce the preliminary data as the first necessary 
step in the process required for planning a larger clinical study.  
However, a clear rationale for the study must be presented.  A rigorous 
project design is required as well.  A thorough summary of the 
published literature that justifies initiating the specific clinical 
project proposed must be presented in the grant application.  In 
addition, applicants should describe their future research plans as 
they relate to how the results of this exploratory/developmental 
research will lead to a larger clinical study.  Furthermore, applicants 
should provide justification regarding why it is important to perform 
the subsequent larger clinical study in the context of the present 
knowledge of clinical research on CAM therapies. 

Large Phase II trials or Phase III trials, with the goal of determining 
efficacy of a CAM therapy, should not be submitted in response to this 
announcement.  Such proposals should be submitted as research project 
(R01) grants.


This PAR will use the NCCAM NIH R21 award mechanism (Exploratory/ 
Developmental Project) award mechanism (see PAR-03-153) .  Note 
that this is different from the NIH-wide R21 program.  As an applicant, 
you will be solely responsible for planning, directing, and executing 
the proposed project.  

The NCCAM R21 award is an exploratory/developmental research grant for 
support of pilot and feasibility CAM research designed to provide 
investigators with an opportunity to produce preliminary data in 
support of a larger project that may be submitted in the future as a 
research project (R01) grant application.  The NIH-wide R21 program 
emphasizes research characterized by novel ideas that may differ 
substantially from current thinking in a field and thus bear 
considerable risk of failure.  While novel ideas are certainly welcome 
in response to this specific program announcement, the emphasis is more 
on providing solid data to support justification for a future clinical 

For R21 grants awarded through this program announcement, applicants 
may request a project period of up to three years with a combined 
budget for direct costs of up $400,000 for the three-year period.  The 
budget request should be tailored to the needs of the project. For 
example, you may request $100,000 in the first year, $200,000 in the 
second year and $100,000 in the third year.  However, no more than 
$250,000 direct costs may be requested in any single year. 

These grants may not be renewed.  However, two revisions of a 
previously reviewed exploratory/developmental R21 grant may be 
submitted as defined in NIH Policy at Competing 
continuation of projects developed under this grant mechanism should be 
submitted through the R01 research grant mechanism.

This PAR uses just-in-time concepts.  It also uses the modular 
budgeting format. (see  
Specifically, if you are submitting an application with direct costs in 
each year of $250,000 or less, use the modular budget format.  This 
program does not require cost sharing as defined in the current NIH 
Grants Policy Statement at 


You may submit an application 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


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.


Letters of support stating that GCRC resources are available for the 
proposed research are required from the GCRC Principal Investigator and 
Program Director at the time of application.  Applications without 
these letters will not be considered for support.

In addition to the required Federal Citations listed below related to 
clinical research, applicants submitting applications in response to 
this announcement should also follow the NCCAM Policy on Terms of Award 
for Clinical Trials where applicable.

If the clinical study will involve a natural product, then the 
applicant must follow the NCCAM Policy Announcement on Quality of 
Natural Products: 

If the proposed research is investigating practitioner-based CAM (e.g., 
acupuncture, chiropractic, massage therapy, etc.), qualified CAM 
practitioners must be included as active members of the research team.


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 For scientific/research questions:

Please contact the appropriate NCCAM program officer listed on this 

o Direct your questions about review of applications to:

Martin Goldrosen, Ph.D.
Chief, Office of Scientific Review
National Center for Complementary and Alternative Medicine
National Institutes of Health
6707 Democracy Blvd., Suite 401
Bethesda, MD 20892 (for express/courier service use 20817)
Telephone: (301) 594 2014
Fax: (301) 480 2419

o Direct your questions about financial or grants management matters 

Mr. George Tucker
Grants Management Branch
National Center for Complementary and Alternative Medicine
6707 Democracy Blvd., Suite 401
Bethesda, MD  20892 (for express/courier service use 20817)
Fax: 301 480 2419


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  The DUNS number should be entered on 
line 11 of the face page of the PHS 398 form. The PHS 398 is available 
at in an 
interactive format.  For further assistance contact GrantsInfo, 
Telephone (301) 710-0267, Email:

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


All application instructions outlined in the PHS 398 application kit 
are to be followed, along with the following requirements for R21 

1.  R21 applications will use the "MODULAR GRANT" and "JUST-IN-TIME" 
concepts, with direct costs requested in $25,000 modules.  Applicants 
may request a project period of up to three years with a combined 
budget for direct costs of up $400,000 for the three-year period.  For 
example, you may request $100,000 in the first year, $200,000 in the 
second year and $100,000 in the third year.  The request should be 
tailored to the needs of your project.  However, no more than $250,000 
may be requested in any single year.

2.  Although preliminary data are not required for an R21 application, 
they may be included.

3.  Sections a-d of the Research Plan of the R21 application may not 
exceed 20 pages, including tables and figures.  

4.  R21 appendix materials should be limited, as is consistent with the 
exploratory nature of the R21 mechanism, and should not be used to 
circumvent the page limit for the research plan.  Copies of appendix 
material will only be provided to the primary reviewers of the 
application and will not be reproduced for wider distribution among 
reviewers.  The following materials may be included in the appendix: 

o  Up to five publications, including manuscripts (submitted or 
accepted for publication), abstracts, patents, or other printed 
materials directly relevant to the project.  These may be stapled as 

o  Surveys, questionnaires, and data collection instruments.  These may 
be stapled as sets.

o  Original glossy photographs or color images of gels, micrographs, 
etc., provided that a photocopy (may be reduced in size) is also 
included within the 20-page limit of items a-d of the research plan.


Applications submitted in response to this program announcement will be 
accepted at the standard application deadlines, which are available at  Application deadlines are also 
indicated in the PHS 398 application kit.


Applications requesting up to $250,000 per year in direct costs must be 
submitted in a modular budget grant format.  The modular budget 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 includes step-
by-step guidance for preparing modular grants.  Additional information 
on modular grants is available at


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)


Applications must be mailed on or before the receipt dates described at  The CSR 
will not accept any application in response to this PAR 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 
unfunded version of an application already reviewed, but such 
application must include an Introduction addressing the previous 

Although there is no immediate acknowledgement of the receipt of an 
application, applicants are generally notified of the review and 
funding assignment within 8 weeks.


Applications submitted for this PA will be assigned on the basis of 
established PHS referral guidelines.  An appropriate scientific review 
group within NCCAM convened in accordance with the standard NIH peer 
review procedures ( ) will evaluate 
applications for scientific and technical merit.  

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 
o Receive a written critique
o Receive a second level review by the National Advisory Council for 
Complementary and Alternative Medicine.  


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 evaluate 
application in order to judge the likelihood that the proposed research 
will have a substantial impact on the pursuit of these goals.  The 
scientific review group will address and consider each of the following 
criteria in assigning the application’s overall score, weighting them 
as appropriate for each application.

o Significance 
o Approach 
o Innovation
o Investigator
o Environment
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.

In addition, preliminary data are not required as a prerequisite for 
submission in response to this PAR, because part of the goal of this 
announcement is to produce the preliminary data as the first necessary 
step in the process required for planning a larger clinical study.  

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? Specifically, does the applicant describe how 
the results of this exploratory/development research will lead to the 
development of a larger clinical study? Does the applicant provide 
justification as to why it is important to perform this larger clinical 
study in the context of the present knowledge of clinical research on 
CAM therapies?

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?  Does the applicant provide a thorough summary of 
the published literature that justifies initiating this specific 
clinical project?  Is a clear rationale for the study presented?  Is a 
rigorous study design described?

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?

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)?  Are CAM 
practitioners adequately integrated into the research team when 

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?  What advantage is there to doing the work on 
the GCRC?  Does the GCRC have expertise in the required areas to 
facilitate the research?  Is there evidence indicating that the 
investigators will have access to GCRC facilities?

ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, the 
following items will be considered in the determination of scientific 
merit and the priority score:

human subjects and protections from research risk relating to their 
participation in the proposed research will be assessed. (See criteria 
included in the section on Federal Citations, below).
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 in the 
sections on Federal Citations, below).

are to be used in the project, the five items described under Section f 
of the PHS 398 research grant application instructions (rev. 5/2001) 
will be assessed.  


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

Applications submitted in response to a PAR 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


HUMAN SUBJECTS PROTECTION:  Federal regulations (45CFR46) require that 
applications and proposals involving human subjects must be evaluated 
with reference to the risks to the subjects, the adequacy of protection 
against these risks, the potential benefits of the research to the 
subjects and others, and the importance of the knowledge gained or to 
be gained. 

DATA AND SAFETY MONITORING PLAN:   Data and safety monitoring is 
required for all types of clinical trials, including physiologic, 
toxicity, and dose-finding studies (phase I); efficacy studies (phase 
II); efficacy, effectiveness and comparative trials (phase III).  The 
establishment of data and safety monitoring boards (DSMBs) is required 
for multi-site clinical trials involving interventions that entail 
potential risk to the participants.   (NIH Policy for Data and Safety 
Monitoring, NIH Guide for Grants and Contracts, June 12, 1998:  

SHARING RESEARCH DATA:  Starting with the October 1, 2003 receipt date, 
investigators submitting an NIH application seeking $500,000 or more in 
direct costs in any single year are expected to include a plan for data 
sharing or state why this is not possible.  Investigators should 
seek guidance from their institutions, on issues related to 
institutional policies, local IRB rules, as well as local, state and 
Federal laws and regulations, including the Privacy Rule. Reviewers 
will consider the data sharing plan but will not factor the plan into 
the determination of the scientific merit or the priority score.

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 

All investigators proposing clinical research should read the "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 
(; a 
complete copy of the updated Guidelines are available at
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 

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, 

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

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

HUMAN EMBRYONIC STEM CELLS (hESC):  Criteria for federal funding of 
research on hESCs can be found at 
and at  
Only research using hESC lines that are registered in the 
NIH Human Embryonic Stem Cell Registry will be eligible for Federal 
funding (see   It is the responsibility of the 
applicant to provide, in the project description and elsewhere in the 
application as appropriate, the official NIH identifier(s) for the hESC 
line(s)to be used in the proposed research.  Applications that do not 
provide this information will be returned without review. 

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

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.

The Department of Health and Human Services (DHHS) issued final 
modification to the “Standards for Privacy of Individually Identifiable 
Health Information”, the “Privacy Rule,” on August 14, 2002.  The 
Privacy Rule is a federal regulation under the Health Insurance 
Portability and Accountability Act (HIPAA) of 1996 that governs the 
protection of individually identifiable health information, and is 
administered and enforced by the DHHS Office for Civil Rights (OCR). 
Those who must comply with the Privacy Rule (classified under the Rule 
as “covered entities”) must do so by April 14, 2003 (with the exception 
of small health plans which have an extra year to comply).  

Decisions about applicability and implementation of the Privacy Rule 
reside with the researcher and his/her institution. The OCR website 
( provides information on the Privacy Rule, 
including a complete Regulation Text and a set of decision tools on “Am 
I a covered entity?”  Information on the impact of the HIPAA Privacy 
Rule on NIH processes involving the review, funding, and progress 
monitoring of grants, cooperative agreements, and research contracts 
can be found at

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 

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 RFA is related to one or more of the priority areas. 
Potential applicants may obtain a copy of "Healthy People 2010" at

AUTHORITY AND REGULATIONS:  This program is described in the Catalog of 
Federal Domestic Assistance at 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)(cite appropriate authorizations) and 
under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92 (cite 
relevant regulations). 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 (also cite 
other relevant policies)

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

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