RELEASE DATE:  July 17, 2003

PA NUMBER:  PAR-03-153 (see addendum NOT-CA-04-006)

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, the portion of this funding opportunity 
relating to these mechanisms expires on the date indicated below. 
Other mechanisms relating to this announcement will continue to be 
accepted using paper PHS 398 applications until the stated expiration 
date below, or transition to electronic application submission. 
Replacement R21 (PAR-06-091), 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

National Center for Complementary and Alternative Medicine (NCCAM)



o Purpose of the PAR
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


The National Center for Complementary and Alternative Medicine (NCCAM) 
invites high quality exploratory/developmental clinical research grant 
applications, in all domains of complementary and alternative medicine 
(CAM), in order to provide preliminary data that can be used as a 
foundation for larger clinical studies. NCCAM defines five domains of 
complementary and alternative medicine, which are alternative medical 
systems; biologically-based therapies; energy medicine; manipulative 
and body-based therapies; and mind-body medicine. These are described 
more fully in the NCCAM five-year strategic plan (2001-2005)
While many CAM therapies are in extensive use by the public, few have 
been thoroughly tested for safety and/or efficacy.  One of the primary 
missions of NCCAM is to support clinical research to test the efficacy 
of CAM therapies being used by the public. However, before investing in 
a large clinical study to test the efficacy of a CAM therapy, it is 
necessary to first provide preliminary data from pilot studies and 
small phase I and phase II trials as a basis for such a larger clinical 
study. Thus, an important goal of this exploratory/developmental 
research grant solicitation is to provide independent investigators, at 
all career levels, with the opportunity to design rigorous feasibility 
and developmental projects in the clinical area that will serve as the 
basis for planning and scientifically justifying larger clinical 
research projects to test the efficacy of CAM therapies.  If the 
results from preliminary studies submitted in response to this program 
announcement, along with published reports in the literature, support 
the performance of a larger clinical study, then a future grant 
application soliciting support for such a study can be submitted 
through the research project grant (R01) mechanism. 

Examples of types of investigations appropriate for this clinical 
exploratory/developmental 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, compliance, delivery of the 
intervention, appropriate inclusion/exclusion criteria, and 
optimization of the overall protocol design for planned clinical 

o Studies to develop and validate testing of biological and behavioral 
outcome measures in humans for use in CAM clinical research.  These 
could include development and/or validation of both the measurement 
procedure itself and delivery to subjects.  Examples include 
optimization of imaging methods and enzymatic assays; development and 
validation of behavioral assessment tools to be used in clinical 
trials, as well as development and validation of self report 
questionnaires and survey instruments to be used in CAM epidemiological 
and health services research, including health outcomes research.  

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

o Small clinical trials to determine safety, toxicity, 
pharmacokinetics, pharmacodynamics and the optimal dosage of an 
intervention as a prelude to a larger efficacy trial.  If the total 
enrollment required is greater than approximately 60 subjects, the 
applicant is strongly encouraged to contact an NCCAM Program Officer to 
discuss whether the R21 or R01 mechanism is most appropriate for the 

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 this 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.

Exploratory/developmental CAM basic and preclinical studies, including 
mechanistic studies in humans, should not be submitted in response to 
this program announcement.  Instead such studies should be submitted in 
response to the NCCAM program announcement on "Basic and Preclinical 
Research on Complementary and Alternative Medicine" (PA-02-124) 


The research objective of this PA is to encourage the submission of 
high quality, preliminary studies that will provide a solid foundation 
and justification for larger clinical studies to determine the efficacy 
of CAM therapies in all five CAM research domains.


This NCCAM PA will use the NCCAM R21 (Exploratory/Developmental 
Project) award mechanism (see  Please note 
that this is different from the NIH-wide R21 program. 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 study.

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. 

As an applicant, you will be solely responsible for planning, 
directing, and executing the proposed project. Facilities and 
Administrative (F&A) costs will be awarded based on the negotiated rate 
at the time of award.  Although the program is provided for in the 
financial plans of the NCCAM, the award of grants pursuant to the PAR 
is contingent upon the availability of funds for this purpose. 
This PAR uses just-in-time concepts.  It uses the modular budgeting 
formats (see 
This program does not require cost sharing as defined in the current 
NIH Grants Policy Statement at  


You may submit (an) application(s) if your institution has any of the 
following characteristics: 

o For-profit or non-profit organizations 
o Public or private institutions, such as universities, colleges,    
hospitals, and laboratories 
o Units of State and local governments
o Eligible agencies of the Federal government  
o Domestic or foreign
o Faith-based 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.   


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:


We encourage your inquiries concerning this Program Announcement and 
welcome the opportunity to answer questions from potential applicants.  
Inquiries may fall into three areas: scientific/research, review of 
application issues, 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 

Ms. Victoria Carper
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).  The PHS 398 is 
available at in 
an interactive format.  For further assistance contact GrantsInfo, 
Telephone (301) 710-0267, Email:

APPLICATION RECEIPT DATES: 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.

CLINICAL STUDIES (R21)APPLICATIONS: All application instructions 
outlined in the PHS 398 application kit are to be followed, along with 
the following requirements for R21 applications:  

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.

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
includes step-by-step guidance for preparing modular grants.
Additional information on modular grants is available at

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)

Two copies should also be sent 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)

APPLICATION PROCESSING: Applications must be mailed on or before the 
receipt dates described at  The CSR 
will not accept any application in response to this Program 
Announcement 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 

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 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 
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 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: 

o Significance 
o Approach 
o Innovation
o Investigator
o Environment

The scientific review group will address and consider each of these 
criteria in assigning the application's overall score, weighting them 
as appropriate for each application.  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 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.  

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? 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?

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?  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?

INNOVATION: Does the project employ novel concepts, approaches or 
methods? Are the aims original and innovative? Does the project 
challenge existing paradigms or develop new methodologies or 

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)?

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?  

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 will be assessed.  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.  


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.


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. 

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:  

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 "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 differences. 

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 

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 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 PA 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) 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 

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) - Home Page Office of Extramural
Research (OER)
  National Institutes of Health (NIH) - Home Page National Institutes of Health (NIH)
9000 Rockville Pike
Bethesda, Maryland 20892
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