Release Date:  January 10, 2000

PA NUMBER:  PA-00-041

National Center for Complementary and Alternative Medicine



The National Center for Complementary and Alternative Medicine (NCCAM) is 
committed to investigating the efficacy and safety of traditional, indigenous 
systems of medicine, including the support of well-designed, well-executed, 
definitive randomized clinical trials (RCT).   The main objective of a full-
scale, definitive RCT (Phase III trial) is to determine whether the 
intervention is more effective than that used in a control (or comparison) 
group.  Before proceeding to a large  RCT (Phase III trial), developmental 
studies are often required.  

The purpose of this Program Announcement (PA) is to support developmental 
studies to establish the methodological feasibility and strengthen the 
scientific rationale for proceeding to full-scale RCTs on the use of 
traditional, indigenous systems of medicine as practiced in the United 
States.  These studies, which should emphasize the development of appropriate 
study designs to investigate safety and efficacy, have the potential to 
identify and address difficult methodological and design issues particular to 
complex medical interventions, as well as to allow for the development of 
contextually and culturally sensitive research more closely mirroring 
practice in the United States.  These "proof of concept" trials could 
potentially, but not necessarily, lead to subsequent, large RCTs of the 
highest quality designed to test the efficacy and safety of traditional, 
indigenous systems of medicine.  Such trials could expedite acceptance of 
these medical systems in the U.S. culture by the conventional biomedical 


The Public Health Service (PHS) is committed to achieving the health 
promotion and disease prevention objectives of "Healthy People 2000," a PHS 
led national activity for setting priority areas.  "Healthy People 2000" does 
not specify a complementary and alternative medicine (CAM) objective, 
although this PA may be applied to several different priority areas within 
the “Healthy People 2000" objectives. Potential applicants may obtain a copy 
of "Healthy People 2000" at


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, Federally-
recognized Indian tribal governments, and eligible agencies of the Federal 
government.  Racial/ethnic minority individuals, women, and persons with 
disabilities are encouraged to apply as Principal Investigators.  
Collaborations between domestic and foreign sites are encouraged as are 
collaborations between complementary and alternative medical institutions and 
conventional medical institutions.


This PA will use the National Institutes of Health (NIH) research project 
grant (R01) and exploratory/developmental grant (R21) award mechanisms.  
Applicants without extensive preliminary data or prior experience with the 
NIH grant application are urged to submit applications for this PA using the 
exploratory/developmental mechanism.  On the other hand, applicants with 
preliminary findings obtained from R21 grants (or other sources) are urged to 
submit R01 applications.  Responsibility for the planning, direction, and 
execution of the proposed project will be solely that of the applicant.

For all research project grant (R01) applications requesting up to $250,000 
direct costs per year, specific application instructions have been modified 
to reflect "MODULAR GRANT" and "JUST-IN-TIME" streamlining efforts being 
examined by NIH.  Complete and detailed instructions and information on 
Modular Grant applications can be found at:  Applications that 
request more than $250,000 in any year must use the standard PHS 398 (rev. 
4/98) application instructions.

Applicants for R21s may request up to two years of support and up to a 
maximum of $125,000 direct costs per year.  R21 grants are non-renewable and 
may not be used to supplement an ongoing project.  Applicants who anticipate 
submitting an R21 grant application should review the NCCAM Web site 
(Research Grants, Applications Guidelines) at for additional 
information on this mechanism.  It is recommended that R21 applicants contact 
the Program Staff listed under INQUIRIES before submission.

Relevant applications and amended applications are welcome throughout the 
duration of this PA (three years).  Application receipt dates are the 
standard application receipt dates for investigator-initiated research as 
specified in the PHS 398 directions.  The earliest possible award date is 
September 29, 2000.



It has been estimated that two-thirds of the world’s population seek health 
care from sources other than conventional biomedicine (Huffard et al., 1992).  
While many of these individuals undoubtedly self-medicate (Eisenberg et al., 
1998), most individuals seek care from learned practitioners of traditional, 
indigenous systems of medicine.  Examples of these systems include Ayurveda, 
Kempo, Native American Medicine in all its variations, Traditional Chinese 
Medicine, Traditional Hawaiian Medicine, Unani, and Latin American folk 
systems.  Despite diverse cultures, languages, geographic locations, world 
views, and health beliefs of the peoples from which these medical systems 
originated, they have common characteristics including: (1) the use of 
complex interventions often involving multiple botanical products; (2) 
individualized diagnosis and treatment of patients; (3) an emphasis on 
disease prevention versus disease treatment; (4) maximizing the body’s 
inherent healing ability; and (5) treatment of the “whole” patient (physical, 
mental, and spiritual) versus a single pathology.

Despite the widespread use of traditional, indigenous systems of medicine, 
most research investigating these systems has stressed minimalist studies of 
one, or perhaps two, interventions  taken out of context when used to treat a 
conventional medical diagnosis.  For instance, there are hundreds of studies 
examining the efficacy of acupuncture needling, alone, for treating such 
diseases or conditions as asthma, pain, hypertension, and nausea; yet in real 
practice, acupuncture would be just one aspect of an arsenal employing, for 
instance, botanical potions, cupping, dietary changes, exercise, meditation, 
and moxibustion.  The same can be said of using yoga alone, or a single herb, 
or chanting alone.  It is readily acknowledged that inclusion of a complex 
intervention greatly complicates the design and implementation of a clinical 
trial, particularly the gold standard of clinical research, the double-blind, 
placebo-controlled, randomized trial (NIH Acupuncture Consensus Statement, 
1997; Margolin et al., 1998).  Given the intense competition for Federal 
research funding, investigators are loath to propose research that might be 
viewed as too ambitious or complicated.

It is possible to design a well-controlled, blinded trial incorporating 
individualized care as demonstrated in a recent study looking at the use of 
Traditional Chinese Medicine to treat irritable bowel syndrome (Bensoussan et 
al., 1998).  Although this three-arm study, which compared individualized 
Chinese herbal formulations, a standard Chinese herbal formulation, and a 
placebo, was less complex than a study of a healing system, it is 
illustrative of some of the methodological and design issues associated with 
individualized therapies.  This dramatically increases the complexity and 
cost of the trial.  As such, the preparation time required for these trials 
is greatly expanded and often requires extensive piloting of individual trial 
components (e.g., blinding, placebo, consist implementation of the 
intervention even if individualized, etc.) prior to initiation of the trial.

The cultural context in which systems are practiced and studied needs to be 
considered.  How systems are applied in the United States may be different 
from how they are applied in their place of origin. For example, 
curanderismo, a folk system used in Latin America, is used among many 
Hispanic-Americans, a rapidly growing population in the United States.  While 
curanderismo may enjoy wide popularity, its application may be influenced and 
transformed by the dominant Western/American culture.  Thus, arises the need 
for further demographic and effectiveness (e.g., outcomes research) studies, 
as well as for studies comparing the original system with the adapted system.

Sensitivity to the culture of a system’s origin needs to be considered from 
two perspectives:  (1) studying the system in cultural context of the 
system’s origin and (2) studying the system as adopted and adapted in other 
cultures.  For example, many people in Native American communities have 
expressed the opinion that their healing systems are fragile and are easily 
disturbed by examination, discussion, and scientific inquiry.  The knowledge 
of specific techniques of healing, sacred songs, and healing rituals is 
acquired by Native American healers directly from elder healers, from spirits 
encountered during vision quest, and as a result of initiation into secret 
societies.  Many Native Americans believe that if this knowledge is shared 
indiscriminately, especially with non-Native Americans, the spiritual power 
of the medicine may be weakened, and use of the information outside the 
communities of its origin may be perceived as contributing to cultural 
exploitation.  In addition, European-Americans’ interest in the adoption of 
Native American healing practices could lead to misrepresentation and 
dramatic transformations of Native American teachings (see previous 
paragraph).  Nevertheless, there is a large literature on the healing 
practices of certain Native American groups, and many Native American healers 
are willing to share knowledge with health care professionals.  This may 
stimulate important cross-cultural insights and prospects for collaboration 
between Native American communities and health researchers.  While Native 
American cultures and healing systems were used to illustrate cultural 
sensitivity, similar issues can be found with most systems of traditional, 
indigenous medicine.


The objective of this PA for “Traditional, Indigenous Systems of Medicine” is 
to increase the quality of clinical research evaluating the efficacy of 
traditional, indigenous systems of medicine for the treatment or prevention 
of disease and related risk factors and accompanying symptoms.  To meet this 
objective, proposed studies must successfully incorporate creative and 
realistic solutions to difficult problems in clinical research for the 
particular disease or condition under study.

The application should directly address how the grant may advance the design 
of a subsequent full-scale RCT.  In preparing for the definitive RCT, these 
studies should address specific questions that are formulated to optimize the 
design of the eventual RCT rather than address the clinical question with 
lower power.  The application should also address the intrinsic scientific 
merit of the study conducted under the pilot grant, regardless of whether a 
full-scale trial is eventually performed. 

The applicant should document that linkages exist between the complementary 
and alternative medical institutions and the conventional institutions, and 
that experienced practitioners of traditional systems collaborate in the 
design and implementation of the study.  In addition, applicants should give 
their utmost attention to the cultural context in which the systems are 
practiced in the United States and in which they intend to study them.

Applications in response to “Traditional, Indigenous Systems of Medicine” may 
include, but are not limited to: 

1.  Qualitative research, such as detailed case studies and patient and 
health care provider interviews, 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. 

2.  Studies of diagnoses including comparisons with those of other 
traditional, indigenous systems of medicine, as well as with conventional 
biomedicine; intra- and inter-practitioner reliability (diagnosis). 

3.  Studies to refine the intervention strategy including: (a) dosing, 
duration, and frequency of treatment; (b) type of treatment; © comparisons of 
different systems of medicine to treat a particular disease/condition; (d) 
intra- and inter-practitioner reliability (intervention); (e) comparisons of 
complex versus simple interventions; (f) evaluation of compliance among 
different patient populations for interventions with varying levels of 

4.  Studies to refine the control strategy including comparisons of different 
types of controls (e.g., invasive control [sham] versus non-invasive control 
[placebo, standard therapy, wait list, etc.]); validation of randomization 
and blinding procedures.

5.  Studies to define and refine the target population (e.g., 
inclusion/exclusion criteria) and develop adequate recruitment procedures.

6.  Studies to determine the feasibility of the treatment strategy and 
develop realistic protocols.

7.  Studies to establish the clinical usefulness (validity, reliability, 
responsiveness and utility) and appropriateness of commonly used assessment 
procedures, especially quality-of-life measures, as well as psychosocial, 
functional, and physiological measures; to construct and validate culturally 
sensitive data collection instruments; to design and pilot outcome measures 
consistent with the tenets of traditional, indigenous systems of medicine and 
comparisons of these outcome measures to those commonly used by conventional 

8.  Collection of preliminary data for establishing measures of efficacy (to 
establish the anticipated benefit of the treatment) and safety (to establish 
approximate rates of complications)  for subsequent sample size calculations.  
(Note: Generally this will be the last in a progression of specific aims.)


It is the policy of the NIH that women and members of minority groups and 
their subpopulations must be included in all NIH supported biomedical and 
behavioral research projects involving human subjects, unless a clear and 
compelling rationale and justification is provided 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 
"NIH Guidelines For Inclusion of Women and Minorities as Subjects in Clinical 
Research," which have been published in the Federal Register of March 28, 
1994 (FR 59 14508-14513) and in the NIH Guide for Grants and Contracts, Vol. 
23, No. 11, March 18, 1994 available on the web at the following URL address:  The research 
plan should describe the composition of the proposed study population in 
terms of gender and racial/ethnic group, and provide a rationale for 
selection of such subjects.  Such a plan should contain a description of the 
proposed outreach programs for recruiting women and minorities as 


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.  Therefore, proposals for research 
involving human subjects must include a description of plans for including 
children.  If children will be excluded from the research, the application 
must present an acceptable justification for the exclusion.
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 

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.


Applications are to be submitted on the grant application form PHS 398 (rev. 
4/98) and will be accepted at the standard application deadlines as indicated 
in the application kit.  The PHS 398 application instructions and forms are 
available on the NIH grants Web site at  Applicants are encouraged to access 
the application instructions and forms via the Internet.  Application kits 
are available at most institutional offices of sponsored research and may be 
obtained from the Division of Extramural Outreach and Information Resources, 
National Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 
20892-7910, telephone 301/710-0267, email:  

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 Institute staff.  The research grant application form PHS 398 (rev. 4/98) 
is to be used in applying for these grants, with the modifications noted in 

Applicants wishing to submit R21 applications are encouraged to contact the 
Program Staff listed under INQUIRIES prior to submission.  The NCCAM has 
guidelines for the preparation and submission of these applications as 
outlined in R21 APPLICATION GUIDELINES below.  Applications for R21 grants 
that do not meet the requirements as outlined in these guidelines will not be 
accepted by the NCCAM.  


o For R21 applications, Direct Costs are limited to a maximum of $125,000 per 
year for a maximum of two years.  Direct Costs requested for the proposed 
period may not exceed $250,000.  Direct costs should be presented in 
increments of $25,000.  Total Costs should equal the modular Direct costs 
plus Facilities and Administrative (F&A) costs.  The award is nonrenewable 
and may not be used to supplement an ongoing project.

o Do not exceed a total of fifteen pages for Items a-d in the Research Plan.  
Tables and figures are included in the page limitation.  Applications that 
exceed the page limitation or NIH requirements for type size and margins 
(refer to PHS 398 application for details) will be returned to the applicant 
without further consideration.  The fifteen-page limitation does not include 
Items e-I (Human Subjects, Vertebrate Animals, Literature Cited, Consortia, 
and Consultants). 

o Color illustrations or original photographs may be included in an Appendix.  
These are allowed only if there are copies of black and white figures 
appearing in the body of the application.  No other appendix material is 

o Applications not following the above instructions will be returned to the 
applicant without review.


Modular Grant applications will request Direct Costs in $25,000 modules, up 
to a total Direct Cost request of $250,000 per year for R01s and $125,000 per 
year for R21s.  Applications that request more than $250,000 direct costs in 
any year must follow the traditional PHS 398 application instructions.  The 
total Direct Costs must be requested  in accordance with the  program 
guidelines and  the modifications made to the standard  PHS 398 application 
instructions described below:

PHS 398
o FACE PAGE: Items 7a and 7b should be completed, indicating Direct Costs (in 
$25,000 increments up to a maximum of $250,000) and Total Costs [Modular 
Total Direct plus Facilities and Administrative  (F&A) costs] for the initial 
budget period Items 8a and 8b should be completed indicating the Direct and 
Total Costs for the entire proposed period of support.

of the PHS 398.  It is not required and will not be accepted with the 

categorical budget table on Form Page 5 of the PHS 398.  It is not required 
and will not be accepted with the application.

o NARRATIVE BUDGET JUSTIFICATION - Prepare a Modular Grant Budget Narrative 
page. (See for 
sample pages.)  At the top of the page, enter the total Direct Costs 
requested for each year.  This is not a Form page.

o Under Personnel, List key project personnel, including their names, percent 
of effort, and roles on the project.  No individual salary information should 
be provided.  However, the applicant should use the NIH appropriation 
language salary cap and the NIH policy for graduate student compensation in 
developing the budget request.

For Consortium/Contractual costs, provide an estimate of Total Costs (direct 
plus Facilities and Administrative) for each year, each rounded to the 
nearest $1,000.  List the individuals/organizations with whom consortium or 
contractual arrangements have been made, the percent effort of key personnel, 
and the role on the project.  Indicate whether the collaborating institution 
is foreign or domestic.  The Total Cost for a consortium/contractual 
arrangement is included in the overall requested modular Direct Cost amount.  
Include the Letter of Intent to establish a consortium.

Provide an additional narrative budget justification for any variation in the 
number of modules requested.

o BIOGRAPHICAL SKETCH - The Biographical Sketch provides information used by  
reviewers in the assessment of each individual's qualifications for a 
specific role in the proposed project, as well as to evaluate the overall 
qualifications of the research team.  A biographical sketch is required for 
all key personnel, following the instructions below.  No more than three 
pages may be used for each person.  A sample biographical sketch may be 
viewed at:

- Complete the educational block at the top of the form page;
- List position(s) and any honors;
- Provide information, including overall goals and responsibilities, on 
research projects ongoing or completed during the last three years.
- List selected peer-reviewed publications, with full citations;

o CHECKLIST - This page should be completed and submitted with the 
application.  If the F&A rate agreement has been established, indicate the 
type of agreement and the date.  All appropriate exclusions must be applied 
in the calculation of the F&A costs for the initial budget period and all 
future budget years.

o The applicant should provide the name and phone number of the individual to 
contact concerning fiscal and administrative issues if additional information 
is necessary following the initial review. 

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 five signed photocopies in one package to:

BETHESDA, MD 20892-7710
BETHESDA, MD 20817 (for express/courier service)

Applications will be accepted on the standard application receipt dates for 
investigator-initiated research as indicated in the PHS 398 directions.  The 
Center for Scientific Review (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 substantial 
revisions of applications already reviewed, but such applications must 
include an introduction addressing the previous critique.


Upon receipt, applications will be reviewed for completeness by CSR staff.  
Incomplete applications will be returned to applicants without further 
consideration.  Applications that are complete will be evaluated for 
scientific and technical merit in accordance with the standard NIH peer 
review procedures.  R01 applications will be reviewed by a Special Emphasis 
Panel (SEP) convened by CSR, while R21 applications will be reviewed by an 
NCCAM SEP.  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 applications under review, will be discussed, assigned a priority 
score, and receive a second level review by the NCCAM 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.

Because the exploratory grant mechanism (R21) is designed to support 
innovative ideas, preliminary data as evidence of feasibility of the project 
are not required.  However, the applicant does have the responsibility for 
developing a sound research plan approach, including appropriate statistical 
analyses and sample size calculations where appropriate.   Innovation of the 
project and potential significance of the proposed research will be major 
considerations in the evaluation of this mechanism.

(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? 

(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? 

(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)? 

(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 

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 

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.


The following will be considered in making funding decisions:  Quality of the 
proposed project as determined by peer review, availability of funds, and 
program priority.


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

Direct inquiries regarding programmatic issues to:

Marguerite Evans, M.S., R.D.
National Center for Complementary and Alternative Medicine
Building 31, Room 5B58
Bethesda, MD 20892
Telephone: (301) 402-5860
FAX: (301) 402-4741

Direct inquiries regarding fiscal matters to:

Suzanne White*
Grants Operations Branch
National Heart, Lung, and Blood Institute
National Institutes of Health
Two Rockledge Center, Room 7150, MSC 7926
6701 Rockledge Drive
Bethesda, MD 20892-7926
Telephone:  301-435-0170
FAX:  301-480-3310

* Note: NHLBI is the Grants Management Service Center for the NCCAM.


This program is described in the Catalog of Federal Domestic Assistance No. 
93.213.  Awards are made under authorization of the Public Health Service 
Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 
USC 241 and 285) 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, and 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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