CENTERS FOR COMPLEMENTARY AND ALTERNATIVE MEDICINE RESEARCH 

Release Date:  November 29, 1999

RFA:  AT-00-001

National Center for Complementary and Alternative Medicine
National Cancer Institute
National Heart, Lung, and Blood Institute


Letter of Intent Receipt Date:    January 7, 2000
Application Information Meeting:  January 21, 2000
Application Receipt Date:         March 14, 2000

PURPOSE

Despite the broad use of complementary and alternative medicine (CAM) 
treatments (Eisenberg et al., 1998) there is a relative paucity of data 
available to demonstrate convincingly the safety, efficacy, effectiveness 
and mechanisms of these CAM practices.  A similar conclusion was reached in 
a 1990 report on unconventional cancer treatments by the U.S. Office of 
Technology Assessment.  This report urges a systematic analysis of 
alternative treatments and their effect on major disease, health and 
wellness (U.S. Office of Technology Assessment, OTA-H-405, 1990, p.225).  

In order to promote high-quality research of CAM, the National Center for 
Complementary and Alternative Medicine (NCCAM), the National Cancer 
Institute (NCI), and the National Heart, Lung, and Blood Institute (NHLBI) 
invite applications for Centers for CAM Research using the P50 Specialized 
Center grant mechanism.  Such Centers will provide the resources necessary 
for the rigorous scientific investigation of CAM.  It is expected that 
research conducted at these Centers will examine the potential efficacy, 
effectiveness, safety and validity of CAM practices, as well as the 
physiological or psychological mechanisms underlying or contributing to the 
effects of these practices.

HEALTHY PEOPLE 2000

The Public Health Service is committed to achieving the health promotion and 
disease prevention objectives of "Healthy People 2000," an initiative for 
setting national health policy and priorities.  Although "Healthy People 
2000" does not specify a CAM objective, this RFA reflects several different 
priority areas within the Healthy People 2000 objectives, such as cancer and 
chronic disabling conditions.


Applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock 
No. 017-001-00474-0 or Summary Report: Stock No. 017-001-00473-1) through 
the Superintendent of Documents, Government Printing Office, Washington, 
D.C.  20402-9325  (Telephone: 202-783-3238).  Applicants may also obtain a 
copy of "Healthy People 2000" at http://odphp.osophs.dhhs.gov/pubs/hp2000/.

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic for-profit and nonprofit 
organizations, public and private, such as universities, colleges, 
hospitals, laboratories, units of State and local governments, and eligible 
agencies of the Federal government.  Applications may include foreign 
components, but foreign organizations are not eligible to apply.  To be 
considered, applicant organizations must have:  (1) a minimum of three 
independent investigators who together represent experience in both basic 
and clinical research; (2) access to a patient care and service facility; 
and (3) the capacity to design, conduct, and evaluate three to four research 
projects that include at least one basic (mechanistic) study and one 
clinical study; Phase III trials (see ASPECIAL REQUIREMENTS - Research 
Projects for definition) and surveys will not be considered.  

Although applications must be submitted from one institution, they may 
include subcontracted collaborative scientific and clinical arrangements 
with scientists from other institutions, including foreign institutions, as 
long as these arrangements are clearly delineated, and formally and 
officially confirmed by signed statements from the responsible officials of 
each institution.  However, a full institutional commitment must come from 
the parent institution receiving the award.

NIH staff (See INQUIRIES below) should be consulted if there are questions 
regarding any of the above requirements or exclusions.

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

MECHANISM OF SUPPORT

Support of this program will be through the NIH P50 Specialized Center Grant 
mechanism.  This mechanism supports the full range of research and 
development from basic to clinical and intervention studies.  P50 Centers 
assemble critical masses of basic and clinical scientists to work together 
collaboratively.  The essential characteristics of a P50 Center include:  
(1) a strong, focused scientific program encompassing basic and clinical 
research that will have a clear impact on human disease and associated 
quality-of-life or disability issues; (2) a strong, innovative program to 
establish and monitor developmental and feasibility studies that can respond 
quickly to new research opportunities; (3) a strong career development 
program to develop and expand the scientific cadre of investigators 
dedicated to research on a specific disease entity or biomedical problem; 
(4) shared core facilities that increase the functional capacity of the 
Center; and (5) a willingness and commitment to work with other Centers and 
scientists in order to maximize research progress.  


Applicants will be responsible for the planning, direction, and execution of 
the proposed Center program.  Awards will be administered under the NIH 
Grants Policy Statement. 

FUNDS AVAILABLE

NIH anticipates making up to three awards with an estimated commitment from 
the NCCAM of $4.5 million total costs for the initial year’s funding.  In 
addition, NCI and NHLBI may provide support to other meritorious 
applications that fit their program objectives.  Funding levels are 
dependent on the receipt of applications of high technical and scientific 
merit, and the continued availability of funds.  Because the nature and 
scope of applications may vary, it is anticipated that the award size will 
vary.  Although this program is provided for in the financial plans of 
NCCAM, the award of grants pursuant to this RFA is contingent upon the 
availability of funds.

Applicants may request three to five years of support.  Applications 
submitted in response to this RFA are limited to $1.5 million total costs 
(direct costs and Facilities and Administration costs) in the first year of 
the award.  Future increases are limited to three percent per year.

RESEARCH OBJECTIVES

1.  Background

The demographics, prevalence, and patterns of use of CAM in the United 
States have been described (Eisenberg et al., 1998).  The most relevant 
findings are the following: a) extrapolation to the population of the United 
States suggests that Americans made approximately 629 million visits to 
providers of CAM therapy during 1997; and b) expenditures associated with 
CAM therapies exceeds non-reimbursed expenses incurred for all 
hospitalizations in the United States.  These findings indicate that CAM 
occupies a larger role in the health care of U.S. citizens than previously 
understood.  Despite this broad use, there are, in general, insufficient 
scientific data that address safety and efficacy questions for CAM 
therapies.  

The NCCAM currently supports eight NIH P50 Centers for CAM Research.  The 
Centers are designed to identify and evaluate promising CAM approaches by 
establishing mechanisms for investigators to have their research ideas 
reviewed, developed and executed in a scientifically rigorous manner.  It is 
expected that work begun at the Centers will provide the basis for 
subsequent investigator-initiated research grant applications to the NIH. 

2.  Goals

A.  General:


This RFA seeks to expand the current NIH Centers for CAM Research program 
with the addition of up to three new P50 Centers.  Centers for CAM Research 
will provide focal points for initiating and maintaining state-of-the-art 
research that will contribute to improved treatment and prevention of human 
disease, or that address the risk factors, rehabilitation or quality-of-life 
issues associated with these conditions.  Centers will not only be expected 
to conduct a wide spectrum of research activities, but also to contribute 
significantly to the development of core research resources, career 
development of new investigators, and the expansion of the research base 
through collaborative research with scientists and clinicians (both CAM and 
conventional) in other institutions locally and nationwide.

Developmental research funds provide support for innovative developmental 
projects that take maximum advantage of new research opportunities, or that 
establish the methodological feasibility and strengthen the scientific 
rationale for proceeding to trials on the use of CAM.  This provides a 
flexible means for responding quickly to new research opportunities.  Career 
development of new and established investigators will generate a cadre of 
scientists who could leave the Center with research experience to develop 
independent CAM research programs.

In order to facilitate achievement of Center program goals, it is expected 
that each center will develop specialized multi-user resource activities, 
such as basic or clinical laboratories, database and data management 
facilities, and/or biostatistical cores.

Requirements for all Centers are annual meetings of the Principal 
Investigators (and other key Center staff) coordinated by the NCCAM.  The 
purposes of these meetings are to share scientific information, assess 
scientific progress, identify new research opportunities, and establish 
priorities that will accelerate the study of CAM.

B.  Specific Objectives:

Specific objectives for the current Center applications include:

o  Performing research related to CAM treatments in one of the listed 
research theme areas (see RESEARCH ACTIVITIES below); 
o  Investigating basic mechanisms of CAM therapeutic and diagnostic 
interventions;
o  Conducting feasibility studies or Phase I and II trials of sufficiently 
developed CAM interventions to facilitate the design and eventual conduct of 
 randomized, masked, controlled trials; 
o  Acting as an institutional focus for training in research methodology, 
bioethics, biostatistics, clinical trial design, epidemiology, health 
services studies and basic laboratory methods that relate to CAM.  This 
could be satisfied by concurrent training supported by other NIH funding 
mechanisms (e.g., K30, T32);
o  Provide plans for establishing an advisory committee (see ASPECIAL 
REQUIREMENTS@ for AC composition) to provide program direction and advice to 
the Principal Investigator of the Center, including prioritization of 
developmental and feasibility studies, and utilization of core facilities;
o  Developing a mechanism for scientific/technical merit review of 
developmental or feasibility studies from investigators;
o  Developing workshops, seminars, etc. for training purposes; and
o  Establishing a system to identify and support basic and clinical 
investigators in their career development, including promotions and tenure.


RESEARCH ACTIVITIES

The overall goals and objectives of the Center’s research agenda for the 
requested funding period should be explicitly stated in the application.  
This should include identification of the Center’s research direction, as 
well as specific disease entities and target populations to be studied.

1.  Research Theme Areas
Applicants should develop a multidisciplinary research focus that 
incorporates basic and clinical research in one of the two following themes. 
The application should describe how the Research Theme will be integrated 
with one or more of the high priority CAM Program Areas (item 2 below).

A.  Asthma:
A number of CAM therapies have been reported to be of use in the treatment 
of asthma.  However, controlled clinical trials are often lacking, and the 
mechanisms of action are not clearly understood.  Further studies are needed 
to assess the efficacy of CAM remedies in allergic disease and asthma.  
Since the symptoms and clinical findings in chronic asthma fluctuate over 
time and can often appear to improve with placebo, larger, well-designed, 
double-blind, placebo-controlled trials appear warranted, as well as careful 
assessment of objective and immunological endpoints.  Although Phase III 
trials will not be considered for this RFA, applicants are encouraged to 
address methodological and other design issues necessary for the 
development, design, and eventual conduct of such trials.  Moreover, the 
mechanism of action of these alternative therapies needs to be investigated 
and defined.   

Examples of some potential areas of interest include the following:

Phase II trials are needed to evaluate the efficacy and physiological 
correlates of hypnotic suggestion in allergic disease and asthma, and the 
pathophysiological pathway mediating the effects.

Phase II trials are needed to evaluate the efficacy and physiological 
correlates of acupuncture in the treatment of asthma.  The mechanisms 
mediating the effects of acupuncture on asthma require clarification.  

Phase II trials are necessary to assess the efficacy and physiological 
correlates of homeopathy in asthma, and pharmacologic studies are necessary 
to identify mechanisms of action.

Herbal remedies, administered as powders or teas, have been popular.  
Controlled clinical trials are needed to assess their effectiveness and 
physiological consequences, and pharmacologic studies are needed to 
determine their potential interactive effect with standard asthma 
medications.  


Ayurvedic medicine is a complex system of health care consisting of numerous 
components that include transcendental meditation, herbal preparations, 
pulse diagnosis, and yoga.  Studies of an Ayurvedic approach to asthma 
management, as well as studies of its separate components would be of 
considerable interest.

The rigorous study of breathing techniques (e.g., yoga breathing exercises 
such as pranayama; and diaphragmatic breathing) in asthma management would 
enhance understanding of asthma self-management techniques and their 
potential role in therapy.

B.  Cancer:  

Centers are sought to conduct and promote basic and clinical research on CAM 
approaches for the treatment of cancer.  Any of the relevant areas of CAM 
listed below (see item 2 below: CAM Program Areas) could be included.  The 
rationale for the choice of a particular CAM modality, as well as the reason 
for its selection instead of other CAM or non-CAM approaches, should be 
provided.  Research topics may include, but are not limited to: 1) 
prevention; 2) modification of disease course; 3) supportive care or symptom 
management (including pain control); 4) management of chemotherapy, surgery 
or radiation induced side-effects; and 5) issues involved in improving 
quality of life of cancer survivors.  Multidisciplinary approaches to study 
the molecular and cellular basis of the mechanism of action of CAM therapies 
in cancer are encouraged, as are collaborations with investigators doing 
basic research in cancer.  The establishment and use of animal and other 
models to study biological effect and mechanism of action of CAM approaches 
and agents is encouraged.

Examples of some potential areas of interest include but are not limited to 
the following:

Phase I/II clinical trials of botanicals.  The conduct of these trials 
should be supported by some preliminary evidence of efficacy.  This evidence 
might include, for example, patterns of traditional use and case series, as 
well as preclinical or pilot clinical data against cancer or for palliation 
of symptoms or side-effects.

Unconventional adjuvant nutritional approaches that either augment the 
therapeutic effect of conventional therapies or ameliorate side effects.  
These approaches should be consistent with the description of CAM modalities 
listed below (see item 2: CAM Program Areas).

Elucidation and systematic evaluation of the mechanisms of action and 
potential clinical significance of drug-botanical interactions.

Comparative analyses of therapeutic indexes of whole botanical products 
versus specific isolated compounds from these products with known anticancer 
activity.

Studies of the potential effect of mind-body modalities (e.g., relaxation, 
imagery, meditation, psychosocial support groups, or psychotherapy) on 
physiologic endpoints (e.g., immune parameters) or disease parameters 
(response rate to conventional therapy, disease-free survival, overall 
survival).  Mental health assessments are not allowed as primary outcome 
measures.


Cancer chemoprevention studies that are oriented to unpurified, whole 
natural substances (e.g., soya products, herbal extracts, etc.).  

Studies to evaluate the potential interaction of antioxidant compounds and 
conventional chemotherapy and/or radiation therapy. 

2.  CAM Program Areas: 

For the purpose of this RFA, investigators must include modalities from the 
following broad program areas in CAM:

o  Alternative Medical Systems (e.g., oriental medicine, Ayurvedic, 
homeopathy, naturopathy); 

o  Manipulative and Body-based Systems (e.g., chiropractic, osteopathic, 
massage therapy or unconventional applications of integrated conventional 
and physical therapies); 

o  Biofield (e.g., energy healing, intentional effects on living systems); 

o  Bioelectromagnetics (e.g., diagnostic and therapeutic application of 
electromagnetic (EM) fields including pulsed EM fields, magnetic fields, 
Direct Current (DC) fields, artificial light therapy, etc.  Note:  This 
category does not include the study of electromagnetic fields as risk 
factors for disease);

o  Pharmacologic Therapies (e.g., metabolic therapies and immunoaugmentative 
therapies as used by CAM practitioners or the public such as 
antineoplastons, Coley’s toxin, Enzyme therapies, the Livingston-Wheeler 
system, the Revici system or 714-X) 

o  Herbal Medicine (Note:  This category DOES NOT include the study or 
isolation of active ingredients from herbal preparations except where 
identification and standardization of optimal whole product are the specific 
aim -- e.g., optimal ratio of glycosides and terpenoids in Ginkgo biloba -- 
or comparisons are being made to the whole product);

(NOTE:  Studies incorporating the following three CAM program areas MUST 
focus on the more unconventional uses of these approaches and MUST involve 
collaborations with expert practitioners of these approaches.  In addition 
compelling arguments that the interventions fall outside the purview of 
conventional medicine MUST be provided in the application.  It is strongly 
recommended that applicants interested in these three areas should contact 
one of the program officers listed under INQUIRIES prior to submission)


o  Mind-Body Medicine:  This RFA is limited to those mind-body approaches 
that address unconventional explanatory models with a focus on their NOVEL 
scientific and clinical use, or that are usually used by the public or 
practitioners outside of a conventional medicine setting (e.g., 
transcendental meditation, imagery, hypnosis, biofeedback, music therapy, 
yoga, spirituality, biological effects of consciousness).  Mind-body 
approaches that are relatively integrated into conventional medicine (e.g., 
patient education, psychotherapy, cognitive-behavioral approaches, 
mindfulness meditation, etc.) will NOT be considered unless physiologic 
endpoints (e.g., immune parameters) or disease parameters (response rate to 
conventional therapy, disease-free survival, overall survival) are the 
primary outcome measures; 

o  Orthomolecular Medicine - This category includes the use of products, 
many of which may be used as nutritional and food supplements (e.g., ultra-
high doses of magnesium, Co-enzyme Q, carnitine, melatonin,  vitamins) when 
investigated for therapeutic or preventive purposes.  These products are 
usually used in combinations and at very high doses (5-10 fold) well above 
the Recommended Daily Allowance (RDA) when such RDAs have been defined.  For 
the purposes of this RFA, orthomolecular medicine may be integrated within 
comprehensive lifestyle changes based on indigenous or non-orthodox systems 
of medicine (e.g., Ornish or Pritikin programs).
 
SPECIAL REQUIREMENTS

Applications must include ALL the following elements to be considered 
responsive to the RFA. Unresponsive application will not be reviewed:

1.  A strong institutional commitment:  

An institution receiving this award should incorporate the Center high 
within its institutional priorities.  The institution should demonstrate a 
strong commitment to the program's stability and success.  The application 
must provide a plan that addresses how the institutional commitment will be 
established and sustained, how it will maintain accountability for promoting 
scientific progress, and how the Center research effort will be given a high 
priority within the institution relative to other research efforts.  The 
institution should demonstrate commitment to the scientific value of the 
proposed research and willingness to consider this research as support for 
tenure and promotion.  This institutional commitment may be in the form of 
commitments to recruit scientific talent, provision of discretionary 
resources to the Center director, faculty appointments for Center 
investigators, assignment of clinical and research space, cost sharing of 
resources, or other ways to be proposed by the applicant.

2.  A qualified principal investigator (PI):  

A leader should be selected as principal investigator who can oversee and 
conduct planning activities and provide direction to the Center.  The PI 
should have documented experience both as a scientist and as administrator 
of a research program.  The PI is required to commit a minimum of 30% effort 
and has to be primary investigator on one (but not more than two) 
subprojects.

3.  Linkages to the CAM community:

The applicant needs to document that linkages to the relevant CAM 
communities exist and that certified or licensed CAM practitioners provide 
appropriate input to, and participate in, Center research projects.  

4.  A substantial patient population:  

The grant application must demonstrate and document access to a patient 
population that is able to participate in, and can benefit from, the 
innovative research activities of the Center.

5.  Research projects:  

Each Center application should include three to four research projects.  At 
least three projects are required to start in year-01 of the award.  Start 
of the fourth project can be postponed until the second or third year of the 
award.  Each of these projects must request at least three, but not more 
than five, years of support in the application.  At least three of the 
submitted projects that begin in year-01 of the award must be judged 
meritorious by the peer-review panel for the application to meet the minimal 
requirements of a P50 Center.  Failure to meet this requirement will remove 
the application from funding consideration.  Subproject principal 
investigators are each required to commit at least 15% time to these  
projects.

The research must be oriented toward the most critically needed areas of CAM 
research, and toward collaborative activities that address new innovative 
possibilities in CAM research.  Whenever feasible, collaborations with 
appropriate certified, licensed or otherwise qualified CAM practitioners are 
required.  Projects should be interactive with each other whenever possible. 
At least one of the approved subprojects has to be a basic (mechanistic) 
study and one has to be a clinical study other than a Phase III trial 
(defined below).  Applications that do not meet this basic requirement will 
be ineligible for funding.  While  epidemiological and health services 
studies that can be completed in five years are permissible, surveys WILL 
NOT be accepted under this RFA.  

For the purpose of this RFA, a Phase III trial is defined as:  a broadly 
based prospective investigation usually involving a substantial number of 
human subjects either at a single site or at multiple sites.  The primary 
objective of such trials is to evaluate an experimental intervention in 
comparison with a standard or control intervention, or to compare two or 
more existing treatments.  In Phase III trials, the primary endpoint is 
usually a significant change in some clinical outcome.  The definition 
includes interventions given for disease prevention, prophylaxis, diagnosis, 
or therapy. 

Research 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:  
http://grants.nih.gov/grants/guide/notice-files/not98-084.html).  In 
addition, NCCAM requires that all masked clinical trials, regardless of 
size, establish an independent data and safety monitoring board.  Funds 
should be budgeted for these activities.  They should not duplicate internal 
review and monitoring systems that are already in place at the institution. 
 


Collaborative arrangements within the Center, within the parent institution 
and with other institutions are encouraged.  All collaborations with 
scientists outside the immediate Center should be documented with 
appropriate letters of commitment as applicable.  Collaborations with other 
institutions, including foreign institutions, may involve subcontracting 
arrangements but an award will be made to one institution only; that 
institution is expected to demonstrate the full institutional commitment 
noted in item 1 above (Strong Institutional Commitment).

6.  Resource Cores:  

A core is defined as a resource shared by multiple investigators that should 
enhance research productivity and increase the functional capacity of the 
Center.  Subproject utilization of these cores is essential and needs to be 
specified in the application.  At a minimum, the Center is required to have 
an administrative core that is responsible for the day-to-day administrative 
details, as well as program coordination and ongoing evaluation of the 
Center.  Also falling within the administrative core would be the Career 
Development Program, the Developmental Research Program and the Advisory 
Committee (items # 7-9 below).  Other cores that benefit the specific 
research activities of the Center may be added as appropriate.  Examples of 
cores would include data management cores, biostatistical cores, clinical 
trial coordinating cores, and laboratory-based cores.  These resources 
should not duplicate resources already available to Center investigators.  
However, fee-for-service cores (i.e., Center use of existing facilities) are 
acceptable with adequate justification.

7.  Career Development:  

The Center should demonstrate a consistent commitment to career development. 
Up to $150,000 (total costs) of the first year budget may be dedicated to 
the salaries and research activities of investigators who wish to pursue 
careers investigating alternative medicine.  Candidates are expected to 
devote full-time to research and appropriate supplemental training.  
Recruitment should encourage the participation of CAM practitioners (with, 
or without previous research experience) and of qualified women and 
minorities where possible.  To this end, each applicant should include a 
clear policy and plans for recruiting minorities and women and scientists 
with disabilities.  The Center application should propose the number of 
slots available, and describe the criteria for candidate eligibility, and 
the selection process.  It is expected that the Advisory Committee (item #9) 
will be involved in this selection process.  Also, the application should 
indicate prospective mentors who are already in place at the proposed 
Center, briefly describe their research programs, and describe CAM 
activities that contribute to the environment for career development (e.g., 
existing training grants, other career development mechanisms and relevant 
programs).  Highly experienced CAM practitioners should be among the 
prospective mentors.  Prospective mentors should document their knowledge of 
CAM. 

Career development research projects should adhere to the list of CAM 
program areas appearing in this announcement.  Rebudgeting of Center funds 
to, or from, the career development program will only be permitted with 
prior approval by NIH staff. 

8.  Developmental Research Program:  


In each year of the award, Centers will allocate a minimum of $100,000 
(total costs) to developmental and feasibility projects that explore 
innovative ideas, or that establish the methodological feasibility and 
strengthen the scientific rationale for proceeding to phase III trials on 
the use of particular CAM modalities.  It is important that Centers use 
developmental funds to stimulate projects that take maximum advantage of new 
research opportunities.  These projects may be collaborative among 
scientists within one or more Centers, or with scientists outside the Center 
environment.  Developmental research projects should adhere to the list of 
CAM program areas appearing in this announcement.  Rebudgeting of Center 
funds to, or from, the developmental program will only be permitted with 
prior NIH staff approval. 

It is not expected or required that feasibility and developmental projects 
will be identified by the time of submission.  However, the Center 
application should include an institutional review process for supporting 
projects that represent the most innovative ideas and that are likely to 
have the greatest impact on CAM research.  These funds are intended to 
remain flexible and to support feasibility and developmental studies of a 
limited duration (two years or less), rather than the duration of the entire 
grant period.  The expectation is that successful feasibility studies will 
become fully developed projects within the Center, or supported through 
other research funding mechanisms, e.g., R01, R21.  NIH staff must be 
notified before the start of each developmental project, such that human and 
animal subject assurances, and Advisory Committee approval can be verified.

9.  Advisory Committee:

Scientific and administrative Center oversight is charged to a 
multidisciplinary Advisory Committee (AC) to be appointed on a rotating 
basis by the Principal Investigator.  The AC shall not be chaired by the 
Principal Investigator who will serve in an ex officio capacity only.  The 
AC should meet at least twice a year and minutes of the meeting should be 
kept.  These minutes shall be made available to NIH staff within 6 weeks of 
the meeting.  The AC should consist of at least nine individuals familiar 
with the Center's research activities.  The AC shall include both a 
biostatistician and epidemiologist to assist with the review of projects and 
the optimal approaches for subsequent data analysis.  The AC MUST have 
representation from the scientific, practitioner and lay communities in BOTH 
CAM and conventional medicine.  Members SHOULD NOT be identified until after 
an award is made.  However, the process by which members will be chosen 
should be specified.

Besides prioritizing developmental research projects submitted by Center or, 
if applicable, Consortium investigators, the AC should periodically review 
Center operations to ensure that Center resources, especially core 
facilities, are used for the most scientifically worthy projects.  The AC 
should take an active role in encouraging younger faculty members to perform 
research and assist them in applying appropriate research concepts and 
methods.  The AC should also be involved in the selection of candidates for 
the career development program.  Support for the AC should be explicitly 
budgeted and justified.

10.  Annual Meeting of Centers:  


Centers will be expected to participate in annual meetings with NCCAM and 
Institute staff to share positive and negative results with other Centers, 
share materials, assess progress, identify new research opportunities, and 
establish interactions, research priorities and collaborations that will 
maximize the impact of the research.  Travel funds for the Principal 
Investigator and selected Project Investigators should be budgeted for this 
purpose.  This may include Project Investigators from other institutions who 
are actively collaborating with Centers investigators.  It is expected that 
the meeting locations will rotate among the active NCCAM Centers. 

11.  Investigational New Drug (or Device) applications (INDs):

It is the sole responsibility of the applicant to obtain all necessary 
clearances from the Food and Drug Administration as required.  It is 
expected that applicants will have started the IND process, if required, 
well before submission.  In addition, applicants are strongly encouraged to 
consult their local Institutional Review Boards (IRBs) concerning IND status 
and the IRB approval process.

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of the NIH that women and members of minority groups and 
their 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:  
http://grants.nih.gov/grants/guide/notice-files/not94-100.html

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of NIH that children (i.e., individuals under the age of 
21) must be included in all human subjects research, conducted or supported 
by the NIH, unless there are scientific and ethical reasons not to include 
them.  This policy applies to all initial (Type 1) applications submitted 
for receipt dates after October 1, 1998.

All investigators proposing research involving human subjects should read 
the "NIH Policy and Guidelines on the Inclusion of Children as Participants 
in Research Involving Human Subjects" that was published in the NIH Guide 
for Grants and Contracts, March 6, 1998, and is available at the following 
URL address: http://grants.nih.gov/grants/guide/notice-files/not98-024.html


Investigators also may obtain copies of these policies from the program 
staff listed under INQUIRIES.  Program staff may also provide additional 
relevant information concerning the policy.

LETTER OF INTENT

Applicants are asked to submit, by January 7, 2000, a letter of intent that 
includes the number and title of this RFA; the name, address, and telephone 
number of the Principal Investigator; the identities of other key personnel 
and participating organizations or institutions, if any; the title of the 
overall proposal.

Although a letter of intent is not required, is not binding, and does not 
enter into the review of applications, the information that it contains will 
be especially helpful to the NIH in planning for the review of applications, 
estimating the potential workload, and avoiding conflicts of interest in the 
review process.  

Mail/Fax letters of intent to:
Dr. Neal B. West
Program Officer
National Center for Complementary and Alternative Medicine
Building 31/ Room 5B58
Bethesda, MD  20892-2182
Telephone:  (301) 402-5867
FAX:  (301) 402-4741
Email:  westn@od.nih.gov

APPLICATION INFORMATION MEETING

In order to improve the quality of applications submitted in response to 
this RFA, as well as to give potential applicants the opportunity to clarify 
any issues or questions concerning the RFA, a meeting will be held.  At the 
meeting, potential applicants will have the opportunity to discuss 
application concepts and outlines of proposed applications with NIH staff 
and other relevant scientific experts.

The meeting will be held at, or in close proximity to NIH on Friday, January 
21, 2000.  Although a registration fee is not associated with this meeting, 
pre-registration is encouraged.  NIH has not allocated funds to pay for 
attendee travel to the workshop; all travel costs are the responsibility of 
the attendee.  Additional information on the meeting, as well as 
registration materials can be obtained from the NCCAM Program Officer listed 
under “INQUIRIES.”  A summary of the presentations and issues discussed at 
the meeting will be made available through the NCCAM Web-site about one week 
after the meeting.  Hard copies will be available for those applicants 
without Web access.


APPLICATION PROCEDURES


The research grant application form PHS 398 (rev. 4/98) is to be used in  
applying for these grants.  These forms are available at most institutional 
offices of sponsored research and from the Division of Extramural Outreach 
and Information Resources, National Institutes of Health, 6701 Rockledge 
Drive, MSC 7910, Bethesda, MD 20892-7910, telephone (301) 435-0714, Email:  
GrantsInfo@nih.gov.  The application is also available at 
http://grants.nih.gov/grants/funding/phs398/phs398.html.

The total page limitation of the application, as specified in the 
instructions of the Form PHS 398, does not apply to this RFA.  Instead, the 
following stipulations apply:  

Table of Contents:
Disregard the Table of Contents page from PHS 398 and, instead, write a 
Table of Contents appropriate for this Center grant application.  The Table 
of Contents should list all items for which funding is sought, in addition 
to each specific activity required of the Center as outlined under “Special 
Requirements.”  Specifically list the locations of the checklist and the 
various supporting documents, including bibliographic sketches and other 
support pages.  Each page of the application should be numbered 
consecutively.  This numbering should be reflected in the Table of Contents.

Budget:
For preparation of the budget, the applicant should present a composite 
budget for all years of support.  This composite budget should include the 
direct costs for each required Center activity (e.g., Advisory Committee, 
Developmental Research Program, Career Development, etc.), as well as each 
research project and each core facility.  This composite budget should be in 
tabular format, with each budget year being listed in a separate column and 
each Center activity, core or subproject being listed in a separate row.  
Budget Form pages 4 and 5 of PHS Form 398 should be completed for each 
Center activity, core or subproject listed in the composite budget.  These 
pages should be clearly labeled as to which Center activity, subproject or 
core they address.   In addition, the utilization relationships between the 
projects and the core(s) should be presented in a table of direct costs, 
with the columns being the projects and the rows being the core(s).

NOTE:  A signed, completed face page (PHS 398, page A) must be provided for 
each subcontract associated with the application, as well as for the 
applicant institution.
 
Bibliographic Sketches:
Bibliographic sketches and other support pages are required for all proposed 
Center personnel and for all investigators associated with the mandatory 
research projects and cores.  These pages should be in alphabetical order 
following the budget pages and should not be duplicated in the descriptions 
of individual component projects and cores.  

Research Projects and Core Facilities:
Each research project and each core facility is allowed 25 pages, excluding 
bibliographies.  


NOTE:  The section on the Administrative Core is to include descriptions and 
justifications of the Advisory Committee, the Developmental Research 
Program, the Career Development Program, and the Center’s overall goals and 
objectives; this combined section is limited to 25 pages.

Descriptions of the research projects and the core facilities should follow 
the PHS 398 format, section 9 (Research Plan) with the addition that each 
project and each core should have its own title page and abstract.  The 
title page should list all investigators (or core staff) and their 
associated institutions, as well as the direct and total costs for the 
project for each year of the award.  In addition, each project must provide 
a detailed description of core utilization, and each core must document its 
contributions to Center research projects.  Each of the six points listed 
under Human Subjects in the PHS 398 application must be addressed for those 
studies involving human subjects.  Although not required at the time of the 
application, Institutional Review Board and Institutional Animal Care and 
Use Committee approval must be obtained for each project listed, if 
appropriate, within 60 days of submission.  

The RFA label available in the PHS 398 application package must be affixed 
to the bottom of the face page of the application.  The affixed label should 
clearly display the RFA number:  AT-00-001.  Failure to use this label could 
result in delayed processing of the application.  In addition, the RFA title 
and number must be typed on line 2 of the face page of the application form 
and the YES box must be marked.

The sample RFA label available at: 
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf has been modified to 
allow for this change.  Please note this is in pdf format.

Submit a typewritten, signed original of the application, four signed 
photocopies, and the completed checklist in one package to:

Center for Scientific Review
National Institutes of Health
Suite 1040
6701 Rockledge Dr. MSC 7710
Bethesda, MD  20892-7710

Applicants who prefer to use express mail or courier service should change 
the zip code above to 20817.

At the time of submission, mail one additional complete copy of the 
application to the following RFA program administrator:

Dr. Richard L. Nahin
National Center for Complementary
and Alternative Medicine
9000 Rockville Pike
Bldg. 31, Room 5B-58
Bethesda, MD  20892-2182


Applications must be received by March 14, 2000.  If an application is 
received after the date, it will be returned to the applicant without 
review.  The CSR will not accept any application that is essentially the 
same as one previously reviewed.  This does not preclude the submission of a 
substantial revision of an application already reviewed, but such an 
application must follow the guidance in the PHS Form 398 application 
instructions for preparation of revised applications, including an 
introduction addressing the previous critique.

Individual subprojects from the P50 Center application may be simultaneously 
submitted to the Center for Scientific Review (CSR) as investigator-
initiated applications (e.g., R01); this fact must be clearly documented in 
the Center application under “pending support.”  If, following review, both 
the Center application and the R01 application are found to be in the 
fundable range, the subproject investigator must relinquish the R01 and will 
not have the option to withdraw from the Center grant.  This is an NIH 
policy intended to preserve the scientific integrity of a multi-project 
grant, which may be seriously compromised if a strong component project(s) 
is removed from the program.  Investigators wishing to participate in a 
multi-project grant must be aware of this policy before making a commitment 
to the Principal Investigator and awarding institution.

REVIEW CONSIDERATIONS

Applications that are complete and responsive to the RFA will be evaluated 
for scientific and technical merit by an appropriate peer review group 
convened by the NCCAM in accordance with the NIH peer review procedures.  As 
part of the initial merit review, all applications will receive a written 
critique and undergo a process, streamlined review, 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 appropriate National 
Advisory Council.

Review Criteria
All applications submitted in response to this RFA will be reviewed 
according to the following review criteria.  Reviewers will consider these 
criteria when assigning a single overall score to each application.  This 
single score should reflect their judgement that the proposed center will 
have a substantial impact on the pursuit of its goals.

Major factors to be considered in evaluation of applications will include:

1.  How the proposed Center combines basic and clinical research with the 
research theme and CAM program areas.

2.  Incorporation of appropriate CAM expertise, including certified or 
licensed practitioners.

3.  The integration of appropriate CAM and conventional expertise.  

4.  Scientific merit of each proposed subproject.  Each research project 
will be reviewed according to the explicitly-stated set of five review 
criteria recently adapted by the NIH:


(a)  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?

(b)  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?

(c)  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 technologies?
 
(d)  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)?

(e)  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.

Each subproject will receive a priority score.  The score reflects not only 
the feasibility of the project and the adequacy of the experimental design, 
but also its relevance to the overall goals of the Center, the appropriate 
utilization of Center resources (e.g., cores), and the integration of CAM 
practitioners.  

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

In addition, the adequacy of the proposed protection for humans, animals or 
the environment will be evaluated to the extent they may be adversely 
affected by the project proposed in the application.

5.  Scientific merit of combining the component parts into a Center (e.g., 
the whole is greater than the sum of its parts);

6.  Technical merit and justification of each core unit;

7.  Adequacy of facilities to perform the proposed research, including 
laboratory and clinical facilities, instrumentation, and data management 
systems, when needed;

8.  Adequacy of plans for interaction among investigators, and the 
integration of the various projects and core units;

9.  Qualifications, experience and commitment of the PI and his/her ability 
to devote time and effort to provide effective leadership;


10.  Scientific and administrative structure, including internal and 
external procedures for monitoring and evaluating the proposed research and 
for providing ongoing quality control and scientific review;

11.  Institutional commitment to the program, and the appropriateness of 
resources and policies for the administration of a Center;

12.  The proposed organization and activities of the Advisory Committee will 
be evaluated, including the process to prioritize developmental/feasibility 
research proposals and the process to choose Committee members after an 
award is made;

13.  Career Development Program including adequacy of the process for 
selecting candidates for career development and plans for recruiting 
minority and women candidates; and adequacy of the individuals available to 
serve as possible mentors of career development candidates;

14.  Developmental Research Program including adequacy of the proposed 
process for continuously reviewing and funding projects for their quality, 
innovativeness and potential impact; and potential of the program to 
generate innovative, high-quality projects on a consistent basis.

15.  Demonstration of an effective relationship among Consortium 
institutions, if any, including documentation of current relationships, as 
well as the functions, commitments and contributions each Consortium member 
will bring to the proposed Center;

16.  The appropriateness of the budget for the proposed program and its 
individual components will be considered independently of the factors 
indicated above.

A single numerical priority score will be assigned to the application as a 
whole.  Although primary emphasis will be placed on scientific merit, 
innovativeness, and past progress (where applicable), significant 
consideration will be given to administrative structure, multidisciplinary 
interactions including those with CAM practitioners, potential for impacting 
on the disease/condition in question, and institutional commitment.

AWARD AND REPORTING REQUIREMENTS

Applications recommended by the NIH Initial Review Group and by the 
appropriate national advisory council will be considered for award based on: 
1) scientific and technical merit as determined by peer review; 2) program 
relevance and balance; 3) availability of funds; and 4) responsiveness to 
the goals and objectives of the RFA. 

Letter of Intent Due:  January 7, 2000 
Application Information Meeting:  January 21, 2000
Application Receipt Date:  March 14, 2000
Review by Advisory Council:  August/September 2000
Anticipated Award Date:  September 2000


INQUIRIES

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

Inquiries regarding programmatic issues should be directed to:

Dr. Neal B. West
Program Officer
National Center for Complementary and Alternative Medicine
Building 31/ Room 5B58
Bethesda, MD  20892-2182
Telephone:  (301) 402-5867
FAX:  (301) 402-4741
Email:  westn@od.nih.gov


Virginia S. Taggart, M.P.H 
Division of Lung Diseases (Asthma)
National Heart, Lung, and Blood Institute
National Institutes of Health
Two Rockledge Center , Suite 10018
6701 Rockledge Dr. MSC 7952
Bethesda, MD  20892-7952
Phone:  (301) 435-0202
Fax:  301-480-3557
Email:  TaggartV@gwgate.nhlbi.nih.gov;

Dr. Jeffrey D. White
Division of Clinical Sciences
National Cancer Institute
National Institutes of Health
9000 Rockville Pike
Bldg. 10, Room 3B38
Bethesda, MD  20892
Phone: (301) 402-2912
Fax: (301) 402-1001
Email:  jdwhite@helix.nih.gov

Inquiries regarding budget issues should be directed to:
Suzanne White*
Grants Operations Branch
National Heart, Lung and Blood Institute
National Institutes of Health
Two Rockledge Center, Suite 7154, MSC 7926
6701 Rockledge Drive

Bethesda, MD 20892-7952
Phone:  301-435-0170
Fax:  301-480-3310
Email: WhiteS@gwgate.nhlbi.nih.gov

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


AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance Nos. 
93.213 (NCCAM, 93.396 (NCI), and 93.837 and 93.838 (NHLBI).  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 PHS grants policies and Federal Regulations 42 FR 52 and 
45 CFR Part 74.  This program is not subject to the intergovernmental review 
requirements of Executive Order 12372 or Health Systems Agency review.

The Public Health Service (PHS) strongly encourages all grant 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, 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.


Return to Volume Index

Return to NIH Guide Main Index


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
  Department of Health and Human Services (HHS) - Home Page Department of Health
and Human Services (HHS)
  USA.gov - Government Made Easy


Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files.