CENTERS FOR COMPLEMENTARY AND ALTERNATIVE MEDICINE RESEARCH

Release Date:  September 24, 1998

RFA:  OD-98-008

P.T.

Office of Alternative Medicine
National Cancer Institute
National Heart, Lung and Blood Institute
National Institute of Arthritis and Musculoskeletal and Skin Disorders
National Institute of Dental Research
National Institute of Neurological Disorders and Stroke
National Institute on Aging

Letter of Intent Receipt Date:  December 11, 1998
Application Receipt Date:  January 22, 1999

PURPOSE

Despite the broad use of complementary and alternative medicine (CAM) treatments
(Eisenberg et al., New England J. Med. 328: 246-352, 1993) 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 Office of Alternative
Medicine (OAM), the National Cancer Institute (NCI), the National Heart, Lung and
Blood Institute (NHLBI), the National Institute of Arthritis and Musculoskeletal
and Skin Disorders (NIAMS), the National Institute of Dental Research (NIDR),
National Institute of Neurological Disorders and Stroke (NINDS), and the National
Institute on Aging (NIA) invite applications for Centers for CAM Research using
the Specialized Center (P50) 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 these practices.

HEALTHY PEOPLE 2000

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.  This PA, Centers for Complementary and
Alternative Medicine Research, is related to the priority areas of cancer,
chronic disabling conditions, heart disease, infectious diseases, nutrition, oral
health and stroke.  Potential 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, DC 20402-9325 (telephone 202-512-1800).

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic for-profit and non-profit
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, an applicant
organization 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) three to six research projects that
include at least one basic (mechanistic) study and one clinical study; Phase III
trials and surveys will not be considered.

Although applications must be submitted from one institution, they may include
subcontracted collaborative scientific 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 program staff listed under INQUIRIES 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 Specialized Center Grant (P50)
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 PHS Grants Policy
Statement.  It is expected that another RFA similar to this one will be issued
in FY 1999.

FUNDS AVAILABLE

The NIH anticipates making six to eight awards with an estimated commitment from
the OAM of $10.5 million total costs for the initial year's funding.  In
addition, NCI, NHLBI, NIA, NIAMS, NIDR, and NINDS may provide support to
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.

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

Funding in response to this RFA is dependent upon the receipt of a sufficient
number of applications of high scientific merit.  Although this program is
provided for in the financial plans of OAM, the award of grants pursuant to this
RFA is contingent upon the availability of funds.

RESEARCH OBJECTIVES

1.  Background

The demographics, prevalence, and patterns of use of CAM in the United States
have been described (Eisenberg et al., New England J. Med. 328: 246-352, 1993). 
The most relevant findings are the following:  a) extrapolation to the population
of the United States suggests that Americans made approximately 425 million
visits to providers of CAM therapy during 1990; and b) expenditures associated
with CAM therapies appear similar to 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 OAM currently supports three 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 eight 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, or
biostatistical cores.

Requirements for all Centers are annual meetings coordinated by the NIH Office
of Alternative Medicine (OAM).  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 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 for the purpose
of developing randomized, 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;
o  Providing a plan for establishing an advisory committee 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 investigators in their career
development;

Competing continuation (renewal) applications must demonstrate progress in the
above areas as indicated by scientific progress, success in the initiation of
competitively-supported research (both federal and non- federal sources of
support can be applied to this criterion), the development of new CAM
investigators, and collaborations with conventional scientists and CAM
practitioners.

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 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).

A.  Arthritis:
The overall goal of the Center will be to conduct and promote basic and clinical
research on CAM approaches for the treatment of arthritis and related diseases,
with emphasis on rheumatoid arthritis and osteoarthritis.  Any of the relevant
areas of CAM listed below (item 2:  CAM Program Areas) could be included.  The
rationale for the choice of a particular CAM modality, as well as the reason for
selection above other CAM modalities, should be provided.  Selected CAM
approaches may target prevention, modification of disease course, amelioration
of clinical activity-symptoms (including pain), prevention of disability or
rehabilitation.  Multidisciplinary approaches to study the molecular and cellular
basis of the mechanism of action of CAM therapies in arthritis are encouraged,
as are collaborations with investigators doing basic research in arthritis.  The
establishment and use of animal and other models to study biological effect and
mechanism of action of CAM approaches and agents are encouraged.

B.  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 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:

Controlled studies are needed to evaluate the effectiveness of hypnotic
suggestion in allergic disease and asthma and the pathophysiological pathway
mediating the effects.

Controlled clinical trials are needed to evaluate the effectiveness of
acupuncture in the treatment of asthma.  The mechanisms mediating the effects of
acupuncture on asthma require clarification.

Controlled clinical trails are necessary to assess the efficacy of homeopathy in
asthma, and pharmacologic studies are necessary to identify the chemical agents
and mechanisms of action.

Preliminary reports suggest that salt reduction and magnesium supplementation may
have value in reducing asthmatic symptoms.  Clinical trials appear warranted.

Herbal remedies, administered as powders or teas, have been popular.  Controlled
clinical trials are needed to assess their effectiveness, 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
aspranayama; and diaphragmatic breathing) in asthma management would enhance
understanding of asthma self-management techniques and their potential role in
therapy.

C.  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 (item 2:  CAM Program Areas) could be included.  The rationale for the
choice of a particular CAM modality, as well as the reason for selection above
other CAM or  non-CAM approaches, should be provided.  Research topics may target
prevention, modification of disease course, supportive care or symptom management
(including pain control), management of chemotherapy-, surgery- or radiation-
induced side effects  and 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.

D.  Craniofacial and Oral Disorders:
Craniofacial and oral diseases, and the approaches used by the public or
professionals to improve oral health, provides unique opportunities for
evaluating CAM interventions.  The relative accessibility of the oral cavity and
craniofacial structures allows non-invasive assessment of changes in tissue
status or function, and thus, can be utilized to strengthen research on effects
of CAM interventions.

Diseases and disorders that manifest in craniofacial and oral tissues include
craniofacial anomalies, such as cleft lift and palate, oral and nasopharyngeal
cancers; salivary and immunological disorders including Sjogrens Syndrome;
aphthous ulcers and other soft tissue lesions; oral concomitants of HIV including
oral candidiasis; acute dental pain associated with injury, infections, or
treatments; and conditions such as TMJ, degenerative changes or masticatory
muscle conditions which produce chronic pain or oral dysfunctions (jaw "locking"
or difficulties in chewing), as well as two widely prevalent infectious diseases
- dental caries and periodontal diseases.

Examples of some potential areas of interest include the following:

Studies evaluating the impact of CAM interventions (e.g., acupuncture, hypnosis)
on pain or tissue repair following oral surgeries or dental procedures.

Studies on the use of CAM interventions to prevent, reduce, or manage persisting
pain in oral-craniofacial tissues (e.g., TMJ and muscle pain)

Studies evaluating herbal, nutritional, pharmacological or other CAM therapies
used to prevent or treat congenital or acquired craniofacial defects, oral
diseases, or oral symptoms (e.g.,  preventing or managing oral candidiasis in
HIV-positive individuals)

Studies evaluating the effects and properties  (e.g., anti- microbial, anti-
biofilm) of "chewing sticks," which are traditionally used for personal oral
hygiene in many areas of the world

Studies to assess whether the use of bioelectromagnetic fields enhances
prevention or treatment of infectious oral diseases involving oral microbial
biofilms (e.g., dental caries, periodontal diseases)

E.  Diseases or Disabilities Associated with the Elderly: Centers are sought to
examine the use and effectiveness of alternative and complementary treatments
that keep older people healthy, as well as help them manage their existing
chronic illnesses and disabilities.  There is special interest in health
promotion and self management strategies, as well as specific treatments for age-
related conditions and problems such as Alzheimer's disease, sleep, urinary
incontinence, sexual dysfunction, problems associated with mobility and frailty,
older women's health issues (including menopause), caregiving stresses, etc. 
More biological, clinical, and psychosocial research is needed on older people's
use of, and effectiveness of, dietary supplements, herbal products, over-the-
counter CAM medications, and other CAM treatments.  Different types of studies
are needed including:  basic studies on factors affecting how older people and
their caregivers make decisions about treatment utilization, research on the
biological processes underlying treatment effectiveness, and applied studies
examining medical and quality-of-life outcomes of the different CAM strategies.

F.  HIV/AIDS:
Centers are sought to conduct and promote basic and clinical research on CAM
approaches for the treatment and prevention of human immunodeficiency virus (HIV)
and acquired immunodeficiency syndrome (AIDS) and their sequelae, including
opportunistic infections.  Areas of interest include, but are not limited to: 
(1) treatment of primary HIV disease, (2) interventions designed to prevent
transmission of HIV; (3) prophylaxis and treatment of opportunistic infections;
and (4) the clinical management of symptoms and syndromes associated with
HIV/AIDS, including pain, cachexia, nausea, fatigue and depression.

G.  Neurological Disorders and Stroke
For most of the more serious common neurological disorders and stroke there are
few treatments of demonstrated efficacy.  Many neurological disorders are
chronic, gradually progressive, and may cause persistent disability for years. 
Alternative therapies are desperately sought by patients.

Because of the complexity of brain function, clinical evaluation of the benefits
of any therapy for chronic neurological disease is difficult to carry out. 
Applicants interested in CAM interventions for neurological disorders and stroke
should design studies able to produce convincing pre-clinical evidence of the
scientific basis of  the intervention or design pilot clinical trials able to 
provide information required for subsequent large Phase III randomized clinical
trials.  Adequate statistical methodology and expertise should be apparent in all
proposed studies (pre-clinical laboratory and pilot clinical studies).  For all
Centers evaluating neurological disorders and stroke, a statistical core with
experience in appropriate long-term neurological outcomes is required for
adequate experimental design and analysis of data.  Applicants interested in
investigating CAM approaches for treating neurological disorders and stroke
should contact the NINDS Program Officers listed under INQUIRIES.

H.  Sleep:
Identify fundamental mechanisms through which light (see "Bioelectromagnetics"
below), food supplements (e.g. melatonin; also see Orthomolecular Medicine"
below), and unconventional applications of exercise entrain sleep and circadian
rhythms; alter sleep regulators (e.g. adenosine and immune system); and influence
neural correlates of sleep including the transition between sleep and
wakefulness, different stages of sleep, and sleep-related alterations in sensory
perception and cognitive processing.

Investigate the risks, benefits, long-term safety, and efficacy of unconventional
pharmacological, herbal and orthomolecular interventions and of unconventional
applications of behavioral and psychotherapeutic interventions for sleep
disturbances including obstructive sleep apnea, insomnia, parasomnias,
narcolepsy, circadian rhythm sleep disorders, restless legs syndrome, and
fibromyalgia; and to limit the effects of daytime sleepiness on performance in
the workplace and classroom.

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, Native
American, 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 fields including pulsed EM fields, magnetic fields, 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, immunoaugmentative
therapies as used by CAM practitioners or the public);

o  Herbal Medicine (Note:  This category does not include isolation of the active
ingredients from herbal preparations for the purpose of drug development)

(Note:  Studies incorporating the following three CAM program areas MUST focus
on the more unconventional uses of these approaches and involve collaborations
with expert practitioners of these approaches);

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 currently in use by the public or practitioners,
usually outside of a conventional medicine setting (e.g., meditation, imagery,
hypnosis, biofeedback, music therapy, yoga, spirituality, biological effects of
consciousness).  Mind-body approaches that are already integrated into
conventional medicine (e.g., patient education, psychotherapy, cognitive-
behavioral approaches, etc.) will NOT be considered;

o  Health Promotion and Disease Prevention (e.g., unorthodox changes in
lifestyle, including risk reduction, when applied as complete systems for chronic
disease management [prevention and treatment] across multiple diagnostic
categories);

o  Orthomolecular Medicine:  This category includes the use of products, many of
which may be used as nutritional and food supplements (e.g., magnesium, Co-enzyme
Q, carnitine, melatonin, DHEA, mega-doses of vitamins) when investigated for
therapeutic or preventive purposes. These products are usually used in
combinations and at very high doses well above the RDA.  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

Each Center must include the following elements; applications that fail to meet
these requirements will be considered unresponsive to the RFA and not 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. 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 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 15% time to administration
of Center activities 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 CAM practitioners provide appropriate input to Center research
projects.

4.  A substantive patient population:

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

5.  Research projects:

Each Center application should include three to six research projects.  Each of
these projects must request at least three, but not more than five, years of
support in the application.  At least three of these submitted projects 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.

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 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.  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 and Phase III trials WILL
NOT be accepted under this RFA.  Subproject principal investigators are required
to commit at least 15% time to these projects.

Research components involving Phase I and II clinical trials must include
provisions for 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 Notice #98-084).  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.  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 1. above.

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 should 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 qualified women and minorities where possible.  To this end,
each applicant should include a clear policy and plans for recruiting minorities
and women.  The Center application should propose the number of slots available,
the criteria for eligibility and for selection of candidates, and describe the
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 complementary activities that contribute to the
environment for career development (e.g., existing training grants, other career
development mechanisms and relevant programs).

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 be permitted only with prior program
approval.

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 trials on the use of CAM.  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 be permitted only with prior program
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
funded through other forms of research support, e.g., R01.

9.  Advisory Committee:

Scientific and administrative Center oversight is charged to a multidisciplinary
Advisory Committee (AC) to be appointed by the Principal Investigator on a
rotating basis.  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 upon request.  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 shall 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 and feasibility 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. 
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 OAM and IC 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 may be budgeted for this purpose.  This may include Project
Investigators from other institutions who are actively collaborating with Centers
investigators.

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.  An initial FDA contact is listed under INQUIRIES.  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.  Investigators may obtain copies from these sources
or from the program staff listed under INQUIRIES.  Program staff may also provide
additional relevant information concerning the policy.

NIH POLICY AND GUIDELINES ON THE 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:
https://grants.nih.gov/grants/guide/notice-files/not 98-024.html

LETTER OF INTENT

Prospective applicants are asked to submit, by December 11, 1998, a letter of
intent that includes a descriptive title of the overall proposed project; the
name, address, telephone and FAX number of the Principal Investigator; the
identities of other key personnel and participating institutions; and the number
and title of this RFA.  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.

The letter of intent is to be sent to:

Dr. Richard L. Nahin
Office of Alternative Medicine
National Institutes of Health
Building 31, Room 5B-38
Bethesda, MD  20892-2182
FAX:  (301) 480-3519 or (301) 594-6757

APPLICATION PROCEDURES

The research grant application form PHS Form 398 (rev. 5/95) is to be used in
applying for this grant.  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 301/710-0267, Email:
GrantsInfo@nih.gov; and may also be obtain on the World Wide Web at 
https://grants.nih.gov/grants/funding/phs398/phs398.html.

Prior to writing the application, applicants should carefully read the
instructions provided with Form PHS 398 and this RFA.

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.

Bibliographic Sketches:
Bibliographic sketches and other support pages are required for all proposed
Center personnel and for all investigators associated with the research projects
and cores.  These pages should be in alphabetical order follow the budget pages
and should not be duplicated in the descriptions of individual  component
projects and cores.

Research Projects and Core Facilities:
Applicants may use up to 25 pages to describe all required Center activities
(including the Advisory Committee, the Developmental Research and Career
Development Programs, the Administrative Core and the Center's overall goals and
objectives) and up to 25 pages each for each of the research projects and for
each core facility (excluding the  Administrative Core), excluding
bibliographies.  Descriptions of the research projects and the core facilities
should follow the PHS 398 format, section 9 (Research Plan).  In addition, each
project should provide a detailed description of core utilization and each core
should 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.  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.

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
6701 ROCKLEDGE DRIVE, SUITE 1040 - MSC 7710
BETHESDA, MD  20892-7710
BETHESDA, MD  20817 (for express/courier service)

At the time of submission, one additional complete copy of the application must
be sent to:

Dr. Richard L. Nahin
Office of Alternative Medicine
National Institutes of Health
Building 31, Room 5B-38
Bethesda, MD  20892-2182

Applications must be received by January 22, 1999.  If an application is received
after the date, it will be returned to the applicant without review.  The Center
for Scientific Review (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 Form PHS 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 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

Upon receipt, applications will be reviewed for completeness by the CSR and
responsiveness by the OAM.  Incomplete and/or unresponsive applications will be
returned to the applicant without further consideration.  In some cases,
individual subprojects that are incomplete or unresponsive will be withdrawn from
the review process while the remainder of the application goes through peer-
review.

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 CSR in accordance with NIH peer review procedures.  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 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 into the
scientific goals and research theme, as well as integration of appropriate CAM
and conventional expertise;

2.  If a competing continuation application, the quality and significance of the
progress made in the previous funding period;

3.  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
the relevance to the overall goals of the Center and the appropriate utilization
of Center resources (e.g., cores).

Each subproject also will be reviewed for 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 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.

4.  Scientific merit of combining the component parts into a Center;

5.  Technical merit and justification of each core unit;

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

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

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

9.  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;

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

11.  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 chose Committee members after an award is made;

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

13.  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.

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

15.  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, potential for impacting
on the disease/condition in question, and institutional commitment.

AWARD CRITERIA

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.

Schedule

Letter of Intent Receipt Date:  December 11, 1998
Application Receipt Date:       January 22, 1999
Review by Advisory Council:     Aug/Sep 1999
Anticipated Award Date:         September 1999

INQUIRIES

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

Inquiries regarding programmatic issues may be directed to:

Dr. Patricia S. Bryant
Behavior, Oral Health Promotion, and Environment Program
National Institute of Dental Research
Natcher Building, Room 4AN-24E
Bethesda, MD  20892-6402
Telephone:  (301) 594-2095
FAX:  (301) 480-8318
Email:  BryantP@de45.nidr.nih.gov

Dr. Cheryl A. Kitt
Programs in Pain, Neuroendocrinology, and Neurotoxicology
National Institute of Neurological Disorders and Stroke
7550 Wisconsin Avenue, Room 504
Bethesda, MD  20892
Telephone:  (301) 496-1431
FAX:  (301) 402-2060
Email:  KittC@ninds.nih.gov

Dr. John R. Marler
Division of Stroke, Trauma and Neurodegenerative Diseases
National Institute of Neurological Disorders and Stroke
7550 Wisconsin Avenue, Room 800
Bethesda, MD  20892
Telephone:  (301) 496-4226
FAX:  (301) 480-1080
Email:  MarlerJ@ninds.nih.gov

Dr. Richard L. Nahin
Office of Alternative Medicine
National Institutes of Health
Building 31, Room 5B-38
Bethesda, MD  20892-2182
Telephone:  (301) 435-5042
FAX:  (301) 402-4741 or (301) 594-6757
Email:  NahinR@OD31EM1.OD.NIH.GOV

Dr. Marcia G. Ory
Social Science Research on Aging Program
National Institute on Aging
7201 Wisconsin Avenue, Suite 533, MSC 9205
Bethesda, MD  20892-9205
Telephone:  (301) 402-4156
FAX:  (301) 402-0051
Email:  Marcia_Ory@NIH.GOV

Dr. Susana A. Serrate-Sztein
Rheumatic Diseases Program
National Institute of Arthritis and Musculoskeletal and Skin Diseases
45 Center Drive, Room 5AS-25E, MSC 6500
Bethesda, MD  20892-6500
Telephone:  (301) 594-5032
FAX: (301) 480-4543
Email:  szteins@exchange.nih.gov

Virginia S. Taggart, M.P.H
Division of Lung Diseases (Asthma)
National Heart, Lung and Blood Institute
6701 Rockledge Drive, Suite 10018, MSC 7952
Bethesda, MD  20892-7952
Telephone:  (301) 435-0202
FAX:  (301) 480-3557
Email:  TaggartV@gwgate.nhlbi.nih.gov

Dr. Michael Twery
Division of Lung Diseases (Sleep)
National Heart, Lung and Blood Institute
6701 Rockledge Drive, Suite 10018, MSC 7952
Bethesda, MD  20892-7952
Telephone:  (301) 435-0202
FAX:  (301) 480-3557
Email:  TweryM@gwgate.nhlbi.nih.gov

Dr. Jeffrey D. White
Division of Clinical Sciences
National Cancer Institute
Building 10, Room 3B38
Bethesda, MD  20892
Telephone:  (301) 402-2912
FAX:  (301) 402-1001
Email:  jdwhite@helix.nih.gov

Although not a formal sponsor of this RFA, the Agency for Health Care Policy and
Research encourages applications for the support of CAM research on patient
outcomes, cost-effectiveness, health-related quality-of-life measures, types of
providers, patients, treatments, and treatment settings.  For more information,
contact:

Dr. Mary A. Cummings
Center for Outcomes and Effectiveness Research
Agency for Health Care Policy and Research
2101 East Jefferson Street, Suite 605
Rockville, MD  20852
Telephone:  (301) 594-1485
FAX:  (301) 594-3211
Email:  mcumming@ahcpr.gov

Although the National Institute of Mental Health (NIMH) is not a cosponsor of
this RFA, applicants interested in research project grants concerning CAM
approaches to treatment of mental disorders may contact:

Jerry Cott, Ph.D.
Division of Services and Intervention Research
National Institute of Mental Health
5600 Fishers Lane, Room 10-75
Rockville, MD  20857
Telephone:  (301) 443-1185
FAX:  (301) 594-6784
Email:  jcott@helix.nih.gov

Inquiries regarding fiscal issues may be directed to:

Carol Fitzpatrick
Grants Management Branch
National Institute of Arthritis and Musculoskeletal and Skin Diseases
45 Center Drive, Room 5AS-43B, MSC 6500
Bethesda, MD  20892-6500
Telephone:  (301) 594-3503
FAX:  (301) 480-4543
Email:  fitzpatc@exchange.nih.gov

Martin R. Rubinstein
Grants Management Branch
National Institute of Dental Research
45 Center Drive, Room 4AN44A, MSC 6402
Bethesda, MD  20892-6402
Telephone:  (301) 594-4800
FAX:  (301) 480-8301
Email:  mr49c@nih.gov

Karen D. Shields
Grants Management Branch
National Institute of Neurological Disorders and Stroke
Federal Building, Room 1004
Bethesda, MD  20892
Telephone:  (301) 496-9231
FAX:  (301) 402-0219
Email:  ShieldsK@ninds.nih.gov

Marie Willett
Grants Operations Branch
National Heart, Lung and Blood Institute
6701 Rockledge Drive, Suite 7154, MSC 7926
Bethesda, MD  20892-7952
Telephone:  (301) 435-0170
FAX:  (301) 480-3310
Email:  WillettM@gwgate.nhlbi.nih.gov

Inquiries regarding FDA issues may be directed to:

Dr. Freddie Ann Hoffman
Deputy Director, Medical Staff
Food and Drug Administration
5600 Fishers Lane, Room 15A08
Rockville, MD  20857
Telephone:  (301) 827-6606
FAX:  (301) 443-2446
Email:  FHoffman@bangate.fda.gov

AUTHORITY AND REGULATIONS

The Office of Alternative Medicine (OAM) was mandated by Congress in 1991 and
permanently established within the Office of the Director, National Institutes
of Health (NIH), through the National Institutes of Health Revitalization Act
(Public Law 103-43, Section 404E).  The congressional language states that "the
purpose of the Office is to facilitate the evaluation of alternative medical
treatment modalities. . ."  The language continues that "in carrying out
subsection b [its purpose], the Director of the Office [of Alternative Medicine]
shall - support research training - for which fellowship support is not provided
under section 487."

This program is described in the Catalog of Federal Domestic Assistance Nos.
93.121, 93.213, 93.396, 93.837, 93.838, 93.846, 93.853, and 93.866.  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 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, 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.

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