Research and Training in Complementary and Alternative Medicine (93.213)

Program

93.213 Research and Training in Complementary and Alternative Medicine

Federal Agency

Agency: Department of Health and Human Services
Office: National Institutes of Health

Authorization

Public Health Service Act, Section 485D, , Title VI, Section 601, Public Law 105-277, 112 Stat. 2681-387, 42 U.S.C 281 as amended.

Program Number

93.213

Last Known Status

Active

Objectives

To evaluate alternative, complementary, or unconventional medical treatments. The following objectives support this goal: (1) coordinate and facilitate the investigation of alternative medical practices through peer-reviewed grant solicitations; (2) interface with the Center's National Advisory Council; (3) conduct technology assessment conferences for the purpose of establishing areas of Clinical and Pre-clinical research that need to be further developed within Alternative Medicine; (4) maintain a comprehensive bibliographic data base in conjunction with the National Library of Medicine; (5) and (6) establish an intra- and extra-mural clinical research fellowship program focusing on broad areas of clinical, scientific, and administrative training in CAM.

The National Center for Complementary and Alternative Medicine (NCCAM) regularly examines and redefines its research priorities. In setting research priorities, NCCAM considers its existing research portfolio, its 5-year strategic plan, the recommendations of the National Advisory Council for Complementary and Alternative Medicine, current scientific advances, the plans of other NIH institutes and centers, and input from expert panels and stakeholders. Research constituting a rigorous evidence base for CAM practices will be developed through a range of research strategies including basic and translational research, and clinical investigation.

Current research priorities are shaped by the following considerations regarding Research Approaches, Areas of Special Interest, and Areas of Lower Program Priority.

Research Approaches
Basic and Translational Research
NCCAM's support of basic research emphasizes and encourages in vitro and in vivo studies of the biological effects and mechanisms of action underlying complementary and alternative medicine (CAM) approaches, as well as studies characterizing the active elements of an intervention, Studies should use state-of-the-art techniques in areas such as imaging, pharmacognosy, proteomics and epigenomics, and employ optimal animal models and methodology.

NCCAM's support of translational research addresses the need for valid, reliable, and relevant research tools, outcome measures, and innovative methodology to enhance the rigor or CAM clinical studies and to ensure that they are maximally informative. Studies intended to identify and validate objective endpoints or biomarkers, assess and measure adherence or treatment fidelity, and otherwise strengthen the design of subsequent CAM clinical trials are emphasized.

Observational Studies and Clinical Investigations
NCCAM's clinical research portfolio utilizes clinical trial, case-control, observational, qualitative, and other experimental methodologies to determine safety and estimate the efficacy of CAM approaches. The clinical research portfolio also includes studies of the contribution to improved health and wellness made by CAM interventions as they are practiced in "real-world" settings.

Studies should be designed to inform decision making about the design of and/or the need for subsequent investigations. Important areas of investigation include examination of pharmacology, bioavailability, and ADME (absorption, distribution, metabolism, and excretion) of biologically based interventions; optimizing dosing of all types of CAM interventions; refinement and validation of outcome measures (including patient-reported outcomes that are particularly relevant to CAM modalities); optimizing control groups, masking strategies, and other methodological enhancements; obtaining preliminary data on safety and efficacy; and conducting early phase clinical investigations to elucidate mechanisms of action and to test models.

In general phase III clinical trials will be supported under the cooperative agreement mechanism after careful consideration by NCCAM Staff. Investigators interested in proposing phase III studies are strongly encouraged to contact a relevant NCCAM Program Officer.

Areas of Special Interest
Although a wide range of research topics are of interest to NCCAM, studies focusing on CAM interventions used frequently by the American public, and on the conditions for which they are most frequently used are particularly encouraged. These would include, but not be limited to, investigations of the impact of CAM modalities in alleviating chronic pain syndromes and inflammatory processes, and improving health and wellness. Among all types of studies, attention to a range of endpoints meaningful to improved health, well-being, and quality of life is strongly encouraged.

Investigators are urged to discuss applications with a relevant NCCAM Program Officer.

Areas of Lower Program Priority
NCCAM is already investing substantial resources in the following areas of research. We will continue to fund novel and significant research on these topics. However, until results of the currently funded studies are available, applications in these areas are likely to be considered of lower program priority. Investigators are strongly urged to contact the relevant NCCAM Program Officer before submitting an application in any of the following areas:

Clinical trials of saw palmetto and African plum (Pygeum) for benign prostatic hypertrophy
Clinical efficacy or effectiveness studies of low-carbohydrate diets for weight loss
Clinical studies of silymarin for chronic liver diseases
Clinical studies using probiotics

Early Stage and New Investigators
NCCAM is strongly committed to assisting new and early stage investigators in establishing a research career. Early stage investigators are those within 10 years of completing their terminal research degree, or their medical residency, or its equivalent. New investigators are those who have yet to compete successfully for a substantial (e.g., R01) NIH research grant. Each Advisory Council round, based on available funds, NCCAM: 1) will consider early stage or new investigator status as one of the criteria for designating grant applications as being of high program priority and 2) may make additional R01 grant awards to new and early stage investigators with percentiles or scores beyond the formal payline.

NCCAM continues to accept applications in areas not listed. All investigators are urged to discuss potential applications with the relevant NCCAM Program Officer.

Types of Assistance

PROJECT GRANTS; TRAINING

Uses and Use Restrictions

Project grants and cooperative agreements may be made to eligible institutions for the support of various projects in CAM. The grants may be used for personnel, consultant costs, equipment, supplies, travel, patient costs, animals miscellaneous items, and indirect costs. For the individual post-doctoral training grant, support is for salary of the trainee, tuition and fees, self-only health insurance, research supplies, equipment, travel to scientific meetings, and related items.

Eligibility Requirements

Applicant Eligibility

The awardee will be either a university, college, hospital, public agency, nonprofit research institution, or for-profit organization that submits an application and receives a grant or cooperative agreement for support of research by a named principal investigator.

Beneficiary Eligibility

Any nonprofit or for-profit organization, company, or institution engaged in biomedical research.

Credentials/Documentation

For-profit organizations costs are determined by in accordance with 48 CFR, Subpart 31.2 of the Federal Acquisition Regulations. Costs will be determined in accordance with HHS Regulations 45 CFR 74, Subpart Q. OMB Circular No. A-87 applies to this program.

Application and Award Process

Preapplication Coordination

Preapplication coordination is required. Environmental impact information is not required for this program. This program is excluded from coverage under E.O. 12372.

Application Procedure

This program is excluded from coverage under OMB Circular No. A-102. This program is excluded from coverage under OMB Circular No. A-110. NIH is in the process of converting to SF424 (Research and Related (R&R)) forms and electronic submission through Grants.gov. Information on this plan and on registering for electronic submission is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-05-067.html . Updates regarding the transition process are at http://era.nih.gov/ElectronicReceipt/.

Award Procedure

Award Procedure: All accepted applications are evaluated for scientific and technical merit by an appropriate scientific peer review panel and by a national advisory council or board. All applications receiving a priority score ranging from the best (10) to worst (90) compete for available funds based on scientific merit, program relevance, and program balance and are made annually. Initial award provides funds for the first budget period (usually 12 months) and Notice of Grant Award (Form PHS 1533) indicates support recommended for remainder of project period, allocation of Federal funds by budget categories, and special conditions, if any.

Deadlines

Contact the headquarters or regional office, as appropriate, for application deadlines.

Range of Approval/Disapproval Time

Grants and Cooperation Agreement: Approximately 10 months. Training: For 9 months.

Appeals

A principal investigator (P.I.) may question the substantive or procedural aspects of the review of his/her application by communicating with the staff of the Office. A description of the NIH Peer Review Appeal procedures is available on the NIH homepage www.nih.gov/grants/guide/1997/97.11.21/n2.html .

Renewals

Applications submitted for renewal are reviewed and selected for funding on a competitive basis.

Assistance Considerations

Formula and Matching Requirements

This program has no statutory formula.

Matching requirements are not applicable to this program.

MOE requirements are not applicable to this program.

Length and Time Phasing of Assistance

Grants and cooperative agreements: Average 3 to 4 years, maximum of 5 years with prior approval before submission. Renewals may be awarded for additional periods of up to 5 years (with prior approval before submission) based on competitive peer review. Funds are provided through Monthly Demand Payment System or an Electronic Transfer System. Method of awarding/releasing assistance: lump sum.

Post Assistance Requirements

Reports

No program reports are required. No cash reports are required. Type 5 progress reports are required. Expenditure reports on a quarterly basis are sent to the data warehouse. Performance monitoring is not applicable.

Audits

In accordance with the provisions of OMB Circular No. A-133 (Revised, June 27, 2003), "Audits of States, Local Governments, and Non-Profit Organizations," nonfederal entities that expend financial assistance of $500,000 or more in Federal awards will have a single or a program-specific audit conducted for that year. Nonfederal entities that expend less than $500,000 a year in Federal awards are exempt from Federal audit requirements for that year, except as noted in Circular No. A-133. In accordance with the provisions of OMB Circular No. A- 133 (Revised, June 24, 1997), "Audits of States, Local Governments, and Non-Profit Organizations," nonfederal entities that expend financial assistance of $300,000 or more in Federal awards will have a single or a program-specific audit conducted for that year. Nonfederal entities that expend less than $300,000 a year in Federal awards are exempt from Federal audit requirements for that year, except as noted in Circular No. A-133. In addition, grants and cooperative agreements are subject to inspection and audits by DHHS and other Federal officials.

Records

Expenditures and other financial records must be retained for 3 years from the day on which the grantee submits the last financial status report for the report period.

Program Accomplishments

Fiscal Year 2008: NCCAM�s approach to research on meditation illustrates on how the Center develops a comprehensive research agenda and identified promising research direction. Meditation, a generic term for a variety of mind/body practices, induces a set of integrated psychological and physiological changes purported to be beneficial in a number of health conditions. Using state of the art imaging, NCCAM funded investigators are characterizing functional activity in the brain during meditation. Other investigators have demonstrate that meditative practices are associated with augmented response to vaccination, suggesting important linkage between medication, positive emotional states, local brain response, and improved immune function.
NCCAM, in collaboration with the National Institute on Aging, sponsored a new initiative, New Interventions for Menopausal Symptoms, to study alternative to menopausal hormone therapy. NCCAM continues to work with the National heart, Lung and Blood Institute on the Trial to Assess Chelation Therapy in heart attack patients, and with the National Institute of Diabetes, Digestive and Kidney Diseases to support multi-center clinical trials of milk thistle for liver disease.
To explore the biological basis for differences in individual response to CAM modalities, NCCAM launched the initiative, Omics and Variable Responses to CAM. NCCAM funded two new Centers of Excellence in CAM Research. Using animal models investigators at the Mount Sinai School of Medicine in New York, and the Center for CAM Research on Autoimmune and Inflammatory Disease the University of South Carolina Research Foundation conduct mechanistic studies of grape based compounds, such as resveratrol, for Alzheimer�s dieses and multiple sclerosis. Fiscal Year 2009: Basic research clarifies fundamental biological effects that are central to the development of the evidence base in CAM and underpins the design of clinical research. To address these needs, NCCAM will continue investigator-initiated basic research and will increase, through targeted initiatives, its support for translational research on CAM.

NCCAM added two new basic research centers to its cornerstone Centers of Excellence for Research on Complementary and Alternative Medicine (CERC) program during FY 2008 (nccam.nih.gov/training/centers). The University of Chicago's Center for Herbal Research on Colorectal Cancer is studying the biological effects of two forms of ginseng and their potential in preventing cancer. The CERC at Montana State University is exploring the potential for certain biologically based therapies to alter the inflammatory response to infections in the lung and intestines. Several basic research awards were funded under the FY 2007 initiative, Mechanisms of Immune Modulation, studies the ability of various interventions to affect inflammatory processes that underlie many conditions, for which Americans frequently use CAM, such as chronic pain and allergy.

The NCCAM extramural research program funds multidisciplinary clinical investigations at leading U.S. biomedical and CAM research institutions on various CAM modalities. Clinical CAM research ranges from small pilot studies to large-scale clinical trials and epidemiological studies supported through solicited research initiatives, collaboration between NIH Institutes and Centers, and investigator-initiated research.

In FY 2008, NCCAM added two new centers on mind-body research to its CERC program. The University of California, San Francisco center is studying the effects of mindfulness-based stress reduction on obesity and the metabolic syndrome. The University of Wisconsin CERC is examining how different forms of meditation affect the brain's regulation of emotion. NCCAM also funded two new projects on Outcomes and Cost Effectiveness studying use of naturopathic care to treat diabetes and CAM approaches to the treatment of chronic fatigue syndrome. NCCAM continued to work collaboratively with other Institutes to support research on pain management.

To define research needs, priorities, and future directions for CAM research, it is essential to characterize and understand the patterns and trends in use of CAM by Americans. NCCAM leads a trans-NIH initiative to obtain the most comprehensive and reliable information available about CAM use in the United States through the National Health Interview Survey (NHIS). The NHIS, carried out by the CDC, is a national survey that annually monitors the Nation's health through personal interviews of a representative sample of the civilian, non-institutionalized U.S. population. In 2007, CAM-related questions were posed to about 30,000 randomly selected NHIS participants. Data from the survey, which became available late in FY 2008, provide insights into the types of CAM people use, the reasons for which they turn to CAM, and the patterns of use. The 2007 data included information on CAM use among children.

Important observations from the data include the following:

Almost 40 percent of adults surveyed reported using some form of CAM during the previous 30 days.
Back pain was, by far, the most frequently cited reason for CAM use. Pain and pain-related problems make up half of the top 20 reasons for using CAM.
Among specific CAM modalities, the largest increases in use compared to the 2002 NHIS data were reported for meditation, massage, and yoga.
CAM use in the previous 30 days was more common among Whites, Asians, and Native Americans (ranging from 40-50%) than among African American and Latino groups (approximately 25%).
The largest increases in CAM use were among Americans over 85 years of age.
CAM use remains more common among individuals with chronic or serious illness, those with higher educational levels, and those between the ages of 50-59.
Preliminary data indicate that CAM use by children was less than and different in type than adult use, and that children were more likely to use CAM approaches if their parents did also.

Herbal medicines, dietary supplements, and probiotics are the most frequently used and widely available CAM products in the United States. However, evidence from rigorous preclinical and clinical research and development to support their use is often lacking. Research on the safety, efficacy, and mechanisms of action of these products present many challenges. First, natural products are inherently variable and may consist of complex mixtures containing many individual components. For example, the time and location of plant growth or harvesting may affect significantly the composition of herbal medicines, which in turn may influence the ultimate biological effects of the product. Second, natural products can be contaminated by substances that alter metabolism or cause adverse effects. For these and other reasons, careful attention to documentation of the sources, composition, and integrity of these products are essential in ensuring that they are safe and that research with them yields valid�and importantly�reproducible results.

To address these challenges, NCCAM has established a quality control program for herbal medicines, dietary supplements, probiotics, and similar products used in NCCAM-supported research. Prior to funding of research grant awards, NCCAM requires that investigators submit information documenting the source, composition, and process of production of the product to be studied. These building blocks of information, critical to the integrity of the research, are reviewed by a panel of scientific experts, the NCCAM Product Integrity Working Group (PIWG). The PIWG's mission is to ensure that the particular product to be used in NCCAM-funded research meets specific criteria of analysis and quality before a grant is issued. Investigators are also required to present a plan to reserve samples for future verification or analyses, should it be needed.

From its establishment in 2006 through the end of FY 2008, NCCAM's product integrity initiative has evaluated product information for more than 220 research projects. The program is now widely recognized for its rigor, and for the standard of excellence that it sets for the field of natural product research. Most important, the program ensures that the ensuing research will be optimally designed, rigorously conducted, and maximally authoritative. Fiscal Year 2010: In FY 2010 NCCAM will make awards under a new initiative (to be released in FY 2009) entitled Program for Translational Tools for CAM Clinical Research, which will fund research on metrics, standard protocols, and outcome measures aimed at improving the quality, consistency, and comparability of clinical CAM research. The Center will also fund studies under its initiatives Dietary Supplements Research Centers: Botanicals; Exploratory/Developmental Grant for Complementary and Alternative Medicine Studies using Cells, Tissues, and Animal Models of Disease; and Biology of Manual Therapies.

In FY 2010, NCCAM will continue to fund a portfolio of investigator-initiated clinical research, including new research projects under its initiatives Effectiveness Research�CAM Interventions and Chronic Back Pain; Exploratory/Developmental Grant for Complementary and Alternative Medicine Studies of Humans; Outcomes, Cost-Effectiveness, and the Decision Making Process to Use Complementary and Alternative Medicine; and Omics and Variable Research Responses to CAM: Secondary Analysis for CAM Clinical Trials.

Financial Information

Account Identification

75-0896-0-1-552.

Obligations

(Project Grants) FY 08 $88,371,000; FY 09 est $88,547,000; FY 10 est not reported.

Range and Average of Financial Assistance

range from low to high: R21, $200,000 to U19 1.955 million.

Regulations, Guidelines and Literature

Not Applicable.

Related Programs

Not Applicable.

Information Contacts

Regional or Local Office

None.

Headquarters Office

Martin Goldrosen 6707 Democracy Blvd
suite 401
, Bethesda, Maryland 20817 Email: goldrosm@mail.nih.gov Phone: 3015942014

Web Site Address

http://nccam.nih.gov .

Examples of Funded Projects

Fiscal Year 2008: No Current Data Available Fiscal Year 2009: No Current Data Available Fiscal Year 2010: No Current Data Available

Criteria for Selecting Proposals

The major elements in evaluating proposals include assessments of: (1) The scientific merit and general significance of the proposed study and its objectives; (2) the technical adequacy of the experimental design and approach; (3) the competency of the proposed investigator or group to successfully pursue the project; (4) the adequacy of the available and proposed facilities and resources; (5) the necessity of the budget components requested in relation to the proposed project; (6) the relevance and importance to the announced program objectives; and (7) the interfacing of conventional researchers and technology with unconventional/alternative clinicians for the purpose of providing clinical and scientific collaborations when and where appropriate.