COMPLEMENTARY/ALTERNATIVE MEDICINE (CAM) AT THE END OF LIFE FOR CANCER 
AND/OR HIV/AIDS

Release Date:  January 16, 2001

RFA:  RFA-AT-01-002

National Center for Complementary and Alternative Medicine
 (http://nccam.nih.gov)
National Cancer Institute
 (http://www.nci.nih.gov/)
National Institute of Allergy and Infectious Disease
 (http://www.niaid.nih.gov/default.htm)
National Institute of Mental Health
 (http://www.nimh.nih.gov/)
National Institute of Nursing Research
 (http://www.ninr.nih.gov/)


Letter of Intent Receipt Date:  February 26, 2001
Application Receipt Date:       April 12, 2001

THIS RFA USES THE "MODULAR GRANT" AND "JUST-IN-TIME" CONCEPTS. IT INCLUDES 
DETAILED MODIFICATIONS TO STANDARD APPLICATION INSTRUCTIONS THAT MUST BE USED 
WHEN PREPARING APPLICATIONS IN RESPONSE TO THIS RFA

PURPOSE

The National Center for Complementary and Alternative Medicine (NCCAM) invites 
research grant applications to generate scientific knowledge on complementary 
and alternative medicine (CAM) therapies that will lead to improved care for 
individuals at the end of life.  The intent of this initiative is to generate 
research that has the potential to improve the quality of life for individuals 
with cancer and/or HIV/AIDS who are at the end of life.

For the purposes of this request for application (RFA), CAM is defined as 
healthcare practices that are not an integral part of conventional medicine.  
Currently, CAM practices may be grouped into five major domains: (1) 
alternative medical systems, (2) mind-body interventions, (3) biologically-
based treatments, (4) manipulative and body-based methods, and (5) energy 
therapies. A classification of CAM approaches may be found on the NCCAM 
website at:  (http://nccam.nih.gov/health/whatiscam/)  

HEALTHY PEOPLE 2010

The Public Health Service (PHS) is committed to achieving the health promotion 
and disease prevention objectives of "Healthy People 2010," a PHS-led national 
activity for setting priority areas.  This RFA entitled CAM Therapies at the 
End of Life for Cancer and/or HIV/AIDS  is related to the priority areas of 
cancer and HIV/AIDS.  Potential applicants may obtain a copy of "Healthy 
People 2010" at http://www.health.gov/healthypeople/.  

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic and foreign, for-profit and non-
profit organizations, public and private, such as universities, colleges, 
hospitals, laboratories, units of State and local governments, and eligible 
agencies of the Federal government.  Proposed foreign grants must     have the 
potential to advance knowledge that will benefit the United States and must 
propose opportunities for unusual talent resources, populations, or 
environmental conditions that are not readily available in the United States. 
See POLICIES GOVERNING FOREIGN INSTITUTIONS AND INTERNATIONAL ORGANIZATIONS 
(PHS GPS 9505) for further guidelines for foreign applications 
(http://grants.nih.gov/grants/policy/gps/app4.htm).  Racial/ethnic minority 
individuals, women, and persons with disabilities are encouraged to apply.

MECHANISMS OF SUPPORT

This RFA will use the National Institutes of Health (NIH) R01 and NCCAM’s R21 
award mechanism.  Responsibility for the planning, direction, and execution of 
the proposed project will be solely that of the applicant.  The total project 
period for an application submitted in response to this RFA may not exceed 2 
years for the R21 or 4 years for the R01.  This RFA is a one-time 
solicitation, and the anticipated award date is September, 2001.

R01 Applications.  R01 awards will vary in size and duration reflecting the 
nature and scope of the research proposed. Future unsolicited competing 
continuation applications will compete with all investigator-initiated 
applications and be reviewed according to customary peer review.

R21 Applications. The objective of the exploratory/developmental mechanism 
(R21) is to encourage applications from individuals who are interested in 
testing innovative or conceptually creative ideas that are scientifically 
sound and may advance treatment options at the end of life with CAM 
approaches.  Another objective is to encourage initial development that is 
necessary to provide a basis for future research project applications.

Exploratory/developmental studies are not intended for large-scale 
undertakings or to support or supplement ongoing research.  Instead, 
investigators are encouraged to explore the feasibility of an innovative 
research question or approach that may not yet be sufficiently justified 
through existing research to compete as a standard research project grant 
(e.g., R01), and to develop a research basis for a subsequent application 
through other mechanisms.  These grants are non-renewable, and the 
continuation of projects developed under the R21 program will be through the 
traditional unsolicited (R01) grant programs. 

FUNDS AVAILABLE 

The Institutes and Centers (ICs) intend to commit approximately $2.25 million 
(up to $1 million allocated for AIDS) for this activity in FY01 to fund new 
competitive grants in response to this RFA.  The total cost over 4 years for 
this initiative is estimated at $9 million (up to $4 million allocated for 
AIDS).  An applicant may request a project period of up to 2 years and a 
budget for total costs of up to $200,000 per year for the R21 or a project 
period of up to 4 years and a budget for total costs of up to $500,000 per 
year for the RO1.  Because the nature and scope of the research proposed may 
vary, it is anticipated that the size of each award will also vary. 
NINR is specifically interested in applications investigating holistic 
approaches that use mind/body interventions in persons with HIV/AIDS who are 
at the end of life. Although the financial plans of The Institutes and Centers 
(ICs) provide support for this program, awards pursuant to this RFA are 
contingent upon the availability of funds and the receipt of a sufficient 
number of meritorious applications.  The earliest anticipated award date will 
be September 1, 2001.

RESEARCH OBJECTIVES

Background: 

The goal of palliative care is to provide for unmet physical, psychosocial, 
and spiritual needs of terminally ill patients and their families.1  The most 
important concerns expressed by hospice patients are the existential, 
spiritual, familial, physical, and emotional aspects of illness; however, 
these concerns are rarely the focus of care at the end of life.2  If cure is 
not an option, maintaining quality of life and controlling symptoms may be 
more appropriate than potentially distressing treatments that offer limited, 
temporary improvement at the cost of physical and emotional suffering.  Social 
and cultural forces are demanding that conventional medicine offer a more 
holistic approach3 that conveys empathy and compassion to the sick and 
dying4and assists individuals sustain dignity and well-being in their final 
days.5  Therefore, treatment options for individual who are dying should be 
expanded and their emotional, social, cultural, and spiritual needs addressed.

At a 1997 meeting on symptoms of terminal illness that was sponsored by six 
NIH Institutes and the former Office of Alternative Medicine, palliative care 
was described as “…care that takes place in a context where …cure is no longer 
possible and disease modification provides diminishing returns.”6  Symptoms 
are complex and include physical (fatigue and pain) and psychological 
distress, and subjective measures should expand beyond absence of pain or 
functional status to include spiritual states, peacefulness, or sense of life 
completion.  The report from that workshop is available at 
http://www.ninr.nih.gov/end-of-life.htm.  A subsequent Program Announcement 
was published in December, 1997, PA-98-019 entitled “Management of Symptoms at 
the End of Life” (http://grants.nih.gov/grants/guide/pa-files/PA-98-019.html).  
Currently, NCCAM cosponsors a Program Announcement entitled “Quality of Life 
for individuals at the End of Life” 
(http://grants.nih.gov/grants/guide/pa-files/PA-00-127.html).  
Many of the objectives for research from that program announcement are subsumed 
within this focused request for applications.  

Public awareness of the limitations of end of life care and interest in 
improving treatment at the end of life is growing.  In October, 1999, a 
Congressional hearing entitled “Improving Care at the End of Life with 
Complementary Medicine reviewed use of these modalites.  In September, 2000, a 
television documentary entitled "On Our Own Terms- Moyers on Dying in America" 
and a Time cover story “Dying on our Own Terms” focused our nation on these 
issues. 7,8  In November, 2000, a newly formed End of Life Research Interest 
Group at the National Institute’s of Health and the primary Institutes that 
comprise the group (National Institute of Nursing Research, National Cancer 
Institute, National Institute on Aging, and NCCAM) sponsored an open forum 
entitled “The End of Our Lives: Guiding the Research Agenda”.  The panelist 
and participants discussed the need for research, including exploration of 
ethnic disparities in end of life care.  Therefore, this initiative responds 
to the public demand to increase programs for and research on the end-of-life 
care, including CAM interventions.  This initiative will focus specifically on 
clinical studies of CAM modalities for related to cancer and/or HIV/AIDS 
because CAM is widely used by these patients with advanced disease and should 
be evaluated.  

Cancer brings fear and hope9 along with 10therapeutic interventions with 
toxicities and sometimes limitations to control or cure disease.  These 
factors may be driving the search by patients for alternatives.11  Although 
CAM is used at various stages along the disease continuum, patients with 
cancer report using CAM by 4 to 6 months after diagnosis when ongoing 
treatment outcomes may be uncertain;12,13 after a diagnosis with a poor 
prognosis,14 with recurrence or disease progression14-16, or at the advanced 
stages of disease.15-18  

In studies conducted in different countries of patients with terminal cancer, 
use of CAM ranged from 7% (70% would have used it if available)19 to 26% and 
60% in Canada,13,18,20 63 to 64% in Hong Kong21 and Taiwan,22 61% in Austria15, 
and 58% in Germany17 and 42% in Norway.12  In several surveys, use was equal 
among men and women20-22 but greater among younger patients.20,22  Herbs and 
herbal teas (Essiac, echinacea, Traditional Chinese Medicines) were used 
predominately,20,21 but patients often could not identify the herbs or pills 
and referred to these as medication not prescribed by their doctor.19,22  The 
other most commonly used agents were vitamins and minerals (beta carotene, 
melatonin, enzymes, hydrazine, coenzyme-Q10)13,20, mind-body approaches 
(imagery/visualization, faith healing, meditation)13, and biologics (cartilage 
and mushrooms)13.  Most patients used one modality for less than 3 months.20-22 
Among patients with metastatic melanoma, mistletoe, herbs, metabolic 
therapies, and mental and spiritual approaches were used at the later stage 
whereas homeopathy was used at the earlier stage of disease.15

For HIV/AIDS, the overall prevalence of use of CAM therapies across 12 surveys 
totaling 1480 individuals in the US (with the exception of one study) ranged 
from 27% to 100%, and the most popular CAM therapies used were vitamins, 
massage, acupuncture and imagery.23 A more recent survey reported the one-year 
prevalence was 67.8%, and herbals were the most widely used.24  Similarly, a 
recent survey of 912 individuals in Australia with HIV/AIDS found prevalence 
of CAM use was 56%, and use was greatest for nutritional supplements, massage, 
herbs and meditation/visualization. 25  An observational study of 1016 AIDS 
patients in the U.S. found that aerobic exercise (48%), prayer (56%), massage 
(54%), acupuncture (48%), meditation (46%), support groups (42%), 
visualization and imagery (34%), breathing exercises (33%), spiritual 
activities (33%), and other exercise (33%) were the most frequently used CAM 
therapies.26  Advanced stage of illness has been associated with CAM use.27  
Despite the frequency of use, clinical research is not reported to support the 
use of these approaches. 23,26 

Hope may be the single greatest reason individuals with cancer and HIV/AIDS 
seek CAM therapies, although reasons for hope are not well measured nor is the 
term well-defined.28 Among cancer patients, CAM use has been classified into 
several themes:  hope after conventional therapy fails; hope for disease 
control, cure, and survival; control of pain and symptoms; and for general 
quality of life13,20-22.  Among HIV/AIDS patients, the three greatest 
motivations for using CAM include hope to strengthen resistance to the 
disease, hope to strengthen the body, and the desire to supplement 
conventional care.23 Other reasons include hope to fight HIV or boost 
immunity; prevent weight loss, nausea or diarrhea; and relieve stress or 
depression.24 

Cancer patients frequently do not understand their prognosis and tend to 
overestimate their probability of long-term survival.  Their limited 
understanding of prognosis and subsequent treatment options may not reflect 
their true values for quality versus quantity of life.  In a large cohort of 
terminally ill cancer patients, those who believed they would survive for at 
least 6 months were more than twice as likely (odds ratio =2.6; 95% confidence 
interval 1.8, 3.7) to favor aggressive, life saving treatments than patients 
who believed they had a small chance (as little as 10%) of not surviving for 6 
months.29   In contrast, the most frequent concern of patients who had AIDS or 
were receiving long-term care or dialysis was the fear of the unwanted 
application of technology to prolong their life.30  

CAM therapies are widely used for HIV/AIDS and cancer; however, the literature 
does not report widespread use of a broad spectrum of CAM for other conditions 
such as systemic lupus erythematosus, Alzheimer’s disease, or multiple 
sclerosis, each of which might otherwise be appropriate targets for studies of 
palliative CAM.  Therefore, this initiative will focus on the potential role 
of a spectrum of CAM approaches for patients with life-threatening illness due 
to cancer and HIV/AIDS.  Integrated programs, holistic regimens, or individual 
CAM approaches may provide additional tools for the palliative care setting.  
In the first systematic review of CAM for palliative care, Pan et al. suggest 
that some approaches may be useful for treating prevalent symptoms in 
terminally ill patients (pain, dyspnea, and nausea/vomiting).  Massage, 
relaxation/imagery, hypnosis, or transcutaneous electrical nerve stimulation 
therapy may augment traditional analgesics for pain management whereas 
acupuncture, acupressure, and relaxation may be useful in treating dyspnea.31 
For the field to advance however, future studies must have larger sample 
sizes, reliable blinding, and specific, clinically relevant outcome measures 
that include the effect on concomitant conventional therapy. 31  As the 
evidence evolves, those CAM therapies that prove beneficial can be integrated 
into interdisciplinary healthcare and provide an option for continued care and 
observation in the conventional setting.  Thus, patients may not be forced to 
seek hope outside the conventional setting, the therapeutic armamentarium may 
be expanded, and the physical, psychosocial, and spiritual needs of patients 
would be better addressed.  

OBJECTIVES:

The primary objective of this research initiative is to identify and evaluate 
CAM interventions for patients with advanced, terminal disease associated with 
cancer or HIV/AIDS.  
Possible patient outcomes would include:

1) Managing or reducing the symptoms associated with the conditions of end 
stage disease for cancer and HIV/AIDS,

2) Preventing or reducing side effects of medications such as 
antiretrovirals, steroids, and chemotherapy/radiotherapy, and  

3) Enhancing the psychological, social, and spiritual well-being and 
quality of life at the end-of life.

RESEARCH FOCUS   

Applications should focus on evaluating CAM therapies alone or in combination 
with other conventional treatment modalities. Integrated programs, holistic 
regimens, or diverse approaches with CAM interventions including, but not 
limited to, aromatherapy, music therapy, spirituality, massage and physical 
approaches, acupuncture, innovative psychosocial support interventions, 
botanicals (ie, drug-like therapies of single herbs or complex herbal 
formulas), vitamins and/or minerals, special dietary approaches, or energy 
approaches (ie, Reiki, therapeutic touch) are appropriate for investigation.   

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.  Applicants should provide a compelling, 
research-based rationale for the CAM modality under investigation.  For those 
CAM modalities that have limited or no published research, investigators 
should include evidence from rigorous studies conducted in patient populations 
assessing similar outcomes with the modality.  Clinical trials of botanicals 
could be supported by some preliminary evidence of efficacy with patterns of 
traditional use, case series, preclinical, or pilot clinical data against 
cancer or for palliation of symptoms or side-effects.

SPECIAL REQUIREMENTS

1.   Study Design:

Research applications should be hypothesis-driven and include developmental 
pilot studies or phase I - II clinical trials aimed at expanding the 
therapeutic and palliative care options beyond technologic and conventional 
pharmacologic treatments with CAM approaches.  Studies might include patients 
who refuse to participate in conventional Phase I trials, who are ineligible 
for protocols of conventional therapy, or who have no further treatment 
options but wish and warrant further treatment.  

The applicant institution must document their experience and capacity to 
recruit and retain study participants; provide a description of the population 
currently available for the proposed protocol; describe the procedures for 
screening this population to identify eligible individuals, for recruiting 
these individuals into the trial; and describe proposed mechanisms for 
monitoring accrual performance and criteria for continued participation by 
each participating institution.

The project should provide new knowledge that can be generalized beyond the 
program being studied, including methodological issues that constrain research 
into the care of the dying.  It is expected that some of this work will lead 
to definitive Phase III trials in which the efficacy of the CAM interventions 
could be proven.  However, Phase III studies (defined below), surveys, health 
services research, epidemiologic, and basic science studies will not be 
accepted for 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. 

2.   Linkages to the CAM community:

The applicant should document that linkages to the relevant CAM communities 
exist and that certified or licensed CAM practitioners will provide 
appropriate input for the research.  Ideally, the project would include 
conventional and CAM practitioners working as an interdisciplinary team.

3. Monitoring Plan and Data Safety and Monitoring Board:

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).  

NCCAM requires that all masked clinical trials, regardless of size, establish 
an independent data and safety monitoring board (DSMB).  Funds should be 
budgeted for these activities.  They should not duplicate internal review and 
monitoring systems that are already in place at the institution.

4. Adverse Events Reporting:
  
All studies should have a structured adverse event determination, monitoring 
and reporting system, including standardized forms and protocols for referring 
and/or treating subjects experiencing adverse events.  The proposed schedule 
for reporting adverse events to the DSMB, the NCCAM Program Officer and/or the 
FDA should be described.

5. Product Characterization and Dose:

Quality control of the source material for dietary supplements should be 
addressed and if possible, from one batch.  Capsule formulation should be 
justified (ie, tablet, powder, soft gel capsule), and product specification 
for the identity, purity, strength, and dissolution of each product discussed. 
The batch should be well-characterized in terms of plant species 
identification (ie, mass spec, HPLC, or chemical fingerprinting), processing 
(good harvesting and manufacturing practices), and bioactivity markers.  If 
several batches are used, procedures to minimize lot-to-lot variability should 
be described.  The purity of plant products should be documented with testing 
of heavy metals, pesticide, other plant(s) contaminants.  Authentication and 
characterization of the material will assure reproducibility for future 
trials. 

Dosing must be carefully considered.  If the dosage is not established but 
based on traditional use, a citation(s) from a well-recognized, accessible 
source to support the proposed dosage should be referenced.  If the dosage 
deviates from traditional use, this decision should be justified.  The 
potential for or known drug-herb-vitamin interactions should be discussed, and 
a thorough literature review of the traditional contraindication for the plant 
and/or the major components described, including the risks for vulnerable 
populations.  

6. 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 of the application.  In addition, applicants are strongly 
encouraged to consult their local Institutional Review Boards (IRBs) 
concerning IND status and the IRB approval process.

7. Institutional Support:

Applicants are encouraged to make use of ongoing research efforts where 
feasible.  The institution should demonstrate a strong commitment to the 
stability and success of the project.  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 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 be in 
the form of commitments to recruit scientific talent, provision of 
discretionary resources to the applicant, assignment of clinical and research 
space, or other ways to be proposed by the applicant. 

Applicants from institutions that have a General Clinical Research Center 
(GCRC) for conducting the proposed research may wish to identify these 
programs as a resource for use or for ongoing clinical trials. Furthermore, 
Hospice Programs and/or National Cancer Institute (NCI) designated Community 
Clinical Oncology Programs  (CCOP) would be appropriate sources of cooperation 
for identifying and recruiting the study population as well as administering 
the intervention and data collection.  A letter of agreement from the GCRC or 
CCOP Principal Investigator and/or the Hospice program director or Principal 
Investigator should be included with the application.  Any cooperating sites 
would be considered subcontractors of the main application and their budgets 
included in the application.

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 sub-populations must be included in all NIH-supported biomedical and 
behavioral research projects involving human subjects, unless a clear and 
compelling rationale and justification are provided indicating that inclusion 
is inappropriate with respect to the health of the subjects or the purpose of  
the research.  This policy results from the NIH Revitalization Act of 1993 
(Section 492B of Public Law 103-43). 

All investigators proposing research involving human subjects should read the 
UPDATED "NIH Guidelines for Inclusion of Women and Minorities as Subjects in 
Clinical Research," published in the NIH Guide for Grants and Contracts on 
August 2, 2000 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-048.html); 
a complete copy of the updated Guidelines are available at  
http://grants.nih.gov/grants/funding/women_min/guidelines_update.htm:  The 
revisions relate to NIH defined Phase III clinical trials and require: a) all 
applications or proposals and/or protocols to provide a description of plans 
to conduct analyses, as appropriate, to address differences by sex/gender 
and/or racial/ethnic groups, including subgroups if applicable; and b) all 
investigators to report accrual, and to conduct and report analyses, as 
appropriate, by sex/gender and/or racial/ethnic group differences.

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  

URLS IN NIH GRANT APPLICATIONS OR APPENDICES

All applications and proposals for NIH funding must be self-contained within 
specified page limitations.  Unless otherwise specified in an NIH 
solicitation, Internet addresses (URLs) should not be used to provide 
information necessary to the review because reviewers are under no obligation 
to view the Internet sites.  Reviewers are cautioned that their anonymity may 
be compromised when they directly access an Internet site.

LETTER OF INTENT

Prospective applicants are asked to submit a letter of intent by February 26, 
2001 that includes a descriptive title of the proposed research, the name, 
address, and telephone number of the Principal Investigator, the identities of 
other key personnel and participating institutions, and the number and title 
of the RFA in response to which the application may be submitted.  Although a 
letter of intent is not required, is not binding, and does not enter into the 
review of a subsequent application, the information that it contains allows 
NCCAM staff to estimate the potential review workload and plan the review.

The letter of intent is to be sent to:

Mary Ann Richardson, DrPH
National Center for Complementary and Alternative Medicine
National Institutes of Health
6707 Democracy Boulevard, Suite 106
Bethesda, MD 20892-5475
Phone: 301-402-1272
FAX:   301-480-3621
Email: marich@od.nih.gov

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.  Applications are also available on the World Wide Web at 
http://grants.nih.gov/grants/forms.htm.

SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS 

The MODULAR GRANT concept establishes specific modules in which direct costs 
may be requested as well as a maximum level for requested budgets. Only 
limited budgetary information is required under this approach. The JUST-IN-
TIME concept allows applicants to submit certain information only when there 
is a possibility for an award. It is anticipated that these changes will 
reduce the administrative burden for the applicants, reviewers and NCCAM 
staff. 

MODULAR GRANT applications request direct costs in $25,000 modules. The total 
direct costs must be requested in accordance with the program guidelines and 
the modifications made to the standard PHS 398 application instructions 
described below: 

(a) PHS 398

o  FACE PAGE: Items 7a and 7b should be completed, indicating Direct Costs in 
$25,000 increments.  The total cost may be up to a maximum of $500,000 
[Modular Direct Cost Total plus Facilities and Administrative (F&A) costs] for 
the initial budget period.  Items 8a and 8b should be completed indicating the 
Direct and Total Costs for the entire proposed period of support.

o  DETAILED BUDGET FOR THE INITIAL BUDGET PERIOD - Do not complete Form Page 4 
of the PHS 398. It is not required and will not be accepted with the 
application.

o  BUDGET FOR THE ENTIRE PROPOSED PERIOD OF SUPPORT - Do not complete the 
categorical budget table on Form Page 5 of the PHS 398. It is not required and 
will not be accepted with the application. 

o  NARRATIVE BUDGET JUSTIFICATION - Prepare a Modular Grant Budget 
 Narrative page. (See http://grants.nih.gov/grants/funding/modular/modular.htm 
for sample pages.) At the top of the page, enter the total direct costs 
requested for each year. This is not a Form page.
 
 Under Personnel, list all project personnel, including their names, percent of 
effort, and roles on the project. No individual salary information should be 
provided. However, the applicant should use the NIH appropriation language 
salary cap and the NIH policy for graduate student compensation in developing 
the budget request.
 
 For Consortium/Contractual costs, provide an estimate of total costs (direct 
plus facilities and administrative) for each year, each rounded to the nearest 
$1,000. List the individuals/organizations with whom consortium or contractual 
arrangements have been made, the percent effort of all personnel, and the role 
on the project. Indicate whether the collaborating institution is foreign or 
domestic. The total cost for a consortium/contractual arrangement is included 
in the overall requested modular direct cost amount. Include the Letter of 
Intent to establish a consortium.
 
 Applicants are strongly encouraged to request the same number of modules for 
each year of funding. Provide an additional narrative budget justification for 
any variation in the number of modules requested.
 
o  BIOGRAPHICAL SKETCH - The Biographical Sketch provides information used by 
reviewers in the assessment of each individual's qualifications for a specific 
role in the proposed project, as well as to evaluate the overall 
qualifications of the research team. A biographical sketch is required for all 
key personnel, following the instructions below. No more than three pages may 
be used for each person. A sample biographical sketch may be viewed at 
http://grants.nih.gov/grants/funding/modular/modular.htm. 

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

o  CHECKLIST - This page should be completed and submitted with the 
application. If the F&A rate agreement has been established, indicate the type 
of agreement and the date. All appropriate exclusions must be applied in the 
calculation of the F&A costs for the initial budget period and all future 
budget years.
 
o  The applicant should provide the name and phone number of the individual to 
contact concerning fiscal and administrative issues if additional information 
is necessary following the initial review. 

(b) Mailing Procedures
The RFA label available in the PHS 398 (rev. 4/98) application form 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 such that it may 
not reach the review committee in time for review. 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 signed, original of the application, including the Checklist, and 
four (4) signed photocopies of the application in one package to: 

CENTER FOR SCIENTIFIC REVIEW (formerly Division of Research Grants)
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710
BETHESDA, MD 20892-7710
BETHESDA, MD 20817 (for express/courier service)

At the time of submission, send one (1) additional copy of the application to:

Chief, Review Branch 
National Center for Complementary and Alternative Medicine
National Institutes of Health
6707 Democracy Boulevard, Suite 106
Bethesda, MD 20892-5475

It is important to send this copy at the same time that the original and four 
copies are sent to the Center for Scientific Review (CSR).

Applications must be received by April 12, 2001.  If an application is 
received after that date, it will be returned to the applicant without review. 
The Center for Scientific Review (CSR) will not accept any application in 
response to this RFA that is essentially the same as one currently pending 
initial review, unless the applicant withdraws the pending application. The 
CSR will not accept any application that is essentially the same as one 
already reviewed. This does not preclude the submission of substantial 
revisions of applications already reviewed, but such applications must include 
an introduction addressing the previous critique.

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed for completeness by the CSR and 
responsiveness by the NCCAM.  Incomplete and/or non-responsive applications 
will be returned to the applicant without further consideration.

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 review criteria stated below.  As part of the 
initial merit review, all applications will receive a written critique and may 
undergo a process in which only those applications deemed to have the highest 
scientific merit, generally the top half of the applications under review, 
will be discussed, assigned a priority score, and receive a second level 
review by the NCCAM National Advisory Council.

Review Criteria

The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  In 
the written comments, reviewers will be asked to discuss the following aspects 
of the application in order to judge the likelihood that the proposed research 
will have a substantial impact on the pursuit of these goals.  Each of these 
criteria will be addressed and considered in assigning the overall score, 
weighting them as appropriate for each application.  Note that the application 
does not need to be strong in all categories to be judged likely to have major 
scientific impact and thus deserve a high priority score.  For example, an 
investigator may propose to carry out important work that by its nature is not 
innovative but is essential to move a field forward.

In addition to the criteria list below, the initial review group will examine: 
the appropriateness of proposed project budget and duration; the adequacy of 
plans to include subjects of both genders, minorities (and their subgroups), 
and children as appropriate for the scientific goals of the research, and 
plans for the recruitment and retention of subjects; the provisions for the 
protection of human and animal subjects; and the safety of the research 
environment.

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

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? For Exploratory/Developmental (R21) Research Projects, what is the 
likelihood that the research will contribute to the development of 
interdisciplinary programs or more mature research endeavors?

o  Degree to which the research will improve our understanding of how we can 
narrow the gap between what is known and what is currently used as end of life 
treatments;
o  Likelihood of the development of interventions that can be applied to a 
variety of conditions and in a range of settings;
 
(2) APPROACH: Are the conceptual framework, design, methods, and analyses 
adequately developed, well integrated, and appropriate to the aims of the 
project? Does the applicant acknowledge potential problem areas and consider 
alternative tactics? 

o  Extent to which the project builds-on or establishes meaningful linkages 
between CAM practitioners, researchers, and conventional practitioners; 
o  Plans for dissemination and implementation of findings within and outside 
of the grantee’s organization.

(3) INNOVATION: Does the project employ novel concepts, approaches or method? 
Are the aims original and innovative? Does the project challenge existing 
paradigms or develop new methodologies or technologies? 

(4) INVESTIGATORS: Is each 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)? 

o  Incorporation of appropriate CAM expertise, including certified or licensed 
CAM practitioners, throughout the design and execution stage is encouraged;

(5) ENVIRONMENT: Does the scientific environment in which the work will be 
done contribute to the probability of success of the project? Do the proposed 
studies take advantage of unique features of the scientific environment or 
employ useful collaborative arrangements?

o  Demonstration of substantial institutional commitment by the health care 
organization/system to the CAM intervention, including use of in-kind support 
and letters of support from clinical and administrative staff;
o  Adequacy of facilities to perform the proposed research, including clinical 
facilities and data management systems, when needed;

In addition to the above criteria, in accordance with NIH policy, all 
applications will also be reviewed with respect to the following:

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

o  The reasonableness of the proposed budget and duration in relation to the 
proposed research.

o  The adequacy of the proposed protection for humans, animals or the 
environment, to the extent they may be adversely affected by the project 
proposed in the application.

SCHEDULE

Letter of Intent Receipt Date:    February 26, 2001
Application Receipt Date:         April 12, 2001
Council Review:                   August, 2001
Earliest Anticipated Start Date:  September, 2001

AWARD CRITERIA

Applications will compete for available funds with all other recommended 
applications submitted in response to this RFA. The following will be 
considered in making funding decisions:

o  The quality of the proposed project as determined by peer review;
 
o  Availability of funds; and
 
o  The research priorities of the NCCAM.

INQUIRIES

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

Direct inquiries regarding specific PROGRAMMATIC ISSUES to: 

Christopher M. Gordon, PhD
Chief, Secondary HIV Prevention & Treatment Adherence
Division of Mental Disorders, Behavioral Research & AIDS
National Institute of Mental Health
National Institutes of Health 
6001 Executive Boulevard, Bethesda, MD 20892-9621
Telephone:  301-443-1613 
Fax:  301-443-9719
E-mail: cgordon1@mail.nih.gov

Ann R. Knebel, RN, DNSc
Division of Extramural Activities
National Institute of Nursing Research
Building 45, Room 3AN12, MSC 6300
Bethesda, MD  20892-6300
Telephone:  (301) 594-5966
FAX:  (301) 480-8260
Email:  aknebel@nih.gov

Katherine W. Muth, R.N., M.S. 
Nurse Consultant 
Office of the Associate Director 
Treatment Research Program 
Division of AIDS, NIAID 
6700-B Rockledge Drive, Room 5215 
Bethesda, MD 20892 
Ph:   (301)496-1189 
FAX: (301)435-9282 
E-mail: KMuth@niaid.nih.gov

Mary Ann Richardson, DrPH
Program Officer, 
National Center for Complementary and Alternative Medicine
National Institutes of Health
6707 Democracy Boulevard, Suite 106
Bethesda, MD 20892-5475
Telephone: 301-402-1272
Fax: 301-480-3621
E-mail: marich@mail.nih.gov

Wendy B. Smith, PhD
Program Manager, Research Development and Support Program
Office of Cancer Complementary and Alternative Medicine
Office of the Deputy Director for Extramural Science
National Cancer Institute
Telephone:  301-435-7980
FAX: 301-480-0075
E-mail: wsmith@mail.nih.gov

Direct inquiries regarding FISCAL MATTERS to: 

Ms. Victoria Putprush
Grants Administration Branch
National Center for Complementary and Alternative Medicine
National Institutes of Health
6707 Democracy Boulevard, Suite 106
Bethesda, MD 20892-5475
Telephone: 301-594-9102
Fax: 301-480-3621
E-mail: vp8g@nih.gov

Mr. Robert Tarwarter
Office of Grants and Contracts Management
National Institute of Nursing Research
Building 45, Room Number 3AN12, MSC 6300
Bethesda, MD 20892-6300
Telephone: (301) 594-2807
FAX: (301) 480-8260
Email: Robert_tarwater@nih.gov

Direct Inquiries regarding REVIEW ISSUES to:

Chief, Review Branch 
National Center for Complementary and Alternative Medicine
National Institutes of Health
6707 Democracy Boulevard, Suite 106
Bethesda, MD 20892-5475
Telephone:  301-496-4252
Fax: 301-480-3621
Email: TBA

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance No. 
93.213 and 93.361.  Awards are made under authorization of Sections 301 and 
405 of the Public Health Service Act as amended (42 USC 241 and 284) and 
administered under NIH grants policies and Federal Regulations 42 CFR 52 and 
45 CFR Parts 74 and 92.  This program is not subject to the intergovernmental 
review requirements of Executive Order 12372 or Health Systems Agency review. 

The PHS strongly encourages all grant and contract recipients to provide a 
smoke-free workplace and promote the non-use of all tobacco products. In 
addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking 
in certain facilities (or in some cases, 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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