THE USE OF COMPLEMENTARY AND ALTERNATIVE MEDICINE (CAM) IN THE MANAGEMENT
OF HIV/AIDS  
 
RELEASE DATE:  September 16, 2004
 
RFA Number:  RFA-AT-05-004  

EXPIRATION DATE:  January 15, 2005

Department of Health and Human Services (DHHS)
 
PARTICIPATING ORGANIZATION:
National Institutes of Health (NIH)
 (http://www.nih.gov/) 

COMPONENTS OF PARTICIPATING ORGANIZATION:  
National Center or Complementary and Alternative Medicine (NCCAM)
 (http://nccam.nih.gov)

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S) 93.213
 
LETTER OF INTENT RECEIPT DATE:  December 14, 2004
APPLICATION RECEIPT DATE:  January 14, 2005  
 
THIS RFA CONTAINS THE FOLLOWING INFORMATION

o Purpose of this RFA
o Research Objectives
o Mechanism of Support 
o Funds Available
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Special Requirements 
o Where to Send Inquiries
o Letter of Intent
o Submitting an Application
o Supplementary Instructions
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations

PURPOSE OF THIS RFA 

This initiative will stimulate research to elucidate the mechanisms, risks,  
and benefits of using complementary and alternative medicine (CAM) in the 
management of HIV/AIDS at institutions with extensive histories of research 
on HIV/AIDS (see “Eligible Institutions” below).  NCCAM is especially 
interested in supporting well-designed studies to identify potential roles 
for the safe and effective use of CAM in the management of HIV/AIDS and its 
complications, to ameliorate medication side effects, or improve quality of 
life.   

RESEARCH OBJECTIVES

Background

Highly-active antiretroviral therapy (HAART) and prophylactic medications for 
opportunistic infections have prolonged life and increased quality of life 
dramatically for persons with HIV/AIDS.  Nonetheless they continue to suffer 
from the physical and emotional consequences of the disease and its 
treatments, leading the majority of HIV-infected individuals by some surveys  
to seek relief through CAM.  While some of these approaches may be 
beneficial, they risk displacing or interfering with proven treatments and 
often exact their own toll through added side effects.  Although there have 
been numerous studies of CAM approaches to HIV/AIDS and its complications, 
few have been of the size or rigor to yield results worthy of being pursued 
in larger scale prospective trials.  The multidisciplinary nature of the 
studies needed to address the possible mechanisms of action, safety, 
pharmacology, and potential clinical utility of CAM approaches for HIV/AIDS 
dictates that the most interesting and feasible CAM approaches for HIV/AIDS 
now be placed before investigators at institutions with the research 
experience and resources commensurate with achieving this RFA’s goals.  NCCAM 
in the past has released RFAs aimed at promoting studies of CAM approaches in 
HIV/AIDS and of botanical/antiretroviral drug interactions.  The science 
resulting from these program announcements indicates that research on HIV and 
CAM is a fruitful area to pursue.  Few of the investigators doing this 
research have been from institutions that have sizable HIV/AIDS patient 
populations or research laboratories and infrastructure that could move this 
field even further forward.  To this end, NCCAM proposes to fund 
investigators at institutions with a substantial history of HIV/AIDS research 
to undertake basic, translational or early phase clinical trials to 
investigate a variety of CAM approaches in HIV/AIDS and its complications.  

CAM practices are described as those not presently considered an integral part 
of conventional medicine.  NCCAM has categorized the wide range of CAM 
modalities into five broad areas: 1) Alternative Medical Systems; 2) Mind-Body 
Interventions; 3) Biologically-based Therapies; 4) Manipulation and Body-based 
Methods; and 5) Energy Therapies.  The medical literature includes reports of 
CAM use from each of the areas in patients with HIV infection. 

1) Alternative medical systems are built upon complete systems of theory and 
practice, and include Traditional Medicine systems that often have evolved 
apart from and earlier than the conventional medical approach used in the 
United States.  Examples of traditional systems, many of which have developed 
in non-Western cultures, include traditional Chinese medicine, Ayurveda, and 
Unani, as well as traditional Native American (American Indian) and 
African/African-American systems.  Examples of alternative medical systems 
that largely have developed in Western cultures include homeopathic medicine 
and naturopathic medicine. 

2) Mind-Body interventions use a variety of techniques designed to enhance the 
mind's capacity to affect bodily function and symptoms.  Some techniques that 
were considered CAM in the past have become mainstream, for example, patient 
support groups and cognitive-behavioral therapy.  Other mind-body techniques 
are still considered CAM, including meditation, prayer, mental healing, and 
therapies that use creative outlets such as art, music, or dance.    

3) Biologically-based therapies in CAM use foods, diets, and dietary 
supplements such as vitamins, herbs, and other natural products.  

4) Manipulation and body-based methods in CAM are based on manipulation and/or 
movement of one or more parts of the body.  Examples include chiropractic or 
osteopathic manipulation, and massage therapy.    

5) Energy therapies are of two types: 1) Biofield therapies (e.g., Qi gong, 
Reiki, and Therapeutic Touch), which are intended to affect energy fields that 
purportedly surround and penetrate the human body, and 2) Bioelectromagnetic-
based therapies that involve the unconventional use of electromagnetic fields 
such as pulsed fields, magnetic fields, or alternating current or direct 
current fields.    

Although literature supporting the effectiveness of CAM for the treatment of 
HIV-related disease is limited, HIV-infected persons reportedly use CAM at 
higher rates than the general population; estimates range from 41% to 84%, and  
HIV-infected persons report substantial increases in CAM use after the 
diagnosis of HIV infection.  Generally, patients with HIV infection use CAM 
modalities in association with, rather than as a substitute for, conventional 
medical care.  Although many patients perceive the use of CAM to be 
beneficial, the absence of controlled studies examining the outcomes of CAM 
use raises questions about the effectiveness of these interventions.  

Patients with HIV infection use CAM for many reasons:  to reduce HIV-related 
symptoms or medication side effects such as nausea, fatigue, and weight loss; 
to strengthen the immune system, maintain health, and slow the progression of 
infection; to enhance energy, increase productivity, promote emotional well 
being, and reduce stress as well as depression; and to increase quality of 
life and perceived control over the disease process.  In view of the potential 
effect of patient expectation on perceptions of benefit, well-designed studies 
are needed on the effectiveness of various CAM interventions used by patients 
with HIV/AIDS.

While the use of ineffective CAM therapies cannot be advocated in place of 
proven pharmaceutical therapy, there are circumstances in the clinical course 
and management of HIV disease where the use of CAM therapies merits study.  
For example, recent changes in recommendations have resulted in later 
initiation of highly active antiretroviral therapy (HAART).  Studies may 
investigate ethically the use of CAM to reduce viral load earlier in the 
course of infection and potentially delay progression of HIV infection prior 
to the time conventional treatment is initiated.  Also, data indicate the 
emergence of drug-resistant virus.  Although more new medications are being 
developed and introduced, individuals with drug-resistant virus may be 
candidates for complementary non-pharmaceutical treatment.  With the increased 
life expectancy afforded by HAART, individuals are taking antiretroviral 
medications for longer periods of time, thereby increasing the risk of side 
effects.  Anecdotal reports and some literature suggest that CAM may have a 
role in ameliorating these side effects.  While the discovery of potent and 
effective CAM antiretroviral treatments may not be highly likely, some agents 
might be found to be sufficiently active to warrant use by individuals who 
cannot tolerate or do not accept conventional drugs.  Moreover, they may be 
adequate to enhance antiviral responses when combined with conventional 
therapy, thereby decreasing required doses of pharmaceuticals, potentially 
lessening medication side effects and improving patient compliance.  Finally, 
the identification of useful CAM antiretrovirals might serve to identify 
promising leads for drug development.  Additional research is needed on a wide 
range of CAM interventions, alone or in combination with conventional 
treatments, to identify those CAM modalities that have potential roles in 
treating HIV/AIDS, its complications, ameliorating medication side effects, or 
improving quality of life.

Objectives

The objectives of this solicitation are to (1) identify potential roles for 
CAM therapies in managing HIV/AIDS and/or its complications: a) prior to 
initiation of HAART; b) in association with HAART; c) by ameliorating HAART 
side effects; or d) through increasing the quality of life for people with 
HIV/AIDS; (2) understand mechanisms of action of CAM interventions that have 
the potential for contributing to or interfering with standard treatments for 
HIV/AIDS and related conditions; and (3) stimulate CAM research at leading 
HIV/AIDS research institutions.  

Applicants are encouraged strongly to collaborate with investigators funded 
in AIDS research and to document (as appropriate) use of a Developmental 
Center or Center for AIDS Research (D-CFAR/CFAR) Core or a patient population 
already being studied in an HIV/AIDS therapeutic clinical trials network.  
Appropriate letters of support should be included in applications utilizing 
resources of a D-CFAR/CFAR or clinical trials network.  

Prospective applicants may speak with the program contact for assistance in 
identifying funded investigators at their institutions who might be potential 
collaborators.  (See “scientific/research issues” below under “Where to Send 
Inquiries.”)

NCCAM is soliciting applications for research projects investigating the 
range of CAM modalities that have the potential to contribute to the 
management of HIV/AIDS.  Projects may range from basic through clinical 
studies, including in vitro, animal model, phase I human trials, and small 
phase II trials.  While R21 applications do not require preliminary data, 
applications proposing clinical studies through this RFA will need to provide 
a persuasive scientific rationale for the intended project.  Both preclinical 
and early clinical data will be needed to justify phase II trials.  Studies 
that investigate interactions between natural products and drugs used to 
treat HIV infection or the clinical outcomes of treatment for HIV infection 
combining natural products with antiretroviral therapy will be considered 
responsive to this solicitation.  Following is a list of the types of studies 
that might be undertaken through this RFA; this list is exemplary, not 
exhaustive.

o Projects that study the effects of CAM interventions (including botanical 
substances or other natural products) alone or in combination with 
antiretroviral therapy, on the progression of HIV infection or on clinical 
outcomes.  
o Studies of CAM interventions in treating HIV in animal model systems.
o Studies on potential roles for CAM interventions (e.g., homeopathic 
remedies, various energy modalities, meditation, mind-body practices, etc.) 
in HIV-infected patients to slow the progression of disease, decrease 
symptoms of HIV infection, ameliorate medication side effects, or improve 
quality of life. 
o Studies of the effects of CAM interventions, alone or in combination with 
antiretroviral therapy, on patient adherence to conventional therapy.
o Projects to characterize and investigate the safety and efficacy of 
interventions from traditional medicine systems (e.g., Traditional Indian 
Medicine, Traditional Chinese Medicine, Ayurveda, etc.) used to treat HIV 
infection or its complications.
o In vitro studies examining antiretroviral properties of herbs or other 
natural products.
o Studies investigating interactions between natural products and drugs used 
to treat HIV infection.
o Clinical studies of natural products shown to have strong anti-HIV activity 
in vitro.  
o Studies of the impact of massage therapy and other manual therapies on 
objective and subjective measures of symptoms, HIV infection, or quality of 
life. 
o The use of CAM interventions to improve the well being or enhance quality 
of life for patients with HIV infection.

MECHANISM OF SUPPORT

This RFA will use the NCCAM R21 award mechanism.  For basic science R21 
applications, the grant award is limited to a two-year project period with 
direct costs of not more than $125,000 per year.  Please see the Program 
Announcement, Basic and Preclinical Research on Complementary and Alternative 
Medicine (http://grants.nih.gov/grants/guide/pa-files/PA-02-124.html) for 
additional information.  For clinical R21 applications, the grant award is 
limited to a three-year project period and total direct costs of $400,000 
over the life of the grant with not more than $250,000 in any one year.  For 
further information regarding NCCAM’s clinical R21 grant mechanism, please 
see the Program Announcement, NCCAM Exploratory/Developmental Grant for 
Clinical Studies (http://grants.nih.gov/grants/guide/pa-files/PAR-03-153.html).
As an applicant you will be solely responsible for planning, 
directing, and executing the proposed project.  This RFA is a one-time 
solicitation.  Future unsolicited, competing-continuation applications based 
on this project will compete with all investigator-initiated applications and 
will be reviewed according to the customary peer review procedures.  The 
anticipated award date is July 2005.  Applications that are not funded in the 
competition described in this RFA may be resubmitted as NEW investigator-
initiated applications using the standard receipt dates for NEW HIV/AIDS 
applications described in the instructions to the PHS 398 application. 

This RFA uses just-in-time concepts.  It also uses the modular budgeting 
format. (See http://grants.nih.gov/grants/funding/modular/modular.htm.)  
Because this solicitation uses the R21 mechanism that limits direct costs in 
any year to $250,000 or less, use the modular budget format.  This program 
does not require cost sharing as defined in the current NIH Grants Policy 
Statement at 
http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part2.htm.  

FUNDS AVAILABLE 
 
NCCAM intends to commit approximately $1.5 million in FY 2005 to fund 4 to 6 
new grants in response to this RFA.  For clinical R21 grants, an applicant 
may request a project period of up to 3 years and a budget for direct costs 
of up to $400,000, not to exceed $250,000 in any one year.  For basic or 
preclinical R21 research grants, an applicant may request a project period of 
up to 2 years and a budget for direct costs of up to $125,000 per year.  
Because the nature and scope of the proposed research will vary from 
application to application, it is anticipated that the size and duration of 
each award will also vary.  Although the financial plans of NCCAM 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.  
 
ELIGIBLE INSTITUTIONS 
 
To be eligible for an award through this solicitation, institutions will be 
required to have a National Institutes of Health grant for a Center for AIDS 
Research (CFAR), a Developmental Center for AIDS Research (D-CFAR), or be a 
unit of an Adult AIDS Clinical Trial Group (AACTG), a Pediatric AIDS Clinical 
Trial Group (PACTG), or the Community Program for Clinical Research on AIDS 
(CPCRA) (including affiliate units).  This solicitation will stimulate basic, 
clinical, and translational research to investigate the range of potential 
uses as well as the risks of CAM use in the treatment of HIV/AIDS at resource 
intensive institutions with a history of substantial involvement in HIV/AIDS 
research.
 
INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS   

Any individual with the skills, knowledge, and resources necessary to carry 
out the proposed research is invited to work with their institution to 
develop an application for support.  Individuals from underrepresented racial 
and ethnic groups as well as individuals with disabilities are always 
encouraged to apply for NIH programs.   
 
SPECIAL REQUIREMENTS 

The following special requirements apply to all applications concerning 
research with natural substances.  Please consult the NCCAM website for 
additional details regarding policies for clinical research using natural 
substances (http://nccam.nih.gov/research/policies/index.htm). 

Many practitioners of complementary and alternative medicine (CAM) believe 
that the polypharmacy of complex natural products has advantages over single-
ingredient drugs by providing greater therapeutic benefit and less overall 
toxicity.  In pursuit of its mission, the National Center for Complementary 
and Alternative Medicine (NCCAM) supports research to determine safety, 
efficacy, and mechanisms of action of complex natural products.  NCCAM will 
support research characterizing single constituents extracted from complex 
natural products if the purpose is to identify and standardize whole 
products, compare the actions of single constituents with the complex 
product, or identify mechanisms of action for the whole product.  NCCAM will 
not accept applications to isolate the active constituents of complex natural 
products for the express purpose of developing these constituents as discrete 
drugs.  Funding support for applications to develop active constituents as 
drugs may be available from other Institutes and Centers at the National 
Institutes of Health (NIH).

Investigators seeking funding from NCCAM for research that involves natural 
products must consider several issues when designing their studies and 
preparing their applications.  Overall, the applicant is responsible for 
convincing NCCAM and NIH review committees that the natural products chosen 
are of sufficient quality to merit study as proposed.

For these products, the levels of characterization, standardization, 
stability, purity, and optimization of the presumed active ingredient(s) will 
vary, and for some, the active ingredient(s) may be unknown.  However, 
natural products should be chemically characterized as thoroughly as the 
state of the science allows, and the methods used must be described.  When 
the active compound is unknown, "marker" compounds may be identified and 
measured.  In addition to testing for what is intended to be in the natural 
products, the products should also be tested for contaminants such as 
microorganisms, pesticide residues, toxic elements, mycotoxins, and drugs. 
For in vitro studies of extracts or isolated chemical constituents of natural 
products that are normally ingested, the concentrations and chemical 
constituents should be physiologically and pharmacologically relevant.

For studies of complex natural products, the experts who serve on NIH peer 
review committees must be convinced that the natural products to be used in 
any study are described in sufficient detail that the results can be 
understood and independently reproduced.  Whether or not the test material 
derives from American or foreign commercial companies or other sources, 
including individually prepared, unique mixtures, evidence must be provided 
that the source of the test material has been reliably identified.  For 
botanical natural products, this evidence may include, but is not limited to, 
the correct plant name (Latin binomial with authority, cultivar where 
appropriate), geographic source of the material, time of harvest, plant part, 
and credentials of the person who collected and/or identified the material.  
The content of the test material should be described by the commercial 
company or tested by an independent laboratory.  This analysis should be 
accomplished through an analytical characterization of the major identified 
components, and, if known, the active component(s) in the product.  
Independent of the study design, verification of the samples before the start 
and at the end of the study is needed to ensure product stability.  
Additional quality control measures may include plans for archiving samples, 
batch to batch reproducibility studies, short-term and long-term stability 
studies, and analysis of contamination with heavy metals, as well as organic 
or inorganic inert or active components.

Applicants should also consider having natural products, including those 
obtained from commercial sources, tested by an independent laboratory. 
Depending on the study design, independent verification of the samples before 
the start and at the end of the study may be necessary to ensure product 
stability.  

For investigators proposing clinical studies of natural products, the 
applicant should provide documentation, at the time of application, that 
contacts with the FDA have begun concerning the necessity of an IND.  
Activities concerned with completion of the IND submission, if required by 
the FDA, may be budgeted in the first 6 months of the application.

If the proposed research is investigating practitioner-based CAM (e.g., 
acupuncture, chiropractic, massage therapy, etc.), qualified CAM 
practitioners must be included as active members of the research team.

Competitive applications in response to this RFA will demonstrate 
collaboration with existing NIH-funded HIV/AIDS programs and utilization of 
existing infrastructure at the institution.  Funds will not be provided to 
establish new clinical cohorts or to develop new core facilities.

WHERE TO SEND INQUIRIES

We encourage inquiries concerning this RFA and welcome the opportunity to 
answer questions from potential applicants.  Inquiries may fall into three 
areas:  scientific/research, peer review, and financial or grants management 
issues:

o Direct your questions about scientific/research issues to:

Morgan N. Jackson, M.D., M.P.H.
National Center for Complementary and Alternative Medicine
National Institutes of Health
6707 Democracy Blvd., Suite 401
Bethesda, MD 20892-5475 
(for express/courier service use Bethesda, MD 20817)
Telephone: 301-402-1278
Fax: 301-480-3621
email: mj145m@nih.gov
 
o Direct your questions about peer review issues to:

Dr. Martin Goldrosen 
National Center for Complementary and Alternative Medicine 
6707 Democracy Blvd., Suite 401 
Bethesda, MD 20892-5475 
Telephone: 301-594-2014 
Fax: 301-480-2419 
Email: mg85x@nih.gov   

o Direct your questions about financial or grants management matters to:

Mr. George Tucker 
Grants Management Branch 
National Center for Complementary and Alternative Medicine 
6707 Democracy Blvd., Suite 401 
Bethesda, MD 20892-5475 
Telephone: 301-594-9102 
Email: george.tucker@nih.hhs.gov  
 
LETTER OF INTENT
 
Prospective applicants are asked to submit a letter of intent that includes 
the following information:

o Descriptive title of the proposed research
o Name, address, and telephone number of the Principal Investigator
o Names of other key personnel 
o Participating institutions
o 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 a subsequent application, the information that it 
contains allows IC staff to estimate the potential review workload and plan 
the review.
 
The letter of intent is to be sent by the date listed at the beginning of 
this document.  The letter of intent should be sent to:

Morgan N. Jackson, M.D., M.P.H.
National Center for Complementary and Alternative Medicine
National Institutes of Health
6707 Democracy Blvd., Suite 401
Bethesda, MD 20892-5475 
Bethesda, MD 20817 (use for express/courier service)

SUBMITTING AN APPLICATION

Applications must be prepared using the PHS 398 research grant application 
instructions and forms (rev. 5/2001).  Applications must have a DUN and 
Bradstreet (D&B) Data Universal Numbering System (DUNS) number as the 
Universal Identifier when applying for Federal grants or cooperative 
agreements.  The DUNS number can be obtained by calling (866) 705-5711 or 
through the web site at http://www.dunandbradstreet.com/.  The DUNS number 
should be entered on line 11 of the face page of the PHS 398 form.  The PHS 
398 document is available at 
http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive 
format.  For further assistance contact GrantsInfo, Telephone (301) 435-0714, 
Email: GrantsInfo@nih.gov.
 
SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS:  Applications 
requesting up to $250,000 per year in direct costs must be submitted in a 
modular grant format.  The modular grant format simplifies the preparation of 
the budget in these applications by limiting the level of budgetary detail.  
Applicants request direct costs in $25,000 modules.  Section C of the 
research grant application instructions for the PHS 398 (rev. 5/2001) at 
http://grants.nih.gov/grants/funding/phs398/phs398.html includes step-by-step 
guidance for preparing modular grants.  Additional information on modular 
grants is available at 
http://grants.nih.gov/grants/funding/modular/modular.htm.

USING THE RFA LABEL: The RFA label available in the PHS 398 (rev. 5/2001) 
application form must be affixed to the bottom of the face page of the 
application.  Type the RFA number on the label.  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 RFA label is also available at: 
http://grants.nih.gov/grants/funding/phs398/labels.pdf.
 
SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten original of 
the application, including the Checklist, and three signed, photocopies, in 
one package to:
 
Center For Scientific Review
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, two additional copies of the application and all 
copies of the appendix material must be sent to:

Dr. Martin Goldrosen 
National Center for Complementary and Alternative Medicine 
6707 Democracy Blvd., Suite 401 
Bethesda, MD 20892-5475
Bethesda, MD  20817 (for express/courier service) 

APPLICATION PROCESSING: Applications must be received by the Center for 
Scientific Review on or before the application receipt date listed in the 
heading of this RFA.  If an application is received after that date, it will 
be returned to the applicant without review. 

Although there is no immediate acknowledgement of the receipt of an 
application, applicants are generally notified of the review and funding 
assignment within 8 weeks.
 
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.  
However, when a previously unfunded application, originally submitted as an 
investigator-initiated application, is to be submitted in response to an RFA, 
it is to be prepared as a NEW application.  That is, the application for the 
RFA must not include an Introduction describing the changes and improvements 
made, and the text must not be marked to indicate the changes from the 
previous unfunded version of the application.  

PEER REVIEW PROCESS  
 
Upon receipt, applications will be reviewed for completeness by the CSR and 
responsiveness by NCCAM.  Incomplete applications will not be reviewed.  If 
the application is not responsive to the RFA, NIH staff may contact the 
applicant to determine whether to return the application to the applicant or 
submit it for review in competition with unsolicited applications at the next 
appropriate NIH review cycle.

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 NCCAM in accordance with the review criteria stated below.  As 
part of the initial merit review, all applications will:

o 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 and assigned a priority score
o Receive a written critique
o Receive a second level review by the National Advisory Council on 
Complementary and Alternative Medicine.

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 evaluate the application in 
order to judge the likelihood that the proposed research will have a 
substantial impact on the pursuit of these goals. The scientific review group 
will address and consider each of the following criteria in assigning the 
application’s overall score, weighting them as appropriate for each 
application. 

o Significance 
o Approach 
o Innovation
o Investigator
o Environment
  
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.

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?  If a clinical study is proposed, will the study impact clinical 
practice or lead to a definitive trial?

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?  If a natural product is being studied, is the product 
adequately characterized and standardized?

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?

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)?  Does the 
investigator have extensive experience studying HIV or its complications?  
Are CAM practitioners adequately integrated into the research team where 
appropriate?  

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?  
Does the institution have a previous history of support for developmental 
projects?  Does the institution have a history of research on HIV/AIDS?  Is 
an HIV-positive population available for any proposed clinical research?  
Does the research team have the ability to accrue and retain a 
demographically diverse patient population consistent with accrual 
projections?  Are community representatives involved in project activities as 
appropriate?  Does the application include appropriate letters of support for 
projects utilizing resources of a D-CFAR/CFAR or clinical trials network?  
Will the project enhance multidisciplinary collaborations? 

PROTECTION OF HUMAN SUBJECTS FROM RESEARCH RISK: The involvement of human 
subjects and protections from research risk relating to their participation 
in the proposed research will be assessed. (See criteria included in the 
section on Federal Citations, below).
 
INCLUSION OF WOMEN, MINORITIES AND CHILDREN IN RESEARCH: The adequacy of 
plans to include subjects from both genders, all racial and ethnic groups 
(and subgroups), and children as appropriate for the scientific goals of the 
research.  Plans for the recruitment and retention of subjects will also be 
evaluated. (See Inclusion Criteria in the sections on Federal Citations, 
below).

CARE AND USE OF VERTEBRATE ANIMALS IN RESEARCH: If vertebrate animals are to 
be used in the project, the five items described under Section f of the PHS 
398 research grant application instructions (rev. 5/2001) will be assessed.  

ADDITIONAL REVIEW CONSIDERATIONS

BUDGET:  The reasonableness of the proposed budget and the requested period 
of support in relation to the proposed research.

COLLABORATION:  The utilization of existing infrastructure at the institution 
and collaboration with existing NIH-funded HIV/AIDS programs. 

RECEIPT AND REVIEW SCHEDULE

Letter of Intent Receipt Date:    December 14, 2004
Application Receipt Date:         January 14, 2005
Peer Review Date:                 March/April 2005
Council Review:                   June 2005
Earliest Anticipated Start Date:  July 2005

AWARD CRITERIA

Award criteria that will be used to make award decisions include:

o Scientific merit (as determined by peer review)
o Availability of funds
o Programmatic priorities.
 
REQUIRED FEDERAL CITATIONS 

HUMAN SUBJECTS PROTECTION:  Federal regulations (45CFR46) require that 
applications and proposals involving human subjects must be evaluated with 
reference to the risks to the subjects, the adequacy of protection against 
these risks, the potential benefits of the research to the subjects and 
others, and the importance of the knowledge gained or to be gained.
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm

DATA AND SAFETY MONITORING  PLAN:  Data and safety monitoring is required for 
all types of clinical trials, including physiologic, toxicity, and dose-
finding studies (phase I); efficacy studies (phase II); efficacy, 
effectiveness and comparative trials (phase III).  The establishment of data 
and safety monitoring boards (DSMBs) is required for multi-site clinical 
trials involving interventions that entail potential risk to the 
participants.  (NIH Policy for Data and Safety Monitoring, NIH Guide for 
Grants and Contracts, June 12, 1998: 
http://grants.nih.gov/grants/guide/notice-files/not98-084.html).  

INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH:  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 clinical research projects unless a 
clear and compelling justification is 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 clinical research should read the "NIH Guidelines 
for Inclusion of Women and Minorities as Subjects in Clinical Research - 
Amended, October, 2001," published in the NIH Guide for Grants and Contracts 
on October 9, 2001 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html);
a complete copy of the updated Guidelines are available at 
http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.
The amended policy incorporates: the use of an NIH definition of clinical 
research; updated racial and ethnic categories in compliance with the new OMB 
standards; clarification of language governing NIH-defined Phase III clinical 
trials consistent with the new PHS Form 398; and updated roles and 
responsibilities of NIH staff and the extramural community.  The policy 
continues to require for all NIH-defined Phase III clinical trials that: a) 
all applications or proposals and/or protocols must 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) investigators must report annual accrual and progress in conducting 
analyses, as appropriate, by sex/gender and/or racial/ethnic group 
differences.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS:  
The NIH maintains a policy 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. 

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 is available at 
http://grants.nih.gov/grants/funding/children/children.htm

REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS:  NIH 
policy requires education on the protection of human subject participants for 
all investigators submitting NIH proposals for research involving human 
subjects.  You will find this policy announcement in the NIH Guide for Grants 
and Contracts Announcement, dated June 5, 2000, at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT: The 
Office of Management and Budget (OMB) Circular A-110 has been revised to 
provide public access to research data through the Freedom of Information Act 
(FOIA) under some circumstances.  Data that are (1) first produced in a 
project that is supported in whole or in part with Federal funds and (2) cited 
publicly and officially by a Federal agency in support of an action that has 
the force and effect of law (i.e., a regulation) may be accessed through FOIA.  
It is important for applicants to understand the basic scope of this 
amendment.  NIH has provided guidance at 
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.

Applicants may wish to place data collected under this PA in a public 
archive, which can provide protections for the data and manage the 
distribution for an indefinite period of time.  If so, the application should 
include a description of the archiving plan in the study design and include 
information about this in the budget justification section of the 
application. In addition, applicants should think about how to structure 
informed consent statements and other human subjects procedures given the 
potential for wider use of data collected under this award.

STANDARDS FOR PRIVACY OF INDIVIDUALLY IDENTIFIABLE HEALTH INFORMATION:  The 
Department of Health and Human Services (DHHS) issued final modification to 
the “Standards for Privacy of Individually Identifiable Health Information”, 
the “Privacy Rule,” on August 14, 2002.  The Privacy Rule is a federal 
regulation under the Health Insurance Portability and Accountability Act 
(HIPAA) of 1996 that governs the protection of individually identifiable 
health information, and is administered and enforced by the DHHS Office for 
Civil Rights (OCR).  

Decisions about applicability and implementation of the Privacy Rule reside 
with the researcher and his/her institution. The OCR website 
(http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including a 
complete Regulation Text and a set of decision tools on “Am I a covered 
entity?”  Information on the impact of the HIPAA Privacy Rule on NIH 
processes involving the review, funding, and progress monitoring of grants, 
cooperative agreements, and research contracts can be found at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

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.  Furthermore, we 
caution reviewers that their anonymity may be compromised when they directly 
access an Internet site.

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 is 
related to one or more of the priority areas. Potential applicants may obtain 
a copy of "Healthy People 2010" at http://www.healthypeople.gov/.

AUTHORITY AND REGULATIONS: This program is described in the Catalog of 
Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the 
intergovernmental review requirements of Executive Order 12372 or Health 
Systems Agency review.  Awards are made under the authorization of Sections 
301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) 
and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. All 
awards are subject to the terms and conditions, cost principles, and other 
considerations described in the NIH Grants Policy Statement.  The NIH Grants 
Policy Statement can be found at 
http://grants.nih.gov/grants/policy/policy.htm.

The PHS strongly encourages all grant recipients to provide a smoke-free 
workplace and discourage the 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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NIH Funding Opportunities and Notices


H H S Department of Health
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