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: firstname.lastname@example.org 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: email@example.com 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: firstname.lastname@example.org 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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