National Institutes of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Funding Opportunity Title
Limited Competition - Women's Interagency HIV Study (WIHS-V) (U01)
U01 Research Project – Cooperative Agreements
Reissue of RFA-AI-07-004
Funding Opportunity Announcement (FOA) Number
Only one application per applicant institution is allowed. See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)
93.855, 93.856, 93.279, 93.396, 93.865, 93.242
The purpose of the Women’s Interagency HIV Study V (WIHS-V) is to characterize the long-term, natural and treated history of HIV infection in the current cohort of women, and recruit and retain new women into the cohort to provide insight into the changing demographics of the HIV epidemic among women in the United States (U.S.) This Limited Competition Funding Opportunity Announcement (FOA) encourages applications from 1) current Clinical Research Sites (CRS), 2) the current Data Management and Analysis Center (WDMAC), and 3 new Clinical Research Site with capacity to enroll targeted populations of women from the Southern region of the U.S. (Alabama, Arkansas, Florida, Georgia, Kentucky, Louisiana, Mississippi, North Carolina, South Carolina, Tennessee, or Texas only). All cooperative agreement awards funded under this FOA will comprise the WIHS – V epidemiologic cohort.
November 29, 2011
Open Date (Earliest Submission Date)
December 22, 2011
Letter of Intent Due Date
January 22, 2012
Application Due Date(s)
February 22, 2012, by 5:00 PM local time of applicant organization.
AIDS Application Due Date(s)
Scientific Merit Review
Advisory Council Review
Earliest Start Date(s)
February 23, 2012
Due Dates for E.O. 12372
Required Application Instructions
It is critical that applicants follow the instructions in the SF 424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.
Part 1. Overview Information
Part 2. Full Text of the Announcement
Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information
The purpose of this FOA is to continue support for clinical, epidemiologic and basic research on an HIV cohort of women who are representative of the U.S. HIV-1 epidemic. The purpose of the Women’s Interagency HIV Study V (WIHS-V) is to characterize the long-term, natural and treated history of HIV infection in the current cohort of women, and recruit and retain new women into the cohort to provide insight into the changing demographics of the HIV epidemic among women in the U.S. This Limited Competition Funding Opportunity Announcement (FOA) encourages applications from 1) current Clinical Research Sites (CRS), 2) the current Data Management and Analysis Center (WDMAC), and 3) a new Clinical Research Site with capacity to enroll targeted populations of women from a geographically limited region of the U.S. (Alabama, Arkansas, Florida, Georgia, Kentucky, Louisiana, Mississippi, North Carolina, South Carolina, Tennessee, or Texas only). All cooperative agreement awards funded under this FOA will comprise the WIHS – V epidemiologic cohort.
Background: HIV-1 Infection and AIDS diagnoses among U.S. Women
The WIHS was established in 1993 as a multi-center prospective cohort study of women who are either HIV-infected or at risk for HIV acquisition. WIHS plays an important role in NIAID’s effort to understand the current epidemiology of HIV infection, disease progression, treatment use and outcomes, and related co-morbidities among U.S. residents with HIV. Understanding differences in HIV disease and treatment outcomes between women compared to men, and in different racial and ethnic groups, is a critical public health goal. To date, WIHS has conducted research on: novel statistics for analyzing observational cohort data; impact of viral resistance; the effect of co-infections such as hepatitis and human papillomavirus (HPV); therapy use and treatment effects in women with HIV; metabolic abnormalities and toxicities; the impact of hormonal factors on HIV disease including the transition into menopause; the effects of aging on HIV disease; behavioral research including substance use; the assessment of neurocognitive functioning, mental health and physical impairment among WIHS participants. WIHS data and specimens also provide the platform for other HIV-related NIH-funded grants. As of June 2011, almost 500 publications have resulted from WIHS-directed and/or collaborative investigations.
The HIV-1 epidemic in the U.S. has undergone substantial changes since the inception of WIHS. Originally an epidemic of men who have sex with men, HIV/AIDS is now a generalized heterosexual epidemic in some cities in the U.S. Rates of HIV-1 infection among women, particularly minority women, have risen over time. HIV is now the third leading cause of death for African American men and women ages 35-44. The U.S. Centers for Disease Control and Prevention reported that 40% of the 455,636 persons living with AIDS and half of those dying from AIDS in the U.S. in 2007 lived in the South. Research indicates that women and men with HIV infection can achieve nearly normal life-spans if treated with effective antiretroviral agents. However, barriers to treatment reduce the proportion of Americans who achieve optimal therapy. In 2011, the HIV Prevention Therapy Network (HPTN) demonstrated in protocol HPTN 052 that the risk of HIV transmission was reduced 92% within discordant dyads when the infected partner was treated with anti-retroviral therapy. This confirmed multiple observational studies and supports the idea that HIV treatment will be an effective method to prevent HIV infection. Understanding how to achieve optimal therapy effectiveness is a priority for improving individual health outcomes and for controlling the spread of HIV. The WIHS cohort is well positioned to study the uptake of antiretroviral medications, as well as the predictors of successful and sustained viral suppression.
WIHS also has the capacity to conduct research to define the clinical outcomes for women with HIV across their full lifespan. Determining the causal factors in disease manifestation requires extensive evaluation of women with and without HIV and across several decades of life. For example, as HIV infection interacts with many elements of cardiovascular health and a women’s risk of cardiovascular disease increases sharply after menopause, studying women across the menopausal transition is important to understanding the epidemiology of HIV-related cardiovascular disease. Multiple cancers are known to be elevated in persons with HIV, but the combined impact of HIV and aging on cancer incidence is not yet known. Persons with HIV are also at higher risk for other pathogenic virus infections such as hepatitis C and B, herpes simplex virus, and the human papilloma viruses. Diabetes, mental illness, renal failure, musculoskeletal disorders have all been shown to be elevated and exacerbated in HIV infected persons. Intertwined in the study of all these conditions is the higher rate of substance use (alcohol, tobacco and illicit drugs), which increases the risk of infection, accelerates disease manifestations, and reduces adherence to care and treatment.
HIV therapies have evolved from complicated, sub-optimal, and toxic regimens to simple, effective regimens with fewer side effects. Patients treated successfully in 2011 have low or undetectable viral loads, and thus have the potential to normalize many of the effects of HIV and the pathology related to the immune response. Furthermore, patients treated earlier in the course of their HIV disease may have different late stage disease manifestation than those in whom the virus remained unchecked for a longer period. As crucial as it is to understand the clinical epidemiology and to optimize the care of women treated with earlier therapy regimens and later in the course of their infection, research to define the epidemiology of women treated in the most recent therapy era is also of importance.
In addition to its role in clinical epidemiology, WIHS conducts high quality pathogenesis research. WIHS specimens are collected and processed under strict quality control to promote the widest possible range of uses for current and future investigations. WIHS is a unique resource for research owing to the depth of data and specimens available. The combination of over 19 years of clinical and interview data has created a database with substantial research potential. These have included evaluations beyond standard of care assessments such as carotid intimal medial thickness, DEXA scan measurements, medical record confirmation of key outcomes, intensive clinical specimen testing, novel research test results (e.g., longitudinal assessment of virologic and immunologic markers), and completion of a 5 million SNP GWAS. Furthermore, return of laboratory and other test results from all WIHS affiliated studies to the overall WIHS database ensures that the depth of WIHS data increases over time. Availability of these data to all investigators is both cost-effective and efficient. These highly characterized women are still in follow-up, and future research opportunities can build upon existing data and specimens. WIHS fosters the development of the next generation of observational and clinical epidemiologists by remaining at the forefront in the collection and statistical analysis of observational data. WIHS collaborates with other HIV-related research groups such as the Multicenter AIDS Cohort Study (MACS), the International Epidemiologic Databases to Evaluate AIDS (IeDEA), and the Pathogenesis of HIV in Women Study.
Clinical Research Site - Current Awardees: NIH recognizes that there is scientific benefit to continue follow-up of the highly characterized women currently enrolled in WIHS. Applications from the current WIHS CRS awardees should address how the site is responsible for following standard WIHS data and specimen collection protocols, as well as recruiting and retaining women in the cohort. CRS applications must also propose a scientific agenda which may include research either limited to their site or extended WIHS-wide. While each application is distinct from each other, the applicants must demonstrate how they will be able to integrate the proposed research agenda into the larger WIHS cohort. Existing WIHS CRSs may propose to recruit up to 100 new women into their cohorts, thus shifting enrollment from a closed cohort to a cohort with rolling enrollment in order to replace women who die. While applicants should describe their enrollment plans in their applications, the final determination of the enrollment criteria for existing WIHS CRSs will be determined by the WIHS-V Executive Committee and NIH, in consultation with the WIHS External Advisory Board.
Clinical Research Site () – New Site: This FOA also encourages applications from new CRSs that can demonstrate capacity to recruit women in the Southern region of the U.S. (as defined earlier). Applications for the new CRS should describe their ability to recruit and retain the targeted participant population, follow the WIHS standard data and specimen collection protocols, maintain a local scientific agenda related to WIHS goals, and contribute to an overall WIHS Scientific Research Agenda. Applications should propose research at the site level in addition to work which could be conducted across multiple WIHS CRSs. In order to ensure sufficient statistical power and meet the goals of WIHS-V, the new CRS must demonstrate capacity to recruit at least 200 women who are representative of the local epidemic, which would include women who are and women who are not engaged consistently in HIV care. Given that the WIHS cohort should represent women across the spectrum of care, receiving HIV care should not be a requirement for enrolling in the WIHS. The disassociation of WIHS participation from care is a key element to understanding the true epidemiology of HIV among women. However, WIHS CRSs should describe how they facilitate access to care. While applicants should describe their enrollment plans in their applications, the final determination of the enrollment criteria for the new CRS will be determined by the WIHS-V Executive Committee and NIH, in consultation with the WIHS External Advisory Board.
Data Management and Analysis Center Applications-Current Awardee: The application from the current WDMAC awardee should describe how they will support the conduct of the WIHS data and specimen protocol, ensure data collection is efficient and accurate, maintain all cohort data, perform analyses for EC-prioritized projects, foster epidemiologic collaborations with other research consortiums, enhance data sharing and data access by non-WIHS investigators, and conduct research in statistics and epidemiology to optimize the outcomes from data collected within observational cohorts.
Cohort Description: The current WIHS clinical sites are located in Bronx/Manhattan, NY; Brooklyn, NY; Los Angeles/Southern California/Hawaii; San Francisco/Bay Area, CA; Chicago, IL; and Washington, DC/Eastern Maryland/Northern Virginia. Each clinical site represents the population of HIV-infected women in the local metropolitan area. The study originally enrolled 3,766 women with 2,200 women currently in follow-up as of October 2010. WIHS has been a closed cohort with three distinct enrollment waves: 1) cohort inception between 1994-1995, 2,625 women were enrolled (2,056 HIV-infected [including those with AIDS or low CD4 cell count] and 569 HIV-negative); 2) cohort expansion in 2001-2002, 1,143 additional women were enrolled (254 HIV positive/no AIDS/HAART naïve, 484 HIV positive/no AIDS prior to HAART/HAART experienced, and 406 HIV-); 3) cohort replenishment during 2011-2012 when clinical sites may recruit as many new participants as have died during WIHS IV (292 HIV-positive women, age 30-55 years, either HAART naïve or started HAART with a regimen that does not include DDI or D4T and 121 HIV-negative women age 35-60 years with one or more risk factors for HIV-infection).
WIHS Working Group: Specific areas of scientific focus are cultivated by collective groups of investigators with common research interests and goals, collectively known as the WIHS Working Groups (WG). Each WG membership will include WIHS Project Directors and/or PD(s)/PI(s) as well as senior and junior investigators at participating institutions, with outside consultations as needed. The WG’s are expected to shepherd WIHS-wide projects through completion, encourage the organization of related efforts across the clinical sites, promote collaboration across the different disciplines represented by the various WIHS WG’s, and explore current and future scientific questions germane to that area of the overall WIHS Scientific Agenda.
WIHS Executive Committee: The WIHS Executive Committee (EC) is responsible for the overall common scientific aims of the WIHS and the progress of WGs, and is composed of the PD(s)/PI(s) from each awardee institution, a WIHS community advisory board member selected by study subjects to represent their interests, and the NIH Project Scientists. EC members are expected to prioritize the WIHS scientific agenda, oversee the completion of research with WIHS and work with investigators outside the consortium who wish to conduct research using current WIHS data, specimens, and other resources. In addition, changes to existing study procedures, and proposals for new research (submitted by internal and external investigators) are reviewed with approval and prioritization based on a consensus decision of the EC. On rare occasions when consensus is not achieved, approval and prioritization may be based on a majority vote of the EC.
WIHS External Advisory Board: For this FOA, the NIAID and partnering components, in consultation with the WIHS EC, will assemble a WIHS External Advisory Board to advise the NIAID and partnering components in assessing current progress, suggesting revisions to timelines, and establishing scientific and funding priorities for projects proposed across the WIHS consortium. The WIHS External Advisory Board will meet on an annual basis at the same time as one of the WIHS EC semi-annual meetings. The WIHS External Advisory Board will be comprised of trans-NIH staff, other governmental experts, members of academia and industry. NOTE to Applicants: Do not suggest the names of potential External Advisory Board members in the application.
WIHS participants will be evaluated at six month intervals after enrollment. The study visit is briefly outlined below. Specifics of the protocol and documentation are available at http://www.niaid.nih.gov/about/organization/daids/Pages/daidsepi.aspx. Clinical Research Sites must demonstrate a capacity to conduct the WIHS data and specimen collection protocol.
Interview: Centrally scripted interviews are conducted at each WIHS visit. Self-reported data collection includes sociodemographic information; health care utilization; general medical as well as obstetric and gynecological histories including contraceptive and other prescription medication use; complete antiretroviral medication inventory; use of alcohol, tobacco and illicit drugs; sexual risk behaviors; beliefs regarding HIV and its treatment; and psychological status. Interview content is evaluated and may be revised every six months by the WIHS EC. To assure the highest quality data, centralized training is conducted by WDMAC or external consultants. Training, periodic assessment of quality and the development of question-by-question guidance materials are the responsibility of WDMAC working with the investigative team leading a research initiative.
Clinical Outcome Confirmation/Ascertainment: All reports of AIDS-related diagnoses are confirmed by medical record abstraction. State cancer registries, local and state tuberculosis registries, and the National Death Registry are used to augment and confirm the outcome data that are collected.
Clinical Examination: Physical examinations conducted at each regular visit by a health care practitioner who has completed the WIHS physical exam training, include standardized assessment of vital signs (e.g., blood pressure); anthropometric measures; a skin and oral examination; an examination of the breasts, lymph nodes and abdomen; and a gynecological examination that includes cervical cytology and collection of specimens for testing and storage according to the visit protocol. The WIHS protocol includes colposcopic examination and biopsy when indicated. Women needing further treatment are referred for care outside of the WIHS and sites have referral mechanisms that take into account the participant’s insurance coverage and ability to cover associated costs.
Laboratory Testing: All WIHS participants are asked to provide whole blood, urine, cervico-vaginal swabs and lavage fluid, and a small sample of hair for baseline and follow-up laboratory monitoring. As new areas of inquiry are identified, additional sample collection may be requested. For example, the collection of fasting whole blood samples was initiated in 2000 in order to improve assessment of cardiovascular and metabolic complications, and limited collection of samples for oral HPV research was initiated in 2010.
National & Local Repositories: Urine, plasma, serum, lymphocytes and cell pellets, genital secretions, hair, and saliva samples will be collected and stored at local WIHS sites and the central DAIDS Repository. Requests from internal and non-WIHS affiliated investigators are made to the WIHS EC via the concept sheet submission process in order to access the reposited samples. In addition, available tissue biopsy samples are provided to the AIDS Cancer Specimen Resource.
Data entry and management: Currently, data are collected at the sites on paper forms which are entered into a web-based data system updated each visit cycle and maintained by WDMAC. A data manager at each clinical site must oversee data entry, and must work with WDMAC to ensure that datasets are complete and ensure methods for recording the data are comparable between sites. WDMAC is responsible for the central management of data, which includes data quality oversight, creation of summary variables to facilitate harmonized analysis, analyzing data for WIHS research, and preparing analytical datasets when non-WDMAC investigators are performing analyses.
The scientific agenda of the WIHS awardees may include, but is not limited to, the following areas of interest to the NIAID and partnering components sponsoring the WIHS:
ANTIRETROVIRAL TREATMENT: The composition of the WIHS cohort will reflect therapy use patterns representative of the U.S. female HIV-positive population. Therapy use in the cohort is therefore likely to be diverse, and differences in therapy exposure, effectiveness, and program delivery are of interest.
COMORBIDITIES: Research in WIHS will be able to maximize use of the WIHS cohort, specimens and data repository to account for the complex interrelationship between covariates, for example, genetics, co-infections, co-morbidities, therapy, behavior, and aging.
SUBSTANCE USE is an underlying issue for many of the women in WIHS. Current or historical use of alcohol, tobacco, illicit drugs and other substances is high. Substance use also relates to other behavioral issues for the cohort including abuse, mental health status, and educational level. Research in all areas of the WIHS scientific agenda should take into account the impact of substance use, in both integrated and specifically focused research studies. Both the determinants and the consequences of substance use are of interest to the extent that they may help explain substance use effects related to HIV, its treatment and its biologic, clinical and/or behavioral outcomes.
PATHOGENESIS: proposed research may take advantage of reposited specimens collected across key time points, may use data already generated on participants including genetic and longitudinal data on immune markers, or may be prospective in nature requiring additional specimen collection and testing.
CANCER: The incidence of many cancers is likely to increase in the next five years of WIHS follow-up. WIHS investigators have access to bio-reposited specimens to study predictors prior to the diagnosis of cancer. WIHS researchers are expected to contribute specimens to the AIDS cancer and specimen repository biobank. Furthermore, WIHS also collaborates with other HIV studies to have sufficient statistical power to address rare cancers.
EPIDEMIOLOGIC and STATISTICAL METHODS Innovative methodological approaches for the conduct, design and analysis of cohort studies of HIV/AIDS are needed to maximize the use of observational data to inform on health outcomes. Novel ways to improve the quality of self-reported data, to improve linkages between health care data (clinical care and pharmacy data), and standardize collection techniques and harmonize data bases are needed to improve research. Development of new statistical approaches to account for the complexity of WIHS data is also encouraged.
Through this FOA, NIAID will support epidemiology of HIV infection and its treatment including the range of acute and chronic pathologies in women over the full course of their adult life with HIV. The FOA also supports research on behavioral components of HIV care including how women access care, remain in care, initiate HIV therapy, suppress virus, and maintain viral suppression. Research on these components, but within the context of treatment as prevention, is particularly encouraged.
It is also expected that the WIHS consortium will continue to provide a platform for collaborations that lead to independent, investigator-initiated research projects. In the past, administrative supplements have been used to supplement WIHS-funded grantees in order to address high priority questions, such as the association of race and gender in response to potent ARV therapy, alternative methods of measuring ARV exposure (hair analysis), and most recently the potential impact of abacavir use on HIV- and cardiac-related inflammation. These additional investigations have resulted in numerous important publications for the field of HIV/AIDS research.
Application Types Allowed
The OER Glossary and the SF 424 (R&R) Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards
NIAID and partner components intend to commit an estimated total of $23.9M to fund 6-8 awards, including the current CRSs, the new CRS and the current data management and analysis center.
Although the financial plans of NIAID and partner components provide support for this program, awards pursuant to this FOA are contingent upon the availability of funds. Funding beyond the first year of the grant will be contingent upon satisfactory progress during the preceding years and availability of funds. .
Application budgets for the Clinical Research Sites (current and new) are capped at $3.5M total costs. Application budgets for the WDMAC are capped at $2.2M total costs.
Award Project Period
The maximum project period for each award is five years.
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.
Applications may be submitted by the current WIHS CRSs and the current WDMAC. Therefore only the following awardees may apply for this limited competition:
U01 AI 35004, Bronx, NY (Montefiore Medical Center)
U01 AI 31834, Brooklyn, NY (SUNY Downstate Medical Center)
U01 AI 34993, Chicago, IL (Hektoen Institute for Medical Research)
U01 HD 32632, Los Angeles, CA (University of Southern California)
U01 AI 34989, San Francisco, CA (University of California - San Francisco)
U01 AI 34994, Washington, DC (Georgetown University)
U01 AI 42590, Baltimore, MD, (Johns Hopkins University) (as the WIHS Data Management and Analysis Center (WDMAC))
In addition, applications may be submitted for a new CRS only from geographically limited sites enrolling the target population. Specifically, institutions proposing research on women who are either HIV+ or HIV- but at risk for HIV infection from the southern U.S. , defined as Alabama, Arkansas, Florida, Georgia, Kentucky, Louisiana, Mississippi, North Carolina, South Carolina, Tennessee, or Texas, may apply for the new CRS limited competition.
At the time of application, PD(s)/PI(s) of a current Clinical Research Site (CRS) award are not eligible to serve as PD(s)/PI(s) on a new CRS application.
Non-domestic (non-U.S.) Entities (Foreign Institutions) are
not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are not allowed.
Applicant organizations must complete the following registrations
as described in the SF 424 (R&R) Application Guide to be eligible to apply
for or receive an award. Applicants must have a valid Dun and Bradstreet
Universal Numbering System (DUNS) number in order to begin each of the following
All Program Director(s)/Principal Investigator(s) (PD(s)/PI(s))
must also work with their institutional officials to register with the eRA
Commons or ensure their existing eRA Commons account is affiliated with the eRA
Commons account of the applicant organization.
All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least 4-6 weeks prior to the application due date.
Any individual(s) with the skills, knowledge, and resources
necessary to carry out the proposed research as the Program Director(s)/Principal
Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization 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 support.
For institutions/organizations proposing multiple PD(s)/PI(s), visit the Multiple Program Director(s)/Principal Investigator(s) Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.
Applications proposing Multiple PD(s)/PI(s) are are particularly appropriate for this program, including those with diverse expertise in clinical infectious diseases and HIV epidemiologic research.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
Applicant organizations may submit only one application per institution (normally identified by having a unique DUNS number or NIH IPF number) in response to this FOA.
NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. .
Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the “Apply for Grant Electronically” button in this FOA or following the directions provided at Grants.gov.
It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.
For information on Application Submission and Receipt, visit Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.
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.
By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:
The letter of intent should be sent to:
Peter R. Jackson, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3133, MSC-7616
6700B Rockledge Drive
Bethesda, MD 20892-7616
Bethesda, MD 20817-7616 (for express/courier service; non-USPS mail)
Telephone: (301) 496-8426
FAX: (301) 480-2408
The forms package associated with this FOA includes all applicable components, mandatory and optional. Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate “optional” components.
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed, with the following exceptions or additional requirements:
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
Clinical Research Sites (CRS) Research Plan
Organize the Research Plan section in the order specified in the SF424 Instructions Section 5.5.2. Within the Research Strategy section, start each section with the appropriate heading in order, addressing Significance, Innovation, and Approach, and including the appropriate information. Explicit experimental details should be cited using the Bibliography and Reference Cited section and need not be detailed in the Research Strategy.
For renewal applications, within the Approach section, include a table that outlines the total number of participants successfully enrolled to WIHS during the first two (of three) recruitment waves, and the percent retained to date in each wave (by HIV serostatus). In addition, provide a table to demonstrate successful enrollment and percent retained to the following sub-studies: Neurocognition, CVD/IMT, Metabolic/DEXA, Intensive PK. Current CRS applicants must also: 1) document efforts to identify and follow WIHS women requiring colposcopic evaluation subsequent to the WIHS gynecologic assessments; 2) report error rates (and associated corrective methods) resulting from all WIHS-III and WIHS-IV data audits; 3) provide a summary of WIHS-related publications in which the PD(s)/PI(s) and site investigators were first or senior author.
For new applications, with the Approach section, provide preliminary studies and data, and the experience pertinent to the application. In addition, new CRS applicants should describe their recruitment plans, demonstrate their experience with enrolling and maintaining women in research, and detail how they will be able to complete the standard WIHS core data and specimen protocol. The new CRS is expected to enroll a minimum of 200, but not more than 300, women who are representative of the local epidemic, which includes women who are and women who are not engaged consistently in HIV care. New CRS applicants should describe how they facilitate access to care. New CRS applicants must demonstrate their capacity and flexibility to accommodate new research and additions to the study protocol, for example DEXA or fMRI studies.
Under the appropriate headings within the Research Strategy section, CRS applicants should describe the proposed research agenda for site-specific and WHIS-wide collaborative research, including plans to collaborate with the data management and analysis center. Although collaboration among CRSs and the data management and analysis center is highly encouraged, each CRS application must contain a fully developed research agenda that can be executed by the staffing proposed within each CRS application. Personnel may contribute their effort to work led by other sites, but the percent effort for that work should be included on the application proposing the research. Study protocol costs over and above core activities, i.e., specialized laboratory or clinical tests, must be costed out for the participants seen at the site proposing the research, even if participants at other sites are anticipated to participate. If the project is deemed meritorious, NIAID will adjust budgets appropriately. CRS applications do not need to include the cost for performing the research visit at other sites. CRS applicants should describe how they intend to provide leadership and intellectual input in the design and conduct of the evolving WIHS research agenda. Each WIHS site should actively engage with the patient community and budget appropriate expenses for the support of these interactions.
Data Management and Analysis Center (WDMAC) Research Plan
Organize the Research Plan section in the order specified in the SF424 Instructions Section 5.5.2. Within the Research Strategy section, start each section with the appropriate heading in order, addressing Significance, Innovation, and Approach, and including the appropriate information. Explicit experimental details should be cited using the Bibliography and Reference Cited section and need not be detailed in the Research Strategy. Within the Approach section, for renewal applications include information demonstrating success of the WDMAC during the previous funding period in the evaluation of the WIHS protocol across the sites. Under the appropriate headings within the Research Strategy section, the WDMAC applicant should describe how preparations are made for each visit wave, describe how the WDMAC oversees conduct of the study during each visit wave, describe how the WDMAC brings each visit wave to an end and facilitates analyses, and supports the analysis on WIHS-wide projects including how effort and resources for pending analyses are prioritized. The applicant for the WDMAC should also propose a clinical research agenda to be conducted at WIHS CRSs and for analyses of WIHS research data. These analyses may include work focused on epidemiologic and statistical methods in observational research, as well as WIHS-wide analyses of WIHS data. Although collaboration among the data management and analysis center and CRSs is highly encouraged, the WDMAC application must contain a fully developed research agenda that can be executed by the staffing proposed within the WDMAC application.
Resource Sharing Plan
Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies; GWAS) as provided in the SF424 (R&R) Application Guide, with the following modifications:
Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit in advance of the deadline to ensure they have time to make any application corrections that might be necessary for successful submission.
Organizations must submit applications via Grants.gov, the online portal to find and apply for grants across all Federal agencies. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration.
Applicants are responsible for viewing their application in the eRA Commons to ensure accurate and successful submission.
Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.
This initiative is not subject to intergovernmental review.
All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Pre-award costs are allowable only as described in the NIH Grants Policy Statement.
Applications must be submitted electronically following the instructions described in the SF 424 (R&R) Application Guide. Paper applications will not be accepted.
Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.
For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically.
All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF 424(R&R) Application Package. Failure to register in the Commons and to include a valid PD(s)/PI(s) Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.
The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the Central Contractor Registration (CCR). Additional information may be found in the SF424 (R&R) Application Guide.
See more tips for avoiding common errors.
Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed.
Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.
Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.
Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).
Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.
Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?
Clinical Research Site: Has the applicant proposed a scientific agenda that maximizes data and specimen collection from the cohort in order to advance our understanding of HIV infection and disease? Does the CRS applicant demonstrate capacity to enroll women representing key demographics of the HIV epidemic among women in the U.S.? Does the application demonstrate leadership in HIV/AIDS research through a strong publication record?
WDMAC: Has the applicant proposed a scientific agenda that maximizes the potential of the overall cohort, including but not limited to, statistical and epidemiologic research that will advance the fields of statistics and epidemiologic methods? Has the applicant proposed novel data coordination and protocol management approaches that enhance data accessibility and rapid dissemination of results? Does the applicant provide a plan to facilitate the use of data and specimens by WIHS PD(s)/PI(s) and external collaborators? Does the application demonstrate leadership in HIV/AIDS research through a strong publication record?
Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD(s)/PI(s), do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?
Do the proposed PD(s)/PI(s) possess the skills, knowledge, commitment, and professional experience in observational clinical research needed to carry out the proposed research plans? Have the PD(s)/PI(s) demonstrated a history of productive working relationships as scientific collaborators? Are the time commitments of staff appropriate to accomplish the stated aims? Do the PD(s)/PI(s) propose an organizational structure that facilitates collaboration within and outside of the WIHS? Have the PD(s)/PI(s) and site investigators demonstrated productivity as first or senior authors on WIHS publications?
Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?
Does the application provide innovative ways to integrate local and WIHS-wide core aims among the proposed projects including the use of technology, non-WIHS sources of clinical data, and other sources of funding to achieve the stated scientific goals? Does the application demonstrate flexibility such that the applicant is likely to be able to respond with innovative systems to address new questions related to HIV as they arise?
Are the overall strategy, methodology, and analyses
well-reasoned and appropriate to accomplish the specific aims of the project?
Are potential problems, alternative strategies, and benchmarks for success
presented? If the project is in the early stages of development, will the
strategy establish feasibility and will particularly risky aspects be
If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?
Does the applicant propose a feasible scientific research agenda for the project that also capitalizes on the full capacity of the WIHS collaboration to achieve significant results beyond what would be possible outside of the collaboration? Are the proposed aims likely to foster significant scientific collaborations? Does the applicant propose a research area that is sufficiently flexible to address new research questions as new findings are released? Does the application propose a cohort which will represent the epidemic among women in their area, and contribute to the WIHS overall ability to represent the US epidemic? Does the application demonstrate an ability to recruit women both in and out of HIV care? Are the scientific goals feasible given the size and make-up of the cohort? Are the core laboratory procedures well-coordinated, with adequate and appropriate quality control?
Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?
Does the environment foster collaboration with other HIV/AIDS research groups through proximity to patient populations, established interactions with community advocacy groups, or access to other sources of funding in areas of science related to the aims of the WIHS?
Ability to Conduct the WIHS Protocol
For Clinical Research Site applications: Does the application demonstrate successful ability to perform the core WIHS data and specimen collection protocol? For renewal applications, does the CRS applicant demonstrate a history of participation in WIHS data and specimen collection protocols, and sub-studies? Has the CRS applicant demonstrated capacity to recruit the target population and retain participants in active follow-up? For new applications, does the applicant for the Southern CRS describe an achievable approach, and alternatives if needed, to recruit and retain the target population including women who are and women who are not engaged consistently in HIV care? Does the applicant describe how the team would be able to enroll women into future WIHS sub-studies?
For the WDMAC application: Does the WDMAC application describe successful approaches to evaluate a CRS in the performance of the core WIHS data and specimen collection protocol?
As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact/priority score, but will not give separate scores for these items.
Protections for Human Subjects
For research that involves human subjects but does
not involve one of the six categories of research that are exempt under 45 CFR
Part 46, the committee will evaluate the justification for involvement of human
subjects and the proposed protections from research risk relating to their
participation according to the following five review criteria: 1) risk to
subjects, 2) adequacy of protection against risks, 3) potential benefits to the
subjects and others, 4) importance of the knowledge to be gained, and 5) data
and safety monitoring for clinical trials.
For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Human Subjects Protection and Inclusion Guidelines.
Inclusion of Women, Minorities, and Children
When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.
The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.
Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.
For Renewals, the committee will consider the progress made in the last funding period.
As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact/priority score.
Applications from Foreign Organizations
Select Agent Research
Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).
Resource Sharing Plans
Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genome Wide Association Studies (GWAS).
Budget and Period of Support
Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.
Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NIAID, in accordance with NIH peer review policy and procedures, using the stated review criteria. Review assignments will be shown in the eRA Commons.
As part of the scientific peer review, all applications:
Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.
Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board . The following will be considered in making funding decisions:
After the peer review of the application is completed, the PD(s)/PI(s) will be able to access his or her Summary Statement (written critique) via the eRA Commons.
Information regarding the disposition of applications is available in the NIH Grants Policy Statement.
If the application is under consideration for funding, NIH
will request "just-in-time" information from the applicant as
described in the NIH
Grants Policy Statement.
A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.
Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.
Any application awarded in response to this FOA will be subject to the DUNS, CCR Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.
All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.
Cooperative Agreement Terms and Conditions of Award
The following special terms of award are in addition to, and
not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB)
administrative guidelines, U.S. Department of Health and Human Services (DHHS)
grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is
applicable when State and local Governments are eligible to apply), and other
HHS, PHS, and NIH grant administration policies.
The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.
The WDMAC PD(s)/PI(s) will have the primary responsibility for:
The CRS PD(s)/PI(s) will have the primary responsibility for:
NIH staff has substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
Project Scientists from NIAID and partnering components will have substantial scientific/programmatic involvement during the conduct of this activity through technical assistance, advice and coordination above and beyond normal program stewardship for grants or cooperative agreements. NIH Project Scientists will be responsible for:
Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.
Other Collaborations include:
WIHS Executive Committee (EC): The WIHS EC consists of PD(s)/PI(s) from the CRS, the WDMAC, a WIHS community advisory board member selected by study subjects to represent their interests, and staff from the NIH co-funding institutes. Each PD(s)/PI(s) (CRS and WDMAC) is a voting member of the EC. In the case of multiple-PD(s)/PI(s), the PD(s)/PI(s) should reach consensus on their position to cast a single vote representative of their site. Awardee members of the Executive Committee will be required to accept and implement policies approved by the EC. The members of the WIHS EC will be responsible for:
WIHS External Advisory Board: The WIHS External Advisory Board consists of trans-NIH staff, other governmental experts, members of academia and industry. The members of the WIHS External Advisory Board will be responsible for:
WIHS Working Groups (WG): The WIHS WG consists of PD(s)/PI(s) of each awardee, senior and junior investigators of awardees and outside consultants as needed. The members of the WIHS WG will be responsible for:
Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.
When multiple years are involved, awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.
A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.
The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement. In the PHS2950, CRSs must provide a brief summary of interactions with local community representatives and support of the WIHS National Community Advisory Board (NCAB). The WIHS NCAB is comprised of community advisory board representatives from each WIHS clinical research site and advises the WIHS EC.
We encourage inquiries concerning this funding opportunity
and welcome the opportunity to answer questions from potential applicants.
Additional information can be found at the following website http://www.niaid.nih.gov/about/organization/daids/Pages/wihs.aspx
GrantsInfo (Questions regarding application instructions and
process, finding NIH grant resources)
eRA Commons Help Desk(Questions regarding eRA Commons
registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
Joana Roe, B.A.
National Institute of Allergy and Infectious Diseases (NIAID)
Richard A. Jenkins, Ph.D.
National Institute on Drug Abuse (NIDA)
Heather Watts, M.D.
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Geraldina Dominguez, Ph.D.
Dianne Rausch, Ph.D.
National Institute of Mental Health (NIMH)
Peter R. Jackson, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: (301) 496-8426
Mildred J. Qualls
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: (301) 402-6611
National Institute on Drug Abuse (NIDA)
Telephone: (301) 774-3803
Bryan S. Clark, MBA
National Institute of Child Health and Human Development (NICHD)
National Cancer Institute (NCI)
Telephone: (301) 496-8791
National Institute of Mental Health (NIMH)
Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
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 Part 52 and 45 CFR Parts 74 and 92.
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