Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	This Funding Opportunity Announcement (FOA) is developed as a Common Fund initiative (http://commonfund.nih.gov/) through the NIH Office of the NIH Director, Office of Strategic Coordination (http://dpcpsi.nih.gov/osc/). The FOA will be administered by the National Human Genome Research Institute (NHGRI/NIH), (http://genome.gov) on behalf of the NIH Division of Program Coordination, Planning and Strategic Initiatives Office of Strategic Coordination (Common Fund) National Human Genome Research Institute (NHGRI) Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) National Institute of Neurological Disorders and Stroke (NINDS)
Funding Opportunity Title	Human Heredity and Health in Africa (H3Africa): Collaborative Centers (U54)
Activity Code	U54 Specialized Center- Cooperative Agreements
Announcement Type	Reissue of RFA-RM-11-008
Related Notices	August 9, 2016 - This RFA has been reissued as RFA-RM-16-016. October 26, 2012 - See Notice NOT-OD-13-005. Notice of Change in Due Date.
Funding Opportunity Announcement (FOA) Number	RFA-RM-12-006
Companion Funding Opportunity	RFA-RM-12-007, Human Heredity and Health in Africa (H3Africa): Research Grants (U01) RFA-RM-12-008, Human Heredity and Health in Africa (H3Africa): Biorepositories (UH2/UH3) RFA-RM-11-010, U41 Human Heredity and Health in Africa (H3Africa): Bioinformatics Network Cooperative Agreements RFA-RM-12-005, Human Heredity and Health in Africa (H3Africa): Ethical, Legal, and Societal Issues (ELSI) Research Program (U01)
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.310, 93.172, 93.853, 93.865
Funding Opportunity Purpose	This NIH Funding Opportunity Announcement (FOA), supported by funds from the NIH Common Fund (Common Fund) and participating NIH Institute(s) and Center(s), invites applications from Institutions in African countries for research centers called H3Africa Collaborative Centers (H3ACCs). This FOA is a component of the Human Health and Heredity in Africa Initiative (H3Africa), an NIH initiative in partnership with the Wellcome Trust to develop the study, in Africa, of genomic/genetic/environmental contributors of human health and disease within Africa using cutting-edge genomic research tools, to increase capacity for biomedical research in Africa, in terms of building infrastructure (including data and research resources), and to increase the genomic proficiency of researchers and trainees in Africa. The H3Africa Initiative is focused on supporting these efforts as part of an effort to promote sustainable research in Africa that will promote health and combat disease. The purpose of this FOA is to call for applications for U54 Collaborative Centers that will provide funding to support multi-project research programs that address the goals of H3Africa and that involve two or more collaborations with investigators from outside the applicant institution. The goals of H3Africa are to support cutting-edge genomics/genetics research on health and diseases important in Africa, to increase the human resources for conducting cutting-edge genomics-based research in Africa, and to improve specific types of infrastructure, i.e., bioinformatics and biorepository capacity, which are needed to do genomics-based and environmental research.

Posted Date	August 22, 2012
Letter of Intent Due Date	September 28, 2012
Application Due Date(s)	(Extended to October 31, 2012 per NOT-OD-13-005), Originally October 29, 2012
AIDS Application Due Date(s)	Not Applicable
Scientific Merit Review	February/March 2013
Advisory Council Review	May 2013
Earliest Start Date(s)	August/September 2013
Expiration Date	(Extended to November 1, 2012 per NOT-OD-13-005), Originally October 30, 2012
Due Dates for E.O. 12372	Not Applicable.

Required Application Instructions

It is critical that applicants follow the instructions in the PHS398 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. While some links are provided, 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 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

Low- and middle-income nations suffer over ninety percent of the world’s burden of premature mortality, as measured in lost years of life. These countries, constituting three-quarters of the world’s population, now must deal with a triple burden: the persistent cluster of infectious diseases, malnutrition, and a growing incidence of chronic disease and disabilities due to increased life spans and the attendant new risk exposures. The NIH has a long-standing commitment to address both communicable and non-communicable diseases around the world through health research and training, and one of NIH’s stated priorities is enhancing efforts in global health. Genomics and other large-scale biological studies provide cutting-edge approaches to research on the genetic and environmental contributors to health and disease, the understanding of which will lead to unimagined advances in medical science and powerful new ways for improving human health. To maximize the impact on the health of people globally, advances in the fields of genetics/genomics/environmental studies must be integrated into the research conducted in developing countries, as well as into their medical education and health services. Notably, however, African researchers and populations are substantially underrepresented in genomics and environmental research endeavors. For example, it has been found, as documented in a recent review, that, worldwide, the majority of the thousands of genetic studies completed to date (about 75%) were conducted exclusively in populations of European descent and only a fraction of the studies done with non-European populations came from Africa (Rosenberg NA, Huang L, et al. (2010). Nat Rev Genet 11(5):356-366). The paradox of limited genomics research conducted in Africa and the centrality of contemporary African populations for our understanding of human evolution and population genetics has been widely noted.

While there are pockets of research excellence in genetics and environmental studies on the African continent done by African and other scientists, a limited number of individuals have the expertise to engage in this work compared to the overall population size and burden of disease there. It is the objective of the H3Africa Initiative to enhance the capability of African scientists and research institutions to use genomics and other powerful new approaches to address problems of African health and disease. Increasing African research capacity by building infrastructure, expanding the genomic proficiency of researchers, and increasing the number of well-trained individuals is essential to promote sustainable efforts to address the challenges to advancing health and combating disease in Africa. While focused on benefitting the people of Africa, such research may also be relevant to the health of individuals in the U.S. and other countries worldwide, particularly those of African descent. For example, many scientists believe that different environmental exposures for a population whose genetic architecture evolved in environments with a scarcity of available resources are an underlying contributor to disease in the U.S.

H3Africa is a partnership among the National Institutes of Health (NIH, USA), the Wellcome Trust (WT, UK), and the African Society of Human Genetics (AfSHG). A set of recommendations for H3Africa was developed by a pair of working groups, composed primarily of African scientific experts, who addressed the major scientific, ethical and practical issues in the development of a large-scale genomics research program in Africa. The working groups formulated a detailed proposal (which can be found in a white paper at www.h3africa.org/whitepaper.cfm) to address the goal of creating and sustaining a network of African Centers that could carry out training and research based on state-of-the-art genomics approaches. Through support for infrastructure development, training, and specific research projects, the working group recommendations were designed to catalyze genomics and environmental research concerning human diversity, health, and disease biology of particular relevance and benefit to African populations and societies. The proposal was discussed at a public meeting held in Cape Town, South Africa in March 2011 and the attendees ratified the white paper’s recommendations. The first set of FOAs soliciting applications for H3Africa were published about one year ago (see Archive Funding Opportunities at https://commonfund.nih.gov/globalhealth/grants.aspx), and funding for the program will begin in the summer of 2012.

The research program described in this and previous FOAs is a response to the disparities in research capacity noted above and is based, in significant part, on the recommendations of the H3Africa white paper and from discussions at the Cape Town meeting. The H3Africa Initiative aims to contribute to the establishment of a viable, productive, and eventually sustainable, African research infrastructure for the study of the genetic and environmental contributors to disease and health. It aims to do so through a combination of the leveraging of existing capacity, expertise and infrastructure with investment in new research, infrastructure-building and training efforts.

H3Africa has three interrelated, interdependent objectives. The first is to increase the human resources for conducting cutting-edge genomics-based research in Africa through training and enhanced collaborations with national and international partners, particularly in other countries within Africa, but also in countries outside the continent. The second is to support cutting-edge genomics/genetics research that will not only generate important findings and discoveries, but will serve as a vehicle for research training and for the improvement of the research capacity of African laboratories where the research is carried out. The third is to support the improvement of specific types of infrastructure, i.e., bioinformatics and biorepository capacity, which are needed to do genomics-based and environmental research. To achieve these objectives, the H3Africa program at NIH will include a research component (this FOA and RFA-RM-12-007), a bioinformatics network component (to be funded in Summer 2012), a biorepository component (RFA-RM-12-008), and a social issues component (RFA RM-12-005). All awards under the NIH H3Africa program will be made to African institutions and the majority of the awarded funds must be spent in Africa. All awardees will participate in the H3Africa Consortium to further enhance the collaborative nature of this Initiative.

H3Africa is funded, in part, through the NIH Common Fund, which supports cross-cutting programs that are expected to have exceptionally high impact. All Common Fund initiatives invite investigators to develop bold, innovative, and often risky approaches to address problems that may seem intractable or to seize new opportunities that offer the potential for rapid progress.

A. Scientific scope

The objective of this FOA is to solicit applications for support of H3Africa Collaborative Centers (H3ACC) that will conduct research that will apply genomic approaches to understand the genetic and, at the investigators discretion, environmental contributors to chronic and infectious diseases and health in Africa. Each H3ACC must include at least three collaborating projects, including at least two outside of the applicant institution, which will interact to provide the complete capacity needed to carry out the genomics-based research effort proposed. Further discussion of the importance and structure of H3Africa collaborations is provided below, and applicants are urged to give adequate emphasis to the collaborative aspect of the proposed program. The Centers must also provide strong training and/or career development to young scientists, and clear organizational and management structures.

The scientific focus of applications responsive to this FOA will be broadly within the scope of human genetic/environmental contributors to disease and other health-related traits in Africa. The following list provides some examples of the types of topics that might be addressed. Applicants should understand, however, that this list is meant only to provide guidance; it is not exhaustive and appropriate topics are not limited to the examples given here.

• The genetic/environmental contributors to non-communicable disease in Africa. The burden of chronic diseases in Africa has been difficult to measure because of the absence of a coordinated process to estimate disease prevalence. However, a small set of prospective studies and hospital experiences has identified the increasingly important impact of chronic disease. Examples include a substantial burden from hypertension, a high mortality rate from stroke, a rapidly growing threat from diabetes, and an increasing recognition of the prevalence of mental illnesses. Some clinical and epidemiologic research on such chronic conditions has been conducted in several sites on the continent, and clinical expertise can be found in many hospitals and tertiary care settings. A small number of linkage, candidate gene, and genome-wide association studies (GWAS) have been completed and, in addition to replicating findings from other studies, have been able to identify potential new genetic loci involved in disease. An H3Africa Collaborative Center project might involve collection of new samples or use of existing samples from one or more populations of interest. The individuals from whom samples are collected should be well-phenotyped to ensure that the disease being studied has been properly diagnosed. Samples may be assayed by one or more genomic technologies, for example genotyping, exome or whole genome sequencing, and/or functional genomics methods, to elucidate the genetic underpinnings of the disease or trait of interest. Analysis of exposure data on these individuals could provide evidence about the environmental factors that, in conjunction with the genetic determinants, could help explain the etiology of the disease under investigation.
• The genetic/environmental contributors to communicable disease in Africa. Infectious diseases, including HIV/AIDS, malaria, tuberculosis, leishmaniasis, trypanosomiasis, schistosomiasis, and others, have historically been a major health problem in Africa. A variety of genetic and environmental factors contribute to the susceptibility to and development of disease, and genomic information may be useful in developing new approaches to treating and preventing infectious diseases. Significant attention and considerable funding have been given to the study of certain communicable diseases, and excellent research facilities for studying them are found throughout Africa. One of the striking aspects of the widespread nature of infectious diseases and the high rates of infection in populations living in similar environmental conditions is the considerable inter-individual phenotypic variability in susceptibility and response to infection, which can range from asymptomatic to death. Contemporary genomic approaches can help to understand the role that host genetics plays in these diseases. Similarly, additional genomic analysis and studies of the genetics of the parasites and vectors involved in the diseases can contribute essential information. HIV/AIDS and malaria are among the most well-studied communicable diseases in Africa and, while NIH will consider study of the host factors involved in susceptibility to HIV infection and diseases that are co-morbid with HIV/AIDS (see below) as being responsive to this FOA, studies of other infectious diseases are encouraged.
• The contribution of the human microbiome to health and disease in Africa. Recent advances in sequencing and other technologies have led to a burgeoning of studies of the role(s) of the human microbiome in health and disease. Changes in the microbiome at particular body sites have been correlated with the onset or progression of several diseases, such as Crohn’s disease, psoriasis and bacterial vaginosis. Most microbiome studies have been done outside of Africa, but given the expectation that microbiome composition is highly dependent on many environmental factors, including geographical location, diet, socio-economic status, as well as host genetics, the relevance of the results of those studies to understanding health and disease in Africa cannot be assumed. As an individual’s microbiome is expected to make a significant contribution to health status, studies of the role of the microbiome in diseases of African interest, and comparative analyses of microbiomes from healthy cohorts, would be appropriate H3Africa research projects.
• Mendelian diseases in Africa. Local founder effects and the cultural practice of consanguineous marriages in many African communities have resulted in the increased prevalence of monogenic traits across the continent. Recent studies have demonstrated that exome sequencing of a limited number of individuals can be used effectively to identify causative mutations in several Mendelian diseases. An analysis of individuals affected by Mendelian diseases to identify causative mutations and modifier genes in African populations would be appropriate research projects for H3Africa Collaborative Centers.
• Pharmacogenomics: Pharmacogenomics research seeks to identify genetic factors that are responsible for individual differences in drug efficacy and susceptibility to adverse drug reactions. African populations have been underrepresented in pharmacogenomics research, yet they show the highest levels of genetic diversity among human populations. Pharmacogenomics can be applied to numerous treatments of illnesses that plague the African continent, for example identification of the genetic variant(s) involved in inter-individual variability in the response to chemotherapy drugs used in cancer treatment, drugs used for the treatment of HIV, malaria, and other infectious diseases, as well as pain medications. Analysis of pharmacogenetic effects in Africans would be an appropriate H3Africa Collaborative Center research project.

While applications submitted in response to this FOA may propose research in any disease or health area that falls within the broad areas of genetic/environmental contributors to disease or health research, there are also specific areas of interest to the NIH components that are participating in H3Africa. These include:

• AIDS and co-morbidities. Research examining the genetic and genomic basis of HIV/AIDS disease and its co-morbidities including, but not limited to, host immune response to HIV infection; interaction of HIV with the host immune system; genomics in the context of HIV vaccine and microbicide development; host factors involved in co-infection, including tuberculosis, hepatitis C and hepatitis B in the context of HIV infection; host factors invovled in AIDS-defining and non-AIDS defining malignancies in HIV-infected individuals; and host factors involved in complications associated with long-term HIV disease and antiretroviral therapy (ART), including metabolic disorders, cardiovascular disease, conditions associated with aging, and neurologic and neurocognitive disorders.
• Neurological disorders and stroke: Research in neurological projects that address the H3 goals are of interest. Study designs may include a broad range of disciplines, such as molecular genetics, pharmacogenomics, epidemiology, stigma research, and intervention research. Quality phenotyping is essential for genetic research; therefore, collection and analysis of genetic material from individuals participating in well characterized, neurological-based cohorts materials are of high interest, particularly in the areas of stroke and stroke risk factors, epilepsy, and susceptibility to peripheral neuropathy due to infection or inflammation, as well as other neurological diseases and disorders. Applications that enhance the NIH-funded Medical Education Partnership Initiative (MEPI) training experience are encouraged (http://www.fic.nih.gov/programs/Pages/medical-education-africa.aspx).
• Genetic and genomic basis of HIV/AIDS disease, abuse of licit or illicit substances (including alcohol, tobacco, cannabis, stimulants, opiates), and related co-infections or co-morbidities: Topics include, but are not limited to studies of the host and viral determinants of immune responses to HIV infection in substance users, particularly related to specific disease phenotypes; the factors related to immune recovery following antiretroviral treatment in the context of substance use; determinants of susceptibility to HIV infection among substance users; complications associated with long-term HIV disease and substance use, such as tuberculosis, HIV/HCV-associated liver disease, cardiovascular disease, metabolic disorders, and neurologic and neurocognitive disorders; and viral evolution in association with injection or non-injection substance use.

B. Implementation of the objectives of H3Africa.

As described above, H3Africa has several specific objectives. Applications submitted in response to this FOA must address all of those objectives, as well as the following issues, (note that, in addition to the following discussion, specific application instructions and guidance are provided in Section IV.2 Research Plan):

Overall Research plan. The application should describe a well-conceived plan for a well-coordinated collaborative effort to investigate the genomic, and at the applicants discretion, the environmental, contributor(s) to a disease or other health-related condition of importance in Africa. The application should describe a compelling justification for the choice of the condition to be studied and should clearly state how the proposed research could lead to an improved understanding of its genetic and environmental origin(s). The application should provide a description of the health impact of the condition in Africa, and the relationship (if any) to the condition in other parts of the world. It is important to note that more than 50% of the funds for this project must be spent in Africa.

The application should present the plan for the overall collaborative center and then, separately, the strategy for each of the collaborating projects (see specific application instructions in Section IV.2 below). The plan for the overall center should discuss the types of data that will be analyzed and how those data will be obtained (see below) and analyzed. The plans for the collaborating projects should describe the specific contribution that each will make toward achieving the collaborative center’s objectives, as well as the specific objectives of the project and how those will be accomplished. The application should also discuss potential problems that might arise in pursuing the proposed strategy and how those problems could be addressed.

Collaborations. Many of the collaborations in which African biomedical research scientists have participated have been with scientists from abroad, rather than with other African investigators. One of the major goals of the H3Africa Initiative is to foster collaboration between and among investigators within Africa, in order to help build a larger African scientific community, which will in turn lead to more training opportunities and cutting-edge science on the continent. Intra-continental collaborations will also contribute to sustainability of African genomics programs. The application submitted must be structured around a significant set of at least three collaborative projects. See Section IV.2 for more information.

Sample collection and Human Subjects Issues. The application must include a detailed and clearly described plan for sample acquisition (either collection of new samples or use of previously collected specimens), and sample handling and storage.

Consent: Applicants should note that samples that are broadly consented for genomic analysis have proven to be very useful for genomic research projects beyond those for which the samples were originally collected. Therefore, investigators are urged to try to obtain consent for the wide sharing of samples and data; justification should be provided if samples and data will not or cannot be shared or only shared in a limited manner. NHGRI has prepared a document entitled "Essential Elements of Informed Consent for H3Africa Research Projects" that may be helpful to applicants in writing their informed consent procedures and documents; it can be found at http://www.h3africa.org/informedConsent.cfm. A timeline for sample collection, as well as a timeline for developing and implementing an informed consent process, including obtaining IRB approval, must be included in the application.

Sample Storage: With respect to long-term sample storage, H3Africa anticipates establishing two or more biorepositories in Africa, but they will likely not be prepared to accept large numbers of samples until 2014. Eventually, all H3Africa samples (blood, DNA or cell lines) are expected to be deposited in the H3Africa Biorepository, consistent with the informed consent under which they were collected, from which they can be distributed and shared for further research . Sample deposition must occur expeditiously, no later than the date of the first publication that describes the samples or by the end of the project, whichever comes first. A statement of commitment from the applicant institution to send samples to the H3Africa Biorepository must be included in the application. This should include a description of the host country’s policies for sending samples out of the country.

Sample Size: The application should include a sufficiently detailed discussion and power calculations to justify the proposed sample size, a detailed discussion of the methodologies to be used, and a thorough discussion of all relevant human subjects issues and informed consent. The application should also discuss potential challenges to achieving the sample collection goals of the proposed program and how those challenges will be addressed if they do.

Phenotyping. The potential of genomics research to yield insight into the biology of disease is dependent on an accurate definition and measurement of the relevant phenotypes and, if environmental issues are addressed, a comprehensive understanding of relevant environmental factors. The application should, therefore, clearly describe the methods of ascertainment of both primary and secondary phenotypic data as well as environmental data if appropriate, and explain how accuracy will be ensured. To allow comparison to other studies, it is important that the data definitions be well-described and, to the extent possible, collected according to standardized practices (see for example, www.phenxtoolkit.org). Where relevant, the application should include questionnaires or survey instruments to be used and describe plans for follow-up or collection of longitudinal data. If samples are to be collected at different sites, the application should discuss the quality assurance and quality control measures that will be implemented to ensure that the data collected at the different sites are comparable. The application should also address the informatics aspects of data collection and storage.

Data Generation. The application should clearly describe how the samples will be prepared for genomic analysis, provide a justification for the type(s) of genomic data to be acquired, and how those data will be generated. If the genomic data are to be generated within the center, the application should discuss the applicants experience with the necessary technologies, the costs of generating the data, and the informatics aspects of data collection, storage and transfer among the participating sites. The availability of samples and supplies should be discussed, as should any issues of long-term maintenance and servicing of the necessary equipment. Any anticipated problems that may be encountered in data acquisition and planned approaches to solving such problems should be described.

However, it is not necessary that all data be generated within the H3ACC itself. For example, it may be more cost effective to send samples out to another genome center or to a commercial service provider(s), either in Africa or overseas. If this approach is chosen, the applicant should provide a justification for that choice, and describe how the samples will be prepared for shipment to the data generator, the type of data expected, and how the data will be returned to the center for analysis. The applicant should also describe any provisions that will be made to obtain training in the relevant technologies for students or technicians.

Data Analysis and Bioinformatics. Whether the data are generated within the center or obtained from outside, the applicants must clearly describe how the resultant data will be analyzed. The bioinformatics capacity of the Collaborative Center should be clearly described, both at the level of the overall center and at the level of each of the collaborating projects. The bioinformatics tools that will be used or developed, and the applicants experience with their use should be described. Issues of data acquisition, data management, data storage, and analytical capability should all be addressed. In particular, for studies involving genomics-based analyses, the applicants should provide justification that the experimental and analytical design will have sufficient power to address the question(s) being asked. The bioinformatics activities may be embedded within the individual projects or may appear as a separate, collaborating bioinformatics project. Additionally, a bioinformatics research project, for example new computational tool development, may be included within the research proposal as one of the collaborative aspects.

Applicants should be aware that the H3Africa Program will fund a separate H3Africa Bioinformatics Network (see expired FOA, RFA-RM-11-010) to provide connectivity among the H3Africa participants. The H3Africa Bioinformatics Network will also have the ability to develop new bioinformatics tools for genomics research in Africa. The H3ACCs, and any other H3Africa-funded activity, will be required to interact with the H3Africa Bioinformatics Network. Therefore, applicants for an H3Africa Collaborative Center award must include a statement from the applicant institution committing it to collaborating and sharing data with the H3Africa Bioinformatics Network consistent with achieving the goals of H3Africa.

Training and Career Building. Establishing the next generation of African researchers to take advantage of genomic approaches to health research is a primary objective of the H3Africa program. Therefore, an H3ACC must include a component which addresses either training, or career development, or both.

• Training. In this FOA, training is meant to include education in genomic science and research techniques for students at both the MS and PhD levels, and of post-doctoral researchers; it also includes technical training of laboratory staff. As different institutions and research sites will have different training needs, other types of training will be considered if appropriately justified. Applicants will have wide latitude in designing the training programs, which may be directed at as many of those levels as appropriate and practical, and for any period of time. Training may include relevant courses at the MS and Ph.D. levels but may not include support for an individual's degree program. While it is expected that the majority of training will take place in African institutions, training opportunities abroad can also be included; in that case, a plan for the return of the trainees back to Africa is required. The training program may include any combination of course work, laboratory experience, and mentoring. The applicants training experience should be adequately described.
• Career development. Fostering the careers of recently trained doctoral-level investigators by recruiting or engaging them in the research programs as leaders of projects is another valuable contribution that the Collaborative Centers can make to establishing the next generation of African researchers; applicants are, therefore, encouraged to include a career development component in. For example, sabbatical leave costs to support project-related training may be requested, as specified in the NIH Grants Policy Statement (see http://grants.nih.gov/polcy/nihgps_2011/nihgps_ch7.htm#selected_cost_items).

Well thought-out plans for the training and career building programs, their applicability to the H3ACC s research and their long-term contributions to the goals of H3Africa should be described. Long-term sustainability and institutional/governmental commitments to the training program and the independent career positions established through the Centers should also be discussed. Applicants should note that the Medical Education Partnership Initiative is a sister initiative to H3Africa within the NIH Common Fund's Global Health Program. H3Africa applicants are encouraged to collaborate with MEPI grantees (see http://www.fic.nih.gov/Programs/Pages/medical-education-africa.aspx) as part of their training program where possible, in order to take advantage of the training infrastructure and opportunities available through MEPI.

In Summary: This FOA solicits applications for H3Africa Collaborative Centers to carry out the research goals of H3Africa, which include:

• establishment of viable, productive, and eventually sustainable, African research programs for the study of the genetic and environmental contributors to disease and health,
• improving the research environment by leveraging current expertise and existing infrastructure with new investments,
• training and career development, and
• exploration of the social implications of genomic research in Africa .

The scientific scope of the Centers component of H3Africa is broad, and may address:

• the genetic/environmental contributors to non-communicable disease in Africa,
• the genetic/environmental contributors to communicable disease in Africa,
• the human microbiome and its contribution to health and disease in Africa,
• Mendelian diseases in Africa,
• pharmacogenomics, and
• other

Funding Instrument	Cooperative Agreement
Application Types Allowed	New Resubmission The OER Glossary and the PHS398 Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	This initiative is supported by NIH Common Fund, Institute(s) and Center(s) and Offices of the NIH that have signed on to support the H3Africa initiative. The amount of funding and the number of awards will rely upon the outcome of peer review, the interests of the NIH institutes, and the availability of funds. The total amount of funds available for these awards is approximately $2.5 million per year (total costs) in FY13 and $2 million per year (total costs) in FY 14-16, contingent upon receiving scientifically meritorious and availability of funds. Up to 2 awards are anticipated from this solicitation.
Award Budget	Applications are limited to $1,000,000 total costs which includes salaries, supplies, training, equipment, travel, and other allowed expenses for research grants. In order to address H3Africa's goals to build infrastructure each applicant may request up to an additonal $250,000 for equipment in the first year. All requests for equipment must be very well justified in terms of the needs of the proposed project. In subsequent years the research plan budget may not exceed $1,000,000 total costs. In each year, $35,000 direct costs/year must also be set aside for participation in the International Extramural Administrative Research Development Program component (see above) under Implementation of H3Africa Objectives section.
Award Project Period	Scope of the proposed project should determine the project period. The maximum period is 4 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.

• Non-domestic (non-U.S.) Entities (Foreign Institutions)

Specifically, African institutions are eligible for the awards:

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant organizations must complete the following registrations as described in the PHS398 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 registrations.

• Central Contractor Registration (CCR) must maintain an active registration, to be renewed at least annually
• eRA Commons

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 least4-6 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 PHS398 Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

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. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the PHS398 Application Guide.

Applicants are required to prepare applications according to the current PHS 398 application forms in accordance with the PHS 398 Application Guide.

It is critical that applicants follow the instructions in the PHS398 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.

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:

• Descriptive title of proposed research
• Name, address, and telephone number of the PD(s)/PI(s)
• Names of other key personnel
• Participating institutions
• Number and title of this funding opportunity

The letter of intent should be sent to:

Jane L. Peterson, Ph.D.
National Human Genome Research Institute
National Institutes of Health
5635 Fishers Lane, Suite 4076, MSC 9305
Bethesda, MD 20892-9305
Phone: 301 496 7531
Fax: 301 480 2770
Email: [email protected]

FedEx/UPS/Other Courier Delivery Address:

NIH/NHGRI/DER
5635 Fishers Lane, Suite 4076, MSC 9305
Rockville, MD 20852

Applications must be prepared using the PHS 398 research grant application forms and instructions for preparing a research grant application. 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 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)

At the time of submission, two additional paper copies of the application and all copies of the Appendix files must be sent to:

Dr. Rudy Pozzatti, PhD
National Human Genome Research Institute
National Institutes of Health
5635 Fishers Lane, Suite 4076, MSC 9306
Bethesda, MD 20892-9306
Phone: 301-402-8739
Fax: 301 435 1580
Email: [email protected]

FedEx/UPS/Other Courier Delivery Address:

NIH/NHGRI/DER
5635 Fishers Lane, Suite 4076, MSC 9306
Rockville, MD 20852

All page limitations described in the PHS398 Application Guide and the Table of Page Limits must be followed, with the following exceptions or additional requirements:

• The Introduction (resubmitted applications only) is limited to 1 page.
• The Specific Aims section is limited to 1 page.
• Each Collaborative Project or Core section is limited to 12 pages in length. No more than 3 to 5 Collaborative Projects are allowed.
• The Training and Career Development Section and the Administration and Management Section are each limited to 12 pages.

The IEARD request is limited to 6 pages.

All instructions in the PHS398 Application Guide must be followed, with the following additional instructions:

The application must include a research plan that is responsive to the objectives of the H3Africa program, as set forth in this FOA (see Research Objectives). The overall research plan is made up of the following:

1. Introduction to resubmission application

2. Specific Aims

3. Collaborative Center Overview

4. Collaborative Research Project Plans

5. Training, Administration and IEARD Plans

6. Biosketches

7. Appendix

Within sections 3, 4 and 5 the application should include a research strategy that addresses the appropriate topics given above in Implementation of the Objectives of H3Africa, using the instructions given below.

An H3Africa Collaborative Center must comprise at least three collaborating research projects that together address one or more research areas of interest to H3Africa. At least two of these projects must be outside of the applicant institution. No more than 5 collaborative research projects should be proposed. Bi- or multi-national collaborations within Africa are strongly encouraged, while collaborations outside of Africa are allowed.

Introduction (Resubmissions only): For resubmitted applications only, the Research Plan must include an introduction to the Application. The introduction is an opportunity for the PI who has revised and is resubmitting an application to address the comments from the initial review of the previous application. It is limited to one page. New applications should not include an introduction. For more information, see specific instructions in PHS 398.

Specific Aims: A concise set of specific aims is required that explain the overall goals and expected outcomes of the research. This section is limited to one page.

Collaborative Center Overview: The application should include an initial section that thoroughly, but concisely,discusses the scientific goal(s) and organization of the center; the specific research to be carried out by each project; the collaborative interactions among the projects and how those will contribute to the functioning and success of the H3ACC; the center-level analyses; challenges and problems that the project might encounter and suggestions as to how they will be solved and how the overall H3ACC will be managed, particularly with respect to collaborations that are not located at the PD(s)/PI(s) home institution. This section is limited to 6 pages.

Collaborative Research Projects: Collaborative Research Projects plans should include a Research Strategy plan, including discussion of the items mentioned under Implementation above and the following:

H3Africa applications are required to be structured around significant collaborative projects within the applicant’s home country, with scientists in other African nations, or both. Collaborations with scientists in non-African countries can also be included. In practice, each H3ACC must be composed of at least three but no more than 5 collaborating projects, at least two of which need to be with investigators outside the home institutuion of the PD(s)/PI(s). These projects must collaborate to provide the complete capacity needed to carry out the proposed genomics-based research effort on a disease or condition important to Africa. Note that more than 50% of the funds for an H3Africa application must be spent in Africa.

In requiring that an H3ACC be comprised of multiple projects, the NIH does not intend to specify what those projects should be or how they are to be organized within the center. In general, genomic research projects include sample acquisition, phenotyping, genomic data generation, and data analysis activities, but there can be many ways to organize these activities. For example, each of these activities could be carried out by a separate project with an H3ACC. Alternatively, an H3ACC could be organized so that each project includes all of these activities, with the individual collaborating projects each studying a different sample population and the results combined at the Center level for a comparative analysis. These two examples are only intended to be illustrative; the roles and organization of the collaborative projects within an H3ACC will be determined by the applicants to be those that will best achieve the proposed Center’s research objectives

The significance of each of the project should be clearly described, indicating the specific contribution that each will make to the overall success of the Collaborative Center. The applicant should also identify any aspects of the application that the applicant considers to be particularly innovative. Applicants should also identify potential major challenges or problems that might be encountered in conducting the proposed research, and discuss how these will be addressed should they arise. Each project should also describe how it will interact with the other projects in the center.

The methods and technologies that will be used must be described along with the investigator(s)’s experience with conducting research and employing the appropriate methods and technologies.

Innovative approarches and technologies that will be employed by the center should also be discussed and the impact of those methods and/or technologies on the future of African science and/or medicine should be explained.

The approaches to meeting the bioinformatics needs of the project, the project’s approach to informed consent and protection of research subjects (if applicable) and research animal welfare (if appropriate) should also be discussed in this section, as well as any other issues that are specific to the individual component.

Each collaborative research project plan is limited to 12 pages and, as noted above, it is recommended that centers be structured so that no more than 3 to 5 collaborative research projects be included in the application. Applicants should be aware that concise and clear applications are important to successfully conveying scientific plans.

Training and Career Development. A description of the Collaborative Center's training and career development objectives and how they will be met should be provided as a separate section, limited to 12 pages in length. The training and career development activities may be presented separately within the 12-page limit. The description should address the objectives of the Collaborative Center s training and career development activities, and how they will promote the scientific careers of the target group(s) in Africa; how the trainees and new investigators will be identified; the specific training and career development activities that will be supported within the Collaborative Center, including mentoring activities; where the training will take place; opportunities for cross-training within the Center’s collaborating components (as applicable); the role of training opportunities outside of the Collaborative Center; and plans for monitoring the progress of individual trainees and new investigators. If aspects of the training program are to be implemented outside of Africa, the issues involved in ensuring that the individuals involved will be able to apply what they have learned abroad in the African research setting must be discussed.

Administration and Management. The organizational structure of the Collaborating Center, and the plans for administering, managing, tracking, and coordinating the activities of the Center and its individual components should be described in a separate section, limited to 12 pages in length. The Collaborative Center s plans for data release, resource release, intellectual property disposition, monitoring and evaluation and institutional and national commitment should be included in this section.

• Data Sharing and Release plan: A plan for data and resource sharing and release is expected for all NIH applications (http://grants.nih.gov/grants/policy/data_sharing/), and an application must have an acceptable Data and Resource Sharing and Release plan before it can be funded. Applicants are, therefore, expected to provide a well thought-out plan for widely sharing data and resources generated by the H3ACC, H3Africa Research Project. After all H3Africa awards have been made, the H3Africa Consortium (see below) will develop a unified policy for data and resource release, and the application must include a statement that the investigators will abide by the Consortium’s data and resource policy, consistent with the relevant NIH policies, laws and regulations. Examples of current data release guidelines under the H3Africa Initiative for NIH programs can be found at: http://www.h3africa.org/dataReleasePolicy.cfm.
• Monitoring and Evaluation Plan: The applications must contain a plan for how the funds and supported activities will be monitored and evaluated over the course of the grant period. The applicant should discuss how the project will be assessed and how success and impact will be defined and determined. The discussion should address how any modifications that will need to be made as a result of the monitoring and evaluation activities will be effected. To facilitate monitoring and evaluation, applications should include a well-defined set of yearly milestones for the proposed research and training activities. These milestones will be negotiated and finalized at the time of award, and will then be included in the Terms and Conditions of the award. The milestones will be subject to change only with the NIH Program Director’s agreement, but will be reconsidered on an annual basis to account for the Center s experience and progress. An example of the level of detail and specificity needed for the milestones can be found in an example set of acceptable milestones from past genomics projects, posted at http://www.h3africa.org/genomicsProjectMilestones.cfm.
• Sustainability: Another of the primary goals of the H3Africa program is to enable African scientists to demonstrate their world-class skills through the establishment of cutting-edge research programs that will lead to more publications and other evidence of productivity, thereby increasing their opportunities for future funding through normal competitive grant processes, as well as through increased investment in research by national governments and private sources. Dedicated funds for H3Africa by the NIH Common Fund will provide 5 years of support. Up to 5 additional years of dedicated funds may become available contingent upon the initial progress of the H3Africa Project. Beyond that, any support for continuation of the research programs and research careers initiated under the auspices of H3Africa will be dependent on other funding. Therefore, applicants need to discuss the issue of future sustainability of their research programs beyond the H3Africa program and how the Collaborative Center activity will contribute to success in continuing the research efforts of all of the participants in the Center. This section of the application should be included in the administration and management section and should refer to the letters of Institutional and National commitments (see below) to provide an overview of the long term prospects for sustained research by the Center and each of its components.
• Institutional and National Commitments: Applications should include letters of support from the appropriate institutional official (University or Medical School President, Dean or Director, or the head research administrator or equivalent) from all collaborating institutions to substantiate the institutions commitment to the proposed research. Each institution should state its commitment to overcoming any administrative obstacles to the implementation of the proposal, such as accommodation for participation by multiple schools at the university or collaboration with other institutions within or outside of the applicant’s country. Appropriate institutional commitment to the program includes the provision of adequate staff, facilities, and resources needed for the success of the planned program. As described in preceding sections, the letter should address institutional commitment to any new faculty whose labs are established within the Center. It should also address commitment to collaborating and sharing data with the H3Africa Bioinformatics Network and the H3Africa Biorepositories. The letter should also briefly discuss the institution's plans for sustaining an active program of scientific research subsequent to the end of the H3Africa program.

The Adminstration and Management section should also include a description of the applicant institution's current capacity for administration of research grants, including information about the placement of the designated research administrative infrastructure (e.g., Office of Research, Office of Sponsored Projects) within the institution and its line of authority, the institutional provision of resources such as office space, administrator salary, office equipment and other in-kind activities, and the applicant institution's plans to support and sustain the research office. The application should also describe any plans the institution has for further development of its research administration program (see next paragraph).

IEARD request: The H3Africa Collaborative Center award will include $35,000 (direct costs) per year to support such further development at the applicant institution. It is expected that by the end of year -01 of the Collaborative Center award, one or more research administrators will have received training equivalent to that provided by the NICHD International Extramural Research Administration Development Award (IEARDA) program. The purpose of the IEARDA program is to increase the knowledge and/or experience of research administrators with funding opportunities, grant applications, research program and project oversight, data management, fiscal accountability, and scientific reporting requirements of the NIH and other international research funding agencies, all of which will be important in the adminstration of the Collaborative Center award. If at least one individual at the applicant institution who will have significant responsibility for the management of the Collaborative Center award has participated in the NICHD program, the application should document that and then describe the applicant institution's plans to use the specified funds to enhance and further strengthen its research administration activities. If no individual at the applicant institution has yet received such training, the specified funds should be used to support an individual to participate in this program at the earliest possible offering after an award is made (the NICHD has agreed to accept one person from each awarded Collaborative Center into its training program). NICHD will review the qualification of the person nominated before accepting him or her in the IEARDA program. The application should thus identify the person or persons who will be responsible for administering the Collaborative Center award and a Biosketch should be provided for each. The application should also include a brief, one to two page, description of the Center's and applicant institution's plans for the administration of the award (equivalent to the Institutional Development Plan of the IEARDA program). Finally, the application should include a statement of support from the applicant institution that provides approval of the nominee’s IEARDA training periods at home through the distance learning component and at the NIH for the NIH residency, and provides the release time for these periods and any financial support needed for training. This statement of institutional support may be included in the required Letter of Institutional Support described in the Implementation of the Objectives of H3Africa section above. The IEARDA application should appear after the Administration and Management section and may be no more that 6 pages. More about this program and details to be included in the application can be found at http://www.H3Africa.org/IAERDinfo.cfm.

Infrastructure. To the extent possible, the Collaborative Centers are expected to utilize existing infrastructure in the clinical and research institutions where the studies will be carried out (as well as the H3Africa Bioinformatics Network and the H3Africa Biorepositories as described elsewhere in this FOA). A detailed, well-documented description of existing institutional infrastructure must be provided in the Resources section of the grant application. Additional infrastructure components may be requested in the application.

Equipment. Equipment may be requested within the annual $1,000,000 total cost cap for an H3ACC. In addition, in the first year only, up to $250,000 more may be requested for equipment beyond that cap (see Section II, Award Budget, below). The additional equipment must be used for the proposed research project and must be well-justified. However, these funds will be restricted for purchase of equipment only, and cannot be used to augment the research budget. The requests for equipment within the $250,000 limit for restricted equipment funds should be made separately from any equipment requests made within the $1,000,000 cap.

H3Africa Consortium Meetings: The NIH and the Wellcome Trust plan to hold two H3Africa Consortium meetings per year, and applicants should request funds to travel to these meetings in their application. Most of the meetings will be held in Africa. However, in 2015, one of the Consortium meetings will be held in Bethesda, MD and in 2016, one meeting will be held in London, UK. It is expected that each research project and administrative core (if part of the U54 structure) will bring 1 to 2 people to the meeting. For the meeting in Bethesda, each research project should be represented by at least the PD/PI and two trainees. Appropriate travel funds for these meetings must be requested in the 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 PHS398 Application Guide. Final, uniform H3Africa policies for resource and data sharing will be determined by the Steering Committee (see below) once all the awards have been made. Preliminary to this, the applicants are expected to propose plans for resource and data sharing in the application consistent with achieving the goals of the H3Africa initiative, and such plans must be approved by H3Africa program staff before the application can be funded. See http://www.h3africa.org/dataReleasePolicy.cfm for examples of data sharing plans under the H3Africa Initiative for NIH programs The applicant should also state his/her willingness to adhere to the final H3Africa Consortium policies on resource and data sharing, once they have been determined, consistent with NIH policies, laws and regulations.

Appendix

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix (please note all format requirements) as described in the PHS398 Application Guide,

Foreign (non-US) Institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the PHS398 Application Guide.

Part I. Overview Information contains information about Key Dates.

Information on the process of receipt and determining if your application is considered on-time is described in detail in the PHS398 Application Guide.

Applicants may track the status of the application in the eRA Commons, NIH’s electronic system for grants administration.

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 received on or before the due dates in Part I. Overview Information. If an application is received after that date, it will not be reviewed.

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, with the following modification:

Letters of support from the relevant national ministries, for example the Ministry of Science, Ministry of Health and/or Ministry of Education; Medical Council; or appropriate government official for the host country should be submitted with the application but may also be submitted post application.

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 proposed H3Africa Collaborative Center (H3ACCt 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 center 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 n H3Africa Collaborative Center that by its nature is not innovative may be essential to advance a field.

Significance

Does the proposed H3ACCt 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?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the H3ACCt? 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? Are the proposed collaborators likely to work together synergistically?

Innovation

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 program promote and support innovation that will strengthen and sustain genomics research in Africa? How important is innovation to the success of the proposed H3ACC?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the H3ACC? 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 managed?

If the H3ACC 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? Will the training and career development program proposed be effective in addressing the H3Africa goal of enhancing the competitiveness of African genomics investigators? Will the Center support the career building objectives of H3Africa? Are the bioinformatics data handling and analysis plans adequate to address the needs of the Center? Are the evaluation plans, milestones and timelines proposed appropriate and adequate for the project? Has the issue of future sustainability been adequately addressed?

Environment

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 Center take advantage of resources available at the collaborating institutions? Does the application identify and plan to take advantage of other resources at the participants' institutions, countries or other countries where necessary?

As applicable for the Collaborative Centert 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.

Center as an Integrated Effort Overall Impact

• Is the proposed collaborative nature of the Center conducive to achieving the Center's goals?
• Does the application provide adequate evidence of the advantages of conducting the proposed research as a collaborative program rather than through separate research efforts? Will the research efforts taken together have more impact on the field than each separate project conducted in isolation? Will the research proposed in individual projects be enhanced by being part of the Collaborative Center?
• Are there adequate mechanisms proposed for regular communication and coordination among investigators in the Collaborative Center?
• Are adequate administrative structures in place for the day-to-day management of the center, including arrangements for internal quality control of ongoing research?

Sustainability

• Do the letters of Institutional and National commitment suggest that the environment is conducive to a sustained research enterprise?
• Do the collaborations among the institutions suggest viable long-term partnerships?

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.

Vertebrate Animals

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.

Biohazards

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.

Resubmissions

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewals

Not Applicable.

Revisions

Not Applicable.

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

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

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 the National Human Genome Research Institute, 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:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact/priority score.
• Will receive a written critique.

Appeals of initial peer review will not be accepted for applications submitted response to this FOA.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center and 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:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• How well the application addresses the goals of H3Africa
• Overall program balance in the H3Africa program

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.

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 recipient’s activities by involvement in and otherwise working jointly with the award recipient 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 awardee(s) for the project as a whole, although specific tasks and activities may be shared among the awardee(s) and the NIH as defined below.

Definitions

Steering Committee (SC):

The Steering Committee is the primary governing body of the Consortium. PI(s)/PD(s) of the cooperative agreements, and NIH Program Directors serve on the committee. See further details about the Steering Committee under "Joint Responsibilities".

Independent Expert Committee (IEC)

The IEC will be composed of senior scientists with relevant expertise who are not PD(s)/PI(s) of a cooperative agreement involved in the H3Africa Consortium. The members will be appointed by the NIH and the Wellcome Trust, the funding partners of H3Africa. The IEC will be responsible for monitoring and assessing the progress of the H3Africa Consortium. See more about the IEC below under this topic .

The PD(s)/PI(s) will have the primary responsibility for:

• All aspects of the study, including any modification of study design, conduct of the study, quality control, data analysis and interpretation, preparation of publications, and collaboration with other investigators, unless otherwise provided for in these terms or by action of the Steering Committee.
• Awardees agree to the governance of the H3Africa Consortium through the Steering Committee and recommendations from the Panel of Scientific Consultants.
• Awardee(s) will agree to accept close coordination, cooperation, and participation of NIH H3Africa staff in those aspects of scientific and technical management of the project as described under "NIH Program Staff Responsibilities."
• Awardee(s) will provide goals and progress toward those goals at regular intervals as requested by NIH H3Africa staff and will ensure that the data produced meets the quality standards agreed to at the beginning of the project by the H3Africa Consortium;
• Awardee(s) will ensure that the data are deposited in the appropriate public database (e.g., GenBank or other, as specified by NIH H3Africa program staff), that resources developed as part of this project are made publicly available according to H3Africa Consortium policies, and that results are published in a timely manner;
• Awardee(s) will adhere to the H3Africa policies regarding intellectual property, data release and other policies that might be established during the course of this activity consistent with applicable NIH policies, laws, and regulations;
• Awardee(s) will integrate with and connect to the H3Africa Bioinformatics Network;
• Awardee(s) will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

• One H3Africa Project Scientist from each participating Institute will serve on the Steering Committee and have one vote; the number of NIH votes may not exceed the number of PD(s)/PI(s) votes on the SC. They and other NIH H3Africa project team scientists may serve on sub-committees or working groups, e.g., data sharing, data release, quality control, core establishment, as appropriate. The NIH H3Africa Project Scientists may work with awardees on issues coming before the Steering Committee and other sub-committees and working groups.
• The Project Scientists will help the other Steering Committee coordinate the group process of exchanging information about research approaches and protocol designs and of the development of Consortium policies
• The Project Scientists will negotiate goals with the awardees as necessary; wlll serve as liaison between the awardees and the Panel of Scientific Consultants, the National Advisory Council for Human Genome Research and other Councils, and the larger international scientific community; will attend all Steering Committee meetings as voting members as described above; and will assist in developing operating guidelines, quality control procedures, and consistent policies for dealing with recurrent situations that require coordinated action.
• The Project Scientists will periodically report progress about the H3Africa Consortium to the Director, Division of Program Coordination, Planning, and Strategic Initiatives; and the Directors NHGRI, FIC, NINDS, and OAR.
• The NIH reserves the right to withhold funding or curtail the study (or an individual award) in the event of (a) substantive changes in, or failure to make sufficient progress, toward the agreed-upon work scope with which the NIH cannot concur, (b) human subject ethical issues that may dictate a premature termination.
• Support or other involvement of industry or any other third party in the study -- e.g., participation by the third party; involvement of study resources or citing the name of the study or NIH support; or special access to study results, data, findings or resources -- may be advantageous and appropriate. However, except for licensing of patents or copyrights, support or involvement of any third party will occur only following notification of and concurrence by NIH.
• Additionally, an agency program official or NIH program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. The assigned program director may also serve as an NIH Project Scientist.

Areas of Joint Responsibility include:

• Steering Committee participation. A Steering Committee (H3ASC) will serve as the main governing board of the H3Africa Consortium. The Steering Committee membership will include the NIH Project Scientist(s) and the P.I. of each award. The Steering Committee Chair will not be an NIH staff member but will be appointed by NIH H3Africa staff. Additional members may be added by action of the Steering Committee. Other government staff may attend the Steering Committee meetings, if their expertise is required for specific discussions. Because the Consortium will include investigators funded as a result of this FOA and of other H3Africa FOAs, it is possible that NIH H3Africa staff will create appropriate subcommittees to handle interests that may be specific to a set of awardees funded as a result of a specific FOA.
• The Steering Committee will:
• Discuss progress in meeting the goals of various H3Africa projects;
• Facilitate coordination and synergy across the entire H3Africa program;
• Develop recommendations for uniform procedures and policies necessary to meet the goals of the Consortium, for example for data quality measures and assessment, conventions for data deposition;
• Schedule the time for, and prepare concise (3 to 4 pages) summaries of, the Steering Committee meetings, which will be delivered to members of the group within 30 days after each meeting. The SC will meet twice a year with intermittent conference calls.
• Each full member (limited to one person per awarded center, in the case of multiple PIs per center) will have one vote. Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.

The Independent Experts Committee(IEC)

The IEC will make regular assessments and provide recommendations to the Directors of NIH funding components and the Director of DPCPSI about progress of the H3Africa components toward the goals of the H3Africa program and about continued support of the components of the H3Africa Consortium.

• The IEC will meet at least once a year. During part of this meeting, there will be a joint meeting with the H3Africa Steering Committee to allow the IEC members to interact directly with the awardees.
• Annually, the IECs will provide assessments regarding the progress of the H3Africa Consortium and of the individual components and, as necessary, will present recommendations regarding any changes that may be necessary in the H3AFrica program to the Directors of the NIH funding components.

Dispute Resolution:

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. The three members will be: 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.

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-710-0267
TTY 301-451-5936
Email: [email protected]

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)
TTY: 301-451-5939
Email: [email protected]

Jane L. Peterson, Ph.D.
National Human Genome Research Institute
National Institutes of Health
5635 Fishers Lane, Suite 4076, MSC 9305
Bethesda, MD 20892-9305
Phone: 301-496-7531
Fax: 301-480-2770
Email: [email protected]

FedEx/UPS/Other Courier Delivery Address:

NIH/NHGRI/DER
5635 Fishers Lane, Suite 4076, MSC 9305
Rockville, MD 20852

Dr. Rudy Pozzatti, PhD
National Human Genome Research Institute
National Institutes of Health
5635 Fishers Lane, Suite 4076, MSC 9306
Bethesda, MD 20892-9306
Phone: 301-402-8739
Fax: 301-435-1580
Email: [email protected]

FedEx/UPS/Other Courier Delivery Address:

NIH/NHGRI/DER
5635 Fishers Lane, Suite 4076, MSC 9306
Rockville, MD 20852

Victoria Bishton
National Human Genome Research Institute
Telephone: 301-451-7928
Email: [email protected]

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.