Participating Organization(s) |
National Institutes of Health (NIH) |
National Institute on Alcohol Abuse and Alcoholism (NIAAA) |
|
Funding Opportunity Title |
Effects of In Utero Alcohol Exposure on Adult Health and Disease (R01) |
Activity Code |
R01 Research Project Grant |
Announcement Type |
New |
Related Notices |
|
Funding Opportunity Announcement (FOA) Number |
PA-12-291 |
Companion Funding Opportunity |
|
Catalog of Federal Domestic Assistance (CFDA) Number(s) |
93.273 |
Funding Opportunity Purpose |
This Funding Opportunity Announcement (FOA), issued by the National Institute on Alcohol Abuse and Alcoholism (NIAAA), is intended to support novel research on how prenatal alcohol exposure may contribute to the etiology of chronic diseases and health conditions later in life. Central to this theme is the developmental origins of health and disease (DOHaD) concept which suggests that fetal adaptations in response to adverse intrauterine conditions may increase the risk for childhood and adulthood disease. The goal of this FOA is to stimulate a broad range of research to: 1) leverage existing prospective birth cohorts to define the role of maternal alcohol consumption in the DOHaD process; 2) investigate the biological, cellular, and molecular mechanisms by which prenatal alcohol exposure may impact disease outcomes later in life; and 3) identify biomarkers associated with gestational alcohol exposure that may predict adult disease susceptibility in exposed offspring. Studies supported by this FOA will provide fundamental insights into a possible fetal-basis to adult disease that is influenced by maternal alcohol use. |
Posted Date |
September 28, 2012 |
Open Date (Earliest Submission Date) |
January 5, 2013 |
Letter of Intent Due Date |
Not Applicable |
Application Due Date(s) |
Standard dates apply, by 5:00 PM local time of applicant organization. |
AIDS Application Due Date(s) |
Standard dates apply, by 5:00 PM local time of applicant organization. |
Scientific Merit Review |
Standard dates apply |
Advisory Council Review |
Standard dates apply |
Earliest Start Date(s) |
Standard dates apply |
Expiration Date |
May 8, 2016 |
Due Dates for E.O. 12372 |
Not Applicable |
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 National Institute on Alcohol Abuse and Alcoholism (NIAAA) invites Research Project Grant (R01) applications to examine a potential association between prenatal alcohol exposure and the development of chronic diseases and conditions across the lifespan (e.g., of the child, adolescent, and adult). Studies applying the developmental origins of health and disease (DOHaD) approach reveal susceptibilities to adult-onset disease (e.g., cardiovascular disease, type 2 diabetes, obesity, select cancers, asthma, behavioral disorders) which are programmed in utero in response to maternal conditions and environmental exposures other than alcohol. As many as 1 in 8 women report alcohol use during pregnancy. Understanding how exposure of the embryo and fetus to alcohol, a known teratogen, may alter health and chronic disease later in life represents a significant public health concern and warrants investigation. Research using animal models and emerging -omic approaches to generate new mechanistic and clinical insights into alcohol’s contributions to the DOHaD paradigm are encouraged. Such work may help to define strategies for disease prevention in exposed individuals as it relates to maternal alcohol use.
Chronic alcohol use represents an enormous global health burden. According to the World Health Organization (2011), harmful alcohol use is a causal factor in more than 60 types of disease and injuries, resulting in approximately 2.5 million deaths annually. Heavy alcohol consumption contributes to the etiology of major diseases involving the liver, pancreas, heart, vascular system and the brain. In addition, alcohol use is a significant risk factor for several types of cancer. By contrast, moderate levels of drinking may have beneficial effects, such as reducing coronary heart disease and preventing osteoporosis. Despite extensive studies on the health consequences of alcohol use during adolescence and adulthood, little is known about how alcohol exposure much earlier in life, prior to birth, will impact the risk for chronic diseases later in life.
Epidemiological research over the last two decades has shaped the DOHaD concept, a theory that physiological adaptations made by the fetus in response to adverse changes in the intrauterine environment may enhance adult disease susceptibility. The DOHaD paradigm originates from observations that newborn birth weight and adult death rate due to ischemic heart disease are inversely correlated. This seminal finding lead to the Barker hypothesis, which suggests that undernutrition during pregnancy reprograms the fetal physiology (e.g., structural, functional, or metabolic changes) in such a way to increase the risk for coronary heart disease later in life. Further investigation lead to the thrifty phenotype hypothesis, a theory of how adult-onset diabetes may arise from permanent alterations in fetal glucose metabolism triggered by maternal malnutrition. The predictive adaptive response further suggests that the fetus may predict the optimal adult phenotype for survival based on intrauterine cues which in turn induce physiological and metabolic adaptations that align best with future expectations. Consequently, adult-onset diseases may emerge if inconsistencies exist between the anticipated and actual postnatal environment. It is now evident that other complex diseases such as hypertension, asthma, obesity, osteoporosis, mental illness, and some cancers may also be developmentally programmed early in life in response to adverse intrauterine conditions.
Although explanations for these epidemiological findings have been offered, the mechanistic basis underlying the fetal programming of adult diseases is not yet fully understood. Proposed mechanisms include: 1) perturbed homeostatic control of fetal growth and development involving the insulin-like growth factor I (IGF-1) pathway and the glucocorticoid-mediated regulation of the hypothalamo-pituitary-adrenal (HPA) axis; 2) altered cellular differentiation leading to structural and physiological changes in tissues and organs 3) increased oxidative stress and mitochondrial dysfunction altering cellular metabolism; and 4) altered gene expression via aberrant modifications to the fetal epigenome. Many of these findings are based on animal data, thus their relative contribution to the DOHaD model in humans remains to be established. Importantly, interplay may exist among these and other mechanisms during the complex interactions between the mother and her offspring in response to an adverse intrauterine environment.
Epigenetics, or the study of heritable changes in gene expression without alterations to the DNA sequence, is a current focus of the DOHaD field. Epigenetic mechanisms allow for developmental plasticity, permitting an organism to alter its phenotype based on interactions with its environment. The molecular bases of epigenetics involve: 1) methylation of CpG-rich promoter and regulatory regions of DNA; 2) post-translational modification of DNA-associated histone proteins with the addition of methyl, acetyl and phosphate groups; and 3) non-coding RNA mediated post-transcriptional effects. In general, these epigenetic marks regulate chromatin accessibility and protein binding along the DNA, either to promote or inhibit gene transcription in a pattern-specific manner. During human development, genome-wide demethylation and subsequent remethylation occur during periods of epigenetic programming in utero. This reprogramming takes place shortly after fertilization and again during primordial germ cell development, characterized by the preservation or re-establishment of methylation patterns to imprinted genes, respectively. Additional marks are further refined in a tissue-specific fashion as cellular differentiation proceeds in utero. Given the dynamic nature of reprogramming events, these developmental periods represent critical windows in which the intrauterine environmental may impinge upon the fetal epigenome.
Indeed, specific aspects of the early life environment do alter the fetal epigenome. Maternal lifestyle choices are a factor, as seen by evidence of aberrant DNA methylation in children prenatally exposed to tobacco smoke. Conditions such as maternal diet, either caloric-limiting or rich, have been shown to modify the epigenetic profiles of exposed offspring, although establishing causality related to disease has been challenging thus far. Many nutrition-related epigenetic changes do influence phenotypic characteristics of the offspring. For example, maternal dietary methyl-donor supplementation in the form of folate, choline, and methionine causes hypermethylation of the variable yellow agouti (Avy) and AxinFu metastable epialleles of mouse offspring, leading to changes in coat color and tail morphology. Perhaps the strongest association between fetal epigenomic alterations contributing to adult health involves exposure to environmental toxicants. Prenatal exposure to vinclozolin, an anti-androgenic fungicide known to alter DNA methylation, promotes transgenerational inheritance of a variety of disease phenotypes in offspring including male infertility, cancer, behavioral abnormalities, and diseases of the prostate, kidney and immune system. A phenomenon propagated through the male germ line, vinclozolin-induced epigenetic reprogramming is detectable in progeny for at least three generations after initial exposure. As well, epigenomic perturbations associated with altered brain development and increased susceptibility to breast and prostate cancer are seen following prenatal and neonatal exposure to the endocrine disruptor bisphenol A (BPA). Interestingly, methyl donor supplementation counteracts the hypomethylating effects of BPA exposure, offering the possibility of therapeutic approaches to lessen the harmful effects on the embryonic and/or fetal epigenome. Despite progress in the DOHaD field, further investigation is needed to understand the mechanistic basis by which these and other adverse exposures alter the fetal epigenome and to what extent these modifications contribute to adult-onset disease.
At this time, the impact of prenatal alcohol exposure on the development of adult-onset disease and health conditions is largely unknown. Epigenetic effects of alcohol are seen in model systems of alcohol-induced injury. Possible modes of action include alteration of one-carbon metabolism, NAD+-dependent enzyme function, histone modification, and microRNA levels. Despite this knowledge, alcohol’s impact on the epigenome appears complex and dependent on cell type, target organ, exposure amount and other variables. Emerging evidence suggests that alcohol-mediated epigenetic effects may contribute to deficits associated with fetal alcohol syndrome/fetal alcohol spectrum disorders (FAS/FASD). Studies using the Avy mouse have linked both preconceptional and early gestational alcohol exposure to epigenetic-mediated phenotypic changes in exposed offspring. Reports of preconceptional effects mediated by paternal alcohol use further support an epigenetic component to FASD etiology. It has been hypothesized that alcohol’s impact on fetal programming of the HPA axis and subsequent vulnerability to stress-related and behavioral disorders later in life may have epigenetic origins. Given the influence of maternal diet on the fetal epigenome, it is important to note that alcoholics often experience nutritional deficiencies during pregnancy. As a caveat, studies modeling FAS/FASD typically explore effects from moderate to high levels of prenatal alcohol exposure thus little is known about the actions of alcohol on the fetal epigenome at lower doses and across a variety of developmental timepoints. Although somewhat limited, evidence does exist that prenatal alcohol exposure may increase the risk for adult diseases typically not associated with FAS/FASD. Animals exposed to alcohol in utero exhibit increase susceptibility to developing breast cancer, respiratory infections, and immune system impairments in adulthood. Alterations in circadian clock function and kidney development have also been noted. Given the prevalence of alcohol use among pregnant women in the United States, the question of whether prenatal alcohol exposure at any level or pattern of exposure may enhance the biological risk for chronic diseases later in life remains largely unexplored and warrants further investigation.
In response to this FOA, investigators are encouraged to examine health conditions and chronic diseases not typically associated with FAS/FASD. The resulting information may be critical in optimizing strategies for disease prevention in individuals with a wide range of alcohol exposure. This FOA does not seek to support applications limited to traditional examination of physical abnormalities or neurobehavioral deficits of FAS/FASD.
Submitted studies should address the functional and molecular bases for the DOHaD model as it relates to prenatal alcohol exposure. Multidisciplinary approaches using animal models and high-throughput -omics technologies are encouraged. Studies focused on low to moderate levels of exposure modeling a broader range of alcohol use are also strongly encouraged.
Research areas warranting attention include but are not limited to the following topics.
A) Research on the epidemiological underpinnings of the DOHaD concept as it relates to prenatal alcohol exposure:
- Determine the effect maternal alcohol use has on the DOHaD paradigm by leveraging resources of existing large prospective cohorts such as the National Children’s Study and others;
- Modify existing longitudinal studies to facilitate follow-up of children with prenatal alcohol exposure for insight into future health outcomes.
- Understand how pre- and postnatal growth perturbations induced by alcohol may influence disease risk across the lifespan;
B) Research on the biological, cellular, and molecular mechanisms by which in utero alcohol exposure may influence adult-onset health outcomes:
- Develop novel or adapt existing animal models of chronic disease to examine the influence of prenatal alcohol exposure and the role of alcohol-induced fetal programming. Conversely, animal models of in utero alcohol exposure may also be adapted to examine appropriate endpoints of adult-onset disease;
- Define critical developmental windows (e.g., preconception, embryonic, and fetal periods) during which alcohol may influence chronic disease etiology;
- Elucidate the biological and molecular mechanisms by which prenatal alcohol exposure may contribute to chronic diseases later in life, based on in vitro studies and/or animal models;
- Assess potential mechanisms using biological samples collected from prospective birth cohorts;
- Explore how the embryonic/fetal epigenome changes over time and define how it may be altered by in utero alcohol exposure;
- Examine the relationship between dose, timing, and pattern of alcohol exposure as it relates to potential genetic and/or epigenetic consequences and disease outcomes in exposed offspring;
- Investigate specific gene-environment interactions influenced by prenatal alcohol exposure that may enhance disease susceptibility in adolescence and adulthood;
- Explore the role of alcohol-induced placental dysfunction and its effects on intrauterine programming of adult health outcomes;
- Examine potential relationships between alcohol and other environmental agents such as tobacco smoke on influencing DOHaD processes.
C) Research on identifying biomarkers associated with prenatal alcohol exposure that may be predictive of adult disease outcomes:
- Identify alcohol-induced epigenomic alterations present in both tissues of the intrauterine environment and the exposed offspring and assess their relationship to adult-onset diseases;
- Investigate the usefulness of the placenta as evidence of past developmental insults by alcohol as it relates to disease outcomes;
- Assess the use of epigenomic biosensors of adverse exposures in the context of alcohol. Biosensors may include metastable epialleles (Avy, AxinFu, CabpIAP, and others) to examine critical developmental windows of alcohol exposure as they relate to disease development in animal models;
- In animal models, evaluate viable therapeutics (e.g. nutritional and dietary supplementation, HDAC inhibitors) for mitigating alcohol-related epigenomic changes and disease outcomes.
Funding Instrument |
Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity. |
Application Types Allowed |
New |
Funds Available and Anticipated Number of Awards |
The number of awards is contingent upon NIH appropriations, and the submission of a sufficient number of meritorious applications. |
Award Budget |
Application budgets are not limited, but need to reflect actual needs of the proposed project. |
Award Project Period |
The scope of the proposed project should determine the project period. The total project period for an application submitted in response to this funding opportunity may not exceed 5 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.
Higher Education Institutions
- Public/State Controlled Institutions of Higher Education
- Private Institutions of Higher Education
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
- Hispanic-serving Institutions
- Historically Black Colleges and Universities (HBCUs)
- Tribally Controlled Colleges and Universities (TCCUs)
- Alaska Native and Native Hawaiian Serving Institutions
Nonprofits Other Than Institutions of Higher Education
- Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
- Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)
For-Profit Organizations
- Small Businesses
- For-Profit Organizations (Other than Small Businesses)
Governments
- State Governments
- County Governments
- City or Township Governments
- Special District Governments
- Indian/Native American Tribal Governments (Federally Recognized)
- Indian/Native American Tribal Governments (Other than Federally Recognized)
- Eligible Agencies of the Federal Government
- U.S. Territory or Possession
Other
- Independent School Districts
- Public Housing Authorities/Indian Housing Authorities
- Native American Tribal Organizations (other than Federally recognized tribal governments)
- Faith-based or Community-based Organizations
- Regional Organizations
- Non-domestic (non-U.S.) Entities (Foreign Institutions)
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 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
registrations.
- System for Award Management (SAM) must maintain an active entity registration (formerly CCR registration), to be renewed at least annually. Use the SAM.gov Manage Entity function to manage your entity registrations. See the Grants Registration User Guide at SAM.gov for additional information.
- Grants.gov
- eRA Commons
All Program Directors/Principal Investigators (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 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/Principal
Investigator (PD/PI) 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 PDs/PIs, visit the Multiple
Program Director/Principal Investigator Policy and submission details in the Senior/Key
Person Profile (Expanded) Component of the SF 424 (R&R) 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 that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for submission:
- To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;
- Of an investigator-initiated application that was originally submitted to an RFA but not paid; or
- Of an application with a changed grant activity code.
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.
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.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
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.
Appendix
Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
Foreign (non-US) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout 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.
Important
reminders:
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/PI 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, NIH. Applications that are incomplete will not be reviewed.
Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact NIH program staff at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF 424 (R&R) Application Guide.
Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.
Important Update: See
NOT-OD-16-006 and NOT-OD-16-011 for updated review language for applications for due dates on or after January 25, 2016.
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.
Significance
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?
Investigator(s)
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/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?
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?
Approach
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
managed?
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?
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?
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.
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
For Renewals, the committee will consider the progress made in the last funding period.
Revisions
For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.
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), 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.
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. 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.
- Relevance of the proposed project to program priorities.
After the peer review of the application is completed, the PD/PI 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
Not Applicable.
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.
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TTY 301-451-5936
Email: [email protected]
eRA Service Desk (Questions regarding ASSIST, 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]
William Dunty, Ph.D.
Program Director
Division of Metabolism and Health Effects
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
National Institutes of Health
5635 Fishers Lane, Room 2120
Bethesda, MD 20892-9304
Rockville, MD 20852-1705 (for express/courier service;
non-USPS service)
Telephone: (301) 443-7351
Fax: (301) 594-0673
Email: [email protected]
Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).
Ms. Judy Fox
Chief, Grants Management Branch
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
5635 Fishers Lane, Room 3023
Bethesda, MD 20892-9304
Rockville, MD 20852-1705 (for express/courier service; non-USPS service)
Telephone: (301) 443-4704
Fax: (301) 443-3891
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.
