Required Application Instructions

It is critical that applicants follow the instructions in the SF424 (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

Ethical challenges have arisen in research on HIV/AIDS from the very beginning of the epidemic, and continue to the present day. Controversies have emerged in relation to clinical trial design, access to drugs, regulatory approval pathways, stigmatized populations, and global health disparities, to name just a few of the many relevant issues. The populations and groups facing high HIV risk, or living with HIV, are often economically, socially or politically disadvantaged. In some cases HIV transmission is linked to socially sensitive or sanctioned behaviors. These characteristics sharpen the ethical tensions in HIV/AIDS research across a wide spectrum of activities such as observational studies, early phase/translational trials, product development, behavioral research, and public health intervention.

Applications for support under this FOA should address ethical issues relevant to research on HIV/AIDS or its co-morbidities. This FOA provides a list of suggested topics, but other topics and areas of inquiry may be proposed. Applications may include conceptual work in bioethics, or empirical work gathering and analyzing data relevant to ethical issues in research, or a combination of the two. For empirical projects, data collection may include quantitative or qualitative methods, or both.

Applications proposing Clinical Trials will not be supported under this FOA.

Applications addressing empirical research on informed consent will not be supported under this FOA, with the exception of informed consent/assent/parental permission related to adolescents as research participants, as described below. Ethical Issues in Research on HIV/AIDS and its Co-Morbidities is available under two separate companion FOAs that are being published concurrently. This FOA encourages R01 applications whereas the companion R21 will support shorter term (up to two years) developmental/exploratory research activities.

The following selected bioethics topics are of particular interest; however, other ethical issues are relevant and this list is not intended to be exhaustive.

Ethics of Research Involving Adolescents and Young Adults

Research with adolescents is urgently needed to meet the needs of HIV prevention, care and treatment for this age group. Clinical research studies are urgently needed to inform biomedical and behavioral interventions as well as mechanisms to strengthen health care systems to serve these youth. A vast proportion of biomedical interventions and therapies used in adolescents are implemented in the absence of specific data to support indications for their use, and are often justified by extrapolation from studies in much older adult populations. Substantial biomedical and psychosocial data suggest that adolescents differ from adults in critical ways. There is an urgent need for primary and secondary prevention among youth populations at high risk of acquisition or transmission of HIV, both globally and domestically. Important milestones have been achieved in HIV prevention and treatment in adult populations, but various scientific, implementation and regulatory concerns are barriers to their expansion to adolescents. Lack of appropriate research is detrimental to developing effective prevention and treatment for serious conditions such as HIV and related co-morbidities.

Investigators frequently encounter a variety of difficulties in working with youth, which create a disincentive to carry out research in these populations. Barriers include individual factors such as non-adherence, risk behaviors and other psychosocial challenges; and structural barriers such as ethical, legal and regulatory problems. An adolescent’s evolving autonomy, cognitive development and decisional capacity all provide a legal and ethical basis for a right to independence and self-determination in accessing health care and research. However, ethical, cultural, legal and regulatory considerations complicate the research picture.

Projects to address issues related to adolescents in research could include, but are not limited to, the following:

• Conceptual and empirical work on issues of evolving adolescent autonomy, decisional capacity, consent, assent and parental permission, particularly in regard to youth at risk for HIV infection and other Sexual Transmitted Infections (STIs) in the US and in other countries;
• Analysis of legal provisions for protection of confidentiality of minors and for rights to self-determination and decision-making by adolescents about participation in research; analysis of these legal and ethical issues in various research settings relevant to research on HIV risk, HIV prevention and HIV care and treatment;
• Research on ethical, legal and/or cultural aspects of waivers of parental permission for research in specific contexts;
• Research on ethical challenges of studies with sexually active adolescents, including issues of reporting requirements for underage sexual activity in various countries; concerns about confidentiality of the research participants and their contacts; social harms; parental and family concerns, and other legal and ethical issues;
• Research on ethical challenges in research with adolescents in settings where sensitive information is involved, such as mood disorders research, sexual behaviors, and substance use, as well as other potential risk determinants for HIV acquisition, such as homelessness, incarceration, truancy, and other circumstances and conditions;
• Projects to gather and analyze biomedical, behavioral and other psychosocial data related to adolescents and young adults to better characterize risks and benefits of research with youth;
• Legal and ethical analysis of different levels of risks in research with adolescents, including minimal risk, minor increase over minimal risk, and greater than minimal risk as defined in human subjects regulations; analysis of when and how risk thresholds should be applied and what ethical implications these risks have for adolescent research participation;
• Development of a conceptual ethical framework for enrollment of adolescents in clinical trials; such a framework should be supported by ethical analysis, data, and stakeholder engagement.
• Gathering and analyzing information from stakeholders (patients, clinicians, researchers, ethics committees/IRBs, regulators) about cultural, ethical, legal or regulatory challenges in research with adolescents.
• Ethical issues in determining best HIV prevention communication and messaging for adolescents, given that HIV risk involves sensitive or stigmatized behaviors, and HIV risk communication may raise cultural, political or parental concerns.

Ethical Issues in Research on an HIV Cure

A new area in HIV research is the search for a means to eradicate the virus from the body an HIV cure. While effective antiretroviral treatment has been hugely successful in reducing morbidity and mortality from HIV infection, the virus is never wholly eliminated from the body and patients must remain on lifelong treatment. The goal of cure research is to determine where and how the virus lies dormant and develop interventions to either eradicate the virus, or result in functional cure of HIV infection that is, control over viral replication in an individual, without lifelong antiretroviral therapy. A significant ethical challenge with this area of research is that early phase and translational trials will need to be conducted with relatively healthy HIV-infected patients. Risks and benefits of this type of research are difficult to assess, and patients may develop misconceptions about the likelihood of success. Projects addressing these issues could include the following:

• Analysis of risks and benefits of HIV cure research to individuals and future patients, for example: analyzing ethical issues associated with non-beneficial research with relatively healthy patients; analyzing the ethical challenges of evaluating risks and benefits in studies in which endpoints are not associated with clinical outcomes;
• Investigation of distributive justice claims with regard to research, development, and access to HIV cure strategies by different populations affected by HIV, including minority populations within the US, women, and populations in resource-limited countries;
• Investigating perceptions, beliefs and attitudes towards cure research amongst various stakeholders including researchers, clinicians, patients, community members, IRB/Ethics committee members, and regulators; analyzing ethical implications of these views for the planning and conduct of cure studies;
• Analyzing ethics of different procedures and interventions in cure studies and choice of study populations, such as: use of analytic treatment interruption; use of study agents that pose significant risks; studies with patients who are acutely infected with HIV; studies with HIV-infected infants and children.

Ethical Issues in Research Related to HIV and Tuberculosis (TB)

Research and public health programs on TB raise multiple ethical issues, due to the characteristics of the disease and its clinical management. These characteristics include the transmissibility of TB, difficulties in TB diagnosis, challenges of TB treatment and follow-up, and the rise of multiple drug resistant (MDR) or extensively drug resistant (XDR) TB. TB in the context of HIV infection is more challenging to prevent, diagnose, and treat, as is TB infection in children. Research and clinical practice in these groups raise more difficult issues regarding risks and benefits of research and effectiveness of public health policies. Ethical issues related to TB to be addressed could include, but are not limited to, the following:

• Analysis of ethical challenges of research on diagnostic tests; should tests that are not fully validated or approved by regulatory authorities be used to inform clinical care, and if so, what parameters should affect these decisions? How should risks and benefits of use of new diagnostic tests, both for patients and others in the community, be evaluated and communicated?
• Analysis of ethical issues in introducing new TB drugs: how can the need for potential benefits of new drugs be balanced with necessary caution in avoiding development of drug resistance, at the level of individual patient care, TB programs, and policies? How do these competing obligations influence the conduct of research and transitions from research to clinical practice;
• Analysis of ethical challenges of determining when new agents should be used outside a clinical trial setting; ethical issues involved in implementing compassionate use or expanded access programs;
• Investigation and analysis of ethical issues with regard to individuals who are not enrolled in trials yet may experience risks or benefits from clinical trial participation of their contacts, including community and household contacts of TB patients enrolled in clinical trials;
• Ethical analysis of risks, benefits and social value of research on new TB regimens, especially in cases where individual patient benefit is unlikely or highly uncertain. Examples include studies of new drug regimens in patients with TB strains already resistant to one or more components of the regimen being tested; or studies of latent TB, where new agents may be studied in TB-infected patients who are otherwise healthy, to ascertain anti-latent TB effects; or studies of treatment-shortening regimens in which there are tradeoff between effectiveness and burden or length of treatment; studies of XDR-TB in which baseline mortality is high and regimens have limited efficacy;
• Ethical issues arising in drug development and regulatory approval pathways for new TB drugs, including challenges of testing and approving combination regimens from multiple companies, and difficulties reconciling commercial and public health concerns;
• Ethical issues in pediatric TB research, including questions of when new drugs or agents should be studied in children and what kind of information must be available from adult research or treatment programs to inform these decisions. Evaluation of ethical questions in enrolling children in research that is greater than minimal risk with or without prospect of direct benefit; development of ethical frameworks to guide appropriate research on drug development and dosing for children with, or at risk for, TB as well as pediatric TB diagnostics.

Ethical issues in research on cancer detection, diagnosis, prevention and treatment in the context of HIV infection

Cancers arising in HIV-infected individuals are important causes of morbidity and mortality. Often, cancer incidence and progression are significantly worse, and treatment options are more limited, in low and middle income countries compared to high income countries. In LMIC with more limited access to ARV treatment, cancer incidence is higher; and treatment options often do not include best standard of care that is available in high income countries. There are important research questions about how best to prevent, manage, treat cancers in the context of HIV infection, and the design and conduct of these studies is made ethically complex by disparities in access to care as well as divergent standards of care across countries and regions.

Some possible topics of interest include, but are not limited to:

• Ethical analysis of standard of care issues in cancer prevention and treatment in different settings;
• Examination of feasibility of introducing different strategies and regimens in the context of research; ethical analysis of the potential impact of research on future policies, post-trial access, and standard of care in host countries where research takes place;
• Ethical analysis of alternative, lower cost strategies for cancer prevention and treatment that are proposed for LMIC;
• Analysis of ethical challenges in cancer prevention and treatment for pregnant women with HIV;
• Ethical challenges in pediatric cancer treatment in the context of HIV;
• Ethical issues raised by potential disparities in access to treatment, quality of treatment or provision of cancer care for different patient groups, for example, HIV-infected compared to HIV-uninfected patients; patients at different socioeconomic levels; patients who face stigma and social exclusion such as sex workers.

Ethical, legal and policy issues in research with big data

New and diverse forms of data are being collected by private and public entities in the context of everyday life: electronic data are generated and gathered through use of social media, cell phones, shopping records, traffic patterns, and multiple diverse activities. Researchers are increasingly turning to these streams of data and combining large datasets in novel ways to analyze patterns associated with outcomes of interest. These big data approaches hold great potential to advance health research, yet raise profound ethical, legal and policy concerns.

In the field of HIV research, these novel combinations of data could help identify factors associated with risk of HIV acquisition, poor access to care, or other important outcomes and thus could form the basis for innovative new public health interventions to address the epidemic. However there is no overarching ethical or policy framework for the use of big data approaches in research, and existing ethical guidance is silent on these new analytic techniques. Legal standards are still evolving and do not fully address the concerns and interests of individuals with regard to use of their data by commercial, public health or government entities. This type of big data research activity urgently needs work on ethics and policy issues that can enable socially beneficial research to go forward while protecting privacy, public trust, and existing channels of electronic communication.

Applications addressing ethical, legal and policy challenges in big data research could include issues such as

• Legal and ethical scholarship to inform a new framework to address privacy and public trust in big data research;
• Ethical analysis of use of non-traditional data sources such as social media, GPS data, commercial and consumer data, etc., in health research, and in particular in research on HIV risk, prevention, treatment and access to care;
• Projects exploring and evaluating engagement mechanisms such as community consultation, public education and community-based participatory research with regard to big data;
• Development and vetting of ethical and policy frameworks for appropriate boundaries on use and transfer of data amongst researchers and amongst public and private entities;
• Integration of data security standards with ethical and policy guidelines for big data;
• Other topics related to legal, ethical and policy concerns raised by big data analytics in public health research

Ethics of Research Involving Pregnant Women

The care and treatment of pregnant women in the US and around the world is hampered by a lack of rigorous clinical trial evidence to support treatment choices. The vast majority of interventions needed by these millions of women are either used without specific evidence of efficacy or safety during pregnancy, or avoided due to concerns about effects on fetal health. As a result, pregnant women and their offspring often suffer from suboptimal health care. Research involving pregnant women is often limited by the difficulty of adjudicating risks and benefits to mother and fetus, and the challenges of obtaining associated regulatory approvals. In HIV research, the early advent of antiretrovirals for prevention of mother to child HIV transmission has resulted in a substantial evidence base for use of these drugs during pregnancy. However, significant gaps remain. More research is needed on treatment of HIV-infected pregnant women for indications other than prevention of maternal to child transmission. Serious co-morbidities such as tuberculosis (TB) are often under-treated in pregnant women, and research to extend new treatment modalities for this population remains ethically challenging. HIV-uninfected pregnant women urgently need HIV prevention interventions, but HIV prevention trials on novel agents rarely include pregnant women. Development of safe and effective HIV prevention is essential for pregnant women, especially since worldwide, women of reproductive age bear a disproportionate burden of HIV infection, there are data showing significant, perhaps even heightened, risk of HIV acquisition during pregnancy, with increased risks to both mother and fetus during acute infection.

Projects which help advance the ethical agenda for research with pregnant women could include, but are not limited to, the following:

• Gathering and analyzing information from stakeholders (patients, clinicians, researchers, ethics committees/IRBs, regulators) about ethical, legal or regulatory challenges in research with pregnant women;
• Projects to gather and analyze biomedical data related to pregnancy and create a scientific and ethical framework for analyzing risks and benefits of research with pregnant women;
• Analysis of ethical and regulatory oversight of research with pregnant women, in the US or in other countries; development of policy strategies for improving research oversight of this area of research;
• Exploration of ethical and scientific tradeoffs in different product development strategies and different types of clinical trial design to inform safe and effective product use for pregnant women;
• Further conceptual work on ethical tensions inherent in strategies designed to provide protection from fetal risk while simultaneously advancing scientific knowledge related to clinical interventions for pregnant women; ethical analysis of the challenges of balancing risks and benefits to mother, fetus, and future patients.
• Project analyzing appropriate scope of research with women who are attempting to conceive and are otherwise appropriate research participants for HIV related clinical trials;
• Projects analyzing contraception requirements in clinical trials, including attitudes, beliefs and preferences of women enrolling in trials; perceptions of burdens of contraception requirements and adjudication of risks thresholds for different requirements in studies.

Ethical Issues in Research Utilizing Human Specimens

Research utilizing specimens is vital to progress in biomedical science and public health. Although research utilizing specimens is usually classified as minimal risk, international collaborative research involving specimens can involve ethical, cultural, legal and political complexities that sometimes stymie important projects. For example, the burden of oversight and regulation of research with specimens may seem disproportionate to the level of risk. There are divergent views amongst stakeholders about how research utilizing specimens should be regulated, whose interests are at stake, and how these interests ought to be protected. Some contentious cases involving human specimens have led to longstanding mistrust and disagreement amongst potential research partners and stakeholders. A variety of other issues have been raised by stakeholders, including perceptions and misconceptions about likelihood of breaches of confidentiality; worries about the acceptability of research with banked specimens from the point of view of the original donors; concern about potential impact of research findings on communities; issues regarding control of specimens in multi-national research collaborations; concerns about the fairness of research partnerships involving researchers from both high income and low or middle income countries; and concerns about access to benefits obtained from research on stored samples.

Possible topics include, but are not limited to, the following:

• Empirical assessments and ethical analysis of documented harms and benefits associated with specimen research, possibly including effects on individuals, research partnerships, communities, clinical practice, public health and science;
• Development of interventions to investigate, describe and address misconceptions or lack of information about HIV-related research with specimens, amongst the general public, communities and individuals at risk of or affected by HIV, ethics committees and IRBs, in the US or in other countries;
• Analysis of ethical and political factors affecting use and re-use of specimens gathered in international collaborative studies. Possible avenues to explore include development of models of shared decision-making and governance for use of specimens in multi-national projects; methods for harmonizing regulatory and ethical oversight structures among multiple countries;
• Frameworks for including capacity-building and fair partnership in international studies involving collection and storage of specimens; or other questions related to use of specimens and the structure of international collaborative research.

Effectiveness of ethics review

The process of research ethics oversight by ethics committees, IRBs and other oversight bodies, a critical part of the ethical conduct of research, by necessity creates some burden on the research enterprise. It is essential to ensure that these review processes are effective and efficient. Multi-center clinical trials and international collaborative research projects pose particular challenges for ethics/IRB review. Some approaches include, but are not limited to, the following:

• Development of tools for the measurement of the effectiveness of ethics committees/IRB deliberations and substantive decision-making (as distinct from adherence to procedural requirements), both in the US and in other countries;
• Development of models for coordination and communication between and among IRBs and ethics committees, and other oversight bodies such as government review panels, ministries of health, DSMBs, and other review boards, with particular focus on international collaborative research;
• Development of tools for enhancing capacity of various review bodies such as research ethics committees, ministries of health, or scientific agencies in international HIV/AIDS-related research; mechanisms for performance evaluation and improvement could take place at the institutional, local or national level.

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
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

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

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • o NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

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 PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (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.

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

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, including Supplemental Grant Application Instructions 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.

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

For all applications, the research team is strongly encouraged to include at least one person with demonstrated expertise and scholarship in bioethics, as demonstrated by academic work and publications in the field.

For projects involving empirical data collection the research team should include at least one social scientist or other researcher with relevant expertise in theory and methodology for conducting the proposed empirical research.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Research Strategy: For projects involving empirical data collection, describe how the data collection will inform current or future ethical deliberations, ethical oversight processes, or policies, or will enhance the ethical conduct of research.

For projects which are purely conceptual or analytical bioethics work and do not involve empirical investigation describe: the current state of scholarship on the topic; why the proposed project is significant and innovative- for example, whether new reasoning is applied to a familiar problem, or whether a new problem is addressed; and what type of theoretical framework or approach will be used to address the problem.

For projects which combine conceptual work in bioethics with empirical data collection, describe how the data collection informs ethical analysis or decision making, in addition to addressing the requirements for conceptual work as stated above.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

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.

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

Foreign (non-U.S.) 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 applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission.

Organizations must submit applications to 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. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

Applicants are responsible for viewing their application before the due date 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 SF424 (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. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues.

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 SF424(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. See Section III of this FOA for information on registration requirements.

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 System for Award Management. 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 and compliance with application instructions by the Center for Scientific Review, NIH. Applications that are incomplete or non-compliant will not be reviewed.

Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact a Scientific/ Research Contact 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 SF424 (R&R) Application Guide.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.

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 score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

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?

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?

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 human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?

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 score, but will not give separate scores for these items.

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 Guidelines for the Review of Human Subjects.

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

For 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.

For Renewals, the committee will consider the progress made in the last funding period.

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 score.

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.

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).

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) Genomic Wide Association Studies (GWAS) /Genomic Data Sharing Plan.

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 Center for Scientific Review, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group 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 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 terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this 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 Research Performance Progress Report (RPPR) 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.

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
Finding Help Online: http://grants.nih.gov/support/index.html
Email: commons@od.nih.gov

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact CenterTelephone: 800-518-4726
Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-710-0267

Liza Dawson, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3210
Email: dawsonl@niaid.nih.gov

Rebecca Liddell Huppi, Ph.D.
National Cancer Institute (NCI)
Telephone: 301-496-4995
Email: liddellr@exchange.nih.gov

Susannah Allison, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 240-627-3861
Email: allisonsu@mail.nih.gov

Bill G. Kapogiannis, MD
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-402-0698
Email: kapogiannisb@mail.nih.gov

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Ann Devine
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-2988
Email: adevine@niaid.nih.gov

Shane Woodward
National Cancer Institute (NCI)
Telephone: 240-276-6303
Email: Woodwars@mail.nih.gov

Aleisha S. James, MPH
National Institute of Mental Health (NIMH)
Telephone: 301-451-9948
Email: jamesaleisha@mail.nih.gov

Bryan S. Clark, MBA
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6975
Email: clark1@mail.nih.gov

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 Part 75.