Expired PA-06-368: Research On Ethical Issues In Human Subjects Research (R21)

Department of Health
and Human Services (HHS)

NIH... Turning Discovery Into Health^®

Part I Overview Information

Department of Health and Human Services

Participating Organizations
National Institutes of Health (NIH), (http://www.nih.gov/)

Components of Participating Organizations
National Cancer Institute (NCI), (http://www.nci.nih.gov/)
National Human Genome Research Institute (NHGRI), (http://www.nhgri.nih.gov/)
National Institute on Aging (NIA), (http://www.nia.nih.gov/)
National Institute on Alcohol Abuse and Alcoholism (NIAAA), (http://www.niaaa.nih.gov)
National Institute of Allergy and Infectious Diseases (NIAID), (http://www.niaid.nih.gov/)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), (http://www.niams.nih.gov/)
National Institute of Child Health and Human Development (NICHD), (http://www.nichd.nih.gov/)
National Institute on Deafness and Other Communication Disorders (NIDCD), (http://www.nidcd.nih.gov)
National Institute on Drug Abuse (NIDA), (http://www.nida.nih.gov/)
National Institute of Environmental Health Sciences (NIEHS), (http://www.niehs.nih.gov/)
National Institute of Mental Health (NIMH), (http://www.nimh.nih.gov/)
National Institute of Neurological Disorders and Stroke (NINDS), (http://www.ninds.nih.gov/)
National Institute of Nursing Research (NINR), (http://www.ninr.nih.gov/)
National Center for Complementary and Alternative Medicine (NCCAM), (http://www.nccam.nih.gov)
Office of Behavioral and Social Sciences Research (OBSSR)
National Heart, Lung, and Blood Institute (http://www.nhlbi.nih.gov/), (http://obssr.od.nih.gov/)
Office of Dietary Supplements (ODS), (http://www.ods.od.nih.gov)

Title: Research On Ethical Issues In Human Subjects Research (R21)

Announcement Type
New

March 24, 2011 - This PA has been reissued as PA-11-182.
April 26, 2010 - See Notice NOT-OD-10-086 Extension of Expiration date.
December 16, 2009 - This FOA has been updated to reflect the new requirements from NIH’s Enhancing Peer Review Initiative. The new requirements are effective for submissions intended for due dates January 25, 2010 and beyond. If submitting an application intended for a due date of January 25, 2010 and beyond, follow the guidance below and be sure to use the Adobe-Forms-B version of the application forms and instructions. If applying for a due date before January 25, 2010, follow the guidance in the archived version of this FOA and be sure to use the Adobe-Forms-A version of the application forms and instructions.
March 17, 2009 - See Notice NOT-OD-09-062 Extension of Expiration Date and announcing that NHLBI and NIDDK will no longer participate in this FOA.
September 17, 2007 - Expiration Date adjusted to accommodate recent changes to standing submission deadlines, per NOT-OD-07-093.
October 31, 2006 - See Notice NOT-HG-07-002 The NHGRI would like to inform the community that it is interested in receiving R03, R21 and R01 applications in response to these three Funding Opportunity Announcements and would thus like to clarify the language in the contact information.
June 9, 2006 (NOT-HL-06-130) - Notice to add NHLBI to list of participating institutes

NOTICE: Applications submitted in response to this Funding Opportunity Announcement (FOA) for Federal assistance must be submitted electronically through Grants.gov (http://www.grants.gov) using the SF424 Research and Related (R&R) forms and the SF424 (R&R) Application Guide.

APPLICATIONS MAY NOT BE SUBMITTED IN PAPER FORMAT.

This FOA must be read in conjunction with the application guidelines included with this announcement in Grants.gov/Apply for Grants (hereafter called Grants.gov/Apply).

A registration process is necessary before submission and applicants are highly encouraged to start the process at least four weeks prior to the grant submission date. See Section IV.

Program Announcement (PA) Number: PA-06-368

Catalog of Federal Domestic Assistance Number(s)
93.989, 93.213, 93.395, 93.837, 93.838, 93.866, 93.853, 93.855, 93.856, 93.846, 93.865, 93.894, 93.279, 93.173, 93.121, 93.847, 93.848, 93.849, 93.242, 93.361, 93.273

Key Dates
Release/Posted Date: April 26, 2006
Opening Date: May 2, 2006 (Earliest date an application may be submitted to Grants.gov)
NOTE: On time submission requires that applications be successfully submitted to Grants.gov no later than 5:00 p.m. local time (of applicant institution/organization).
Letters of Intent Receipt Date(s): Not applicable
Application Submission Date(s): http://grants.nih.gov/grants/funding/submissionschedule.htm
AIDS Application Submission Date(s): http://grants1.nih.gov/grants/funding/submissionschedule.htm#AIDS.
Peer Review Date(s): http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward.
Council Review Date(s): http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward.
Earliest Anticipated Start Date(s): http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward.
Additional Information To Be Available Date (Activation Date): Not Applicable
Expiration Date: (Extended to May 8, 2011 per NOT-OD-10-086) , New Date September 8, 2010 Per NOT-OD-09-062; Changed to (now May 8, 2009 per NOT-OD-07-093); Original Expiration Date: May 2, 2009

Due Dates for E.O. 12372
http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part9.htm#_Toc54600164

Not Applicable

Additional Overview Content

Executive Summary

The National Institutes of Health (NIH) invites Exploratory/Developmental Research Grant applications (R21) to investigate ethical issues in human subjects research.
Mechanism: This FOA will utilize the Exploratory/Developmental (R21) grant mechanism (http://grants.nih.gov/grants/funding/r21.htm) and runs in parallel with FOAs with identical scientific scope, PA-06-369 and PA-06-367 that solicit applications under the R01 and R03 mechanisms, respectively.
Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary.
The total project period for an application submitted in response to this funding opportunity may not exceed two years. Direct costs are limited to $275,000 over an R21 two-year period, with no more than $200,000 in direct costs allowed in any single year.
Eligible organizations: For profit organizations; Non-profit organizations; Public or private institutions, such as universities, colleges, hospitals and laboratories; Units of State government; Units of local government; Eligible institutions of the Federal government; Domestic institutions; Foreign institutions; Faith-based or community-based organizations; Indian/Native American Tribal Government (Federally Recognized); Indian/Native American Tribal Government (Other than Federally Recognized); and Indian/Native American Tribally Designated Organization.
Eligible Project Directors/Principal Investigators (PD/PIs): Individuals with the skills, knowledge, and resources necessary to carry out the proposed research are invited to work with their institution to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
Applicants may submit more than one application, provided each application is scientifically distinct.
All investigator-initiated exploratory/developmental grant applications described in this announcement will be assigned to Institutes and Centers (ICs) according to standard Public Health Service (PHS) referral guidelines and specific program interests.
See Section IV.1 for application materials. The SF424 (R&R) Application Guide for this FOA is located at these Web sites:

For general information on SF424 (R&R) Application and Electronic Submission, see these the following Web sites:

SF424 (R&R) Application and Electronic Submission Information: http://grants.nih.gov/grants/funding/424/index.htm
General information on Electronic Submission of Grant Applications: http://era.nih.gov/ElectronicReceipt/

Telecommunications for the hearing impaired is available at: TTY 301-451-5936 .

Table of Contents

Part I Overview Information

Part II Full Text of Announcement

Section I. Funding Opportunity Description
1. Research Objectives

Section II. Award Information
1. Mechanism of Support
2. Funds Available

Section III. Eligibility Information
1. Eligible Applicants
A. Eligible Institutions
B. Eligible Individuals
2. Cost Sharing or Matching
3. Other - Special Eligibility Criteria

Section IV. Application and Submission Information
1. Request Application Information
2. Content and Form of Application Submission
3. Submission Dates and Times
A. Submission, Review, and Anticipated Start Dates
1. Letter of Intent
B. Sending an Application to the NIH
C. Application Processing
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements

Section V. Application Review Information
1. Criteria
2. Review and Selection Process
A. Additional Review Criteria
B. Additional Review Considerations
C. Sharing Research Data
D. Sharing Research Resources
3. Anticipated Announcement and Award Dates

Section VI. Award Administration Information
1. Award Notices
2. Administrative and National Policy Requirements
3. Reporting

Section VII. Agency Contact(s)
1. Scientific/Research Contact(s)
2. Peer Review Contact(s)
3. Financial/Grants Management Contact(s)

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement

Section I. Funding Opportunity Description

1. Research Objectives

This Funding Opportunity Announcement (FOA) issued by the National Institutes of Health (NIH) solicits Exploratory/Developmental Research Grant applications (R21) addressing ethical issues that accompany the conduct of research involving human subjects

The purpose of this funding opportunity announcement is to solicit research addressing the ethical challenges of human subjects research in order to optimize the protection of human subjects and enhance the ethical conduct of human subjects research.

Recent developments in biomedical and behavioral research which include the rapid growth of new interventions and technologies, increasing involvement of foreign populations in human subjects research, and concerns about financial conflicts of interest among researchers, challenge investigators' abilities to interpret and apply the regulations. Other situations (e.g., research with vulnerable populations, research on stigmatizing diseases or conditions) may present difficulties for identifying strategies, procedures, and/or techniques that will enhance/ensure the ethical involvement of human subjects in research. Thus, research on ethical issues in human subjects research is necessary to enhance interpretation and application of ethical principles and regulatory requirements.

The research design for studies on ethical issues in human subjects research should be appropriate to the nature of the project(s) proposed and the disciplines involved. Given the conceptual and methodological complexity of many of these research questions, interdisciplinary and collaborative projects are encouraged, particularly those involving clinical researchers, ethicists, and behavioral/social scientists.

In conducting research on ethical issues in human subjects research, different conceptual frameworks for ethics (e.g., principlism, deontology, utilitarianism, rights, ethics of care, etc.) exist and may provide presuppositions and theoretical foundations from which bioethical questions can be formulated and tested. The questions and strategies for testing these issues must be consistent with existing Federal requirements. Currently, research supported by the Department of Health and Human Services (DHHS which includes NIH) follows the Code of Federal Regulations Protection of Human Subjects (45 CFR Part 46). For research conducted internationally, alternative guidelines that describe protections equivalent to those required by 45 CFR 46 may be used (http://www.hhs.gov/ohrp/humansubjects/assurance/filasur.htm), such as those developed by the World Health Organization, the Council for International Organizations of Medical Sciences, and other internationally recognized groups.

This FOA seeks applications for empirical or conceptual research that address the ethical challenges of research involving human subjects with the goal of optimizing protections. See http://grants.nih.gov/grants/funding/r21.htm for a description of the NIH Exploratory/Developmental Research Grant Program. The NIH is also issuing FOAs on the same topics using two other grant mechanisms: the R01 will support empirical research; the R03 will support conceptual as well as empirical research.

See http://grants.nih.gov/grants/guide/contacts/pa-06-367_368_369_differences.doc for an explanation of R01, R21, and R03 mechanisms.

Examples of the types of topics that would be appropriate for applications submitted under these announcements include, but are not limited to, the following:

1. Assessing Risks in Human Subjects Research

Assess how perceptions of risk may differ among investigators, IRB members, and potential subjects and their families, groups, and communities. Examine how features of the research, context of the research, or characteristics of research subjects (e.g., age, health status and stage of disease including those near the end of life, ethnic/cultural background, cognitive capacity, emotional or mental state, social status, gender, incarceration, enthusiasm/ optimistic expectation about research) may alter risk perception. Identify and evaluate strategies to respond to differing perceptions of risks by stakeholders.

Assess the severity and frequency of social, psychological, and/or economic harms (e.g., stigma, discrimination, personal and familial distress, depression, breaches of confidentiality, loss of insurance coverage, loss of employment, loss of housing, loss of benefits, domestic violence, incarceration) that may be associated with participation in or withdrawal from research. Develop and test methods to evaluate prospectively and minimize psychosocial risks in research. For example, formative research in a community may identify social or cultural issues or concerns prior to the conduct of research. Researchers may compare different methods to reduce risk, such as, for example, modifications to study design to reduce risks, or provision of additional services to research subjects.

Develop and test models of prospective risk assessment in human subjects research, including, but not limited to, risks of new technologies. Risk assessment can be particularly challenging in the case of early human trials of new technologies. How can preclinical data best be used to assess the risk of new technologies used in first human trials? How can estimates of risk be translated from animal and in vitro studies to clinical trials in human populations? How can the need to advance new technologies into clinical application be balanced with caution about exposing research subjects to unknown risks, and specifically, what scientific and ethical criteria are relevant to making these determinations? How can an assessment of the risks and benefits of research take into account the severity of disease and the urgency of need for new treatments as well as the possibility of therapeutic misconception?

Develop models for design of clinical trials of new technologies. What study designs are most appropriate to allow consideration of safety issues in the first human trials? How can information from clinical trials of related interventions be used in designing new trials and in assessing safety data?

Assess risks to privacy and confidentiality. Specific topics might include (but are not limited to): a) models for assessing confidentiality risks in research, including interventional research, social and behavioral research and research with data and specimens; b) research to assess the use and understanding of Certificates of Confidentiality and the role they play in IRB assessments of risks to subjects.

2. Issues in Informed Consent

Identify and evaluate strategies, procedures, or techniques for improving comprehension and voluntariness in the process of informed consent for research. This could include evaluation of communication processes that take place before, during or after the research, and/or measurement of comprehension, willingness to participate or continue participation, assent, and attitudes towards research. Examine how different aspects of the informed consent process affect these outcomes, including such parameters as:
Mode of presentation (e.g. oral, written, graphic, video);
Readability, complexity, and format of the language used;
Presentation of positive or negative aspects of participation in research, relative emphasis on benefits or burdens of participation;
Characteristics of the subject, such as language preference, age, gender, health status, education, emotional or mental state, cognitive capacity, cultural or ethnic background, views about medical professionals, and personal motivations;
Contextual features or circumstances in which informed consent takes place, including characteristics of the research staff; presence of an interpreter, location of the research (e.g., research hospital, private office, home); involvement of family members; involvement of subject advocates.
Evaluate different methods and identify best-practice strategies for consulting with communities in the United States and/or other countries regarding comprehension, willingness to participate, or willingness to continue with research at the individual, group, community, or population level.
Assess stakeholder attitudes regarding re-contacting subjects to obtain informed consent for additional uses of their data or to invite participation in other studies; examine the effect of re-contact on comprehension and willingness to participate.
Assess the extent to which prospective subjects decisions about joining research are voluntary. Explore models of decision-making and the effect of situational and individual characteristics on the decision-making process. Evaluate investigators attitudes regarding participants decision-making process. Assess the effects of incentives such as monetary compensation, provision of medical care or other benefits of research on decision-making and perceptions of research by potential or actual participants or study communities.
Assess the impact of communicating or not communicating individual test results, incidental findings, study progress, and/or study results on participants' willingness to continue participating in research and/or on attitudes towards research.
Assess the ethical and legal implications of various models to handle illegal behavior by participants enrolled in or being screened for a study.
Knowledge or perception of conflict of interest on the part of the investigator(s) or institution: Assess the impact of disclosing varying degrees of financial conflicts of interest involving the principal investigator, members of oversight committees, sponsor, institution, etc. on subjects willingness to participate and/or continue with research, and/or subjects understanding of the research.

3. International Research

Evaluate different methods and identify best-practice strategies for consulting with communities and stakeholders in host countries as well as in the United States during all phases of human subjects research (planning, execution, and dissemination of results). Identify and test models from participatory research that are appropriate in different settings. Community consultation might address issues such as the significance or priority of the research project in light of local public health priorities; choice of timing of consultation during the development of the research plan; assessment of community members likely comprehension of the research; community perspectives on the design of the research; the willingness of community members to join or continue participation in research; and plans for feedback of information to communities during and after the research.
Identify and evaluate strategies for investigators and sponsors of research to build trust and collaborative partnerships with host country communities, investigators and health care delivery systems.
Evaluate how foreign human subjects protection systems are applied to US-funded international research. Evaluate the extent to which such protections could satisfy U.S. regulatory requirements for equivalent protections. Evaluate experiences of investigators dealing with foreign regulatory systems and develop models for dealing with multiple human subjects protections systems and standards.
Identify and evaluate strategies to protect research subjects in countries with different political and cultural environments and different attitudes towards personal autonomy.
Develop methods to assess vulnerability, including economic and social vulnerability, in resource-limited settings and evaluate remedies to enhance human subjects protections of vulnerable populations or groups.
Address the ethical and practical aspects of providing medical care in the context of human subjects research in low-resource settings, particularly in the international setting. Assess stakeholders perceptions of requirements or requests to provide ancillary care during the conduct of human subjects research.
Identify and evaluate strategies to build health care and/or human subjects research capacity; assess durability of capacity building strategies; recommend best practices.

4. Study Design in Clinical Trials and Its Relationship to Medical Care

Identify the ethics implications of specific scientific parameters in clinical trial design, such as the choice of appropriate control arm(s) in clinical trials of biomedical and/or behavioral interventions. Develop and/or evaluate strategies to address study design issues that pose particular ethical and scientific challenges.
Evaluate how different study designs might entail different risks or benefits to subjects or to society at large in terms of social value of the research, including issues such as social acceptability, protection of the welfare of subjects in the trial, scientific rigor, relevance, feasibility, and timeliness.
Evaluate the scientific and ethical implications of different types of controlled trials, including consideration of choice of flexible versus controlled conditions, physician or patient preferences in medical care, and strategies for handling scientific and medical disputes about usual or standard care. These issues can arise in studies that include biomedical interventions, behavioral interventions, or both.
Evaluate the scientific and ethical acceptability of placebo-controlled trials in different scenarios, the societal and individual benefit from different trial designs and criteria to guide the conduct of trials using placebo or active controls.

5. Research Oversight: IRBs, DSMBs, and COI Committees

Identify and evaluate strategies to improve the oversight of protections for human subjects by IRBs. Examples might include:
Assessment of different models of IRB review, such as cooperative review arrangements for multi-site or complex research protocols; collaborative IRB arrangements for multi-site studies or complex research projects; collaborative IRB arrangements in international studies; or division of labor among multiple IRBs reviewing the same research plan;
Development and testing of models for effective communication, delegation of responsibilities, and joint decision-making of multiple Institutional Review Boards in international research;
Assessment of stakeholder attitudes toward different IRB models including views of researchers, IRB members, institutional officials, community members, and research sponsors;
Development of appropriate outcomes measures and quality indicators for the IRB review process for measurement of adequate protection of human subjects. Development and testing of a framework for assessing IRB review quality; determination of when variability in IRB outcomes would be acceptable and when such variation would indicate inconsistent quality.
Develop and test models or outcome measures for assessing the functioning of Data and Safety Monitoring Boards (DSMB). For example, develop and test models for effective communication, delegation of responsibilities, and joint decision making among multiple IRBs and DSMBs; compare and evaluate different methods and strategies for facilitating the submission and enhancing the interpretation of adverse event reports submitted to review bodies. Compare and evaluate different methods and strategies for identifying, reporting, and handling adverse events, severe adverse events, or unanticipated problems based on the perspectives of individual participants, institutions, DSMBs, and/or IRBs.
Evaluate effectiveness of Conflict of Interest (COI) committees. For example, identify and evaluate strategies to address non-financial COI among research teams, sponsors, advisory boards or other stakeholders. Assess the impact of perceived or real conflicts of interest among members of oversight committees on decision-making about the acceptability of research protocols, interpretations of adverse events, and/or perceptions of "independence of review" by the research community.

6. Research with Specimens and Data

Assess the perspectives and attitudes of subjects about the use of specimens and/or data in research, including special cultural or religious beliefs and attitudes concerning the use of discarded clinical specimens.
Assess how much subjects expect to know about how their specimens and/or data will be used in research.
Develop novel approaches for obtaining informed consent for research use of specimens and data collected during the course of routine clinical care.
Explore and develop ways of addressing ethical issues related to the return of individual research results to subjects, including studies of associated risks and harms.
Explore and develop ways of addressing ethical issues related to intellectual property and ownership of specimens.
Explore issues related to benefit sharing in the context of tissue research. Identify models and mechanisms that can be used to engage communities, sponsors, and researchers in benefit-sharing arrangements and assess the social and ethical acceptability and practicability of these arrangements.
Identify and evaluate strategies for balancing the responsibility for protecting and/or minimizing disclosure of private information with the obligation for maximizing the social value of research when identifiable data are:
Collected via the internet or other electronic method;
Preserved for secondary analysis, e.g., a tissue or gene bank, data archive or warehouse.

7. Dissemination of Research Findings

Explore when and how research results and incidental findings should be reported and disseminated to lay communities, including research subjects and the general public.
Develop and evaluate methods for communicating research results and incidental findings with medical implications to research subjects and families.
Develop and evaluate scientific and ethical parameters that should be considered when reporting generalized, aggregate research findings; develop and evaluate methods for communicating the evolving and sometimes conflicting nature of scientific evidence to lay audiences.

To assist you in identifying which NIH Institute/Center most closely matches your research topic, the following website provides additional information about Institute/Center-specific research interests that will be supported by this FOA: http://grants.nih.gov/grants/guide/contacts/pa-06-367_368_369_contacts.doc

The evolution and vitality of the biomedical sciences require a constant infusion of new ideas, techniques, and points of view. These may differ substantially from current thinking or practice and may not yet be supported by substantial preliminary data. By using the R21 mechanism, the NIH seeks to foster the introduction of novel scientific ideas, model systems, tools, agents, targets, and technologies that have the potential to substantially advance biomedical research.

The R21 mechanism is intended to encourage new exploratory and developmental research projects. For example, such projects could assess the feasibility of a novel area of investigation or a new experimental system that has the potential to enhance health-related research. Another example could include the unique and innovative use of an existing methodology to explore a new scientific area. These studies may involve considerable risk but may lead to a breakthrough in a particular area, or to the development of novel techniques, agents, methodologies, models, or applications that could have a major impact on a field of biomedical, behavioral, or clinical research.

Applications for R21 awards should describe projects distinct from those supported through the traditional R01 mechanism. For example, long-term projects, or projects designed to increase knowledge in a well-established area, will not be considered for R21 awards. Applications submitted under this mechanism should be exploratory and novel. These studies should break new ground or extend previous discoveries toward new directions or applications. Projects of limited cost or scope that use widely accepted approaches and methods within well established fields are better suited for the R03 small grant mechanism. Information on the R03 program can be found at http://grants.nih.gov/grants/funding/r03.htm.

See Section VIII, Other Information - Required Federal Citations, for policies related to this announcement.

Section II. Award Information

1. Mechanism of Support

This Funding Opportunity Announcement (FOA) invites applications for Exploratory/Developmental Research projects. The R21 mechanism is intended to encourage exploratory/developmental research projects by providing support for the early and conceptual stages of development. The applicant will be solely responsible for planning, directing, and executing the proposed project.

This FOA uses just-in-time concepts. It also uses the modular budget formats (see the Modular Applications and Awards section of the NIH Grants Policy Statement. Specifically, if you are submitting an application with direct costs in each year of $250,000 or less (excluding consortium Facilities and Administrative [F&A] costs), use the PHS398 Modular Budget component provided in the SF424 (R&R) Application Package and SF424 (R&R) Application Guide (see specifically Section 3.4, Modular Budget Component, of the Application Guide).

Exploratory/developmental grant support is for new projects only; competing renewal (formerly competing continuation) applications will not be accepted. Applicants may submit a resubmission, but such application must include an Introduction addressing issues raised in the previous critique (Summary Statement).

For specific information about the R21 program, see: http://grants.nih.gov/grants/funding/r21.htm

2. Funds Available

Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. Although the financial plans of the Institutes and Centers (ICs) provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the submission of a sufficient number of meritorious applications.

The total project period for an application submitted in response to this funding opportunity may not exceed 2 years. Although the size of award may vary with the scope of research proposed, it is expected that applications will stay within the budgetary guidelines for an exploratory/developmental project; direct costs are limited to $275,000 over an R21 two-year period, with no more than $200,000 in direct costs allowed in any single year. Applicants may request direct costs in $25,000 modules, up to the total direct costs limitation of $275,000 for the combined two-year award period. NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this Program Announcement funding opportunity.

Facilities and Administrative (F&A) costs requested by consortium participants are not included in the direct cost limitation. See NOT-OD-05-004.

Section III. Eligibility Information

1. Eligible Applicants

1.A. Eligible Institutions

You may submit an application(s) if your organization has any of the following characteristics:

For-profit organizations
Non-profit organizations
Public or private institutions, such as universities, colleges, hospitals, and laboratories
Units of State government
Units of Local government
Eligible agencies of the Federal government
Foreign Institutions
Domestic Institutions
Faith-based or community-based organizations
Indian/Native American Tribal Government (Federally Recognized)
Indian/Native American Tribal Government (Other than Federally Recognized)
Indian/Native American Tribally Designated Organization

1.B. Eligible Individuals

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research as the Project 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.

2. Cost Sharing or Matching

Not applicable. This program does not require cost sharing as defined in the current NIH Grants Policy Statement.

3. Other-Special Eligibility Criteria

Applicants may submit more than one application, provided each application is scientifically distinct.

Section IV. Application and Submission Information

To download a SF424 (R&R) Application Package and SF424 (R&R) Application Guide for completing the SF424 (R&R) forms for this FOA, link to http://www.grants.gov/Apply/ and follow the directions provided on that Web site.

A one-time registration is required for institutions/organizations at both:

Grants.gov (http://www.grants.gov/GetStarted) and
eRA Commons (http://era.nih.gov/ElectronicReceipt/preparing.htm)

PD/PIs should work with their institutions/organizations to make sure they are registered in the eRA Commons.

Several additional separate actions are required before an applicant institution/organization can submit an electronic application, as follows:

1) Organizational/Institutional Registration in Grants.gov/Get Started

Your organization will need to obtain a Data Universal Number System (DUNS) number and register with the Central Contractor Registration (CCR) as part of the Grants.gov registration process.
If your organization does not have a Taxpayer Identification Number (TIN) or Employer Identification Number (EIN), allow for extra time. A valid TIN or EIN is necessary for CCR registration.
The CCR also validates the EIN against Internal Revenue Service records, a step that will take an additional one to two business days.
Direct questions regarding Grants.gov registration to:
Grants.gov Customer Support
Contact Center Phone: 800-518-4726
Business Hours: M-F 7:00 a.m. - 9:00 p.m. Eastern Time
Email [email protected]

2) Organizational/Institutional Registration in the eRA Commons

To find out if an organization is already Commons-registered, see the "List of Grantee Organizations Registered in NIH eRA Commons.
Direct questions regarding the Commons registration to:
eRA Commons Help Desk
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Business hours M-F 7:00 a.m. 8:00 p.m. Eastern Time
Email [email protected]

3) Project Director/Principal Investigator (PD/PI) Registration in the NIH eRA Commons: Refer to the NIH eRA Commons System (COM) Users Guide.

The individual designated as the PD/PI on the application must also be registered in the NIH eRA Commons. It is not necessary for PDs/PIs to register with Grants.gov.
The PD/PI must hold a PD/PI account in the Commons and must be affiliated with the applicant organization. This account cannot have any other role attached to it other than the PD/PI.
This registration/affiliation must be done by the Authorized Organization Representative/Signing Official (AOR/SO) or their designee who is already registered in the Commons.
Both the PD/PI and AOR/SO need separate accounts in the NIH eRA Commons.

Note that if a PD/PI is also an NIH peer-reviewer with an Individual DUNS and CCR registration, that particular DUNS number and CCR registration are for the individual reviewer only. These are different than any DUNS number and CCR registration used by an applicant organization. Individual DUNS and CCR registration should be used only for the purposes of personal reimbursement and should not be used on any grant applications submitted to the Federal Government.

Several of the steps of the registration process could take four weeks or more. Therefore, applicants should immediately check with their business official to determine whether their organization/institution is already registered in both Grants.gov and the Commons. The NIH will accept electronic applications only from organizations that have completed all necessary registrations.

1. Request Application Information

Applicants must download the SF424 (R&R) application forms and SF424 (R&R) Application Guide for this FOA through Grants.gov/Apply.

Note: Only the forms package directly attached to a specific FOA can be used. You will not be able to use any other SF424 (R&R) forms (e.g., sample forms, forms from another FOA), although some of the "Attachment" files may be useable for more than one FOA.

For further assistance, contact GrantsInfo: Telephone 301-710-0267, Email: [email protected].

Telecommunications for the hearing impaired: TTY 301-451-5936.

2. Content and Form of Application Submission

Prepare all applications using the SF424 (R&R) application forms and in accordance with the SF424 (R&R) Application Guide (MS Word or PDF).

The SF424 (R&R) Application Guide is critical to submitting a complete and accurate application to NIH. There are fields within the SF424 (R&R) application components that, although not marked as mandatory, are required by NIH (e.g., the Credential log-in field of the Research & Related Senior/Key Person Profile component must contain the PD/PIs assigned eRA Commons User ID). Agency-specific instructions for such fields are clearly identified in the Application Guide. For additional information, see Tips and Tools for Navigating Electronic Submission on the front page of Electronic Submission of Grant Applications.

The SF424 (R&R) application is comprised of data arranged in separate components. Some components are required, others are optional. The forms package associated with this FOA in Grants.gov/APPLY will include all applicable components, required and optional. A completed application in response to this FOA will include the following components:

Required Components:
SF424 (R&R) (Cover component)
Research & Related Project/Performance Site Locations
Research & Related Other Project Information
Research & Related Senior/Key Person
PHS398 Cover Page Supplement
PHS398 Research Plan
PHS398 Checklist
PHS398 Modular Budget

Optional Components:
PHS398 Cover Letter File
Research & Related Subaward Budget Attachment(s) Form
Note: While both budget components are included in the SF424 (R&R) forms package, the NIH R21 uses ONLY the PHS 398 Modular Budget. (Do not use the detailed Research & Related Budget.)

Foreign Organizations
Several special provisions apply to applications submitted by foreign organizations:

Charge back of customs and import fees is not allowed.
Format: Every effort should be made to comply with the format specifications, which are based upon a standard U.S. paper size of 8.5 x 11 within each PDF.
Funds for up to 8% administrative costs (excluding equipment) may be requested. See NOT-OD-01-028, March 29, 2001.
Organizations must comply with Federal/NIH policies on human subjects, animals, and biohazards.
Organizations must comply with Federal/NIH biosafety and biosecurity regulations. See Section VI.2., Administrative and National Policy Requirements.
Additional information regarding foreign grants is available in the NIH Grants Policy Statement (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part12.htm#_Toc54600260).

Proposed research should provide special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions in other countries that are not readily available in the United States or that augment existing U.S. resources.

3. Submission Dates and Times

See Section IV.3.A for details.

3.A. Submission, Review, and Anticipated Start Dates
Opening Date: May 2, 2006 (Earliest date an application may be submitted to Grants.gov)
Letter of Intent Receipt Date(s): Not applicable
Application Submission Date(s): http://grants.nih.gov/grants/funding/submissionschedule.htm
AIDS Application Submission Date(s): http://grants1.nih.gov/grants/funding/submissionschedule.htm#AIDS
Peer Review Date(s): http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
Council Review Date(s) http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
Earliest Anticipated Start Date(s): http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward

3.A.1. Letter of Intent

A letter of intent is not required for the funding opportunity.

3.B. Sending an Application to the NIH

To submit an application in response to this FOA, applicants should access this FOA via http://www.grants.gov/Apply and follow steps 1-4. Note: Applications must only be submitted electronically. PAPER APPLICATIONS WILL NOT BE ACCEPTED.

3.C. Application Processing

Applications may be submitted on or after the opening date and must be successfully received by Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization) on the application submission/receipt date(s). (See Section IV.3.A. for all dates.) If an application is not submitted by the receipt date(s) and time, the application may be delayed in the review process or not reviewed.

Once an application package has been successfully submitted through Grants.gov, any errors have been addressed, and the assembled application has been created in the eRA Commons, the PD/PI and AOR/SO have two business days to view the application image.

If everything is acceptable, no further action is necessary. The application will automatically move forward for processing by the Division of Receipt and Referral after two business days.
Prior to the submission deadline, the AOR/SO can Reject the assembled application and submit a changed/corrected application within the two day viewing window. This option should be used if the AOR/SO determines that warnings should be addressed. Reminder: warnings do not stop further application processing. If an application submission results in warnings (but no errors) it will automatically move forward after two business days if no action is taken. Please remember that some warnings may not be applicable or may need to be addressed after application submission.
If the two day window falls after the submission deadline, the AOR/SO will have the option to Reject the application if, due to an eRA Commons or Grants.gov system issue, the application does not correctly reflect the submitted application package (e.g., some part of the application was lost or did not transfer correctly during the submission process). The AOR/SO should first contact the eRA Commons Helpdesk to confirm the system error, document the issue, and determine the best course of action. NIH will not penalize the applicant for an eRA Commons or Grants.gov system issue.
If the AOR/SO chooses to Reject the image after the submission deadline for a reason other than an eRA Commons or Grants.gov system failure, a changed/corrected application still can be submitted but it will be subject to the NIH late policy guidelines and may not be accepted. The reason for this delay should be explained in the cover letter attachment.

Both the AOR/SO and PD/PI will receive e-mail notifications when the application is rejected or the application automatically moves forward in the process after two days.

Upon receipt applications will be evaluated for completeness by the Center for Scientific Review (CSR), NIH. Incomplete applications will not be reviewed.

There will be an acknowledgement of receipt of applications from Grants.gov and the Commons . Information related to the assignment of an application to a Scientific Review Group is also in the Commons.

The NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial merit review unless the applicant withdraws the pending application. The NIH will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of an application already reviewed with substantial changes, but such application must include an Introduction addressing the previous critique. Note such an application is considered a "resubmission" for the SF424 (R&R).

4. Intergovernmental Review

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

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. A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new award if such costs: are necessary to conduct the project, and would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee must obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new award.

The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project. See the NIH Grants Policy Statement.

6. Other Submission Requirements

The NIH requires the PD/PI to fill in his/her Commons User ID in the PROFILE Project Director/Principal Investigator section, Credential log-in field of the Research & Related Senior/Key Person Profile component. The applicant organization must include its DUNS number in its Organization Profile in the eRA Commons. This DUNS number must match the DUNS number provided at CCR registration with Grants.gov. For additional information, see Tips and Tools for Navigating Electronic Submission on the front page of Electronic Submission of Grant Applications.

Renewal (formerly competing continuation or Type 2) applications are not permitted.

All application instructions outlined in the SF424 (R&R) application are to be followed, with the following requirements for R21 applications:

R21 applications will use the modular budget format and "Just-in-Time" concepts, with direct costs requested in $25,000 modules, up to the total direct costs limitation of $275,000 over an R21 two-year period. No more than $200,000 in direct costs will be allowed in any single year.
Although preliminary data are not required for an R21 application, they may be included.
Item 3 of the R21 application may not exceed 6 pages, including tables, graphs, figures, diagrams, and charts.
Introduction (required for a resubmission application) is limited to one page.
Preliminary data are not required but may be included if available.

Note: While each section of the Research Plan needs to be uploaded separately as a PDF attachment, applicants are encouraged to construct the Research Plan as a single document, separating sections into distinct PDF attachments just before uploading the files. This approach will enable applicants to better monitor formatting requirements such as page limits. All attachments must be provided to NIH in PDF format, filenames must be included with no spaces or special characters, and a .pdf extension must be used.

R21 appendix materials should be limited, as is consistent with the exploratory nature of the R21 mechanism. The following materials may be included in the appendix:
Up to five publications, manuscripts (accepted for publication), abstracts, patents, or other printed materials directly relevant to this project. Do not include manuscripts submitted for publication.

Publications in press: Include only a publication list with a link to the publicly available on-line journal article or the PubMed Central (PMC) submission identification number. Do not include the entire article.
Manuscripts accepted for publication but not yet published: The entire article may be submitted electronically as a PDF attachment.
Manuscripts published but an online journal link is not available: The entire article may be submitted electronically as a PDF attachment.

Surveys, questionnaires, data collection instruments, clinical protocols, and informed consent documents.
Graphic images of gels, micrographs, etc. provided that the image (may be reduced in size) is also included within the 6-page limit of Item 3. No images may be included in the Appendix that are not also represented within the Research Plan.
Do not use the Appendix to circumvent the page limitations of the Research Plan. An application that does not observe these limitations may be delayed in the review process.

Plan for Sharing Research Data

The precise content of the data-sharing plan will vary, depending on the data being collected and how the investigator is planning to share the data. Applicants who are planning to share data may wish to describe briefly the expected schedule for data sharing, the format of the final dataset, the documentation to be provided, whether or not any analytic tools also will be provided, whether or not a data-sharing agreement will be required and, if so, a brief description of such an agreement (including the criteria for deciding who can receive the data and whether or not any conditions will be placed on their use), and the mode of data sharing (e.g., under their own auspices by mailing a disk or posting data on their institutional or personal website, through a data archive or enclave). Investigators choosing to share under their own auspices may wish to enter into a data-sharing agreement. References to data sharing may also be appropriate in other sections of the application.

All applicants must include a plan for sharing research data in their application. The data sharing policy is available at http://grants.nih.gov/grants/policy/data_sharing. All investigators responding to this funding opportunity should include a description of how final research data will be shared, or explain why data sharing is not possible.

The reasonableness of the data sharing plan or the rationale for not sharing research data will be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the impact/priority score.

Sharing Research Resources

Not applicable

Section V. Application Review Information

1. Criteria (Update: Enhanced review criteria have been issued for the evaluation of research applications received for potential FY2010 funding and thereafter - see NOT-OD-09-025).

Only the review criteria described below will be considered in the review process.

2. Review and Selection Process

Applications submitted for this funding opportunity will be assigned to the ICs on the basis of established PHS referral guidelines.

Appropriate scientific review groups convened in accordance with the standard NIH peer review procedures (http://www.csr.nih.gov/refrev.htm) will evaluate applications for scientific and technical merit.

As part of the initial merit review, all applications will:

Undergo a selection process in which only those applications deemed to have the highest scientific merit, generally the top half of applications under review, will be discussed and assigned an impact/priority score.
Receive a written critique.
Receive a second level of review by the appropriate national advisory council or board.

Applications submitted in response to this funding opportunity will compete for available funds with all other recommended applications. The following will be considered in making funding decisions:

Scientific merit of the proposed project as determined by peer review.
Availability of funds.
Relevance to program priorities.

The NIH R21 exploratory/developmental grant is a mechanism for supporting novel scientific ideas or new model systems, tools, or technologies that have the potential to significantly advance our knowledge or the status of health-related research. Because the Research Strategy is limited to 6 pages, an exploratory/developmental grant application need not have extensive background material or preliminary information as one might normally expect in an R01 application. Accordingly, reviewers will focus their evaluation on the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Reviewers will place less emphasis on methodological details and certain indicators traditionally used in evaluating the scientific merit of R01 applications, including supportive preliminary data. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Preliminary data are not required for R21 applications; however, they may be included if available.

The goals of NIH supported research are to advance our understanding of biological systems, to improve the control of disease, and to enhance health. In their written critiques, reviewers will be asked to comment on each of the following criteria in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, weighting them as appropriate for each application.

Significance
Approach
Innovation
Investigator
Environment
Additional Review Criteria

Note that an application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a high impact/priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward.

Overall Impact. 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 five core review criteria, and additional review criteria (as applicable for the project proposed).

Core Review Criteria. Reviewers will consider each of the five review criteria below in the determination of scientific and technical 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 investigators appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the PD/PI and other researchers? Does the investigative team bring complementary and integrated expertise to the project (if applicable)?

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: Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed studies benefit from unique features of the scientific environment, or subject populations, or employ useful collaborative arrangements? Is there evidence of institutional support?

2.A. Additional Review Criteria:

As applicable for the project proposed, reviewers will consider the following additional items in the determination of scientific and technical merit, 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.

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.

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.

Resubmission Applications. When reviewing a Resubmission application (formerly called an amended application), 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.

Renewal Applications. When reviewing a Renewal application (formerly called a competing continuation application), the committee will consider the progress made in the last funding period.

Revision Applications. When reviewing a Revision application (formerly called a competing supplement application), 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.

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.

2.B. Additional Review Considerations

As applicable for the project proposed, reviewers will address 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.

Budget and Period Support. Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Select Agents 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).

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.

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 (http://grants.nih.gov/grants/policy/data_sharing/data_sharing_guidance.htm); 2) Sharing Model Organisms (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-042.html); and 3) Genome Wide Association Studies (GWAS) (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html).

2.C. Sharing Research Data

Data Sharing Plan: The reasonableness of the data sharing plan or the rationale for not sharing research data will be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the impact/priority score. The presence of a data sharing plan will be part of the terms and conditions of the award. The funding organization will be responsible for monitoring the data sharing policy.

2.D. Sharing Research Resources

Not applicable

3. Anticipated Announcement and Award Dates

Not Applicable

Section VI. Award Administration Information

1. Award Notices

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 NIH eRA Commons.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official.

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. See Section IV.5., Funding Restrictions.

2. Administrative and National Policy Requirements

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.

3. Reporting

When multiple years are involved, awardees will be required to submit the Non-Competing Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

Section VII. Agency Contacts

We encourage your inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into three areas: scientific/research, peer review, and financial or grants management issues:

1. Scientific/Research Contacts:

Central NIH Program Contact (for general inquiries):

Office of Extramural Programs, OD, NIH
1 Rockledge Centre, Room 3531
6705 Rockledge Drive, MSC 7963
Bethesda, MD 20892-7963
Telephone: (301) 451-4225
Fax: (301) 480-0146
Email: [email protected]

NIH Institute/Center Program Contacts:

National Cancer InstituteKim Witherspoon
Clinical Grants and Contracts Branch
Cancer Therapy Evaluation Program
Division of Cancer Treatment and Diagnosis
National Cancer Institute
6130 Executive Blvd (EPN), Rm 7009
MSC 7432
Bethesda, MD 20892-7432

National Institutes of Health
Phone: 301-496-8866
Fax: 301-480-4663
Email: [email protected]

National Human Genome Research Institute
Elizabeth J. Thomson, MS, RN, CGC, FAAN
Building 31, Room B2B07
31 Center Drive, MSC 2033

National Institutes of Health
Bethesda, MD 20892-2033
Telephone: (301) 402-4997
FAX: (301) 402-1950
Email: [email protected]

National Institute on Aging
Neil Buckholtz, Ph.D.
Neuroscience and Neuropsychology of Aging Program
National Institute on Aging
Gateway Building, Suite 350
7201 Wisconsin Avenue Bethesda, MD 20892-9205
Telephone: (301) 496-9350
FAX: (301) 496-1494
Email: [email protected]

National Institute on Alcohol Abuse and Alcoholism
Page Chiapella, Ph.D.
Division of Treatment and Recovery Research
National Institute on Alcohol Abuse and Alcoholism
5635 Fishers Lane, Suite 2044, MSC 9304
Bethesda, MD 20892-9304
Telephone: (301) 443-4715
FAX: (301) 443-8774
Email: [email protected]

National Institute on Allergy and Infectious Diseases
Lawrence J. Prograis, Jr., M.D.
DAIT
6700 B Rockledge, Room 5134
Bethesda, MD 20892
Telephone: (301) 496-1886
FAX: (301) 402-2571
Email: [email protected]

National Institute of Arthritis and Musculoskeletal and Skin Diseases

Madeline Turkeltaub, RN, PhD, CRNP, FAAN
Clinical Research Project Manager
NIAMS, Extramural Program
One Democracy Plaza
6701 Democracy Blvd., Suite 800
MSC 4872
Bethesda, MD 20892-4872
Telephone: (301) 451-5888
FAX: (301) 480-4543
Email:[email protected]

National Institute of Child Health and Human Development
Lisa Freund, Ph.D.
Building 6100, Room 6B05D MSC7510
Bethesda, MD 20892
Telephone: (301) 435-6879
FAX: (301) 408-0230
Email: [email protected]

National Institute on Deafness and Other Communication Disorders
Ling Chin, M.D., M.P.H.
Chief, Clinical Trials and Epidemiology, Biostatistics
6120 Executive Blvd EPS Room 400C MSC-7180
Bethesda, MD 20892-7180
Telephone: (301) 435-0598
FAX: (301) 402-6251
Email: [email protected]

National Institute on Drug Abuse
Ruben Baler, Ph.D.
Science Policy Branch
Office of Science Policy and Communications
6001 Executive Boulevard, Room 5248
Bethesda, MD 20892-9541
Telephone: (301) 443-6070
FAX: (301) 480-2485
Email: [email protected]

National Institute of Environmental Health Sciences
Kimberly A. McAllister, Ph.D.
Susceptibility and Population Health Branch
Division of Extramural Research and Training
National Institute of Environmental Health Sciences
P.O. Box 12233 (MD EC-21)
Research Triangle Park, NC 27709
Phone: (919) 541-4528
FAX: (919) 316-4606
Email: [email protected]

National Institute of Mental Health
William T. Riley, Ph.D.
Division of AIDS and Health Behavior Research
6001 Executive Boulevard, Room 6226, MSC 9615
Bethesda, MD 20892-9615
Telephone: (301) 435-0301
Fax: (301) 480-2920
Email: [email protected]

National Institute of Neurological Disorders and Stroke
Barbara Radziszewska, Ph.D., M.P.H.
Clinical Research Project Manager
Clinical Trials Cluster
6001 Executive Blvd., Room 2216
Bethesda, MD 20892-9520
Telephone: (301) 496-2076
FAX: (301) 480-1080
Email: [email protected]

National Institute of Nursing Research
Josephine E. A. Boyington, PhD, MPH, RN
Program Director, Office of Extramural Activities
National Institute of Nursing Research, NIH
6701 Democracy Blvd., Rm. 715
One Democracy Plaza
Bethesda, MD 20892-4870
Telephone: (301) 594-2542
Fax: 301-480-8260
Email: [email protected]

National Center on Complementary and Alternative Medicine
Jack Killen, M.D.
Director, Office of International Health Research
National Center for Complementary & Alternative Medicine
6707 Democracy Boulevard, Suite 401
Bethesda, MD 20892-5475
Telephone: (301) 594-7103
Fax: (301) 480-3621
Email: [email protected]

2. Peer Review Contacts:

Not applicable

3. Financial or Grants Management Contacts:

National Cancer Institute
Eileen Natoli
6120 Executive Boulevard, EPS 243
Bethesda, MD 20892-7180
Telephone: (301) 496-8791
FAX: (301) 496-8601
Email:[email protected]

National Human Genome Research Institute
Cheryl Chick
5635 Fishers Lane, Rm 4076
Bethesda, MD 20892-9306
Telephone: (301) 435-7858
FAX: (301) 402 -1951
Email: [email protected]

National Institute on Aging
Jeff Ball
Grants Management Specialist
7201 Wisconsin Avenue
Gateway Building, Suite 2N212
Bethesda, MD 20892-9205
Telephone: (301) 402-7732
FAX: (301) 402-3672
E-Mail: [email protected]

National Institute on Alcohol Abuse and Alcoholism
Judy Fox
Grants Management Branch
National Institute on Alcohol Abuse and Alcoholism
5635 Fishers Lane, Room 3023, MSC 9304
Bethesda, MD 20892-9304
Telephone: (301) 443-4704
Email: [email protected]

National Institute on Allergy and Infectious Diseases
Cindy McDermott
Division of Extramural Activities
6700-B Rockledge Drive, Rm 2132, MSC 7614
Bethesda, MD 20892-7614
Telephone: (301) 594-7456
FAX: (301) 480-3780
Email:[email protected]

National Institute of Arthritis and Musculoskeletal and Skin Diseases
Melinda Nelson
Grants Management Officer
Building 45, Rm 5AS49F
Bethesda, MD 20892-6500
Telephone: (301) 594-3535
FAX: (301) 480-5450
Email: [email protected]

National Institute of Child Health and Human Development
John Chris Robey
6100 Executive Boulevard, Rm 8A01, MSC 7510
Rockville, Maryland 20892
Express Mail Zip: 20852
Phone: (301) 435-6996
FAX: (301) 402-0915
Email:[email protected]

National Institute on Deafness and Other Communication Disorders
Christopher Myers
6120 Executive Boulevard, EPS 400B, MSC 7180
Bethesda, MD 20892-7180
Telephone: (301) 402-0909
FAX: (301) 402-1758
Email: [email protected]

National Institute on Drug Abuse
Gary Fleming, J.D., M.A.
Grants Management Branch
Office of Planning and Resource Management
6001 Executive Boulevard, Room 3131, MSC 9541
Bethesda, MD 20892-9541
Telephone: (301) 443-6710
FAX: (301) 443-6847
E-mail: [email protected]

National Institute of Environmental Health Sciences
Donald Ellis
EC 3175
PO Box 12233
(MD EC-20)
Research Triangle Park, NC 27709-2233
Telephone: (919) 541-1874
FAX: (919) 541-2860
Email: [email protected]

National Institute of Mental Health
Rebecca D. Claycamp, CRA
6001 Executive Boulevard, Room 6122, MSC 9605
Bethesda, MD 20892-9605
Telephone: (301) 443-2811
FAX: (301) 443-6885
Email:[email protected]

National Institute of Neurological Disorders and Stroke
Maxine Davis-Vanlue
Neuro Science Center, Rm 3248
6001 Executive Boulevard
Rockville, MD 20892
Telephone: (301) 496-9231
FAX: (301) 402-0219
Email:[email protected]

National Institute of Nursing Research
Brian Albertini
6701 Democracy Boulevard, Rm 710
One Democracy Plaza
Bethesda, MD 20892-4870 (Courier use 20817)
Phone: (301) 594-6869
FAX: (301) 402-4502
Email: [email protected]

National Center for Complementary and Alternative Medicine
Ms. Andra A. Standberry
6707 Democracy Blvd.
Democracy Two, Suite 401
Bethesda, MD 20892-5475
Telephone: (301) 594-3788
FAX: (301) 480-3621
Email: [email protected]

Section VIII. Other Information

Required Federal Citations

Vertebrate Animals:
Recipients of PHS support for activities involving live, vertebrate animals must comply with PHS Policy on Humane Care and Use of Laboratory Animals (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf) as mandated by the Health Research Extension Act of 1985 (http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA Animal Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm) as applicable.

Human Subjects Protections:
Federal regulations (45 CFR 46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

Data and Safety Monitoring Plan:
Data and safety monitoring is required for all types of clinical trials, including physiologic toxicity and dose-finding studies (phase I); efficacy studies (Phase II); efficacy, effectiveness and comparative trials (Phase III). Monitoring should be commensurate with risk. The establishment of data and safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risks to the participants (NIH Policy for Data and Safety Monitoring, NIH Guide for Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

Sharing Research Data:
Investigators submitting an NIH application seeking $500,000 or more in direct costs in any single year are expected to include a plan for data sharing or state why this is not possible (http://grants.nih.gov/grants/policy/data_sharing).

Investigators should seek guidance from their institutions, on issues related to institutional policies and local IRB rules, as well as local, State and Federal laws and regulations, including the Privacy Rule. Reviewers will consider the data sharing plan but will not factor the plan into the determination of the scientific merit or the impact/priority score.

Access to Research Data through the Freedom of Information Act:
The Office of Management and Budget (OMB) Circular A-110 has been revised to provide public access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are (1) first produced in a project that is supported in whole or in part with Federal funds and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this funding opportunity in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award.

Sharing of Model Organisms:
Not applicable

Inclusion of Women, Minorities, and Children:
It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported clinical research projects unless a clear and compelling justification is provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing clinical research should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the SF424 (R&R) application; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences.

Inclusion of Children as Participants in Clinical Research:
The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all clinical research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them.

All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines" on the inclusion of children as participants in research involving human subjects (http://grants.nih.gov/grants/funding/children/children.htm).

Required Education on the Protection of Human Subject Participants:
NIH policy requires education on the protection of human subject participants for all investigators submitting NIH applications for research involving human subjects and individuals designated as key personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

Human Embryonic Stem Cells (hESC):
Criteria for federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-09-116.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (http://escr.nih.gov). It is the responsibility of the applicant to provide in the project description and elsewhere in the application as appropriate, the official NIH identifier(s) for the hESC line(s) to be used in the proposed research.

NIH Public Access Policy:
NIH-funded investigators are requested to submit to the NIH manuscript submission (NIHMS) system (http://www.nihms.nih.gov) at PubMed Central (PMC) an electronic version of the author's final manuscript upon acceptance for publication, resulting from research supported in whole or in part with direct costs from NIH. The author's final manuscript is defined as the final version accepted for journal publication, and includes all modifications from the publishing peer review process.

NIH is requesting that authors submit manuscripts resulting from 1) currently funded NIH research projects or 2) previously supported NIH research projects if they are accepted for publication on or after May 2, 2005. The NIH Public Access Policy applies to all research grant and career development award mechanisms, cooperative agreements, contracts, Institutional and Individual Ruth L. Kirschstein National Research Service Awards, as well as NIH intramural research studies. The Policy applies to peer-reviewed, original research publications that have been supported in whole or in part with direct costs from NIH, but it does not apply to book chapters, editorials, reviews, or conference proceedings. Publications resulting from non-NIH-supported research projects should not be submitted.

For more information about the Policy or the submission process, please visit the NIH Public Access Policy Web site at http://publicaccess.nih.gov/ and view the Policy or other Resources and Tools, including the Authors' Manual.

Standards for Privacy of Individually Identifiable Health Information:
The Department of Health and Human Services (DHHS) issued final modification to the "Standards for Privacy of Individually Identifiable Health Information", the "Privacy Rule", on August 14, 2002. The Privacy Rule is a federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health information, and is administered and enforced by the DHHS Office for Civil Rights (OCR).

Decisions about applicability and implementation of the Privacy Rule reside with the researcher and his/her institution. The OCR website (http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including a complete Regulation Text and a set of decision tools on "Am I a covered entity?" Information on the impact of the HIPAA Privacy Rule on NIH processes involving the review, funding, and progress monitoring of grants, cooperative agreements, and research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) should not be used to provide information necessary to the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site.

Healthy People 2010:
The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This PA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

Authority and Regulations:
This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

The PHS strongly encourages all grant recipients to provide a smoke-free workplace and discourage the use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.

Loan Repayment Programs:
NIH encourages applications for educational loan repayment from qualified health professionals who have made a commitment to pursue a research career involving clinical, pediatric, contraception, infertility, and health disparities related areas. The LRP is an important component of NIH's efforts to recruit and retain the next generation of researchers by providing the means for developing a research career unfettered by the burden of student loan debt. Note that an NIH grant is not required for eligibility and concurrent career award and LRP applications are encouraged. The periods of career award and LRP award may overlap providing the LRP recipient with the required commitment of time and effort, as LRP awardees must commit at least 50% of their time (at least 20 hours per week based on a 40 hour week) for two years to the research. For further information, please see: http://www.lrp.nih.gov.