Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	National Institute of Neurological Disorders and Stroke (NINDS) National Eye Institute (NEI) National Institute of Allergy and Infectious Diseases (NIAID) National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) National Institute of Environmental Health Sciences (NIEHS) National Institute of General Medical Sciences (NIGMS)
Funding Opportunity Title	Countermeasures Against Chemical Threats (CounterACT) Cooperative Research Projects (U01)
Activity Code	U01 Research Project Cooperative Agreements
Announcement Type	Reissue of PAR-10-180
Related Notices	April 25, 2013 - This PAR has been reissued as PAR-13-208.
Funding Opportunity Announcement (FOA) Number	PAR-11-155
Companion FOA	PAR-10-181, U54, Countermeasures Against Chemical Threats (CounterACT) Research Centers of Excellence (U54); PAR-10-019, R21, Countermeasures Against Chemical Threats (CounterACT) Exploratory/Developmental Projects in Translational Research (R21)
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.853, 93.867, 93.856, 93.846, 93.865, 93.113, 93.859
FOA Purpose	This Funding Opportunity Announcement (FOA) encourages grant applications for Countermeasures Against Chemical Threats (CounterACT) Cooperative Research Projects (U01s). The mission of the CounterACT U01 program is to develop new and improved therapeutics for chemical threats. Chemical threats are toxic chemicals that could be used in a terrorist attack or accidentally released from industrial production, storage or shipping. They include traditional chemical warfare nerve agents such as sarin and VX, and toxic industrial chemicals and pesticides such as cyanide, chlorine, parathion, and sodium fluoroacetate. The scope of the research to be supported includes basic target and candidate identification and characterization studies, through candidate optimization and demonstration of in vivo efficacy, through Investigational New Drug (IND) submission and Phase 1 clinical trials when appropriate. Each project must include milestones that create discrete go or no-go decision points in a progressive translational study plan.

Posted Date	March 16, 2011
Open Date (Earliest Submission Date)	August 14, 2011
Letter of Intent Due Date	August 14, 2011; August 14, 2012
Application Due Date(s)	September 14, 2011; September 14, 2012, by 5:00 PM local time of applicant organization.
AIDS Application Due Date(s)	Not Applicable
Scientific Merit Review	February/March 2012; February/March 2013
Advisory Council Review	May 2012; May 2013
Earliest Start Date(s)	July 1, 2012; July 1, 2013
Expiration Date	September 15, 2012
Due Dates for E.O. 12372	Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the SF 424 (R&R) Application Guide except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of the Announcement
Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Purpose and Nature of this Research Opportunity

The overall goal of the NIH CounterACT program is to reduce mortality and morbidity during and after emergency events involving the release of chemical threat agents. Chemical threat agents are toxic chemicals that could cause mass casualties after being released by a deliberate terrorist attack, or by industrial accident or natural disaster (see below for categories and examples of chemicals). The purpose of this U01 research opportunity is to foster and support the development of Food and Drug Administration (FDA)-approved therapeutics that can be used effectively to treat individuals during a chemical emergency event. This announcement requests new applications, as well as renewal applications of existing projects within the CounterACT Network (see www.ninds.nih.gov/counteract).

Background

The NIH has developed a comprehensive CounterACT Research Program that includes a research network of Research Centers of Excellence, individual research projects, contracts and Interagency Agreements with the Department of Defense. The network conducts basic, translational, and clinical research aimed at the discovery and/or identification of better medical countermeasures against chemical threat agents, and it supports their movement through the regulatory process. The CounterACT U01 program described in this FOA is part of this overall larger effort, and is designed to support investigator-initiated individual research projects. To ensure that the research is translational in nature, CounterACT research projects will be milestone-driven U01 cooperative agreements with substantial scientific and programmatic involvement by NIH staff.

CounterACT cooperative agreement U01 Principal Investigators will become members of the CounterACT Research Network, and will be able to utilize its resources such as the CounterACT Preclinical Development Facility (CPDF) (see below). They will be expected to participate in annual meetings of the national CounterACT Research Network to share information and ideas. The CounterACT program at NIH is part of the larger biodefense program at the National Institute of Allergy and Infectious Diseases (NIAID) that includes biological and radiation/nuclear threats (http://www3.niaid.nih.gov/topics/BiodefenseRelated/). Also see www.medicalcountermeasures.gov which facilitates communication between federal government agencies and public stakeholders to enhance the Nation's public health emergency preparedness.

Examples of Threat Agents

The civilian chemical threat spectrum includes chemical warfare agents, and toxic industrial chemicals, pesticides, toxins and other chemicals. The following is a list of examples of chemical threat agents based on their primary target tissue and physiological effects:

• Anticholinesterase and GABA-inhibiting agents that cause seizures and neuropathology such as sarin, VX, soman, parathion, phosphamidon, aldicarb, picrotoxin, and tetramine (TETS);
• Metabolic poisons and agents that target the blood such as cyanide, sodium fluoroacetate, thallium sulfate, arsine, arsenic trioxide, and strychnine
• Agents that target the respiratory tract and cause pulmonary edema such as chlorine, ammonia, phosgene, hydrogen sulfide, phosphine
• Vesicating agents that cause blisters and other skin pathologies such as Lewisite and nitrogen mustard

Chemicals not included on this list may also be eligible. Applicants are strongly urged to contact the Program Officials listed in this FOA to determine if their proposed threat agent or countermeasure is of high enough programmatic priority to be considered for funding under the CounterACT U01 program.

Special Biosafety Certification

Many of the chemical threat agents are extremely hazardous to humans. This FOA will only consider supporting studies deemed safe for research personnel and the environment by appropriate official institutional biosafety review. This must be addressed in the application, including a description of adequate protection and safeguards if required.

Because of the special biosafety concerns with some chemical agents, applicants are encouraged to collaborate with laboratories that are certified to work with restricted chemical agents, such as the US Army Medical Research Institute of Chemical Defense and others. Applicants are strongly encouraged to contact the NINDS program official listed in this FOA for further information on working with restricted chemical agents.

Broad Spectrum Therapeutics

Antidotes that are specific to a chemical will be considered, however, applicants should also consider research on acute effects and pathologies that are common to several chemical threat agents, so that the therapeutics being developed will have a broader spectrum of activity against more than one chemical. Some of these effects include:

• Seizures and excitotoxicity within the nervous system
• Inflammation and oxidative damage within the respiratory track and skin
• Disruption of cellular respiration and oxygenation of the blood

Scope of Research

This FOA will only support translational research. Translational research is the process of applying ideas, insights, and discoveries generated through basic scientific inquiry to the treatment or prevention of human disease. The categories of research supported under this program include but are not limited to:

• Mechanistic research to identify targets for therapeutic development
• Creation and development of screening assays for therapy development. The assay must also be validated and the method of validation well-justified, e.g. appropriate pharmacology, robustness, relevant pathology, etc.
• Creation and validation of animal models of chemical effects on humans. The goal of this research is to develop models of lethality and serious morbidity that can be extrapolated to humans, and the intended use of the model must be for therapeutic development
• Identification of candidate therapeutics using primary or secondary screening efforts
• Development of preliminary proof-of-principle data on the efficacy of candidate therapeutics
• Advanced efficacy studies with appropriate animal models using current Good Laboratory Practices (GLP)
• Preliminary and advanced preclinical research including safety and pharmacokinetic studies with candidate therapeutics
• Clinical studies, including trials, when appropriate

The scope of research covered by this FOA is also described by Technology Readiness Levels (TRLs) for Medical Countermeasure Products listed at https://www.medicalcountermeasures.gov/Integrated_TRLs.aspx. This FOA generally covers research that would produce a medical countermeasure that would be rated at the TRL 3 through TRL 6 at the end of the project period.

Milestones

Each CounterACT U01 application must include clearly stated project milestones. Milestones toward therapeutic intervention are not a description of specific aims and experiments, but rather are discreet goals that create go or no-go decision points in the project that include quantitative success criteria. For examples of acceptable milestones, see http://www.ninds.nih.gov/research/counterterrorism/developing_milestones.htm. Milestones for each year of the project should be listed in the Research Strategy section of the application. Annual milestones may be modified in negotiations with NIH program officials before an initial award is made, and during the review of annual non-competitive renewal applications. Unmet milestones will have a negative impact on the review and approval of these annual renewal applications.

If a specific new therapy has not yet been identified, the proposed translational research should demonstrate a clear path towards identification of a lead compound by the end of the project period. Lead compounds are biologically active compounds or hits where affinity, potency, and selectivity have been established. If the project goals are related to model development, then the model(s) should be fully developed and validated by the end of the project period. Validation includes a demonstration of the model’s predictive value for screening compounds for the desired therapeutic effect. The application should describe in detail how the proposed research will lead to the development of a validated model and/or lead compound, and it should present milestones related to achieving that goal.

Use of the CounterACT Preclinical Development Facility (CPDF)

In order to leverage resources already established by the CounterACT program, applicants may propose preclinical studies to be conducted at the CounterACT Preclinical Development Facility (CPDF) at no cost to the applicant. The types of studies available at this facility include:

• Chemistry and Manufacturing Services
  • Developing and performing analytical methods to characterize therapeutic agents
  • Current GMP (cGMP)-compliant stability studies
  • Synthesis, resynthesis, purchase, or acquisition of reagent grade or clinical grade compounds
  • Develop cGMP-compliant manufacturing processes and procedures
  • Manufacture of pharmaceutical materials in compliance with cGMP regulations in amounts sufficient for preclinical evaluation
  • Formulation and manufacture of 50 g of drug using cGMP to demonstrate cGMP capability in support of an IND application
  • Formulation appropriate for in vivo studies
• Preclinical Safety, Toxicology, and Pharmacodynamics/pharmacokinetics (PD/PK) Services
  • Determination of maximum tolerated dose and no observed effect levels (NOEL)
  • Acute and subchronic toxicity; single and repeated dose toxicity studies
  • Determination of relevant pharmacokinetic/toxicokinetic parameters
  • Bioavailability studies; biotransformation assays conducted in vitro
  • Absorption, distribution, metabolism, and excretion studies
  • Various toxicity studies (e.g. genotoxicity, carcinogenicity, reproductive, cytotoxicity, immunotoxicity)
  • Behavioral pharmacology
  • Cell permeability

Applicants must justify inclusion of these studies as part of a logical and progressive milestone-driven drug development plan. Experimental details of the proposed studies in these categories should not be included in the application. However, each proposed study must be well-justified as an essential component of the overall study plan. The costs of these studies should not be included in the budget of the application. See http://www.ninds.nih.gov/research/counterterrorism/developing_milestones.htm for an example of a milestone that includes studies to be conducted at the CPDF (Example B, Year 5). In order to qualify for including CPDF studies in the application, the following steps must be taken at least six weeks before the application receipt date:

• Step1: Send Specific Aims and Milestones, including those that would require studies to be conducted at the CPDF, to the NINDS Scientific Contact provided in this FOA.
• Step 2: NIH will determine if these studies are within the capabilities of the CPDF.
• Step 3: NIH will send applicant a pre-certification letter that the CPDF has the capabilities to complete the proposed studies.
• Step 4: Applicant must include the letter from NIH with the application.

Alternatively, applicants may choose to conduct these studies in laboratories other than the CPDF. In this case, the costs of these studies should be included in the application budget, if needed.

Research Topic Examples

Specific examples of relevant research topics include but are not limited to those listed below:

• Studies on the special vulnerabilities of pediatric populations and pregnant women as they relate to the development of therapeutics, e.g. acute effects on the developing brain that have long-term effects, the need for therapeutics dosing schedules and routes of administration that are more suitable for children and pregnant women
• Research on the molecular mechanisms of toxicity for the purpose of identifying novel targets, e.g. the mechanisms of nerve agent-induced seizures with respect to temporal and regional changes, roles of cardiac versus neuronal mitochondria in cyanide toxicity, cellular and molecular basis for agent-induced pulmonary edema
• Therapies based on acute toxicity of the chemical threat agent, e.g. development of new and/or improved anticonvulsants, neuroprotectants, new approaches to counteract pulmonary edema, relevant anti-inflammatory drugs, surfactants, antioxidants, the development of better skin and eye protectants
• Research on short- and long-term pathophysiology resulting from sublethal acute exposures to threat agents for the specific and demonstrated purpose of developing medical countermeasures, e.g. neuroprotectants for neurodegeneration and other neurological sequelae, drugs to prevent long-term fibrosis in the lung
• Therapies based on sequestration or inactivation of the chemical agent in vivo, such as stoichiometric or catalytic scavengers, cyanide sulfur donors
• Therapies based on mechanism of action of the threat agent, e.g. reactivation/protection of acetylcholinesterase, preservation of mitochondrial respiration
• Alternate routes of administration for new or approved therapies that would be safe, effective, and easy to administer during a mass casualty scenario, e.g. intranasal and intramuscular routes

Special considerations related to the significance of proposed research:

Because of the urgency in need, and the lengthy time and expense for bringing a new compound to regulatory approval, applicants are encouraged to consider drugs that are already approved by the FDA for other indications. Some of these drugs have been shown to be effective in treating victims of chemical exposures, and in some cases, the length of time to regulatory approval for a new indication may be shorter than for a novel compound. Applicants are urged to contact the Scientific Contacts listed in this FOA for more information related to the FDA, including FDA contacts.

This FOA will only support translational research that is clearly relevant to the development of therapeutics that will enhance our medical response capabilities during an emergency. New medical countermeasures that have no practical use during a mass casualty situation will not be considered. Drugs that are only effective if given prior to chemical insult (pre-treatment), or those that must be given within a very short period (1-15 minutes) after the insult will be of low priority. Because many chemical threats have rapid modes of action, the drug should act rapidly to counter these effects. The ultimate intended use of a drug should be discussed within the application, including timing and route of administration that is consistent with its effective use in an emergency setting. For example, drugs that are only effective when administered intravenously would be of low priority since its use would be impractical in a mass casualty situation. Model development, screening activity and efficacy studies should be designed and justified with these ultimate requirements under consideration.

Special consideration will be given to research relevant to people who are particularly vulnerable, including the young, the elderly, and individuals with pre-existing medical conditions. Pregnant women, infants and children are particularly vulnerable to the effects of chemical agents. Animal models and studies that address these vulnerabilities will be of high priority.

Competitive Renewal Applications

Competitive renewal applications must adhere to special instructions described in the PHS 398 application instructions (see http://grants.nih.gov/grants/funding/phs398/phs398.html). A competitive renewal application must be consistent with the scope of research of this FOA and clearly build upon the scientific advances made during the previous award.

Funding Instrument	Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, scientific or program staff will assist, guide, coordinate, or participate in project activities.
Application Types Allowed	New Renewal Resubmission Revision The OER Glossary and the SF 424 (R&R) Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	The number of awards is contingent upon NIH appropriations, and the submission of a sufficient number of meritorious applications. The participating Institutes intend to commit approximately $6 million per year in Fiscal Years 2012, and 2013 to fund new and/or competing renewal awards.
Award Budget	Budgets for direct costs per year will depend upon specific project requirements. The expected direct cost for individual awards is $300,000-$500,000 per year for most studies within the scope of this FOA.
Award Project Period	A project duration of up to five years may be requested.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

Higher Education Institutions:

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

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American tribal organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

Non-domestic (non-U.S.) Entities (Foreign Organizations) are not eligible to apply, but may be members of consortia headed by U.S. institutions.

Foreign (non-U.S.) components of U.S. Organizations are allowed.

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

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

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.

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

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

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide.

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

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

The letter of intent should be sent to:

David A. Jett, Ph.D.
Program Director, NIH CounterACT Research
National Institutes of Health, NINDS
6001 Executive Blvd.
NSC, Room 2177, MSC 9527
Bethesda, MD 20892-9527
Rockville, MD 20852 (for express/courier service; non-USPS service)
Telephone: 301-496-6035
Email: [email protected]

The forms package associated with this FOA includes all applicable components, mandatory and optional. Please note that some components marked optional in the application package are required for application submission. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate optional components.

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

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

Resource Sharing Plan

Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following modifications:

• 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.

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit in advance of the deadline to ensure they have time to make any application corrections that might be necessary for successful submission.

Organizations must submit applications via Grants.gov, the online portal to find and apply for grants across all Federal agencies. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration.

Applicants are responsible for viewing their application in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

Applications must be submitted electronically following the instructions described in the SF 424 (R&R) Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically.

Important reminders:
All PD/PIs must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF 424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the Central Contractor Registration (CCR). Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review, NIH. Applications that are incomplete will not be reviewed.

Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact NIH program staff at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF 424 (R&R) Application Guide.

Travel

When appropriate, awardees will be expected to collaborate; share novel reagents, assays, and animal models; and share both positive and negative results that would help guide the research and development activities of other CounterACT awardees. These activities will be facilitated by annual meetings of CounterACT investigators. Budgets should include cost for travel to one annual meeting of CounterACT investigators, in addition to other anticipated travel associated with the research.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

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

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

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? Will the proposed therapeutic likely reduce mortality and morbidity during and after emergency events involving the release of chemical threat agents? Will the proposed model or assay have utility for developing a therapeutic relevant to this FOA?

Investigator(s)

Are the PD/PIs, collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?

If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed? Are the proposed project milestones adequate for advancing the goals of the project in a timely manner? Are these milestones described with quantitative success criteria that facilitate go or no-go decisions?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact/priority score, but will not give separate scores for these items.

Protections for Human Subjects

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

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

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed. Are special biosafety precautions for working with highly toxic chemicals adequate? Have all proposed studies been deemed safe for research personnel and the environment by appropriate official institutional biosafety review? If working with chemical warfare agents, are Department of Defense approvals in place?

Resubmissions

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

Renewals

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

Revisions

For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact/priority score.

Applications from Foreign Organizations

Not Applicable

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genome Wide Association Studies (GWAS).

Budget and Period of Support

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

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s)convened by the Center for Scientific Review , in accordance with NIH peer review policy and procedures, using the stated review criteria. Review assignments will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

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

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications . Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:

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

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to the DUNS, CCR Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

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

• Defining objectives and approaches, and to plan, conduct, analyze, and publish results, interpretations, and conclusions of their studies.
• Awardees are responsible for developing and proposing specific milestones toward the development of therapeutics that will be achieved during the project period.
• Awardees agree to participate in the overall NIH research effort to develop medical countermeasures against chemical threats. This participation includes collaboration and consultation with other CounterACT research awardees at annual meetings of the CounterACT Research Network. Collaboration may include sharing of information and research materials.
• Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

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

• An NIH Project Scientist [or Project Coordinator, or Project Collaborator, or Intramural Scientist ] will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
• Each project will have the support of one or more Project Scientists from NIH program staff who are assigned an administrative role for the project and have expertise in the implementation of the CounterACT research program.
• NIH Project Scientists will have substantial scientific-programmatic involvement during conduct of this activity, through technical assistance, advice, and coordination above and beyond normal program stewardship for grants.
• NIH Project Scientists will be responsible for assessing the progress of the projects toward the accomplishment of specified milestones, and for recommending if further funds should be released to the project.
• NIH Project Scientists will facilitate the establishment of contacts and collaborations between awardees of the CounterACT research program and other persons or organizations whose participation will assist with the accomplishment of project goals. These persons or organizations may include the FDA, disease voluntary organizations, pharmaceutical companies, or research organizations that can provide essential services on contract.
• An important part of the CounterACT research program is the coordination of research efforts across different funding mechanisms and research structures, and coordination among efforts aimed at different countermeasures. NIH Project Scientists will have the primary responsibility for this overall coordination.
• Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. The assigned program director may also serve as an NIH Project Scientist.

Areas of Joint Responsibility include:

• None; all responsibilities are divided between awardees and NIH staff as described above.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

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

A final progress report, invention statement, and Financial Status Report are required when an award is relinquished when a recipient changes institutions or when an award is terminated.

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.

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading or navigating forms)
Contact Center Phone: 800-518-4726
Email: [email protected]

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

eRA Commons Help Desk(Questions regarding eRA Commons registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Email: [email protected]

Primary contact for questions concerning the overall CounterACT program or for questions related to the mission of NINDS and its role in the CounterACT program:

David A. Jett, Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-6035
Email: [email protected]

For questions related to the mission of NEI and its role in the CounterACT program:

Houmam Araj, Ph.D.
National Eye Institute (NEI)
Telephone: 301-451-2020
Email: [email protected]

For questions related to the mission of NIAID and its role in the CounterACT program:

Gennady E. Platoff Jr., Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-451-4416
Email: [email protected]

For questions related to the mission of NIAMS and its role in the CounterACT program:

Hung Tseng PhD
National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-496-0810
Email: [email protected]

For questions related to the mission of NICHD and its role in the CounterACT program:

David A. Siegel, M.D.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-594-8670
Email: [email protected]

For questions related to the mission of NIEHS and its role in the CounterACT program:

Elizabeth A. Maull, Ph.D.
National Institute of Environmental Health Sciences (NIEHS)
Telephone: 919-316-4668
Email: [email protected]

For questions related to the mission of NIGMS and its role in the CounterACT program:

Richard T. Okita, Ph.D.
National Institute of General Medical Sciences (NIGMS)
Telephone: 301-594-3827
Email: [email protected]

Jonathan Ivins, Ph.D.
Center for Scientific Review (CSR)
Telephone: 301-594-1245
Email: [email protected]

Denise Chatman
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301- 496-5707
Email: [email protected]

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.