Required Application Instructions

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

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

The purpose of this Funding Opportunity Announcement (FOA) is to solicit applications from single institutions and consortia of institutions to participate in the Sustained Release for Antiretroviral Treatment or Prevention (SRATP) of HIV Infection program. Applicants may propose development of either treatment or prevention products containing antiretroviral agents delivered using sustained release delivery platforms (oral, injection, implant, transdermal or direct delivery to HIV target mucosa). The sustained release product(s) developed for treatment should provide a minimum of one week efficacy. The sustained release product(s) developed for prevention should provide a minimum of one month protection. Applications proposing products specifically focused on children, adolescents and/or pregnant women that do not meet the minimum durations of efficacy (above) will be allowed if they are likely to result in significant advances of HIV treatment or prevention for children, adolescents and/or pregnant women. Applicants may propose up to 3 independent Sustained Release Strategies (SRSs). The SRATP application must also contain one each of the following sections: Program Operation Section (POS), Clinical Trial Section (CTS), IND-Enabling Section (IND-ES) and Administrative Coordination Section (ACS). At least one of these sections must include participation by a private sector for-profit or not-for-profit company that is expected to contribute in a positive and significant way to the overall scientific agenda of the SRATP. The overarching objective of the SRATP application should be to advance into Phase 1 clinical testing the best product supported by a SRS during the period of the award. Additional Scientific Projects Sections (SPSs) and Scientific Support Sections (SSSs) that will facilitate the achievement of the SRATP sustained release objectives may be included.

NOTE: While Phase I clinical trials are a required element for the application, this FOA will not support Phase II or III clinical trials nor the production of drug substance or final sustained release products to perform preclinical or clinical studies outside of this award. Applicants are encouraged to seek other sources of support for these activities.

Clinical experience for both the HIV treatment and prevention fields has established that adherence is a significant factor in the success of the HIV treatment regimen and/or the prevention strategy. Effective treatment of HIV-infected individuals requires strict adherence to a multi-component regimen of antiretroviral agents that currently must be taken at least daily for the remainder of a patient’s life. Non-adherence can lead to emergence of drug-resistance and loss of therapeutic effectiveness. Effective prevention requires that the inhibitor be present at the right time, place, duration and concentration to stop HIV transmission and acquisition. Although many factors (social, behavioral and individual preference) can influence adherence, one that is addressable using drug discovery/development tools is the use of drug delivery systems to provide for a longer therapeutic exposure or window of protection, thus lowering the barrier to achievement of consistent use for the infected and/or uninfected individual. The goal of developing safe, effective, well-tolerated and acceptable sustained release formulations/regimens is thus to improve adherence by significantly simplifying dosing requirements while maintaining consistent and effective drug levels in plasma and HIV target tissues (CNS/CSF, semen, lymph nodes, female and male reproductive tracts, gastrointestinal (GI) tract, Gut-associated Lymphoid tissue (GALT), etc.).

The treatment goals can be achieved in part by matching HIV treatment drugs with drug delivery systems designed to enable a minimum of one (1) week efficacy. The prevention goals can be achieved in part by matching inhibitors of HIV transmission/acquisition with drug delivery systems designed to enable a minimum of one (1) month of efficacy.

There are a wide range of drug development systems available as platforms for both systemic and mucosal delivery of antiretrovirals to inhibit HIV replication and/or infection. These delivery systems include systemic delivery strategies such as, but not limited to, oral, implant, injection and transdermal, and direct mucosal delivery strategies including, but not limited to, vaginal and/or rectal quick dissolve or osmotic tablets, films, enemas and suppositories. Within each of these platforms pharmaceutical and formulation science can offer additional options, such as the use of nanotechnology to modify tissue distribution and targeting. Options are further increased by the availability of a wide range of active pharmaceutical ingredients such as small and large chemically-defined antiretrovirals, proteins, peptides, antibodies and gene-silencing techniques. The charge for sustained release drug delivery systems development is then to create strategies that deliver effective drug concentrations for longer periods of time, thereby simplifying drug taking behavior, resulting in increased adherence in order to provide more effective overall treatment and prevention.

The research objectives of the SRATP are to:

• Improve the outcomes of HIV disease treatment through the discovery and evaluation of sustained release products to treat HIV disease, leading to significant and durable improvements in therapy.
• Halt the spread of HIV infection by the development of sustained release prevention strategies, which provide for more durable protection from infection in HIV target tissues.

The scope of work will be the development and testing of either a treatment or a prevention sustained release antiretroviral strategy that allows for continuous delivery of a single or a combination of Active Pharmaceutical Ingredients (API) for a minimum of 1 week or 1 month, respectively. Applications focused on children, adolescents and/or pregnant women may propose a continuous delivery strategy for shorter periods, if this strategy would likely advance the current state of knowledge, licensure and availability for the given agent(s) in children, adolescents and/or pregnant women. In order to achieve these objectives the SRATP will be composed of required and optional sections that when combined result in a coherent and integrated sustained release development program that advances either the treatment or prevention strategy to Phase 1 clinical testing.

The required Sections of a SRATP application are:

Sustained Release Strategy (SRS):

Up to three SRSs can be proposed, and must propose development of either a HIV treatment or prevention sustained release product or strategy. Each SRS will focus on the preclinical development and advancement to clinical testing of a single sustained release product/strategy. Progress will be monitored by the Scientific Advisory Board (SAB) and NIH Project Scientist and used to periodically adjust funding of the award. The SAB and NIH Project Scientist may recommend that individual SRS efforts be ended or reduced based on each SRS s achievement of critical objectives - such as Milestones, a Targeted Product Profile (TPP), or Go/No-Go criteria.

Examples of the types of SRSs that can be proposed are:

• One antiretroviral strategy (single drug or combination of drugs) with different/discrete drug delivery systems, with the aim of identifying the optimal sustained release delivery system for the antiretroviral(s).
• Multiple antiretroviral strategies (each based on a single drug or combination of drugs) with a single sustained release drug delivery system, with the aim of identifying the antiretroviral with the best release profile.
• One or more antiretroviral strategies that are focused on children, adolescents and/or pregnant women.
• Any combination of above, including applications with multiple SRSs of which at least one or more are focused on children, adolescents and/or pregnant women.

Administrative Coordination Section (ACS):

Each application must include an Administrative Coordination Section headed by the contact PDPI that will provide for the overall management, coordination and supervision of the SRATP program. The Administrative Coordination Section will oversee the day-to-day operations of the SRATP.

Program Operation Section (POS):

The POS will provide oversight to the scientific operations and product selection efforts of the SRATP. The POS will describe the work plan or roadmap for the development, testing and advancement of products to Phase I clinical studies. The POS must include a TPP, detailed milestones and Go/ No-Go Selection criteria, a Scientific Advisory Board (SAB) and support of SRATP quality control and oversight activities. The POS may include other activities at the discretion of the PD(s)/PI(s) such as regulatory support, clinical operations, statistical support and other SRATP scientific oversight activities.

Clinical Trial Section (CTS):

The CTS will provide support to the proposed Phase 1 clinical trial to be conducted on the sustained release product derived from the SRS(s). In addition to assessing safety, SRATP Phase 1 clinical trials are required to incorporate assessments of the tolerability and acceptability of the sustained release product and delivery system. Applicants are encouraged to incorporate exploratory endpoints that will further characterize the impact of the sustained release strategy and its active components on HIV target cells and mucosa.

Clinical studies may include HIV positive cohorts, specific at-risk populations, such as children, adolescents, and young adults, pregnant women, post-menopausal women, specific ethnicities, intravenous drug users (IDUs) and alcohol users and abusers when scientifically appropriate and within the scope of the Phase 1 clinical trial.

IND-Enabling Section (IND-ES):

The IND-ES will provide support for the performance of the nonclinical safety studies required to obtain regulatory approval to conduct the Phase 1 clinical trial. The focus of the IND-ES will be to support (oversee, conduct, etc.) the studies required to meet applicable regulatory requirements, e.g. submission of Investigational New Drug (IND), Investigational Device Evaluation (IDE), and New Device Exception (NDE) applications.

The optional Sections of a SRATP application are the Scientific Project and Scientific Support Sections (SPSs and SSSs): The SRATP application may contain up to three additional Scientific Projects and up to three Scientific Support Sections to address critical gaps in the SRATP development plan that cannot be effectively addressed by one of the required Sections. Examples include but are not limited to work that addresses medicinal chemistry, pharmacology, animal efficacy testing, and behavioral/social assessments of the sustained release product. Specific examples of Scientific Projects and Support Sections are performance of in vitro, ex vivo and in vivo screening and testing, centralization of methods for measuring drug device release and performance of analytical test methods to support preclinical and clinical activities.

Industry Partnerships

The SRATP application must include an industrial partner as a significant contributor to the SRATP development strategy. For the purposes of this FOA, industry is broadly defined as for-profit or not-for-profit pharmaceutical, biotechnology, bioengineering, or chemical companies that are large or small, domestic or foreign in origin. Contract Research Organizations (CROs) whose sole role will be providing fee-for-service resources do not meet this Industry Partner requirement.

Industrial partners are expected to contribute in a positive and significant way to the overall scientific agenda of the SRATP. Industry partners may fulfill roles such as application PD(s)/PI(s) (note this includes PD(s)/PI(s) designation on a multiple PD/PI application), or act as key personnel with commensurate time commitments to a Strategy or a Section. Although industry applicants are not required to involve collaborators from academic and/or non-profit research organizations, they are encouraged to include members of these organizations when appropriate to the scope and focus of the application.

NIAID and NIMH Areas of Interest

Development of Sustained Release Formulations for HIV Treatment

• Drug delivery strategies designed to be administered once per week or less frequently
• Studies that investigate the pharmacology of the proposed products in animals to confirm the proposed delivery systems are providing effective drug levels in plasma and if appropriate, target tissues (e.g., CNS/CSF, semen, lymph nodes, GALT).
• State-of-the-science acceptability studies conducted with end-user target populations during pre-clinical development of one or more SRS’s that will directly inform the choice of the specific SRS or product that will advance to Phase 1 clinical testing. Any acceptability research conducted during pre-clinical development should employ state-of-the-science acceptability measures and methods, such as discrete choice experiments and conjoint analysis involving the specific SRSs, examination of product prototypes, or consideration of parallel products in current use.
• Assessments of product acceptability among Phase 1 trial participants through quantitative and qualitative methods. Acceptability assessments in Phase 1 studies are encouraged to measure not only likelihood of future product use, but also likelihood of product use compared to other HIV treatment modalities (e.g., oral formulations), as well as attitudes and perceptions regarding product characteristics, adherence requirements, and side effects. Acceptability research in the Phase 1 trial may further include baseline assessments of behavioral, psychosocial, and contextual factors that may influence product acceptability or adherence in the context of either clinical trial or real-world use.

Development of Sustained Release Formulations for HIV Prevention

• Drug delivery strategies designed to deliver potentially protective doses of single or combination inhibitors by oral, injection, implant, transdermal or direct application to target mucosa once per month or less frequently.
• Development of sustained release drug delivery systems for delivery of prevention modalities that can be characterized as topical microbicides or topical pre-exposure prophylaxis (PrEP) and systemic PrEP.
• Pharmacology (PK or toxicokinetic) studies and modeling of the drug delivery systems in animal models and clinical trials to confirm potentially effective and safe drug levels in male and female genital and GI tissues. Where applicable, Phase 1 clinical trials may include a biopsy determination of Pharmacodynamics (PD) (ex-vivo HIV biopsy challenge model).
• Assessment of the impact of genital and gastrointestinal (GI) applied sustained delivery systems on the micro- and macro- mucosal environment, such work could include alterations in the microbiome, changes in innate and adaptive defenses against HIV infection, modulation of the inflammasome and/or changes in pro-inflammatory mediators and cytokine/chemokine production.
• State-of-the-science acceptability studies conducted with end-user target populations during pre-clinical development of one or more SRS’s that will directly inform the choice of the specific SRS or product that will advance to Phase 1 clinical testing. Any acceptability research conducted during pre-clinical development should employ state-of-the-science acceptability measures and methods, such as discrete choice experiments and conjoint analysis involving the specific SRSs, examination of product prototypes, or consideration of parallel products in current use.
• Assessments of product acceptability among Phase 1 trial participants or their partners through quantitative and qualitative methods. Acceptability assessments in Phase 1 studies are encouraged to measure not only likelihood of future product use, but also likelihood of product use compared to other HIV prevention modalities, as well as attitudes and perceptions regarding product characteristics, adherence requirements, and side effects. Acceptability research in the Phase 1 trial may further include baseline assessments of behavioral, psychosocial, and contextual factors that may influence product acceptability or adherence in the context of either clinical trial or real-world use.

NICHD Areas of Interest

Development of Sustained Release Formulations for HIV treatment or prevention specifically for children, adolescents and young adults and/or pregnant women

• Drug delivery strategies designed to be administered at a schedule less frequent than that of the most conveniently dosed antiretroviral medications currently licensed and available to the specific pediatric age group of interest.
• Development of sustained release formulations for HIV treatment in formulations and/or drug platforms that are appropriate for administration to infants and children, particularly formulations that do not require a cold chain and are not liquids with solid and parenteral dosage forms scaled for the age of the individual, i.e. smaller size or lower volume, respectively.
• Evaluation of sustained release formulations in pregnant animals, including toxicity studies for mother/fetus as well as assessments for teratogenicity.
• Evaluation of sustained release formulations in human reproductive safety studies among women who become pregnant after they have completed use of the drug and have surpassed the defined pharmacokinetic period of drug efficacy but when systemic drug concentrations may still be present at high enough levels to affect the fetus.
• Studies in animals that investigate the pharmacology of the proposed formulations to determine transplacental passage, concentration in amniotic fluid, and passage into breast milk.
• Studies involving the investigation of pharmacologic properties of proposed formulations in animal models to understand the interaction of the formulation with endocrine, physiologic and other biochemical changes experienced among children, adolescent and young adult populations (e.g. effects on reproductive organs, growth, changes in volume of distribution [e.g. due to potential portioning in fat], hormonal effects, potential for unique toxicities [e.g. bone, CNS]).
• Assessments of product acceptability for the SRATP treatment or prevention strategy. This work may include assessments of baseline conditions or practices within children, adolescents and young adults and/or pregnant women that could directly inform on the most acceptable biophysical properties of the SRATP strategy. It is essential for the applicant to demonstrate the relevance and need for these studies within the SRATP.
• Studies to evaluate key pharmacologic interactions of sustained release formulations with agents commonly used by and behaviors typically practiced among adolescent and young adult populations (e.g. contraceptives, alcohol, smoking, illicit substances, erratic eating behaviors).

Applications focusing on or including the following areas will not be considered responsive and will not be reviewed:

• Applications to develop sustained release products for both treatment and prevention products.
• Applications proposing Phase II or III clinical trials.
• Applications focusing on the basic science of HIV transmission/acquisition.
• Applications proposing the production/manufacturing of clinical trial product supplies for trials to be conducted outside the SRATP award.
• Sustained release approaches using intravaginal rings (IVR) or development of new IVRs.
• Sustained release strategies for HIV or Sexually Transmitted Infection (STI) vaccines.
• Further development or testing of the current TMC-278 LA or S/GSK1265744 LAP sustained release formulations. However these formulations may be used as comparator controls in a phase 1 clinical test of the sustained release treatment or prevention strategy developed within this application. Applicants also may propose development of alternative drug delivery systems for these Active Pharmaceutical Ingredients (APIs) that are designed to improve the delivery of the drug(s) and/or address issues such as cold chain requirements, dosing volumes, acceptability, etc.
• Development of multipurpose prevention technologies (MPT) and/or approaches designed to inhibit STIs or be contraceptive.
• Sustained release vaginal products that incorporate a barrier device (male and female condom, diaphragm or cervical cup) as a component of the HIV prevention strategy.
• Sustained release products relying on the administration of unmodified and/or genetically modified cells, bacterial and/ or viruses to release natural and/or recombinant agents that inhibit HIV replication.
• Community and stakeholder surveys and studies designed to provide community or population level assessment of societal or individual attitudes toward theoretical products and/or education to support a proposed introduction of a theoretical drug product.
• Structural and/or behavioral interventions to enhance projected product use or prepare for product roll-out or introduction.

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

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

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

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations
• Non-domestic (non-U.S.) Entities (Foreign Institutions)

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

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

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

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

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

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

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

An investigator may not serve concurrently as the overall PD/PI for more than one SRATP application. However, a PD/PI may serve as senior/key personnel on one or more applications.

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

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

NIH will not accept any application that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for submission:

• To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;
• Of an investigator-initiated application that was originally submitted to an RFA but not paid; or
• Of an application with a changed grant activity code.

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

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

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

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 activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Bruce Sundstrom
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-5045
Email: [email protected]

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed, with the following exceptions or additional requirements:

Research Strategy should consist of the following sub-sections with the indicated page limits:

A. SRATP Overview: one required-12 pages

B. Administrative Coordination Section (ACS): one required-6 pages

C. Program Operation Section (POS): one required-30 pages

D. Sustained Release Strategies (SRS): one required up to three maximum-12 pages each

E. Clinical Trial Section (CTS): one required-12 pages

F. IND-Enabling Section (IND-ES): one required-12 pages

G. Scientific Project Strategies Sections (SPSS): optional, up to three maximum-12 pages each

H. Scientific Support Strategies Sections (SSSS): optional, up to three maximum-6 pages each

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

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

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

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

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

Facilities and Other Resources: For the Scientific Support Section include a description of how the scientific environment in which the service or resource will be conducted contributes to the probability of success (e.g., institutional support, physical resources, and intellectual rapport).

All instructions in the SF424 (R&R) Application Guide must be followed. Each required or optional Section must identify a Senior Key Personnel. For Section B it will be the PD/PI, for sections C-H it can be the PD/PI or another person.

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

• It is recommended that senior key personnel leading required Sections devote a minimum of 2.4 person months per year effort to ensure success of the complex SRATP program. This level of commitment can be all in one activity or a total effort across several activities within a single application. If effort is devoted to multiple activities the level of effort is expected to be commensurate with the direct involvement necessary to ensure successful implementation and management of each Section the applicant participates in.
• Travel funds may be requested for attendance of one scientific meeting per year by the PD(s)/PI(s) and one meeting per year by each senior key personnel.
• Travel funds for the PD(s)/PI(s), other key SRATP personnel, and SAB members to attend a Kick-Off meeting and annual SRATP meetings should be included.
• Applicants that propose Phase I clinical trials or coordination of CRO activities where travel is required for quality oversight or auditing may include additional travel funds within the POS for this activity.
• As part of the POS’s overarching coordination activities, requests for additional travel to visit subcontractor or consortium sites for discussion and planning involved in supplying specific assays or services must be specifically justified. Applicants should provide assurances that the personnel traveling are qualified to conduct proposed audits and quality oversight activities.
• Travel in support of regulatory activities at Phase I clinical trial site(s) may be requested. Travel should be justified and the issues to be addressed at trial sites should be outlined. However, if clinical trial regulatory activities are not included in the POS, then travel funds should be requested.
• Travel for other POS operation activities, such as special meetings of the SAB and visits to U.S. regulatory authorities may also be requested with appropriate justification.
• Travel funds to perform oversight of IND-enabling activities must be clearly identified and justified.
• Funding for the overall administrative efforts should include secretarial, and/or other administrative services, expenses for publications demonstrating collaborative efforts, and communication expenses.
• Applicants are encouraged to identify and budget for staff and a program manager to manage daily operations and communication within the SRATP program.
• Funds for Clinical Trial protocol development and site readiness can be requested for all years of the SRATP award.
• A budget to conduct the Phase 1 trial must be provided for those years the trial is proposed to be conducted.
• Budgets (personnel, statistical support and report writing) for the development of an ICH3 compliant clinical trial final report at the completion of the clinical trial should be requested here.
• It is recognized that the participation and types of personnel needed to support the clinical program may change during the award period. Applicants are advised to commit adequate time to assure protocol development and site preparedness activities are completed in a timely manner, and that the Phase 1 clinical trial support personnel have adequate time commitments. The CTS PD/PI should commit sufficient time for oversight of all aspects of the clinical trial development and conduct.
• The IND-Enabling Section should only request resources needed to enable the required Phase 1 clinical trial, such as safety, toxicology and Chemistry Manufacturing and Control (CMC) studies. Resources should not be requested to support the production of clinical supplies for subsequent trials or support specific studies to support or enable clinical testing beyond Phase 1.

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

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

Specific Aims: List in priority order the broad overarching long-range objectives and goals of the proposed SRATP program. Concisely and realistically describe the hypothesis or hypotheses to be tested.

Research Strategy: The Research Strategy must consist of the following sub-sections uploaded as a single attachment:

A-SRATP Overview

This narrative section summarizes the overall research strategy for the application. The SRATP application should be viewed as a confederation of interrelated research efforts, each capable of standing on its own scientific merit, but complementary to one another. This is an important section for it provides the group of investigators an opportunity to give conceptual wholeness to the overall program by giving a statement of the general problem area and by laying out a broad strategy for attacking the identified problem. As the strategy develops, each required section within the SRATP program should be cited briefly as to its place in the overall scheme. Briefly summarize the special features in the environment and/or resources that make this application strong or unique.

Describe the integration of the overall program, and how it establishes an iterative approach to the developmental problem(s) of producing a single sustained release treatment or prevention product/strategy. If more than one SRS is proposed, broadly outline how the SRSs will use either individual or overarching application TPPs, milestones and Go/No-Go-driven decisions to select a single product in an iterative down selection process, for advancement to Phase 1 clinical testing. If a single SRS is proposed in the application, describe how the TPP, milestones and Go/No-Go-driven decisions will support optimization of the delivery system and API to support moving to clinical testing.

Describe the expertise of the SRATP development team and how this expertise will facilitate the required Sections and overarching objective(s) of the SRATP program.

Describe the private sector involvement. The expertise, activities, other resources and processes that would not otherwise be available to the investigators and their integration into the proposed SRATP program should be discussed.

The specific and overarching objectives of each required or optional Section should be discussed in the context of the TPP(s), proposed milestones, Go/ No-Go decision points and Gantt charts/timelines of the SRATP application.

Overarching SRATP milestones and timelines should be placed at the end of the Overview Research Strategy section and fall within the page limit. Milestones and Go/No-Go decision points should not be a restatement of the application’s Specific Aims or TPP criteria, but a quantifiable description of the outcome of the development process and TPP requirements. Describe plans to address success or failure to achieve milestones and Go/ No-Go criteria and describe how futility will be addressed.

B-Administrative Coordination Section (ACS)

Describe how the Administrative Coordination will oversee SRATP communications, i.e. group meetings, website development, teleconferences, and establish policies for presentations at scientific meetings, and publication of results.

Describe how the Administrative Coordination will oversee the day-to-day administrative operations of the SRATP and provide leadership for the program. Describe and justify staffing of the Administrative Coordination to support its role in SRATP operations. Describe the activities needed to demonstrate its potential for leadership by describing the processes and procedures that enable routine administrative actions and activities. Describe administrative procedures for revising SRATP development plans and addressing delays in meeting Go/ No-Go decision points, milestones, starting animal and/or clinical studies, and how the Administrative Coordination will support SRATP business and scientific operations. Plans for leadership succession, and dispute resolution should be described.

Describe how the Administrative Coordination will organize and support a face-to-face Kick-Off meeting within three months of award and annual meetings thereafter.

Describe how the Administrative Coordination will coordinate internal sharing of information and shipping of reagents.

Describe the formation and operations of the Executive Committee (EC; composed of key SRATP personnel and the assigned Program/Project Officer and the PD/PI). The EC is expected to convene monthly using telecommunication resources for sharing of SRATP progress. Describe how the EC will evaluate progress and overall functioning of the SRATP award and the methods it will use to follow-up on and resolve action items.

The overall contribution of a private sector (industrial), if included in the Administrative Coordination, should be justified and described.

ACS Milestones and timelines should be placed at the end of the ACS Research Strategy section and fall within the page limits. Milestones and Go/No-Go decision points should not be a restatement of the application s Specific Aims or TPP criteria, but a quantifiable description of the outcome of the development process and TPP requirements. Describe plans to address success or failure to achieve milestones and Go/ No-Go criteria and describe how futility will be addressed.

C-Program Operation Section (POS)

Each SRATP application must propose a Program Operation Section (POS) which will be responsible for scientific oversight of the SRATP program. The POS will be composed of both required and optional sections designed to assist in the advancement of the best candidate to Phase I clinical testing.

Describe the sections (required and optional) of the POS and how they will be used to guide product selection to meet the SRATP goals and objectives and provide operational scientific oversight to the SRATP. This oversight will not replace the Administrative Coordination management of day-to-day activities of the SRATP, but will be involved with the scientific prioritization and management of the SRATP selection process. The POS's relevance to the primary theme of the application should be addressed. Describe the conceptual procedures, and analyses to be used to accomplish the Specific Aims of the POS. Describe any innovative approaches to SRATP scientific management and its advantage over existing/other approaches. Describe any novel concepts, approaches, tools, or technologies for the proposed management activities. Discuss the potential difficulties and limitations that may arise as a result of POS oversight, and discuss alternative approaches to address the POS scientific oversight requirements for the proposed SRATP program.

A Targeted Product Profile (TPP) must be proposed and described as an integral part of the POS and SRATP application. The TTP will be the roadmap for achieving the objectives of the SRATP application. Applicants should describe critical minimal attributes of the final product(s) proposed for development within each proposed SRS. A description of how the TPP parameters will be used to facilitate selection of a SRS product for advancement toward clinical testing is required. Potential TPP attributes to describe could be: targeted total sustained release time, delivery/injection/implant volume, pharmacokinetic (PK) maximums and minimums, stability and storage requirements, desirable physical attributes, acceptability and outcomes of required GLP IND-enabling preclinical toxicology studies. Applicants are encouraged to consider cost-of-goods, cold chain requirements and feasibility of GMP production as components of the TPP. If multiple SRSs are proposed a single overarching TPP may be established for the SRATP application or the applicant may choose to create individual TPPs for each SRS.

Describe how the TPP, milestones, Go/ No-Go decisions and other methods used for product selection flow down to the other required sections, and how the TPP(s) will be implemented by SRATP personnel to enable advancement of the product for an application proposing a single SRS or prioritization and selection of the single best product for applications proposing multiple SRSs. Describe how the milestones and Go/ No-Go decision points will be used to identify and quantify both success and failure of candidates at each development decision point. Describe how No-Go decisions will be implemented in the context of candidate down-selection and the selection of final products for advancement into IND-enabling and clinical studies. No-Go plans should also include futility plans for continuation of the SRS selection process and during later stages of development in the IND-ES and CTS. Milestones and Go/No-Go decision points should not be a restatement of the application’s Specific Aims or TPP criteria, but a quantifiable description of the outcome of the development process and TPP requirements. Describe plans and processes to revise and revisit the TPP and its milestones and Go/No-Go criteria during the SRATP award, and how changes in the product election process will be implemented and monitored.

Describe the formation and operations of the Scientific Advisory Board (SAB). The application must not name the proposed members for the SAB, but should describe the expertise that will make up the SAB. The SAB should consist of three or more investigators not affiliated with any of the institutions comprising the SRATP, but who may be collaborators with SRATP investigators and have relevant expertise. Any mix of expertise can be proposed; however, it is recommended that the proposed SAB minimally contain expertise in sustained release drug delivery systems, clinical trial conduct, GLP IND enabling activities and GMP manufacturing. Describe the process for formation of the SAB within three months of award. Describe the processes to engage the SAB in SRATP operations using teleconferences, web-meetings and face-to-face meeting. Describe how recommendations made by the SAB will be implemented, addressing such issues as communication, reporting to the PD/PI and SRATP Executive Committee, voting processes and resolution of disputes.

The POS should house SRATP quality control and oversight activities. The SRATP should be a centralized area responsible for management of CROs and other contract activities. Describe POS quality oversight of GLP, GMP and/or GCP activities. Describe plans for vendor selection of CROs and contract suppliers, which may take the form of on-site audits and direct observations of contracted activities. Plans for CRO audits and on-sight observations of contracted services should be described, if appropriate.

If the POS is proposed to house regulatory, clinical operations, statistical activities and/or other elements essential for the scientific oversight of the SRATP, describe how these functions will be carried out and how they will interact with other elements of the POS and SRATP program. If the personnel committed to these activities are not Key Personnel, their expertise should be described. Additionally the activity should be justified as to its role and contribution to achieving the objective of product selection within the SRS(s) and IND-ES, as well as impact on selection of the final product for clinical testing in the CTS.

Activities included in the POS should not overlap with those proposed for standalone Scientific Sections, Scientific Support Sections or the Administrative Coordination. Activities other than research oversight, e.g. biological or analytical assay support/performance should not be included in the POS.

If the POS has private sector involvement the expertise, activities, other resources and processes that would not otherwise be available to the investigators should be described. The contribution of the private sector (industrial) to the POS should be justified and described.

POS Milestones and timelines should be placed at the end of the POS research strategy section and fall within the page limits. Milestones and Go/No-Go decision points should not be a restatement of the application s Specific Aims or TPP criteria, but a quantifiable description of the outcome of the development process and TPP requirements. Describe plans to address success or failure to achieve milestones and Go/ No-Go criteria and describe how futility will be addressed.

D-Sustained Release Strategies (SRS)

Repeat this section for each of the Sustained Release Strategies. If proposing more than one SRS, identify each of them with a number and title. Each SRS should have designated key personnel.

Each SRATP application must contain at least one SRS. Applicants may propose up to three SRSs. Each SRS is to focus on the development of a separate product. All applications must propose iterative development of the API and sustained release delivery system to select the best candidate for clinical testing. Applications that propose multiple SRSs should establish iterative and cooperative interactions between the SRSs to achieve the selection of the best API and drug delivery system to advance to clinical testing.

Describe how the proposed research will contribute to meeting the SRATP goals and objectives, and explain the rationale for selecting the methods to accomplish the Specific Aims. Each SRS, in addition to stating the biological significance of the research, should address its relevance to the primary theme of the application.

Describe the research design, conceptual procedures, and analyses to be used to accomplish the Specific Aims of the SRS. Describe any new methodology and its advantage over existing methodologies. Describe any novel concepts, approaches, tools, or technologies for the proposed studies. Discuss associations with clinical project(s). Discuss the potential difficulties and limitations of the proposed procedures and alternative approaches to achieve the aims.

Describe the individual research focus of each SRS, and the products it will be developing. Describe how each individual SRS research agenda will be pursued to deliver a product to other Sections, for subsequent development and/or testing. Describe any proposed integration of research activities or commonalities when more than one SRS is proposed that might promote synergy in product development or assist in final product selection. In cases where more than 1 SRS is proposed describe the integration of the individual SRS into a drug development platform that will adequately measure the potential for success or failure of the individual SRP, allowing the identification of a single sustained release treatment or prevention product for advancement to Phase 1 clinical testing.

Describe how the TPP, milestones and Go/No-Go criteria will identify a product for advancement to Phase 1 clinical testing no later than the start of year 5 of the award. When multiple SRSs are proposed, describe how the product to be advanced to clinical testing will be selected using the TPP, milestones and Go/No-Go criteria. Describe how progress in selection of products to advance will be monitored by the Scientific Advisory Board (SAB) and NIH Project Scientist and their guidance used to adjust development activities and internally award activities (funding and effort) as required to achieve objectives.

Describe how the contributions of the other required Sections will help the individual SRS achieve its development objectives.

Describe how the products developed by the SRS will meet the FOA defined requirements for a minimum of 1 week or 1 month sustained release for treatment or prevention, respectively.

Discuss the rationale for the specific drug delivery system(s) and antiretroviral drug(s) to be developed within the SRS. Describe how the targeted product(s) represents an optimal approach to the sustained release product goals of the application.

If the SRP has private sector involvement the expertise, activities, and other resources should be described.

SRS(s) Milestones and timelines should be placed at the end of each SRS Research Strategy section and fall within the page limits. Milestones and Go/No-Go decision points should not be a restatement of the application’s Specific Aims or TPP criteria, but a quantifiable description of the outcome of the development process and TPP requirements. Describe plans to address success or failure to achieve milestones and Go/ No-Go criteria and describe how futility will be addressed.

E-Clinical Trial Section (CTS)

Applicants must propose a Phase 1 clinical trial. Clinical protocol development and site preparedness can start in any year of the award. Initiation of the clinical trial can begin when the SRATP product is ready to advance to clinical testing.

Describe the CTS and how it will meet the SRATP goals and objectives. In addition to stating the biological significance of the research, indicate the CTS’s relevance to the primary theme of the application.

In applications proposing multiple SRS the description and approach to the design of the clinical trial will depend upon the final product /strategy selected for advancement. Therefore the description of the proposed clinical trial should take into account the potential variations in trial conduct that could arise from selection of the final product.

Describe the research design, conceptual procedures, and analyses to be used to accomplish the Specific Aims of the CTS. Describe any novel concepts, approaches, tools, or technologies for the proposed studies. Applicants must propose a Phase 1 clinical trial to be conducted on the treatment or prevention sustained release product identified by the iterative down-selection process of the individual SRPs and other SRATP elements and sections.

Describe the plans for enabling Phase 1 clinical testing. Describe site preparation and protocol development and its timing within the CTS and SRATP program. Discuss the potential difficulties and limitations of the proposed approaches and alternative approaches to achieve the aims. A proposed clinical concept should be included in the application. Provide a description of a protocol to test the TPP identified final product. Describe how proposed safety, PK, PD and acceptability determinations will be incorporated into the trial and how the resulting data will be analyzed. Describe the use of any specific at risk populations or HIV positive cohorts and how their use is justified based on the SRATP development objectives. Describe any unique issues that may be associated with clinical testing of a sustained release formulation/device and how these issues will be dealt with to ensure participant safety and adherence.

Applicants should not propose or depend solely upon the NIAID DAIDS-supported clinical trial networks to perform the proposed SRATP Phase 1 clinical trial as a means to expand the size or scope of the clinical trial allowed in this FOA. If collaborations with DAIDS clinical trial networks are proposed the conduct of the collaborative trial must be the responsibility of the SRATP. In cases of Network collaboration, provide a description of the proposed interactions and responsibility of each party for the trial’s conduct.

Describe any agreements between the SRATP, product sponsors, DAIDS clinical trial networks (only if collaboration is proposed) and/or regulatory authorities that will need to be negotiated, providing timelines for initiating and obtaining agreements. If these agreements are to be negotiated through the POS or Administrative Coordination element, describe the communication that will be required with the CTS to assure timelines and milestones are met. Describe approaches and procedures to identify, address and mitigate administrative delays that may arise during development of these documents.

Describe the resources required to submit a clinical trial report that meets the International Conference on Harmonization (ICH) E3 reporting requirements to the appropriate sponsors, regulatory agency(s) and the NIAID Program Officer at the conclusion of the Phase 1 clinical trial.

If the CTS has private sector involvement the expertise, activities, other resources and processes that would not otherwise be available to the investigators should be described. The contribution of the private sector (industrial) to the CTS should be justified and described.

Phase 1 clinical trials for prevention sustained release products must not be conducted outside the continental United States. Phase 1 clinical trials for treatment sustained release products may be conducted outside the continental United States; in these cases, describe the agreements with other parties that will enable them to assume regulatory sponsorship responsibility for the trial as needed. For all proposed clinical trials describe the foreign clinical site(s) and their qualifications for conducting a clinical trial of a sustained release product.

CTS Milestones and timelines should be placed at the end of the CTS research strategy section and should fall within the page limits. Milestones and Go/No-Go decision points should not be a restatement of the application’s Specific Aims or TPP criteria, but a quantifiable description of the outcome of the development process and TPP requirements. Describe plans to address success or failure to achieve milestones and Go/ No-Go criteria and describe how futility will be addressed.

F-IND-Enabling Section (IND-ES)

The SRATP application must propose a single IND-Enabling Section (IND-ES) with the overarching objective of performing the preclinical toxicology needed to obtain regulatory approval to conduct the Phase 1 clinical trial.

Describe the elements and activities of the IND-ES and how they will be used to guide accomplishment of IND-enabling/supporting safety data. In addition to justifying the study design and performance in the context of FDA requirements, indicate the IND-ES relevance to the primary theme of the application.

Describe the research design, conceptual procedures, and analyses to be used to accomplish the Specific Aims of the IND-ES.

Describe any modifications of FDA required IND-enabling studies that may be required to test the specific delivery systems or antiretroviral candidates and the advantage(s) over existing/standard methodologies/approaches. Describe any novel concepts, approaches, tools, or technologies for the proposed studies. Discuss associations with the CTS. Discuss the potential difficulties and limitations of the proposed procedures.

Describe how the IND-ES will perform the nonclinical safety studies and manufacturing of the clinical trial product required to meet applicable regulatory requirements. Describe the processes by which the IND-ES will assure that it meets applicable United States Pharmacopeia (USP), good laboratory practice (GLP) and good manufacturing practice (GMP) requirements and regulations. ICH Safety guidelines and FDA nonclinical safety study guidance’s can be found at http://www.ich.org/products/guidelines/safety/article/safety-guidelines.html and at http://www.fda.gov/RegulatoryInformation/Guidances/ucm129520.htm, respectively. Applicants are cautioned that development of sustained release products may require referencing other FDA guidance’s and consultation with the FDA.

Describe the proposed IND enabling study order and types of studies including animal species and role in supporting the IND. Relevant regulatory guidance should be cited and used to justify the order and scope of proposed acute and chronic toxicology in rodent and non-rodent models, pharmacology studies [absorption, distribution, metabolism and excretion (ADME)], pharmacokinetic (PK), pharmacodynamic (PD), toxicokinetic (TK) studies, determining of specific organ system toxicology (CNS, dermal [hypersensitivity], cardiovascular and respiratory studies), development of a clinical dosage form (formulation), ISO 10993 compliant extractable/leachable studies from solid-phase delivery devices, reproductive toxicology, genotoxicity, analytical method development/validation and studies to address CMC requirements for the API and its delivery vehicle to be performed by the IND-ES. Applicants are reminded that the FDA does not require animal efficacy model data to support a clinical trial or to enable the IND. If applicants feel this data is essential to their application then animal efficacy studies should be outlined in a Scientific Project.

Describe how the IND-ES will use POS oversight, TPPs, milestones, and Go/ No-Go decisions, as well as specific IND-EC milestones and Go/ No-Go decisions to guide the selection and performance of the IND-enabling safety and toxicology studies. IND-ES individual milestones and Go/No-Go criteria for completion of IND-enabling studies and filing the IND should be compatible with the overarching POS and SRATP milestones and Go/ No-Go decisions. The flow and timing of animal safety and toxicology study conduct should be described in the context of supporting the Phase 1 clinical trial.

Describe how No-Go decisions will be implemented in the context of product selection if multiple SRPs are proposed and how final products for clinical testing will be chosen. For applications proposing a single SRP, describe how the SRP product will advance to the IND-ES and how results from studies may inform on optimizing the product further in the SRP. No-Go plans should also include futility plans for continuation of the SRP selection process and during later stages of development in the IND-ES and CTS.

If plans for quality management and oversight GLP and GMP studies are not described in the PO, they should be discussed and described here. If quality management and oversight GLP and GMP studies are described in the POS, discuss how they will be communicated to and utilized by the IND-ES.

If the IND-ES has private sector involvement the expertise, activities, other resources and processes that would not otherwise be available to the investigators should be described. If included in the POS, the contribution of the private sector (industrial) component to the IND-ES should be justified and described.

IND-ES Milestones and timelines should be placed at the end of the IND-ES research strategy section and should fall within the page limits. Milestones and Go/No-Go decision points should not be a restatement of the application’s Specific Aims or TPP criteria, but a quantifiable description of the outcome of the development process and TPP requirements. Describe plans to address success or failure to achieve milestones and Go/ No-Go criteria and describe how futility will be addressed.

G-Scientific Projects Section (SPS)

Repeat this section for each Scientific Project proposed. If proposing more than one SP, identify each of them with a number and title. Scientific Projects must perform a critical role in the development of the sustained release candidate and are included at the discretion of the applicant. Scientific Projects should be designed to address critical gaps in the SRATP development plan that cannot be effectively addressed by one of the mandatory sections or elements. Scientific Projects cannot be used to circumvent the page limit of any of the required sections.

Describe how the proposed research will contribute to meeting the SRATP and Scientific Project goals and objectives and explain the rationale for selecting the methods to accomplish the Specific Aims. Describe the research design, conceptual procedures, and analyses to be used to accomplish the Specific Aims of the project. Describe any new methodology and its advantage over existing methodologies. Describe any novel concepts, approaches, tools, or technologies for the proposed studies. Discuss associations with clinical project(s). Discuss the potential difficulties and limitations of the proposed procedures and alternative approaches to achieve the aims.

Scientific Projects should be described and justified in the context of the required SRATP Sections and descriptions should demonstrate that they meet a significant need and have a defined role in the development of the sustained release antiretroviral candidate and its delivery system. The activities of Scientific Projects should not overlap with those of another proposed Scientific Project or other SRATP Section. Scientific Projects should be constituted to provide broad-based hypothesis-driven research that supports the efforts of the SRS(s), CTS and/or IND-ES to advance a product to clinical testing.

Since the FDA does not require animal model efficacy for filing an IND, SRATP applicants that incorporate a Scientific Project proposing animal efficacy studies should describe how their proposed studies follow the Program proposed guidelines for animal efficacy studies when being used as a Gateway for justifying feasibility as a clinical candidate. Investigators are strongly encouraged to design animal efficacy studies that: (1) include superiority assessments (selecting best or most potent candidate) with a positive control and/or placebo arm as a comparator, and (2) use sufficient numbers of animals in all groups to allow for powered statistical analysis of study endpoints, similar to those used for human clinical studies. Applicants are cautioned that inclusion of too few animals in groups or failure to adequately justify the number of animals to be used will be assessed by the study section in terms of the animal studies and overall application. Studies in which antiretroviral candidates are delivered in a sustained release drug delivery system without establishing retention of antiviral activity, API stability or release from the delivery vehicle are strongly discouraged. Program encourages inclusion of additional study endpoints such as PK and PD determinations and safety measurements (colposcopy, histology, monitoring of vaginal pH, microflora analysis and/or measurement of adaptive/innate immune factors, etc.) as a means to maximize the information obtained. If a Scientific Project has private sector involvement the private sector (industrial) should be justified and described.

Scientific Projects milestones and timelines should be placed at the end of the SPS Research Strategy section and fall within the page limits. Milestones and Go/No-Go decision points should not be a restatement of the application’s Specific Aims or TPP criteria, but a quantifiable description of the outcome of the development process and TPP requirements. Describe plans to address success or failure to achieve milestones and Go/ No-Go criteria and describe how futility will be addressed.

H-Scientific Support Section (SSS)

Repeat this section for each SSS proposed. If proposing more than one SSS, identify each of them with a number and title and indicate which required or optional section they will support.

The SSS must be well justified and clearly non-duplicative of other services or facilities available to the SRATP investigators. Scientific Support Sections cannot be used to circumvent the page limit of any of the required sections.

Describe how the proposed Scientific Support Section activities will contribute to meeting the SRATP goals and objectives and explain the rationale for selecting the general methods and approaches proposed to accomplish the Specific Aims. In addition, this section should indicate the relevance of the Scientific Support Element to the primary theme of the application.

Describe the Scientific Support Section activities emphasizing their provision of shared resources that do not overlap or duplicate other activities in the SRATP application.

Describe the facilities, techniques, and skills that the core will provide to SRATP activities, and the role of the Scientific Support Section key participants in providing the core’s service to the overall award. A Scientific Support Section should not be created solely for the coordination of SRATP contractual activities (GLP, GMP, etc.); these activities are best coordinated within the POS. If a Scientific Support Section will be responsible for coordinating a contracting activity critical to its operation then it should be described and a justification for the use of contractual resources provided.

If the Scientific Support Section has private sector involvement the contribution of the private sector (industrial) to the Scientific Support Section should be justified and described.

Describe Scientific Support Section specific quantifiable and scientifically justified milestones.

Milestones should be presented via a Gantt chart or equivalent, with associated timelines and identified outcomes. Individual SSS specific milestones and timelines should be placed at the end of the Research Strategy section for each SSS and fall within the page limits. Milestones and Go/No-Go decision points should not be a restatement of the application s Specific Aims or TPP criteria, but a quantifiable description of the outcome of the development process and TPP requirements. Describe plans to address success or failure to achieve milestones and Go/ No-Go criteria and describe how futility will be addressed.

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 modification:

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

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

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

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

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

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

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

This initiative is not subject to intergovernmental review.

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

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

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

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

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

Important reminders:
All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

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

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed.

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

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

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the SRATP program-sections A-H 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 section proposed).

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

Significance

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

Investigator(s)

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

Are the time commitments of the PD(s)/PI(s) and other key personnel to the program appropriate? Does the Program Director(s)/Principal Investigator(s) have the leadership and scientific ability to develop an integrated and focused research program? Will the PD(s)/PI(s) and other key personnel devote adequate time and effort to the program?

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

Are the required Sections (SRS, POS, CTS, IND-ES) integrated in a manner that will allow efficient selection of the optimal lead sustained release strategy for Phase 1 clinical testing? Does the integration of the overall program establish an iterative approach to creating a sustained release treatment or prevention product? Are the Sections appropriate and focused on the common theme? If multiple SRPs are proposed are they focused on identifying an optimal product to advance to clinical testing? Does the private sector (industrial) involvement provide access to expertise, activities, other resources and processes that would not otherwise be available to the investigators? Is the private sector participation well integrated into the program?

TPP, Milestones and Go/ No-Go Criteria

Given the critical nature of the TPP(s), milestones and Go/ No-Go criteria in guiding the development of a sustained release treatment or prevention product, do they represent well-defined goals with quantifiable measures that are appropriate for guiding product development? Is the TPP adequately described and feasible, and are the targeted properties of the proposed sustained release product identified and justified? Do the milestones and Go/No-Go criteria provided in the individual Sections identify quantifiable and achievable outcomes within their proposed time-frame(s)? Are the TPP, milestones and Go/No-Go criteria well-integrated into the hypothesis and Specific Aims of the SRATP application and individual Sections? Is it clear how the research will evolve as milestones and Go/No-Go criteria are met? Are there plans to address failure to achieve milestones or meeting No-Go criteria, and do they incorporate futility assessments? Are there plans to revisit and revise individual and overarching milestones and Go/ No-Go criteria as part of SAB oversight activities?

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?

In cases where subcontracts are proposed for carrying out specific tasks, are the quality/appropriateness of the personnel, facilities and procedures (laboratory methods, work plan and/or quality oversight procedures) adequate?

Reviewers will provide an overall impact score for the individual SECTIONS below (B-H) to reflect an assessment of the likelihood that the Section will contribute in an important way to the success of the SRATP program.

Reviewers will consider each of the review criteria below, as appropriate for the individual SECTION in the determination of merit and will give an overall impact score for each SECTION but will not give separate scores for each criterion.

B-Administrative Coordination Section (ACS)

Are the Administrative Coordination organizational structure and the resources committed adequate to accomplish its SRATP administrative oversight objectives? Does the overall leadership of the SRATP Administrative Coordination have the experience, level of commitment and an established competence in organizing and overseeing a complex program? Are the operational activities of the Administrative Coordination appropriately justified as supporting the various sections? Are the plans for coordination, problem identification and resolution appropriate and the personnel committed to these tasks adequate to support the day-to-day administrative oversight operations of the SRATP? Does the management plan provide for ongoing formal and informal communications within the SRATP? Has an administrative structure been proposed that allows for decisions to be made in the absence of the SRATP Program PD/PI or key person to replace him/her if the need arises? Are the proposed plans, if included here, to manage subcontracts and fee-for-service activities adequate to assess the quality/appropriateness of the facilities, methods and resources to be used? Are the Administrative Coordination milestones and timelines appropriate?

C-Program Operation Section (POS)

Will the proposed POS provide adequate scientific oversight to the SRATP program and facilitate the selection of a sustained release product for clinical testing by the end of the award? Does the required TPP describe the anticipated properties of the sustained release product and do the properties align with the theme of the application in selecting an optimal sustained release treatment or prevention strategy? If other methods (algorithms, decision trees, etc.) are used to illustrate the critical decision points and criteria for the SRATP, do they reflect the TPP description of the product to be developed? Are the types of expertise to be included in the SAB identified and is that expertise appropriate? If regulatory, statistical and/or clinical operations are included in the POS are they well described and do they support the overall scientific operations of the SRATP and the product selection process? Are POS quality control and oversight activities appropriate for oversight of CROs that may be engaged to support the objectives of the SRATP? Are the qualifications, competence, and commitment of the key personnel appropriate?

D-Sustained Release Strategies (SRSs)

Is the proposed research for each proposed SRS critical and justified? In cases where multiple SRSs are proposed are the individual SRSs integrated into a drug development platform that will adequately measure the potential for success or failure of the individual SRS, allowing advancement of the best product to clinical testing? Do the provided plans for sustained release products include targets for duration of at least 1 week for treatment and 1 month for prevention, and do the plans include anticipated problems, addressing how TPP criteria will or will not be met? Is the quality of the relevant facilities and research environment devoted to the SRS appropriate? Are the qualifications, competence, and commitment of the key personnel appropriate? Does each SRS have plans to use the information generated by the Scientific Projects, and/or other Sections to support the SRATP strategy selection process and is the timing of receipt of this information appropriate to assist in the SRS optimization/selection process?

E-Clinical Trial Section (CTS)

Are the resources committed to the CTS adequate to conduct the clinical trial? Does the proposed clinical protocol adequately address the potential safety issues of the sustained release products identified for development, and will the proposed design provide an adequate safety and PK assessment of the product? Are the proposed acceptability studies state of the science, and will the proposed tolerability and acceptability assessments support the development of the proposed SRS? Is the clinical site selected for performance of the clinical trial qualified to conduct the trial, e.g. have the appropriate experience and qualified personnel needed to carry out the proposed trial? If conducting a treatment trial in a foreign site have the applicants properly justified use of the site and described the agreements in place to support the trial? Have the applicants identified plans to submit a clinical trial report that meets the International Conference on Harmonization (ICH) E3 report requirements? Are the facilities and support services provided by the SRS and other Sections adequate to support conduct of the clinical activity? Are the qualifications, competence, and commitment of the CTS key personnel and clinical trial support staff adequate?

F-IND-Enabling Section (IND-ES)

Are the proposed activities of the IND-ES and described performance of nonclinical safety studies adequate for obtaining regulatory approvals to conduct a Phase 1 clinical trial? Are GLP, GMP and GCP requirements adequately met? Do the IND-ES, TPP, milestones and Go/No-Go criteria describe and control the flow and timing of the preclinical safety and toxicology studies needed to enable the proposed clinical trial? Where required, is consultation with regulatory authorities and the SAB and SRATP consultants identified, and are the processes by which their input will be obtained well described and appropriate? Will the composition and proposed expertise of the SAB support the activities of the IND-ES? Are the qualifications, competence, and commitment of the IND-ES leadership appropriate? Are the SRATP personnel, scientific and administrative resources committed to the IND-ES adequate?

G-Scientific Project Section (SPS)

Is the Scientific Project justified in the context of the required Sections and does it meet a significant need and have a defined role in the development of the sustained release product? Is the Scientific Project critical for SRATP success? Is there any scientific or activity overlap between the Scientific Project and other strategies or sections? Are the qualifications, competence, and commitments of the key personnel appropriate? Are the facilities to support the Scientific Project appropriate and adequate? Is this Scientific Project essential to the success of the SRATP?

If this Scientific Project is involved in performing animal efficacy studies, are the studies necessary for the selection and advancement of the sustained release product? Do the proposed studies meet the following FOA guidance for the conduct of an animal efficacy study?

For applications to develop sustained release formulations for HIV treatment do the studies proposed investigate the pharmacology of the proposed products in animals to confirm the proposed delivery systems are providing effective drug levels in plasma and if appropriate, target tissues (e.g., CNS/CSF, semen, lymph nodes, GALT)?

Are proposed pharmacology (PK or toxicokinetic) studies in animal models and clinical trials designed to adequately measure and/or model drug levels in male and female genital and GI tissues, and do the results support proposed safety and efficacy of the drug delivery system?

For applications proposing animal efficacy studies are there sufficient justification and linkage to regulatory guidance for the order and scope of proposed studies?

H-Scientific Support Section (SSS)

Is provision of resources and services for the individual Strategies and Sections critical and justified? Are the milestones of the SSS well-described, quantifiable, and scientifically justified? Is the relationship of a SSS to the central focus of the overall program strong? Are the facilities, techniques, and skills that the SSS will provide to SRATP activities described? Are there criteria for prioritization and usage of SSS resources? Are the qualifications, competence, and commitment of the Support Section key personnel appropriate? Are the facilities appropriate and adequate to support at least two Scientific Sections and/or Strategies? Is the relationship of each SSS to the central focus of the overall SRATP established and well justified? Are the criteria for prioritization and usage of the SSS facilities or services described?

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

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 Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Children

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

Vertebrate Animals

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

Biohazards

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

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

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

Applications from Foreign Organizations

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

Select Agent Research

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

Resource Sharing Plans

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

Budget and Period of Support

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

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

As part of the scientific peer review, all applications:

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

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

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA Following initial peer review, recommended applications will receive a second level of review by the National Advisory Allergy and Infectious Diseases Council. The following will be considered in making funding decisions:

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

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

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

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

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

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

Any application awarded in response to this FOA will be subject to the DUNS, SAM 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:

• The PD(s)/PI(s) retain primary responsibility for the performance of the scientific activity, and understand the role of the Program Officer in the Cooperative Agreement award mechanism as described below.
• The PD(s)/PI(s) will be solely responsible for:
  • planning, directing, and executing the proposed project,
  • organizing, attending and chairing the SRATP Kick-Off, annual meeting and Executive Committee (EC),
  • integrating and implementing the recommendations of the SAB into the SRATP program,
  • assuring compliance of the SRATP Program with all applicable Federal, State, Local, regulations, and all applicable DHHS/NIH/NIAID/DAIDS policies for conduct of research and clinical trials.
• Kick-Off and Annual SRATP Meetings
• ll awardees are required to host a Kick-Off and annual SRATP meeting attended by Scientific key personnel, SAB members, other key SRATP, NICHD, NIMH, and NIAID staff. The PD(s)/PI(s) and other SRATP members shall present for the Kick-Off meeting the proposed TPP, milestones, Go/ No-Go decision points and time lines with the goal of informing and obtaining SAB input on the SRATP immediate plans for oversight and initiation of the research. For annual meetings the PD(s)/PI(s) and other SRATP members shall present: (1) an update on the results achieved for each strategy or section of the SRATP, (2) a review of progress in meeting the TPP and milestones and Go/No-Go criteria within the previous year, (3) discussion of scientific, technical and other problems and obstacles encountered and the methods/approaches proposed or implemented to overcome and/or resolve obstacles and problems, and (4) future plans for achieving remaining milestones, address identified or potential problems that may impede or slow progress, and propose methods/approaches for dealing with such problems, including contingency plans for delays, acceleration of timelines, and/or modifications to established milestones and timelines.
• Phase 1 Clinical Trial
  • In addition to assessing safety, SRATP Phase 1 clinical trials are required to incorporate assessments of the tolerability and acceptability of the delivery system.
  • Applicants are encouraged to familiarize themselves with Division of AIDS Clinical Research Policies, which specify requirements for conducting clinical research under Division of AIDS sponsorship, (http://www3.niaid.nih.gov/research/resources/DAIDSClinRsrch/). Protocols for clinical trials must be reviewed and approved by the appropriate Division of AIDS Sciences Review Committee prior to implementation. In addition, awardees engaged in the conduct of clinical trials will be required to adhere to the NIAID Clinical Terms of Award (http://www.niaid.nih.gov/ncn/pdf/clinterm.pdf),
  • NIAID policy requires that Phase 1 studies be monitored commensurate with the degree of potential risk to study subjects and the complexity of the study. AN UPDATED NIAID policy was published in the NIH Guide on July 8, 2002 and is available at: http://grants.nih.gov/grants/guide/notice-files/NOT-AI-02-032.html. The full policy, including terms and conditions of award, is available at: http://www.niaid.nih.gov/ncn/pdf/clinterm.pdf. All clinical research activities performed outside of the U.S. must, in addition to U.S. Federal regulations, comply with the host country regulations for human subjects,
  • The PD(s)/PI(s) is/are responsible for providing information to the IND holder required FDA annual IND reports, http://www.ich.org/products/guidelines/efficacy/article/efficacy-guidelines.html.
  • The PD(s)/PI(s) is responsible for developing and/or negotiating all clinical trial documents (SOPs, case report forms, regulatory binders, etc.) and legal instruments (Clinical Trial Agreements and other documents required by the FDA or DAIDS Clinical Trial Policies and procedures),
  • At the completion of the trial the PD(s)/PI (s) are responsible for writing and submitting to the proper authorities an ICH Compliant E3 clinical report.
• All activities involving animal research performed outside of the U.S. must, in addition to U.S. Federal Regulations, comply with the host country regulations and the International Guiding Principles for Biomedical Research Involving Animals.
• The PD(s)/PI(s) are responsible for Intellectual Property. The successful development of sustained release drug delivery systems and their associated HIV inhibitors may require substantial investment and support by private sector industries, and may involve collaborations with other organizations such as pharmaceutical companies, academic institutions and/or non-profit research institutions not directly involved in the SRATP. It is the intent of this initiative to encourage the formation of the appropriate public-private partnerships that are essential to meet urgent public health needs. NIAID recognizes that intellectual property rights are likely to play an important role in achieving the goals of this program. To this end, all awardees shall understand and acknowledge the following:
  • The PD(s)/PI(s) and the applicant institution are solely responsible for the timely acquisition of all appropriate proprietary rights, including intellectual property rights, and all materials needed for the applicant to perform the project.
  • Before, during, and subsequent to the award, the U.S. Government is not required to obtain for the awardee any proprietary rights, including intellectual property rights, or any materials needed by the awardee to perform the project.
  • The applicant institution is required to report to the U.S. Government all inventions made in the performance of the project, as specified by 35 U.S.C. Sect. 202 (Bayh-Dole Act).
  • PD(s)/PI(s) are expected to make new information and materials known to the research community in a timely manner through publications, web announcements, reports to the NIAID, and other mechanisms.
• Publications: The PD(s)/PI(s) will be responsible for the timely submission of all abstracts, manuscripts and reviews (co)authored by project investigators and supported in whole or in part under this Cooperative Agreement. The PD(s)/PI(s) and key persons are requested to submit manuscripts to the NIH Project Scientist after acceptance for publication so that an up-to-date summary of program accomplishments can be maintained. Publications and oral presentations of work conducted under this Cooperative Agreement are the responsibility of the PD(s)/PI(s) and appropriate key personnel and will require appropriate acknowledgement of NIH support. Timely publication of major findings is encouraged.
• 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 will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

• During performance of the SRATP award, the NIH Project Scientist will provide appropriate assistance, advice, and guidance by: participating in scheduled meetings and teleconferences that may include, but are not limited to, EC meetings and teleconferences to discuss program coordination and/or progress; participating in Kick-Off and annual meetings and SAB deliberations; participating in the design of the activities; facilitating collaboration with other NIH-supported research resources; and advising in project management and technical performance. The role of the NIH Project Scientist will be to facilitate and not to direct the activities. It is anticipated that the NIH Project Scientist, and other NICHD, NIMH, and NIAID staff identified by the PD(s)/PI(s), the Steering Committee and/or the NIH Project Scientist as having relevant expertise, may be given the opportunity to offer advisory input. The NIH Project Scientist will facilitate liaison activities for partnerships, and provide assistance with access to NIH-supported resources and services.
• Other appropriate NIH program staff assistance will be coordinated by the NIH Project Scientist and may include Medical Officer(s), clinical operations and regulatory staff and other expertise as required. The NIH Project Scientist, with the support of appropriate staff and expertise, will provide coordination and assistance to the awardee to meet the Division of AIDS requirements for clinical protocol content, Sciences Review Committee review and Phase I clinical trial initiation and conduct. NIAID reserves the right to terminate or curtail a clinical trial in the event of (a) substantial shortfall in participant recruitment, follow-up, data reporting, quality control, or other major breach of the protocol, (b) substantive changes in the consensus protocol to which the NIAID does not agree, (c) reaching a major study endpoint substantially before schedule with persuasive statistical significance, or (d) human subject ethical issues that may dictate a premature termination.
• The Government, via the NIH Project Scientist, will have access to data generated under this Cooperative Agreement and may periodically review the data and progress reports. NIAID staff may use information obtained from the data for the preparation of internal reports on the activities of the study. However, awardees will retain custody of and have primary rights to all data developed under these awards.
• The assigned agency program official or IC program director may also serve as an NIH Project Scientist.
• 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.

Areas of Joint Responsibility include:

• Executive Committee (EC)
  • Establish an EC following award of the grant.
  • The EC will be housed in the Coordination Section and support its administrative oversight function for the SRATP. The EC will consist of the designated senior key persons for each Section, the NIH Project Scientist, other NIH scientists as identified by the PD(s)/PI(s) and/or EC, and any other key personnel identified by the PD(s)/PI(s). The EC may add additional members by majority vote, and each full member will have one vote. The NIH Project Scientist will participate in the activities of the EC as required, providing verbal or written responses to the EC or its designated subcommittees upon request.
  • The EC will act to enable and implement policies approved by the EC, and will serve as the main day-to-day administrative governing board of the SRATP Program.
  • The EC will assist the PD(s)/PI(s) in achieving the goals of the SRATP Program, create subcommittees, evaluate progress of the SRATP and make recommendations for achieving milestones and implementing Go/ No-Go decisions. This may include recommending alterations in the level of effort for specific Strategies and/or Sections, such that efforts may be terminated to allow more productive avenues of development to proceed.
  • The EC will assist the PD(s)/PI(s), as required, in implementing SAB recommendations and preparing formal reports summarizing SRATP activities and/or progress as needed. The EC will also advise the NIH Project Scientist on scientific opportunities, emerging needs and impediments.
  • The EC will advise on implementation of the TPP and Milestone and Go/ No-Go decisions. The EC will assist the PD(s)/PI(s) and NIH Project Scientist in prioritization of products and research efforts. The EC will also assist the PD/PI and the CTC in clinical study protocol development and human subject issues as needs arise.
• SRATP Scientific Advisory Board (SAB)
  • The SRATP leadership (Executive Committee and/or PD/PI) will establish an SAB of at least three investigators not affiliated with any of the institutions participating in the SRATP research program. The SAB will be housed in the POC and will assist the SRATP program in the scientific administration of the award.
  • SAB membership will be identified in consultation with the NIH Project Scientist, and the SAB should be constituted promptly following award.
  • The members of the SAB are expected to attend the Kick-Off meeting and one or more of the SRATP annual meetings during the award period. The complete SAB membership is not required to attend all annual meetings, but at least one member of the SAB must attend each annual meeting.
  • The SAB members in attendance at annual meetings will assist in review of the SRATP activities and evaluate progress and assess the continued relevance of each activity to the overall goals of the research program. The SAB may recommend new directions as appropriate and will provide the PD(s)/PI(s) with a comprehensive written evaluation of their recommendations after the annual meeting, if required by the NIH Project Scientist or the PD/PI.
  • For members of the SAB not present at annual meetings the PD/PI will create a summary of the meeting and provide the absent members a list of action items and recommendations of the SAB members in attendance and then facilitate communication of the absent members opinions to the EC and other members of the SAB.
  • The SAB may be called upon to evaluate the overall SRATP or individual progress of the SRP(s), IND-ES and CTS. The SAB may also make recommendations for which products to advance or if required halt development of specific products.
  • The SAB may, at the discretion of the PD/PI and/or NIH Project Scientist, be called upon to evaluate the timing and feasibility of initiating the Phase 1 clinical study.
• The TPP, milestones, Go/No-go decisions, timelines and Gantt charts proposed by the PD(s)/PI(s) shall be referenced in the terms and conditions of award. It is recognized that these may require revision and renegotiation during the project period. The PD(s)/PI(s) and NIAID must agree to all such revisions.

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 annual Non-Competing Progress Report (PHS 2590 or RPPR) and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

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

eRA Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Finding Help Online: http://grants.nih.gov/support/index.html

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

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact CenterTelephone: 800-518-4726

Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: [email protected]

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

NIAID Contact for Treatment:
Steven Turk, Ph.D.
National Institute of Allergy and infectious Diseases (NIAID)
Telephone: 240-627-3092
Email: [email protected]

NIAID Contact for Prevention:

Jim Turpin, Ph.D.
National Institute of Allergy and infectious Diseases (NIAID)
Telephone: 301- 451-2732
Email: [email protected]

NICHD Contact:

Bill Kapogiannis, M.D.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-402-0698
Email: [email protected]

NIMH Contact:

Dr. Michael Stirratt
National Institute of Mental Health (NIMH)
Telephone: 301-443-6802
Email: [email protected]

J. Bruce Sundstrom, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-5045
Email: [email protected]

Devon Bumbray-Quarles
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-2950
Email: [email protected]

Bryan Clark, M.B.A.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6975
Email: [email protected]

Rita Sisco
National Institute of Mental Health (NIMH)
Telephone: 301-443-2805
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.