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

This Funding Opportunity Announcement (FOA) is an initiative to support the development of cancer-relevant technologies suitable for use in low- and middle-income countries (LMICs). Specifically, the FOA solicits applications for projects to adapt, apply, and validate existing or emerging technologies into a new generation of user-friendly devices or assays that are affordable in the LMIC setting. These technologies may include imaging, in vitro detection/diagnosis, or treatment of pre-cancerous (pre-neoplastic) or cancerous lesions that are treatable in persons living in LMICs. Strong emphasis is placed on technologies that directly provide or immediately lead to treatment options available in the LMIC setting.

Under the UH2/UH3 phased innovation cooperative agreement award mechanism, applicants responding to this FOA must address both the UH2 exploratory phase and UH3 validation phase. The UH2 phase is a feasibility study to demonstrate technical functionality and clinical potential of the technology/assay/device/treatment for use in LMIC settings by meeting specific performance milestones. The most promising projects will be selected for the UH3 phase for clinical validation.

Projects proposed in response to this FOA will require multidisciplinary efforts to succeed, and, therefore, all applicant teams must include expertise in engineering/assay/treatment development, oncology, global healthcare delivery/in-country expertise, and business development.

Note: Throughout the following text, references to either the LMIC setting or the global health setting refer specifically to target LMIC settings for a proposed technology.

It is estimated that nearly two-thirds of the 7.6 million annual cancer deaths in the world occur in LMICs. Furthermore, the incidence rate of cancer is on the rise in populations of many LMICs, with substantial inequalities in cancer survival rates across the world. Access to cancer prevention, screening, detection, diagnosis, and treatment is a significant challenge in many LMICs, especially in rural areas with limited infrastructure.

Recently developed technologies, such as lab-on-a-chip, mobile health (mHealth), cryotherapy, biosensors, imaging, and spectroscopy have potential for use in LMICs, and recent developments in consumer electronics, microfabrication, cellular phone communications, and hand-held computers further improve their prospects for adaptation into sensitive, low-cost versions suitable for use in remote locations. While many types of cancer are currently not preventable or treatable in low-resource settings, success has been reported for some cancers even in the least developed countries (e.g., Hodgkin lymphoma). Cancers that are amenable to prevention, early detection, and treatment in LMICs include those associated with HPV infection, leukemias, lymphomas, and hepatocellular, cervical, oral-pharyngeal, breast, and colorectal cancers. While treatment of cancer in LMICs is challenging, those treatments that are minimally invasive have higher likelihood to yield successful outcomes. Treatment is also more likely to succeed if the cancer is detected early and still localized. Furthermore, relatively low-cost therapies such as cryotherapy or generic drugs may suffice for cancers that are localized and detected early. Most available technologies for cancer detection or treatment are not suitable for use in low-resource settings due to expense, dependency on extensive medical infrastructure, or both. Furthermore, environmental conditions, such as heat and humidity, pose significant challenges for medical devices in low-resource settings. Additionally, various existing portable technologies and minimally invasive diagnostic/treatment methods might be suitable for low-resource settings. Nonetheless, there is a paucity of data on the application and effectiveness of such approaches. This situation warrants translational efforts to develop appropriate technologies that could help improve treatment of cancers in resource-poor settings.

Applications in response to this FOA must propose to adapt, apply, engineer, and validate existing or emerging technologies or assays into a new generation of technologies and assays for detection, imaging, screening, in vitro diagnosis, or treatment of cancers preventable (e.g., treatment of pre-cancerous (pre-neoplastic) lesions) or treatable in an LMIC.

• Modify an existing assay or device such that it can be used for/is more appropriate for the detection or treatment of targeted cancers in an LMIC.
• Simplify or add new features to a device or assay to enable the device to operate outside a laboratory in an LMIC, e.g., areas in which the people have limited access to electricity.
• Apply existing or emerging technologies that have not been previously used for cancer detection, diagnosis, or treatment in LMICs.
• Perform statistically rigorous validation of the analytical and clinical performance of the device or assay to detect or treat a specific cancer in an LMIC.

Scope

The project must focus on a specific cancer type that is preventable or treatable in the proposed LMIC setting and must show promise to deliver medical utility for improved health outcomes. Suitable technologies/devices/assays/treatments to be proposed for development/adaptation must be based on a working prototype (for new technologies) or an existing device (which will serve as a basis for adaptation) demonstrating general feasibility of the proposed approaches. The demonstration of their usability for a chosen cancer is not a prerequisite for application. After program implementation, the proposed technologies/devices are expected to provide clear clinical utility to the specific LMIC healthcare delivery system. The technology must comply with the applicable regulations and international standards/guidelines [such as Good Laboratory Practice (GLP), Good Manufacturing Practice (GMP), WHO guidelines, FDA Investigational New Drug (IND), FDA Investigational Device Exemption (IDE) or local regulations in LMICs]. Additionally, investigators should demonstrate familiarity with international regulatory requirements.

Note: NCI supports research concerning HIV-associated cancers and applications targeted at this population are within the scope of this announcement.

Note: Drug development is not within the scope of this funding opportunity.

Cancers preventable/treatable in an LMIC Setting:

• Because of the translational nature of this FOA, it is important that proposed technologies be targeted towards preventable or treatable cancers in the proposed LMIC setting. Specifically, cancers must be preventable or treatable within the technical capabilities and resource restrictions of the LMIC.
• Prevention/treatment must also be affordable within the LMIC context.
• Furthermore, cancer epidemiology must be considered in the choice of the cancer to be treated in the proposed LMIC. Additionally, co-infections and co-morbidities should be considered where they are appropriate (e.g., applications for work in Sub-Saharan Africa should typically include HIV/AIDS when considering the cancer treatment landscape).

Relevant technologies include but are not limited to:

• In vitro diagnostic assays or technologies: Point-of-Care analytical tools for complex samples such as blood, saliva, or urine (e.g., lab-on-a-chip and biosensors that allow the performance of relevant chemical and/or biological assays outside of laboratory environments);
• Imaging technologies for cancer detection/diagnosis (e.g., optical imaging, spectroscopy, and ultrasound);
• Treatment-related technologies: any type of treatment modality as well as technologies/devices that may aid/facilitate standard treatment modalities. In particular, tools for various, potentially portable, minimally invasive treatment methods are appropriate, including, but not limited to surgical devices, technologies related to drugs/vaccines/chemotherapy/immunotherapy, and tools for cryotherapy and laser therapy, radiofrequency ablation, low-power-density sonication, high-intensity focused ultrasound, and photodynamic therapy.
• Note: The proposed technology may be lab-based, where appropriate. In this case, it is incumbent upon the applicant to address the availability of the lab equipment required, affordability and stability of reagents, and the technical expertise of local staff.

General Technology Characteristics

To the extent possible, the proposed assays or technologies should be:

• Usable for patient management in LMIC local conditions;
• Non-invasive or minimally-invasive;
• Low cost (meaning that the cost of a test/treatment should be comparable to, or lower than, e.g., the local median daily income, the local cost of HIV medication dose, or the local cost of HPV immunization).
• Further, devices/technologies should be affordable in the local setting and, where there are existing technologies supported by non-governmental organizations, charities, and development agencies for similar or related applications, the proposed technologies should be comparable in price.
• User friendly: the device, technology, or assay must be suitable for use in the chosen setting by caregivers receiving local training in its operation and maintenance.
• The proposed technology should represent the state-of-the-art in terms of comparable technologies available in the global health setting and should be of similar or lower-cost.

Specific Required Attributes

a) Portable;
b) Operable in locations with limited or no medical infrastructure (e.g., limited access to electricity, landline communication, refrigeration, or central water supply);
c) Manufacturable at low cost and with low-cost disposables;
d) Simple to operate by locally trained healthcare staff;
e) Rapid results (for diagnostic technologies);
f) Sustainable and affordable by local providers (either low enough in cost to easily replace, easily replaceable parts/ease of repair, or durability)

Specific Desirable Attributes

a) Connectivity to the internet or telephone network (e.g., to allow for telemedicine);
b) Modular design to increase reliability ease-of-use, and to simply maintenance;
c) Incorporation of internal checks of device/assay performance, self-calibration, and error diagnosis;
d) Open source hardware or software;
e) Standard readily available off-the-shelf components, such as power supplies, software, cell phones, or approved imaging probes;
f) Widely used assay formats.

Device Pre-requisites and Preliminary Data

The applicants must have a working prototype or an existing assay/device (not necessarily already used for cancer applications) and preliminary data to demonstrate its potential for detection, diagnosis, or treatment of a cancer in LMIC settings.

Clinical Validation Studies in LMICs

All the projects must include appropriate clinical studies to validate the use and benefits of the technology/device/assay/treatment and establish the device’s potential clinical utility in the targeted low-resource environments. The validation studies required for the second phase of the projects must be conducted in LMICs.

Two-phase Projects

Initial cooperative agreement awards will be granted for an exploratory (UH2) phase to demonstrate technical functionality and clinical potential in cancer-specific applications. The most promising projects will be selected for transition to the validation (UH3) phase of the award. The primary focus of the UH3 phase is to conduct appropriate validation trials in LMICs.

Objectives for UH2 Exploratory Phase:

During the UH2 phase, the investigators are to adapt, apply, and/or engineer an existing prototype or existing device/assay/treatment for use in a low-resource setting. Applicants will have to demonstrate the analytical and clinical performance of the assay or technology for cancer, as well as its potential suitability for use in a low-resource setting. The investigators must also address business aspects that cover manufacturing, regulatory requirements, and dissemination.

The UH2 phase will focus on two main aspects:

• Adaptation if needed and testing of the assay/device/treatment to demonstrate that its analytical and clinical performance is comparable to a currently used technology;
• Steps to ensure that the assay or device will be ready to be tested in an LMIC (it is not necessary that the device incorporate all attributes described above in technical scope or tested in LMICs).

Other expectations for the UH2 phase include:

• Demonstration of a working relationship with local LMIC site(s);
• Updatsed business plan based on UH2 phase experience;
• Updated validation study design;
• Identification of a clinical research network to conduct the validation studies;
• Plans for potential regulatory approval for UH3 validation study.

Note: The goal of this work is translational in nature, rather than speculative. Therefore, if a detection application relies on novel biomarkers, these biomarkers should have been previously validated or currently in use in clinical setting for the cancer in question.

Transition from UH2 to UH3:

After administrative review by NCI and NIBIB program staff (with consultation with External Scientific Consultants [ESC] if needed), successful UH2 projects will be prioritized for selection and transition to UH3 funding.

Criteria used to determine which UH2 projects will be continued into the UH3 phase include the following:

• Successful achievement of specifications defined in milestones for the UH2 period of the project;
• Meeting the recruitment goals for testing the assay/device/treatment;
• Analytical and clinical performance of the assay/device/treatment;
• Potential of assay/device/treatment performance;
• Potential for meeting the goals of the initiative;
• Potential of the plan for successful conduct of a clinical validation study in an LMIC, including statistical power to determine the technology's clinical performance, plans for IRB approval, and plans for human subject recruitment (including addressing applicable IDE/IND/local LMIC regulations);
• Availability of funds;
• NCI program priorities;

Objectives for UH3 Validation Phase:

The goal of the UH3 phase is to optimize the assay/device/treatment if needed and to validate the clinical usefulness in an LMIC setting.

Expected outcomes for UH3 phase include:

• Completion of any additional engineering, development and optimization required to test the assay/device/treatment in an LMIC;
• Incorporation of the attributes described in technical scope;
• Adequate accrual of patients with real-time review of quality control (QC) and endpoint data;
• Completion of the validation trial;
• Demonstration of performance, effectiveness, and promise of the validated technology for clinical utility;
• Updated business plan for production, premarketing, commercialization, distribution, and maintenance of assay/devices;
• Updated training plan for health care delivery users, to help assure progression toward clinical utility and benefit from the validated technology;
• Plans for completion of regulatory approval, and deployment for clinical use in the LMIC site or sites.
• Report on the sustainability/durability of the device/assay in the low-cost environment.

Trans-network Interactions and Program Governance

The awardees supported under this FOA will be required to be members of a Steering Committee (for details, see Section VI.2. Cooperative Agreement Terms and Conditions of Award).

NCI will hold a pre-application informational webinar for this FOA. Date, time, and other details will be posted at: http://www.cancer.gov/aboutnci/organization/global-health/events

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.

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

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

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

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

In addition, the NIH will not accept a resubmission (A1) application that is submitted later than 37 months after submission of the new (A0) application that it follows. The NIH will accept 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, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

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

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:

Paul Pearlman, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-5810
Fax: 240.276.5820
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:

• For this specific FOA, the Research Strategy section is limited to 30 pages. This total page limit can be divided into UH2 and UH3 phases as applicants deem appropriate.

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. Additional instructions are defined below.

Facilities and Other Resources: This should include a description of the proposed LMIC site (its clinical capabilities to treat the cancer and how use of the proposed technology comports with its cultural sensitivities);

All instructions in the SF424 (R&R) Application Guide must be followed. The expertise of the team should include the following areas:

• Engineering/assay/treatment development: Expertise relevant to the development of technologies, assays or devices to ensure their suitability for use in an LMIC;
• Oncology: Expertise in cancer detection/diagnosis and/or treatment is required to ensure the assay/device/treatment will show clinical effectiveness for screening, early detection or diagnosis, and treatment of cancers that can be locally managed or treated in an LMIC setting;
• Global healthcare delivery: Expertise in global health care delivery is required to establish collaborations with health care workers in the local sites for validation and utilization of the assay or device. In addition, expertise is needed to assure cultural appropriateness of the overall project with respect to patient expectations, health care worker training, and deployment and acceptance of the assay/device/treatment.
• Business Development: An industrial partner is required to provide expertise in fabrication, help with governmental regulatory approvals including in-country regulatory expertise, and prepare, disseminate, and sustain the technology for clinical use.

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

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

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

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

Specific Aims: Provide the overall goals for the entire application and indicate Specific Aims to be accomplished in the UH2 phase and in the UH3 phase.

Research Strategy: Organize the Research Strategy in the subsections identified below.

1) Background and Significance

• Define the cancer problem to be addressed, including type(s) of cancer targeted;
• Outline the proposed technology/assay/device/treatment and its potential to improve cancer treatment for people living in LMICs.

2) Preliminary Data

• Describe the technology/assay/device/treatment to be developed, as new or adapted from existing ones, by addressing diverse aspects of cancer detection/diagnosis (using imaging as well as non-imaging approaches) or cancer treatment and how the proposed technology would be tested;
• Summarize preliminary data documenting the proposed technology s potential to achieve both analytical and clinical sensitivity and specificity comparable to a currently used technology;
• Describe its potential for fast, low-cost, and accurate detection, diagnosis, and/or treatment of a preventable or treatable cancer at an affordable cost in a low-resource setting.

3) Activities and Management of the Investigator Team in an LMIC setting

• Describe how collaborations will be set up between health care workers and hospitals, medical schools, charities, local governments, community groups, Non-Governmental Organizations (NGOs), and governmental entities with expertise in the local setting;
• Describe the processes for validation, utilization, and acceptance of the treatment. assay or device;
• Describe the process of dissemination and sustaining the technology for clinical use.

4) Approach divided in two parts corresponding to the UH2 and UH3 phases:

UH2 exploratory phase - address each of the items listed below.

• Plans to develop new, or adapt/improve existing, technology/assay/device/treatment for cancer treatment in a low-resource setting. Discuss its deployment potential in terms of costs and operability;
• Plans to test functionality with clinical specimens or patients. (While it is not necessary in the UH2 phase to test the assay/device/treatment in LMICs, data must be generated to show likelihood that it will be usable in an LMIC setting);
• Potential clinical utility (i.e., what clinical problem the assay/device/treatment addresses, how it will solve the clinical problem, and its potential specificity, sensitivity, selectivity, and other key functional parameters);
• Plans to address regulatory issues at the local LMIC site(s), including human subject issues;
• Specific performance milestones to be achieved during the UH2 phase, e.g., analytical and clinical specificity, selectivity, and sensitivity.

Milestones and timeline

A timeline (Gantt chart) including milestones is required. Milestones are goals that create go/no-go decision points in the project and must include clear and quantitative objective criteria for success. Annual milestones should function as indicators of a project's continued progress, thus revealing emergent difficulties, and will be used to evaluate the application not only in peer review but also in consideration of the awarded project for funding of non-competing award years. Milestones should be well-defined in the application. For examples of appropriate milestones, see http://imat.cancer.gov/resources/milestones.asp. Furthermore, timelines must include assessment of progress in both the UH2 and UH3 phases, including specific milestones for progressing from the UH2 phase to the UH3 phase. At the end of the "Approach" section for the UH2 and UH3 subsections, milestones and timelines should be provided under separate headings. The following are particularly important:

a) Provide appropriately detailed (quantitative) criteria by which milestone achievement will be assessed.
b) Provide a detailed timeline for the anticipated attainment of each milestone and the overall goal.
c) Identify any impediments that could require an addendum to the research plan, milestones, or timeline with a discussion of alternative approaches.

UH3 validation phase - address each of the items listed below.

• Plans for any additional engineering or development that might be needed to optimize the assay or device for operability in an LMIC setting, for example by adding desirable attributes;
• Plans to validate the use of the technology in an LMIC;
• Plans for collaborative arrangements with a local entity (hospital, medical school, charity, local government, community group, Non-Governmental Organization, or governmental entity) to test the assay/device/treatment and train local staff;
• Description of a preliminary business plan and industrial participant(s) for fabrication, distribution, sustainability, equipment maintenance, consumable supplies, and premarketing regulatory approvals. This preliminary business plan must specifically address interaction with the health care community in countries where the assay/device/treatment will be tested, and plans for future distribution via NGOs, government agencies, or local assay/device distributors. The business plan must also specifically address sustainability and propose a scenario for technology distribution mechanism. Such a scenario must address the possibility that the investigators may abandon the plans for full commercialization;
• Plans to address regulatory requirements for the use of the assay/device/treatment in an LMIC site;
• Problems and obstacles anticipated for engineering/assay development, clinical, local site, and business aspects;
• Specific performance specifications and milestones to be achieved during the UH3 phase.

Letters of Support: A letter of support from the LMIC clinical site is required and should include information about the organization's technical and clinical expertise and capabilities, which populations are served, other funding sources, plans to deploy the technology in the stated setting, and other relevant information.

Additionally, a letter of support is required attesting to the ability of the global health or business partner’s ability to navigate and experience with navigating the international regulatory environment.

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

• All applications submitted for the January 25, 2015, due date or after are expected to comply with the NIH Genomic Data Sharing Policy as detailed in NOT-OD-14-111, as applicable.
• All applications, regardless of the amount of direct costs requested for any one year, should address a Resource and Data Sharing Plan.

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

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

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

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

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

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

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues.

Important reminders:

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

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

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by NCI. Applications that are incomplete, non-compliant 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.

This FOA is focused on new technologies or modifications of existing technologies that can have a significant impact on cancer detection, diagnosis, monitoring, and treatment in limited resource settings, such as those often encountered in Low- and Middle- Income Countries. Therefore, the potential of the proposed projects to result in a tool useful for a specific cancer-related clinical need of the targeted LMIC and suitable for an LMIC setting is essential and will be a main factor in assessing the overall merit of the applications.

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

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

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

Specific for this FOA: Does the technology proposed address an appropriate cancer problem that is significant in the proposed settings of a given LMIC? What is the potential of the proposed technology to be sufficiently and broadly adopted by local health care providers in the proposed setting? Will the technology offer immediate relief through treatment or lead fairly directly to clinically actionable strategies that would reduce cancer morbidity/mortality in the LMIC setting?

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?

Specific for this FOA: Is the team expertise appropriate and sufficiently diverse to effectively manage the steps necessary to develop and test the technology in the chosen low-resource settings? For example, does the team include appropriate expertise for assay/device/treatment development including engineering, oncology, business, and site-specific global health expertise? What is the likelihood that all the collaborators and partners will work together effectively and complete the proposed technology translation?

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?

Specific for this FOA: How innovative are the proposed approaches in terms of combining low cost (at the manufacturing and operation levels) with functionality and usability in the selected low-resource setting?

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

Specific for this FOA: How coherent is the plan to develop, test, and validate a technology/ assay/device/treatment that has potential for clinical utility in the chosen LMIC setting? What is the likelihood that the described technology will be adapted to specifications appropriate to LMIC settings with clinical performance comparable to medical delivery in high resource settings? How appropriate is the design of the UH3 clinical validation trial (e.g., in terms of sufficient statistical power to assess the clinical effectiveness of the technology)?

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

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

Specific for this FOA: Is the range of proposed collaborations sufficient in terms of including appropriate organizations in the U.S. and the LMIC site? How appropriate is the foreign site in LMIC for the proposed UH3 validation trial? Are the commitments of all partnering institutions sufficient for the conduct of the proposed studies?

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.

Milestones

How well thought out is the overall plan for the progression from UH2 to the UH3 validation phase? Is the sequence of elements/steps in the phased UH2/UH3 project clearly defined, logical, and complete? Are milestones provided for the UH2 and UH3 phases properly objective and quantitative whenever appropriate? Are these milestones well aligned with the specific aims of each phase? How realistic are these milestones and associated timelines? Do the proposed milestones and timelines clearly identify benchmarks for successful completion of the UH2 phase that could serve as a decision point to advance studies to the UH3 phase? Are other critical go/no go decision points and timelines well defined and appropriate?

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

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

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

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

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

Not Applicable

Not Applicable

Not Applicable

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

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

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

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

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

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NCI, 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 on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Cancer Advisory Board. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.
• Priority in funding considerations will be given to technologies that are likely to be sustainable and projects with a high potential for fast, low-cost application in low resource settings.

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

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

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

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

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

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

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

Cooperative Agreement Terms and Conditions of Award

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 (HHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

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

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

• Defining the overall research objectives and approaches of the consortium;
• Determining experimental approaches, designing protocols, setting project milestones, and overseeing the conduct of experiments;
• Overseeing and coordinating the effort of the multi-disciplinary team and participating institutions and ensuring their optimal integration;
• Overseeing the conduct of UH2/UH3 research projects and ensuring their scientific rigor;
• Ensuring compliance with the applicable mandatory regulations (including protection of human subjects) in the U.S. and an LMIC as required by specific research activities;
• Adhering to the NIH policies regarding intellectual property, data release, and other policies that might be established during the course of this activity;
• Submitting twice a year during the UH2 phase and quarterly during the UH3 phase updates on progress and problems in a brief format as agreed upon with the NCI;
• Submitting monthly updates on human subject and accrual reports upon initiation of validation studies;
• Participating as Members of the Steering Committee;
• Implementing guidelines and procedures developed by the Steering Committee;
• Participating in monthly teleconferences with NCI program staff;
• Attending annual Steering Committee meetings organized by the NCI Center for Global Health.

Awardees will retain custody of and have primary rights to the data, technologies, and software developed under these awards, subject to Government rights of access consistent with current HHS, 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:

An NCI Program staff member(s) acting as a Project Scientist(s) will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below. Additional NCI staff members may be designated to have substantial involvement. The NCI Project Scientist(s) and any other substantially involved staff members will not attend peer review meetings of renewal (competing continuation) and/or supplemental applications. If such participation is deemed essential, these individuals will seek NCI waiver according to the NCI procedures for management of conflict of interest.

Additionally, an NCI Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. Some Program Officials may also have substantial programmatic involvement (as Project Scientists/Coordinators). In that case, the individual involved will not attend peer review meetings of renewal (competing continuation) and/or supplemental applications or will seek NCI waiver as stated above.

The main activities of the NCI substantially involved staff members include but are not limited to the following aspects:

• Providing input on experimental and clinical approaches, assisting in designing protocols, and consulting on updates to project milestones;
• Providing advice to the awardees on specific scientific, analytical, and clinical issues;
• Assisting and advising awardees with regard to various regulatory and compliance issues;
• Participating in monthly teleconferences with PDs/PIs to monitor progress and facilitate cooperation;
• Monitoring progress of the projects towards meeting milestones and adherence to the strategic goals of the program;
• Tracking monthly accrual of participants for clinical testing to ensure proper completion of this essential step;
• Participating in the activities of the Steering Committee and the implementation of its guidelines and procedures;
• Stimulating interactions among awardees;
• Attending annual Steering Committee meetings organized by the NCI; and
• Contributing to publications and presentations resulting from the project if appropriate.

NCI reserves the right to terminate or curtail any individual award, including the UH3 phase, if there is insufficient progress towards meeting milestones.

Areas of Joint Responsibility

Steering Committee:

The awardees funded under this FOA will form a Steering Committee.

The Steering Committee will consist of the following voting members:

• PDs/PIs from each cooperative agreement UH2/UH3 award (one vote per award even when multiple PDs/PIs are designated); and
• NCI-assigned Project Scientists, a representative from the NCI Center for Global Health, and a representative from the NCI SBIR Development Center, who will collectively have one vote for the NIH.

The Committee will be chaired by one of the UH2/UH3 PDs/PIs.

Other NIH staff members may participate in the activities of the Committee as needed as non-voting members.

The Steering Committee will be responsible for communication and coordination among funded projects, including sharing ideas, logistics, and solutions to technical issues. When feasible and appropriate, the Steering Committee will seek to establish consensus on platform interoperability in areas such as control software, data analysis, communication protocols, and standard power sources. Other shared advice may include promise of clinical potential, manufacturability, regulatory issues, and deployment into local resource limited settings. The members of the Steering Committee will meet once a year in person and by conference calls as needed.

Panel of External Scientific Consultants:

Panel of External Scientific Consultants will operate as a subcommittee to the Steering Committee, advising the Steering Committee and providing technical expertise to awardees. The members of the panel will be selected by NCI in consultation with the UH2/UH3 awardees to provide independent assessments and recommendations to awardees on the progress. The panel will consist of scientists with relevant expertise who are not participants in any of the cooperative agreement awards resulting from this FOA. The ESC will meet once a year. Part of this meeting may be in conjunction with the Steering Committee meeting to allow members of both groups to interact directly with each other.

Dispute Resolution:

Any disagreements that may arise in scientific and/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 HHS regulation 45 CFR Part 16.

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

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

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

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

eRA 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
Email: [email protected]

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Contact CenterTelephone: 800-518-4726
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Email: [email protected]

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

Paul Pearlman, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-5810
Email: [email protected]

Tiffani Lash, Ph.D.
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Telephone: 301 451-4778
Email: [email protected]

Referral Officer
National Cancer Institute (NCI)
Telephone: 240-276-6390
Email: [email protected]

Silvia Torres
National Cancer Institute (NCI)
Telephone: 240-276-6322
Email: [email protected]

Angelos Bacas
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Telephone: 301-451-4782
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.