Cancer Detection, Diagnosis, and Treatment Technologies for Global Health (UG3/UH3)

Cancer Detection, Diagnosis, and Treatment Technologies for Global Health (UG3/UH3) is sponsored by National Institutes of Health (NIH). Supports the development of innovative technologies for cancer detection, diagnosis, and treatment in low-resource settings.

Expired RFA-CA-15-024: Cancer Detection, Diagnosis, and Treatment Technologies for Global Health (UG3/UH3) This notice has expired. Check the NIH Guide for active opportunities and notices. Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) of Participating Organizations National Cancer Institute ( NCI ) National Institute of Biomedical Imaging and Bioengineering ( NIBIB ) Funding Opportunity Title Cancer Detection, Diagnosis, and Treatment Technologies for Global Health (UG3/UH3) UG3 / UH3 Phase Innovation Awards Cooperative Agreement NOT-OD-16-004 - NIH & AHRQ Announce Upcoming Changes to Policies, Instructions and Forms for 2016 Grant Applications (November 18, 2015) NOT-OD-16-006 - Simplification of the Vertebrate Animals Section of NIH Grant Applications and Contract Proposals NOT-OD-16-011 - Implementing Rigor and Transparency in NIH & AHRQ Research Grant Applications Funding Opportunity Announcement (FOA) Number Companion Funding Opportunity Additional Information on Eligibility .

Catalog of Federal Domestic Assistance (CFDA) Number(s) Funding Opportunity Purpose This Funding Opportunity Announcement (FOA) supports 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, low-cost technologies for imaging, detecting, diagnosing, preventing, and/or treating cancers in humans living UG3 applicants should have a working assay or device prototype (not necessarily already capable of cancer applications).

The initial UG3 exploratory phase will be a feasibility study to demonstrate technical functionality and clinical potential for use of the device or assay in LMIC settings by meeting specific performance milestones. UG3 projects that have met their milestones will be administratively considered by NCI and prioritized for transition to the UH3 validation phase.

UH3 awards will support improvements and validations of the technologies in the LMIC settings. Projects proposed in response to this FOA will require multidisciplinary efforts to succeed; therefore, all applicant teams must include expertise in engineering/assay/treatment development, oncology, global healthcare delivery, and business development.

Investigators responding to this FOA must address both the UG3 and UH3 Open Date (Earliest Submission Date) Letter of Intent Due Date(s) February 9, 2016, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on this date.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date. AIDS Application Due Date(s) February 9, 2016, by 5:00 PM local time of applicant organization. All types of AIDS and AIDS-related applications allowed for this funding opportunity announcement are due on this date.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date. Required Application Instructions It is critical that applicants follow the instructions in (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 I. Funding Opportunity Description Section II. Award Information Section III.

Eligibility Information Section IV. Application and Submission Section V. Application Review Information Section VI.

Award Administration Information Section VII. Agency Contacts Section VIII. Other Information Full Text of Announcement Section I.

Funding Opportunity Description This Funding Opportunity Announcement (FOA) supports 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 cancer-relevant technologies into a new generation of user-friendly technologies that are practical and 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 UG3/UH3 phased innovation cooperative agreement award mechanism, applicants responding to this FOA must address both the UG3 exploratory phase and the UH3 validation phase. The UG3 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, it is encouraged that all applicant teams have expertise in engineering/assay/treatment development, oncology, global healthcare delivery/in-country expertise, and business 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 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.

Many leading edge, innovative technologies, such as lab-on-a-chip, mobile health (mHealth) solutions, cryotherapy, biosensors, imaging, and spectroscopy have potential for use in LMICs. 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. 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 patients in LMICs is challenging, those treatments that are minimally invasive have higher likelihood to yield successful outcomes. Treatment of patients 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 or dust and dirt, 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 detecting, imaging, screening, diagnosing, or treatment of cancers preventable (e.g., treatment of pre-cancerous (pre-neoplastic) lesions) or treatable in an LMIC.

Applicants may propose to: 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 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; and/or Perform statistically rigorous validation of the analytical and clinical performance of the device or assay to detect or treat a specific 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 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 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.

Note: NCI supports research concerning HIV-associated cancers and applications targeted at this population are within the scope of this announcement. 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 Prevention/treatment must also be affordable within the LMIC 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 In vitro diagnostic assays or technologies: Point-of-Care analytics 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 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 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 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 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 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; 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 detecting, diagnosing, and/or treating cancer in people 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.

Initial cooperative agreement awards will be granted for an exploratory (UG3) phase to demonstrate technical functionality and clinical potential in cancer-specific applications. The most promising projects will be may be approved for transition to the validation (UH3) phase of the award.

The primary focus of the UH3 phase is to conduct appropriate validation trials in Objectives for UG3 Exploratory Phase: During the UG3 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.

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).

expectations for the UG3 phase include: Demonstration of a working relationship with the local LMIC site(s) where UH3 study will take place; Updated business plan based on UG3 phase experience; Updated validation study design; Identification of a clinical research network to conduct the 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 be currently in use in clinical setting for the cancer in question.

Transition from UG3 phase to UH3 phase: After administrative review by NCI program staff (with consultation with External Scientific Consultants [ESC] if needed), successful UG3 projects will be prioritized and may be approved for transition to UH3 funding.

used to determine which UG3 projects will be continued into the UH3 phase Successful achievement of specifications defined in milestones for the UG3 period of the project; Meeting the recruitment goals for testing the Analytical and clinical performance of the 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 Objectives for UH3 Validation Phase: The UH3 phase must include plans to optimize the assay/device/treatment if needed and to validate its clinical usefulness in an 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 healthcare delivery users, to help assure progression toward clinical utility and benefit from the validated 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. 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 ). uncertain as to whether their intended technology development project meets the requirements of this FOA are strongly encouraged to contact the Scientific/Research 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 Section II. Award Information Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement.

Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. Application Types Allowed Glossary and the SF424 (R&R) Application Guide provide details on Funds Available and Anticipated Number of Awards The National Cancer Institute: $3 million, six awards for the UG3 phase.

The number of awards is contingent upon the submission of a sufficient number of meritorious applications. The National Institute of Biomedical Imaging and Bioengineering: $500,000, one award for the UG3 phase. The award is contingent upon the submission of a meritorious application.

Future year amounts will depend on annual appropriations and the number of awards that will be transitioning the UG3 to Issuing IC and partner components intend to commit an estimated total of $3. 5 million to fund seven awards. Applicants may request up to $325,000 direct costs for the UG3 phase per year and up to $650,000 direct costs for the UH3 phase per year.

The proposed project period for the initial development phase (UG3) must not exceed 2 years (but may be shorter). The proposed project period for the second validation phase (UH3) must not exceed 3 years. 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 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 Nonprofits Other Than Institutions of Higher Education Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Nonprofits without 501(c)(3) IRS Status (Other than Institutions For-Profit Organizations (Other than Small Businesses) City or Township Governments Special District Governments Indian/Native American Tribal Governments (Federally Recognized) Indian/Native American Tribal Governments (Other than Federally Eligible Agencies of the Federal Government U.S. Territory or Possession 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 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 Foreign components, as defined in the NIH Grants Policy Statement , are allowed. 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 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 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. 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.

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 must have an active DUNS number and SAM registration in order to complete the 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.

Eligible Individuals (Program Director/Principal 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 This FOA does not require cost sharing as defined in the NIH Grants Policy Statement . 3.

Additional Information on Eligibility 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 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 ). Section IV. Application and Submission Information 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 . 2. Content and Form of Application Submission It is critical that applicants follow the instructions in (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 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 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: National Cancer Institute All page limitations described in the SF424 Application Page Limits must be followed, with the following exceptions or additional For this specific FOA, the Research Strategy for both the UG3 (Phase I) and UH3 (Phase II) combined is limited to 30 pages.

This total page limit can be divided into UG3 and UH3 phases as applicants deem appropriate Instructions for Application Submission The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an All instructions in the SF424 (R&R) Application Guide SF424(R&R) Project/Performance Site Locations All instructions in the SF424 (R&R) Application Guide must SF424(R&R) Other Project Information All instructions in the SF424 (R&R) Application Guide SF424(R&R) Senior/Key Person Profile All instructions in the SF424 (R&R) Application Guide Combined, the multidisciplinary team should have expertise Engineering/assay/treatment development: Expertise relevant to the development of technologies, assays or devices to ensure their suitability 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.

Examples of suitable collaborations in the target country include hospitals, medical schools, charities, local governments, community groups, Non-Governmental Organizations (NGOs), and governmental entities with expertise in the local setting.

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. Additionally, investigators should demonstrate familiarity with international regulatory requirements.

All instructions in the SF424 (R&R) Application Guide All instructions in the SF424 (R&R) Application Guide PHS 398 Cover Page Supplement All instructions in the SF424 (R&R) Application Guide All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions: Aims: Provide the overall goals for the entire application and indicate separately Specific Aims to be accomplished in the UG3 phase and in Strategy: Organize the Research Strategy in the subsections Background and Significance Define the cancer problem to be addressed, including type(s) of Outline the proposed technology/assay/device/treatment and its potential to improve cancer treatment for people living in LMICs.

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.

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. Approach divided in two parts corresponding to the UG3 and UH3 phases: UG3 exploratory phase - address each of the items listed 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 UG3 phase to test the assay/device/treatment in LMICs, data must be generated to show likelihood that it will be usable in 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 Description of the proposed LMIC site, including its clinical capabilities to treat the cancer and how use of the proposed technology comports with its cultural sensitivities.

Plans to address regulatory issues at the local LMIC site(s), including human subject issues. Specific performance milestones to be achieved during the UG3 phase, e.g., analytical and clinical specificity, selectivity, and sensitivity. 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 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 A timeline (Gantt chart) including milestones is required for each phase (UG3/UH3). 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,