CITEC Solicitation 2024 Duplicate 1 - POCTRN

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null CITEC Solicitation 2024 Duplicate 1

Point-of-Care Tools to Improve Detection of Pre-Cancer and Early Cancer in Medically Under-Served Settings

Funding Opportunity

The Center for Innovation and Translation of Point-of-Care Technologies for Equitable Cancer Care (CITEC) seeks to support and accelerate the development and adoption of new technologies to improve the early detection of pre-cancer and cancer in low-resource settings in the US and globally. This solicitation prioritizes support for point-of-care (POC) tests to improve screening, early detection and/or diagnosis of pre-cancers and early cancers that arise in epithelial surfaces in organ sites accessible for early detection, because this is where point-of-care technologies can have the most immediate impact. High-priority organ sites include the uterine cervix, gastrointestinal tract (esophagus, stomach, colon, rectum, anus), and oral cavity. Priority will be given to platform technologies with the potential for more than one organ site.

Funds available     
A total of $150,000 USD is available for 2-3 sub-awards to support improvements to POC technologies for early cancer detection. 

Number of projects anticipated    
CITEC may award $50,000 USD sub-awards with a performance period not to exceed six months or $100,000 USD sub-awards with a performance period not to exceed 12 months.

Clinical Need To Be Addressed     

Cancer is the first or second leading cause of premature death in 134 of 183 countries, and it is estimated that over 35 million new cancer cases will occur in 2050, a 77% increase over the number of cases estimated in 2022 (World Health Organization, 2024). The number of cases is projected to double in countries with low Human Development Index; these countries have the least resources and infrastructure to adequately care for cancer patients. Disparities exist within countries; in the US, racial and ethnic minorities and other medically underserved populations share a disproportionate burden for many types of cancer. Most cancers can be cured if detected early and treated effectively. To reduce premature death, the World Health Organization recommends implementing early cancer detection and prevention programs at the primary care level. Yet, existing tests for early cancer detection are too complex and/or expensive to implement in primary care settings, particularly in medically underserved areas. CITEC is working to identify high-priority clinical needs for POC cancer technologies; to accelerate development of effective, affordable POC technologies to meet these needs; to evaluate and improve the clinical and public health impact of POC technologies in diverse settings; and to train developers and users to create and disseminate more equitable POC technologies. CITEC prioritizes development of POC tests to improve screening, detection, and diagnosis of pre-cancers and early cancers that arise in epithelial tissues accessible for early detection.

Relevant link can be found here.

Representative Clinical Scenarios To Be Addressed

Cervical Cancer: In May 2018, the Director-General of the WHO announced a global call to action to eliminate cervical cancer, underscoring renewed political will to make elimination a reality. It will be impossible to meet WHO goals with existing screening and diagnostic technologies. In high-resource settings, the standard of care includes: 1) cervical screening with cytology and/or HPV testing (Cancer Research UK, 2023; Office on Women’s Health, 2021; 2) diagnosis of screen-positive patients with colposcopy and biopsy; and 3) treatment of precancerous lesions (cervical intraepithelial neoplasia grade 2 (CIN 2) or more severe [CIN2+]) with loop electrosurgical excision procedure (LEEP) (Perkins et al., 2020). This requires three visits, with a need for both pathology services and skilled clinicians at each step. As a result, many women are lost to follow-up and incompletely treated, especially in LMICs. The 2021 WHO guidelines include a Screen & Treat approach, where women are screened with HPV testing and, if positive, directly undergo treatment with ablation (cryotherapy or thermal ablation) or excision with a LEEP without the need for a cervical biopsy and histologic diagnosis (World Health Organization, 2021). This allows for a single-visit approach, decreasing loss to follow-up and obviating the need for gynecology and pathology services, which are often lacking in LMICs. A major limitation is that it results in overtreatment, as the majority (50-70%) of women infected with HPV do not, and will not, have high-grade cervical disease.

The preferred approach in the WHO guidelines is Screen, Triage & Treat, where treatment is based on a positive primary screening test followed by a positive second “triage” test with or without a histologically confirmed diagnosis (World Health Organization, 2021). The WHO suggests HPV genotyping, colposcopy, visual inspection with acetic acid (VIA) or cytology as possible triage tests, with the choice depending on feasibility, training, program quality assurance and local resources (World Health Organization, 2021). Unfortunately, these triage tests are not widely available in many LMICs (Bogdanova et al., 2022) due to cost (HPV genotyping), lack of trained personnel and infrastructure (cytology, colposcopy) and limited patient access due to transportation or financial barriers. Moreover, some of these strategies (e.g., VIA) have limited reproducibility and accuracy. Point-of-care technologies are needed both to improve access to screening and to provide immediate, accurate triage.

Anal Cancer: In the US, the incidence of anal cancer is over 30 times more common in persons living with HIV than in the general population (Colón-López et al., 2018). A compromised immune system makes people living with HIV (PLWH) susceptible to coinfection with HPV in the anal canal, linked to 90% of anal cancer cases (de Martel et al., 2017). The recently published ANCHOR (Anal Cancer/HSIL Outcomes Research) study showed that treatment of anal cancer precursor lesions reduces cancer risk for PLWH (Palefsky et al., 2022), and clinical experts recommend screening with anal cytology and/or HPV testing (Albuquerque et al., 2019). Screen-positive patients are asked to return for a second visit to undergo high-resolution anoscopy (HRA) (Clarke & Wentzensen, 2018). Suspicious areas are biopsied and evaluated by a pathologist. HRA-guided biopsy requires a high degree of expertise; new HRA practitioners take around 200 cases to begin consistently identifying all precancerous lesions (high-grade squamous intraepithelial lesions (HSIL) or anal intraepithelial neoplasia grade 2 or more severe (AIN 2+) (Richel et al., 2014). Patients diagnosed with AIN 2+ return for a third visit to receive treatment. While treatment of anal precancer has been shown to reduce the risk of progression to cancer significantly, the multiple visit approach has led to high patient loss-to-follow-up rates (Fernandez, 2021). A study on the outcomes of an anal cancer-screening program from 2009 to 2019 found that only 58% of patients diagnosed with AIN 2+ returned for treatment (Silvera et al., 2021). Simplifying screening for HPV and early detection of AIN 2+ using point-of-care methods could improve anal cancer prevention. By offering an in vivo diagnosis during HRA, more selective biopsies could be performed. Additionally, the ability to delineate normal from neoplastic mucosa in real-time may facilitate “Screen & Treat” and “Screen, Triage & Treat” approaches, reducing the number of patients lost to follow-up.

Diagnostic Pathology: Histopathology plays a crucial role in early detection and treatment of cancer and precancer. Microscopic examination of cells and tissues is currently the only way to diagnose cancer, and is needed to assess disease severity, help determine and manage treatment plans, and to monitor response to therapy. Despite widespread availability of microscopes, access to diagnostic pathology is limited in many settings, including community hospitals in the rural US and in large portions of LMICs, because of the high cost of equipment (e.g., microtomes and slide stainers) and the need for trained personnel (e.g., histotechnologists and expert pathologists) (Fleming et al., 2016) (Wilson et al., 2018). In one study performed in Pakistan, the average cost of five frozen margins in a patient was reported to be US $75 (Junaid et al., 2013), a cost noted to be out of reach for half the world’s population. Given the shortage of expert pathologists (especially in medically underserved communities), these bottlenecks limit or delay clinical decision-making and eventually treatment, resulting in worse outcomes.

Given its critical importance, it has been recommended that Level 2 pathology labs with histopathology services should be established at all district hospitals in LMICs. Barriers to expanding access to pathology services in low-resource settings include insufficient workforce capacity, inadequate infrastructure, inadequate training programs (Reiche et al., 2021), and insufficient standards and accreditation programs (Wilson et al., 2018). Affordable point-of-care tools to support quality histopathologic diagnosis are needed.

Scope of Projects   

The proposed project must focus on a specific need related to screening or early detection of epithelial pre-cancer or early cancer in a medically underserved setting and must show promise to improve health outcomes. The proposed project may consist of technology development activities including developing and/or refining technology, clinical field testing, establishing test characteristics, obtaining feedback on user steps from end users, evaluating usability, conducting market research on product concepts or prototypes with distributors, implementers, procurement agencies, policy makers or other stakeholders, evaluating test implementation, and assessing feasibility. The application should describe how additional funding and/or targeted expertise from CITEC or other consultants will enable the technology to move forward in the development pathway.

Relevant technologies that will be considered for funding include, but are not limited to, POC technologies that work with non-invasive or minimally invasive samples, POC technologies for in vitro and in vivo imaging, paper-based POC sensors, and/or mobile-based platforms. Qualified projects should be: based on a working prototype or an existing device to be adapted; demonstrate test characteristics compatible with the ReASSURED criteria (Land et al., 2019). 

Expected Technology Maturity

Applicants with a working prototype or an existing assay/device (not necessarily used for the proposed application) and preliminary data to demonstrate its potential for screening or early detection of epithelial cancer in medically underserved settings will have priority. 

Minimum preferred maturity levels in the product development cycle domains of CIMIT's GAITS (Guidance and Impact Tracking System) are:  

  • Technology:  proof of concept (3) or preferably proof of feasibility (4); 
  • Regulatory: proof of concept (3) or preferably proof of feasibility (4); 
  • Marketing/Business: proof of concept (3) or preferably proof of feasibility (4); 
  • Clinical: proof of concept (3) or preferably proof of feasibility (4).

Applicant Eligibility 

Applications from all sources, including domestic or foreign, public or private, and non-profit or for-profit, will be considered. Awards under this solicitation may be made only to NIH-eligible applicants. Details regarding specific requirements can be found in the NIH Grants Policy Statement Part II: Terms and Conditions of the NIH Grant Awards. Foreign parties (governments, universities, corporations, or individuals) will be screened against the various US government-restricted party lists as required by NIH guidelines.

CITEC Resources Available to Awardees

CITEC makes adjunct resources available to awardees and other interested point of care technology researchers. These include: 

  • NIH resources, such as the I-Corps program
  • Access to the Point of Care Technology Resource Network (POCTRN)
  • CITEC Technology Core Support: Access to a network of experts to support the design, fabrication, and rapid optimization of point-of-care imaging technologies, point-of-care molecular sensors, and machine learning based on image analysis strategies appropriate for mobile platforms. Engineering resources to support design, prototyping, technical evaluation, usability assessment, and design for manufacture for a wide variety of POC diagnostic technologies, including POC imaging tools, POC molecular diagnostics, machine‐learning and artificial intelligence‐based algorithm development, and POC mobile technology platforms. In addition, CITEC can provide navigator services to CITEC-funded investigators and develop a tailored package of support for commercialization activities and regulatory support. CITEC Partnerships in Brazil provide a unique mechanism to develop and disseminate technology for use in global markets, including LMICs.
  • CITEC Clinical Core Support: Access to a network of experts in clinical evaluation and translation of tools for cancer screening and early detection, including study design, IRB protocol development, and access to study sites in low-resource settings in the US, Brazil, and Mozambique. The clinical core can provide clinical input and feedback for technology development, optimization, validation, biostatistical expertise for study design and evaluation, pathology expertise for correlation and evaluation, and simulation center support for ex vivo or simulation models.

Expression of Interest

The application form can be accessed here.

Expression of Interest forms, invited full proposal forms, and associated PDF files may be accessed at the link noted above. Only electronic submissions will be accepted. Submissions must be time-stamped by the submission system prior to or at the cut-off date and time listed in the timeline. Please note that all deadlines are in Eastern Time (ET). The Center will not consider proposals which are in the process of submission but not yet submitted prior to the cut-off and not stamped as received in time. Information that is relevant to your organization’s intellectual property should be marked “Business Sensitive” or “Proprietary.” Classified information or markings such as the word “Sensitive” alone must not be used in any part of the submission.

Expression of Interest Review Criteria

  • Has achieved target maturity level based on GAITS criteria 
    • development of a prototype(s) 
    • supportive experimental results 
    • institutional IP disclosure
  • Innovation /novelty of the approach 

EOIs determined to meet the requirements outlined in this solicitation will be recommended for full proposals in order to elaborate on the proposed POCT solution.

The deadline for this opportunity has passed.