HHS SBIR RFA-DE-15-002

The high demand for improved rapid tests and POC diagnostics for oral infections and cancers is driven by the burden of oral diseases globally.  To improve patient care and stem disease epidemics, there is a need to bring rapid, robust and highly accurate diagnosis to all at risk populations.  Enhanced diagnostics could save, extend and improve lives.  Nevertheless, early diagnosis and rapid treatment initiation face challenges due to the lack of clinical diagnostic tools with better sensitivity and specificity than those currently available.  The goal of this SBIR FOA is to support research to develop the next-generation of rapid tests and POC diagnostic devices.  These tools must use oral biospecimens for detecting oral pathogens and biomarkers of associated oral diseases, for screening, monitoring and diagnosing these diseases, including those linked to HIV/AIDS.  The ultimate goal is to produce highly reliable, reproducible, specific and sensitive tools.  These new methods must demonstrate superior technical performance compared with current technologies while not increasing costs and minimizing the invasiveness of specimen collection from patients.  Specifically, this FOA will stimulate research to:

• Develop, optimize and validate the next-generation of rapid tests and POC devices for oral pathogen detection, to serve purposes of primary or confirmatory screening, monitoring disease progression, or diagnosing oral diseases caused by oral viruses, bacteria and fungi
• Develop, optimize and validate POC devices for clinical diagnosis of oral diseases in resource-limited settings without the use of adjunctive laboratory equipment
• Focus on diagnostic technologies that can detect more than one oral pathogen at a time
• Utilize optimal visual formats for unambiguous test results that are reliably transferred electronically to central databases, and that use the appropriate controls
• Develop tests to: a) measure HIV persistence and residual reservoirs in oral cells from HIV infected individuals under antiretroviral therapy; and b) distinguish and quantify changes between replication-competent HIV and integrated provirus in oral cells 

The expected outcome of this initiative will be the production of the next-generation of oral biospecimen-based rapid tests and POC devices for detecting oral pathogens and biomarkers of associated diseases to facilitate screening, monitoring, or diagnosing oral diseases, including those associated with HIV/AIDS.

Prompt clinical care in oral medicine relies on early disease diagnosis that is often based on the detection of an etiological agent, or disease biomarker present in an oral biospecimen.  Diagnostic tests that have additional clinical utility would be simple and robust enough to detect diseases outside of traditional healthcare settings.  Such tests could be administered in resource poor places where populations gather and could be effectively screened.  The goal of this FOA is to promote research to improve the sensitivity, specificity and robustness of existing assays.  Its goal also is to create the next generation of methodologies needed to enhance rapid diagnosis, primary or confirmatory screening and monitoring of oral diseases.  This FOA will also support new assays for HIV, including those to detect HIV latency, persistence and reactivation in oral cells as well as its associated oral infectious comorbidities. 

The rapid tests and POC devices that have the greatest clinical utility are those that show the following characteristics:

• Require minimal laboratory equipment and involve few steps and handling
• Represent low costs
• Involve easy to use procedures
• Require noninvasive or minimally invasive collection of oral biospecimens
• Deliver reliable and electronically transferable results promptly and securely
• Have optimized capacity for multiplex detection of oral pathogens and disease biomarkers 

In addition, oral biospecimen-based rapid tests and POC devices offer the advantage of serving special populations such as children and the elderly, or in clinical situations when standard volumes of blood typically used in commercial assays cannot be obtained.

The success of the “test and treat” clinical approach to manage the HIV epidemic depends on the development and application of state-of-the-art emerging technologies.  For example, while substantial advances have been made in developing and applying rapid diagnostic tools for HIV, more progress is needed for equally rapid diagnosis of AIDS-related infectious comorbidities.  Yet, some of these infectious comorbidities such as oral candidiasis, caused by Candida albicans, and HPV-associated oral cancer, seem to persist in some populations regardless of treatment status.  Further, the situation is less clear for the rapid diagnosis of agents such as KSHV, the etiological agent for oral and systemic Kaposi’s sarcoma; EBV, causing Hairy Leukoplakia; and HSV, inducing Oral Ulceration.  For these agents that latently persist in oral cells, pathogen detection is insufficient to diagnose the associated oral diseases.  Therefore, measuring changes in viral load thresholds through rapid tests and POC devices is necessary to quickly tie them with pathology, disease development, clinical manifestations, progression and the subsequent remission upon effective treatment.

This FOA will support research projects that may include, but are not limited to the following:

• Developing rapid diagnostic tests and POC devices that could be used in settings outside the traditional clinic for initial screening and monitoring of pathogens and biomarkers linked to oral diseases
• Applying nanotechnologies that: a) use nanomaterials, microfluidics and chip-based diagnostics; b) include algorithms to perform diverse assays on a single platform; c) improve oral fluid-based assay sensitivity and specificity; d) maximize miniaturization in POC device design; and/or
• e) include high-throughput multiplex detection of pathogens and biomarkers for oral diseases
• Developing novel, rapid tests and POC devices to: a) detect a low copy number of nucleic acids for replication competent pathogens in latently infected oral cells; b) quantify pathogen persistence; and/or c) measure pathogen reactivation in oral reservoirs
• Developing, standardizing and validating rapid diagnostic tools and POC devices to reliably measure oral pathogens and surrogate biomarkers indicative of responses to therapeutic strategies, drug resistance and adherence to treatment

This FOA will NOT support research projects that include the following:

• Projects proposing clinical trials.  Applicants who wish to conduct clinical trials must use the R34 / U01 mechanism under the NIDCR Clinical Trials Program (see http://www.nidcr.nih.gov/Research/DER/ClinicalResearch/ClinTrials.htm)
• Rapid tests and POC devices that propose using non-human oral biospecimens and disease biomarkers to model oral diseases in humans
• Rapid tests and POC devices that do not use oral biospecimens and biomarkers for oral diseases or that the main focus is the clinical diagnosis of systemic diseases in humans
• Tests and POC devices that utilize only biomarkers or surrogate markers of oral diseases without including detection of an oral pathogen