Non-invasive Diagnostics to Improve Gynecologic Health (R43/R44 - Clinical Trial Optional) Activity Code

Purpose

The purpose of the Non-invasive Diagnostics in Gynecologic Health RFA is to support SBIR projects to small businesses using advanced technologies (e.g., bio-chips, microfluidics, and mobile technologies) to develop novel or improved diagnostic approaches, tools, or devices for endometriosis, adenomyosis, and/or uterine fibroids.

The ultimate goal of the program is to improve human gynecologic health by fostering partnerships between small businesses and experts in diverse fields of research to commercialize approaches that improve accuracy and decrease the delay in diagnosis of the named gynecologic conditions. These projects will also encourage collaborations with investigators and small businesses who have not yet applied their expertise to gynecologic research, thereby expanding the potential scientific insight and investigational toolkit available to these projects. It is anticipated that, through rigorous collaborative R&D efforts, safe and effective techniques, instruments, and devices can be developed for use in the evaluation and diagnosis of women with endometriosis, uterine fibroids, or adenomyosis.

Within the disorders noted above, projects that address a specific and well-characterized clinical need will be considered of high potential impact.  The technologies developed with funding through this FOA are expected to be integrated systems or, if they are novel components, to be easily integrated into existing systems. Some other technical features that are expected are the following: reliability, robustness, safety, simplicity, reliance on the appropriate baseline information, contextual awareness, and inclusion of software to support decision-making where appropriate.  Proposed tools and technologies should incorporate existing standards and consider regulatory requirements where appropriate.  In addition, improved access to underserved areas, and cost-effectiveness should be highlighted.

Background

Created in 2012, the Gynecologic Health and Disease Branch (GHDB) serves as the epicenter of gynecologic research at NIH, with a mission to improve women's health by supporting, encouraging, and framing research and career development programs in gynecologic health and disease. To this end, the GHDB held a Scientific Vision Workshop on May 5-6, 2016. The meeting recognized that emerging imaging techniques and insights into the biology of gynecologic tissues provide opportunities to develop innovative approaches for the early detection and clinical monitoring of gynecologic conditions.  Furthermore, the group noted a gap in the existence of diagnostic tests that are ideally non-invasive, rapid, inexpensive, and widely available, as well as highly sensitive and specific. From this meeting, GHDB identified a high program priority (HPP) to promote the development and/or application of novel imaging methods, biomarkers, and other non-invasive diagnostic tools to gynecologic disorders.

The gynecologic conditions covered by this RFA can severely impact quality of life and are highly prevalent; a majority of women will experience at least one of these conditions in their lives. Detrimental effects of these conditions include abnormal uterine bleeding, pelvic adhesions, chronic pelvic pain, infertility, miscarriage, and preterm labor, as well as substantial psychosocial morbidity including depression. The financial burden of these conditions is very high, with endometriosis and fibroids alone costing the United States between $28-56 billion every year.

Despite the high incidence of these conditions, considerable diagnostic challenges exist. Symptoms can overlap with other conditions, such as dysmenorrhea, irritable bowel syndrome, and pelvic inflammatory disease. Conversely, the conditions may be present in the absence of symptoms. For these and other reasons, there can be a substantial delay (up to 10 years for some conditions) from symptom onset to diagnosis, leading to unnecessarily prolonged patient suffering and greater socioeconomic cost.

Research Scope

This initiative requires that the research projects address areas of research that are directly relevant to any one of the following conditions:

• Fibroids
• Endometriosis
• Adenomyosis

The scope of this RFA includes applied translational and clinical projects that will enable the development of more effective strategies for the diagnosis of the selected gynecologic condition. Project aims that utilize mammalian model systems are acceptable, provided that such studies have a clear path for eventual translation to humans. Of note, approaches that can be used to screen for the absence of these conditions (normal gynecologic function with regard to endometriosis, adenomyosis, and fibroids) are also of interest. Emphasis on early detection is especially encouraged. Additionally, collaboration with investigators and/or small businesses that have not previously applied their expertise to gynecological health research is encouraged.

For the purpose of this FOA, non-invasive procedures will be defined as procedures that do not require incision or contact with a bodily orifice beyond natural orifices. Venipuncture, finger pricks, and transvaginal imaging modalities will be considered responsive to this FOA.

Projects of high priority for this FOA include, but are not limited to:

• Identification of new biomarkers from serum, saliva, or other samples that can be collected non-invasively. The use of menstrual effluent as a source of samples is of particular interest.
• Approaches to accurately distinguish between benign and malignant uterine disorders.
• Studies utilizing data obtained from state-of-the-art genomic, epigenomic, and transcriptomic technologies to address the diagnosis of the selected gynecologic health issues. 
• Application of, or improvement to, existing advanced imaging techniques that can reliably, reproducibly, and sensitively help diagnose any of these conditions. The development of novel modalities is also encouraged. The development of targeted probes used for such imaging are also of interest.  
• Studies that utilize an adolescent population for proof of concept of early detection approaches.
• Measures of normal gynecologic function that can be obtained in population-representative, community-based samples.
• Point of care technologies that can efficiently, inexpensively and rapidly diagnose a patient with any of the gynecologic conditions. 
• Investigation of the influence of infectious disease status on the reliability, accuracy, or accessibility of non-invasive diagnostics for the named gynecologic conditions.  

Projects of lower priority for this FOA include, but are not limited to:

• Studies that solely or predominately focus on the detection of uterine cancer, without effectively distinguishing from benign conditions, will be considered lower priority.
• Studies of apps or other mobile technologies to collect only self-reported data in the absence of biological sampling.

Projects that will be considered non-responsive for this FOA include:

• Biopsies and laparoscopic or other surgical interventions of any kind.
• The study of bacterial vaginosis, HPV, or screening for HPV cervical lesions.

This list of high priority and lower priority projects is not comprehensive; applicants are STRONGLY ENCOURAGED to contact the scientific/research contact for this FOA to discuss projects before submission. 

See Section VIII. Other Information for award authorities and regulations.