Small Business Initiatives for Innovative Diagnostic Technology for Improving Outcomes for Maternal Health (NOT-EB-21-001)

Small Business Initiatives for Innovative Diagnostic Technology for Improving Outcomes for Maternal Health (NOT-EB-21-001) is sponsored by National Institutes of Health (NIH). This funding opportunity invites Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) applications to develop technologies or tools to quantitatively predict or indicate an increased risk for maternal morbidity and mortality.

It is part of the IMPROVE initiative, supporting research to reduce preventable maternal deaths and improve women's health during and after pregnancy.

Expired NOT-EB-23-005: Notice of Special Interest (NOSI): Small Business Initiatives for Innovative tools and Technologies for Improving Outcomes for Maternal Health This notice has expired. Check the NIH Guide for active opportunities and notices.

Notice of Special Interest (NOSI): Small Business Initiatives for Innovative tools and Technologies for Improving Outcomes for Maternal Health First Available Due Date: New Date September 9, 2025 (Prior Date NOFO s for this NOSI include the following or their subsequent reissued equivalents: July 12, 2023 – PHS 2023-2 Omnibus Solicitation of the NIH, CDC and FDA for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44] Clinical Trial Not Allowed).

See PA-23-230 July 12, 2023 – PHS 2023-2 Omnibus Solicitation of the NIH and CDC for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44] Clinical Trial Required). See PA-23-231 July 12, 2023 – PHS 2023-2 Omnibus Solicitation of the NIH for Small Business Technology Transfer Grant Applications (Parent STTR [R41/R42] Clinical Trial Not Allowed).

See PA-23-232 July 12, 2023 – PHS 2023-2 Omnibus Solicitation of the NIH for Small Business Technology Transfer Grant Applications (Parent STTR [R41/R42] Clinical Trial Required). See PA-23-233 August 20, 2021 – Blueprint Medtech: Small Business Translator (U44-Clinical Trial Optional). See PAR-21-282.

July 16, 2021 – NINDS Exploratory Clinical Trials for Small Business (R41/R42 Clinical Trial Required). See PAR-21-267 . July 16, 2021 – NINDS Exploratory Clinical Trials for Small Business (R43/R44 Clinical Trial Required).

See PAR-21-266 . Feb 22, 2021 – Notice of Special Interest (NOSI): Small Business Initiatives for Innovative Diagnostic Technology for Improving Outcomes for Maternal Health.

See NOT-EB-21-001 National Institute of Biomedical Imaging and Bioengineering ( NIBIB ) National Heart, Lung, and Blood Institute ( NHLBI ) National Institute of Arthritis and Musculoskeletal and Skin Diseases ( NIAMS ) National Institute of Mental Health ( NIMH ) National Institute of Neurological Disorders and National Institute on Minority Health and Health Disparities ( NIMHD ) National Center for Advancing Translational Sciences ( NCATS ) All applications to this funding opportunity announcement should fall within the mission of the Institutes/Centers.

The following NIH Offices may co-fund applications assigned to those Institutes/Centers.

Office of Research on Women's Health ( ORWH ) NIBIB, NHLBI, NIMH, NCATS, and NIMHD will accept responsive applications submitted to the following NOFOs: Activity Code NOFO First Available Due Date R41, R42 PA-23-232 – PHS 2023-2 Omnibus Solicitation of the NIH for Small Business Technology Transfer Grant Applications (Parent STTR [R41/R42] Clinical Trial Not Allowed) September 05, 2023 R41, R42 PA-23-233 –PHS 2023-2 Omnibus Solicitation of the NIH for Small Business Technology Transfer Grant Applications (Parent STTR [R41/R42] Clinical Trial Required) September 05, 2023 R43, R44 PA-23-230 – PHS 2023-2 Omnibus Solicitation of the NIH, CDC and FDA for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44] Clinical Trial Not Allowed) September 05, 2023 R43, R44 PA-23-231 – - PHS 2023-2 Omnibus Solicitation of the NIH and CDC for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44] Clinical Trial Required) September 05, 2023 NINDS will accept responsive applications submitted to the following NOFOs: Activity Code NOFO/FOA First Available Due Date R41, R42 PA-23-232 – PHS 2023-2 Omnibus Solicitation of the NIH for Small Business Technology Transfer Grant Applications (Parent STTR [R41/R42] Clinical Trial Not Allowed) September 05, 2023 R41, R42 PAR-21-267 - NINDS Exploratory Clinical Trials for Small Business (R41/R42 Clinical Trial Required) September 5, 2021 R43, R44 PA-23-230 – PHS 2023-2 Omnibus Solicitation of the NIH, CDC and FDA for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44] Clinical Trial Not Allowed)\ September 05, 2023 R43, R44 PAR-21-266 - NINDS Exploratory Clinical Trials for Small Business (R43/R44 Clinical Trial Required) September 05, 2021 NIAMS will accept responsive applications submitted to the following NOFOs : Activity Code NOFO First Available Due Date R41, R42 PA-23-232 – PHS 2023-2 Omnibus Solicitation of the NIH for Small Business Technology Transfer Grant Applications (Parent STTR [R41/R42] Clinical Trial Not Allowed) September 5, 2023 R43, R44 PA-23-230 – PHS 2023-2 Omnibus Solicitation of the NIH, CDC and FDA for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44] Clinical Trial Not Allowed) September 5, 2023 NINDS will accept responsive applications submitted to the following NOFO: Activity Code NOFO First Available Due Date U44 PAR-21-282 – Blueprint Medtech: Small Business Translator (U44 - Clinical Trial Optional) September 05, 2023 Background Rising rates of maternal morbidity and mortality (MMM) constitute a serious health crisis in the U.S., with an estimated 700 maternal deaths each year from conditions related to or associated with pregnancy or childbirth and over 50,000 women experiencing severe maternal morbidity (SMM).

The MMM rates of are even higher among Black, Hispanic, and American Indian/Alaska Native women. To prevent the occurrence or advancement of diseases associated with pregnancy and to improve the health of pregnant and postpartum women, early identification of those who are at risk for MMM is needed.

This identification of risk could be done in clinical settings to inform treatment and prevention approaches and/or in-home settings using continuous monitoring to alert clinicians or patients about potential risks and encourage prevention and treatment steps in real time.

Over the past few years, significant advances have been made in the discovery of biomarker signatures to identify risk for MMM, including those for biological and behavioral states related to disease prevention and identification. Many of these advances have been made because of the development of new and improved imaging, genetic, mobile, and machine learning technologies.

Additionally, the development of devices that can measure such biomarkers at the point of care (POC) or in wearable fashion have become common place. It now appears feasible to develop clinical tools that can measure biomarkers or surrogate markers for MMM. Such an objective tool would allow for improved clinical MMM research, prevention, and treatment.

Currently, there is an urgent need for personalized treatment options for pregnant women at risk for MMM. However, MMM research and diagnosis are hampered due to the lack of technology to measure these objective predictors of risk for MMM in a POC or wearable continuous monitoring fashion for early detection. Quality research and treatment require quantitative measurement; these tools could improve the prevention and treatment of MMM.

This NOSI is intended to encourage interest in the small business community to develop various approaches, technologies, and tools to address the health issues of maternal morbidity and mortality by achieving a wide array of outcomes, such as 1) the identification, phenotyping, subtyping, and stratification of patients at a greater risk of MMM, 2) multi-level interventions to address racial disparities in MMM, and 3) clinical decision-making that considers social and cultural biases.

Furthermore, this NOSI focuses on the development and validation of tools, technologies, and approaches, including artificial intelligence (AI) and machine learning, that indicate states of increased risk for and presence of MMM.

This includes but is not limited to development of tools and technologies that: Measure factors associated with increased risk for MMM, including but not limited to blood pressure, heart rate, maternal/fetal physiology, or pupil dilation and facial expression. Measure biometrics associated with the onset and exacerbation of various diseases of MMM, including but not limited to depression or preeclampsia.

Predict risk from a variety of data sources, for example, medical charts and electronic health records. Alert patients and clinicians to potential risk factors. Suggest various prevention and treatment approaches.

Technologies that are affordable, scalable, and easy to implement within a variety of clinical settings, including primary care, will maximize the benefit to the patient population. Moreover, technologies that take social and cultural norms into the design consideration to maximize adoption by the patient population are of critical importance.

These devices could be used at the point of care or in-home settings, where these devices could be worn by pre- and post-partum women and/or health-care providers when there is increasing risk.

Due to the many recent advances in monitoring devices to predict health conditions by measuring behavioral and biomarkers, this NOSI is particularly interested in the development of new technologies that can combine different behavioral and biomarker measurements.

This NOSI is intended to encourage interest in the small business community to develop various approaches, technologies, and tools to address the health issues of maternal morbidity and mortality by achieving a wide array of outcomes, such as 1) the identification, phenotyping, subtyping, and stratification of patients at a greater risk of MMM, 2) multi-level interventions to address racial disparities in MMM, and 3) clinical decision-making that considers social and cultural biases.

Furthermore, this NOSI focuses on the development and validation of tools, technologies, and approaches, including artificial intelligence (AI) and machine learning, that indicate states of increased risk for and presence of MMM.

This includes but is not limited to development of tools and technologies that: Measure factors associated with increased risk for MMM, including but not limited to blood pressure, heart rate, maternal/fetal physiology, or pupil dilation and facial expression. Measure biometrics associated with the onset and exacerbation of various diseases of MMM, including but not limited to depression or preeclampsia.

Predict risk from a variety of data sources, for example, medical charts and electronic health records. Alert patients and clinicians to potential risk factors. Suggest various prevention and treatment approaches.

Technologies that are affordable, scalable, and easy to implement within a variety of clinical settings, including primary care, will maximize the benefit to the patient population. Moreover, technologies that take social and cultural norms into the design consideration to maximize adoption by the patient population are of critical importance.

These devices could be used at the point of care or in-home settings, where these devices could be worn by pre- and post-partum women and/or health-care providers when there is increasing risk.

Due to the many recent advances in monitoring devices to predict health conditions by measuring behavioral and biomarkers, this NOSI is particularly interested in the development of new technologies that can combine different behavioral and biomarker measurements.

The National Institute of Biomedical Imaging and Bioengineering ( NIBIB ) NIBIB is interested in projects focused on the development, engineering and design of technologies that can monitor or diagnose pre- and post-partum women for MMM factors.

Examples of research of interest to NIBIB include, but are not limited to: Advanced AI algorithms, modeling, and simulation technologies Point-of care technologies for the clinical or hospital setting Clinical decision support technologies Wearable technologies for continuous monitoring, diagnostic or therapeutic purposes A complete list of programmatic interests in NIBIB can be found at: https://www. nibib. nih.

gov/research-funding . NOTE: For projects submitted to NIBIB proposing clinical trials, note that NIBIB will only support early-stage clinical trial applications, i.e., feasibility, Phase I, first-in-human, safety, or other small clinical trials, that inform early-stage technology development.

This guidance applies to applications submitted using notice of funding opportunity (NOFOs ) listed in the “ Application and Submission Information ” section, and their subsequent reissuances. Under these announcements, NIBIB will not support applications proposing pivotal, Phase II, III, IV, or trials in which the primary outcome is efficacy, effectiveness, or a post-market concern.

National Heart, Lung, and Blood Institute ( NHLBI ) NHLBI is interested in projects focused on detecting, predicting, and/or monitoring heart, lung, blood, and sleep-related (HLBS) disorders during pregnancy and/or the post-partum period.

Examples of peri- and postpartum disorders and conditions of interest to NHLBI include, but are not limited to: Hypertensive disorders of pregnancy, including chronic hypertension, gestational hypertension, pre-eclampsia, and eclampsia Postpartum cardiomyopathy Sleep disordered breathing in pregnancy In addition to the above pregnancy-related or pregnancy-induced disorders, the NHLBI is also interested in projects that enhance the monitoring and management of women with existing HLBS-specific disorders and risk factors who enter pregnancy or are considering becoming pregnant.

Technologies that take social and cultural factors into design consideration to maximize their adoption are also encouraged. NHLBI also encourages dissemination and implementation projects that address barriers to uptake of evidence-based practices for HLBS conditions and disorders. A complete list of scientific focus areas in the NHLBI can be found at: https://www.

nhlbi. nih. gov/science .

National Institute of Mental Health ( NIMH ) NIMH’s mission is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery, and cure.

For this NOSI, NIMH is interested in supporting the development of technologies that can predict, detect, monitor, prevent, and/or treat perinatal depression and associated psychiatric morbidity (e.g., bipolar disorder, perinatal psychosis, self-harm and suicide attempts) in individual patients and can alert patients and clinicians in near-real time.

Examples of research of interest to NIMH include, but are not limited to: Development of algorithms that leverage passive mHealth data to predict, detect and monitor symptoms associated with perinatal depression and associated psychiatric morbidity (e.g., bipolar disorder, perinatal psychosis, self-harm, and suicide attempts). Testing of wearable technology to accurately monitor symptoms.

Development and testing of real time remote clinical decision support technology. Development of technology that incorporates established prevention and treatment approaches into just in time adaptive interventions to prevent and treat perinatal depression and associated psychiatric morbidity (e.g., bipolar disorder, perinatal psychosis, self-harm and suicide attempts).

Applications submitted to NIMH that involve a clinical trial (CT) should comport with NIMH CT expectations, including utilization of an experimental therapeutics approach for the development and testing of therapeutic, preventive, and services interventions. For more information on mechanistic, treatment, prevention or services CTs at NIMH see: https://www. nimh.

nih. gov/funding/opportunities-announcements/clinical-trials-foas/index. shtml .

Prospective applicants are strongly encouraged to contact NIMH prior to submission. National Center for Advancing Translational Sciences ( NCATS ) NCATS is interested in projects focused on bioinformatics and clinical research management tools and technologies that address pre- and post-partum factors related to MMM.

Examples of research of interest to NCATS include, but are not limited to: Pre-clinical drug discovery and development tools Biomedical, Clinical & Health Research Informatics Clinical Research Management tools A complete list of programmatic interests can be found at: https://ncats. nih.

gov/smallbusiness/priorities NOTE: For applications submitted to this NOSI that propose clinical trials, NCATS does not support applications proposing any clinical trials in the submitted application. Applicants are encouraged to contact NCATS staff at [email protected] prior to submitting their application in order to ensure it is aligned with NCATS’s SBIR/STTR research interests.

National Institute of Neurological Disorders and Stroke ( NINDS ) The mission of NINDS is to reduce the burden of neurological disease—a burden borne by every age group, by every segment of society, by people all over the world ( https://www. ninds. nih.

gov/About-NINDS/Who-We-Are/Mission ). To this end, the Institute supports and conducts research on the healthy and diseased brain, spinal cord, and peripheral nerves. For this NOSI, NINDS is interested in the development of technologies that address maternal morbidity and mortality (MMM) within the scope of the NINDS mission space.

Potential NINDS areas of interest related to maternal mortality and morbidity include but are not limited to stroke, cerebral venous thrombosis (CVT), migraine, peripheral neuropathies, chorea, and posterior reversible encephalopathy syndrome (PRES). NOTE: NINDS does not support applications to the omnibus clinical trial NOFOs PA-23-233 or PA-23-231 .

Small Business concerns proposing clinical trials under the NINDS mission space should consider applying directly to PAR-21-267 : NINDS Exploratory Clinical Trials for Small Business (R41/ R42), or PAR-21-266 NINDS Exploratory Clinical Trials for Small Business (R43/ R44).

In addition, applicants are encouraged to consider Small Business U44 Cooperative Agreement mechanisms under the NINDS Translational Neural Devices program https://www. ninds. nih.

gov/Current-Research/Research-Funded-NINDS/Translational-Research/Funding-Programs-Researchers/Translational-Devices . National Institute on Minority Health and Health Disparities ( NIMHD ) NIMHD has an ongoing interest in technology to improve maternal health and to reduce, eliminate or prevent disparities in maternal mortality and morbidity especially given the higher MMM rates experienced by US racial and ethnic minority women.

When developing new technologies, the voices of these women should be included to mitigate unintended consequences and prevent the exacerbation of disparities.

The excess burden of maternal mortality and morbidity experienced results from factors operating within and across multiple domains (e.g., biological, behavioral, socio-cultural, environmental, physical environment, healthcare system) and multiple levels (e.g., individual, interpersonal, community, societal) (see the NIMHD Research Framework ).

Projects must include a focus on one or more of the following NIH-designated populations experiencing health disparities in the United States: African Americans, Latinos/Hispanics, American Indians and Alaska Natives, Asian Americans, Native Hawaiians and other Pacific Islanders, less privileged socioeconomic (SES) groups, and underserved rural populations.

Projects leading to commercially available, affordable, accessible, and culturally acceptable technologies disrupting or preventing the interactions and processes responsible for or implicated in the creation, promotion or sustainment these and associated disparities are encouraged. Projects should consider social determinants of health and be informed by the NIMHD Research Framework.

Applicants are strongly encouraged to include community partners, patients, or end users in the development of technologies and leverage the capabilities of design thinking or similar systems or societal level thinking. Employing multidisciplinary teams are also encouraged.

Examples of potential topic areas include, but are not limited to the following among racial and ethnic women who are at highest risk for maternal morbidity and mortality: Technologies targeted at improving health outcomes among women with or at risk for comorbidities (e.g., diabetes, cardiovascular disease, obesity) ultimately leading to MMM during preconception, perinatal, or the postpartum periods Technologies that help integrate and coordinate care, treatment, patient monitoring, and services (e.g., wrap-around services) Innovative technologies for identifying high risk for pregnancy complications Patient-centered technologies for identifying and leveraging sociocultural protective and resiliency factors (e.g., community support) Disruptive technologies leveraging multiple digital technologies, for example, Fast Healthcare Interoperability Resources, PhenX Toolkit, personalized medicine, and electronic health records for preventing mortality and morbidity disparities Technology with high success in predicting health care delivery and care strategies for disrupting health disparities outcomes for high risk for adverse health care delivery outcomes Technologies disrupting or preventing the impact of discrimination, bias, indifference, and racism on maternal mortality and morbidity outcomes across systems of care and levels of influence (interpersonal, system, and structural) Technology leading to decision aids for risk assessment (especially to promptly identify onset of chronic diseases or complications during the first year postpartum) and utilizing evidence from multiple levels and domains, including life course, family history, health care systems, and organizational data Technology interventions that address low health literacy and Limited English Proficiency in shared decision-making and informed choice Technologies for strategic multilevel and multidomain risk assessment and monitoring and integrating patient, provider, life course, clinical, organizational, community, and societal level data for predicting maternal mortality and morbidity risk and preventive interventions, especially during the first year postpartum and beyond Technology leading to equal access, effective continuity of care, and provision of quality care through disruption of the limitations resulting from factors like insurance coverage, socioeconomic status, access to community resources, and site of care Technology to eliminate the severe morbidity experienced by racial and ethnic minority women resulting from pregnancy-related complications (e.g., hemorrhage, sepsis, eclampsia, cardiovascular events).

This technology must also consider the higher prevalence of chronic conditions (e.g., hypertension, obesity, cardiovascular disease) that may exacerbate maternal morbidity Technology exploiting protective factors to decrease rates of maternal morbidity and maternal mortality across SES levels and among rural populations Technology that addresses preconception and pregnancy-related health concerns of underserved women; Technology for improvements in quality of obstetric care (including preconception perinatal, and postnatal care) to eliminate racial disparities in maternal outcomes National Institute of Arthritis and Musculoskeletal and Skin Diseases ( NIAMS ) NIAMS supports research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases ( https://www.

niams. nih. gov/about ).

NIAMS is interested in small business technological innovations that address maternal morbidity and mortality within the scope of the NIAMS mission.

For this NOSI, potential NIAMS areas of interest related to maternal mortality and morbidity include, but not limited to: systemic rheumatic and autoimmune diseases such as rheumatic arthritis, lupus, and systemic scleroderma; musculoskeletal diseases and conditions such as muscular dystrophy, osteogenesis imperfecta, and bone deformities.

Office of Research on Women’s Health ( ORWH ) Understudied and underreported women such as racial and ethnic minority populations of women or women residing in rural or underserved areas. Women with complex health needs such as the co-occurrence of cardiovascular disease, diabetes, or obesity, along with co-morbid conditions.

Women experiencing homelessness or living in overcrowded congregate housing, or women incarcerated or under community supervision. By identifying risks factors relate to the social determinants of maternal health (i.e. low socioeconomic status, access to care, food security) Health by determining risk factors related to the intersectional dimensions of pregnant women such as race, age, geolocation.

Application and Submission Information This notice applies to due dates on or after September 5, 2023 and subsequent receipt dates through September 6, 2026. Submit applications for this initiative using one of the following notices of funding opportunity (NOFOs) or any reissues of these announcements through the expiration date of this NOSI.

PA-23-232 – PHS 2023-2 Omnibus Solicitation of the NIH for Small Business Technology Transfer Grant Applications (Parent STTR [R41/R42] Clinical Trial Not Allowed) PA-23-233 – PHS 2023-2 Omnibus Solicitation of the NIH for Small Business Technology Transfer Grant Applications (Parent STTR [R41/R42] Clinical Trial Required) PA-23-230 – PHS 2023-2 Omnibus Solicitation of the NIH, CDC and FDA for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44] Clinical Trial Not Allowed) PA-23-231 – PHS 2023-2 Omnibus Solicitation of the NIH and CDC for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44] Clinical Trial Required) PAR-21-267 – NINDS Exploratory Clinical Trials for Small Business (R41/R42 Clinical Trial Required) PAR-21-266 – NINDS Exploratory Clinical Trials for Small Business (R43/R44 Clinical Trial Required) PAR-21-282 – Blueprint Medtech: Small Business Translator (U44 - Clinical Trial Optional) All instructions in the SF424 (R&R) Application Guide and the notice of funding opportunity used for submission must be followed, with the following additions: For funding consideration, applicants must include NOT-EB-23-005 in the Agency Routing Identifier field (box 4B) of the SF424 R&R form.

Applications without this information in box 4B will not be considered for this initiative. Applicants planning to apply in response to this NOSI are strongly encouraged to contact and discuss their proposed research/aims with an NIH Program Officer listed on this NOSI well in advance of the application due date. Applications nonresponsive to terms of this NOSI will not be considered for the NOSI initiative.

Please direct all inquiries to the Scientific/Research, Peer Review, and Financial/Grants Management contacts in Section VII of the listed notice of funding opportunity.

Scientific/Research Contacts National Institute of Biomedical Imaging and Bioengineering (NIBIB) National Institute of Biomedical Imaging and Bioengineering (NIBIB) Office Of Research On Women's Health (ORWH) E-mail: [email protected] Division of Services and Intervention Research National Institute of Mental Health (NIMH) National Institute of Neurological Disorders and Stroke (NINDS) Jasmina Varagic, M. D. , Ph.

D. National Heart, Lung, and Blood Institute (NHLBI) Julia Berzhanskaya, Ph. D.

National Heart, Lung, and Blood Institute (NHLBI) National Center for Advancing Translational Sciences (NCATS) Krishna Balakrishnan, PhD, MBA National Center for Advancing Translational Sciences (NCATS) E-mail: [email protected] National Institute on Minority and Health and Health Disparities (NIMHD) Telephone: (301) 402-2516 National Institute of Arthritis and Musculoskeletal and Skin Diseases ( NIAMS ) Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Financial/Grants Management Contact(s) National Institute of Biomedical Imaging and Bioengineering (NIBIB) National Heart, Lung, And Blood Institute (NHLBI) E-mail: [email protected] National Institute of Mental Health (NIMH) National Institute on Minority Health and Health Disparities (NIMHD) E-mail: [email protected] Chief Grants Management Officer National Institute of Neurological Disorders and Stroke (NINDS) National Institute of Arthritis and Musculoskeletal and Skin Diseases ( NIAMS ) Weekly TOC for this Announcement NIH...

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