What-if statement:

What if women were empowered to address their healthcare needs through diagnostics and treatments at home across all ages and stages of life?

Problem statement and opportunity:

Many women are facing considerable barriers to accessing routine preventive healthcare, which is crucial for early detection and management of potential health issues. Primary obstacles include childcare responsibilities, which often prevent women from prioritizing their personal health needs; financial constraints, which can make regular healthcare visits unaffordable; transportation issues, which can make it challenging to reach healthcare facilities; and cultural or family perceptions, which may discourage women from seeking medical attention.

There is an urgent need to address these barriers and develop comprehensive strategies and innovative, affordable, and easy-to-use solutions to ensure that all women have access to routine preventive healthcare. Although technologies capable of diagnosing and possibly treating diseases across all ages and stages of a woman’s life within the privacy of one’s own home are increasingly possible, very few are affordable and/or currently available in the marketplace, or they are not easy-to-use or designed with the customer in mind.

ARPA-H aims to catalyze the development of innovative and impactful platform technologies capable of diagnosing and/or treating women’s health issues in the home environment. Novel platform technologies that monitor, diagnose, administer, treat, or maintain healthy status across all ages and stages of women’s health are of interest. These novel capabilities should empower women to take control of their health and detect and treat disease early, in the privacy of their own home. Successful concepts will improve quality of life by decreasing the complexity and time spent to access healthcare, and measurably improve health outcomes.

Examples of potential capabilities may include, but are not limited to: devices or wearable sensors to assess breast, hormonal, cervical, and pelvic health or diagnose infections (UTIs, STDs); vaginal specimen collection and drug delivery innovations; predicting and preventing premature labor; postpartum and maternal health; mental health and wellness; nutritional support; innovations in telehealth; and healthy microbiomes to support a broad range of women’s health topics.

What-if statement:

What if prioritizing ovarian health throughout a woman’s life could actively prevent or delay the onset of a diverse array of acute and chronic conditions and diseases associated with peri-menopause and menopause?

Problem statement and opportunity:

Ovarian aging is an ongoing physiological process, culminating in menopause, which signifies the cessation of ovarian function. The ovary has both reproductive and endocrine functions. This topic is focused exclusively on maintaining and enhancing endocrine functions of the ovary through mid-life and beyond. As women age through mid-life and beyond, the decline in estrogen levels that occurs in peri-menopause and menopause results in both short-term and long-term health implications for women. Short-term effects involve hot flashes, night sweats, palpitations, headaches, vaginal discomfort, and urinary issues, while long-term consequences include osteoporosis and a higher risk of cardiovascular and neurological diseases.

While Hormone Therapy (HT) is the primary treatment for these symptoms, not all women are candidates for hormone therapies due to their personal or family histories. The lack of solutions that enable simple, timely (continuous or time of need), and cost-effective measurement of hormone levels further exacerbates the challenges of understanding and regulating ovarian, hormone, endocrine, and metabolic health. Further, the optimal time for intervention—which may be decades prior to anticipated decline of ovarian function—is not yet understood.

ARPA-H seeks revolutionary solutions to promote ovarian health and preserve endocrine function past mid-life, thereby enhancing women’s health over the life span and proactively addressing both short- and long-term health effects associated with menopause and ovarian aging. This initiative aims to explore novel treatments, interventions, and research that prioritize conservation of ovarian function, maintaining or restoring hormone levels, including exploration of solutions that promote natural ovarian health beyond mid-life. By prioritizing the development of groundbreaking solutions that improve the ovarian function and overall health through the middle and later stages of a woman’s life, we aim to prevent and mitigate diseases and conditions associated with women’s aging, ensuring a healthier and extended quality of life.

Examples of promising innovations may include but are not limited to: safe and accessible pharmaceutical interventions to promote ovarian health; understanding ovarian aging in the context of other systems (neuro, osteo, cardio, etc); cell and gene therapies; implantable bioelectronics; and ovarian tissue preservation and reimplantation.

Note 1: The focus of this topic is improvement of ovarian function for endocrine outcomes to prevent acute and chronic disease that follows menopause; thus specifically excluded are topics that address fertility or extended reproductive age.

Note 2: It is also anticipated that this topic will require the development of novel capabilities to non-invasively measure or modulate hormone or hormone-like substance levels at home to augment and inform the use of treatment interventions. These solutions may be proposed here as a companion to a given intervention, or as stand-alone efforts or under the Women’s Health at Home topic.

What-if statement:

What if we could revolutionize female-specific research models to ensure equitable and effective treatments?

Problem statement and opportunity:

Despite the well known sex differences between males and females, research often neglects the impact of sex on study outcomes, with a predominant reliance on male animal tissues and cell models in pre-clinical research. This oversight has led to flawed and biased results, particularly affecting women by contributing to safety issues, healthcare disparities, data bias, and inequity, especially in diseases more prevalent in females.

The absence of female-specific models poses a significant barrier in understanding female biology and in developing safe and effective drugs and medical devices. The FDA Modernization Act 2.0, enacted in 2023, marks a pivotal shift by endorsing alternatives to traditional animal testing, including in vitro and in silico models, such as organ-on-a-chip systems and computational approaches. These advancements promise to enhance the development of therapies that are more effective and predictive for women, addressing a critical gap in women’s healthcare.

ARPA-H aims to catalyze the development of innovative female-specific model platforms, which are tailored and optimized to study women’s health issues. The aim is to enable a transformative leap forward in how women’s health issues are modeled and subsequently addressed. While developing women-specific models, the platform technology should adequately represent female biology and physiology, including the reproductive system, hormonal fluctuations, and genetic and epigenetic differences between males and females.

Further proposals could consider how female- and male-specific behavioral and psychological factors may influence research outcomes, such as stress responses or social behaviors. Examples of potential capabilities for physical or digital female models may include, but are not limited to:

• Development of customizable “healthy” models that emulate the response of a tissue, organ, or organ system that is critical for women’s health over the life course.
• Development of customizable disease models that accurately mimic how diseases manifest and progress in females, considering conditions that predominantly affect women or present differently in women compared with men.
• Development of models that facilitate an improved understanding of disease heterogeneity based on sex and gender.
• Development of models that include novel features, functions, and design choices that improve the ability to predict the response of women to therapies and interventions.

What-if statement:

What if targeting our brain’s lymphatic system improved outcomes for women at risk for neurological and neurogenerative diseases?

Problem statement and opportunity:

Neurodegenerative diseases like Alzheimer’s disease (AD), Parkinson’s disease, and Multiple Sclerosis (MS) exhibit distinct sex differences in presentation, prevalence, or disease course. For example, women represent nearly two-thirds of the 6.7 million Americans living with AD, and they often bear the brunt of caregiver responsibility, leading to significant emotional, physical, and financial impacts. Meningeal lymphatics and glymphatics play a crucial role in maintaining brain health by facilitating waste clearance, regulating immune responses, and supporting brain fluid balance. Impairment of these systems, common in aging individuals, has been linked to various neurodegenerative diseases like AD and MS, as well as major depressive disorder.

Despite this, the influence of sex differences in the lymphatic system on brain health has not been extensively investigated as a potential prevention or treatment approach for the millions of women affected by these diseases. There is a pressing need to explore the lymphatic system’s potential for the prevention, early detection, and treatment of many neurodegenerative diseases, including AD, Parkinson’s disease, MS, and depressive disorders.

ARPA-H aims to catalyze neurodegenerative disease research by investing in innovative technology that addresses the key challenges in meningeal lymphatics and glymphatic research, diagnosis, treatment, and care. We aim to bring together an interdisciplinary group of researchers, clinicians, and technology experts to accelerate these solutions. All proposed solutions should be developed to ensure fit to the onset, phenotype, and presentation of these disease states in women.

Examples of promising innovations may include, but are not limited to: novel diagnostics leveraging the lymphatic and glymphatic systems’ unique functions for disease prediction and monitoring; high-throughput drug studies using advanced discovery methods to identify compounds that penetrate the blood-brain barrier, targeting the lymphatic and glymphatic system to enhance waste clearance; and research focusing on the impact of sex and age on lymphatic vasculature variability, which could shed light on neurodegenerative disease pathology.

Note: Proposers interested in brain health topics that do not specifically include lymphatic system targeting should consider Topic 6: Wild Card.

What-if statement:

What if women’s pain were taken seriously?

Problem statement and opportunity:

Women experience pain and pain mitigation differently than men do. There are measurable, sex-based differences in the perception of a variety of pain stimuli, hormone-mediated effects on pain perception, psychosocial effects on pain perception, and sex-based differences in response to opioids. The etiology of these differences is not well understood. Women are also more likely to suffer from chronic pain conditions, rheumatoid arthritis, and migraines.

Lack of adequate assessment of women’s pain, due in part to gender, racial, and other stereotypes, can lead clinicians to underestimate and undertreat women’s pain, resulting in prolonged suffering, delayed diagnosis and treatment, and a reluctance to seek medical care. The challenge is exacerbated by the absence of objective, quantitative markers of pain that do not rely primarily on self-reporting. The lack of biomarkers complicates the stratification of patients and the prediction of disease progression or response to treatment, reducing the success rate of pain treatment clinical trials by nearly 20%. Addressing this, a recent NIH-led workshop highlighted the urgent need for developing and validating objective pain biomarkers to advance pain management and contribute to resolving the opioid crisis.

ARPA-H seeks to develop methods to objectively, quantitatively, and longitudinally measure pain across a variety of chronic conditions, including nociceptive pain, neuropathic pain, and pain due to central nervous system sensitization. These methods should enable clinicians to evaluate disease evolution and to determine how well a patient’s course of treatment is addressing their pain. The pain measurement method should be simple, inexpensive and deployable in a range of settings.

Solutions that enable time-resolved, at-home pain monitoring are highly encouraged. While it is acknowledged that a multitude of markers may be needed for a precise and accurate evaluation, it is desired for these markers to be of similar origin (e.g., multiple blood or urine biomarkers, as opposed to MRI exam + genomic screen + blood-based biomarkers + urine-based biomarkers). The design and intended use of the pain measurement method should consider the psychosocial component of pain and the fact that gender, background, and life circumstances affect a person’s response to pain (e.g., people who cannot afford to skip a day of work may force themselves to be more mobile despite high pain levels).

The solution is intended to quantify and support a patient’s claims about their comfort and well-being and must agree with self-reported assessments. Methods that accurately identify the location of the pain generator and that distinguish between different pain types are encouraged, as are wearables.

What-if statement:

What if we could shatter the glass ceiling of women’s health research with innovations so bold, they rewrite the rules of the game?

Problem statement and opportunity:

ARPA- H recognizes that some revolutionary advances in women’s health may be hindered by the inability to secure public or private sector funding because the concepts are considered too technically challenging and are not covered in the topics above. In the Wild Card topic, we seek to catalyze breakthroughs that will transform the paradigm of women’s health, acknowledging the critical gaps in data, the historical underrepresentation in clinical trials, and the lack of focused research on the unique health needs of women throughout their lives.

By advocating for innovative solutions that transcend mere data collection, ARPA-H aims to revolutionize the methodologies for data generation, analysis, and application in women’s health. We invite proposals that employ cutting-edge research, novel technologies, new business models to sustain investment, and interdisciplinary approaches to forge personalized and effective strategies, addressing the comprehensive and specific health challenges women face.

This topic is dedicated to reshaping women’s health research into a more comprehensive, inclusive, and forward-thinking endeavor, ensuring significant improvements in global health outcomes for women. If successful, the concepts pursued under this topic will change the conversation—and, more importantly, the practice—of how we engage women’s health day-to-day.

Specifically excluded from this topic are iterative and standard approaches, including traditional clinical trials and work that is already well supported by other private and public funds, or is otherwise specifically described and solicited in Sprint Topics 1-5.