3
Regulatory and Science Policy
Regulatory and science policies steer research, evidence, and product pipelines. Yet sex and gender considerations are fragmented, underenforced, and uneven globally, hindering innovation. Strengthened, aligned policies can prioritize women’s health across the lifespan and embed sex and gender insights throughout R&D, improving access and outcomes.
Regulatory and science policies profoundly shape (1) the types of health research pursued and methods used, (2) scientific understanding of the biological mechanisms driving how people experience health conditions across their lives, and (3) the types of health interventions that enter the R&D pipeline, proceed to market authorization, and ultimately reach populations.
Policy levers can be utilized across the health research and product R&D ecosystem to promote sex and gender equity in health, address significant gaps in scientific understanding of health conditions affecting women, and introduce interventions that address women’s health needs. These levers include the policies that shape research agendas, funding, product development, research conduct, reporting of findings, and mechanisms for market authorization.
Efforts to include sex and gender considerations in regulatory frameworks are variable and fragmented. For example, the WHO’s global benchmarking tool for national regulatory system standards does not include considerations of sex and gender. Across countries, regulatory decision-making on products used by women varies and may be underenforced, which limits innovators’ ability to design solutions that adequately serve diverse populations. Although sex- and gender-informed guidance exists—such as requirements for industry to submit sex-disaggregated data—implementation and accountability are often lacking. These challenges add to the complexity of bringing a product from concept to market, with regulatory processes that vary considerably across geographic regions and may be unfamiliar to academic researchers and entrepreneurs. In some settings, regulatory requirements lack clarity, consistency, and a benefit-risk approach, which may inhibit innovation—especially from under-resourced entrepreneurs—that addresses differences by sex and gender. In other settings, regulatory and surveillance capabilities need significant strengthening to ensure outcomes by sex and gender are captured and reported.
Science policy is also vital to ensure that women’s health needs are reflected in the products they will use.
For example, since the NIH’s SABV Policy was introduced in 2015, approximately half of NIH-funded clinical study participants are women. While this progress is noteworthy, women may still be underrepresented in specific disease areas relative to prevalence, and similar policy tools are lacking or underutilized in other geographic regions and sectors. Science policy should prioritize solutions that promote the health of women across the lifespan—including products that are designed for women as well as those used by all sexes and genders—and consider factors including improved health outcomes, causes of women’s morbidity and mortality, public health impact, feasibility, local needs, and novelty. Policy can also introduce incentives and disincentives that spur research relevant to women, such as intellectual property and patent law and other mechanisms to address unique or complex liability concerns or reputational risks associated with products under development.
By adopting the science policy and regulatory tools detailed below, women’s health stakeholders can ensure that sex- and gender-specific insights are identified throughout all stages of the R&D continuum, enabling more tailored innovation and more equitable access.
Overview Regulatory and Science Policy
3.1 Science policy frameworks
Historically, biomedical researchers and innovators developing new technologies for human health have failed to consider sex- and gender-specific differences in physiology; for decades, many medical specialties defined the standard patient as a 70-kilogram adult male. Studies that do enroll both sexes may not be designed to account for biological differences when collecting, analyzing, and publishing data. This oversight may lead to missed findings, such as variations in responses to therapeutics between sexes and genders, and may overlook adverse effects in female patients, such as reproductive system toxicity or differences in response due to menopausal status. Challenges also surround the inclusion of trans women and non-binary individuals in clinical studies. Since historically the terms sex and gender have been used interchangeably in the medical field, researchers have limited understanding of how cisgender and transgender women respond to clinical interventions. Structural and societal barriers have also limited transgender women’s participation in clinical trials.
Regulators can play a critical role in overcoming these barriers to promote innovation in women’s health by ensuring appropriate recognition of the burden of women’s health. Greater recognition could lead to the alleviation of symptoms associated with conditions that are non-life threatening but impact women’s quality of life and relationships, and result in improvements in therapeutic offerings and unmet medical needs. Further, harmonization and collaboration mechanisms must be developed between funders, researchers, publishers, regulatory agencies, and civil society to accelerate the development of innovations that improve women’s health.
Progress Assessment
Progress made against Opportunities, from the 2024 Progress Report
Status Moderate Progress
0 % Achievement
Solution Strategies
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Require plans for appropriate sex- and gender-disaggregated data collection, analysis, and reporting as a condition for research funding from grant-making and funding agencies.
- Any proposed research that does not include adequate sampling and analytical approaches to assess sex or gender differences must justify why this approach has not been adopted (e.g., in the case of conditions that only affect biological males).
- Expectations should be clearly articulated to prospective grantees and researchers, and funding application review and decision processes should embed sufficient assessment of these approaches (with appropriate expertise in peer-review and review committee membership).
- Progress reports and dissemination requirements should ensure that milestones are met (with any needed adjustments in protocols, sampling, and procedures introduced) and agreed-upon methods are implemented in the conduct of
the research. - Funding requirements may appropriately vary for different kinds of research across basic biology, pre- and non-clinical studies, clinical trials, and other types of interventional or observational research.
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Ensure adequate representation and prospective consideration of sex differences within industry/pharma-led research by training principal investigators, clinical trialists and designers, and study leaders. Regulators should also ensure accountability; for example, if sex differences are not adequately and prospectively considered and analyzed, an application may not move forward unless otherwise scientifically justified.
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Require compliance with SAGER guidelines in publications and centralized databases, such as PubMed Central.
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Solicit patient input, particularly women’s input regarding specific disease areas or conditions, through engaged research approaches that guide the design and protocols of trials to ensure appropriate and representative inclusion of relevant populations of women across ages and life stages. This includes attention to sampling strategies, indicators, and endpoints, as well as any accommodations that can facilitate the participation of study populations with gendered care responsibilities or other barriers to participation. In turn, patient groups should conduct education and awareness-building activities on the need to understand patient representation, sex differences and outcomes, the importance of inclusion in research, and how to participate.
3.2 Legal and regulatory frameworks
Regulatory paradigms should be flexible to balancing pre- and post-market requirements as well as evidence for innovations that improve the health of women—including the use of real-world evidence. Women are diverse—with different hormonal statuses, sizes and weights, ages, and racial and ethnic backgrounds. Physical and identity differences across populations may produce variations in outcomes between men and women and within different sub-sets of women across their life course. Finding the right benefit-risk balance is critical in obtaining the correct data at the right time and to ensure understanding of the benefits and risks of products across various populations. The existing benefit-risk paradigm can be used to balance data collection for the groups most likely to benefit with reasonable risk and allow post-market data collection for other sub-groups at later time points. An unstudied or understudied sub-group should not require a higher regulatory burden.
Additionally, guidance for the appropriate inclusion in R&D of all women throughout the lifespan—including women of childbearing potential, pregnant women, lactating women, and menopausal and post-menopausal women—should be synthesized and adoption of such guidance should increase.
Progress Assessment
Progress made against Opportunities, from the 2024 Progress Report
Status Moderate Progress
0 % Achievement
Solution Strategies
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Set clear definitions for terminology used (e.g., SABV, women’s health).
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Establish a global independent working group of key stakeholders with relevant expertise in science, regulation, and related areas to create a template and decision tree that sponsors can submit to regulatory authorities at various time points throughout their R&D programs, and that outlines a step-by-step plan of action for how and when they will generate sex-specific information. The working group should develop appropriate guidance for each stage of development, and the template should be easily tailored to meet national regulatory needs while facilitating harmonization.
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Create an Independent Global Advisory Committee to advise on sex- and gender-based differences; this group could be the sponsor for the template mentioned above and would also be the go-to group to weigh in on decisions that affect sex and gender in R&D. This committee may be encouraged to interact with regulatory agencies to build shared expertise and could be used as a mechanism to share success cases across regions.
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Develop a global repository of robust examples of instruments, guidance documents, legal frameworks, case studies, etc., and conduct a landscaping of current regulatory pathways to see where it would be possible to layer on sex-based considerations. This landscaping can inform updates to guidance—or the creation of new guidance—that facilitate innovation relevant to women’s needs today rather than of decades ago, e.g., by informing advocacy efforts for legislative action to drive critical updates.
3.3 Product labeling and inserts
It is important to highlight the sex and gender disparities in healthcare where women may face unique health challenges, experiences, and outcomes that differ from men. Historically, medical research and product development have predominantly focused on male diseases and outcomes, leading to a lack of understanding and appropriate interventions if female outcomes differ or in conditions that predominantly impact women.
Requiring the reporting of sex- and gender-specific outcomes in healthcare product labeling and package inserts can enhance transparency and provide essential information to healthcare professionals and patients. This data can enable clinicians to make informed treatment decisions, consider potential risks and benefits specific to women (including pregnant women), and improve overall health outcomes.
Post-market surveillance—the monitoring of drugs, medical devices, and other healthcare products after regulatory approval and introduction to the market—is an important activity that generates information required for label revisions. By implementing sex- and gender-disaggregated surveillance, regulators can identify potential safety concerns, adverse events, or disparities in treatment outcomes specific to women.
Progress Assessment
Progress made against Opportunities, from the 2024 Progress Report
Status Unchanged Progress
0 % Achievement
Solution Strategies
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Include a section on sex- and gender-specific evidence and outcomes in all product package inserts/labels at the time of product authorization, with relevant information about the nature of the evidence (human vs. animal), relevant details regarding potential differences in benefit-risk assessment, and dosing. Allow for appropriate exclusion of this section in cases where it would be inapplicable or misleading.
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Set regulation on an appropriate minimum standard and schedule for required updating of the label, depending on the state of sex- and gender-disaggregated evidence at the time of market authorization and the agreed-upon post-market data collection activities.
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Develop guidance and requirements for converting labels of previously authorized health interventions to comply with new labeling norms to assist with updates to product labels and package inserts for products already on the market.
3.4 Post-market surveillance
Although women may be included in substantial numbers in many development programs, outcomes by sex and age are often only analyzed as exploratory sub-groups that are not powered to detect sex differences and are rarely discussed or questioned. Labeling and post-market updates sometimes provide the demographics of the population studied (e.g., percent females versus males). Still, outcomes are usually presented in aggregate rather than by sex. This practice hampers the ability to uncover potential differences by sex once the product is on the market. (e.g., by applying meta-analysis techniques).
Progress Assessment
Progress made against Opportunities, from the 2024 Progress Report
Status Moderate Progress
0 % Achievement
Solution Strategies
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Ensure regulations and guidance are routinely amended to incorporate updated best practices for sex-gender data harmonization and standardization. New evidence may include novel endpoints, new/updated technologies, and data uncovering differences between males and females or at different female life stages. For example, regulations can be updated for contraception to provide both hormonal and non-hormonal guidance—as non-hormonal contraception options are needed for women who cannot or will not use hormonal products due to contraindications, medical history, side effects, or other considerations.
3.5 Regulatory and policy incentives
Challenges arise from the higher costs and longer timelines that may be associated with larger sample sizes required to conduct sex‐ and gender-specific analyses. These challenges may also slow the approval process for therapeutically novel drugs, impeding progress to improve women’s inclusion and sex- and gender-specific analyses. Incentives can address this by motivating and rewarding researchers and developers for adopting a new R&D paradigm that prospectively incorporates sex- and gender-specific considerations in their innovation programs.
Progress Assessment
Progress made against Opportunities, from the 2024 Progress Report
Status Moderate Progress
0 % Achievement
Solution Strategies
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Develop policies to prioritize and incentivize innovations that improve the health of women, such as faster approval, tax incentives, funding from the government matched by private investment, zero application fees for programs that appropriately address sex- and gender-based differences, early access to medicines for patients, competitions with prizes, women’s health innovation hubs that require women and underserved patients’ involvement in determining fund allocation, and more. Developing a decision tree (see 3.2.B) on what specific actions are suitable for incentives will provide clarity to all involved stakeholders.
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Establish a pooled insurance scheme to de-risk innovation, e.g., modeling after the vaccine injury compensation fund.
