4

A Governance Framework for Aligning Innovation in Health and Medicine with Equity

The prior chapters describe various ways in which the innovation life cycle can lead to anticipated and unanticipated patterns of inequity. Those chapters also establish an ethical imperative for improved governance of innovation in health and medicine and make a business case for moving toward an innovation framework that is more aligned with principles encompassing equity. This chapter describes such a framework. It begins by articulating the five key imperatives that guide the framework, and then explains how the application of these imperatives enables the forms of equity defined in Chapter 2 to be integrated more fully into the innovation life cycle described in Chapter 3, thereby helping stakeholders identify points at which the current ecosystem is misaligned with the principles of equity and fairness. The final sections of this chapter translate the governance framework to the phases of technology innovation, provide illustrative examples of these imperatives in practice and a vision for various stakeholders of what is possible, and describe leverage points in innovation life cycles that might be used to shift structural and institutional dynamics to realign those pathways with equity. Chapter 5 presents the committee’s recommendations for concrete actions that would advance this more equitable innovation ecosystem.

FIVE IMPERATIVES THAT GUIDE THE FRAMEWORK

The equity-aligned governance framework proposed in this report is designed to help a wide range of social actors in the innovation system see how they are positioned to effect change toward a system that centers equity as a social good and a normative principle in scientific innovation. Social equity aligns with scientific and business opportunities for innovation and with shared responsibilities for the ecosystem. And alignment with equity can be enhanced as levers and incentive structures in the innovation system are changed. The aim of this report is to draw attention to the alignment of these imperatives for equity with the need for innovation and scientific advancement.

The purpose of the governance framework is to help diverse people, organizations, and institutions with different stakes and roles in the innovation system prioritize equity as a norm, and to allow them to envision how a renewed focus on equity can shift common innovation pathways toward more equitable processes and outcomes for users, the system, and society as a whole. This framework provides a way of identifying who the actors are, what they should do individually and together, and when they should do it. Taken together, the five imperatives reorient and redirect the various actors involved toward the cross-sectoral work of building a more equitable technological ecosystem across the health care landscape. It is important to stress that a flexible conceptual framework is needed to encompass the broad and complex social dynamics and interactions that unfold in the domain of health and medicine. It is important as well to note that each element of this framework can and must be applied in cross-cutting fashion—that is, iteratively and actively over the entire life course of any given technology or set of technologies.

Centering equity as a norm among the many stakeholders involved in science innovation is an expansive undertaking that will require cultural transformation across the many efforts involved in conceiving, funding, developing, evaluating, and using scientific innovations. Centering equity will entail fundamental changes that shift practice and professional norms by encouraging the use of new principles, tools, incentives, and methods of accountability; by developing new norms for how varied stakeholders engage early and often with users and affected communities; and by developing new practices that incorporate equity principles, evidence, and considerations into technology development. A framework for aligning innovation with equity will also require stakeholders across this system to develop new cultures of innovation in which awareness and curiosity are enhanced, and to develop routines and practices that prioritize engagement with users in ways that enhance equitable outcomes. To these ends, the following five cross-cutting imperatives underpin this new governance framework and will need to be embraced by innovators, funders, investors, purchasers, and users:

• broadening participation and sharing responsibility to empower a wider range of stakeholders;
• aligning incentives to encourage equitable decision making;
• determining how inequities develop along technology innovation life cycles and taking responsibility for mitigating them;
• crafting timely guidance for pursuing equitable ends; and
• sharpening ongoing, iterative oversight and evaluation along innovation life cycles.

Broadening Participation and Sharing Responsibility to Empower a Wider Range of Stakeholders

The first imperative focuses on broadening participation and responsibility in technological innovation by empowering groups to take actions that prioritize and center equity. New social groups must be brought into the innovation process, and groups of people that have long been part of the process will need to be reoriented toward equity. This process of democratization involves identifying, convening, and incentivizing diverse groups of people to work in a coordinated fashion to center equity in their respective roles along the innovation pathway and to take collective responsibility for the ecosystem as a whole.

An important principle of governance begins with expectations about what it means to “do better” by the governed. This report posits that health technologies should be developed and disseminated in ways that are fair, just, and beneficial to the broadest possible popula-

tion and with the fewest unanticipated consequences for health and well-being. In light of the pervasive inequities experienced in the United States, this means that emerging health technologies should not simply benefit the largest possible number of people but should reflect the full diversity of users and their experiences, including historically marginalized communities. This is not an “expectation” in the sense that it is not what is expected to happen on its own. Rather, it is what one would expect and value from an ecosystem that prioritizes equity.

Guided by concepts of equity (Chapter 2), broadening participation is important both for making innovations more equitable and for building and maintaining public trust in science, technology, and medicine. New people, perspectives, and experiences need to be brought into the process of technological innovation in health and medicine. These people include (1) those that have previously been seen primarily as sources of biological and/or experiential data in the name of technological innovation (e.g., through participation as research subjects in clinical trials) or have not even been included in biological data collection; and (2) experts such as social scientists and humanities scholars who historically have not been included in the innovation process but whose expertise is crucial for building a more equitable and fair ecosystem. The evidence shows that innovation in health and medicine has thus far been insufficiently informed by the diverse range of people’s lived experiences with technologies and the localized social and cultural contexts in which those experiences take place. This imperative focuses on empowering people, many of whom are not necessarily organized into formal advocacy groups or other fixed social groups, in new ways as participants in a process of design and innovation.

Large and diverse groups of people have stakes in a more equitable ecosystem for technological innovation in health and medicine, and the framework presented here engages constituencies of people beyond the language of economic stakes and private ownership. Individuals and groups differ with respect to how their power and position can impact the life cycle and trajectory of technologies. Groups that are active in innovating or are seeking to make innovation equitable represent various structural positions in society—positions linked to structures of age, disability, race and ethnicity, indigeneity, gender, sexuality, social class, language, nationality, living in state custody, and others—that provide the institutional, cultural, and social-psychological architecture through which individuals and groups live out their daily lives, and that also constitute the social and political determinants of health. Therefore, efforts are necessary to address the power differentials that exist among these groups as they participate in the visioning, design, and research processes that lead to technological innovations.

In addition to engaging new groups of people in the innovation process, this imperative asks that everyone take on new responsibilities in the name of equity. All individuals who participate in the innovation process are responsible not only for their part in the process but also for the shared recognition that their actions need to come together synergistically to form a complex ecosystem. Fostering this recognition of responsibility on the part of traditional stakeholders will not come cheap; investments will be needed to raise awareness and incentivize the adoption of new understandings about how the technological ecosystem has led to inequities.

Aligning Incentives to Encourage Equitable Decision Making

Broadening participation and democratizing the innovation process will require actions that encourage, incentivize, and empower traditional innovation actors to take on new responsibilities for equity. Many people and groups play roles throughout the technology

development life cycle and have interests in and responsibility for the patterns of inequity that accompany that process for any given technology. The motivations and interests of these parties can vary widely and are not always aligned with expectations for equitable technological innovation. For example, equity considerations are often distant considerations for private companies, innovators, and some funders. To bridge these gaps in motivations and vested interests will require incentives that invite developers, designers, funders, firms, and other innovation actors to center and prioritize equity in their work.

Incentives will be particularly important in contexts where profit margins and most profitable markets are a main reason for innovation, a motivation that is often perceived as being in conflict with that of prioritizing greater equity in innovation. In fact, however, there are compelling arguments to be made that pursuing equity can increase profitability, such as by increasing the pool of potential customers for products and services, increasing the pool of potential innovators and entrepreneurs, improving the purchasing power of historically marginalized groups, and increasing economic stability at a societal level. There are also potential benefits to be realized in terms of a company’s environmental, social, and governance rating and its reputation with customers, investors, and employees. The existence of investment firms whose strategy is to foster entrepreneurs from underrepresented groups and businesses targeting underserved markets is a testament to the fact that this strategy does not put investors at an automatic disadvantage. Thus, innovations that address unmet needs can benefit both business interests and people’s health.

In some cases, however, prioritizing consideration of equity may come at a cost, or at least the perception of one. Adding constraints to investment decisions can increase costs and discourage or slow some innovation; some investors may choose to consider the implications of their investments for equity, while others may not. The burdens of inequity are often externalities—costs arising from the private sector but borne by the public sector. In this sense, efforts to increase equity that impose a financial burden on private-sector actors may represent a shifting of costs from one sector to another rather than an actual increase in costs overall. Indeed, some of those costs might in effect be shifted back, relieving the burden on private-sector actors with public–private partnerships in which the public partner brings to the collaborative both funding and a commitment to equity.¹ Another factor is timing: While venture capitalists and start-ups often make investment decisions with the goal of achieving a payoff within a few years, the financial gains that can be realized from reducing inequity (both for private businesses and society broadly) will play out on the scale of decades and generations.

One result of this complexity is that it is exceedingly difficult to quantify the trade-offs associated with prioritizing equity in health innovation. It is impossible to say that efforts to increase equity in innovation will always cost money, or that they will always save or make money. The trade-offs, where they exist, will likely be different across sectors and types of technology, and even across businesses within the same sector. This uncertainty does not mean the issue can be ignored. Indeed, even if the committee were able to determine that centering equity in health innovation will always reduce private-sector profits, the argument could still be made that it is worth doing. The constitutional concept of all persons being created equal—being of equal value and deserving of individual recognition with basic human rights—provides one basis for this argument. Thus the concept of equity as set forth

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¹ Examples include BioMADE, the federal government’s manufacturing innovation public–private partnership, and the Advanced Research Projects Agency for Health (ARPA-H), a new government agency that funds the development and commercialization of risky but impactful ideas to advance equitable health and medicine. These examples are discussed further in later sections of this chapter.

in this report is no more than a restatement of constitutionally bestowed rights and privileges, such that asking the U.S. innovation system to better align its incentives to enhance equity is the same as asking it to better abide by the U.S. Constitution than it has in the past. Further supporting this argument is that equity is a value in and of itself that is worth money. There are many examples in which society has prioritized public benefit over private profit. One example is the requirements imposed on the automotive industry in the 20th century: While equipping vehicles with seatbelts, impact-absorbing bumpers, and emissions-reduction technologies increased the cost of manufacturing vehicles, these costs were deemed worth incurring to realize the benefits to public safety and air quality. Sometimes it is worth doing the right thing even if it costs money.

Incentives are an important consideration for many other groups in the innovation system in addition to businesses and investors, including government actors (to encourage coordination across institutional sectors) and affected and underserved communities (to encourage engagement in processes from which they might otherwise be excluded). If incentives are to be worthwhile and sustainable, however, it is important to design guidance, regulations, and enforcement mechanisms and other governance strategies and incentives in ways that minimize the costs and unintended consequences while ensuring accountability for the desired outcomes.

Determining and Taking Responsibility for Inequities along Technology Innovation Life Cycles

People who are responsible for innovation systems need to pursue a more holistic approach to understanding the implications of technologies in society with respect to their impacts on health and well-being. The third imperative in the committee’s framework is focused on building and renewing collective curiosity among innovation participants regarding the dynamic causes and patterns of inequity along innovation life cycles. These causes and patterns may not be predictable at early stages of conception and development; inequities often become clear in hindsight or only after a technology has been introduced into people’s lives and broad-scale medical practice. One aspect of prioritizing equity is engaging in an active and open inquiry about the possible social harms and inequities that might reasonably flow from a particular technology in health and medicine. In other words, how can the equity dimensions of a technology’s development and use be identified in advance and proactively and periodically reassessed as further information is gained? This imperative thus focuses on establishing norms and practices throughout the innovation life cycle in which stakeholders ask these questions, and the answers influence the choices they make.

Which questions about equity are asked, in what phase of innovation they are asked, and who is empowered to ask them are important to the framework.² Any technology’s potential implications (including for equity) need to be analyzed and addressed early and often in the innovation life cycle. This process begins with questions about which technologies should be developed, why, and how, and extends to postmarket evaluations after a technology has become part of public life. This inquiry about potential harms encompasses and exceeds the normative risk-based assessments often carried out by private firms when conducting research and development on their products and markets. Traditional stakeholders tend to

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² While this report is focused on governance of emerging science, technology, and innovation, an important question for governments, innovators, and other public and private stakeholders is whether the approach considered is the most effective and accessible solution to the problem. Sometimes developing a new technological solution does not address the root cause of a challenge or is not the most equitable approach.

focus on questions of risk, safety, feasibility, cost-effectiveness, profitability, and research ethics as they carry out their work. Centering equity involves new configurations of stakeholders asking and answering new questions about the distribution of benefits and harms of a technology or combination of technologies.

This curiosity about and awareness of how innovation can enhance equity should lead stakeholders to establish ethical norms and design practices that reflect what is learned through this more democratic and equity-focused inquiry. What should be done to steer a technology toward more equitable ends is a highly context-dependent question, one that needs to be pursued in a less hierarchical way that redistributes power over which scientific questions are posed, which technologies are designed, and what decisions are made in that case. Tools are needed to assist innovators and other actors in systematically asking and answering questions about the equity impacts of their particular technologies and what practices they can use to mitigate any related concerns. These questions need to be posed along the innovation life cycle to elucidate who holds responsibility for advancing equity and what those responsibilities look like as choices are made during the process—the moments at which actors’ decisions lead to more (or less) equitable outcomes. In the past, equity has rarely been considered explicitly during these choice points.

However equity outcomes are measured, data on equity do not speak for themselves; they require theoretical frameworks for interpretation. Theoretical explanations for inequity are linked to specific remedies that, in turn, aim to repair or lessen that inequity. The social situations in which technologies are deployed have emergent equity dynamics that are not predestined, partly as a result of user innovations and unanticipated practices. Nonetheless, without the production of additional empirical data about inequity, it will be difficult to implement or audit practices that hold designers and governors accountable.

Crafting Timely Guidance for Pursuing Equitable Ends

The fourth imperative focuses on restructuring decision-making processes across and within public-, private-, and nonprofit-sector institutions involved in innovation in health and medicine. Strong context-specific guidance is needed for actors that include designers, funders, and firms about how to shift innovation pathways as they make decisions about what to do at various choice points based on what is learned iteratively through equity-focused data collection and analysis. The most actionable guidance on aligning innovation with equity is likely to be context-dependent, with the details affected by the particular area of emerging science and technology and by which actors have the greatest ability to influence decisions during different phases of development. In the artificial intelligence/machine learning (AI/ML) development community, for example, equity-relevant guidance has focused on identifying and disseminating best practices and strategies for accurate problem definition, elimination of bias, uses and limitations of training data sets, the importance of performance testing and auditability, and other practices (see also Box 3-3 in Chapter 3).

The application of this fourth imperative can involve diverse groups of people, including emerging science and technology innovators, public and private organizations that train investigators and conduct research and development, organizations that provide funding and approvals associated with emerging science and technology, those that assess, manage, and invest in the intellectual property that results; and those active in the provision and delivery of resulting products in health care and consumer settings. Once these actors have collectively determined what could be done to shift an innovation pathway toward more equitable ends that do not unduly cause social harms (in accordance with the third imperative), new and traditional actors will have to confront how to implement

these changes based on where they are positioned along innovation life cycles and their institutional capacity for making different choices and for implementing a new process for decision making.

Sharpening Ongoing, Iterative Oversight and Evaluation along Innovation Life Cycles

The fifth imperative is focused on sharpening the governance process for emerging technologies around questions of equity. Broad structures of oversight and evaluation are needed to track equity along innovation life cycles, going beyond the actions of individuals and groups in single institutions. Oversight provides a mechanism for encouraging or enforcing actions that shape ecosystem dynamics and advance equity, including the establishment of methodologies for better evaluating the equity alignment and potential risks of particular technologies. Oversight and other governance mechanisms can be voluntary or mandatory; mechanisms can be targeted at systems or particular parties; and they can be centralized or decentralized. These governance mechanisms can be formal regulatory policies, with both premarket and postmarket applications; they can be professional guidance, such as guidelines on partnering with affected communities or on inclusive design practices; they can be nongovernmental actions, as when payers decide which therapies are covered by insurance; and they can also be consumer focused, with attention to providing information that maximizes safe and effective uses by health care providers, patients, and consumers or that supply financial support for those who cannot otherwise access the technology.

One issue to consider is the permanence of these mechanisms. In public policy, the staying power of a policy often depends on the form it takes. Legislation is among the “stickiest” approaches since it is difficult to change or replace once enacted. Regulations also tend to stick. Nonbinding guidance and professional community norms are easier to change and update, and spending priorities are typically the most vulnerable to shifting priorities. In the private sector, company culture is strongly intertwined with the organization’s focus and values. Once considering equity becomes embedded into the ethos of an organization, it becomes more difficult to take this value away. An ongoing and iterative program of governance, including oversight and evaluation, is necessary for addressing the cross-sector misalignments in innovation that allow for stratified processes and outcomes.

The Imperatives in Context: Learning from a Regenerative Medicine Case Example

If equity in innovation is to be advanced the five cross-cutting imperatives detailed above will need to be applied to understand and shape the dynamics of particular technologies as they travel along innovation life cycles. One case study that informed the committee’s analysis (see Appendix A) is focused on regenerative medicine and governance approaches shaping this field, including the use of legislation, federal agency oversight, and the promulgation of professional norms and standards (Mathews et al., 2023). This example explores an area of emerging medical technology and illustrates how the framework imperatives can help identify and parse equity issues that arise in the development of this and other emerging technologies in health and medicine.³

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³ The observations on the case example presented here do not include references; extensive references are provided in Mathews et al. (2023); see Appendix A.

An overall observation illustrated by this case example is that expectations and practices for responsible and ethical research and innovation have advanced and continue to evolve. The history of stem cell transplantation involves recognizing the therapeutic options such cells can provide to patients with blood cancers, blood diseases, and radiation and burn injuries. However, early clinical trials took place before institutional and professional ethics infrastructures for approaches to informed consent and other protections for human participants in research had been developed. Since human pluripotent stem cells were first isolated, the field has seen evolving commitments to ethical practices for communicating and balancing benefits and harms to research participants, and recognition has grown of the importance of patient and public engagement and accountability in the development of new technologies. The need for oversight in regenerative medicine was identified at various points in the innovation ecosystem, and roles played by relevant bodies changed over time. In the 1970s, for example, the National Institutes of Health’s (NIH’s) Recombinant DNA Advisory Committee (RAC) established guidelines and initially reviewed all gene transfer research protocols. As the safety of DNA technology became clearer, responsibilities for evaluating proposed uses shifted more to biosafety committees at research institutions. In 2019, a successor to the RAC was reimagined, and the Novel and Exceptional Technology and Research Advisory Committee (NExTRAC) now provides advice on developments in a broader array of emerging biotechnologies.⁴

As stem cell technologies developed, research and clinical communities identified new scientific challenges and technical and logistical strategies for overcoming them, reflecting the iterative nature of innovation. For example, scientific progress in the derivation of induced pluripotent stem cells (IPSCs) intersected with concerns among some members of the public and restrictions on certain avenues of research (for example, on access to and use of human embryos for research, or on the use of federal funds to derive new human embryonic stem cell lines), helping to propel greater use of such options as IPSCs for approaching some scientific questions. In addition to the development of new stem cell sources, examples include the identification of factors underlying immune rejection to improve transplant safety and efficacy; the creation of stem cell donor registries and networks to expand the availability of donor cells; and the incorporation of emerging technologies, such as genome editing, into stem cell developments, to generate new classes of therapies.

All five of the framework’s imperatives are relevant to this evolution, which will continue as scientific possibilities and societal values change. The imperative to broaden participation in innovation informs efforts to expand who joins the science, technology, engineering, and mathematics (STEM) workforce and the expectation that technology developers will seek input from a wider range of users and affected communities. Taking responsibility reflects the recognition that many actors involved in the innovation system have opportunities to mitigate misalignments between an emerging technology and foundational ethical principles. This case example also illustrates the use of incentives and disincentives; the creation and dissemination of federal, state, and professional guidance; and the role of ongoing evaluation and oversight in helping to propel change and support a responsible innovation enterprise in health and medicine.

Several additional equity-relevant observations can be drawn from this case example on the evolution of stem cell transplantation, as described below.

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⁴ Changes to the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules were issued in 2019 (84 FR 17858). For role of the NExTRAC, see also https://osp.od.nih.gov/policies/novel-and-exceptional-technology-and-research-advisory-committee-nextrac/ (accessed June 30, 2023).

Disparities exist in the medical conditions that are prioritized for research. Given its prevalence, sickle cell disease has garnered relatively lower funding compared with several diseases affecting primarily people with greater social power. Framework imperatives that can aid in addressing this disparity include broadening participation to empower a wider range of innovation stakeholders and aligning incentives to encourage equitable policies and decision making. As noted previously, the inclusion of diverse perspectives in decision making influences how research and innovation priorities are set, how clinical trials are designed, and which incentives and disincentives are used to shape behavior. For example, funding devoted to technological advances such as stem cell transplantation and gene therapy must be balanced against funding to enhance access to current medical care and appropriate pain management for people with conditions such as sickle cell disease. Such choices about prioritization are often made by legislators through agency appropriations and mandates and program priorities set by public and private funders, reflecting the values and choices of a society as well as the views of those stakeholders consulted in the priority-setting process. Historically marginalized or affected communities have often lacked power to influence budget choices. Patient advocacy groups also vary in size, budget, and advocacy capacity—features that pose challenges when such groups are lobbying for research to address individual rare diseases and diseases affecting historically underserved or marginalized populations.

Inequities in access to effective stem cell transplantation arise from the limited availability of diverse, human leukocyte antigen (HLA)-matched donor stem cells. Currently, genomics data and stem cells available for research and care are disproportionately derived from people of European descent, limiting access for those with other ancestries. Framework imperatives associated with addressing this concern include aligning incentives and sharpening ongoing, iterative oversight and evaluation. Incentives provided through funding or regulatory requirements could be used to encourage the collection and banking of more diverse cells. The role of financial incentives in encouraging stem cell donation could also be revisited to increase the probability that an appropriate HLA match for patients in need of a transplant can be identified. Both the sale of bone marrow and use of financial donation incentives are banned under the 1984 National Organ Transplant Act (NOTA), and the potential benefits and harms of incentivizing such donations would need to be further explored.

The history of public and private donor registries and stem cell banks is associated with differential access to stem cell–based treatments. The creation of networks of stem cell banks and registries and the establishment of standards and accrediting bodies have been positive developments in the field. However, information on and access to these resources are uneven. In umbilical cord blood banking, for example, fee-charging private banks are more heavily advertised and accessible to parents compared with free public banks, although private banks are subject to fewer standards and have been found to have lower overall cord blood quality. Framework imperatives associated with addressing this concern include crafting timely guidance, aligning incentives, and providing iterative oversight and evaluation in response to the evolution of the market for these resources.

Stem cell clinics that market unproven remedies have emerged, posing the potential for harm to patients in the absence of demonstrable benefit. Framework imperatives that can aid in addressing this concern include members of the innovation system taking responsibility for conducting high-quality and ethically aligned research that advances the understanding and use of stem cell treatments, along with responsibility for facilitating and enhancing patients’ abilities to fairly evaluate the accuracy of claims. Stem cell clinics arose and expanded rapidly in the United States and around the world, highlighting the importance of timely guidance and oversight capacity from regulatory and professional bodies on responsible

standards and practices in this field, as well as the importance of revisiting national and cross-border governance approaches in response to developments in such fast-moving fields.

A FRAMEWORK FOR GOVERNANCE OF INNOVATION: APPLYING THE IMPERATIVES TO ENHANCE THE INNOVATION SYSTEM IN HEALTH AND MEDICINE

The governance framework proposed in this report enhances the alignment of emerging science, technology, and innovation in health and medicine with ethical principles by drawing on the five key imperatives described above throughout the innovation life cycle, as shown in Figure 4-1.

The five overarching imperatives are listed at the left of the figure. Drawing on these imperatives to inform the choices made throughout the life cycle of a technology is what enables the framework to produce the desired outcome—the meaningful incorporation of equity into the innovation system for emerging science and technology. To apply the framework, actors in the innovation system would look to the five imperatives for guidance on how to make more equitable decisions.

The central image in Figure 4-1 represents the simplified, conceptual innovation model described in Chapter 3. In this model, emerging science and technology pathways include the phases of conceiving of and embarking on an idea; researching, developing, and assembling a technology; evaluating performance for widespread use; accessing and using a technology; and learning from postmarket use. Choices are made during each phase that stimulate or impede how a technology continues toward the next phase. As depicted in the figure and described in more detail in Chapter 3, these choices encompass the receipt of

funding and research approvals; identification, management, and licensing of intellectual property, and continued investment in as well as scale-up of research and development; determinations and approvals (where required) of sufficient performance to support widespread public availability; decisions affecting cost, insurance coverage, and other factors affecting the availability of the product; and the analysis of postmarket information, including public reactions and responses.

The left side of the figure represents the goal of aligning innovation with equity as defined in Chapter 2 and arising from guiding ethical principles of justice, fairness, and the common good. People are rarely represented directly in images of innovation. In emphasizing the advancement of equitable innovation, the framework also aims to recognize and incorporate the participation of humans as central to medical innovation and health.

The five imperatives are essential concepts in this framework. To apply the framework in practice, actors should pose the following types of questions during each innovation phase, enabling them to explore how each imperative can be incorporated into their work and helping them understand alignments and misalignments between their innovation and equity and opportunities for further action to support equity:

• Broadening participation: How are diverse groups brought into the innovation process and empowered to share responsibility at this stage of development?
• Aligning incentives: How are incentives at this stage aligned toward equity?
• Taking responsibility: How is responsibility for equity shared among stakeholders at this stage of development?
• Timely guidance: How are stakeholders empowered to offer guidance to each other about design choices and decision making at this stage of development?
• Sharpening oversight: What governance mechanisms can help foster equity during this phase of the innovation process?

The practical application of these questions to the phases of innovation is summarized in Table 4-1. The table identifies key leverage points and example choices made during each phase, provides examples of the types of questions that actors should consider during each phase to apply the five framework imperatives, and elaborates on how the eight dimensions of equity defined in Chapter 2 (Table 2-1) apply in aligning equity with technology development. While the table is not intended to capture every nuance of a complex ecosystem in emerging science and technology, it provides a guide to the overall system and to the ways in which interventions can nudge innovation toward equity.

ILLUSTRATING HOW THE FRAMEWORK CAN INFLUENCE THE INNOVATION ECOSYSTEM

This section explores how applying the governance framework described above to the phases of emerging science and technology development supports an innovation system better able to anticipate and address inequities. As a technology evolves from research insight to commercialization, an increasingly broad network of actors and institutions builds around it, bringing an increasingly complex array of motivations and requirements. While it may be desirable to limit inequities that are introduced or amplified along the way, preventing inequities in the early phases of innovation is likely to be more impactful than attempting to remedy them later on. On the other hand, the equity implications of an emerging technology are often undeveloped or unclear or cannot be fully anticipated at the early stages of

TABLE 4-1 Examples of Leverage Points and Choices, Questions Raised by the Framework Imperatives, and Applications of the Dimensions of Equity at Each Phase of the Innovation Life Cycle

NOTE: At each innovation phase, timely guidance is also needed on practical strategies supporting action on identified equity considerations.

research and development, and it is important for later phases to incorporate strong evaluative mechanisms so these gaps can be recognized and addressed should they emerge.

As described elsewhere in this report, applying the governance framework to innovation requires culture change. All participants in the innovation ecosystem should acknowledge that inequity, injustice, or unfairness can arise during the development of a technology and be aware of the long history of inequities in health and medicine. Thus, all members of the system have a responsibility to be mindful that their choices could mitigate or exacerbate inequity; attention to equity should be considered a legitimate and essential element of responsible science, technology, and innovation. How to actualize this culture of awareness and define specific obligations that should fall on individual actors are complex matters that are explored further in the sections below.

Conceiving of and Embarking on an Idea

Scientific and technological innovation begins with an idea. Equity considerations most relevant to this phase often involve the culture and norms that guide research communities, structural and organizational policies, and portfolio priorities and decisions. As shown in Table 4-1, important choices include which research questions are asked and by whom, how research studies are designed, and what processes are involved in obtaining research approvals and funding.

Broadening Participation

The concepts of topical equity and innovator equity suggest that ideas in an innovation portfolio and the innovators who pursue these ideas should reflect diverse populations, including those that have traditionally been marginalized and underserved. Applying the framework’s imperatives expands the social contract for science by identifying a broader range of actors engaged in innovation and taking steps to ensure that they are seen as equal partners. Diversifying the STEM pipeline can aid in this effort by empowering a broader range of researchers to ask diverse questions. As a result, the innovation system in health and medicine will be able to support research and development priorities identified not only by scientists and engineers but also by affected communities. Engagement will need to include traditionally marginalized and underserved communities and organizations that represent them, along with social scientists, humanities scholars, and other professionals who offer an understanding of the circumstances and constraints experienced by these communities, as well as a critical lens on how society and technology interact. To this end, researchers and research organizations may need to apply other imperatives of the framework, drawing on timely guidance on opportunities and responsibilities to better align their work with equity and strategies for translating these concepts into practice in their particular fields.

Some community organizations may not currently have the infrastructure and experience needed to identify and engage in research partnerships on topics that directly affect them. Funders can respond to this challenge not only by fostering partnerships but also by directly funding community organizations to build their organizational, scientific, and technological capacity to engage in innovation. For example, the Chan Zuckerberg Initiative is supporting advocacy organizations for rare diseases in becoming more successful at directing and incentivizing research in their disease areas (see also Chapter 3). Funders will need to apply the framework’s imperatives in identifying when and how they can better foster such partnerships.

Taking Responsibility for Determining and Mitigating Inequities, Aligning Incentives, and Sharpening Oversight to Support Equitable Innovation

How a problem in health and medicine is studied has implications for how the problem is understood. Researchers customarily turn to the techniques with which they are familiar or those seen as most rigorous in their fields. Applying the framework to research design requires reflecting on the assumptions and values that underlie given research methodologies. In addition, a technical breakthrough often generates excitement and leads to new avenues of research, such as in genomics or machine learning. The availability of new tools can also trigger new funding resources, which further shape ideas about which problems to tackle and how urgent they are. The rise of CRISPR-based genome editing and its potential to address genetic diseases, for example, made the problem of sickle cell disease—which

affects approximately 100,000 Americans⁵—more urgent because it opened new avenues to address it. The development of CRISPR-based tools, arising from basic discoveries in bacteria, also illustrates how the potential impacts of subsequent human applications could be recognized, leading to multiple calls for ethical, social, and governance guidance on the technology’s uses and limits (summarized further in report such as NASEM [2017]). Early-stage studies will not always provide the ability to anticipate such downstream implications.

Applying the framework requires researchers, research institutions, and funders of emerging science and technology to play roles in aligning their work with equity. Consistent with this report’s call for culture change, researchers and developers should be mindful of the intersection of their proposed designs with the aspects of equity described in Chapter 2. Potential impacts on equity should be considered when the research question is posed and the research approach is designed. For example, will the findings draw on or apply to only a specific group (for example, having differential effects by biological sex because of the specific genetic material used, or not being usable by people with visual impairment)? Researchers can ask themselves whether decisions made in the design and conduct of their proposed study have equity implications; the answer to this question could be no, but the intent is to stimulate reflection, awareness, and dialogue. Research institutions and funders can ask themselves whether their cultures and organizational policies support success by a diverse innovation workforce. And funders can ask themselves whether they have considered equity in constructing the portfolio of areas and questions to fund.

Government agencies play an important role in generating the foundations of medical innovation because research funding is dominated by public sources. Philanthropic and private funding also provide valuable research support, and these funders can be leaders in catalyzing emerging or underrecognized areas of research. Some funders and institutions already take steps to recognize equity and other ethical or social considerations when setting program directions. For example, the newly established Advanced Research Projects Agency for Health (ARPA-H) has extended the Heilmeier Catechism traditionally used by the Defense Advanced Research Projects Agency (DARPA) when evaluating programs to include two new criteria: “To ensure equitable access for all people, how will cost, accessibility, and user experience be addressed?” and “How might this program be misperceived or misused (and how can we prevent that from happening)?”⁶

Some funders have also begun to incorporate the expertise of underserved populations in decision making. NIH, for example, convenes a Tribal Advisory Committee⁷ to help ensure that Tribes and American Indian and Alaska Native people have meaningful input into NIH policies, programs, and priorities. Yet despite these efforts, equitable representation remains a challenge; a recent study found that women, for example, continue to have less influential roles than men on NIH study sections (Volerman et al., 2021). NIH and other funding agencies can continue and expand current efforts, or they could create similar forums for other underrepresented groups whose perspectives are crucial to areas of innovation, along with mechanisms for using their priorities to inform agency agendas. Similarly, universities and

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⁵ See Data & Statistics on Sickle Cell Disease at https://www.cdc.gov/ncbddd/sicklecell/data.html (accessed June 30, 2023).

⁶ The Heilmeier Catechism comprises a set of questions developed by a former DARPA director and used by the agency’s program managers when evaluating proposed projects. It includes questions on the project’s objectives, risks, cost, and time; why it can be successful; and what difference its achievement will make (see https://www.darpa.mil/work-with-us/heilmeier-catechism; accessed May 23, 2023). The adapted list of ARPA-H questions used in evaluating new program pitches, including the two additional equity-relevant criteria, is found at https://arpa-h.gov/careers/program-managers (accessed May 23, 2023).

⁷ See https://dpcpsi.nih.gov/thro/tac (accessed June 30, 2023).

companies could create community advisory committees to provide input on whether and how to invest in particular research areas.

The alignment of proposed research with equity can also be incorporated into research review processes, drawing on existing models such as those used in assessing human subjects research and data management plans. Whether by choice, policy guidance, executive order, or legislative mandate, research funders and institutions can require certain projects⁸ to evaluate equity implications; provide feedback to investigators on how they might address identified equity considerations; and provide investigators with assistance from technical experts, social scientists and humanities scholars, and/or community experts on strategies for ensuring that such projects are designed equitably. Questions might include, for example, how a clinical research project considered the needs and priorities of affected communities in its focus and approach, and what steps can be taken to minimize the likelihood that inequities will arise during the phases of research and development. The history of institutional review boards (IRBs) suggests that once a particular type of review has been accepted as a best practice in responsible research, even those institutions that are not required to do so will adopt it (Babb, 2020). The development and dissemination of additional equity-relevant metrics or methods would also be needed to guide the evaluations of institutions, funders, investigators, and community organizations.

Illustrative Examples of Research Partnerships

There are at least two ways to center community knowledge, concerns, and priorities in research formulation and technological design. The first is by using deliberative democratic methods, where representative cross-sections of a population discuss problems and, working together, produce a priority list or short report describing their concerns (Ada Lovelace Institute, 2021; Phadke, 2013; Scharff et al., 2010). A second approach gathers information from leaders who are highly respected and well integrated into their communities (Barnhill-Dilling et al., 2020). In both methods, openness, humility, and respect are key, and researchers must be willing to accept knowledge offered by members of these communities, value the community’s time, and commit to following the guidance provided, factors crucial to establishing community trust and participation (Brown, 2006; Kleinman et al., 2007). Effective and sustained collaborations are not easy to construct or maintain, and staff with technical, social science, and community expertise may be required to guide partnership development and serve as core members of a research team.

Initiatives are emerging across the country and the world that can serve as models. For example, research centers sponsored by the National Institute for Environmental Health Sciences, in consultation with the National Breast Cancer Coalition, pioneered a partnership model in which scientists and women with breast cancer collaborated on research priorities and design (Osuch et al., 2012). These collaborations enhanced trust because “patients felt that scientists saw them as more than just biological samples, data points, or people that needed to be educated or convinced” (Parthasarathy, 2021 p. 6). The collaborations also

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⁸ The committee’s charge (Box 1-2 in Chapter 1) addresses emerging science and technology broadly in health and medicine and supports the importance of awareness and consideration of equity as one of the ethical principles guiding innovation. This does not mean that every institution and funder should require all individual investigators to explicitly assess all types of proposed research studies with respect to all aspects of equity. Such an exercise would quickly devolve into superficiality for fundamental knowledge discovery. Judgment and guiding criteria would be needed to identify which types of proposals require additional equity-focused scrutiny—for example, because proposed research will use certain types of patient-provided biological materials and data, conduct clinical trials, or have other salient characteristics.

changed research as scientists integrated patients’ insights on prevention and treatment into choices about the research and technology to pursue. For example, women with breast cancer taught researchers investigating the impacts of environmental pollutants why they should conduct analyses by zip code rather than by county (McCormick et al., 2004). In another example, participants convinced scientists to assess low-level radiation exposure even though doing so required different measurement tools (McCormick et al., 2004; Parthasarathy, 2021). Members of communities also bring important knowledge about technology design and viability. Developers of a mobile app to improve cardiovascular health among the Black community, for example, discovered through community-based participatory research that the technology made incorrect assumptions about the accessibility of parks and sidewalks for exercise and the availability of fresh foods and vegetables (Cielito Robles et al., 2021).

Such programs help ensure high-quality science, and these partnerships can play roles across an institution’s research enterprise, including by developing and disseminating metrics, tools, presentations, and playbooks that help ensure consideration of equity at the earliest stages of innovation. Other examples are provided by the Healthy Flint Research Coordinating Center (HFRCC) and Flint Center for Health Equity Solutions (FCHES), which were designed as equitable partnerships between residents and university researchers to identify needs, develop solutions, give appropriate credit to community members, create research efficiencies, and ensure ethical practices (see Box 4-1).

A cautionary example is provided by the engagement of an Arizona State University geneticist with the Havasupai tribe, in which practices that might be seen as efficient—reusing samples across studies—led members of the Havasupai to feel that their civil rights were not being respected and that the research reinforced a distorted understanding of their history. In 1989, tribe members approached a researcher to study the prevalence of diabetes among their population (Garrison et al., 2019). The researcher agreed to collect and analyze their DNA but did not inform them of a grant to study the tribe’s genetic risk of schizophrenia. It has been widely reported that the researcher performed both analyses and accessed the tribe’s medical records to enhance the quality of her work. The resulting publication drew conclusions about schizophrenia and inbreeding. The tribe sued the scientist and university after discovering that this topic had been investigated without their consent, feeling that they had inadvertently contributed to the production of harmful analyses about their community (Garrison, 2013; Garrison et al., 2019). While this narrative is not without controversy (Lewis, 2013), the broader lesson on the importance of thoughtful engagement, transparency, and shared decision making remains. The case, Havasupai Tribe v. the Arizona Board of Regents, was ultimately settled for $700,000 (Garrison et al., 2019; Harmon, 2010).

Researching, Developing, and Assembling a Technology

Choices in this phase reflect how research and technology are designed and tested; how value, including in the form of intellectual property, is identified, managed, and licensed; and what is selected for further investment and development. The framework imperatives introduce iterative governance and broaden partnerships and engagement in innovation, expanding who is involved in this phase and strengthening innovation by bringing diverse perspectives to bear on an area of emerging science and technology.

Broadening Participation

Once experts and interested parties have converged on a technology to develop and have received funding and research approvals, the challenge shifts to design and develop-

ment. This has traditionally been the province of scientists, engineers, and their funders at both public and private organizations. The science and technology under development and its intended uses will necessarily inform who needs to be most actively involved. Funders such as NIH and the Patient-Centered Outcomes Research Institute (PCORI) provide guidance on the process of stakeholder engagement, but under the current system, innovation developers must generally think through which groups they expect to be impacted by their products and identify how to engage with them. Not all scientific and technical communities have the knowledge, infrastructure, and capacity to do this well, nor do all potential partner community organizations. Governance interventions, such as including grant requirements to craft and provide practical guidance and making flexible use of incentives such as supplemental funding or expedited review, can support the establishment and maintenance of

partnerships in applicable areas of technology development. Several examples of initiatives supporting community engagement in research and models for benefit sharing to value the contributions of research participants are highlighted in Box 4-2.

Taking Responsibility for Determining and Mitigating Inequities, Aligning Incentives, and Sharpening Oversight to Support Equitable Innovation

Patent and technology transfer systems can take steps to address equity without disturbing the right to intellectual property. These steps include assessment of patent “quality” and determinations about the categories of patentable subject matter, as well as issuing of narrower patents, steps that have been taken in other countries (Parthasarathy, 2017). Patent stakeholders in the U.S. system can explore similarities and differences in approaches taken by other countries, and how these policies have impacted innovation and equity (see Box 4-3).

For patents arising from public funding, the federal government also has the ability under the Bayh-Dole Act (35 USC §§ 200–212) to exercise “march-in” licensing rights if “action is necessary to alleviate health or safety needs which are not reasonably satisfied by the contractor, assignee, or their licensees.” No funding agency has yet chosen to exercise these rights (Cook-Deegan et al., 2022), and NIH declined another such request in 2023, although the Department of Health and Human Services and Department of Commerce recently announced a review of march-in authority (HHS, 2023b). It has also been argued that under patent law (28 USC § 1498), the government could step in to distribute generic versions of a drug to combat high prices, an option that was discussed in the context of hepatitis C drugs (Brennan at al., 2016; see also Box 3-2 in Chapter 3), although it was not exercised.

It may be possible to broaden the range of actors involved in patenting and licensing conversations to help achieve input equity (Chapter 2), subject to applicable authorities and regulations. The U.S. Patent and Trademark Office (USPTO) has established programs, such as the Council for Inclusive Innovation, aimed at increasing the participation of underresourced

inventors,⁹ and in support of Executive Order 14036 (“Promoting Competition in the American Economy” 2021) has established collaborative initiatives with the U.S. Food and Drug Administration (FDA) on patenting, particularly in pharmaceuticals.¹⁰ While it frequently convenes town hall meetings to understand and prepare for emerging areas of technology, participants usually include only prospective inventors, patent agents, and lawyers rather than members of affected communities who might speak to, for example, their concerns about implicit biases embedded in ML technologies that can limit utility. USPTO also convenes a Patent Public Advisory Committee to advise the director on “matters relating to policies, goals, performance, budget, and user fees” (35 USC § 5; 86 FR 99:28084–28085),¹¹

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⁹ See https://www.uspto.gov/initiatives/equity/ci2 (accessed June 30, 2023).

¹⁰ See https://www.uspto.gov/initiatives/fda-collaboration/what-are-uspto-fda-collaboration-initiatives (accessed June 30, 2023).

¹¹ See https://www.uspto.gov/about-us/organizational-offices/public-advisory-committees/patent-public-advisory-committee-ppac (accessed June 30, 2023). The Patent Public Advisory Committee was established under P.L 106–113 (1999).

although historically, this committee has been composed of the same types of stakeholders as town hall meetings and has not included civil society members. If USPTO were to take a more expansive approach to public engagement, including explicit attention to the concerns of marginalized communities, it might identify changes to administration and examination practices that could enhance the consideration and incorporation of equity. To further support this goal, a variety of other patent reforms have been proposed, the implications of which could be further explored (for example, see I-MAK’s proposals for patent reform¹²).

Universities realize financial gain from patenting and licensing the intellectual property created by their researchers, and have created guidance in this area. To foster alignment with the governance imperatives in this report, research institutions could consider expanding their understanding of responsibilities and practices encompassed by the “Nine Points to Consider in Licensing University Technology” document (AUTM, 2007), particularly the application of point nine on provisions that address unmet needs.

Socially mindful technology licensing initiatives provide one model. An example is the Socially Responsible Licensing Program of the University of California, Berkeley, which aims to stimulate investment in products that bring benefits in developing countries, and to promote “affordability and accessibility of drugs, therapies, diagnostics, crops, and vaccines to the developing world by stimulating investment where it has been traditionally lacking under profit-motivated business models” (Mimura, 2006). A case example is the development of semisynthetic artemisinin, in which researchers and developers paid explicit attention to the roles of technology licensing and the needs of populations in countries in which malaria is prevalent (see Box 4-4).

Collaborations, such as public–private partnerships and product development partnerships, can also be instrumental in spurring translational research and sharing or reducing the risk involved in long-term, large-scale research and development investments. One example is BioMADE, an institute launched in 2021 with support from the U.S. Department of Defense’s Manufacturing Innovation Institute program.¹³ BioMADE is designed to speed the development of a substantial infrastructure for biotechnology-based manufacturing, a crucial support for the growing bioeconomy. At the request of the government, the successful BioMADE proposal included a section addressing ethical and social issues related to this area of biotechnology research and development, and the institute’s website states: “A commitment to incorporating safety, security, sustainability, and social responsibility (4S) is part of the fabric of BioMADE. All technical and education and workforce development projects must include elements dedicated to relevant 4S topics…. BioMADE will create new models and norms for 4S bioindustrial manufacturing.”¹⁴ In developing this concept, BioMADE adopted principles and values that include a commitment to meet or exceed existing standards for reducing risks of harm in the workplace or to the environment, welcoming people representing a diverse range of viewpoints into every stage of its activities, and collaborating with those working to diversify the pipeline for the biotechnology workforce. It also made a commitment to seeking ways to make its products and processes as useful as possible to society, with attention to equitable distribution of benefits and risks and to responsiveness to society’s needs and values. BioMADE is still in its start-up phase, so it is too early to evaluate how this commitment affects the speed and efficiency of its efforts to promote innovation in manufacturing. It is notable, however, that the focus on 4S values reflects a joint decision by the U.S. Department of Defense and the private-sector companies involved in this collaboration.

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¹² See https://www.i-mak.org/patent-reform/ (accessed June 30, 2023).

¹³ See https://www.biomade.org/ (accessed June 30, 2023).

¹⁴ See https://www.biomade.org/social-dimensions (accessed June 30, 2023).

Another example is ARPA-H,¹⁵ a new agency in the Department of Health and Human Services that also promotes public–private and product-development partnerships. ARPA-H features a new operating and funding model that seeks to identify, develop, prototype, and commercialize high-risk, high-consequence strategies with the potential to transform health and medicine. Notably, from the very first step in advancing an idea for ARPA-H support, applicants are compelled to state explicitly the elements of equity and social justice that their project will address.

A collaborative effort is also under way among representatives of academic institutions and venture capital and law firms that has developed a model term sheet for the launch of a life science start-up and plans to release a full license agreement template (MIT, 2023). Although this effort is not focused on social benefit, it could similarly provide an opportunity to explore how this report’s governance framework could be applied to start-up formation.¹⁶ Other tools that could be explored as potential strategies for addressing these challenges include the use of patent pools and efforts to mitigate patent ‘thickets” (Mattioli and Merges, 2017; Rai and Price, 2021; Sherkow, 2017).

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¹⁵ See https://arpa-h.gov/ (accessed June 30, 2023).

¹⁶ See https://tlo.mit.edu/resources/news-events/representative-term-sheet-launching-life-science-startups (accessed June 30, 2023).

Another mechanism for incentivizing innovation in certain areas is the Orphan Drug Act (21 CFR Part 316), which incentivizes drug development to treat diseases that affect fewer than 200,000 people in the United States. Because drugs for diseases that affect relatively small populations are less lucrative than drugs with broader use, these diseases are unlikely to be targets of research and development efforts in the absence of incentives. Among other measures, the act extended patent exclusivity to 7 years and provided a tax credit for a portion of research and development expenses, making it more appealing for companies to invest in developing drugs that would qualify for these advantages. This approach involves trade-offs, and efforts to assess its effectiveness have found mixed results, leading some to call for reforms to better align its incentives with desired outcomes (Fiore, 2023). Nevertheless, the act is widely perceived as a success within the pharmaceutical industry, and orphan drugs now constitute about half of all FDA-approved drugs (Cavazzoni, 2022).

Beyond the initial decision of whether and how much to invest in a technology or company, there are many points at which investors or companies can choose to keep investing or not, but the core incentive remains largely the same: How big a payoff is expected? Therefore, applying the governance framework to influence such decisions will likely need to connect to ultimate financial returns. In this context, investors are highly attuned to signals from downstream payers; investors are unlikely to prioritize equity if an end payer is not willing to pay for it. Investing in a drug that disproportionately benefits a group that has historically received inequitable care will incur a loss if government or private payers do not view the drug as worth paying for. Price, access, and coverage concerns have been raised around emerging but expensive gene and drug therapies, including for sickle-cell disease and beta thalassemia, which benefit a relatively small number of patients, many of whom are in historically marginalized groups (Allen et al., 2023; DeMartino et al., 2021; Hiltzik et al., 2022; O’Donnell and Mathis, 2019; Thuret et al., 2022). This situation underscores the need for continued work on how incentives can be aligned across the full innovation life cycle to meet the needs of multiple actors and users.

The diversity of the innovators, investors, and entrepreneurs who pursue emerging technology development is another factor to consider. Representation—or its lack—has been shown to influence what gets invented and patented. For example, one study found that fewer women than men held biomedical patents, but their patents were more likely to focus on women’s health (Koning et al., 2021). It has also been reported that “demographically underrepresented students innovate at higher rates than majority students, but their novel contributions are discounted and less likely to earn them academic positions” (Hofstra et al., 2020, p. 9284). In 2019, only 1 percent of venture capital funding went to companies with Black founders, and 2.7 percent went to companies with all-female founders (Cooper et al., 2020). Investing in underrepresented entrepreneurs and in firms that serve untapped markets can not only help combat historical underinvestment but also bring financial gains for investors. Examples of such funds include Jumpstart Nova, IndieBio, VentureWell, Harlem Capital, Backstage Capital, Black Angel Tech Fund, Kapor Capital, and others.

Other investors emphasize opportunities to align profit with approaches that also consider environmental, social, and governance (ESG) practices and frameworks for engaging in responsible innovation¹⁷ or for considering the roles of these factors in investment decisions.

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¹⁷ The term “responsible research and innovation (RRI) gained visibility in Europe through, for example, European Commission scientific and technological programs such as Horizon 2020. Various venture capital and investment firms also use approaches designated as or aligned with responsible innovation (for example, General Catalyst; https://www.generalcatalyst.com/mission; and Phoenix Court Group; https://www.businesswire.com/news/home/20220620005322/en/Phoenix-Court-Group-Introduces-500m-in-New-Funds-to-Support-Founders-From-Seed-to-the-Public-Markets-and-Beyond; accessed June 30, 2023).

These efforts can represent potential models for supporting and investing in emerging science innovations in ways that recognize the role of profit in innovation while aligning with the equity imperatives described in this report. In particular, limited partners (LPs) can influence the priorities of venture capitalists through the venture funds in which they chose to invest. Many LPs, especially those associated with nonprofits such as university endowments and foundations, are already exerting pressure on venture funds to prioritize technologies that support decarbonization in line with goals for mitigating climate change; these investors could similarly exert pressure on venture capitalists to elevate equity considerations. The development of criteria for rating venture capital portfolios on various dimensions of equity could provide a mechanism for increasing attention to this issue and facilitating equity audits by interested LPs.

Evaluating a Technology’s Performance

Whether part of required approval processes (such as through the FDA) or as part of a company’s development plans, the performance of health and medical technologies is evaluated in various ways before it sees widespread use.

Broadening Participation. Taking Responsibility for Determining and Mitigating Inequities, Aligning Incentives, and Sharpening Oversight to Support Equitable Innovation

Applying the imperatives of the framework at this stage involves asking how performance and outcomes are evaluated; in which subsets of anticipated users; whether there are biases or other issues in the data, metrics, and input considered in the evaluations; and whether the innovation appears to impact equity in positive or negative ways. One example of a failure to take these steps is the recognition during the COVID-19 pandemic that many pulse oximeters inaccurately assessed blood oxygen levels among people with darker (melanated) skin (see Box 2-1 in Chapter 2). This case demonstrates the importance of conditioning approval of a device on explicit attention to how well it would perform across the entire population of users. There have also been publicized cases of bias in AI-based and other data-derived clinical algorithms. For example, racial scaling factors have been found to produce biased outcomes in algorithms for measuring kidney function and assessing disability resulting from brain injuries (Oliveira, n.d.; Vyas et al., 2020). These cases increased recognition of the problems that can arise downstream when performance data include only a subset of a technology’s future users.

Applying the framework means recognizing the potential for such inequities to arise and crafting guidance to address and mitigate them, processes that are already under way in some areas. Over the past few years, a number of efforts have been directed at ethical and equitable AI, including how to benchmark for the representativeness of data. The FDA has also advanced efforts to enhance demographic diversity in participation in and the data obtained from clinical trials,¹⁸ and recently announced plans for new requirements for late-stage clinical trials (Kozlov, 2023). Researchers are developing expanded measures for evaluating inclusion and diversity in trials, including by gender, race, ethnicity, and age (Varma et al., 2023). Companies that develop tools for clinical research can work to ensure that such tools advance equity- and inclusion-oriented objectives in a variety of ways, such as by ensuring

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¹⁸ See, for example, https://www.fda.gov/consumers/minority-health-and-health-equity/enhance-equity-initiative (accessed June 30, 2023).

that content is accessible and understandable to as many potential participants as possible. For example, multiple types of media (e.g., explanatory videos) can be used in addition to traditional text consent forms while adding cultural context to broaden access and inclusion.

For products that undergo premarket review, such as new drugs and some medical devices, current regulatory reviews focus largely on assessing safety and efficacy, although these are not the only considerations. In the case of drugs for HIV/AIDS, for example, advocacy from affected communities and others highlighting the urgency of the health need led to changes designed to expedite drug performance assessment, commercialization, and patient access (see Box 4-6).

The FDA can take other approaches as well, such as considering benefit implications for subpopulations. For example, if a medical product benefits many but has limited benefit (or entails extra risks) for a subpopulation, the agency often provides guidance through labeling or “dear doctor” letters about avoiding use by those at added risk or drawing attention to populations that might benefit but have been overlooked. Drawing on the framework, enhancements to the methods, mandates, and consistency with which products are assessed for equity-relevant factors could be considered. Any such changes would likely require further and more detailed analysis of potential advantages and costs, and could in some cases require legislative changes. For example, current reviews for safety and efficacy could be expanded to include effectiveness measures that could be used to explore predicted effectiveness within various subpopulations or the predicted distribution of product use postapproval to inform decisions on the need for and makeup of potential postmarket studies. Or the reviews could be expanded to include input on a wider range of ethical and social considerations beyond safety and efficacy or to include a broader array of input from members of the public or affected and underserved communities.

Accessing and Using a Technology

Even if a technology is shown to perform well and is approved for use, there is no guarantee that it will reach and benefit all potential users. Many factors affect who will and will not have access to a technology, including where and to whom it is made available, how much it costs and who pays that cost, the process for gaining access to it, and the requirements for using it.

Broadening Participation. Taking Responsibility for Determining and Mitigating Inequities, Aligning Incentives, and Sharpening Oversight to Support Equitable Innovation

A variety of factors can create barriers to equitable access to and use of a technology. For example, many technologies used in medical settings—even seemingly simple ones such as the scale—were not designed with consideration for the needs of people with disabilities, thus limiting these people’s access to care and exacerbating the discrimination they experience (Iezzoni et al., 2021). Even when technologies are effective, they may be so expensive that people with limited incomes cannot afford them. Hepatitis C, for example, affects approximately 5 million people nationwide, 20 percent of whom will develop severe complications that require medication, hospitalization, and liver transplant. In recent years, the FDA has approved a handful of new drugs for hepatits C (Trooskin et al., 2015), but the limited number of available treatments enables companies to charge prices on the order of $84,000 to $95,000 for a 12-week regimen, limiting the use of the drugs (Henry, 2018) (see also Box 3-2 in Chapter 2). Another example is the newest drug treatments for obesity, originally developed for type 2 diabetes but having shown benefit for people trying to lose weight (Jastreboff et al., 2022). When prescribed for obesity alone, this is often considered an off-label use and is usually not covered by insurance. Even if the drugs are approved specifically for obesity, a major insurer—Medicare—will be precluded from coverage, as it is not allowed to pay for weight loss medications (McGinley and Bernstein, 2022). Obesity is most prevalent among lower-income populations, who are least able to afford paying out of pocket for such expensive drugs (Anekwe et al., 2020). Using the power of the government to ensure coverage of these drugs to treat obesity could be viewed as a step toward more equitable access to this class of drugs, although a more detailed analysis of benefits, costs, and trade-offs would be required.

The Open Insulin Foundation is one example of an initiative exploring new models and opportunities for reducing costs of and improving access to health technologies and for bringing production closer to a technology’s end users. In the Open Insulin project, technical experts and people with diabetes work together to understand needs and develop local sources of safe, affordable, and high-quality insulin (see Box 4-7).

Health care organizations and payers could incorporate equity considerations into health technology assessments to inform purchasing decisions or to support or require post-implementation surveillance that would illuminate impacts on equity as a basis for altering purchasing or coverage decisions. To take advantage of this opportunity may require incentives or requirements on the part of health care organizations or payers. Insurers’ coverage decisions are subject to state and federal law, which offers one potential avenue for expanding analyses of ethical and equity implications as part of purchasing and coverage decisions. In addition, developing and using equity-focused metrics would require the collection and use of relevant data. Accordingly, a coordinated framework must consider what, when, and how data are collected, analyzed, and used to advance equity.

Organizations that play outsize roles in the overall health care ecosystem also have an opportunity to lead the way in advancing equity. For example, the Veterans Health Administration (VHA) is the largest integrated health care network in the United States, serving 9 million veterans each year at 1,255 health care facilities.¹⁹ Processes or requirements implemented by the VHA with regard to ensuring equity in access to health technology not only impact technology access and use within the VHA network but also can have ripple effects throughout health care more broadly by influencing how companies design and deploy technologies. With its extensive data on those it serves, the VHA is also well positioned to study technology impacts and gaps, as well as to experiment with approaches to improving equity in technology design, performance evaluation, and deployment. Another example is the Centers for Medicare & Medicaid Services (CMS). As the single largest payer

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¹⁹ See https://www.va.gov/health/aboutvha.asp (accessed June 30, 2023).

for health care in the United States through its Medicare, Medicaid, and Children’s Health Insurance Plan (CHIP) programs, CMS has significant influence on the health care system. Its coverage decisions have broad implications for who can benefit from health innovations, how much the innovations cost, and the processes for gaining access to them. With the recent launch of its Framework for Health Equity 2022–2023, CMS established five priorities for advancing its infrastructure for equity-related assessment, fostering structural change, and ensuring equitable access to its services and coverage, positioning the agency to pave the way for the advancement of equity principles (CMS, 2023). The CMS Innovation Center has also announced that it is exploring a new model for expanding access to certain types of very high-cost therapies (the Cell and Gene Therapy Access Model, in which CMS would help state Medicaid agencies coordinate agreements with manufacturers) (HHS, 2023a).

Learning from a Technology’s Deployment

An important imperative guiding the governance framework is to sharpen iterative oversight and evaluation along innovation life cycles. Applying this imperative requires collecting relevant information after a technology has been deployed and using it to learn and change. This process is similar to the “learn” phase of the design, build, test, learn (DBTL) cycle commonly used in engineering disciplines. In the life sciences, the DBTL cycle has been embraced in such fields as synthetic biology. The emphasis is on learning from prior attempts to improve subsequent designs and create more effective or efficient methods and outcomes (Lawson et al., 2019; NASEM, 2018).

Broadening Participation. Taking Responsibility for Determining and Mitigating Inequities, Aligning Incentives, and Sharpening Oversight to Support Equitable Innovation

Several existing mechanisms facilitate postmarket data generation and use in the context of health innovations. For some technologies, there are regulatory requirements to evaluate performance in the postmarket context. Payers also may condition reimbursement or payment for medical technologies on the generation of follow-up data, which often helps them determine which treatment options are most effective in a real-world context. Companies engaged in health care delivery may be incentivized to participate in postmarket performance evaluation to the extent that they depend on payer reimbursement that is conditioned on such evaluation. Systems used for collecting postmarket data include registries, electronic health record (EHR) systems and case report forms, patient-reported outcome surveys, claims records, and public health data from government sources, among others. For example, the importance of ongoing postmarket analyses and audits of AI/ML-based tools is increasingly being recognized (see also Box 3-4 in Chapter 3 for a case study of AI/ML technologies in health care).

While most existing mechanisms are geared toward assessing the safety and efficacy of technologies, there are also opportunities to identify additional impacts of a technology, such as the distribution of burdens and benefits, as well as how the technology fits into the overall delivery of care. A useful framework for this purpose is the concept of a learning health system, advanced by the National Academies and others and supported by agencies such as the U.S. Department of Health and Human Services’ Agency for Healthcare Research and Quality (AHRQ, 2019) (see also IOM, 2007; NASEM, 2016). As articulated at a 2006 Institute of Medicine workshop, a learning health care system is “designed to generate and apply the best evidence for the collaborative health care choices of each patient and provider; to drive the process of discovery as a natural outgrowth of patient care; and to ensure innovation, quality, safety, and value in health care” (IOM, 2007, p. ix). Accomplishing these goals requires an iterative process that includes input from affected communities and considers the views and responses of consumers or members of the public in order to translate research to practice more effectively and achieve better outcomes and better value.

Learning from a technology’s deployment can influence both how that technology is used and how future ones are developed. The pregnancy drug Makena provides an example of the former (Box 4-9) and the MakerNurse initiative provides an example of the latter (Box 4-10). Fostering participation by nurse innovators enables the practical experiences and lessons from real-world health care practice to be further incorporated into the innovation life cycle, thereby informing new directions for research and innovation. It also helps broaden who becomes part of the innovation workforce.

LEVERAGE POINTS FOR INFLUENCING THE SYSTEM TO IMPLEMENT THE FRAMEWORK

As the examples presented throughout this chapter illustrate, there are multiple opportunities to take action at every phase of the innovation life cycle to align emerging science, technology, and innovation in health and medicine with equity goals. Governance levers represent tools or capabilities that can be used to implement change in the system, and thus present opportunities for reimagining or revising the incentives and disincentives that affect the choices and behaviors of those who take part in innovation. Determining the points at which changes could be implemented, which players and actions should be incentivized, and for which purposes requires making choices about priorities, costs, benefits, and potential trade-offs. Identifying these priorities and weighing these trade-offs will require ongoing horizon scanning and evaluation to understand where populations are currently underserved and what impacts result.

Incentives Can Represent Both Pushes and Pulls

The forces that influence actors’ decisions along innovation life cycles include both pushes and pulls.

Push incentives propel actors toward certain choices. Examples include a grant proposal requirement that clinical or translational investigators explain how their research design anticipates and addresses an equity issue, or how it values the contributions of participating patients and communities; enforcement of requirements for diversity in clinical trials to increase the chances that an approved product will be widely useful; and increased use and enforcement of Phase IV postapproval trials to confirm safety and efficacy across the broad population of users. Push incentives tend to yield more immediate short-term results relative to pull incentives, but risk overly centralizing power in the hands of those with the pushing power, such as funders. They can also risk imposing unrealistic demands and costs on entities that are unready, unable, or unwilling to change.

Pull incentives make a certain action more enticing. Examples include offering a grant specifically for work that imagines a more equitable version of an existing therapy or delivery system; opportunities for expedited FDA review; policies such as the Orphan Drug Act, which make certain areas of research and development more enticing by enhancing the rewards for success; and the issuance of priority review vouchers for a profitable product in exchange for focusing attention on products for underserved populations. Pull incentives are more about weighting aspects of the market and letting the market respond. They may

be more politically or culturally palatable than push incentives in some contexts, although they also risk expending funds without necessarily achieving outcomes that meet the need.

Combining push and pull incentives can address the different pressures to which various stakeholders best respond and help create a comprehensive system that invites innovative ways to address inequities and inspires desired outcomes. The 3P project provides an example of push and pull levers aimed at an equity outcome—in this case, the goal of accelerating innovation toward an affordable, accessible 1-month tuberculosis regimen (MSF, 2016).

In general, interventions supporting equity and mitigating inequities in early phases of emerging science and technology development—for example, by diversifying the STEM workforce or enhancing substantive research partnerships with affected communities—are likely to be more impactful than attempts to mitigate inequities that are introduced later and amplified along the way. However, the equity implications associated with an emerging technology may only become apparent or may change in nature in light of further development or widespread use. Push and pull incentives can also have unintended consequences as stakeholders attempt to use them to their advantage, a circumstance that has arisen, for example, with the Orphan Drug Act (Daniel et al., 2016; Tribble and Lupkin, 2017). Since it is nearly impossible to create a perfect system, ongoing, iterative governance and evaluation are necessary to ensure that the outcomes of interventions targeted at advancing equitable innovation continue to align with intended goals.

Leverage Points in the System Can Be Used to Implement Change

Examples of leverage points that provide key opportunities to incentivize or disincentivize changes to the innovation system in health and medicine are summarized below. This is not an exhaustive list, and not all levers will be appropriate to all areas of technology, types of actors, or points within the system. Choosing to apply some levers may require policy and regulatory changes or new funding, while essential elements may already in place for others such that they require only community or political will. Choices about which levers to apply and when and how to apply them may also have significant budgetary and workforce implications.

Leverage Point: Priority Setting and Research Funding.

Significant research support is provided by government agencies, with additional support being provided by philanthropic and private funders. Research funders influence the innovation system and its alignment with ethical principles, including equity, through such levers as

• issuing requests for proposals in an equity-aligned area, supporting increased research attention to a given topic, and decreasing uncertainty involved in making downstream investments in that area;
• supporting the generation and use of data relevant to identifying inequities and their sources;
• incorporating proposal requirements, checklists, or proposal review criteria relevant to equity;
• requiring and incorporating diverse perspectives on agency program teams, review panels, and funded research teams; and
• building capacity within community organizations to enable their participation in research agenda setting and research partnerships.

Leverage Point: Research Approvals and Technology Performance Assessments.

It is valuable to assess explicitly how a product will perform across the entire population of intended users. Regulatory agencies, research-conducting organizations, and health care organizations influence how clinical testing is conducted and what evidence is required before a product sees widespread use. For example, the FDA recently issued guidance for industry on increasing racial and ethnic diversity in clinical trials (FDA, 2022). Norms guiding professional conduct and best practices in a field can also be important. Potential levers include

• requirements that clinical testing meet minimum standards for geographic, racial, ethnic, and/or other types of study diversity and data representativeness;
• use of expedited regulatory reviews in targeted areas;
• expansion of current reviews for safety and efficacy to include effectiveness measures that reflect equity considerations, such as predicted distribution of use or predicted effectiveness within various subpopulations; and
• requirements to evaluate postmarket performance data on effectiveness and uses in order to identify inequities that may arise.

Leverage Point: Recruitment for and Participation in Clinical Trials.

Patient and consumer participation in research is a cornerstone of the advancement of science, technology, and innovation, and recruitment and retention is one of the most critical aspects of clinical trials. Patient advocacy and community organizations can play roles in fostering equity, including by funding and helping to design clinical trials and recruiting patients to participate. Half of all clinical trial sites underenroll, and 11 percent of sites fail to enroll a single patient.²⁰ Health care organizations can also play gatekeeping roles in approving research involving their patients, care teams, and EHR data. Levers include

• actions by patient and community groups to assist, support, or discourage members’ participation in trials, including the power to pressure researchers and technology developers to design, conduct, and recruit in ways that are responsive to and aligned with community needs;
• conditions for clinical trial or site approvals requiring community advisory boards or community-based research locations that expand patient and community engagement or address such issues as data ownership and fair remuneration for those who contribute to the research; and
• support and/or requirements from funders for the involvement of patients and community groups in recruitment and participation for clinical trials and their engagement on community advisory boards.

Leverage Point: Management of Intellectual Property.

Governments set the terms and conditions for intellectual property rights, providing a powerful lever that influences the behavior of a range of actors in the innovation system, including private companies. Research-conducting organizations, such as universities, also exert influence through their technology transfer and licensing practices. Potential levers include

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²⁰ See https://csdd.tufts.edu/ (accessed June 30, 2023).

• terms and conditions set by government, such as the nature, scope, and length of patent exclusivity;
• use of socially responsive licensing provisions aimed at addressing particular equity goals;
• exercise of government “march-in” rights to require additional licensing by a university or its licensee if “such action is necessary to alleviate health or safety needs” that are not being satisfied (35 U.S.C. § 203);²¹ and
• exercise of government power under 28 U.S.C. § 1498 to enable the government to use any “invention described in and covered by a patent of the United States” without a license, provided that the use is “by or for the United States,” and the patent holder is afforded “reasonable and entire compensation.”

Leverage Point: Investment Choices.

Technology investors such as venture capital firms make decisions about which companies to invest in and how much to invest, and companies make choices about which products to develop, commercialize, and promote. Some funds focus on investing in historically underrepresented innovators, for example, but expected profit, including development cost, time to market, and expected return, is a key driver of investor and company choices. Two ways to influence decisions are to increase the expected profit or decrease the uncertainty involved. Actions or policies that achieve these outcomes can tip the scales toward investments that advance equity by making such investments more attractive from a financial standpoint. Potential levers include

• government policies that stimulate innovation in particular areas by offering favorable market advantages, such as opportunities for expedited FDA review, which shortens the time to market, or the Orphan Drug Act, which incentivizes the development of treatments for rare diseases;
• public or philanthropic investment in early-phase science in areas identified as equity promoting, such as the Gates Foundation’s funding of nonprofit One World Health to develop yeast-synthesized artemisinin for treatment of malaria, thereby increasing the pipeline of innovations that might be commercialized and reducing downstream risk and uncertainty;
• the incorporation of equity implications of a health innovation into the criteria for assessing environmental, social, and governance factors for companies involved in its development, which could potentially improve a company’s reputation and attract investors who value these factors; and
• the conduct of equity audits or other means of imposing pressure for companies to attend to equity concerns in their investment portfolios by large-scale investors such as managers of university endowments, foundations, and pension funds.

Leverage Point: Legislative Incentives or Prohibitions in Targeted Areas.

Through their legislative and policy-making authority, federal, state, and local governments can take action to incentivize or discourage choices in the innovation system. Examples of levers include

___________________

²¹ While the mechanism for this lever exists, no federal agency has ever begun the process for using it and NIH has declined to initiate the process despite requests over the years (Rai and Cook-Deegan, 2017).

• legislation to incentivize the development of technologies that benefit certain groups—the Orphan Drug Act is a potential model, and although aimed at benefiting people with rare conditions, could inform use of a similar approach to incentivize investments that benefit people in other groups or situations, such as those who live in certain geographic areas, have certain racial or ethnic backgrounds, or have low incomes;
• legislation altering return on investment through direct grants, tax incentives, or nontax incentives (such as FDA priority review vouchers that incentivize the development of therapeutics for tropical diseases); and
• legislation that prohibits or restricts certain activities, such as the Genetic Information Nondiscrimination Act, which restricts use of personal genetic information by health insurance companies.

Leverage Point: Health Care Purchasing and Coverage Decisions.

Regulations and decisions about insurance coverage can send signals about potential market size and economic viability that affect investment decisions. Coverage decisions by insurers are subject to both state and federal law, and health care organizations also make decisions about the products they purchase and use. Potential levers include

• government requirements to, for example, cover drugs for certain underrepresented or underserved populations, thus increasing access to such drugs and incentivizing companies to invest in their development, although trade-offs with this approach could include increasing overall drug costs;
• public or private payer policies that enable companies to predict the price they will receive and a timeline for reimbursement;
• requests or requirements established by health care organizations, CMS, or private health insurers, such as requiring equity-focused health technology assessment as a prerequisite for purchasing, implementation, or coverage determinations (Culyer and Bombard, 2012);²² and
• alternative pricing models aimed at reducing the high costs of certain new types of therapies, such as CAR-T and gene therapies—for example, a public–private collaboration could potentially amortize the costs of such therapies as savings emerge from prevention and disease mitigation, use outcomes-based contracts to provide payers with rebates in the event of lack of efficacy, or apply subscription-based arrangements to mitigate risk for both payers and manufacturers.

Leverage Point: Product Liability.

Federal and state liability rules and liability insurers also influence decisions in the health and medicine arena. Potential levers include

• liability rules that allow a product, even if approved for market use, to be subject to claims of design defect if it disproportionately fails to function in a particular population;
• policies or practices that reduce potential liability should a product lack efficacy or produce inequitable risks or side effects in a given population—for example,

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²² CMS does not currently conduct technology assessment of this type but could consider developing additional capacity to do so.

the National Vaccine Injury Compensation Program was established in the 1980s to provide compensation in rare cases of vaccine-caused injury, reducing risks and costs to industry and incentivizing vaccine development; and

• requirements from liability insurers to incorporate equity considerations and potential equity risks into technology assessments as a condition for coverage.

Leverage Point: Public and Consumer Expectations and Pressure.

In addition to patient advocacy organizations and organizations representing affected and historically marginalized communities, members of the broader public have expectations around the development, assessment, and use of emerging technologies and products, including what standards should be used to evaluate such issues as ethics, safety, efficacy, and privacy and the role of government in regulation. Issues of equity have also become more prominent in the public discourse within the past decade, including as a result of the disproportionate impact of COVID-19 on people by virtue of race and ethnicity, age, health status, residence, occupation, socioeconomic condition, or other contributing factors. Examples of levers include

• government calls for comments on proposed policy and regulatory decisions; and
• public opinion surveys on areas of science and technology that may influence researchers and policy makers, such as those informing recent reports on uses of AI, human enhancement, and animal-derived organs for transplant, although not focused on equity issues.²³

CHAPTER CONCLUSIONS

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²³ See https://www.pewresearch.org/topic/science/science-issues/biotech/ and https://www.brookings.edu/series/public-opinion-surveys-on-ai-and-emerging-technologies/ (accessed June 30, 2023).

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