The State of the U.S. Biomedical and Health Research Enterprise: Strategies for Achieving a Healthier America (2024)
Chapter: 2 A Strategic and Coordinated Approach to the U.S. Biomedical Research Enterprise
2
A STRATEGIC AND COORDINATED APPROACH TO THE U.S. BIOMEDICAL RESEARCH ENTERPRISE
To achieve the vision for an improved and more robust U.S. biomedical research enterprise laid out in Chapter 1, the federal government, academia, philanthropy, venture capital, and all other stakeholders must consider and plan for America’s needs in a more coordinated, thoughtful, and strategic manner.
FRAGMENTATION STANDS IN THE WAY OF MAXIMUM POTENTIAL
The collective investment of the federal government, venture capital, industry, and philanthropy into the biomedical research enterprise is significant—in 2019, U.S. spending accounted for 27% of the global total investment in research and development (R&D), the highest absolute dollar investment of any country (NSF NSB, 2022).
Despite this massive investment, the “buckets” of money committed to the enterprise in the United States sometimes have competing priorities, diluting the effectiveness of such a remarkable amount of money. The type of funding source—even inadvertently—can influence research priorities, goals, and approaches—for better or worse. Not all agendas benefit all stakeholders, because each sector has its own priorities for spending.
For example, the private sector—including biotechnology, pharmaceuticals, and venture capital—is driven by market pressures and returns on investment, and therefore focuses primarily on research that will result in products, including therapeutics and devices. Although these therapeutics and devices are usually available to all consumers, industry-driven basic research often relates directly to business strategies and is therefore confidential, which contributes in a siloed and skewed manner to the U.S. knowledge capital and may not benefit other researchers.
In contrast, the goal of the National Institutes of Health (NIH)—the largest federal funder of the biomedical research enterprise—is to seek fundamental knowledge and apply that knowledge broadly (NIH, 2017). Interpreted narrowly, that goal might include only basic research, but NIH actually funds everything from basic to applied research. Per NIH’s data, the distribution of its budget spent on basic versus applied research over the past 20 years has ranged from approximately 60–40 to approximately 50–50 (Lauer, 2023) (see Figure 2-1). NIH-funded research is publicly available to anyone who is interested in accessing the data and findings, and much—although not all—of the research does not directly result in an immediately marketable product.
Philanthropic gifts, although often given with significantly fewer restrictions than private- or public-sector funds, are often driven by personal desires, experiences, or emotions. For example, gifts may be given by grateful patients to individual researchers rather than an overall institution, or larger gifts may be restricted to focusing only on one disease state or type of disease, disallowing the use of those funds for emerging or urgent issues.
Because the goals and approach of the public, private, and philanthropic sectors in biomedical research are at odds, it is easy to see how fragmentation could occur and how these drivers could lead to outcomes that do not serve the greatest social need. However, the issue is deeper still. Even within the government agency that funds most biomedical research, fragmentation likely abounds. Each of NIH’s 27 institutes is responsible for setting much of its research agenda (NIH, 2018). The Division of Program Coordination, Planning, and Strategic Initiatives within NIH exists to help coordinate research around “emerging scientific opportunity or rising public health challenges” but it is easy to imagine duplicative, overlapping, or conflicting research projects being funded by different NIH institutes (NIH, 2018).
The siloed nature of these funding sources, conflicting agendas, and the lack of a cohesive strategy with buy-in from all stakeholders is concerning, because addressing the emerging, complex health conditions plaguing the American people will require sustained, coordinated, and focused research involving scientists from many different backgrounds.
THE ROLE OF NIH
Because NIH, via the Department of Health and Human Services, is the largest federal funder of American biomedical research, its structure and function have been central to setting biomedical research priorities and agendas since its inception (NSF NSB, 2020). As mentioned above, Congress allocates funding
NOTE: The proportion of the actual NIH budget spent on basic (black line) and applied (gray line) research.
DATA SOURCE: NIH, 2023b.
to individual NIH institutes, which are then empowered to set their research agendas and allocate much of their funding themselves. Some institutes have historically and regularly received larger allocations than other institutes (including the National Cancer Institute [NCI] and the National Heart, Lung, and Blood Institute [NHLBI], outlined in Chapter 1) which have enabled them to grow both in terms of employees and research portfolios, which then require even larger allocations in the future (NIH OB, n.d.). Allocating funding strictly based on the size of the NIH institute may not necessarily serve the greatest public good at the time, because emerging issues may fall under the umbrella of less-well-funded institutes.
The topline NIH budget also includes funding for infrastructure and special projects such as the Cancer Moonshot and pandemic preparedness, which do not require cross-agency coordination—or the Cancer Moonshot and cancer efforts at the Advanced Research Projects Agency for Health that distribute funding across agencies and may fragment what should be cohesive and coordinated efforts (NIH NCI, n.d.b; The White House, 2023). Appropriations bills can add specific text to direct how NIH institutes spend their budgets, and lobbying groups and other nonprofit coalitions go directly to Congress to push disease-specific agendas, which can receive different degrees of attention depending on how disease-specific agendas originate, thus resulting in different degrees of funding success during the appropriations process (Wouters, 2020). These many competing priorities and the lack of a central strategy often lead to complex, layered agenda-setting and may result in appropriations that do not entirely or accurately reflect overarching national needs.
As established in Chapter 1, dedicated federal funding is likely to significantly impact how Americans are impacted by a specific disease. For example, funding for NCI and NHLBI has increased dramatically since 2000, and mortality rates for both cancer and cardiovascular diseases have, overall, declined (CDC, 2024a; NIH NCI, 2023; NIH NHLBI, 2024). Even though the direct correlation between funding and mortality is difficult to calculate, it seems that these longstanding institutes with significant federal budget allocations have contributed to decreased mortality. Lower funding levels and/or lower funding increases are also reflected in disease mortality data, which suggest that deliberate attention and associated appropriations are required to address America’s emerging health challenges. For example, since 2000, the age-adjusted prevalence of diabetes has significantly increased among adults aged 18 years and older, but NIDDK has one of the lowest rates of funding increase among the NIH institutes—from $1.693 billion in fiscal year 2013 to $2.3 billion in fiscal year 2023 (NIH NIDDK, 2013, 2024).
Sustained and robust investments in NIH have led to the training of thousands of biomedical- and physician-scientists, effective therapies for diseases that were once death sentences, and, more recently, the rapid development of effective COVID-19 vaccines. A thriving U.S. biomedical research enterprise also created a strong U.S. knowledge capital, robust biotechnology and pharmaceutical industries, and hundreds of thousands of high-wage jobs, and continues to add billions of dollars each year to the U.S. gross domestic product (GDP) (The Science Coalition, 2024). Without clear, overarching goals guided by a thoughtful and coordinated central strategic vision, too many priorities compete for a limited pool of funds. This competition may lead NIH to hedge its bets and award funding to relatively safe and incremental proposals—rather than research that is risky but could advance the biomedical enterprise in bold and rewarding ways. A national strategic vision could also help NIH and other funders better understand which investments would most benefit the American public—even if, or especially if, those investments do not track with the size or longevity of a certain focus area.
WHY A NATIONAL STRATEGIC VISION IS NECESSARY
The United States needs to break down existing funding, information, and coordination silos to support the success of a national strategic vision for the biomedical research enterprise—under which many current efforts can continue. Strategic planning at a national scale would enable the entire biomedical research enterprise to be proactive against future health threats, create a communal direction toward achievable goals, improve operational efficiencies, increase productivity, and advance cost-effective health care delivery. Likewise, national-scale strategic planning could and should be used to determine the amount of biomedical research funding required over time. The current economic and public health climates heighten the urgency for the U.S. government to seize the opportunity to establish a national strategic vision so that impending threats, such as those that follow, can be ameliorated.
American Life Expectancy Is Falling
By most health metrics, the U.S. population faces several significant health challenges—many of which are reflected in life expectancy, which is generally seen as a bellwether for the overall health of a nation. An analysis conducted by The Washington Post in 2023 found that American life expectancy has been falling for the past decade compared to other wealthy nations (Achenbach et al., 2023). Life expectancy in 2010 in the United States was 78.6 years, compared to 80.2 in
Germany, 81.3 in Canada, and 82.2 in Switzerland (WHO, 2020). In 2022, life expectancy in the United States was 77.5, down 1.1 from 2010 (Peterson-KFF Health System Tracker, 2024). Comparatively, in 2022 Germany and Switzerland’s life expectancy rose to 80.8 and 83.5, respectively, and Canada’s life expectancy stayed stable at 81.3 (Peterson-KFF Health System Tracker, 2024).
Life expectancy also differs significantly between racial and ethnic groups. Within the United States, provisional data for 2021 show a decline in U.S. life expectancy since 2019 of 6.6 years for American Indian and Alaska Native individuals, 4.2 years for Hispanic individuals, 4 years for Black individuals, 2.4 years for White individuals, and 2.1 years for Asian individuals (Arias et al., 2022). This continued decline—and associated disparities—requires prompt attention.
Women’s Health Concerns Are Growing and Poorly Understood
Although women comprise more than half of the U.S. population, conditions that disproportionately impact women and individuals who identify as women are under-researched and underdiagnosed (Blakeslee et al., 2023; Whiting, 2024). Additionally, although U.S. women experience longer life expectancy than men do, between 2021 and 2022, male life expectancy increased by 1.3 years, compared to only 0.9 years in women (see Figure 2-2). This apparent slowing of life expectancy growth is further complicated by the fact that “women spend 25% more of their lives in debilitating health than men,” meaning that despite their longer lives, women generally experience poorer health spans than men do (Whiting, 2024).
According to the National Health Interview Survey conducted annually by the Centers for Disease Control and Prevention, women fare worse than men in many aspects of health, including respiratory diseases, cancer, arthritis, and obesity (see Table 2-1). More women than men also reported that they have only fair or poor health and that they did not receive needed medical care due to cost (see Table 2-1).
Diseases and conditions that exclusively or disproportionately affect female patients and/or patients who identify as women receive significantly less federal funding than diseases exclusively or predominantly affecting male patients and/or patients who identify as men (Smith, 2023; Temkin et al., 2023). Likewise, an analysis of cancer funding showed that gynecological cancers are not as well funded as other cancers when considering their lethality (Rush et al., 2021).
The United States spends more on health care per capita than any other high-income country—”on average, other large, wealthy countries spent about half
SOURCE: Kochanek et al., 2024.
TABLE 2-1 | Health Conditions Impacting Women and Men in the United States, 2022
| Health Condition | Men (% having health condition in 2022) | Women (% having health condition in 2022) |
| COPD, emphysema, or chronic bronchitis | 4.1 | 5.0 |
| Asthma episode in the past 12 months | 2.1 | 5.1 |
| Any type of cancer | 8.6 | 10.4 |
| Arthritis | 18.0 | 25.0 |
| Obesity | 32.8 | 33.5 |
| Fair or poor health status | 13.8 | 15.2 |
| Did not get needed medical care due to cost in the past 12 months | 5.4 | 7.1 |
NOTE: COPD = chronic obstructive pulmonary disease.
SOURCE: CDC NCHS, 2018.
as much per person”—and still experiences the highest infant and maternal mortality rates—more than three times as high as other wealthy countries (Gunja et al., 2022; Wagner et al., 2024). It should be noted that recent studies have questioned the validity of U.S. maternal mortality rates, attributing their elevation to issues with data reporting and aggregation, and noting that when adjusted for these data irregularities, they may be approximately equivalent to other wealthy countries (Simmons-Duffin, 2024). However, these studies also emphasize that even if these data are inaccurately reported and the overall rate is significantly lower, extreme disparities between ethnic and racial minorities are still present at alarming rates and must be addressed (Simmons-Duffin, 2024).
The U.S. maternal mortality rate for 2022 was lower than for 2021—22.3 deaths versus 32.9 per 100,000 live births, respectively—and maternal mortality rates for all groups decreased over this same period (Hoyert, 2024). However, the maternal mortality rate for non-Hispanic Black women in 2022 was 49.5 deaths per 100,000 live births, more than twice that of White women (19 per 100,000) and nearly three times that of Hispanic women (16.9 per 100,000) (Hoyert, 2024) (see Figure 2-3). In 2020, Norway’s infant mortality rate was 1.6 deaths per 1,000
1Statistically significant decrease from previous year (p < 0.05).
2Hispanic people may be of any race.
NOTE: Race groups are single race.
SOURCE: Hoyert, 2024.
live births, while the United States experienced 5.4 deaths per 1,000 live births (Petrullo, 2023). In 2022, the Netherlands had the lowest maternal mortality rate of surveyed wealthy countries at 1.2 deaths per 100,000 live births, whereas the United States had 55.3 deaths per 100,000 live births (Gunja et al., 2022). High maternal death rates in the United States could be reversed by increasing access to primary care, providing comprehensive postpartum support, and implementing a “maternal health care workforce mainly comprising midwives covered by insurance” (Gunja et al., 2022, 2024).
Women comprise more than half of the U.S. population and experience overall worse health for more of their lives than men do, yet diseases that disproportionately impact this population are underfunded and understudied. Addressing these issues will not only significantly accelerate progress toward achieving health equity but is also a moral imperative in care for half of the American population.
Health Disparities Persist
Many health challenges affect subpopulations of the American public differently, a trend that has worsened in many disease areas despite concerted work to eliminate or ameliorate such disparities. This chapter touches on disparities related to gender, geographic location, and race/ethnicity but is in no way comprehensive. Chapter 4 of this publication examines health disparities—and the need for federal focus on their impacts—in greater detail.
Adults 35–64 who live in the American South and Midwest are currently dying at a higher rate than they were 40 years ago (Achenbach et al., 2023). There are many complex reasons for this increase, but they include a lack of comprehensive and high-quality health care—including having to travel long distances to access such care—and a prevalence of untreated or poorly treated chronic disease (Achenbach et al., 2023).
Health disparities along racial and ethnic lines plague almost every disease type but are most stark when the impacts of chronic diseases are considered. “American Indian/Alaska Native, Native Hawaiian and other Pacific Islander, and Black people [are] more than twice as likely as White people to die from diabetes, and Black people [are] more likely than White people to die from heart disease” (Hill et al., 2023). Health disparities not only impact the presence of disease but also impact their outcomes, as “[a]lthough Black people did not have higher cancer incidence rates than White people overall and across most types of cancer that were examined, they were more likely to die from cancer” (Hill et al., 2023). These stark health disparities show that the benefits of the U.S. biomedical research enterprise are not reaching all Americans equally. Historically marginalized and
minoritized populations cannot continue to suffer disproportionately, and their care must be carefully planned and accounted for.
Deaths of Despair
Recent increases in early death rates among Americans—especially White Americans—are overwhelmingly due to deaths of despair, including mortality due to suicide, drug overdoses, and alcohol use (JEC, 2019).
Deaths by suicide increased from 10.4 deaths per 100,000 in 2000 to 14.1 per 100,000 in 2021—accounting for more than 48,000 Americans per year (CDC, 2024b). Health disparities are also present in deaths by suicide because American Indian/Alaska Native and White individuals are the most likely to die by suicide compared to other racial and ethnic groups—28.1 individuals per 100,000 and 17.4 per 100,000, respectively. Men were also 4.5 times more likely to die by suicide than women were in 2021 (Garnett and Curtin, 2023) (see Figure 2-4).
Drug overdose deaths in the United States have increased drastically across all populations in the past 20 years and have doubled in the past decade (NIH NIDA, 2024). Notably, overdose deaths decreased by 3% in 2023 compared to 2022, but an excess of 100,000 preventable deaths is by no means a success (CDC NCHS, 2024). Deaths related to opioids—primarily fentanyl—decreased, but deaths due to cocaine and methamphetamine increased, signaling, potentially, a new area of necessary focus (CDC NCHS, 2024).
“Deaths due to excessive alcohol use, including partially and fully alcohol-attributable conditions, increased … 29% between 2016 and 2021” (Esser et al., 2024). Although alcohol-related deaths among men are more common—119,606 deaths in 2020–2021—rates of death among women increased more dramatically—from 43,565 in 2016 to 58,701 in 2021, or a 35% increase (Esser et al., 2024).
The types of mortality that compose the deaths of despair are, by their nature, complex—including biological and mental components—and are heavily influenced by the social determinants of health. The U.S. biomedical research enterprise will, more likely than not, be unable to invent a drug or single therapy to address deaths of despair. A coordinated, strategic approach to each type of mortality will be necessary to reverse these trends and prevent their recurrence.
Obesity
Worldwide obesity has tripled since 1975 (WHO, 2024). In the late 1980s, about 20% of U.S. adults older than 20 had a body mass index (BMI) of 30 or higher, which defines them as obese according to the World Health Organization
1No statistically significant trend from 2001 through 2006; significant increasing trend from 2006 to 2018; no statistically significant trend from 2018 through 2021, p < 0.05. The rate in 2021 was significantly higher than the rate in 2020, p < 0.05.
2No statistically significant trend from 2001 through 2006; significant increasing trend from 2006 to 2018, with different rates of change over time; no statistically significant trend from 2018 through 2021, p < 0.05. The rate in 2021 was significantly higher than the rate in 2020, p < 0.05.
3Significant increasing trend from 2001 to 2017; significant decreasing trend from 2017 through 2021, p < 0.05. The rate in 2021 was significantly higher than the rate in 2020, p < 0.05.
NOTES: Suicide deaths are identified using International Classification of Diseases, 10th Revision underlying cause-of-death codes U03, X60–X84, and Y87.0. Age-adjusted death rates are calculated using the direct method and the 2000 U.S. standard population. Access data table for Figure 1 at https://www.cdc.gov/nchs/data/databriefs/db464-tables.pdf#1.
SOURCE: Garnett and Curtin, 2023.
(WHO, 2024). As of 2018, 42%—or twice as many—of U.S. adults have a BMI of 30 or higher, and the trend appears to be increasing (NIH NIDDK, 2021). Additionally, childhood obesity has become increasingly dire in the United States, where 1 in 5 children and adolescents have obesity (CDC, 2024c). Obesity is an especially complex condition because it is caused by an interconnected and inextricable web of factors, including food intake, lack of physical activity, sleep habits, socioeconomic status, geographic location, and other social determinants of health (NIH NIDDK, 2021). Such a complex condition requires the input of many experts from a variety of fields—a strong argument for the necessity of a coordinated national strategic vision and a convergence science approach.
Diseases of Aging
More Americans are living longer, and the size of the population of baby boomers, in particular, will add to the number of diseases of aging appearing and being treated—especially dementias including Alzheimer’s disease (Knickman and Snell, 2002). In 2017, more than 250,000 deaths were attributed to dementia, and 50% of those deaths were attributed to Alzheimer’s disease (Kramarow and Tejada-Vera, 2019). As of 2021, 6.2 million Americans over 65 are living with Alzheimer’s disease, which is estimated to grow to 13.8 million by 2060 (No author, 2022b). While deaths from cardiovascular disease and HIV have decreased, deaths due to Alzheimer’s disease have increased by more than 145% since 2000 (No author, 2021) (see Figure 2-5). Aging is the biggest risk factor for Alzheimer’s disease, and it doubles every 5 years over the age of 65 (Brookmeyer et al., 2011). Living longer is not meaningful unless the extra years lived are healthful, and as such, diseases of aging demand the attention of the U.S. biomedical research enterprise.
NOTE: Dementia deaths are identified according to the International Classification of Diseases, 10th Revision underlying cause-of-death codes: F03 (unspecified dementia), G30 (Alzheimer’s disease), F01 (vascular dementia), and G31 (other degenerative diseases of nervous system).
SOURCE: Kramarow and Tejada-Vera, 2019.
The Next Pandemic
The probability of facing another pandemic with COVID-19-level impact—which cost the world trillions of dollars and more than 7 million lives—was recently estimated at 1 in 50 in any given year (CEPI, 2024; Worldometer, 2024). This means that an individual’s chance of experiencing another pandemic over their lifetime is approximately 38% (CEPI, 2024). With hundreds of emerging or re-emerging pathogens affecting human health and hundreds of thousands of uncatalogued pathogens in existence, this is a crucial moment to strengthen the biomedical research enterprise for health security nationally and globally. Biomedical research is critical for tracking, preventing, addressing, and mitigating another such calamity, as well as ensuring that scientific infrastructure and person-power can be leveraged to avoid human suffering.
Climate Change
Climate change is a looming environmental threat as well as an urgent public health threat, because millions of people die every year due to health issues related to climate change (NAM, 2024). Climate change can exacerbate existing diseases and create new ones, including “respiratory and heart diseases, Lyme disease, West Nile virus, water- and food-related illnesses, and injuries and deaths” (EPA, 2024). By its very nature, climate change requires a convergence science approach to address its root causes and reverse its multiple cascading effects.
PUBLIC TRUST IS CRITICAL FOR THE ACCEPTANCE OF A NATIONAL STRATEGIC VISION
The American public has recently shown a significant mistrust of science and public health officials—a disturbing trend that, if prolonged, will likely negatively impact the nation’s health. Even if the U.S. biomedical research enterprise produces revolutionary and life-saving treatments, if the public does not trust science and medicine and will not accept the treatments, then the effort will have been for naught.
Beyond general trust in science, patient engagement is also critical for the success of the U.S. health care system—with the added benefit of directly leading to improved outcomes for patients and their clinicians (Marzban et al., 2022). Patient engagement is an ethical practice—reflecting the “nothing about us without us” principle that has guided disability activism—and a powerful path to meaningful scientific progress and improved health outcomes for all (United
Nations Enable, 2004). Progress in improving health over the years has wholly depended on public trust and patient engagement—and, specifically, enough public trust and patient engagement for individuals to actively participate in clinical trials. Experimental treatments cannot advance without such partnership. To achieve the levels of engagement and participation needed to advance science and medicine, the public must trust science and scientists.
Shawn Otto, author of The War on Science, reviewed the history of science and public trust and has asserted that funding for science after the Second World War caused scientists to turn inward, cultivating the scientific community and not engaging the public as they had before the war (Otto, 2016). The result, he says, was that the public discourse around science, including the politicization of science, largely did not include scientists themselves. Otto reflected on this time, “[s]cience creates knowledge—knowledge is power, and that power is political” (Otto, 2016). Science has, in 2024, become so complex that few members of the lay public can appreciate the challenges of the practice or the value of the outputs, which often leads to fear and mistrust. Mistrust is exacerbated by intentional misdirection or manipulation—often amplified by social media—as well as current challenges with reproducibility in scientific and medical experiments (Kington et al., 2021; NASEM, 2019a).
According to The Pew Research Center, which has been measuring public trust in science for more than 20 years, most Americans are still more confident that scientists and clinicians are acting in the public’s best interest than other groups are, but that confidence has fallen since COVID-19 (Kennedy and Tyson, 2023). In 2020, 89% of American adults had a great deal or a fair amount of confidence in clinicians to act in the best interests of the public, with 11% having not too much or no confidence at all (Kennedy and Tyson, 2023). Since then, survey results show that confidence in clinicians has fallen by 8% and scientists by 14%, with a reciprocal increase of about one-quarter of American adults having not too much or no confidence at all that clinicians or scientists act in the best interests of the public (see Figure 2-6).
When asked whether science has had a positive or negative impact on society, the share of adult Americans who believe it has been a net positive has also declined since 2020, and the share who believe it has been a net negative has more than doubled from 3% in 2019 to 8% in 2023 (Kennedy and Tyson, 2023). More concerning is how these views differ across racial and ethnic groups, and how they may directly influence the outsized health inequities described throughout this Special Publication. More than 50% of White and Asian Americans say science has had a mostly positive impact on society, whereas that sentiment is held by less than 50% of Black and Hispanic Americans (see Figure 2-7). In
NOTE: Respondents who did not give an answer are not shown.
SOURCE: Kennedy and Tyson, 2023.
addition, positive views on the effect of science on society increase with the level of education. Among individuals with a high school education or less, only 42% say science is a net positive, whereas 72% of those with college degrees say science is a net positive (Kennedy and Tyson, 2023). As noted, these trends likely contribute to health and health care disparities and should be addressed
* Estimates for Asian adults are representative of English speakers only.
NOTES: Survey of U.S. adults conducted September 25–October 1, 2023. Sample sizes for Black and Asian Republicans are too small to analyze responses separately. Respondents who did not give an answer are not shown. White, Black, and Asian adults include those who report being only one race and are non-Hispanic. Hispanic adults are of any race.
SOURCE: Kennedy and Tyson, 2023.
to increase necessary representation in health science research, which will help improve health outcomes for all.
Given its enormous influence on biomedical research, NIH should work to ensure that the U.S. biomedical research enterprise continues to embrace and actively pursue improved patient engagement. As part of this effort, NIH leadership should continue to prioritize the National Library of Medicine’s efforts to modernize the clinical trials clearinghouse located at https://www.clinicaltrials.gov. This modernization process, which has been informed by broad engagement with patients and other members of the research community, will meaningfully improve both patients’ and providers’ experiences in seeking opportunities to participate in clinical research (NIH NLM, 2023). NIH should also focus on expanding platforms that support collaboration with the patient community, including those hosted by the Patient-Centered Outcomes Research Institute (PCORI) and Clinical and Translational Science Awards (NIH NCATS, 2024; PCORI, n.d.).
Although the history of engaging non-scientists in NIH advisory panels and other patient engagement efforts is long, a full embrace of public engagement in biomedical research remains a work in progress and requires a strong foundation of trust on which to grow (NIH, n.d.a). Work in this area should include not only a rigorous commitment to elevating patient voices in research but also efforts to foster meaningful trust-building and improved communication between scientists and the public they serve. Prioritizing public trust to enhance patient engagement is critical for advancing biomedical research in the United States.
MORE EFFECTIVE CLINICAL TRIALS WILL BENEFIT ALL RESEARCH
A healthy person with low trust in science and scientists could certainly carry that mistrust into their own medical journey if faced with serious illness or life-threatening health challenges, and that mistrust would likely lead to challenging engagement with the health system. Patient engagement in the United States is inconsistent at best, and if improved would expand trust and might also accelerate the development of new treatments. Patients play a critical role in the design and execution of research by participating in clinical trials for promising new drugs and other treatments. Early data from PCORI suggest that involving patients throughout the clinical research process—including study design, conduct, and dissemination of results—leads to improved research that focuses on topics important to patients, maximizes their participation, decreases patient and provider burden, enhances enrollment, and improves data quality (Forsythe et al., 2019).
Adequate and diverse clinical trial participation continues to vex NIH and industry partners alike because recruiting and retaining participants remains a challenge. According to one pharmaceutical executive, less than 5% of eligible patients participate in clinical trials, 30% of those who do enroll drop out, and 20% of trial sites fail to enroll patients at all (Smalley, 2018). A study published in 2021 reported that “convenience-enhancing” solutions such as transportation arrangements, child care, and the use of mobile apps may meaningfully increase patient engagement in clinical trials, particularly among underrepresented populations (Sine et al., 2021). This study reveals an important lesson—that patient concerns about participating in research are not solely about scientific approaches or clinical settings. In addition to a diagnosis, people bring their personal circumstances, knowledge, and preferred ways to receive and manage their medical information to all interactions with the health care system and the biomedical research enterprise. Acknowledging the whole person—not just the patient’s disease—will likely generate greater trust between scientists and clinical trial participants.
Relatedly, challenges surrounding patient engagement are often framed as a communications gap, when scientific experts describing their research fail to connect with patients. In reality, this disconnect is about more than language—patients need researchers to acknowledge and support the value of the patient in all stages of research and development.
The COVID-19 pandemic caused many in-person clinical trial sites to shut down and gave rise to an increase in decentralized trials. These trials rely less on frequent, in-person office visits by using mobile apps and virtual and digital platforms to track data, symptoms, and outcomes and conduct interventions when needed (Hanley et al., 2023). Decentralized trials, which have been in development for years but were slowly adopted until they were necessary in 2020, have the potential to remove many barriers to broader participation.
There is a need for more Americans in general to participate in clinical trials, but there is a particularly urgent need to diversify clinical trial cohorts. To produce generalizable results and ensure the safety and efficacy of novel drugs and treatments, a clinical trial cohort must reflect the composition of the population it is intended to serve, and America’s current clinical trial structure and recruiting approaches do not support or ensure this diversity (Acuña-Villaorduña et al., 2023). A National Academies consensus study found that a lack of progress on this issue could compromise the generalizability of research to the entire U.S. population, cost hundreds of billions of dollars in decreased life expectancy and years in the labor force, and may impede discoveries, among other impacts (NASEM, 2022). Diversity in clinical trial cohorts could be improved in several ways, all of which require a reimagining and restructuring of how clinical trials are executed. A
low-effort intervention is suggested by the finding that, despite a pervasive belief among biomedical researchers that underrepresented populations do not want to participate in clinical trials, these populations are “no less likely, and in some cases are more likely, to participate in research if they are asked” (emphasis added) (NASEM, 2022). Ensuring the participation of racial and ethnic minorities and individuals who live in rural areas is of outsized importance to appropriate cohort diversity and “effective delivery of potentially efficacious investigational therapies to patients … without other available treatment options” (Acuña-Villaorduña et al., 2023). Novel approaches to solve these pervasive issues could include embedding clinical trials within communities, rather than locating them at large hospitals or academic medical centers, which are disproportionately located in large cities; providing additional funding to assist participants with the expenses of participating in a clinical trial; and broadly employing and utilizing patient navigators (Acuña-Villaorduña et al., 2023). Expanding pools of clinical trial participants and ensuring that they are representative of the actual composition of the population the intervention is intended to serve will require a sea change in how clinical trials are imagined, structured, and executed, but will ultimately help to move all biomedical research forward more expeditiously.
GLOBAL BEST PRACTICES AND LESSONS LEARNED
Despite the United States’ long leadership in biomedical research, over the past few decades, other nations have started to invest more heavily in their own research efforts. Although the United States continues to spend more in absolute dollars, other nations are now investing a greater percentage of their GDP in R&D than the United States does (see Figure 2-8). U.S. federal investment in biomedical research has mostly remained level since 2010 when accounting for inflation.
Many of America’s peer nations have enacted long-term strategic plans for science and technology that couple with and support their increased financial investments. China’s first 12-year plan was the Long-term Plan for the Development of Science and Technology 1956–1967 (Embassy of the People’s Republic of China in the Hellenic Republic, 2004). Its most recent plan—the 15-year Medium- to Long-Term Plan for the Development of Science and Technology—includes goals to invest 2.5% of its GDP in R&D, limit its dependence on imported technology, increase the overall number of patents, and have “Chinese-authored scientific papers [be] among the world’s most cited” (Cao et al., 2006) (see Box 2-2). In 1995, Japan enacted its Science and Technology Basic Law and then established strategic plans every 5 years (NRC, 2009). Its most recent plan aims to improve access to data for all of its citizens; collaboratively address global issues such as
NOTES: Each line represents expenditures for basic science research as a percentage of gross domestic product (GDP) for each country, where each country is represented by different colored lines. Dotted lines indicate linear trends over time, with corresponding equations shown above each trend line. Research expenditures include all research and are not limited to biomedical research. Parameters for the data shown in Figure 2-8 within the Main Science and Technology Indicators database are as follows: time period = 2000–2021; reference areas = South Korea, United States, China, and Japan; measure = basic science research expenditure; and unit of measure = percentage GDP.
SOURCE: OECD, n.d.b.
climate change and COVID-19; and build a “resilient, safe, and secure society” (Government of Japan, 2021). Singapore created its National Technology Plan in 1991 to “steer the development of science and technology . [and] enhance [its] economic competitiveness” (Ministry of Trade and Industry Singapore, 2006). Its most recent plan includes broadening the scope of research to address emerging needs, expanding the nation’s research base in terms of topics and funding, and driving technology translation (National Research Foundation, Prime Minister’s Office Singapore, n.d.) (see Box 2-1). The European Union’s strategy for 2020–2024 focuses on environment and climate, the digital future, jobs and economy, “protecting our citizens and our values,” Europe in the world, and democracy and rights (European Commission, 2020) (see Box 2-3).
As America’s peer nations continue to scale up their investment—in funding and person-power—in biomedical research and utilize strategic planning to guide these major investments, it follows that the United States would be well served to follow suit. The U.S. national strategic vision should draw from the successes and best practices established by our peer nations, and three key examples are outlined in Boxes 2-1, 2-2, and 2-3 below.
BOX 2-1
National Agenda Setting Example 1: Singapore
In 2000, the Singaporean government, motivated to increase its knowledge capital, established a National Biomedical Science Strategy. This Strategy established A*STAR—the Agency for Science, Technology and Research—under the Ministry of Trade and Industry and in 2003, opened Biopolis, a biomedical R&D hub (Science, 2007). The number of Singapore-based biotech companies increased from 7 in 2012 to 52 in 2022, and large international pharmaceutical companies, such as Sanofi, BioNTech, and Merck have established local offices in Singapore (Weidong, 2024). Furthermore, Duke University and the National University of Singapore collaborated to open a new medical school, Duke-NUS (DukeNUS Medical School, 2022).
Singapore’s biomedical science manufacturing output increased from $6 billion in 2000 to $29.4 billion in 2012 (Antara, 2013). During the same period, employment in biomedical science grew from 6,000 to 15,700 (Antara, 2013). As of 2019, Singapore’s biomedical manufacturing sector represents 4% of its total GDP (Whellams, 2021). Between 2000 and 2020, Singapore invested $10 billion into R&D and its current Research, Innovation and Enterprise 2025 strategic plan includes $19 billion in government funding (Tan, 2021).
BOX 2-2
National Agenda Setting Example 2: China
Launched in 2006 by China’s State Council, the Medium- and Long-Term Plan for the Development of Science and Technology 2006–2020 (MLP) aimed to achieve four goals:”increase the nation’s expenditure on R&D to 2.5% GDP, increase the contribution of science and technology progress to economic growth from less than 40% to more than 60%, reduce dependence on foreign technology to 30% or less, and become one of the top five countries in terms of number of invention patents and manuscript citations” (Cao et al., 2006).
China has directed its national science and technology 5-year plans, which have existed since 1953, toward achieving MLP goals. Additionally, China prioritized funding for 16 “mega-engineering programs”—covering topics such as circuit manufacturing, oil and gas exploration, drug development, smart grid, big data, and health security—and four “mega-science programs”—including a deep-sea space station, quantum computing, and brain science—as funding priorities (Sun and Cao, 2021). The MLP aimed to address challenges that arose from decentralization of R&D spending, which Sun and Cao say resulted from a lack of top-level design, unified planning, and coordination (Sun and Cao, 2021). Through its national science and technology programs, China reconfigured its public funding system to align basic, applied, and development research with 3- to 5-year timelines.
China achieved all targets set by the last MLP. By 2020, China was investing 2.4% of GDP into R&D, just shy of its 2.5% goal (Sun and Cao, 2021). By 2019 the contribution of science and technology progress to economic growth bloomed from 40% to 59.5%, just shy of its 60% goal (Sun and Cao, 2021). An original goal was to reduce dependence on foreign technology to 30% or less, but China stopped using this measure in 2016. However, in that same year China reduced its dependence to 31.2%, just shy of the initial goal (Sun and Cao, 2021). Lastly, in 2018, China ranked third globally for triadic patents and second globally for manuscript citations (Sun and Cao, 2021).
China has since launched its new Medium- and Long-Term Science and Technology Development Plan 2021–2035. However, unlike previous plans, the current plan has not been publicly released (Cheung et al., 2022).
BOX 2-3
National Agenda Setting Example 3: European Union
The Framework Programmes for Research and Technological Development were launched in 1984 as 5-year funding cycles to foster and coordinate research across the European Research Area (SERI, n.d.). In 2014, the cycle length was extended to 7 years and renamed Horizon 2020. The budget for the current Horizon Europe 2021–2027 is €95.5 billion (European Commission, 2021a). Horizon Europe aims to tackle climate change, boost European Union growth and innovation, support knowledge creation, and create new jobs and technologies (European Commission, 2021a). About one quarter of the Horizon Europe plan is dedicated to “excellent science.” Of the approximately €25 billion earmarked for excellent science, €16 billion will be competitively funded to support investigator research through The European Research Council; €6.6 billion will fund doctoral education and postdoctoral and visiting scholar training through Marie Sklodowska-Curie Actions; and €2.4 billion will be directed toward integrating and improving research infrastructures across Europe (European Commission, 2021b). Under a separate pillar aimed at boosting European industrial competitiveness, €8.25 billion is dedicated to “generating new knowledge, developing innovative solutions and integrating where relevant a gender perspective to prevent, diagnose, monitor, treat and cure diseases” as well as developing health technologies; mitigating health risks; protecting populations; promoting good health and well-being; making public health systems more cost-effective, equitable, and sustainable; preventing and tackling poverty-related diseases; and supporting and enabling patient participation and self-management (European Commission, 2021c).
A robust evaluation system measuring success across three performance indicators is central to the success of Horizon Europe. The three performance indicators are scientific impact that includes creating high-quality new knowledge, strengthening human capital, and fostering dissemination and open science; economic impact that encompasses business creation and growth that will create direct and indirect jobs; and societal impact that addresses European Union priorities and global challenges, including United Nations Sustainable Development Goals (European Commission, 2023).
As of 2024, Horizon 2020 funded more than 35,000 projects that resulted in more than 4,000 patents and trademarks, grew employment by 20%, produced 276,000 peer-reviewed publications, supported 33 Nobel Prize winners, and provided 24,000 researchers globally with access to Europe’s research infrastructure (European Commission, 2024).
CALL TO ACTION
The U.S. biomedical research enterprise is currently limited by fragmented research agendas dictated primarily by funding source rather than by strategic national public health needs. Despite spending more on R&D than any other nation, research expenditures in America are driven not by a national mission to improve health, but by motivations such as marketability and profit margins, which likely do not serve the nation’s most pressing needs.
Relatedly, the federal government’s current process of launching new initiatives in parallel or under the umbrellas of specific agencies decentralizes and diffuses national priorities. As multidisciplinary biomedical research and convergence science become more integral to all scientific progress, a coordinating and vision-setting body that sits above all federal agencies with the power to set strategy, provide guidance on resource allocation, and receive input from a broad variety of stakeholders is necessary to guide the U.S. biomedical research enterprise of the future.
The development and work of this advisory body should be informed by the vision-setting bodies of other nations—especially how they set strategy and coordinate funding to maximize efficiency and minimize redundancy. As other nations focus the efforts of their biomedical research enterprises with careful strategic planning, dedicate increasing amounts of their GDP to their enterprises, and work to become leaders in biomedical research, the United States should develop and deploy its own comprehensive strategy to maintain global leadership in biomedical research.
To achieve this vision, the authors of this Special Publication propose the following:
Priority 1-1: A U.S. biomedical research enterprise advisory body, created by the President of the United States and Congress, to galvanize national leadership, develop a national strategic vision, and coordinate efforts and resources.
Priority 1-2: This advisory body could:
- Be composed of leading scientists from a wide variety of disciplines, such as life, physical, social, and behavioral sciences; engineering; economics; and the humanities to ensure a convergence science approach to addressing all emerging needs;
- Engage with multiple relevant federal agencies;
- Be established with long terms;
- Be empowered to set national goals and benchmarks;
- Provide input on resource allocation that matches strategy;
- Consider, examine, and utilize global best practices in all aspects of its work, but especially as guidance for developing the national strategic vision;
- Include patients, caregivers, and members of the public to provide transparency and public engagement;
- Have clear, measurable goals and timelines;
- Coordinate with the National Economic Policy Council and the Domestic Policy Council to ensure the engagement of all relevant stakeholders; and
- Monitor their progress and report to Congress and the American public annually on their work.
Priority 1-3: The advisory body’s national strategic vision could:
- Directly address the current fragmentation in funding and agenda-setting present in the U.S. biomedical research enterprise, in concert with the efforts proposed in Priorities 4-1 and 4-2. The national strategic vision cannot succeed without coordination and alignment of funding and agenda-setting, which, conversely, cannot be coordinated and aligned without the guidance of a national strategic vision. These Priorities cannot be separated.
- Set priorities for the use of convergence science and implement a roadmap for bringing together relevant agencies and scientific disciplines to achieve this collaborative approach (see also Priority 4-2).
- Consider and propose funding to address:
- Existing and emerging health challenges, including but not limited to infant and maternal mortality, women’s health concerns, deaths of despair, obesity, climate change, health disparities, diseases with pandemic potential, and diseases of aging;
- Future health threats such as increasing risks of extreme heat and other natural disasters due to climate change and emerging or existing infectious diseases;
- Public engagement in the entire U.S. biomedical research enterprise, but especially focused on increased participation in clinical trials;
- Deteriorating public trust in science and medicine;
- Prioritization and development of new and innovative research approaches to reduce and eliminate health disparities; and
- The needs of the U.S. biomedical research enterprise workforce, including adjusting historical pathways to employment or tenure as emerging health challenges, approaches to science, or the needs of the American public change.
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