Creating More Equitable Clinical Trials With Health Systems Science

By Douglas P. Slakey, MD, MPH, Professor and Chair, Center for Health Systems Science, Thomas F. Frist, Jr. College of Medicine, Belmont University

The evolving landscape of clinical trials presents an opportunity to enhance the rigor and relevance of medical research. Incorporating health systems science (HSS) into clinical trials can be transformative and help us shape the future of ensuring value in healthcare delivery for individuals, communities, and populations. HSS encompasses a broad understanding of how health systems influence patient care and outcomes, integrating policy, financial considerations, and emerging technologies such as artificial intelligence (AI). Incorporating HSS into clinical trial design, implementation, and interpretation is crucial for achieving more equitable and effective health outcomes.

Understanding Health Systems Science

Health systems science is a multidisciplinary field that examines how various healthcare system components interact and influence patient outcomes. It includes systems thinking, population health, health policy, health economics, and medical informatics. HSS acknowledges that a health system is not monolithic, especially from the patient's perspective. Instead, as each patient journey is unique, the way the system responds and the healthcare resources needed and used are variable. That is the reason for using "systems" to describe the field.

Furthermore, health systems are complex. As I discuss in The Process Manifesto: Improving Healthcare in a Complex World, managing complexity is facilitated by creating teams of teams — emphasizing multidisciplinary understanding and sharing a range of stakeholder perspectives. We must consider this a priority as we strive to ensure that clinical trials reflect a social contract to provide care that meets individuals' and populations' needs and expectations. All too often, clinical trials have been designed from within silos that naturally occur in healthcare. For example, the endpoint of a surgery device study might be hospital length of stay.  When presenting results to an audience of surgeons, it might seem impressive if the length of stay was reduced from 24 hours to 6 hours.  However, what does that mean for the single older adult with no support?   Is that patient better off being discharged at night on the day of surgery, or would their experience and outcome be improved by staying in the hospital until the following day?  By adopting an HSS perspective, researchers and clinicians can better understand the complex factors that affect healthcare delivery. This comprehensive approach is essential for addressing the multifaceted challenges of modern clinical trials.

The Current State Of Clinical Trials

Traditional clinical trials often fail to capture the full spectrum of patient experiences and outcomes. When considering health, patient experiences may include relationships with, or isolation from, family, friends, and community.   For example, one significant challenge can be travel to the clinical trial site.  The patient may not be able to drive themselves and may not have family or friends who can or will accompany them.  The potential clinical trial participants may have caregiving responsibilities of their own, such as driving children to and from school.  There can be many contributing factors, including cost and fear of losing a job, if not considered in a trial, and these realities can dissuade patients from participating.

Similarly, the spiritual and cultural impacts of treatment protocols, including clinical trials, are essential but often ignored.  It is not unusual for people to mistrust the healthcare system, and cultural and spiritual norms may reinforce this.    Will a clinical trial design encourage or discourage attending religious services or fasting obligations?   Will the investigators and trial coordinators be educated about these factors?  If not, patients may consider the trial inconsistent with their spiritual practices.

A significant limitation in many studies is the lack of diversity among trial participants, which undermines the generalizability of findings.  Authors such as Goodson et al. have pointed out that many groups are at risk of being underrepresented in clinical trials.  There are many reasons for this, but some include structural limitations of our healthcare systems.  For example, physician contracts that are strictly work RVU-based can disincentivize clinical trial participation due to the fear of not meeting wRVU targets.   Key performance indicators established by health system leadership must match the goals and design of clinical trials. 

Additionally, the conventional focus on clinical endpoints viewed as necessary by the physician and the healthcare team may neglect the broader context in which patients receive care.   In addition to the length of stay example, other outcomes make sense when focusing on what we see within the walls of the hospital or clinic, but that might not reflect the patient care journey for a patient with multiple comorbidities.  If a patient receives care from more than one specialty and at more than one location, the clinical trial design may fail to consider the consequences of this.   Ultimately, patients with multiple comorbidities are often excluded from clinical trials, even if they represent an essential patient population.  These shortcomings highlight the need for a more holistic approach that considers the social, economic, and environmental determinants of health.

Regulatory and ethical challenges further complicate the landscape of clinical trials. Stringent regulatory requirements, while essential for ensuring safety and efficacy, can slow down the initiation and progression of trials. Designers of clinical trials must acknowledge ethical considerations, especially when involving vulnerable populations. Technological advancements, such as digital health tools, telemedicine, and wearable devices, offer promising avenues to enhance data collection and patient monitoring, potentially reducing the burden on participants and increasing engagement.

Moreover, there is a growing movement toward patient-centered clinical trials, where patients are actively involved in the design phase to ensure that the research addresses their needs and concerns. Integrating clinical trial data with real-world evidence (RWE) can provide valuable insights into how treatments perform outside the controlled environment of a clinical trial, thereby improving the applicability of the findings. However, the high costs and resource demands of conducting extensive studies can limit their feasibility, particularly in underfunded areas of research. Globalization has also impacted clinical trials, introducing variability in standards of care across different countries but offering opportunities to study diverse populations, ultimately aiming for more inclusive and representative research outcomes.

Integrating Health Systems Science Into Clinical Trials

Health systems science is a relatively new concept.  Fundamentally, it evolved from the recognition that we should be teaching physicians, nurses, and other healthcare team members about the systems in which they work.  As HSS develops, the field includes how healthcare can best be delivered, how healthcare team members collaborate to improve access and outcomes, and how the systems can become more reliable and value-based.  Global, environmental, and technological health considerations are increasingly included in the study of HSS.  The Association of American Medical Colleges website is a good resource, as is the textbook Health Systems Science by Skochelak et al.  

Incorporating HSS into clinical trials can significantly enhance their design and execution. By considering social determinants and the broader context of health and health disparities, researchers can ensure that trials are more representative of the population, thereby increasing the generalizability of their findings. Policy and financial considerations are crucial as they influence patient access to trials and protocol adherence. HSS helps identify systemic barriers that impede participation, such as logistical challenges and mistrust of the medical system, a first step toward ensuring that trials are more inclusive.

Moreover, an HSS approach facilitates interdisciplinary collaboration, bringing together stakeholders from various fields, including healthcare providers, policymakers, and community leaders. This collaboration ensures that the design and implementation of trials consider patients' diverse perspectives and needs. By incorporating a wide range of stakeholders, those responsible for clinical trials can better understand the study's implications from the patient's perspective, leading to more patient-centered and meaningful outcomes.

The Role Of Technology And AI.

Technological advancements, particularly in AI, hold promise for revolutionizing clinical trials. A.I. can streamline patient recruitment by identifying eligible participants through electronic health records (EHRs) and social media. It also can enhance data analysis by uncovering patterns that might be missed through traditional methods. Powered by AI, personalized medicine can tailor treatments to individual patients based on their genetic and environmental profiles.  Environment profiles can include rural versus urban, living close to public transportation versus walking a mile to the nearest bus stop, living at high altitudes, or living in an area where seasonal isolation may occur, such as rural Alaska.  As we consider the power of AI, incorporating factors that influence and impact the patient healthcare journey will be achievable in ways not previously imagined.  However, addressing ethical concerns and ensuring that technology complements, rather than replaces, the human element in clinical research is vital.

Promoting Diversity In Clinical Trials

Achieving greater diversity in clinical trials requires deliberate and sustained efforts. Community engagement is critical to building trust and fostering participation among underrepresented groups. Partnerships with community organizations, advocacy groups, and local leaders can facilitate this process. HSS provides a framework for identifying and addressing barriers to participation, such as socioeconomic factors, cultural beliefs, and access to care. By prioritizing diversity, researchers can enhance the validity and impact of clinical trials.

HSS can improve the ethical and practical aspects of clinical trials by promoting transparency and trust between researchers and participants. This approach enhances recruitment and retention rates and ensures that the trials address real-world issues that matter to patients. Ultimately, integrating HSS into clinical trial design fosters a more equitable and effective research environment, paving the way for innovations that truly benefit all segments of the population.

Health Systems Science In Action

One notable example of integrating HSS into clinical trials is the All of Us Research Program by the NIH. This program aims to gather health data from 1 million or more people in the United States to accelerate research and improve health outcomes. By emphasizing diversity and inclusion, All of Us seeks to ensure that traditionally underrepresented populations are adequately represented in medical research, thus enhancing the applicability of findings across different demographic groups.

The NIH Pragmatic Trials Collaboratory is another effort that acknowledges the complexity of our healthcare system and focuses on integrating RWE into clinical trial design. This collaborative incorporates many HSS principles to address practical issues such as patient adherence, healthcare delivery variations, and economic factors influencing health outcomes. By using EHRs and other real-world data (RWD) sources, these trials can provide more relevant and actionable insights for everyday clinical practice.

Conclusion

Incorporating health systems science into clinical trials is essential for advancing medical research and improving patient outcomes. Researchers can design more inclusive and effective trials by adopting a holistic approach that considers the complexities of healthcare systems. The integration of technology and a focus on diversity will further enhance the impact of clinical research. As the medical and research communities increasingly consider and embrace HSS as a critical component of their work, clinical trials better serve the diverse needs of individuals, communities, and populations, contributing to a healthier future for all.

References:

1. Slakey, Douglas. The Process Manifesto: Improving Healthcare in a Complex World. New Orleans, 2023.
2. Anderson, A., & McCleary, K. K. (2016). From passengers to co-pilots: Patient roles expand. Science Translational Medicine, 8(343), 343ps10.
3. Denny, J. C., Rutter, J. L., Goldstein, D. B., Philippakis, A., Smoller, J. W., Jenkins, G., & Dishman, E. (2019). The "All of Us" Research Program. New England Journal of Medicine, 381(7), 668-676. doi:10.1056/NEJMsr1809937
4. Goodson, N., Wicks, P., Morgan, J. et al. Opportunities and counterintuitive challenges for decentralized clinical trials to broaden participant inclusion. npj Digit. Med. 5, 58 (2022). https://doi.org/10.1038/s41746-022-00603-y
5. NIH PRAGMATIC TRIALS COLLABORATORY. https://rethinkingclinicaltrials.org/about-nih-collaboratory/. Accessed July 25, 2024.
6. Association of American Medical Colleges (AAMC) Health Systems Science.  https://www.ama-assn.org/topics/health-systems-science
7. Skochelak, Susan, ed. Health Systems Science, 2^nd ed. Elsevier, 2020.

About The Author:

Douglas P.  Slakey, MD, MPH, FACS, is an internationally recognized transplant surgeon, healthcare professional, and administrator. He is the best-selling author of The Process Manifesto: Improving Healthcare in a Complex World. 

Doug is currently a professor and founding chair of health systems science at the Frist College of Medicine, Belmont University. He has created a center that is an innovative hub for research, implementation, and scaling creative strategies to improve healthcare delivery and value. Doug is also the senior healthcare partner for A.I. MIR.

Doug sits on the editorial boards of major medical journals, has nearly 40 referenced abstracts, and has authored more than 150 peer-reviewed articles. He received his Bachelor of Arts and Master of Public Health degrees at UC Berkeley and his M.D. at the Medical College of Wisconsin. Residency and fellowship training were at the Medical College of Wisconsin, the University of Oxford, and Johns Hopkins.