Are Decentralized Clinical Trials the Answer to Increasing Subject Inclusion and Diversity?

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Clinical trial research is a systematic process, often involving human subjects, that is intended to examine the safety and efficacy of a drug or device in treating, preventing, or diagnosing a disease or a medical condition.¹ Clinical trial design is meticulously scrutinized and carefully monitored by various oversight bodies such as ethics committees or Institutional Review Boards (IRBs). In most circumstances a clinical trial protocol must meet certain minimum criteria and receive approval prior to launch (Figure 1).²

Clinical trials are an important step in determining if a new intervention is safe, works better, and/or has fewer side effects than an existing treatment or intervention.³ The wide range of currently available effective medical treatments have been developed as a direct result of previously conducted clinical trials. Furthermore, clinical trial findings are the cornerstone of evidence-based medical treatments.  

In addition, clinical trials can examine ways to detect disease processes early or prevent health-related problems altogether. For example, diagnostic tests such as point-of-care imaging and biomarker detection are relatively new interventions being used in the wound care space. These advancements aid health care providers to determine the extent or existence of a pathophysiological state. The field of diagnostic trials has grown tremendously in the last 40 years.⁴ 

Suffice to say, clinical trials are an invaluable method for evaluating new treatments to improve the quality of life of people who have an illness or chronic medical condition. Thus, there is a need for diversity and inclusion in clinical trials. People may experience the same disease differently. It is essential that clinical trials include people with a variety of life experiences, including variations in race and ethnicity, age, sex, and sexual orientation. All communities should benefit from scientific advances.

Historically, clinical trials did not always recruit participants who represented the individuals most affected by a particular disease, condition, or behavior. Certain populations such as women, some ethnic and racial groups, and other marginalized people are notably underrepresented in many clinical trials.⁵ There is a push to overcome this issue by patient advocates, health care practitioners, payers, policy makers, and industry key opinion leaders.⁵ Recently the National Academies of Sciences, Engineering, and Medicine examined this issue and identified several action items to bring about reform in clinical research to support broader subject inclusion.⁵

Lack of clinical trial diversity produced gaps in understanding diseases and conditions, preventive factors, and treatment effectiveness across populations. Additionally, marginalized populations can perceive the lack of diversity in clinical trials as exclusionary thus perpetuating distrust in the health care system. Collaborating with community-based health care providers, medical device companies, and drug manufacturers to increase enrollment in underrepresented subjects has not brought about widespread results. Lack of confidence in clinical trial results that do not represent diverse subjects can impede the quality of health care decision making, ability to counsel people on ways to reduce their risk, optimal treatment responses, and even the development of more effective medications or interventions.

A recently published study illustrates how important inclusive study enrollment practices are in instilling confidence in the effectiveness of new treatments. When Black patients were presented results from 1 of 2 trials of a new drug for hypertension, showing both drugs were equally effective, the belief that the drug would be effective for them increased by 20% when presented with the trial results where 15% of trial participants were Black versus when less than 1% of subjects were from that representative racial group.⁶ 

Most investigators can agree that clinical trials should be easily accessible to all populations yet lack of geographically convenient clinical trial sites can hinder study participation, particularly for rural residents. Even in densely populated regions, where most US residents live, trial locations may not be easy to access. Seidler et al examined the geographic distribution of clinical trials across the continental United States.⁷ Their analyses revealed that the distribution of clinical trial sites per person was highly clustered around urban centers across the continental United States.⁷ The investigators concluded that from a practical standpoint of conducting clinical research, it is understandable to see the observed increase in clinical trial sites in areas with greater numbers of health care and/or social service facilities, but practicality should not be the main determinant of clinical trial site location.⁷ Feyman et al concluded that even in densely populated regions, where most US residents live, trial locations may not be optimized to maximize access.⁸ Unequal distribution of trial sites relative to certain populations may impede patients’ participation in clinical studies contributing to the well-documented low representation of minorities in clinical studies.

Recruitment (the process of selection and enrollment of participants into a trial) and retention (the process of keeping participants in the study) can be challenging. Ineffective subject recruitment and/or retention may lead to inconclusive or invalid study results.⁹ A potential pitfall contributing to trial recruitment shortfalls is the investigator’s tendency to overestimate the pool of available patients who meet the inclusion criteria and would consent to enrolling in a particular trial. This phenomenon is known as the “funnel effect” where patients available to join a trial drop by 90% the day the trial begins (Figure 2). Research has estimated that the number of qualified patients who go on to enroll in a trial can be as low as 1 out of 10 of what was originally estimated.¹⁰

Trial participation can be demanding for patients. Frequent clinic appointments or testing can significantly disrupt daily routines. Carving time out to attend study visits may interfere with work and household schedules. Studies have shown that requiring patients to change their routine daily behaviors creates a disturbance in their personal and social lives resulting in emotional distress.¹¹ Additionally, travel to trial sites may be costly and/or inconvenient especially in older patients with limited mobility or for participants without access to a vehicle. Buses and taxis can be costly and difficult to access. Transportation is an even larger barrier in rural populations.¹² Many rural communities offer fewer transportation options, thus the prospect of traveling to a clinical facility for research purposes may present a formidable obstacle resulting in reluctance to participate. 

Acknowledging that the largest barrier to study participation was related to study burden, investigators must design studies that minimize the difficulties that participants may encounter to boost study recruitment, enrollment, and retention. 

Could decentralized clinical trials (DCTs) be the solution to increasing trial recruitment and retention while supporting diversity in patient participation? DCTs are studies where some or all clinical activities occur at locations other than a traditional clinical trial site. These alternate locations can include the participant’s home, a local health care facility, or a nearby laboratory. It can be easier to recruit trial subjects and keep them enrolled if they do not have the restriction of one particular geographic location or the burden of extended travel. Because they reduce barriers to participation compared to conventional clinical trials, DCTs can support rapid participant recruitment, increase participant retention, and significantly improve the diversity of the enrolled populations.¹³

For example, older individuals and people with disabilities may find it physically exerting to travel to a traditional clinical trial site but could participate in a clinical trial from their home or a nearby clinic. People with household and childcare responsibilities may also find it difficult to meet prescribed timeframes for clinical site visits. Individuals from racial and ethnic minority groups may disproportionately live in areas without clinical research facilities, and DCTs may open access to research for them.

DCTs can also help close gaps in representation by building inclusive trial models in underserved communities. This is a particularly promising step that can facilitate participation in diverse patients’ participation and also promote a more equitable distribution of medical innovations thus supporting the adoption of new medical treatments in these communities.

In addition to convenience, DCTs can collect data much more frequently than scheduled trial visits, sometimes even continuously by utilizing new ways of capturing the individual experience of patients in real-world settings by incorporating technical solutions into trial workflows. Traditionally, clinical trial data are collected by intermediaries, trained members of a study team, who manually record protocol-specified data into case report forms or electronic data capture systems. This is a time-consuming process and may involve many hours, increasing costs over the course of a study. DCTs can reduce time and expenses in the long term, limiting or eliminating the need for the resources associated with a traditional site of service.

By leveraging innovative platforms to support remote patient monitoring and telehealth, DCT design can make it easier to collect, transfer, and store electronic data. When utilized as end points, validated remote collection of trial data has been shown to reduce trial sample size by enabling the development of individualized thresholds for measuring treatment effects because of high-frequency data collection.¹⁴ Patients and providers are becoming much more tech savvy. This trend was indeed accelerated by the COVID-19 pandemic. New advanced digital platforms designed to support patient care are entering the market at a rapid pace. These same technologies can support the expansion of DCTs. 

DCTs extend the reach of clinical research to where patients live, making remote data collection possible to reflect the individual experience of patients in real-world settings. The advancements in digital platform design supporting DCTs could provide the solution to overcoming several of the challenges around clinical trial inclusion and diversity. This new era of patient-centered clinical research, where inclusivity and diversity are preferred, will create more opportunities for patients with historically limited access to study participation. 

Windy Cole, DPM, CWSP