Lack of access to healthcare services in rural communities contributes to the greater rates of morbidity and mortality observed in these communities compared to metropolitan areas (Kozhimannil et al 2019; Summers-Gabr 2020; Mishra et al 2021). Similarly, fewer members of rural populations are included in clinical trials, which can result in decreased generalizability and external validity of results. Therefore, it is important to consider access to both healthcare and the benefits of clinical trials when designing research for optimal impact on population health.

Decentralized trials can mitigate access issues and optimize benefits for all communities by meeting participants where they are. Some patients face barriers to accessing care in rural and remote areas, which may have limited infrastructure, lack complementary and integrative health clinics, offer few reliable transportation options, and involve extended travel times. Some populations may also feel uncomfortable visiting a research site due to past injustices or concern over insurance status or payment. Additionally, competing priorities, lack of access to technology, and low health literacy can be barriers for rural and other populations (Boyd et al 2023). For example, many rural populations do not use patient portals, and text messages or direct phone calls may be needed to engage these populations. (Boyd et al 2023).

Key questions to consider:

• Have clinics in decentralized trials established trust within their communities?
• Do potential participants have internet access?
  • If not, is there a way to provide it?
• If devices are used, will they be provided?
  • Does the protocol include training on digital literacy, and how is this evaluated?
• Will there be a cost for receiving text messages?
• Will telehealth visits be conducted at a time when patients are available?
• Do the potential participants use patient portals?
  • If not, what other modes of outreach can be used?

Challenges

Lack of Access to Patient Portals

Middle-aged, college-educated, urban populations are more likely to use online patient portals than other populations (Gordon and Crouch 2019), highlighting that other outreach models are needed to promote usage in rural patient groups and patients with lower educational attainment. EHR data regarding types and frequency of portal use can be leveraged to match outreach strategies with patients’ technology usage patterns.

• The OPTIMUM study (Greco et al 2021) mailed opt-out letters and flyers about the study through the US Postal Service. People who did not opt out were contacted by telephone, often prior to an upcoming office visit. In addition, flyers were embedded in the EHR that could be printed with post-visit instructions. Employing multiple recruitment methods helped the study reach a wide variety of potentially eligible participants.
• In the NOHARM trial (Redmond et al 2022), the research team conducted direct outreach through printed mailings and interactive voice recognition calls to patients who did not use the online portal. The team also identified participants’ preferred mode and language for completion of the patient-reported outcome measures.

Low Health-Related Digital Literacy

Health-related digital literacy may be low in some populations, and work must be done, often with community advisory boards and patient partners, to optimize the reading level of trial materials. This is especially important when there is no one there to explain the content, as would be the case with text messages and patient portals.

For example, in the Nudge trial (Ho et al 2024), the research team tested the intervention text messages with patients and partner groups to make sure the messages were at a 5^th grade level. This step helped to minimize factors that might limit patient understanding and use of the intervention.

Lack of Access to Complementary and Integrative Health Therapies

Unequal access to complementary and integrative health (CIH) therapies—such as acupuncture and mindfulness—is a problem for some populations, who may not have insurance for these therapies or transportation to clinics offering them. This leads to knowledge gaps about effectiveness of CIH therapies in these populations.

The GRACE trial is evaluating the effects of guided relaxation and acupuncture for people with sickle cell disease (Doorenbos et al 2023). To address gaps in access to CIH therapies and CIH-related research, the trial expanded the range of community locations for acupuncture and is providing transportation coverage, tablets, and data plans if needed (Boyd et al 2023).

Poor Generalizability

Decentralized research is vulnerable to poor generalizability due to differences in data capture and access to care for different populations, which, if left unaddressed, can affect health and the healthcare system. Consequently, investigators may need to monitor response rates for electronic patient-reported outcome measures and other outcomes and consider multiple modes of outreach if information is incomplete or missing.

“Poor generalizability can occur because detailed information about specific populations is missing, and critically, is missing not at random.” (Boyd et al 2023).