Reservations, Great Plains and rural counties ripe for decentralized trials: Milken report

Contract research organizations aiming to get into the decentralized trials game in the U.S. may find the biggest opportunity in the Great Plains and on Native American reservations—parts of the country with high disease prevalence but where patients likely have to travel long distances to participate in a clinical trial, a Milken Institute report (PDF) published June 24 suggests.

"If you're a CRO looking at decentralized trials then it's not just a logistical question of how, but also a question of where,” Andrew Friedson, Ph.D., director of the research department at Milken and the lead author on the report, told Fierce CRO in an email. “High distance/low access is part of the equation, the other part is which of these places has a denser than average patient population."

The report puts concrete figures and an interactive map behind a public health issue that’s well known to researchers, clinicians and politicians. Rural areas have higher rates of cancer, diabetes, stroke and lung disease than urban areas but lower access to care that could treat those conditions, including clinical trials. Distance from a trial isn't the only barrier to trial participation, but it's an important determinant with clear remedies, Milken researchers noted in the report. 

The study utilized data on trial locations from the Clinical Trials Transformation Initiative’s Aggregate Analysis of the database. Researchers collected data from all phase 2 and 3 trials registered between Jan. 1, 2017 and Sept. 30, 2023, encompassing nearly 14,600 studies total. When the data were restricted to U.S. sites, the researchers came out with about 256,600 study site and trial combinations, as many trials use multiple sites. They then matched each site to the county where it was conducted, finding about 1,200 counties had at least one site. 

The researchers then repeated the process for 30 diseases, including cancer, diabetes, substance abuse disorder, Alzheimer’s and more. In total, they found that less than 1% of the population lived farther than 60 miles away from a clinical trial for any disease—or, in other words, was “remote” from a clinical trial. However, there were plenty of counties that had high prevalence for a disease but were remote from a clinical trial targeting it. 

“Living within 60 miles of a phase 2 or 3 clinical trial does not mean that the clinical trial a person lives near is relevant to their health issues,” the researchers wrote in the report. “Being close to cutting-edge research for cancer treatment does not help someone who would benefit from being close to cutting-edge research for the treatment of Alzheimer’s disease.” 

People living in remote counties accounted for the largest share of the population living with hepatitis C, sickle cell disease and substance abuse disorder, the report found. Substance abuse disorder had the largest population of people living in remote counties, with more than 55% of the U.S. population living more than 60 miles away from a county where a phase 2 or 3 trial was taking place. 

In terms of demographics, remote counties were home to higher proportions of Native Americans than non-remote counties—Native Americans made up 8.1% of remote counties but less than 1% of counties that were within 60 miles of a trial. This was aligned with what Milken called the “community profiles” of remote counties: The average residents of Great Plains counties and Native reservations often lived more than 120 miles from a phase 2 or 3 trial. 

The study identified many counties with a high prevalence of cancer, chronic obstructive pulmonary disease (COPD), diabetes and Alzheimer’s but low access to clinical trials on treatments for those conditions. Regions with high rates of cancer and low cancer trial access tended to be clustered in Plains states and portions of Montana, Idaho and the Dakotas, while remote counties with high rates of COPD were concentrated in Southeastern states near the southern Mississippi river. A large portion of New Mexico had a high prevalence of diabetes but few diabetes trials. Central and southern states had the highest numbers of counties with high Alzheimer's prevalence but low access to trials for the condition.  

Other characteristics of remote regions were higher poverty rates, lower health insurance enrollment and a larger proportion of veterans, the report found. And, while there were relatively more Native Americans in remote counties than non-remote ones, most residents of remote counties were white or Latino. That suggests that factors other than physical distance from a trial, at least in the way it was measured in the study, may account for low trial participation among Black and Asian populations, according to the report.

There are some limitations to the study, the researchers noted. While the focus on mid- and late-stage trials was meant to be a proxy for the time commitment for study participation, there are other types of trials, like trials for nondrug interventions, that weren’t captured by the analysis. Furthermore, just because someone lives in a non-remote area doesn’t mean they have a short travel time to a study site or won’t be impeded by transportation issues. 

Ultimately, high-prevalence remote counties are an opportunity for expanding trial access, according to the researchers’ findings. Strategies for expanding access, such as decentralized clinical trials, would have “larger-than-average returns,” the report read.