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Summary in Thirty Seconds
Rural patients are underrepresented in cancer clinical trials. Rural residents differ from urban dwellers in many notable ways which increase the likelihood of being excluded from cancer clinical trials with stringent inclusion criteria.
While rural patients have slightly lower cancer incidence rates, their mortality rates are higher. This may be due to poorer access to oncology providers and diagnoses at later disease stages.
People in rural areas must travel further distances to see their oncologists and participate in cancer clinical trials.
Rural patients and healthcare providers have lower levels of awareness about clinical trials, although rural patients are equally willing to participate in cancer clinical trials compared with urban/suburban people with cancer.
Solutions to improving rural patient participation in cancer clinical trials include sending more oncologists into rural settings, easing trial exclusion criteria, offering financial assistance/incentives for participants, using patient navigators/medical liaisons to educate patients and providers about participation and raise awareness, and using mobile diagnostic devices and telemedicine to make trials more patient-centric.
Diversity in Cancer Clinical Trials
Poor racial diversity in cancer clinical trials is a well-established problem. However, poor diversity is also evident when considering rural vs. urban trial participants. Numerous studies have found that rural patients are under-represented in cancer clinical trials[1],[2],[3] although these findings have not been entirely consistent.[4]
Rural vs. Urban Differences
It is important to recognize that rural people differ from urban/metropolitan patients in notable ways. This includes higher levels of poverty, a higher proportion of elderly people, and reduced access to health services, leading to lower cancer screening[5] (e.g., PSA, mammography, and Pap smear testing) and vaccination rates (e.g., HPV vaccination).[6] Smoking,[7] alcohol use,[8] and obesity rates are also higher in rural areas, resulting in greater preventable illness/disease problems. And because of reduced access to healthcare services and lower screening rates, patients in rural settings are more likely to have their cancer discovered at a more advanced stage.[9] Such differences might lead to more exclusions of rural versus urban patients based on stringent clinical trial eligibility criteria.[10]
Differences in Incidence and Mortality
While cancer incidence and mortality rates have been steadily falling in the United States over the past decades, rural areas have shown different changes compared to urban regions. Rural areas have shown slightly lower age-adjusted incidence rates (442 cases per 100,000 people in rural vs. 457 per 100,000 in urban regions) but higher mortality rates (180 deaths per 100,000 people in rural vs. 158 per 100,000 in urban regions).[11] This higher mortality may be because people in rural areas have poorer access to oncology providers (and are diagnosed at more advanced disease stages).[12] 15-20% of the US population lives in rural areas (depending on how “rural” is defined)[13] while about 3-7% of oncologists work from rural locations.[14],[15],[16] An ASCO survey found that 40% of rural patients versus 22% of urban patients indicated there were not enough oncologists in their area.[17]
Studies have found higher incidence and mortality rates in rural areas for cervical, colorectal, kidney, lung, melanoma, and oropharyngeal cancer.[18] Studies have also found treatments vary by location, with rural patients more likely to receive mastectomies (rather than less aggressive surgical interventions for urban patients) and less likely to receive radiotherapy.[19]
Why Including Rural Patients Matters in Cancer Clinical Trials
The above-listed findings emphasize the importance of representatively including people from rural areas in cancer clinical trials. Importantly, research has found that when treatment approaches are made consistent, such as is seen in clinical trials, the disparity in cancer survival rates between rural and urban patients is eliminated.[20] However, unless gains are made in access to clinical trials for rural patients, rapid advances in cancer care will worsen already existing gaps in outcomes for rural patients.[21]
Distance from Cancer Clinical Trials
An issue for people with cancer in rural areas is the distance they must travel to participate in clinical trials. A 2021 study by the Mayo Clinic compared the distance traveled by clinical trial participants at Mayo’s three US locations and found that urban participants traveled 68 (± 88) miles to the trial site whereas rural participants traveled 103 (± 104).[22] One study of people with colon cancer found that patients who traveled more than 50 miles for their diagnostic testing were more likely to have metastatic cancer versus those 50 miles or closer to a center.[23] An ASCO survey revealed rural cancer survivors drove a median of 50 minutes to reach their oncologists versus 30 minutes for urban cancer survivors.[24] Such distance disparities are highlighted by a large survey of clinical trial sites which found that sites are highly clustered around urban centers across the US.[25]
Awareness of Cancer Clinical Trials
Rural patients also have lower levels of awareness about clinical trials than urban and suburban patients.[26] One study of rural patients who had low awareness of clinical trials found that these patients expressed a desire for information and training to increase their clinical trial knowledge and confidence.[27] One small study of rural (and inner-city) patients evaluated from where information about clinical trials was obtained. Half of the participants learned about clinical trials from the media (particularly advertisements), half learned about them from searching online, and almost all from their healthcare providers.[28] An interesting finding is that urban and rural patients are equally willing to participate in clinical trials; however, rural patients are less aware of clinical trials and have lower knowledge about trials in general.[29]
Addressing Disparities
A systematic review of studies reporting on cancer clinical trials found barriers to participation included travel distance, cost, and physician and patient attitude and knowledge. Enablers of participation included multi-disciplinary tumor board meetings (allowing for better exchange of information), molecular profiling (identifying specific patients for targeted trials), larger hospitals (where there are more resources and more opportunities for information sharing), the willingness of patients and their families to travel, financial support, and improved physician and patient attitude and knowledge.[30] Another study found differences in motivators for clinical trial participation, including a greater emphasis on family/community factors in rural patients, leading the authors to suggest more effective approaches to recruit rural patients including working with schools and churches and word of mouth.[31]
Clinical trial investigators infrequently communicate about clinical trials outside of the medical setting or partner with community organizations or local doctors to reach rural patients.[32] Thus, finding ways to educate, connect, and improve the awareness of clinical trials in rurally based healthcare providers may lead to increases in the participation rates of their rural cancer patients. One rurally based oncologist suggests forming rural consortia that band otherwise isolated practitioners together to promote clinical education and information sharing as well as serving as a single study site.[33]
A review of centers working toward increasing rural participation recommended the following interventions:[34]
assist with community access by sending oncologists to rural sites not only to see patients directly but also to meet with rural oncologists and raise their awareness of cancer clinical trials
use of less restrictive eligibility criteria
reduce financial barriers to enrollment
use of patient navigators, HCPs, and community health workers to form community connections providing education about encouraging trial participation
incorporate mobile diagnostic services (e.g., mobile mammography) to provide community screening
provide training to increase the number of people who can conduct clinical trials
use of telemedicine and telementoring to reach remote patients and caregivers.
The Bottom Line
To have truly representative cancer clinical trials means not only proportionally balancing racial and gender diversity, but also rural vs. urban disparities. Rural patients have notable differences from urban patients in a variety of factors, some of which are general while others are specific to types of cancer and treatments. When treatment practices are equalized, as is seen in clinical trials, cancer mortality rate differences are eliminated or at least reduced. And rural patients appear to be as willing to participate in trials compared with their urban counterparts, but rural patients tend to be less aware of cancer clinical trials. Many steps can be taken to improve not only patient but healthcare provider awareness and knowledge of trials that will make cancer clinical trials far more patient-centric, representative and beneficial to all people with cancer.
[1] American Society of Clinical Oncology Educational Book 2019; 39:11-18 [2] Clin. Invest. 2014; 4(4):373-380 [3] JMIR Cancer. 2022; 8(2)e33240 [4] JAMA Netw. Open. 2018; 1(4):e181235 [5] J Prim Care Community Health. 2011; 2:240-9 [6] About Rural Health | CSELS | Rural Health | CDC [7] Prev. Med. 2017; 104:79-85 [8] J of Rural Health. 2007;23:314-321 [9] JMIR Cancer. 2022; 8(2)e33240 [10] J. of Clin. Oncol. 2017 35(33):3745-3752 [11] MMWR Surveill Summ. 2017; 66(14):1-13 [12] Access to Cancer Care in Rural Populations: Barriers and Solutions (ascopubs.org) [13] Health in Rural America | NIH News in Health [14] JCO Onc. Pract. 2018; 14(7):e412-e420 [15] Oncologist. 2018; 23(10): 1242–1249 [16] J Oncol Pract. 2014;10(1):32-38 [17] The Harris Poll. ASCO 2018 Cancer Opinions Survey [18] Cancer Epidem, Biomark, & Prev. 2017: 26(78):992-997 [19] Cancer Epidem. Biomark. & Prev. 2013; 22:1657-1667 Cancer Epidem. Biomark. & Prev. 2013; 22:1657-1667 [20] JAMA Netw. Open. 2018; 1(4):e181235 [21] J of the Nat. Cancer. Inst. 2022; 114(7):940-952 [22] J Clin Transl Sci. 2021; 5(1): e190 [23] J Clin Oncol. 2019 Aug 1; 37(22): 1935–1945 [24] The Harris Poll. ASCO 2018 Cancer Opinions Survey [25] Clin. Invest. 2014; 4(4):373-380 [26] Patient Educ. Counsel. 2011; 85(2):e69-e74 [27] Urol. Oncol: Sem & Orig. Invest. 2019; 37(8):529.e9-529.e18 [28] Cont. Clin. Trials Comm. 2017; 5:72-79 [29] Asia-Pacific J of Clinical Oncol. 2010; 7(1): 27-33 [30] Clinical Trials. 2022l 19(4):464-476 [31] Am. J of Health Promo. 2015; 29(5): 332-338 [32] Cont. Clin. Trials. 2015; 41:39-44 [33] Improving Access to Clinical Trials for Rural Populations (accc-cancer.org) [34] JCO Clinical Oncol. 2020; 16(7):422-430