Barriers and Solutions to Cancer Clinical Trial Enrollment
Updated: Feb 17
Summary in 30 Seconds
Cancer clinical trials suffer from low enrollment rates even though most people with cancer are willing to participate; however, three factors often impede participation:
Financial concerns (travel costs, co-pays, missed work, etc.) can be aided by financial assistance in a variety of ways.
Logistical issues (risk/benefit analysis, complicated informed consent, clinician biases) can be mitigated by clear, concise, and structured communication.
Lack of family/friend support in the process can be helped by the use of patient navigators (in a variety of ways).
Creative and effective efforts to enhance abysmal clinical trial enrollment rates are key to better, more representative, and more efficient trials, which ultimately produce life-improving and saving medications.
The Low Enrollment Problem
Low enrollment is a major barrier to successful cancer clinical trials (CCT). While 70% of people with cancer are willing or inclined to participate in clinical trials, only 2-5% of adult cancer patients enroll in a trial. And the rate of participation has not significantly changed over time. This is particularly problematic when 25% of trials fail because of insufficient enrollment. What are the factors hindering enrollment? A meta-analysis of 13 studies including over 8,880 patients found that approximately 55% of people with cancer do not participate in trials because no trial is available for the patient’s cancer type and/or stage at their local clinical center. Is it possible that trials may have been available but these patients and/or their healthcare providers were unaware of such trials? This same meta-analysis found that another 21.5% were ineligible because of specific enrollment criteria. Beyond these barriers, a 2019 ASCO Educational Book describes three impediments to CCT enrollment: Financial concerns, logistical issues, and lack of support.
Direct and indirect healthcare costs are a huge issue for people with cancer. Out-of-network costs and non-funded procedure costs lead to high out-of-pocket medical expenditures. Such financial burdens can lead patients to skip care appointments or inconsistently follow medical advice to lessen financial burdens. Recent studies demonstrate that patients with low incomes/financial resources including uninsured, rural, and minority patients—are frequently underrepresented in CCTs. People miss work to attend doctor visits and treatment procedures, and they may even lose or have to quit their jobs. This is particularly true for people who live in rural areas necessitating travel or overnight stays to reach appointments at clinics and hospitals. While all people with cancer experience such “financial toxicity,” enrolling in a CCT can exacerbate ongoing financial hardship through additional costs of clinic visits, missed work, and trips to emergency departments due to adverse effects. A 2015 survey of over 1,000 people with cancer found that financial concern, and specifically, worry about coverage of clinical care costs was one of the largest barriers to cancer clinical trial enrollment.
What might be done to address the financial concerns of people considering cancer clinical trial enrollment? In the past, hospitals and charities have provided housing for people coming from long distances for trial participation. Giving financial assistance for travel and lodging to those participating in trials has led to increased enrollment. A policy statement from ASCO suggests methods to address financial issues related to CCT participation, including providing potential participants with more clarity about clinical trial cost payment policies and transparent information about trial-related costs and offering financial assistance to help defray the costs of participation.
Uncertainties regarding CCT participation are another significant barrier to patient enrollment. Potential participants often experience difficulty in balancing risk-benefit decisions. One study examining decision-making in people with cancer found that patients tend to emphasize the adverse effects of treatment when considering CCT participation. Informed consent forms are often complicated and lengthy, so participants have difficulty understanding them, particularly patients with low education or who have concerns about ethical issues regarding participation. Sometimes treating physicians serve the dual role of caregiver and investigator, potentially introducing bias into the informed consent process. Such bias can lead to misestimations regarding a specific patient (e.g., because minority patients have traditionally been less likely to participate in trials, a clinician may approach such a patient with less positivity regarding participation). Clinicians may also be concerned about damaging their “working alliance” with patients over concerns that their suggestion of CCT participation will be rejected or lead a patient to view the healthcare provider with suspicion.
Possible solutions to logical issues include improving communication and mutual understanding between clinicians and patients via question-prompt lists provided to patients and clinicians ahead of visits. Additionally, the order in which information is presented to potential CCT candidates can influence their choices. Research on the choice process suggests that if the negative effects of cancer without participating in a CCT are discussed first, followed by probabilities of how participation could reduce these effects, enrollment levels may increase.
Lack of Support
Cancer not only affects the person who is experiencing the disease, but also the person’s family and community. If the family and/or community of that person is not supportive of CCT participation, the likelihood of their enrollment is notably reduced. For several reasons, including past abuses in clinical research, enrollment rates of ethnic minorities are low, resulting in limitations in the findings of CCT results outside the demographics of the study.
The use of patient navigators—people who have gone through a similar procedure or trial and can give potential participants not only information but hope—has been shown to increase treatment completion rates and even enrollment rates, particularly among minority patients. This is most significant when the patient navigators come from similar ethnic minority groups and/or communities. Patient navigators can not only assist at the time of enrollment, but can be involved in the screening process, pre-planning of visits, and follow-up post-enrollment to ensure positive communication and support between the patient and clinical site.
The Bottom Line
While some of these enrollment issues may be addressable, factors such as restricted eligibility may be less amenable to simple remedies. Nevertheless, efforts to enhance access to CCTs are vital to improving abysmal enrollment rates. The Covid-19 pandemic has demonstrated that technology can be used to overcome what were once seen as insurmountable barriers. Technology can clearly be used to build awareness and access to CCTs. Additionally, sponsors and clinicians may consider ways in which technology may reduce financial burdens on patients (e.g., virtual visits that reduce travel), improve communication and other structural barriers (e.g., websites providing easy-to-understand information and allowing for prescreening of potential candidates), and provide improved support to people with cancer. Such steps can improve enrollment rates, leading to better, more representative, and more efficient trials, which ultimately produce life-improving and saving medications.
 J Clin Oncol. 2003; 21:830-835  ascopubs.org/doi/10.1200/JOP.2012.000598  JNCI. 2019, March; 111(3):245–255  Contemporary Clinical Trials Comm. 2018; 11:156–164  JNCI. 2019, March; 111(3):245–255  ASCO Educational Book. 2019; 39:105-114  British Journal of Cancer. 2014; 111:1684–1687  Eur. J Cancer Care. 2015; 24(1):28-38  The Oncologist. 2016; 21(4):467-474  J Clin Oncol. 2018; 36(33):3331-3339  Supportive Care in Cancer 2019; 27:1613–1637  Cancer Contr. 2016; 23:327-337  ibid  Science. 1981; 211:453-458  Psychooncology. 2006; 15:273-284  JAMA. 2004; 291:2720-2726  J Natl Cancer Inst. 2014; 106(6):dju115  J Oncol Pract. 2016; 12(6):556-563  JAMA Oncol. 2021; 7(10):1559-1566  BMJ 2011; 342:d3662