Fear, Distrust and Distance: What 131 Studies Reveal About Why Cancer Patients Avoid Clinical Trials

Fewer than one in twenty newly diagnosed cancer patients in Canada ever sets foot in a clinical trial, according to figures cited by the Canadian Partnership Against Cancer, and a sweeping new analysis suggests the reasons lie less in indifference than in fear, confusion and logistics. A team of Canadian researchers has completed one of the most comprehensive syntheses to date of what patients and their unpaid caregivers actually say stops them from joining cancer treatment trials, drawing on 131 studies published over nearly five decades. Their scoping review, appearing in the open-access journal Cancer Reports, distills a vast and scattered literature into three interlocking categories of obstruction: psychosocial, logistical and informational. The findings arrive at a pivotal moment, as precision oncology promises tailored therapies that remain largely confined to research settings, making trial participation the gateway to tomorrow’s cancer care.

The scale of the undertaking is itself remarkable. The research team, led by Sarah Scruton and colleagues affiliated with the Marathon of Hope Cancer Centres Network Patient Voices Initiative, searched five databases spanning Ovid MEDLINE, PubMed, Scopus, CINAHL Complete and Web of Science, retrieving 7,918 candidate studies. After rigorous screening calibrated with statistical agreement measures, 131 studies published between 1979 and 2026 met their criteria. Roughly half were conducted in the United States, with the remainder scattered across the United Kingdom, Canada, Australia, China, Denmark, South Korea and beyond. Most focused exclusively on patients rather than caregivers, and more than half included participants who had declined or never been offered a trial, giving the review a rare window into the minds of the hesitant rather than only the committed.

The dominant barrier, reported in all but five of the included studies, was psychosocial. Fear in its many forms topped the list: fear of side effects from experimental treatments appeared in nearly 62 percent of studies, fear of being experimented on, the so-called guinea pig phenomenon, in just under 52 percent, and fear of randomization in about 41 percent. The dread of receiving a placebo or sugar pill was specifically voiced in 22 studies. In one breast cancer cohort, 44.7 percent of women who declined a trial said random assignment would discourage them, compared with just 12.4 percent of those who accepted. Among adolescent and young adult patients, qualitative work revealed a deeper anxiety: the fear of decisional regret if randomization assigned them to an inferior treatment arm, with parents shouldering the blame.

Distrust emerged as a second psychosocial pillar, reported in 37.4 percent of studies. Participants questioned whether research served their interests or those of physicians, pharmaceutical companies and career-minded investigators. In a Danish study, 34 percent of trial participants and 23 percent of non-participants agreed that medical research primarily promotes doctors’ careers. More strikingly, 17 studies documented distrust rooted in historical abuse, particularly among Black and Hispanic participants and older adults, with the Tuskegee Syphilis Study cited explicitly as a touchstone of medical betrayal. This legacy of racism in medicine continues to shape willingness to enroll, a finding the authors argue demands relationship-building and transparency rather than simple reassurance.

Logistical burdens formed the second major theme, raised in 73.3 percent of studies. Travel to trial sites, out-of-pocket costs, extra hospital visits and tests, time off work, and strain on family members all weighed heavily. In one Australian survey, 54 percent of patients said they would not join a trial if any out-of-pocket costs were involved, and 57 percent said they would refuse if it required changing oncologists. Among older adults, 82.7 percent identified needing care from family or friends as a barrier. Caregivers described relocating to be closer to cancer centers and absorbing the scheduling demands of appointments, yet fewer than 10 percent of the included studies captured their perspectives at all, a gap the review identifies as significant given caregivers’ central role in transportation, medication adherence and decision-making support.

Informational barriers, reported in 68.7 percent of studies, proved equally pervasive. Patients frequently did not know relevant trials existed, with 12 studies reporting that physicians never discussed trials as an option. Those who searched on their own found the process confusing and overwhelming; in one UK study of patients with secondary breast cancer, 53 percent of those who consulted a trial registry could not find the information they needed. Misconceptions about trial purpose and randomization were widespread, with one study reporting that 94.2 percent of trial refusers lacked understanding of the trial’s goal. Consent forms were described as lengthy, complex and intimidating, and language barriers compounded the problem for Asian American and Hispanic patients, one of whom ranked language as the second-highest obstacle to participation.

The interplay between fear and information emerged as perhaps the review’s most consequential insight. The authors note that fear-based and informational barriers often co-occurred, suggesting that limited understanding may fuel anxiety about experimental treatments, and that health literacy may explain the relationship, since trial awareness and participation are consistently higher among more educated individuals. If fears stem from missing or muddled information, they may be mitigated by clear, accessible communication, a hypothesis supported by prior evidence that web-based education programs, decision aids and simplified consent materials improve knowledge and foster more positive attitudes toward participation across health literacy levels.

Patients themselves offered a roadmap for improvement. Clear, credible and accessible information was the most commonly recommended facilitator, cited in 42 percent of studies, including plain-language consent forms, multiple information formats and centralized trial databases. Building trust came second, with participants emphasizing conversations with knowledgeable, respectful providers, and for racialized groups, research teams that share their ethnicity. Logistical supports ranked third: expense reimbursement, transportation and lodging, childcare, telehealth options and flexible scheduling. Some participants suggested trial designs granting more autonomy, and others called for mental health, spiritual or peer support during participation.

The review’s limitations are acknowledged candidly. Most studies did not specify trial phase or intervention type, limiting conclusions about which barriers dominate in early-phase versus late-phase research. Nearly half the literature is American, raising questions about transferability to other healthcare systems. Few studies compared barriers across racial or ethnic groups despite documented disparities in trial access, and none systematically examined how geography, income or education shape participation decisions. The authors also note that their review, consistent with scoping methodology, mapped the evidence rather than appraising its methodological quality.

Nevertheless, the synthesis arrives with clear implications. Structural solutions already exist in pockets: Canada’s ULink and Hope Air programs assist with travel and lodging, the Canadian Remote Access Framework for Clinical Trials guides delivery to rural patients through satellite centers, and Australia’s Tele-Trial Model brings trial procedures closer to home. What the review adds is the patient’s own voice, systematically assembled, arguing that recruitment will not improve through persuasion alone but through redesigned trials that respect fear, honor distrust, lighten logistical loads and speak plainly. As precision oncology expands the menu of targeted therapies, the bottleneck may no longer be scientific discovery but the human architecture of participation itself.

Subject of Research: Barriers to cancer clinical trial participation reported by patients and caregivers

Article Title: Patient and Caregiver Reported Barriers to Cancer Clinical Trial Participation: A Scoping Review

Article References: Scruton, S., Ito, C., Bohnen, J., Urquhart, R., Hessels, C., Konechny, S., Kraft, R., Thompson, R., Ho, C., Weymann, D., Bombard, Y., Krebs, E., Denburg, A., Hanna, T. P., Lim, H. J., Shareen, S., Regier, D. A., & Pollard, S. (2026). Patient and Caregiver Reported Barriers to Cancer Clinical Trial Participation: A Scoping Review. Cancer Reports, 9(10), Article e70700. https://doi.org/10.1002/cnr2.70700

Image Credits: AI Generated

DOI: 10.1002/cnr2.70700

Keywords: cancer clinical trials, patient barriers, caregivers, scoping review, psychosocial barriers, distrust in medicine, health literacy, informed consent, precision oncology, trial recruitment, health equity, logistical barriers