Barriers to Cancer Clinical Trial Enrollment

In Clinical Trials by Barbara Jacoby

By: Andrea S. Blevins Primeau, PhD, MBA

From: cancertherapyadvisor.com

Clinical trials are critical to developing new therapies and improving existing regimens for better efficacy and safety.1 Clinical trials can only be conducted if they enroll sufficient numbers of patients, and the more rapid the accrual, the sooner results can be collected and analyzed, and, ultimately, translated to the clinical setting. However, it has been estimated that almost 39% of trials terminated prematurely were due to lack of accrual.2 It is also estimated that just 8% of patients with cancer participate in clinical trials.2

Given the continued need for better therapies for patients with cancer, and the difficulty with enrolling patients, it is important to understand why participation rates have historically been low.

A meta-analysis of 13 studies (representing 8883 patients) conducted in the academic and community settings identified structural and clinical barriers as the primary causes of low levels of patient participation in clinical trials.1 In the analysis, 56% of patients were unable to participate in a clinical trial because there were none available for their cancer type or stage. Of the remaining patients, 22% did not meet eligibility criteria for the available trials and 15% who were eligible did not enroll. Ultimately, 8% of the patients represented across the 13 studies enrolled in clinical trials. Interestingly, enrollment was higher at academic institutions (16%) compared with the community setting (7%; P <.001), with no differences in eligibility and non-enrollment. There were fewer trials available at the community centers, although the result was not determined to be significant.

There are multiple barriers that prevent clinical trial enrollment. The meta-analysis demonstrated that trial availability and eligibility criteria are major barriers.1 Other barriers include patient- or physician-related factors.

Patient-Related Barriers

Many barriers that patients experience, particularly those of underserved populations or racial or ethnic minorities, are barriers to access.3,4 Some of these factors are related to the clinical trial availability issue, as patients must find a cancer center in a geographic area that is a reasonable distance from their home — and one that is also associated with a reliable and affordable means of transportation.3 Other access barriers include the ability to take time away from work, finding child care, and having access to insurance.

Patient attitudes and beliefs can also be a barrier to clinical trial participation. Some patients may fear the idea of randomization or unknown potential toxicities associated with experimental therapy.3 One survey found that 12% of patients who were aware of clinical trials chose not to participate due to fear of receiving placebo, and 21% did not enroll because they thought a trial would not help them.5 Some patients do not enroll because they may already have a strong opinion about which treatment they want to receive.3

Patients may also fear the financial burden that can be linked to trial participation, despite the fact that private insurers and Medicare are typically required to cover normal medical costs associated with clinical trial visits. However, lower socioeconomic status is associated with lower levels of clinical trial participation, despite there being little difference in trial-related treatment costs compared with treatment outside of a trial setting.3 This appears to support the theory that indirect costs, such as travel and loss of work days, may prevent some patients from enrolling.

There are also racial and ethnic disparities — African American, Asian, Hispanic, and Native American populations have lower rates of trial participation than whites.4 A disproportionate number of minorities receive care at under-resourced institutions, where clinical trial availability is typically also low. Minorities also are more likely to be underinsured or have comorbidities that exclude them from trial eligibility. There may also be some provider bias, whether conscious or unconscious, as discussions about clinical trials occur less frequently with African American and Asian patients compared with Caucasian patients of European descent.5 For example, a focus group found that some physicians were less likely to discuss trials with African American patients because the physicians felt that these patients were likely to mistrust physicians and medical institutions.6

Physician-Related Barriers

Physicians are critical to clinical trial enrollment because the majority of patients learn about clinical trials through their health care providers — in one study, 93% and 76% of patients who eventually enrolled or did not enroll in a trial, respectively, learned about the trial from their provider.5

And, although more than 83% of physicians practicing in the community setting believe that clinical trials benefit patients and provide high quality care, the practitioners do not always discuss available clinical trials with their patients.3,5 For example, in a study of more than 2100 patients with stage III/IV lung cancer or stage IV colorectal cancer, 26% of patients recalled discussing clinical trials with their physician.5 However, there are many resources now available to patients to help them find clinical trials for which they may be eligible.

Some physicians may avoid discussing clinical trials because they may have already formed a strong opinion about an optimal treatment for the patient and feel that a clinical trial would be unnecessary.3 Others may believe that their patients will not meet eligibility criteria. There are also structural barriers for physicians that serve to prevent them from enrolling patients into clinical trials. These could include  the extra time spent explaining clinical trials, enrolling patients, and acquiring their formal consent to participate. In addition, the described treatment/evaluation protocol described by trial investigators may be prohibitive.

Conclusions

Although clinical trial enrollment is important to advance cancer research, clinical trial participation remains low. Clinical trial availability and eligibility criteria are major barriers to clinical trial participation, but other patient- and physician-related factors can also create additional barriers. Addressing these barriers directly may potentially improve trial participation rates.

References

  1. Unger JM, Vaidya R, Hershman DL, Minasian LM, Fleury ME. Systematic review and meta-analysis of the magnitude of structural, clinical, and physician and patient barriers to cancer clinical trial participation. JNCI J Natl Cancer Inst. 2019;111:djy221.
  2. Mahmud A, Zalay O, Springer A, Arts K, Eisenhauer E. Barriers to participation in clinical trials: a physician survey. Curr Oncol. 2018;25(2):119-125.
  3. Unger JM, Cook E, Tai E, Bleyer A. Role of clinical trial participation in cancer research: barriers, evidence, and strategies. Am Soc Clin Oncol Educ Book. 2016;35:185-198.
  4. Hamel LM, Penner LA, Albrecht TL, et al. Barriers to clinical trial enrollment in racial and ethnic minority patients with cancer. Cancer Control. 2016;23(4):327-337.
  5. Kehl KL, Arora NK, Schrag D, et al. Discussions about clinical trials among patients with newly diagnosed lung and colorectal cancer. J Natl Cancer Inst. 2014;106(10):dju216.
  6. Pinto HA, McCaskill-Stevens W, Wolfe P, et al. Physician perspectives on increasing minorities in cancer clinical trials: an Eastern Cooperative Oncology Group (ECOG) initiative. Ann Epidemiol. 2000;10(8 suppl):S78-S84.