Low Trial Participation Among Patients With Cancer Attributable to Structural, Clinical Barriers

Joseph M. Unger, PhD, MS, Fred Hutchinson Cancer Research Center, Seattle, WASWOG Statistical Center, Washington, spoke with Oncology Learning Network about the clinical significance of his team’s recent study on the magnitude of different barriers to clinical trial participation faced by patients with cancer.

Results from the study by Dr Unger and colleagues underscore the tremendous need to improve patient access to clinical trials, which is obstructed by structural and clinical barriers for >75% of patients with cancer (J Natl Cancer Inst. 2019;111[3]:245-255).

What existing data led you to evaluate the different domains of barriers obstructing patients from participating in cancer clinical trials?

In my own research, I have used trial registration data, patient survey data, and prospective cohort data to examine patterns of barriers to cancer clinical trials. This provided me with a strong familiarity with the literature about trial barriers.

Over time, I realized that to better understand the type and magnitude of trial barriers, it is best to consider the entirety of the clinical trial treatment decision-making process. Beginning when a patient enters a clinic for their first visit, a series of evaluations are conducted, including whether a trial is available, and if one is, whether the patient is eligible, and if they are, whether the physician discusses and offers a trial to the patient.

With this pathway in mind, we formulated a framework describing this trial decision-making pathway. We then systematically reviewed the existing literature going back 2 decades to identify all studies which examined patient decision-making about trials in this manner.

We identified 13 studies and included their results in a meta-analysis.

Please briefly describe your study findings. Were any of the outcomes particularly surprising?

We found that nearly 56% of patients did not have a trial available to them at their institution and nearly 22% were deemed ineligible for an available trial. So together these structural and clinical barriers alone were the reasons >3 out of 4 cancer patients did not participate in trials. 

We also found that ultimately 8% of patients enrolled in trials. This contrasts with the typical estimates for trial participation for adults with cancer, which are between 2% and 3% based on studies in the 1990s and early 2000s.

This very low statistic has been cited frequently, but was largely was based on enrollments to government-sponsored trials, when actually about twice as many patients enroll in pharmaceutical-sponsored trials. We believe the estimate of 8% is likely more reflective of the rate of participation to any type of cancer clinical trial, whether government-sponsored or pharmaceutical-company sponsored. 

Another important observation is that when patients are offered an available clinical trial, they choose to participate about 50% of the time. This leaves a very different impression about the role of patients in clinical trial participation, indicating that they are much more willing to participate than is commonly assumed. It is also consistent with the idea that structural and clinical barriers—rather than patient barriers—are the predominant reason for low participation rates.

What are the possible real-world applications of these findings in clinical practice?

Although our estimate of the overall trial participation rate is higher than has been commonly assumed, it remains low, indicating that only 1 out of 12 patients participate in trials. This has real-world implications.

First, it indicates that opportunities for patients to receive the newest treatments in trials are very limited. This is a problem since it reduces treatment options for many patients.

Second, many trials end up closing due to poor accrual, and the trials that do complete often take a long time to do so, leading to results that are less timely.

If more patients were able to participate in trials, trials could be completed more quickly, and new treatments could be identified more quickly, leading to better outcomes for all patients with cancer.

Do you and your co-investigators intend to expand upon this research?

Clearly, structural barriers are the dominant reason patients do not go onto trials, especially the absence of an available study locally at the site. In this context, travel distance alone comprises a largely unexamined barrier to clinical trial participation and is a future area of research.

Travel distance is a complex construct and has multiple clinical and financial ramifications. For instance, many patients cannot travel to where the trials are available because of the constraints of having to take time off work, family constraints and child care, and the costs of having to travel to another location and potentially stay there for long periods to receive care.

This can also induce income disparities in clinical trial participation since patients with greater financial means will be more likely to be able to travel far distances to receive care in a trial. Thus, reimbursing patients for the costs of participating in trials is also vitally important.

So, my research interest going forward is to better understand how to bring the trials to the patients or bring the patients to the trials.