There are multiple reasons why the majority of breast cancer patients do not participate in clinical trials. One reason often emphasized is that patients simply decide not to participate when asked and if we improve how doctors talk to patients about trials, more would participate. However, a recent article looking at several studies of barriers to clinical trial participation found most of the barriers are system related, not doctor/patient related [1]. While this does not minimize the importance of the way in which doctors discuss trials with their patients; it indicates that there are also system barriers that must be overcome in order to increase the number of patients who have the opportunity to decide to participate. Two common system barriers to participation are the lack of access and narrow eligibility criteria.

Lack of access to clinical trials

There are several challenges contributing to the lack of access to clinical trials. The first challenge is to find a trial. Patients rely on their doctors to inform them about the possibility of participating in a trial. However, even doctors who are well aware of and accrue to trials at their own cancer centers, do not have the time or resources to monitor and recommend them at other sites. This means searching for a trial is often left to patients, which is not easy and a barrier for many. A second challenge is where the trial is conducted. Many are only available in larger academic cancer centers, which can pose travel challenges to patients in rural communities. Many patients are treated in rural cancer centers, which lack resources and do not have a large enough patient population to open complex trials in specific subtypes of cancer. This results in a lack of access in rural and diverse populations. A third barrier is that there must be a clinical trial available in the patients’ specific disease. Even though breast cancer is not a rare cancer, it can be a challenge to find available trials in a specific subtype of breast cancer.

There are solutions proposed to improve access to clinical trials. One solution is to decentralize clinical trials by changing where and how the data are collected [2]. For example, moving away from collecting data at a large academic cancer center to collecting data from a community cancer center, or even from the patient’s home, can ease travel barriers. Likewise, moving from data entered by a healthcare professional to fully virtual data capture can reduce patient burden by decreasing the number of clinic visits required. Although there are challenges to decentralization, there are many advantages, including faster accrual, increased diversity of the participants and most importantly, greater control and comfort for patients [3].

Narrow eligibility criteria

Unfortunately, even if a clinical trial is available and accessible, there is still another hurdle for patients to overcome; they must qualify to participate. Qualification is based on eligibility criteria – defined by inclusion and exclusion criteria – a patient must fit before they can consider participation. These tend to identify a very narrow, healthy patient population, which excludes many patients. There is currently an effort through an American Society of Clinical Oncology (VA, USA) and Friends of Cancer Research (DC, USA) collaboration to broaden eligibility criteria and include more patients that accurately represent the patient population with the disease. The first set of recommendations was published in 2017 [4–8] and more are expected in 2020. A recent study presented at the 2019 American Society of Clinical Oncology Annual Meeting (IL, USA; 31 May to 4 June 2019) [9] looked at CancerLinQ data illustrating the potential impact of implementing broader eligibility. This study showed that under traditional eligibility criteria 47.7% were excluded, whereas when using broadened eligibility (based on the 2017 recommendations) only 1.5% were excluded from potential participation.

Additionally, under-represented populations increased in the eligible population. This is important to patients, as it is frustrating to find a suitable trial and then not qualify for it. There are patients, particularly those living with metastatic breast cancer, who are actively looking for clinical trials. In some cases, not qualifying can be heartbreaking if participation would allow access to a new therapy.

Eligibility criteria for breast cancer clinical trials should be thoughtfully chosen based on safety and scientific rationale. Patient safety should always come first when selecting eligibility criteria, which will depend on the intervention and the patient population. Scientific rationale can also guide the selection of certain criteria, limiting the population based on previous scientific information. In breast cancer there are broader eligibility criteria that should be considered across every clinical trial. For example, they should include both men and women and should avoid an upper age limit. This is important as not only would it allow trial participants to be more representative of breast cancer patients, but would also increase access to more patients. Some criteria are particularly important to patients with metastatic breast cancer. For example, including restrictions on prior therapies or lines of therapy can be barriers to many patients with metastatic breast cancer. There are many patients surviving longer and enduring multiple lines of therapy, who have limited access to clinical trials because of narrow eligibility criteria. These are just a few of many restrictions that should be scientifically justified before they are used as eligibility criteria.

Deciding to participate in a clinical trial

Once there is a clinical trial available and patients are eligible to participate, they have to decide to enroll. This decision can be heavily influenced by the patients doctor, so it is important to consider how we talk to patients about participating in clinical trials. The trial should be explained to the patient using clear and understandable words and clinicians need to keep in mind that there may be parts of the trial that require a more detailed explanation to ensure understanding of what participation will entail. Patients should always be given the opportunity to take information home, so they can discuss options with family and friends. Doctors must realize that each patient is different and has a life outside the cancer center so they may not always understand the patient or their situation and how this may affect their decision to enroll. A conversation about how participation will affect their daily living is important, particularly highlighting how it will differ from their usual cancer care. Most importantly, every patient who qualifies should be asked to participate in a clinical trial, doctors should never assume they know whether a patient will participate or not.

Summary

Patients face multiple barriers to participating in clinical trials. There are three critical steps to take before patients can participate: they need to find a trial in their disease, they need to be eligible and they need to decide to enroll. Increasing patient participation must include strategies to overcome all barriers, both system and patient related. It is not just that patients are not deciding to enroll, they are not given the opportunity to enroll because of system barriers. All of these barriers are important and addressing them collectively will be the only way to expand access, so more patients can benefit from participation in clinical trials.

As a patient who has searched for and participated in two clinical trials, I have experienced these barriers. As a research patient advocate, I continue to advocate for more patient-centered clinical trials so future patients will not experience the same barriers I faced. Clinical trials are critical to the advancement of new treatments for breast cancer. Only trials that complete accrual have the potential to impact patient care and unfortunately not all achieve this goal. The patient perspective is critical to consider when developing trials to ensure accrual by reducing barriers to participation.

https://www.futuremedicine.com/doi/full/10.2217/bmt-2020-0004