As part of our coverage of the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 2–6 in Chicago, we spoke about patient participation in clinical trials with Julia Beaver, MD, acting director of the Division of Oncology Products 1, Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, at the US Food and Drug Administration (FDA) in Beltsville, Maryland.
Cancer Network: How big of a problem is accrual of participants in clinical cancer treatment trials?
Dr. Beaver: Cancer trials are known to have very low accrual rates; it has been estimated that fewer than 3% of patients with cancer participate in a clinical trial. Reasons for low clinical trial accrual rates stem from patient-level, physician-level, institutional-level, and protocol-level barriers. For example, patients may fear clinical trials will delay initiation of standard cancer drugs or require additional morbid testing and procedures. In addition, availability of clinical trials at a given institution varies, and there may be a lack of knowledge regarding potential clinical trials for patient referral. Overly restrictive eligibility criteria can also limit patient enrollment, reducing access to investigational agents as well as impacting the interpretability of the trial results in a more representative patient population.
Cancer Network: Have eligibility criteria for clinical cancer trials been too narrow or strict?
Dr. Beaver: Yes. Although eligibility criteria are designed specifically to protect patients, overly restrictive criteria can lead to trials that do not provide useful information about how the therapy may work in a broader set of patients that will ultimately get the approved treatment. We often see eligibility criteria simply duplicated from trial to trial in lieu of a systematic way of considering how the drug might be used in certain populations. A lack of sound scientific reasoning for excluding potential trial participants unnecessarily limits accrual and meaningful data on the drug’s effect in a more heterogeneous patient population.
Cancer Network: How has this affected how well clinical trial findings translate to real-world clinical benefits?
Dr. Beaver: Patients with certain characteristics are regularly excluded from clinical trials for cancer treatments, including those with HIV, a history of previous cancers, organ dysfunction, brain metastases, and patients under the age of 18 years. By excluding patients like this, we lack the understanding of the drug’s safety and effectiveness in patients who have certain cancer characteristics, comorbidities, or who are children or adolescents. In addition, many of these criteria, particularly comorbidities, will restrict entry of the older adult population.
Cancer Network: What can be done?
Dr. Beaver: We’ve outlined some suggested approaches in a recent New England Journal of Medicine article. The article states that “a logical approach to defining eligibility could allow for detection of safety signals in early clinical trials that use broad eligibility criteria and permit modification of subsequent criteria throughout the drug development process as knowledge emerges.” We advocate for a more rational and nuanced approach to defining eligibility throughout the drug development process.
Cancer Network: What is the FDA doing to help improve patient participation in cancer clinical trials?
Dr. Beaver: The FDA has been actively encouraging sponsors to take a more thoughtful approach to determining eligibility criteria and to reevaluate the practice of simply copying criteria from one protocol to the next. We’ve had productive one-on-one meetings with sponsors encouraging them to critically evaluate the common restrictions we see in eligibility criteria, so that we can have a more accurate picture of a drug’s safety and efficacy in the broader patient population that will ultimately receive the drug.
In addition to directly engaging sponsors, we are also participating in an effort with the ASCO and Friends of Cancer Research (FoCR) Modernizing Eligibility Criteria Project, which includes academic, government, industry, and patient advocate representatives to explore this issue and provide a forum for dialogue about ways sponsors can implement a more nuanced approach to eligibility. Further publications are expected from the ASCO and FoCR group on considerations related to specific populations of patients who are commonly excluded, such as patients with HIV, patients with organ dysfunction, patients with history of prior malignancy, patients with brain metastases, and patients under 18 years of age. We also have another working group meeting planned this year that will focus on implementation of the recommendations and will also consider new criteria such as concomitant medications or other triggers for exclusion of the older adult.