The U.S. Food and Drug Administration (FDA) recently finalized three guidance documents that aim to make clinical trials for oncology drugs more accessible to patients by encouraging sponsors to reconsider eligibility criteria.
Issued by the FDA’s Oncology Center of Excellence, the documents address performance status, washout periods, and concomitant medications and laboratory values. Experts say that the documents could work to broaden trial participation by addressing restrictive trial criteria that have traditionally limited enrollment and leave patients treated with an approved therapy underrepresented in the evidence base.
“As our therapies have really evolved over time, the way of assessing patients has not evolved,” said Allison Magnuson, DO, a geriatric oncologist at the University of Rochester School of Medicine in New York. “We need to equally be evolving how we are designing clinical trials to ensure that all populations are eligible.”
Key Takeaways
- The FDA guidance addresses performance status, washout periods, concomitant medications, and laboratory values that can restrict cancer trial participation.
- Liberalizing eligibility criteria responsibly can expand patient access because relatively minor laboratory or performance differences frequently exclude patients, Dr. Patt said.
- Guidance alone will not change trial designs; sponsors and contract research organizations must adopt the FDA’s recommended approaches.
Fewer than 5% of patients with cancer who are receiving treatment participate in clinical trials, despite estimates showing that around 70% are interested in doing so. The FDA notes that overly restrictive eligibility criteria can slow enrollment, limit access, and produce trial populations that do not adequately reflect real-world patients.
Debra Patt, MD, PhD, MBA, executive vice president and chief clinical officer at Texas Oncology in Austin, said that eligibility criteria can exclude patients for relatively minor differences in measures such as laboratory values or performance status.
“These eligibility criteria kick patients out of clinical trials like half the time,” Dr. Patt told Oncology News Central (ONC). “So liberalizing them in ways that are responsible makes sense and allows more patients to have access.”
The updated performance status guidance addresses a particularly common challenge: The metric measures a patient’s ability to perform everyday activities; however, the FDA noted that poor performance status may sometimes be driven by the cancer itself and could improve with treatment.
The other two guidance documents address additional barriers that can disproportionately affect patients with more complex medical histories. The FDA encourages sponsors to reconsider whether fixed washout periods between therapies are clinically necessary and to take a more individualized approach to concomitant medications. The laboratory values guidance similarly calls for eligibility thresholds to be grounded in scientific and safety considerations rather than automatically carried forward from previous trials.
Those issues can become more prominent with age and when patients are more likely to have multiple medical conditions and take several medications, Dr. Magnuson told ONC. She added that these patients are historically underrepresented in clinical research.
The FDA’s updated recommendations fit into a broader effort to modernize clinical research, including decentralized trials, electronic consent, remote monitoring, and electronic patient-reported outcomes, Dr. Patt said. At her practice, patients receiving active therapy have used electronic patient-reported outcomes for six years.
Still, the new guidance alone will not actually change cancer clinical trial designs, Dr. Patt said. Sponsors and contract research organizations also need to adopt the approaches outlined by the agency. “It’s not enough to have FDA guidance,” Dr. Patt said. “We need manufacturers and [clinical] research organizations to adopt more progressive clinical trial strategies to make increasing accrual a reality.”
The three guidance documents were developed after workshops that involved the FDA, the American Society of Clinical Oncology, and Friends of Cancer Research and advance a goal of the Department of Health and Human Services’ Operation TrialBlazer initiative, which calls for improving access and engagement in clinical trials.
Broader eligibility could help generate evidence for patients who have historically been left out of trials, while preserving the need to understand safety and treatment effects in different populations, Dr. Magnuson said.
“Our treatments are so sophisticated,” she said. “We need to be matching that with our trial design and our enrollment.”
Dr. Patt reported various financial relationships.
Dr. Magnuson reported research funding with FAIR Health.