FDA Seeks to Broaden Clinical Trial Eligibility Criteria

To reduce the time and cost involved with conducting clinical research on new biopharmaceuticals, regulators and researchers are looking to broaden outmoded criteria for identifying and enrolling individuals in clinical trials. Sponsors traditionally have shied away from including young patients and those with infectious diseases or comorbidities that might raise safety issues or compromise efficacy results. Their aim is for clinical trials to generate data that will support market approval of new drugs, biologics, and medical products, and to avoid studies that involve children, small patient populations, or patients in poor health that may generate confusing or questionable data.

At the same time, restrictions on clinical trial participation may “slow patient accrual, limit patients’ access to clinical trials, and lead to trial results that do not fully represent treatment effects in patients that ultimately will use the drug,” explained outgoing FDA Commissioner Scott Gottlieb March 12 in unveiling a series of guidance documents that provide strategies for achieving broader patient inclusion in oncology trials. New policies are needed because long-established and widely-used eligibility criteria become set in stone over time, discouraging new approaches despite changing technology and patient preferences.

The new guidances specifically address clinical studies for new cancer treatments, where a broadening of eligibility criteria would enable more people to participate in oncology trials, a field where patient accrual is difficult, but where the serious nature of disease may lend itself to more flexibility in enrollment criteria. Including children, adolescents, and individuals with infectious diseases, malignancies, and metastases may yield results that are more generalizable and help improve our understanding of a therapy’s benefit-risk profile across populations likely to receive the drug in clinical practice, Gottlieb explained.

One guidance finalizes an earlier proposal for including adolescents in adult oncology trials where the age of 18 is the traditional cutoff point. The rationale is that many cancers found in younger patients often behave similarly in adults, and that excluding adolescents from clinical studies may delay their access to potentially effective therapy. The guidance advises on criteria for enrolling these patients in studies, recommendations for dosing and safety monitoring, and relevant ethical considerations to support treatment. A draft guidance similarly addresses how and where it is appropriate for sponsors to include pediatric patients in adult cancer trials to obtain more accurate information more quickly on appropriate dosing and treatment of children of different age levels.

Patients with HIV or hepatitis infections should not be ruled out of participation in clinical trials, says FDA in another draft guidance, especially when cancer treatment may be particularly important for individuals with such chronic conditions. Eligibility may be limited for AIDS patients with particularly low CD4 cell counts or more serious infections, and timing of treatment may be important in certain situations.

Another guidance addresses criteria for cancer trials to include patients with organ dysfunction (renal, cardiac, hepatic) or previous malignancies. The policy notes that excluding such individuals may skew recruitment to younger patients, which may not be fully representative of the population likely to receive treatment.

FDA sees a need to study patients living with cancer who increasingly are diagnosed with brain metastases, in an effort to discourage exclusion of such individuals from clinical research.

The four new draft guidances were developed by FDA with input from the American Society of Clinical Oncology and Friends of Cancer Research. These policies aim to ensure that clinical trials are designed to reflect “the diversity of the population that receives drugs in the real world,” said Gottlieb, and to help design oncology trials to be “more representative of the patients that may ultimately benefit from novel treatments.”