FDA Wants Researchers to Rethink Patient Eligibility Criteria

Although the purpose of eligibility criteria is to protect patients from unnecessary harm, define the study population, and allow researchers to collect safety and efficacy data for a specific population, unnecessary restriction may not capture the heterogeneity of real-world patients. This was the gist of a perspective piece authored by experts from the FDA, including Richard Pazdur, MD, who heads the Oncology Center of Excellence.

The article, published in the New England Journal of Medicine, recommends relaxing the stringency of patient eligibility requirements for trial participation, so that the presence of a more heterogenous population allows for detection of safety signals in early stages. This could help inform criteria for subsequent trial participation.

The article makes a few suggestions on potential changes when recruiting patients in oncology trials:

• Rather than prevent patients infected with human immunodeficiency virus (HIV) from participating, allow patients with HIV whose CD4+ counts exceed a predetermined level or who have no opportunistic infections, to participate.
• Allow patients with a prior history of cancer to participate if the stage or type of their cancer has a low probability of recurrence, or who have passed the period of likely recurrence of their previous cancer. Patients with a history of treatment-related toxic effects should be excluded.
• Eligibility restrictions for organ system dysfunction should consider the specific organ system that the drug being evaluated is metabolized in; restrictions not relevant to these excretion or metabolic pathways may be unnecessary.
• Include patients with prior brain metastases; exclude those who have seizures or take medication to control their seizures that have known drug interactions.
• A progressive approach to pediatric oncology drug development would be to enroll pediatric patients 12 years and older in adult trials once the safety and dosing information in adults is confirmed. Younger children can be enrolled once safety has been established in the adolescent cohort.

The authors note that a heterogenous population would broaden the labelling claims for the pharmaceutical industry

“For example, if efficacy and safety were demonstrated in patients with brain metastases, a marketing claim could include an indication for this population in addition to the general indication,” they wrote. A more heterogenous clinical trial population could also ease some of the postmarketing regulatory requirements of safety and pharmacokinetics, especially in patients with organ system dysfunction.

Reference

Beaver JA, Ison G, Pazdur R. Reevaluating eligibility criteria—balancing patient protection and participation in oncology trials. N Engl J Med. 2017;376:1504-1505. doi: 10.1056/NEJMp1615879.