Eligibility Guidelines on the Way
Everyone is rethinking eligibility criteria – the guidelines in protocols that dictate exactly which patients can enroll onto that study. They've been percolating for a while, but new guidelines are finally on the way.
Next month, CTEP is expected to release new eligibility criteria templates to SWOG and other groups in the NCTN, for use in all treatment trials. This revised language will reflect changes suggested last year by ASCO and Friends of Cancer Research. In October, those groups called for more inclusive criteria for cancer clinical trials, in a special series of articles published in the Journal of Clinical Oncology.
In the articles, the ASCO/Friends team noted that eligibility criteria exist for two reasons – to protect patients and to clearly define the population for any given study. If criteria are too loose, patient safety can be in jeopardy. If they’re too restrictive, trials can be slow to accrue – and the generalizability of trial results may be threatened.
The ASCO/Friends team focused on areas likely to generate consensus – ones that have been almost “automatic” for decades. Here’s their list, and their positions:
• Brain metastases: Patients with treated or clinically stable brain metastases should be routinely included in trials and only excluded if there is compelling rationale.
• Minimum age requirements: In initial dose-finding trials, pediatric-specific cohorts should be included based on strong scientific rationale for benefit. Later phase trials in diseases that span adult and pediatric populations should include patients > age 12 years.
• HIV/AIDS status: HIV-infected patients who are healthy and have low risk of AIDS-related outcomes should be included absent specific rationale for exclusion.
• Organ dysfunction: Renal function criteria should enable liberal creatinine clearance, unless the investigational agent involves excretion by the kidneys.
• Prior and concurrent malignancies: Patients with prior or concurrent malignancies should in general be included, especially when the risk of the malignancy interfering with either safety or efficacy endpoints is very low.
These positions, and the joint research statement issued by ASCO/Friends, reflect a much more inclusive spirit. “To maximize generalizability of results, trial enrollment criteria should strive for inclusiveness,” the research statement says. “Rationale for excluding patients should be clearly articulated and reflect expected toxicities associated with the therapy under investigation.”
Andrea Denicoff of CTEP is leading the NCTN template review, and reports that the new templates will be circulated to the network groups in a few weeks. Before they are, a select group of SWOG members – including members of our patient advocate, AYA, and recruitment and retention committees – will review them and provide feedback. These templates will provide guidance for NCI-funded trials. The U.S. Food and Drug Administration is working on new eligibility criteria for industry studies.
Expect more changes to eligibility criteria, according to Dr. Paul J. Hesketh of Lahey Health Cancer Institute, who represented SWOG on the ASCO/Friends team and was an author on the joint research statement. “I think this is just the beginning of a larger process of looking at eligibility criteria,” Hesketh says. “There is a lot more progress to be made. At the same time, ASCO is also interested in developing metrics to assess impact. Did changes to eligibility criteria actually make a difference with trial accrual?”
I could not be happier to see this critical conversation kicked off. I’m sure we will discuss the NCTN templates and their utilization as soon as they come in.