Increasing trial complexity and a stubborn rise in exclusion criteria are discouraging subject participation—and the trend shows no sign of abatement. For example, there’s been an estimated 60% increase in exclusion criteria in National Cancer Institute–sponsored trials over the past 20 years, according to a new study from researchers at the University of Texas (UT) Southwestern Medical Center.
It’s a complex scenario that demands new ideas for addressing the problem, experts say.
“New treatments will have new safety concerns that will need new exclusion criteria,” notes study coauthor Dr. David Gerber, an associate professor of internal medicine and of clinical sciences and associate director for clinical research at the medical center’s Harold C. Simmons Comprehensive Cancer Center. However, the clinical trial industry does not appear to be doing a good enough job examining old exclusion criteria, he adds.
There are several root causes, Gerber says. One problem is that considerations for older treatments—such as strict minimum blood count requirements for conventional chemotherapy—remain on exclusion lists for newer therapies. “Rather than the new eligibility criteria replacing older eligibility criteria, they’re being added on,” Gerber adds.
One outcome? Less efficient and “illuminating” clinical trials. “As eligibility criteria become more restrictive, the applicability of the trial results to the real-world patient population can be problematic,” says Dr. David Johnson, a study coauthor and professor and chairman of internal medicine at UT Southwestern. “It may create uncertainty for the practicing physician who deals with a broader, less restrictive population in the real-world setting.”
Gerber and other research team members are working to identify novel targets for targeting tumors, performing laboratory testing of new treatment strategies, and developing new biomarkers and clinical trials. “We’re in the trenches with the [clinical trial practitioners] doing the research,” he says, also praising the commitment he sees from clinical research coordinators and other professionals.
An effective exclusion criteria program starts with two simple questions: Do the potential exclusion criteria protect patients and/or protect the integrity of the science? “If not, [an exclusion] can often be removed or relaxed,” Gerber says. He urges teams developing exclusion criteria to carefully consider those questions and use them as guidelines.
“There is a tendency to continue to use the criteria used” in the past and carry those forward without careful examination of their relevance, Gerber says. “Our research suggests there might be a substantial” list of exclusion criteria that can, at the minimum, be relaxed.
Author: Michael Causey