Exclusion Criteria for Clinical Trials Poses Major Barrier to Patient Enrollment

UT Southwestern researchers say that clinical investigators continue to increase the number of exclusion criteria, preventing more patients from participating in clinical trials. In the 20-year period between 1986 and 2016, exclusion criteria in National Cancer Institute-funded lung cancer clinical trials increased by nearly 60 percent.

The statistic was generated after the researchers analyzed 74 lung cancer studies. According to Dr. David Gerber, Associate Professor of Internal Medicine at UT Southwestern, patient enrollment in these clinical trials is just too low.

“It’s a tired but persistent statistic that only about 3 percent of adults with cancer are enrolled in clinical trials,” said Gerber, who is also an Associate Professor of Clinical Sciences and Associate Director for Clinical Research in the Harold C. Simmons Comprehensive Cancer Center. “Increasingly complex and numerous exclusion criteria are a key factor.”

Gerber and his team noted that the increase in exclusion criteria was particularly striking in clinical trials testing new drug treatments for lung cancer. In the time period studied, the exclusions stayed relatively consistent in studies of non-drug interventions, such as radiation therapy and surgery.

Lung cancer clinical trials conducted between 1986 and 1995 had a median of 16 exclusion criteria; between 1996 and 2005, this number had increased to 19. The median number of exclusion criteria made the biggest jump between 2006 and 2016, to a total of 27.

“Starting about 10 years ago there were major calls on a national level to simplify clinical trial eligibility and procedures,” said Gerber. “Yet it’s clear that obstacles to participation have not only persisted but also increased. Change needs to occur.”

Gerber is the Co-Director of UT Southwestern’s Experimental Therapeutics Program, an initiative focused on identifying novel drug targets, testing new tumor treatments in the lab, and finding biomarkers which could be useful in clinical trials. The research team published their report on clinical trial exclusion criteria in the Journal of Thoracic Oncology.

Gerber suggests that two main factors are contributing to the growing list of exclusion criteria used in modern oncology trials. First, exclusion criteria for clinical trials testing new technologies like immunotherapy are very different compared to conventional drugs, such as chemotherapy. For example, patients with an autoimmune disease who would have previously been accepted into a chemotherapy study, may be excluded from participating in an immunotherapy trial.

Second, clinical investigators tend not to remove older requirements from exclusion lists, regardless of whether or not they are relevant in trials of modern therapies. “Rather than the new eligibility criteria replacing older eligibility criteria, they’re being added on,” said Gerber.

While the use of exclusion criteria is designed to protect patient safety and maintain the integrity and applicability of clinical trial results, the growing list for lung cancer studies could be contributing to enrollment challenges and depriving patients of the opportunity to receive potentially life-saving therapies. In light of these findings, Gerber urges clinical researchers to “double down on efforts to design more elegant trials.”

“As eligibility criteria become more restrictive, the applicability of the trial results to the real-world patient population can be problematic,” said Dr. David Johnson, Professor and Chairman of Internal Medicine. “It may create uncertainty for the practicing physician who deals with a broader, less restrictive population in the real-world setting.”