Lung cancer clinical trial elig criteria and requirements increased in number and complexity
Eligibility criteria continue to increase in number and complexity for lung cancer clinical trials.
Cancer clinical trials have complex requirements for design, study, and eligibility criteria that often act as a barrier to the development of new clinical trials as well as patient enrollment. With the advent of molecular targeted therapies and immunotherapy, requirement criteria have continued to increase in number and complexity. Despite calls to streamline cancer clinical trial processes and efforts to improve cancer clinical trial patient accrual, completion rates and generalizability, fewer than two percent of adults with cancer in the United States participate in clinical trials.
A group of investigators in the United States conducted a retrospective study to evaluate contemporary trends in cancer clinical trial inclusiveness and complexity. The group quantified and categorized eligibility criteria in lung cancer clinical trials sponsored or endorsed by the Eastern Cooperative Oncology Group (ECOG) Thoracic Committee from 1986 through 2016. Associations between clinical trial characteristics and eligibility criteria were analyzed by nonparametric statistical methods, such as the Wilcoxon two-sample test and the Kruskal-Wallis test.
The results of the study were published in the Journal of Thoracic Oncology, the official journal of the International Association for the Study of Lung Cancer (IASLC) . A total of 74 lung cancer clinical trials sponsored or endorsed by the ECOG Thoracic Committee with full study protocols were identified. Medical therapy trials (targeted therapy and immunotherapy) had an increase in eligibility criteria over time from 17 in 1986-1995 to 28 in 2006-2016 (p<0.001), whereas there was no significant change in eligibility criteria for surgery or radiation therapy trials. There was no association between trial phase and number of criteria (p=0.45). Disease stage showed an increased trend in eligibility criteria with a median 12 for early stage, 21 for locally advanced stage and 19 for advanced stage (p=0.08). The following categories had statistically significant increases in eligibility criteria: cardiac, concurrent medications, gastrointestinal, hematologic, hepatic, inflammatory, neurologic, renal and prior cancer therapy (p<0.05). There was no significant change in eligibility criteria in the pulmonary and endocrine categories. The study also demonstrated an increase over time in the number of required screening procedures, such as blood tests.
The authors comment that, "Medical therapy lung cancer clinical trials are becoming more complex, with growing numbers of eligibility criteria and screening procedures. While this trend may hypothetically increase the scientific yield or safety of a protocol, it also potentially hinders patient accrual, decreases study completion rates, limits generalizability and increases costs. The increase in eligibility criteria appears to reflect the general practice of adding new criteria relevant to contemporary treatments such as immunotherapy and molecularly targeted therapies, without revisiting and removing criteria not pertinent to these interventions. With federal funding for cancer clinical trials decreasing and a substantial proportion of NCI-sponsored cancer clinical trials not completing accrual, ongoing efforts to simplify eligibility and procedures will be critical moving forward. Tailoring inclusion and exclusion criteria to match the intervention under study represents a key step in this process."