Abstract / Summary
Importance Clinical trial enrollment is essential to advancing cancer care, yet participation among patients with advanced cancer remains low. While patient-level barriers are frequently cited, the role of health care delivery factors—specifically physician- and practice-level variation—has been poorly quantified. Objective To quantify variation in clinical trial participation and identify associated delivery system factors among patients with advanced cancer. Design, Setting, and Participants This cohort study included adults with advanced or metastatic cancers diagnosed and treated between January 1, 2011, and December 31, 2024, by 1664 physicians across 107 trial-available oncology practices across the US. Data were obtained from the Flatiron Health Research Database. Analyses were conducted between January and April 2025. Exposures Patient-level (eg, demographic characteristics, cancer type, and performance status), physician-level (eg, patient volume, subspecialization, and prior trial enrollment activity), and practice-level (eg, size, research engagement, and patient composition) factors. Main Outcomes and Measures The primary outcome was clinical trial participation, defined as receipt of a clinical study drug. Mixed-effects logistic regression models were used to decompose the proportion of variation attributable to patient-, physician-, and practice-level factors. Multivariable logistic regression was used to identify characteristics associated with trial participation. Results Among the 205 743 patients with advanced or metastatic cancer (mean [SD] age at advanced cancer diagnosis, 67.5 [11.3]; 107 370 males [52.2%]), 10 785 (5.2%) participated in a clinical trial over the study period, increasing from 235 of 5964 (3.9%) in 2011 to 638 of 9336 (6.8%) in 2024. Participation remained highly concentrated: of 1664 physicians, 389 (23.4%) accounted for 9018 (83.6%) of all enrollments (10 785), while 21 of 107 practices (19.6%) accounted for 8686 (80.5%) of all enrolled patients. Additionally, 494 of 1664 physicians (29.7%) enrolled no patients. Physician-level (12.3%) and practice-level (15.1%) factors explained a greater share of variation in trial participation than observable patient-level characteristics (11.4%), with physician- and practice-level contributions increasing over time. Physician’s subspecialization (treated 1-2 cancer groups: odds ratio [OR], 4.11 [95% CI, 2.53-6.68], P = .002; treated 3-4 cancer groups: OR, 2.38 [95% CI, 1.37-4.14], P < .001), physician’s prior trial enrollment activity (enrolled patients in the 2 previous years: OR, 1.58; 95% CI, 1.43-1.76; P < .001), and practice’s research engagement (OR, 2.68; 95% CI, 2.12-3.39; P < .001) were associated with higher odds of trial participation. Conclusions and Relevance In this cohort study of patients with advanced cancer, clinical trial participation increased moderately but remained low over the study period, with physician- and practice-level factors consistently accounting for a substantial share of participation variation. Improving trial accrual requires interventions targeting structural factors in enrollment, including research infrastructure and physician engagement.