Growth in eligibility criteria content and failure to accrue among National Cancer Institute (NCI)-affiliated clinical trials.

Abstract

1515 Background: Cancer clinical trial accrual across diverse socioeconomic and demographic groups is a national priority, yet up to 20% of trials fail due to poor accrual. Eligibility criteria content may contribute to poor accrual, but effects are challenging to measure. We sought to evaluate growth of eligibility criteria within NCI-affiliated cancer trials and the impact on trial accrual over the past decade. Methods: We conducted a retrospective study with the Aggregate Analysis of ClinicalTrials.gov (AACT) (abstracted: 02/02/2021). We included NCI-affiliated, interventional Phase II or III trials that initiated between 01/01/2008 and 12/13/2018. We excluded active and recruiting trials that lacked accrual data on the Cancer Trials Support Unit website. Trials whose status was “Withdrawn”, “Terminated”, or “Suspended” due to low accrual, or had less than 50% target accrual after two years active were deemed accrual failures. Eligibility criteria were extracted from inclusion and exclusion criteria and complexity was estimated by the number of unique content words, calculated by removing duplicates and stop words from the word count. Association of unique word count with accrual failure was evaluated by univariable and multivariable logistic regressions, adjusting for other predictors of low accrual identified in earlier research. Results: Of 1197 trials included, 231 (19.3%) failed due to low accrual. Eligibility criteria increased in length from a median of 214 (IQR [23, 282]) unique content words in 2008 to 417 (IQR [289, 514]) in 2018. The rate of trial accrual failure increased with unique word count decile from 11.8% in the first decile (12 to 112 words) to 29.4% in the tenth decile (445 to 750 words) (P = 0.004). On multivariable analysis, unique word count remained independently associated with low accrual (OR: 1.07 per decile, 95%CI [1.01-1.13], P = 0.02), as did Phase III and metastatic disease settings (Table). Conclusions: Eligibility criteria content has increased dramatically in the last decade in NCI-affiliated trials. Increasing eligibility criteria content associates strongly with accrual failure, even after adjusting for multiple known predictors of accrual. These findings underscore the need for efforts to simplify eligibility criteria to improve trial accrual. Further investigation is ongoing to determine specific criteria qualities that portend accrual failure.[Table: see text]