Clinical Trial Characteristics and Barriers to Participant Accrual: The MD Anderson Cancer Center Experience over 30 years, a Historical Foundation for Trial Improvement

Abstract

Purpose: Slow-accruing clinical trials delay the translation of basic biomedical research, contribute to increasing health care costs, and may prohibit trials from reaching their original goals.Experimental Design: We analyzed a prospectively maintained institutional database that tracks all clinical studies at the MD Anderson Cancer Center (Houston, TX). Inclusion criteria were activated phase I-III trials, maximum projected accrual ≥10 participants, and activation prior to March 25, 2011. The primary outcome was slow accrual, defined as <2 participants per year. Correlations of trial characteristics with slow accrual were assessed with logistic regression.Results: A total of 4,269 clinical trials met inclusion criteria. Trials were activated between January 5, 1981, and March 25, 2011, with a total of 145,214 participants enrolled. Median total enrolment was 16 [interquartile range (IQR), 5-34], with an average enrolment rate of 8.7 participants per year (IQR, 3.3-17.7). There were 755 (18%) trials classified as slow accruing. On multivariable analysis, slow accrual exhibited robust associations with national cooperative group trials (OR = 4.16, P < 0.0001 vs. industry sponsored), time from trial activation to first enrolment (OR = 1.13 per month, P < 0.0001), and maximum targeted accrual (OR = 0.16 per log10 increase, P < 0.0001). Recursive partitioning analysis identified trials requiring more than 70 days (2.3 months) between activation and first participant enrolment as having higher odds of slow accrual (23% vs. 5%, OR = 5.56, P < 0.0001).Conclusions: We identified factors associated with slow trial accrual. Given the lack of data on clinical trials at the institutional level, these data will help build a foundation from which targeted initiatives may be developed to improve the clinical trial enterprise. Clin Cancer Res; 23(6); 1414-21. ©2017 AACR.

Figure 1

Frequency distribution of total trials and slow accruing trials (fewer than 2 participants per year). (A) Trial activation over time with the proportion of slow accruing trials displayed. (B) Frequency of total trials by phase and trial activation year. (C) Slow-accruing trials by trial phase. (D) slow-accruing trials by source of trial support.

Figure 2

(A) Schematic of the trial approval process at MD Anderson. (B) Time from protocol submission to institutional review board (IRB) approval, (C) time from IRB approval to study activation, and (D) time from trial activation to first participant enrolled stratified by participant enrollment rate.

Figure 3

Frequency of slow-accruing trials (fewer than 2 participants per year) with respect to (A) the total number of trials activated in that department or (B) number of trials activated within the same year in the same department. Proportion of slow-accruing trials is shown at the top of each bar.