Speed of accrual into published phase III oncology trials: A comparison across geographic locations.

Abstract

6074 Background: There is a perception that patient accrual may be slower in the US than it is in Europe (Wang-Gillam A et al, J Clin Oncol 2010;28:3803-3807). However, a systematic study has not been performed. We seek to determine the speed at which patients are accrued into published phase III oncology trials across geographic locations and to identify factors that may influence this process. Methods: We searched MEDLINE and identified all original phase III oncology therapeutic trials published in 2006-2010 (N = 567). Trials with no reported activation and completion dates were excluded (n = 20). Accrual speed per trial was expressed as patients per month and was calculated by dividing the number of patients enrolled by number of months a trial was open. Results: The 547 trials included in our study enrolled 281,340 patients. Most trials were for adults only (95.6%), late stage cancers (77.5%), and involved multinational participation (44.1%). Funding sources were cooperative groups (45.5%), industry (33.8%) and academic centers (20.5%). The top 5 cancers studied were hematologic (19.2%), gastrointestinal (16.5%), lung (16.3%), breast (15.4%), and gynecologic (8.4%). Trial results were negative (57.4%), positive (38.2%), or equivalent (4.4%). The mean (+SD) accrual speeds varied according to trial location (multinational [25.0+25.4], US [13.3+16.5], other countries [11.4+15.7], Europe [8.7+11.8]; [P= .001]), funding source (industry [28.3+24.7], cooperative groups [13.3+19.0], academic [6.8+6.5]; [P= .001]), and cancer type (breast [24.0+29.4], gastrointestinal [20.2+24.2], lung [19.3+22.7], gynecologic [15.3+19.2], hematologic [11.2+10.7]; [P= .001]). After adjusting for funding source, accrual speeds were significantly different across trial locations only in 2 cancers: gastrointestinal (multinational [25.2+3.7], US [24.1+8.2], Europe [11.5+3.7], other [7.5+8.5]; P= .046) and gynecologic (multinational [28.9+5.4], other [10.5+7.8], US [6.6+5.3], Europe [4.2+5.9]; P= .004) studies. Conclusions: Among published phase III oncology trials, multinational studies accrued patients faster in gastrointestinal and gynecologic cancers and at a similar speed in other cancers.

Trial-level factors affecting accrual and completion of oncology clinical trials: A systematic review

“…Sponsor/funder was one of the examined background factors. Amongst published phase III oncology clinical trials, industry sponsored trials were among the fastest accruing [ 18 ]. Also, with poor accrual being the most common cause of early terminated clinical trials, industry sponsored immune checkpoint inhibitor trials were significantly less likely to terminate early compared with those that were sponsored by federal and academic institutions [ 19 ].…”

“…Multinational trials were among the fastest accruing. However, there were no significant differences in accrual time between trials conducted in the United States compared to Europe among phase III oncology clinical trials [ 18 ].…”

“…Among NCI Cooperative Group phase III clinical trials, fewer breast cancer trials terminated due to inadequate accrual [ 25 ]. Also, Ruther et al [ 18 ] found the fastest accruing trials among phase III oncology clinical trials were those for breast cancer. However, Hernandez-Torres et al [ 24 ] demonstrated breast cancer clinical trials were associated with lower accrual of older adults.…”

“…However, Bennette et al [ 17 ] found no associations between low accrual and placebo use. Also, Ruther et al [ 18 ] reported there were no significant differences in accrual time between placebo and non-placebo use in published phase III oncology clinical trials.…”