A sense of urgency: Evaluating the link between clinical trial development time and the accrual performance of cancer therapy evaluation program (NCI-CTEP) sponsored studies

Abstract

Purpose: Postactivation barriers to oncology clinical trial accruals are well documented; however, potential barriers prior to trial opening are not. We investigate one such barrier: trial development time.

Experimental design: National Cancer Institute Cancer Therapy Evaluation Program (CTEP)-sponsored trials for all therapeutic, nonpediatric phase I, I/II, II, and III studies activated between 2000 and 2004 were investigated for an 8-year period (n = 419). Successful trials were those achieving 100% of minimum accrual goal. Time to open a study was the calendar time from initial CTEP submission to trial activation. Multivariate logistic regression analysis was used to calculate unadjusted and adjusted odds ratios (OR), controlling for study phase and size of expected accruals.

Results: Among the CTEP-approved oncology trials, 37.9% (n = 221) failed to attain the minimum accrual goals, with 70.8% (n = 14) of phase III trials resulting in poor accrual. A total of 16,474 patients (42.5% of accruals) accrued to those studies were unable to achieve the projected minimum accrual goal. Trials requiring less than 12 months of development were significantly more likely to achieve accrual goals (OR, 2.15; 95% confidence interval, 1.29-3.57, P = 0.003) than trials with the median development times of 12 to 18 months. Trials requiring a development time of greater than 24 months were significantly less likely to achieve accrual goals (OR, 0.40; 95% confidence interval, 0.20-0.78; P = 0.011) than trials with the median development time.

Conclusions: A large percentage of oncology clinical trials do not achieve minimum projected accruals. Trial development time appears to be one important predictor of the likelihood of successfully achieving the minimum accrual goals.

Figure 1

Identification of CTEP-Sponsored Clinical Trials Used for the Analysis of Development Time and Accrual Achievement

Figure 2

Development Time and Percentage of Total Trials that Attained Accrual Goal by Phase Phase III development time is significantly greater than phase I, phase I/II, phase II trials (Mann-Whitney test with Bonferroni-adjusted alpha level: p≤0.008). Phase III accrual performance is significantly lower than phase I, phase I/II, phase II trials (Kruskal –Wallis test: p≤0.001)

Figure 3

Number (and Percentage) of Clinical Trial Participants Enrolled on Trials that Attained the Accrual Goal vs. Trials that Did Not Attain the Accrual Goal

Figure 4

Likelihood of Attaining Accrual Goals with Respect to the Development Time for CTEP-Sponsored Trials, 2000–2004 The triangles indicate the the calculated odds ratios with reference to the median development time. The vertical lines represent the 95% confidence intervals. The dotted line indicates the referent as defined by the median development time of the sample.