Predicting accrual achievement: monitoring accrual milestones of NCI-CTEP-sponsored clinical trials

Abstract

Purpose: The need to increase the number oncology clinical trials with sufficient enrollments is a well-known issue, particularly for trials targeting therapeutic applications. It is critical to identify early predictors of eventual study accrual achievement.

Experimental design: All nonpediatric phase I, I/II, II, and III therapeutic studies supported by the National Cancer Institute Cancer Therapy Evaluation Program (NCI-CTEP) between 2000 and 2007 (n = 764) were analyzed for accrual performance. Accrual achievement is defined as those enrolling 100% or more of the stated minimum accrual goal at the time of trial closure. Two accrual milestones were analyzed per trial: time to first patient enrollment and expected time to accrual goal. Multivariate logistic regression analysis was used to calculate the OR with respect to the likelihood of clinical trial accrual achievement.

Results: A total of 81.5% (n = 623) of the trials did not achieve the projected accrual goals within the anticipated accruing period. Furthermore, 37.2% (n = 284) of trials failed to achieve the minimum projected accrual at study closure regardless of time the trial was open. Trials that accrue the first enrollment beyond 2 months (n = 379, 49.6%) are significantly less likely to achieve the accrual performance than those trials that enroll patients under 2 months (OR: 0.637, 95% CI: 0.464-0.875, P = 0.005). Of the studies that are open beyond the anticipated enrollment period (n = 603), those do not achieve at least 60.0% of the projected minimum accrual (n = 391, 64.8%) have a significantly less likelihood of achieving final accruals by study closure (OR: 0.190, 95% CI: 0.055-0.652, P = 0.008).

Conclusions: The time to first patient enrollment and expected time to accrual goal are shown to be valid measures to evaluate the likelihood of achieving the minimum projected accrual.

Figure 1

Identification of NCI-CTEP Supported Trials Used for the Analysis of Accrual Performance

Figure 2. Definition for Observation Points and Timing Analysis

Figure 1 illustrates an example of a phase III clinical trial contained in the sample. The date of activation was on September 2002 with the first patient enrolled on the study on January 2003. Therefore, the time-to-first enrollment was calculated from these two dates to be 4 months. The projected accrual rate for this study was 29 patients per month and the minimum projected accrual was 1058 patients. Using the time-to-first enrollment as a reference point for calculating the expected period to achieve the minimum accrual goal, the expected period was 37 months (rounded to the following month to ensure that all accruals were accounted for). Therefore the expected date that the study was to achieve the minimum accrual object was set at January 2006. On January 2006, the milestone at which the study was expected to achieve the minimum projected accrual; the number of accruals on the study was 195 patients. The actual accrual performance at the expected period to achieve the minimum projected accrual was calculated by dividing the accrual (195) by the accrual goal (1058), which resulted in accrual performance of 18.43% of the expected accrual performance. At study closure, the final accrual performance was calculated by dividing the final accrual of 357 patients by the minimum projected accrual of 1058 patients. This resulted in an accrual performance at study closure to be 33.74%. Because the final accrual performance is ≥100% of the minimum projected accrual, this study is identified to not attain the anticipated accrual goal. This calculation was conducted on the entire sample of 764 clinical trials and analyzed collectively.