Predicting Low Accrual in the National Cancer Institute's Cooperative Group Clinical Trials

Abstract

Background: The extent to which trial-level factors differentially influence accrual to trials has not been comprehensively studied. Our objective was to evaluate the empirical relationship and predictive properties of putative risk factors for low accrual in the National Cancer Institute's (NCI's) Cooperative Group Program, now the National Clinical Trials Network (NCTN).

Methods: Data from 787 phase II/III adult NCTN-sponsored trials launched between 2000 and 2011 were used to develop a logistic regression model to predict low accrual, defined as trials that closed with or were accruing at less than 50% of target; 46 trials opened between 2012 and 2013 were used for prospective validation. Candidate predictors were identified from a literature review and expert interviews; final predictors were selected using stepwise regression. Model performance was evaluated by calibration and discrimination via the area under the curve (AUC). All statistical tests were two-sided.

Results: Eighteen percent (n = 145) of NCTN-sponsored trials closed with low accrual or were accruing at less than 50% of target three years or more after initiation. A multivariable model of twelve trial-level risk factors had good calibration and discrimination for predicting trials with low accrual (AUC in trials launched 2000-2011 = 0.739, 95% confidence interval [CI] = 0.696 to 0.783]; 2012-2013: AUC = 0.732, 95% CI = 0.547 to 0.917). Results were robust to different definitions of low accrual and predictor selection strategies.

Conclusions: We identified multiple characteristics of NCTN-sponsored trials associated with low accrual, several of which have not been previously empirically described, and developed a prediction model that can provide a useful estimate of accrual risk based on these factors. Future work should assess the role of such prediction tools in trial design and prioritization decisions.

Figure 1.

Conceptual model of factors associated with low trial accrual. The scientific rationale for a trial can be a disease- and/or treatment-related factor. State-level coverage of clinical trial costs is not applicable prospectively and was therefore excluded from the set of candidate predictors.

Figure 2.

Calibration plot for cooperative group-sponsored trials registered in ClinicalTrials.gov and started between 2000 and 2011. The calibration figure shows the average risk of poor accrual for trials grouped into deciles by their predicted risk (x-axis) compared with the actual percentage of trials in these groups that experienced poor accrual (y-axis). Vertical lines correspond to 95% confidence intervals. Perfect calibration would fall on the 45-degree diagonal line where predicted risks equal observed rates of poor accrual. χ² for Hosmer-Lemeshow goodness-of-fit test was 3.36 (P = .97)