Accrual monitoring in cardiovascular trials.

OBJECTIVE

To provide brief guidance on how to design accrual monitoring activities in a clinical trial protocol.

SETTING

Two completed clinical trials that did not achieve the planned sample size, the Cost of Strategies After Myocardial Infarction (COSTAMI) trial and the Biventricular Pacing After Cardiac Surgery (BiPACS) trial.

DESIGN

A Bayesian monitoring tool, the constant accrual model, is applied retrospectively to accrual data from each case study to illustrate how the tool could be used to identify problems with accrual early in the trial period and to frame the conditions in which the approach can be used in practice.

RESULTS

After 312 days and 155 patients enrolled in the COSTAMI trial, accrual could be classified as 'off target' on the basis of statistical criteria outlined in the protocol. As for the BiPACS trial, after 2 years, it was already evident that the accrual was 'considerably off target'.

CONCLUSIONS

Prompt awareness of a high risk of accrual failure could trigger different interventions to overcome protocol-related, patient-related or investigator-related barriers to recruitment or ultimately contribute to an early stopping decision due to recruitment futility.Accrual prediction models should be included as standard tools for routine monitoring activities in cardiovascular research. Among them, methods relying on the Bayesian approach are particularly attractive, as they can naturally update past evidence when actual accrual data becomes available.