A non-parametric approach to predict the recruitment for randomized clinical trials: an example in elderly inpatient settings.

Background: Accurate prediction of subject recruitment, which is critical to the success of a study, remains an ongoing challenge. Previous prediction models often rely on parametric assumptions which are not always met or may be difficult to implement. We aim to develop a novel method that is less sensitive to model assumptions and relatively easy to implement.

Methods: We create a weighted resampling-based approach to predict enrollment in year two based on recruitment data from year one of the completed GRIPS and PACE clinical trials. Different weight functions accounted for a range of potential enrollment trajectory patterns. Prediction accuracy was measured by Euclidean distance for enrollment sequence in year two, total enrollment over time, and total weeks to enroll a fixed number of subjects, against the actual year two enrollment data. We compare the performance of the proposed method with an existing Bayesian method.

Results: Weighted resampling using GRIPS data resulted in closer prediction evidenced by better coverage of observed enrollment with the prediction intervals and smaller Euclidean distance from actual enrollment in year 2, especially when enrollment gaps were filled prior to the weighted resampling. These scenarios also produced more accurate predictions for total enrollment and number of weeks to enroll 50 participants. These same scenarios outperformed an existing Bayesian method for all 3 accuracy measures. In PACE data, using a reduced year 1 enrollment resulted in closer prediction evidenced by better coverage of observed enrollment with the prediction intervals and smaller Euclidean distance from actual enrollment in year 2, with the weighted resampling scenarios better reflecting the seasonal variation seen in year (1) The reduced enrollment scenarios resulted in closer prediction for total enrollment over 6 and 12 months into year (2) These same scenarios also outperformed an existing Bayesian method for relevant accuracy measures.

Conclusion: The results demonstrate the feasibility and flexibility for a resampling-based, non-parametric approach for prediction of clinical trial recruitment with limited early enrollment data. Application to a wider setting and long-term prediction accuracy require further investigation.