Bayesian methods for validating patient reported outcomes and predicting patient accrual in clinical trials

Abstract

Slow recruitment in medical research leads to increased costs and resource utilization, which includes the goodwill contribution of patient volunteers. Careful planning and monitoring of the accrual process can prevent the unnecessary loss of these resources. We propose two hierarchical extensions to the existing Bayesian constant accrual model: the accelerated prior and the hedging prior. The new proposed priors are able to adaptively utilize the researcher's previous experience and current accrual data to produce the estimation of trial completion time. The performance of these models, including prediction precision, coverage probability, and correct decision-making ability, is evaluated using actual studies from our cancer center and simulation. The results showed that a constant accrual model with strongly informative priors works very well when accrual is on target or slightly off, producing smaller mean squared error, high percentage of coverage, and a high number of correct decisions whether or not continue the trial, but it is strongly biased when off target. Flat or weakly informative priors provide protection against an off target prior, but are less efficient when the accrual is on target. The accelerated prior performs similar to a strong prior. The hedging prior performs much like the weak priors when the accrual is extremely off target, but closer to the strong priors when the accrual is on target or only slightly off target. We suggest improvements in these models and propose new models for future research.