Implementing Probabilistic Baseline Covariate Adaptive Randomizations for Clinical Trials Primary Interest Area: Advances in Clinical Trial Methodologies; Probabilistic Baseline Covariate Adaptive Randomizations; Clinical Trial Technological Applications

Synopsis: The average expenditure related to development of a drug candidate has doubled over the last decade. Each day that informed decisions about a drug candidate are delayed carries with it opportunity costs, tangible costs, and patient risk. Adaptive trial design is a clinical methodology that is receiving significant attention from pharmaceutical companies and regulatory agencies because it can increase flexibility and therefore efficiency within the clinical trial process. In an adaptive trial, flexibility is derived from decision making rules that are defined in the protocol. The most controversial of these rules is the allocation rule. The allocation rule is the foundation for probabilistic baseline covariate adaptive randomization (pBAR). Probabilistic baseline covariate adaptive randomization can be used to enhance the statistical design of a clinical trial by balancing treatment groups for known covariates. This is especially critical in trials with high strata to patient ratios, where well designed and implemented interactive clinical technology can be used to enable the implementation of increasingly complex pBAR designs.