Design and implementation of pragmatic clinical trials using the electronic medical record and an adaptive design.

Abstract

ObjectivesTo demonstrate the feasibility of pragmatic clinical trials comparing the effectiveness of treatments using the electronic medical record (EMR) and an adaptive assignment design.MethodsWe have designed and are implementing pragmatic trials at the point-of-care using custom-designed structured clinical documentation support and clinical decision support tools within our physician’s typical EMR workflow. We are applying a subgroup based adaptive design (SUBA) that enriches treatment assignments based on baseline characteristics and prior outcomes. SUBA uses information from a randomization phase (phase 1, equal randomization, 120 patients), to adaptively assign treatments to the remaining participants (at least 300 additional patients total) based on a Bayesian hierarchical model. Enrollment in phase 1 is underway in our neurology clinical practices for 2 separate trials using this method, for migraine and mild cognitive impairment (MCI).ResultsWe are successfully collecting structured data, in the context of the providers’ clinical workflow, necessary to conduct our trials. We are currently enrolling patients in 2 point-of-care trials of non-inferior treatments. As of March 1, 2018, we have enrolled 36% of eligible patients into our migraine study and 63% of eligible patients into our MCI study. Enrollment is ongoing and validation of outcomes has begun.DiscussionThis proof of concept article demonstrates the feasibility of conducting pragmatic trials using the EMR and an adaptive design.ConclusionThe demonstration of successful pragmatic clinical trials based on a customized EMR and adaptive design is an important next step in achieving personalized medicine and provides a framework for future studies of comparative effectiveness.