Background
EVENTS, EVENT
Over the past decade, there has been a significant shift in approaches to evidence generation in clinical medicine. Recognizing the need to transform conventional randomized clinical trials (RCT) to produce evidence more quickly and efficiently, key stakeholders have begun to test pragmatic methods for addressing common clinical questions [For trials that use EHR to ascertain clinical study data, referred to here as “EHR-sourced” trials, part of the consideration about whether EHR data are fit-for-use in regulatory environments is the uncertainty about how to leverage existing trial sites’ infrastructure to operationalize study goals. In addition to study design questions, this uncertainty includes questions about the feasibility of methods for integrating EHR data into clinical trial data infrastructure, and how to facilitate the scaling of these practices beyond early adopters [Towards this end, the VESALIUS-CV EHR Demonstration Project was an industry, regulator, and academic research organization collaboration led by the Duke Clinical Research Institute (DCRI) with two aims. The first aim was to develop empirically driven recommendations to support the evaluation of real-world data (RWD) within large trials [An additional aim was to understand operational considerations, with a particular interest in assessing organization or site-level characteristics that drive readiness to participate in EHR-sourced multi-center trials. We conducted this work within the context of a contemporary multi-center pharmaceutical industry outcomes trial that used traditional processes of study visits, baseline, and follow-up event capture, electronic CRFs for data collection, and event adjudication to study the effect of lowering low-density lipoprotein cholesterol (LDL-C) with evolocumab on major cardiovascular events in high-risk adults. (ClinicalTrials.gov Identifier: NCT03872401).This demonstration project utilized a central coordinating center, consisting of project management, data management/programming, and informatics expertise, to support participating US sites in addressing the technical, governance, and operational aspects of EHR use. In this paper, we discuss operational considerations related to site selection, data extraction, site participation, data transfer, and quality review, and we outline challenges and lessons learned. Lastly, we offer recommendations for future work to support clinical trial infrastructure and sites adapt to the use of EHR data.