Integrated rapid-cycle comparative effectiveness trials using flexible point of care randomisation in electronic health record systems

Abstract

Whilst the Randomised Controlled Trial remains the gold standard for deriving robust causal estimates of treatment efficacy, too often a traditional design proves prohibitively expensive or cumbersome when it comes to assessing questions regarding the comparative effectiveness of routinely used treatments. As a result, patients experience variation in practice as clinicians lack the evidence needed to personalise treatments effectively. This variation may be classified as unwarranted, where existing evidence is ignored, or legitimate where in the absence of evidence, clinicians rely on experience, expert opinion, and inferred principles from basic science to make decisions.We argue that within the right ethical and technological framework, legitimate variation can be transformed into a mechanism for evidence generation and learning. Learning Health Systems which harness existing variation in practice, represent a novel approach for generating evidence from everyday clinical practice. The development of these systems has gained traction due to the increased availability of modern Electronic Health Record Systems. However, despite their promise, overcoming hurdles to successfully integrating clinical trials within Learning Health Systems has proven challenging.This article describes the origins of integrated clinical trials and explores two main barriers to their further implementation - how best to obtain informed consent from patients to participate in routine comparative effectiveness research, and how to automate and integrate randomisation into a clinical workflow. Having described these barriers, we present a potential solution in the form of a research pipeline using a novel form of flexible point-of-care randomisation to allow clinicians and patients to participate in studies where there is clinical equipoise.