What is a minimal clinically important difference for clinical trials in patients with disorders of consciousness? a novel probabilistic approach

Over the last 30 years, there has been a growing trend in clinical trials towards assessing novel interventions not only against the benchmark of statistical significance, but also with respect to whether they lead to clinically meaningful changes for patients. In the context of Disorders of Consciousness (DOC), despite a growing landscape of experimental interventions, there is no agreed standard as to what counts as a minimal clinically important difference (MCID). In part, this issue springs from the fact that, by definition, DOC patients are either unresponsive (i.e., in a Vegetative State; VS) or non-communicative (i.e., in a Minimally Conscious State; MCS), which renders it impossible to assess any subjective perception of benefit, one of the two core aspects of MCIDs. Here, we develop a novel approach that leverages published, international diagnostic guidelines to establish a probability-based minimal clinically important difference (pMCID), and we apply it to the most validated and frequently used scale in DOC: the Coma Recovery Scale-Revised (CRS-R). This novel method is objective (i.e., based on published criteria for patient diagnosis) and easy to recalculate as the field refines its agreed-upon criteria for diagnosis. We believe this new approach can help clinicians determine whether observed changes in patients' behavior are clinically important, even when patients cannot communicate their experiences, and can align the landscape of clinical trials in DOC with the practices in other medical fields.

Automated summary

In the past 30 years, there has been an increasing trend in clinical trials to assess novel interventions not only based on statistical significance, but also on clinically meaningful changes for patients. However, in the context of Disorders of Consciousness (DOC), there is currently no consensus on what constitutes a minimal clinically important difference (MCID). To address this issue, researchers have developed a probability-based approach using published diagnostic guidelines to establish a MCID and applied it to the Coma Recovery Scale-Revised (CRS-R), the most validated and frequently used scale in DOC.