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

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Consciousness Disorders*/diagnosis ; Consciousness Disorders*/therapy ; Minimal Clinically Important Difference*; Humans ; Benchmarking ; Coma ; Consciousness ; Persistent Vegetative State/diagnosis

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.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2023 Monti et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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DP2 HD101400 United States HD NICHD NIH HHS; R21 NS109627 United States NS NINDS NIH HHS; RF1 NS115268 United States NS NINDS NIH HHS; R01 GM135420 United States GM NIGMS NIH HHS

Date Created: 20230824 Date Completed: 20230828 Latest Revision: 20230917

20230917

PMC10449161

10.1371/journal.pone.0290290

37616196