Indices of Responsiveness for The Coma Recovery Scale - Revised in a Clinical Trial of Amantadine for Patients With Disorders of Consciousness

Research Objectives: To establish indices of responsiveness on the Coma Recovery Scale - Revised (CRS-R) for patients with disorders of consciousness (DoC): (1) minimal detectable change with 95% confidence interval (MDC95), (2) conditional MDC95 (cMDC), and (3) distribution-based minimally clinically important difference (MCID). To compare participants’ change in CRS-R scores between the control and placebo group of the Amantadine Trial.

Design: Retrospective analysis of data collected during a randomized, placebo-controlled clinical trial of participants with DoC.

Setting: Inpatient rehabilitation facilities.

Participants: 180 adult participants with DoC resulting from traumatic brain injury (age: mean=36.4 years, SD=15.3; gender: 130 males, 50 females ; condition: 92 Amantadine, 88 placebo).

Interventions: Amantadine or placebo was administered to patients for four weeks.

Main Outcome Measures: CRS-R was administered to patients at baseline and four weeks later. We transformed CRS-R total raw scores (0 to 23) to a 10-unit equal-interval scale using Rasch analysis. All responsiveness indices are in CRS-R units.

Results: For the full sample, MDC95=11, cMDC 95 range=11-42, MCID: .20SD=4, .33SD=6, .50SD=9.

Experimental group: Mean CRS-R change (20.4 units) exceeded all MCID values. 63 (68.5%) participants improved beyond MDC 95; 53 (57.6%) participants improved beyond cMDC 95.

Control group: Mean CRS-R change (16.8 units) exceeded all MCID values. 54 (61.4%) participants improved beyond MDC 95; 42 (48.9%) participants improved beyond cMDC 95. The experimental group made a mean CRS-R change that was nearly 4 units greater than the control group.

Conclusions: The MDC95 and MCID statistics account for differences over the four weeks between the two CRS-R administrations. The cMDC95 accounts for measurement error in change scores on a pair-wise basis and thus provides a more precise index to identify individual patients who are likely to have truly changed. Participants in the amantadine group improved, on average, nearly CRS-R 4 units greater than the control group which represents a small (.20SD) important difference. As none of the distribution-based MCIDs exceed the MDC95 or cMDC95 values, MCIDs should not be applied to interpret individual patient change.

Author(s) Disclosures: N/A