Background
Assessing the evolution of severely brain-injured patients with disorders of consciousness (DOC) with tools like the Glasgow Outcome Scale-Extended (GOS-E)1 remains a challenge. At the bedside, the most reliable diagnostic tool is the Coma Recovery Scale–Revised (CRS-R)2,3. It distinguishes between patients in an unresponsive wakefulness syndrome (UWS)4, patients in a minimally conscious state (MCS) and patients who have emerged from MCS (EMCS)5,6. The present international multi-centric study aims to validate a new phone outcome questionnaire (POQ) based on the CRS-R and compare it to the CRS-R performed at the bedside and to the GOS-E. The POQ allows clinicians to probe the evolution of a patient’s state of consciousness based on caregivers’ feedback. This project is part of the IBIA-DOC-SIG and DOCMA consortium.

Methods 
Five centres were involved in this study with at least two blinded examiners per centre. Examiner A conducted a phone interview with the patient’s main caregivers, asked for the caregivers’ and patients’ demographical data and administered the POQ, which evaluates the presence and frequency of purposeful behaviors based on CRS-R items, as well as the GOS-E. Examiner B performed at least 3 evaluations with the CRS-R7,8,9 within one week of the phone interview and the best CRS-R diagnosis was retained3. We measured diagnostic agreement between the CRS-R’s best diagnosis, the POQ and the GOS-E using Kappa tests. 

Results
Ninety-two DOC patients (37 UWS, 44 MCS, 11 EMCS; 31 females; 47±17 years old; median: 10,4 months; 30 traumatic injury; 14 home, 69 rehabilitation centres, 8 nursing home, 1 other place) were enrolled (28 in ULiège, 27 in ICS Maugeri, 19 in NISA, 14 in Santa Lucia, 4 in Cuneo) and 92 caregivers (67 females; 49±15 years old) who frequently visited their relative were contacted by phone. We found 62/92 matches (67%; Weighted k=0.514, p≤0.01) between the CRS-R and the POQ and 69/92 matches (75%; k=0.459, p≤0.01) between the CRS-R and the GOS-E. We observed a 48/92 match (52%; Weighted k=0.518, p≤0.01) between the CRS-R and the POQ, when we distinguish MCS- and MCS+ (i.e., absence or presence of language processing, respectively). In case of discrepancy, caregivers tended to observe higher levels of behaviors compared to clinicians who performed the CRS-R. Finally, we found a 82/92 match (89%; k=0.776, p≤0.01) between the POQ’s and GOS-E’s diagnosis. 

Conclusions
This study showed an excellent agreement between the POQ and GOS-E, and a moderate agreement between the CRS-R, the GOS-E, and the POQ. Further analyses will be done to better understand the discrepancy between families’ observations and repeated standardized assessments. In conclusion, even though the POQ lacks sensitivity to diagnosis, it better differentiates DOC diagnostic entities compared to the GOS-E and so can be recommended for the use of long-term longitudinal studies with DOC patients. 

Acknowledgments
The study was supported by the University and University Hospital of Liège, the Belgian National Funds for Scientific Research (FRS-FNRS), the European Union’s Horizon 2020 Framework Programme for Research and Innovation under the Specific Grant Agreement No. 720270 (Human Brain Project SGA1) and SGA2 from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement N° 778234. CA and LS are research fellows, AT is a postdoctoral researcher and SL is research director at FNRS. CC is a Marie Sklodowska-Curie fellow (H2020-MSCA-IF-2016-ADOC- 752686).

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International validation of the Phone Outcome Questionnaire for patients with Disorders Of Consciousness