Overt hepatic encephalopathy: development of a novel clinician reported outcome tool and electronic caregiver diary.
Clinical management and clinical trials of patients with overt hepatic encephalopathy (OHE) are compromised by lack of standardized and reproducible tools for its clinical diagnosis or for caregiver (CG) identification of OHE manifestations which merit medical evaluation. Using an iterative Delphi method, Steering Committee and international hepatologist panel, the West Haven (WH) scale was modified to develop and operationalize a clinician tool for OHE identification and grading (HE Grading Instrument, HEGI™). Major diagnostic criteria included disorientation to time, place, and person, asterixis, lethargy, and coma. Minimum HEGI requirements for OHE diagnosis included: (1) disorientation, or (2) presence of both lethargy and asterixis, or (3) coma. Inter- and intra-rater HEGI reproducibility were 97 % and 98 %, respectively. When applied to a phase II clinical trial population of 178 patients with 388 OHE episodes, HEGI demonstrated excellent concordance with investigator judgement. Additionally, a multi-stage study was conducted to develop a daily CG e-diary, based on OHE manifestations recognizable by CG including speech difficulties, unusual behavior, forgetfulness, confusion, disorientation and level of consciousness. The e-diary was designed for use on smart phone, laptop or desktop, utilized branching logic and skip patterns, incorporated automatic daily completion reminders and real time alerts to clinical sites to facilitate daily standardized CG input and was found to be user friendly and understandable. The HEGI and e-diary, which were developed using methodology accepted by regulatory authorities, are designed to facilitate the design and interpretation of clinical trials for OHE and improve outcomes for OHE patients in clinical practice.
Virginia Commonwealth University and McGuire VA Hospital, Richmond, VA, USA.
J S
JS
Bajaj
California Pacific Medical Center, San Francisco, CA, USA.
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RT
Frederick
University of California, San Francisco, CA, USA.
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NM
Bass
Indiana University, Indianapolis, IN, USA.
M
M
Ghabril
Evidera, Bethesda, MD, USA.
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Coyne
Patient-Centered Outcomes Research Institute, Washington, DC, USA.
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MK
Margolis
Horizon Pharma, 150 S Saunders Road, Lake Forest, IL, 60045, USA.
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Santoro
Horizon Pharma, 150 S Saunders Road, Lake Forest, IL, 60045, USA.
D F
DF
Coakley
Horizon Pharma, 150 S Saunders Road, Lake Forest, IL, 60045, USA.
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M
Mokhtarani
Horizon Pharma, 150 S Saunders Road, Lake Forest, IL, 60045, USA.
M
M
Jurek
Horizon Pharma, 150 S Saunders Road, Lake Forest, IL, 60045, USA. bruce.scharschmidt@gmail.com.
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Scharschmidt
D000368:Aged; D017028:Caregivers / Q000523:psychology* / Q000639:trends; D003697:Delphi Technique; D057286:Electronic Health Records / Q000639:trends; D005260:Female; D006501:Hepatic Encephalopathy / Q000175:diagnosis / Q000523:psychology*; D006801:Humans; D008297:Male; D008499:Medical Records; D008875:Middle Aged; D010820:Physicians / Q000639:trends; D016896:Treatment Outcome
Altered mental status; Chronic liver disease; Cirrhosis; Clinical trial; Liver failure