title: Video Rating in Neurodegenerative Disease Clinical Trials: The Experience of PRION-1.
abstract: OBJECTIVE
  Large clinical trials including patients with uncommon diseases involve assessors in different geographical locations, resulting in considerable inter-rater variability in assessment scores. As video recordings of examinations, which can be individually rated, may eliminate such variability, we measured the agreement between a single video rater and multiple examining physicians in the context of PRION-1, a clinical trial of the antimalarial drug quinacrine in human prion diseases.
  
  
  METHODS
  We analysed a 43-component neurocognitive assessment battery, on 101 patients with Creutzfeldt-Jakob disease, focusing on the correlation and agreement between examining physicians and a single video rater.
  
  
  RESULTS
  In total, 335 videos of examinations of 101 patients who were video-recorded over the 4-year trial period were assessed. For neurocognitive examination, inter-observer concordance was generally excellent. Highly visual neurological examination domains (e.g. finger-nose-finger assessment of ataxia) had good inter-rater correlation, whereas those dependent on non-visual clues (e.g. power or reflexes) correlated poorly. Some non-visual neurological domains were surprisingly concordant, such as limb muscle tone.
  
  
  CONCLUSIONS
  Cognitive assessments and selected neurological domains can be practically and accurately recorded in a clinical trial using video rating. Video recording of examinations is a valuable addition to any trial provided appropriate selection of assessment instruments is used and rigorous training of assessors is undertaken.
authors.affiliation: MRC Prion Unit and Department of Neurodegenerative Disease, University College London Institute of Neurology, and National Prion Clinic, National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Trust, London, UK.
authors.forename: Christopher
authors.initials: C
authors.lastname: Carswell
authors.forename: Michael
authors.initials: M
authors.lastname: Rañopa
authors.forename: Suvankar
authors.initials: S
authors.lastname: Pal
authors.forename: Rebecca
authors.initials: R
authors.lastname: Macfarlane
authors.forename: Durre
authors.initials: D
authors.lastname: Siddique
authors.forename: Dafydd
authors.initials: D
authors.lastname: Thomas
authors.forename: Tom
authors.initials: T
authors.lastname: Webb
authors.forename: Steve
authors.initials: S
authors.lastname: Wroe
authors.forename: Sarah
authors.initials: S
authors.lastname: Walker
authors.forename: Janet
authors.initials: J
authors.lastname: Darbyshire
authors.forename: John
authors.initials: J
authors.lastname: Collinge
authors.forename: Simon
authors.initials: S
authors.lastname: Mead
authors.forename: Peter
authors.initials: P
authors.lastname: Rudge