title: External validation of a prognostic model for seizure recurrence following a first unprovoked seizure and implications for driving.
abstract: OBJECTIVE
  In the United Kingdom and other European Union countries guidelines for driving following a first unprovoked seizure require the risk of another seizure in the next year to be less than 20%. Using data from one clinical trial, we previously developed a prognostic model to inform driving guidelines. The objective of this work is to externally validate our published model and demonstrate its generalisability.
  
  
  METHODS
  A cohort of 620 people with a first unprovoked seizure was used to develop the original model which included variables for aetiology, first degree relative with epilepsy, seizures only while asleep, electroencephalogram, computed tomography or magnetic resonance scan result, and treatment policy. The validation cohorts consisted of 274 (United Kingdom), 305 (Italy), and 847 (Australia) people. The model was evaluated using discrimination and calibration methods. A covariate, missing from the Italian dataset, was handled via five imputation methods. Following external validation, the model was fitted to a pooled population comprising all validation datasets and the development dataset. The model was stratified by dataset.
  
  
  RESULTS
  The model generalised relatively well. All methods of imputation performed fairly similarly. At six months, the risk of a seizure recurrence following a first ever seizure, based on the pooled datasets, is 15% (95% CI: (12% to 18%)) for patients who are treated immediately and 18% (95% CI: (15 to 21%)) otherwise. Individuals can be reliably stratified into risk groups according to the clinical factors included in the model.
  
  
  CONCLUSIONS
  Our prognostic model, used to inform driving regulations, has been validated and consequently has been proven as a valuable tool for predicting risk of seizure recurrence following a first seizure in people with various combinations of risk factors. Additionally, there is evidence to support one worldwide overall prognostic model for risk of second seizure following a first.
authors.affiliation: Department of Biostatistics, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Laura Jayne
authors.initials: LJ
authors.lastname: Bonnett
authors.affiliation: Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Marson
authors.affiliation: Medical Research Council Biostatistics Unit, Cambridge Institute of Public Health, Cambridge, United Kingdom; Medical Research Council Clinical Trials Unit, London, United Kingdom.
authors.forename: Anthony
authors.initials: A
authors.lastname: Johnson
authors.affiliation: Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Lois
authors.initials: L
authors.lastname: Kim
authors.affiliation: National Institute for Health Research, University College London Hospitals Biomedical Research Centre, London, United Kingdom; University College London Institute of Neurology, London, United Kingdom; Epilepsy Society, Chalfont St Peter, United Kingdom.
authors.forename: Josemir W
authors.initials: JW
authors.lastname: Sander
authors.affiliation: Western Australian Comprehensive Epilepsy Centre, Royal Perth and Fremantle Hospitals, Perth, Australia.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Lawn
authors.affiliation: Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
authors.forename: Ettore
authors.initials: E
authors.lastname: Beghi
authors.affiliation: Clinica Neurologica, Ospedale Maggiore della Carità, Novara, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Leone
authors.affiliation: Department of Biostatistics, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Catrin Tudur
authors.initials: CT
authors.lastname: Smith
mesh_terms: D001334:Automobile Driving; D006801:Humans; D008962:Models, Theoretical; D011379:Prognosis; D012008:Recurrence; D012640:Seizures / Q000503:physiopathology*