title: A prospective study of direct medical costs in a large cohort of consecutively enrolled patients with refractory epilepsy in Italy.
abstract: OBJECTIVE
  To evaluate direct medical costs and their predictors in patients with refractory epilepsy enrolled into the SOPHIE study (Study of Outcomes of PHarmacoresistance In Epilepsy) in Italy.
  
  
  METHODS
  Adults and children with refractory epilepsy were enrolled consecutively at 11 tertiary referral centers and followed for 18 months. At entry, all subjects underwent a structured interview and a medical examination, and were asked to keep records of diagnostic examinations, laboratory tests, specialist consultations, treatments, hospital admissions, and day-hospital days during follow-up. Study visits included assessments every 6 months of seizure frequency, health-related quality of life (Quality of Life in Epilepsy Inventory 31), medication-related adverse events (Adverse Event Profile) and mood state (Beck Depression Inventory-II). Cost items were priced by applying Italian tariffs. Cost estimates were adjusted to 2013 values.
  
  
  RESULTS
  Of 1,124 enrolled individuals, 1,040 completed follow-up. Average annual cost per patient was € 4,677. The highest cost was for antiepileptic drug (AED) treatment (50%), followed by hospital admissions (29% of overall costs). AED polytherapy, seizure frequency during follow-up, grade III pharmacoresistance, medical and psychiatric comorbidities, and occurrence of status epilepticus during follow-up were identified as significant predictors of higher costs. Age between 6 and 11 years, and genetic (idiopathic) generalized epilepsies were associated with the lowest costs. Costs showed prominent variation across centers, largely due to differences in the clinical characteristics of cohorts enrolled at each center and the prescribing of second-generation AEDs. Individual outliers associated with high costs related to hospital admissions had a major influence on costs in many centers.
  
  
  CONCLUSIONS
  Refractory epilepsy is associated with high costs that affect individuals and society. Costs differ across centers in relation to the characteristics of patients and the extent of use of more expensive, second-generation AEDs. Epilepsy-specific costs cannot be easily differentiated from costs related to comorbidities.
authors.affiliation: Unit of Clinical and Experimental Pharmacology, Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.|Division of Child Neuropsychiatry, University of Insubria, Varese, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Luoni
authors.affiliation: Division of Neurology 2, Department of Health Science Medicine, Surgery, Dentistry, San Paolo Hospital, University of Milan, Milan, Italy.
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Canevini
authors.affiliation: Department of Child Neuropsychiatry, Epilepsy Center, C. Poma Hospital, Mantua, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Capovilla
authors.affiliation: Department of Health Science and Pharmacovigilance Centre Calabria Region, University Hospital Mater Domini, University of Catanzaro, Catanzaro, Italy.
authors.forename: Giovambattista
authors.initials: G
authors.lastname: De Sarro
authors.affiliation: C. Mondino National Neurological Institute, Pavia, Italy.
authors.forename: Carlo Andrea
authors.initials: CA
authors.lastname: Galimberti
authors.affiliation: Unit of Clinical and Experimental Pharmacology, Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Gatti
authors.affiliation: Neuroscience Department, Pediatric Neurology Unit and Laboratories, A. Meyer Children's Hospital, University of Florence, Florence, Italy.
authors.forename: Renzo
authors.initials: R
authors.lastname: Guerrini
authors.affiliation: Clinic for Nervous System Diseases, University of Bari, Bari, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: La Neve
authors.affiliation: Unit of Clinical and Experimental Pharmacology, Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.
authors.forename: Iolanda
authors.initials: I
authors.lastname: Mazzucchelli
authors.affiliation: 3rd Neurology Division and Epilepsy Center, Careggi Hospital, Florence, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Rosati
authors.affiliation: Epilepsy Center, Clinic of Nervous System Diseases, Ospedali Riuniti, University of Foggia, Foggia, Italy.
authors.forename: Luigi Maria
authors.initials: LM
authors.lastname: Specchio
authors.affiliation: Department of Neurosciences, Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Striano
authors.affiliation: IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.|Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Tinuper
authors.affiliation: Unit of Clinical and Experimental Pharmacology, Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.|C. Mondino National Neurological Institute, Pavia, Italy.
authors.forename: Emilio
authors.initials: E
authors.lastname: Perucca
mesh_terms: D000293:Adolescent; D000328:Adult; D015331:Cohort Studies; D004827:Epilepsy / Q000191:economics* / Q000453:epidemiology* / Q000628:therapy; D005260:Female; D005500:Follow-Up Studies; D017048:Health Care Costs; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011788:Quality of Life; D055815:Young Adult
keywords: Antiepileptic drugs; Direct medical costs; Italy; Prospective study; Refractory epilepsy