Erik L Bao1, Ling-Ya Chao1, Peiyun Ni1, Lidia M V R Moura1, Andrew J Cole1, Sydney S Cash1, Daniel B Hoch1, Matt T Bianchi1, M Brandon Westover2. 1. From Harvard-MIT Health Sciences and Technology (E.L.B., L.-Y.C., P.N.), Harvard Medical School; and Department of Neurology (L.M.V.R.M., A.J.C., S.S.C., D.B.H., M.T.B., M.B.W.), Massachusetts General Hospital, Boston. 2. From Harvard-MIT Health Sciences and Technology (E.L.B., L.-Y.C., P.N.), Harvard Medical School; and Department of Neurology (L.M.V.R.M., A.J.C., S.S.C., D.B.H., M.T.B., M.B.W.), Massachusetts General Hospital, Boston. mwestover@mgh.harvard.edu.
Abstract
OBJECTIVE: To compare the expected quality-adjusted life-years (QALYs) in adult patients undergoing immediate vs deferred antiepileptic drug (AED) treatment after a first unprovoked seizure. METHODS: We constructed a simulated clinical trial (Markov decision model) to compare immediate vs deferred AED treatment after a first unprovoked seizure in adults. Three base cases were considered, representing patients with varying degrees of seizure recurrence risk and effect of seizures on quality of life (QOL). Cohort simulation was performed to determine which treatment strategy would maximize the patient's expected QALYs. Sensitivity analyses were guided by clinical data to define decision thresholds across plausible measurement ranges, including seizure recurrence rate, effect of seizure recurrence on QOL, and efficacy of AEDs. RESULTS: For patients with a moderate risk of recurrent seizures (52.0% over 10 years after first seizure), immediate AED treatment maximized QALYs compared to deferred treatment. Sensitivity analyses showed that for the preferred choice to change to deferred AED treatment, key clinical measures needed to reach implausible values were 10-year seizure recurrence rate ≤38.0%, QOL reduction with recurrent seizures ≤0.06, and efficacy of AEDs on lowering seizure recurrence rate ≤16.3%. CONCLUSION: Our model determined that immediate AED treatment is preferable to deferred treatment in adult first-seizure patients over a wide and clinically relevant range of variables. Furthermore, our analysis suggests that the 10-year seizure recurrence rate that justifies AED treatment (38.0%) is substantially lower than the 60% threshold used in the current definition of epilepsy.
OBJECTIVE: To compare the expected quality-adjusted life-years (QALYs) in adult patients undergoing immediate vs deferred antiepileptic drug (AED) treatment after a first unprovoked seizure. METHODS: We constructed a simulated clinical trial (Markov decision model) to compare immediate vs deferred AED treatment after a first unprovoked seizure in adults. Three base cases were considered, representing patients with varying degrees of seizure recurrence risk and effect of seizures on quality of life (QOL). Cohort simulation was performed to determine which treatment strategy would maximize the patient's expected QALYs. Sensitivity analyses were guided by clinical data to define decision thresholds across plausible measurement ranges, including seizure recurrence rate, effect of seizure recurrence on QOL, and efficacy of AEDs. RESULTS: For patients with a moderate risk of recurrent seizures (52.0% over 10 years after first seizure), immediate AED treatment maximized QALYs compared to deferred treatment. Sensitivity analyses showed that for the preferred choice to change to deferred AED treatment, key clinical measures needed to reach implausible values were 10-year seizure recurrence rate ≤38.0%, QOL reduction with recurrent seizures ≤0.06, and efficacy of AEDs on lowering seizure recurrence rate ≤16.3%. CONCLUSION: Our model determined that immediate AED treatment is preferable to deferred treatment in adult first-seizure patients over a wide and clinically relevant range of variables. Furthermore, our analysis suggests that the 10-year seizure recurrence rate that justifies AED treatment (38.0%) is substantially lower than the 60% threshold used in the current definition of epilepsy.
Authors: Allan Krumholz; Samuel Wiebe; Gary S Gronseth; David S Gloss; Ana M Sanchez; Arif A Kabir; Aisha T Liferidge; Justin P Martello; Andres M Kanner; Shlomo Shinnar; Jennifer L Hopp; Jacqueline A French Journal: Neurology Date: 2015-04-21 Impact factor: 9.910
Authors: Jong Woo Lee; Andrew D Norden; Keith L Ligon; Alexandra J Golby; Rameen Beroukhim; John Quackenbush; William Wells; Kristen Oelschlager; Derek Maetzold; Patrick Y Wen Journal: Epilepsy Res Date: 2014-03-12 Impact factor: 3.045
Authors: Erica Sanford Kobayashi; Bryce Waldman; Branden M Engorn; Katherine Perofsky; Erika Allred; Benjamin Briggs; Chelsea Gatcliffe; Nanda Ramchandar; Jeffrey J Gold; Ami Doshi; Elizabeth G Ingulli; Courtney D Thornburg; Wendy Benson; Lauge Farnaes; Shimul Chowdhury; Seema Rego; Charlotte Hobbs; Stephen F Kingsmore; David P Dimmock; Nicole G Coufal Journal: Front Pediatr Date: 2022-01-24 Impact factor: 3.418