Personalised selection of medication for newly diagnosed adult epilepsy: study protocol of a first-in-class, double-blind, randomised controlled trial.
| Title: | Personalised selection of medication for newly diagnosed adult epilepsy: study protocol of a first-in-class, double-blind, randomised controlled trial. |
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| Authors: | Thom D; Department of Neuroscience, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia.; Department of Neurology, Alfred Hospital, Melbourne, Victoria, Australia.; Chang RS; Department of Neuroscience, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia.; Department of Neurology, Alfred Hospital, Melbourne, Victoria, Australia.; Lannin NA; Department of Neuroscience, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia.; Allied Health Directorate, Alfred Health, Melbourne, Victoria, Australia.; Ademi Z; Department of Neuroscience, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia.; Health Economics and Policy Evaluation Research Group, Monash Institute of Pharmaceutical Sciences Centre for Medicine Use and Safety, Parkville, Victoria, Australia.; Ge Z; Department of Data Science and AI, Monash University, Clayton, Victoria, Australia.; Reutens D; Department of Neurology, Royal Brisbane and Women's Hospital, Herston, Queensland, Australia.; O'Brien T; Department of Neuroscience, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia.; Department of Neurology, Alfred Health, Melbourne, Victoria, Australia.; D'Souza W; Department of Neurology, St Vincent's Hospital Melbourne Pty Ltd, Fitzroy, Victoria, Australia.; Perucca P; Bladin-Berkovic Comprehensive Epilepsy Program, Department of Neurology, Austin Health, Heidelberg, Victoria, Australia.; Epilepsy Research Centre, Department of Medicine (Austin Health), The University of Melbourne, Melbourne, Victoria, Australia.; Reeder S; Department of Neuroscience, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia.; Nikpour A; Department of Neurology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.; Wong C; The Brain and Spine Centre, Westmead Hospital, Westmead, New South Wales, Australia.; Kiley M; Department of Neurology, Royal Adelaide Hospital, Adelaide, South Australia, Australia.; Department of Neurology, Queen Elizabeth Hospital, Adelaide, South Australia, Australia.; Saw JL; Department of Neurology, Royal Perth Hospital, Perth, Western Australia, Australia.; Nicolo JP; Department of Neurology, Alfred Hospital, Melbourne, Victoria, Australia.; Department of Neurology, The Royal Melbourne Hospital, Melbourne, Victoria, Australia.; Seneviratne U; Department of Neurology, Monash Medical Centre, Clayton, Victoria, Australia.; Carney P; Department of Neurosciences and Eastern Health Clinical School, Eastern Health, Box Hill, Victoria, Australia.; Jones D; Department of Neurology, Royal Hobart Hospital, Hobart, Tasmania, Australia.; Somerville E; Department of Neurology, Prince of Wales Hospital, Sydney, New South Wales, Australia.; Stapleton C; Lived Experience Expert, Sydney, New South Wales, Australia.; Foster E; Department of Neuroscience, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia.; Department of Neurology, Alfred Hospital, Melbourne, Victoria, Australia.; Vadlamudi L; Department of Neurology, Royal Brisbane and Women's Hospital, Herston, Queensland, Australia.; The University of Queensland, Brisbane, Queensland, Australia.; Vaughan DN; Epilepsy Research Centre, Department of Medicine (Austin Health), The University of Melbourne, Melbourne, Victoria, Australia.; Florey Institute of Neuroscience and Mental Health, Heidelberg, Victoria, Australia.; Lee J; Department of Neurology, Royal North Shore Hospital, St Leonards, New South Wales, Australia.; Farrar T; Department of Neurology, Royal North Shore Hospital, St Leonards, New South Wales, Australia.; Howard M; Department of Philosophy, Monash University, Melbourne, Victoria, Australia.; Sparrow R; Department of Philosophy, Monash University, Clayton, Victoria, Australia.; Chen Z; Department of Neuroscience, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia.; Department of Neurology, The Royal Melbourne Hospital, Parkville, Victoria, Australia.; Kwan P; Department of Neuroscience, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia patrick.kwan@monash.edu.; Department of Neurology, Alfred Hospital, Melbourne, Victoria, Australia. |
| Source: | BMJ open [BMJ Open] 2025 Apr 05; Vol. 15 (4), pp. e086607. Date of Electronic Publication: 2025 Apr 05. |
| Publication Type: | Journal Article; Clinical Trial Protocol |
| Language: | English |
| Journal Info: | Publisher: BMJ Publishing Group Ltd Country of Publication: England NLM ID: 101552874 Publication Model: Electronic Cited Medium: Internet ISSN: 2044-6055 (Electronic) Linking ISSN: 20446055 NLM ISO Abbreviation: BMJ Open Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [London] : BMJ Publishing Group Ltd, 2011- |
| MeSH Terms: | Epilepsy*/drug therapy ; Epilepsy*/diagnosis ; Anticonvulsants*/therapeutic use ; Precision Medicine*/methods; Humans ; Double-Blind Method ; Adult ; Randomized Controlled Trials as Topic ; Australia ; Quality of Life ; Machine Learning ; Female ; Prospective Studies ; Treatment Outcome ; Male |
| Abstract: | Introduction: Selection of antiseizure medications (ASMs) for newly diagnosed epilepsy remains largely a trial-and-error process. We have developed a machine learning (ML) model using retrospective data collected from five international cohorts that predicts response to different ASMs as the initial treatment for individual adults with new-onset epilepsy. This study aims to prospectively evaluate this model in Australia using a randomised controlled trial design.; Methods and Analysis: At least 234 adult patients with newly diagnosed epilepsy will be recruited from 14 centres in Australia. Patients will be randomised 1:1 to the ML group or usual care group. The ML group will receive the ASM recommended by the model unless it is considered contraindicated by the neurologist. The usual care group will receive the ASM selected by the neurologist alone. Both the patient and neurologists conducting the follow-up will be blinded to the group assignment. Both groups will be followed up for 52 weeks to assess treatment outcomes. Additional information on adverse events, quality of life, mood and use of healthcare services and productivity will be collected using validated questionnaires. Acceptability of the model will also be assessed.The primary outcome will be the proportion of participants who achieve seizure-freedom (defined as no seizures during the 12-month follow-up period) while taking the initially prescribed ASM. Secondary outcomes include time to treatment failure, time to first seizure after randomisation, changes in mood assessment score and quality of life score, direct healthcare costs, and loss of productivity during the treatment period.This trial will provide class I evidence for the effectiveness of a ML model as a decision support tool for neurologists to select the first ASM for adults with newly diagnosed epilepsy.; Ethics and Dissemination: This study is approved by the Alfred Health Human Research Ethics Committee (Project 130/23). Findings will be presented in academic conferences and submitted to peer-reviewed journals for publication.; Trial Registration Number: ACTRN12623000209695.; (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY. Published by BMJ Group.) |
| Competing Interests: | Competing interests: RS-KC was supported by Centrally Awarded Scholarship for Monash University Doctor of Philosophy (0047). NAL was supported by Heart Foundation Australia (GNT106762). TO'B was supported by an NHMRC Investigator Grant (APP1176426). Outside of the submitted work his institution has received consultancy fees and/or research grants from Eisai, UCB, Livanova, ES Therapeutics, Epidarex, Kinosis Theraputics. PP is supported by an Emerging Leadership Investigator Grant from the Australian National Health and Medical Research Council (APP2017651), The University of Melbourne, Monash University, the Austin Medical Research Foundation, and the Norman Beischer Medical Research Foundation. He has received speaker honoraria or consultancy fees to his institution from Chiesi, Eisai, LivaNova, Novartis, Sun Pharma, Supernus, and UCB Pharma, outside the submitted work. He is an Associate Editor for Epilepsia Open. J-PN/his institution has received consultancy fees from Eisai, outside the submitted work. EF is supported by Monash Partners STAR Clinician Fellowship, Sylvia and Charles Viertel Charitable Foundation; The Royal Australian College of Physicians Fellows Research Establishment Fellowship. Outside the submitted work, she/her institution has received honoraria and/or research grants from Brain Foundation (Australia), GPCE, LivaNova (USA), Lundbeck Australia and the limbic. LV is supported by the Metro North Clinician Research Fellowship. Outside the submitted work she has received consultancy fees from Eisai and UCB Pharma. She has received educational support from LivaNova. MH was supported by a Monash University Internal Funding Scheme (Emerging Research Strength Seed Scheme) and an Eisai IIS research grant. ZC was supported by an Early Career Fellowship from the NHMRC of Australia (GNT1156444). PK is supported by the NHMRC Investigator Grants (GNT2025849). Outside the submitted work he/his institution has received consultancy fees and/or research grants from Eisai, Jazz Pharmaceuticals, LivaNova, SK Life Science and UCB Pharma. |
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| Contributed Indexing: | Keywords: Artificial Intelligence; Clinical Trial; Epilepsy; Machine Learning |
| Substance Nomenclature: | 0 (Anticonvulsants) |
| Entry Date(s): | Date Created: 20250405 Date Completed: 20250405 Latest Revision: 20250816 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC11973792 |
| DOI: | 10.1136/bmjopen-2024-086607 |
| PMID: | 40187776 |
| Database: | MEDLINE |
Journal Article; Clinical Trial Protocol