International workshop: what is needed to ensure outcome measures for Rett syndrome are fit-for-purpose for clinical trials? June 7, 2023, Nashville, USA.

Autor: Downs J; The Kids Research Institute Australia, Centre for Child Health Research, University of Western Australia, 15 Hospital Avenue, Nedlands, Perth, WA, 6009, Australia. Jenny.Downs@thekids.org.au.; Curtin School of Allied Health, Curtin University, GPO Box U1987, Perth, WA, 6845, Australia. Jenny.Downs@thekids.org.au., Pichard DC; International Rett Syndrome Foundation, 4500 Cooper Road, Suite 204, Cincinnati, OH, 45242, USA., Kaufmann WE; Department of Human Genetics, Emory University School of Medicine, 615 Michael St, Atlanta, GA, 30322, USA.; Department of Neurology, Boston Children's Hospital, 300 Longwood Ave, Boston, MA, 02115, USA., Horrigan JP; Duke Center for Autism and Brain Development, Duke University, 2608 Erwin Road, Suite 300, Durham, NC, 27705, USA., Raspa M; RTI International, 3040 East Cornwallis Road, Research Triangle Park, Durham, NC, 27607, USA., Townend G; School of Psychology and Clinical Language Sciences, University of Reading, Whiteknights Campus, Reading, RG6 6ES, UK., Marsh ED; Division of Child Neurology and University of Pennsylvania Perelman School of Medicine, Departments of Neurology and Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Leonard H; The Kids Research Institute Australia, Centre for Child Health Research, University of Western Australia, 15 Hospital Avenue, Nedlands, Perth, WA, 6009, Australia., Motil K; USDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX, 77030, USA., Dietz AC; Shape Therapeutics, Inc, Seattle, USA., Garg N; International Rett Syndrome Foundation, 4500 Cooper Road, Suite 204, Cincinnati, OH, 45242, USA., Ananth A; University of Alabama at Birmingham, Birmingham, AL, USA., Byiers B; Department of Educational Psychology, University of Minnesota, 56 E River Rd, Room 250, Minneapolis, MN, 55455, USA., Peters S; Vanderbilt Kennedy Center, Vanderbilt University Medical Center, 230 Appleton Place, Nashville, TN, PMB4037204, USA., Beatty C; Department of Pediatrics, Division of Neurology, Nationwide Children's Hospital and, The Ohio State University College of Medicine, 700 Children's Drive, Columbus, OH, 43205, USA., Symons F; Department of Educational Psychology, University of Minnesota, 56 E River Rd, Room 250, Minneapolis, MN, 55455, USA., Jacobs A; Isabelle Rapin Division of Child Neurology, Montefiore Medical Center, Albert Einstein College of Medicine, New York, USA., Youakim J; Acadia Pharmaceuticals Inc., 502 Carnegie Center, Suite 300, Princeton, NJ, 08540, USA., Suter B; Department of Pediatrics & Neurology, Baylor College of Medicine, Houston, TX, USA., Santosh P; Department of Child and Adolescent Psychiatry, Developmental Neuropsychiatry & Psychopharmacology, King's College, London, UK.; Centre for Interventional Paediatric Psychopharmacology and Rare Diseases (CIPPRD) & CIPP Rett Centre, Maudsley Hospital, London, UK.; HealthTracker Ltd, Gillingham, UK., Neul JL; Department of Educational Psychology, University of Minnesota, 56 E River Rd, Room 250, Minneapolis, MN, 55455, USA., Benke TA; School of Medicine Depts of Pediatrics, Neurology and Pharmacology, Children's Hospital Colorado/University of Colorado, 12800 E 19th, MS8102, Aurora, CO, 80045, USA.
Jazyk: angličtina
Zdroj: Trials [Trials] 2024 Dec 21; Vol. 25 (1), pp. 845. Date of Electronic Publication: 2024 Dec 21.
DOI: 10.1186/s13063-024-08678-6
Abstrakt: Introduction: The clinical, research and advocacy communities for Rett syndrome are striving to achieve clinical trial readiness, including having fit-for-purpose clinical outcome assessments. This study aimed to (1) describe psychometric properties of clinical outcome assessment for Rett syndrome and (2) identify what is needed to ensure that fit-for-purpose clinical outcome assessments are available for clinical trials.
Methods: Clinical outcome assessments for the top 10 priority domains identified in the Voice of the Patient Report for Rett syndrome were compiled and available psychometric data were extracted. The clinical outcome assessments measured clinical severity, functional abilities, comorbidities and quality of life, and electrophysiological biomarkers. An international and multidisciplinary panel of 29 experts with clinical, research, psychometric, biostatistical, industry and lived experience was identified through International Rett Syndrome Foundation networks, to discuss validation of the clinical outcome assessments, gaps and next steps, during a workshop and in a follow-up questionnaire. The identified gaps and limitations were coded using inductive content analysis.
Results: Variable validation profiles across 26 clinical outcome assessments of clinical severity, functional abilities, and comorbidities were discussed. Reliability, validity, and responsiveness profiles were mostly incomplete; there were limited content validation data, particularly parent-informed relevance, comprehensiveness and comprehensibility of items; and no data on meaningful change or cross-cultural validity. The panel identified needs for standardised administration protocols and systematic validation programmes.
Conclusion: A pipeline of collaborative clinical outcome assessment development and validation research in Rett syndrome can now be designed, aiming to have fit-for-purpose measures that can evaluate meaningful change, to serve future clinical trials and clinical practice.
Competing Interests: Declarations. Ethics approval and consent to participate: Workshop involving literature review, ethics approval not necessary for this study. Consent for publication: Not necessary for this study. Workshop participants are the authors for this manuscript. Competing interests: JD: Consultancy for Marinus, Ultragenyx, Acadia, Avexis, Orion, Neurogene, Taysha and Takeda; Clinical Trials with Anavex and Newron. All consultancies are unrelated to this work and all remuneration has been made to her department. DCP: None. WEK: Past Chief Scientific Officer of Anavex Life Sciences Corp. He received funding from the National Institutes of Health (NIH) and the Centers for Disease Control and Prevention (CDC), and he has been a consultant for Anavex, Acadia, EryDel/Quince, Neuren, Newron, GW Pharmaceuticals, Marinus, Biohaven, Zynerba, Ovid Therapeutics, Stalicla, Unravel Biosciences and Tetra Therapeutics. He has done clinical trials with Ipsen and Neuren. JPH: Employee at AMO Pharma, based in Wornesh, United Kingdom. MR: None. GT: None. EM: The PI for Stoke therapeutics, Zogenix Pharmaceuticals, Acadia Pharmaceuticals, Marinus Pharmaceuticals, Takeda Pharmaceuticals, Epygenix Pharmaceuticals. He has received research support from NIH, Penn Orphan Disease center, International Rett syndrome foundation, International CDKL5 Research Foundation, Curaleaf Inc., is a consultant for Acadia Pharmaceuticals, and has prepared an educational programme for Medscape. HL: Consultancy for Marinus, Acadia, Avexis and Orion; Clinical Trials with Anavex and Newron; All remuneration has been made to her department. KM: None. ACD: Work completed while an employee and equity holder of Shape Therapeutics, Inc. Current employee and equity holder of Ensoma, which had no oversight or funding of this work. NG: None. AA: Research funding from Acadia Pharmaceuticals, Zogenix Inc. Consulting for Sanofi, Acadia. BB: Currently research funding from the NIH (NICHD) and Acadia Pharmaceuticals. SP: Dr. Peters has received research funding from the MECP2 Duplication Foundation, the ActiGraph Corporation, and the National Institutes of Health. She is a consultant for Ionis Pharmaceuticals and Acadia Pharmaceuticals. CB: Consultant for Acadia Pharmaceuticals. FS: None. AJ: None. JY: Employee of Acadia Pharmaceuticals. BS: Received research funding from the International Foundation for CDKL5 Research, Loulou Foundation, the National Institutes of Health, International Rett Syndrome Foundation, the Rett Syndrome Research Trust, and the Grace Science Foundation; consultancy for the IONIS pharmaceuticals, Neurogene, and Taysha; clinical trials with Acadia Pharmaceuticals Inc., Marinus Pharmaceuticals, Neurogene, and the Rett Syndrome Research Trust. All remuneration has been paid to Baylor College of Medicine. PS: Lead of the CIPP Rett Centre, UK, which is partially funded by Reverse Rett, UK. P.S. was a previous Principal Investigator (PI) in the Sarizotan (Protocol Number Sarizotan/001/II/2015; ClinicalTrials.gov Identifier: NCT02790034) and the Anavex Life Sciences Corp. (Protocol Number: ANAVEX2-73-RS-002) clinical trial on Rett Syndrome (RTT). P.S. is currently the PI in the Anavex Life Sciences Corp. (Protocol Number: ANAVEX2-73-RS-003) clinical trial. P.S. is the co-inventor of the HealthTrackerTM and is the Chief Executive Officer and shareholder in HealthTrackerTM. JLN: Received research funding from the National Institutes of Health, the International Rett Syndrome Foundation, and Rett Syndrome Research Trust; served as investigator for clinical trials conducted by Acadia Pharmaceuticals, GW Pharmaceuticals, Neuren Pharmaceuticals, and Newron; received personal consultancy for Acadia Pharmaceuticals Inc, Analysis Group, Anavex, AveXis, GW Pharmaceuticals, Hoffmann-La Roche, Ionis Pharmaceuticals, Myrtelle, Neurogene, Newron Pharmaceuticals, Signant Health, and Taysha Gene Therapies, and the preparation of CME activities for the France Foundation, MedEdicus, Medscape, PeerView Institute, Medscape, TotalCME; served on the scientific advisory board of Alcyone Lifesciences; was a scientific co-founder of LizarBio Therapeutics; and a member of a data safety monitoring board for clinical trials conducted by Ovid Therapeutics and Ultragenix. TAB: Received research funding from GRIN2B Foundation, the International Foundation for CDKL5 Research, Loulou Foundation, the National Institutes of Health, and Simons Foundation; consultancy for Alcyone, AveXis, GRIN Therapeutics, GW Pharmaceuticals, the International Rett Syndrome Foundation, Marinus Pharmaceuticals, Neurogene, Ovid Therapeutics, and Takeda Pharmaceutical Company Limited; clinical trials with Acadia Pharmaceuticals Inc., GW Pharmaceuticals, Marinus Pharmaceuticals, Ovid Therapeutics, and Rett Syndrome Research Trust; all remuneration has been made to his department.
(© 2024. The Author(s).)
Databáze: MEDLINE
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