International workshop: what is needed to ensure outcome measures for Rett syndrome are fit-for-purpose for clinical trials? June 7, 2023, Nashville, USA
Jenny Downs,
Dominique C. Pichard,
Walter E. Kaufmann,
Joseph P. Horrigan,
Melissa Raspa,
Gillian Townend,
Eric D. Marsh,
Helen Leonard,
Kathleen Motil,
Andrew C. Dietz,
Nupur Garg,
Amitha Ananth,
Breanne Byiers,
Sarika Peters,
Christopher Beatty,
Frank Symons,
Aleksandra Jacobs,
James Youakim,
Bernhard Suter,
Paramola Santosh,
Jeffrey L. Neul,
Tim A. Benke
Affiliations
Jenny Downs
The Kids Research Institute Australia, Centre for Child Health Research, University of Western Australia
Dominique C. Pichard
International Rett Syndrome Foundation
Walter E. Kaufmann
Department of Human Genetics, Emory University School of Medicine
Joseph P. Horrigan
Duke Center for Autism and Brain Development, Duke University
Melissa Raspa
RTI International
Gillian Townend
School of Psychology and Clinical Language Sciences, University of Reading
Eric D. Marsh
Division of Child Neurology and University of Pennsylvania Perelman School of Medicine, Departments of Neurology and Pediatrics, Children’s Hospital of Philadelphia
Helen Leonard
The Kids Research Institute Australia, Centre for Child Health Research, University of Western Australia
Kathleen Motil
USDA/ARS Children’s Nutrition Research Center, Baylor College of Medicine
Andrew C. Dietz
Shape Therapeutics, Inc
Nupur Garg
International Rett Syndrome Foundation
Amitha Ananth
University of Alabama at Birmingham
Breanne Byiers
Department of Educational Psychology, University of Minnesota
Sarika Peters
Vanderbilt Kennedy Center, Vanderbilt University Medical Center
Christopher Beatty
Department of Pediatrics, Division of Neurology, Nationwide Children’s Hospital and, The Ohio State University College of Medicine
Frank Symons
Department of Educational Psychology, University of Minnesota
Aleksandra Jacobs
Isabelle Rapin Division of Child Neurology, Montefiore Medical Center, Albert Einstein College of Medicine
James Youakim
Acadia Pharmaceuticals Inc.
Bernhard Suter
Department of Pediatrics & Neurology, Baylor College of Medicine
Paramola Santosh
Department of Child and Adolescent Psychiatry, Developmental Neuropsychiatry & Psychopharmacology, King’s College
Jeffrey L. Neul
Department of Educational Psychology, University of Minnesota
Tim A. Benke
School of Medicine Depts of Pediatrics, Neurology and Pharmacology, Children’s Hospital Colorado/University of Colorado
Abstract 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.
