Publication Date
12-21-2024
Journal
Trials
DOI
10.1186/s13063-024-08678-6
PMID
39709426
PMCID
PMC11663341
PubMedCentral® Posted Date
12-21-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Humans, Clinical Trials as Topic, Congresses as Topic, Consensus, Endpoint Determination, Functional Status, Outcome Assessment, Health Care, Predictive Value of Tests, Psychometrics, Quality of Life, Reproducibility of Results, Research Design, Rett Syndrome, Severity of Illness Index, Treatment Outcome, Internationality, Rett syndrome, Clinical trial readiness, Clinical outcome assessments, Validation, Meaningful change
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.