Consistently High Agreement Between Independent Raters of Niemann-Pick Type C1 Clinical Severity Scale in Phase 2/3 Trial
| Autor: | Danielle Rodriguez, Donald M. Bushnell, Nicole Y. Farhat, Elizabeth Berry-Kravis, Laurie Bailey, Forbes D. Porter, Katherine Friedmann |
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| Rok vydání: | 2021 |
| Předmět: |
Male
medicine.medical_specialty Electronic data capture Adolescent Intraclass correlation Diagnostic Techniques Neurological Natural history of disease Severity of Illness Index Article Developmental Neuroscience Double-Blind Method Internal medicine Medicine Humans Prospective Studies Child Reliability (statistics) business.industry Reproducibility of Results Niemann-Pick Disease Type C Confidence interval Clinical trial Inter-rater reliability Neurology Child Preschool Pediatrics Perinatology and Child Health Disease Progression Female Neurology (clinical) business Kappa |
| Zdroj: | Pediatr Neurol |
| ISSN: | 1873-5150 |
| Popis: | Background Niemann-Pick Disease, type C1 (NPC1) is a rare neurodegenerative genetic disorder characterized by impaired intracellular transport of cholesterol and other lipids. The Niemann-Pick Disease, type C1 Severity Scale (NPC-SS) was developed to quantify neurological progression of NPC; it is used to monitor the natural history of disease progression and assess response to treatment. Objective The objective of the study was to examine the inter-rater reliability of the NPC-SS in a Phase 2/3 clinical trial. Methods Study data were from a multicenter, prospective, randomized, double-blind, trial of adrabetadex in 56 subjects with NPC1. Clinical data recorded at each study site were distributed to two independent blinded central raters to generate a severity score. A composite four-item score was utilized as the primary clinical study endpoint, while a five-item focused score has been utilized in other NPC1 trials. Inter-rater reliability was assessed using two-way mixed models for instrument stability, Cohen's kappa, weighted kappa, and percent agreement for the four-item and five-item scores. Results The frequency distribution and mean (SD) of the NPC-SS domain assessments by the raters were almost identical. Evaluation at the patient visit level showed wide variability between visits, however, weighted kappa calculation provided a lower variability between visits. The average kappa coefficients ranged between 0.69 to 0.89, indicating good to very good agreement between raters. Conclusion These results support the NPC-SS, including derived 4- and 5-item composite scores, as reliable measures for use in a clinical trial setting. |
| Databáze: | OpenAIRE |
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