A Bayesian hierarchical surrogate outcome model for multiple sclerosis.
Pharm Stat
; 15(4): 341-8, 2016 Jul.
Article
en En
| MEDLINE
| ID: mdl-27061897
ABSTRACT
The development of novel therapies in multiple sclerosis (MS) is one area where a range of surrogate outcomes are used in various stages of clinical research. While the aim of treatments in MS is to prevent disability, a clinical trial for evaluating a drugs effect on disability progression would require a large sample of patients with many years of follow-up. The early stage of MS is characterized by relapses. To reduce study size and duration, clinical relapses are accepted as primary endpoints in phase III trials. For phase II studies, the primary outcomes are typically lesion counts based on magnetic resonance imaging (MRI), as these are considerably more sensitive than clinical measures for detecting MS activity. Recently, Sormani and colleagues in 'Surrogate endpoints for EDSS worsening in multiple sclerosis' provided a systematic review and used weighted regression analyses to examine the role of either MRI lesions or relapses as trial level surrogate outcomes for disability. We build on this work by developing a Bayesian three-level model, accommodating the two surrogates and the disability endpoint, and properly taking into account that treatment effects are estimated with errors. Specifically, a combination of treatment effects based on MRI lesion count outcomes and clinical relapse was used to develop a study-level surrogate outcome model for the corresponding treatment effects based on disability progression. While the primary aim for developing this model was to support decision-making in drug development, the proposed model may also be considered for future validation. Copyright © 2016 John Wiley & Sons, Ltd.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Imagen por Resonancia Magnética
/
Teorema de Bayes
/
Descubrimiento de Drogas
/
Esclerosis Múltiple
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Pharm Stat
Asunto de la revista:
FARMACOLOGIA
Año:
2016
Tipo del documento:
Article
País de afiliación:
Estados Unidos