Predictive probability of success using surrogate endpoints.
Stat Med
; 38(10): 1753-1774, 2019 05 10.
Article
em En
| MEDLINE
| ID: mdl-30548627
ABSTRACT
The predictive probability of success of a future clinical trial is a key quantitative tool for decision-making in drug development. It is derived from prior knowledge and available evidence, and the latter typically comes from the accumulated data on the clinical endpoint of interest in previous clinical trials. However, a surrogate endpoint could be used as primary endpoint in early development and, usually, no or limited data are collected on the clinical endpoint of interest. We propose a general, reliable, and broadly applicable methodology to predict the success of a future trial from surrogate endpoints, in a way that makes the best use of all the available evidence. The predictions are based on an informative prior, called surrogate prior, derived from the results of past trials on one or several surrogate endpoints. If available, in a Bayesian framework, this prior could be combined with data from past trials on the clinical endpoint of interest. Two methods are proposed to address a potential discordance between the surrogate prior and the data on the clinical endpoint. We investigate the patterns of behavior of the predictions in a comprehensive simulation study, and we present an application to the development of a drug in Multiple Sclerosis. The proposed methodology is expected to support decision-making in many different situations, since the use of predictive markers is important to accelerate drug developments and to select promising drug candidates, better and earlier.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Modelos Estatísticos
/
Teorema de Bayes
/
Determinação de Ponto Final
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Stat Med
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Itália