Performance Measures in Dose-Finding Experiments

Flournoy, Nancy ; Moler, José ; Plo, Fernando (Universidad de Zaragoza)

Resumen: In the first phase of pharmaceutical development, and assuming that the probability of positive response increases with dose, the main statistical goal is to estimate a percentile of the dose–response function for a given target ¿. We compare the Maximum Likelihood and centred isotonic regression estimators of the target dose and we discuss several performance criteria to assess inferential precision, the amount of toxicity exposure and the trade-off between them for a set of some exemplary adaptive designs. We compare these designs using graphical tools. Several scenarios are considered using simulation, including the use of several start-up rules, the change of slope of the dose-toxicity function at the target dose and also different theoretical models, as logistic, normal or skew-normal distribution functions.

Idioma: Inglés

DOI: 10.1111/insr.12363

Año: 2020

Publicado en: INTERNATIONAL STATISTICAL REVIEW 88, 3 (2020), 728-751
ISSN: 0306-7734

Factor impacto JCR: 2.217 (2020)

Categ. JCR: STATISTICS & PROBABILITY rank: 38 / 125 = 0.304 (2020) - Q2 - T1

Factor impacto SCIMAGO: 1.05 - Statistics, Probability and Uncertainty (Q2) - Statistics and Probability (Q2)

Financiación: info:eu-repo/grantAgreement/ES/MINECO/MTM2014-53340-P
Financiación: info:eu-repo/grantAgreement/ES/MINECO/MTM2016-77015-R

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Estadís. Investig. Opera. (Dpto. Métodos Estadísticos)