Time dependent analysis of assay comparability: a novel approach to understand intra- and inter-site variability over time.
J Comput Aided Mol Des
; 29(9): 795-807, 2015 Sep.
Article
em En
| MEDLINE
| ID: mdl-25697964
ABSTRACT
We demonstrate here a novel use of statistical tools to study intra- and inter-site assay variability of five early drug metabolism and pharmacokinetics in vitro assays over time. Firstly, a tool for process control is presented. It shows the overall assay variability but allows also the following of changes due to assay adjustments and can additionally highlight other, potentially unexpected variations. Secondly, we define the minimum discriminatory difference/ratio to support projects to understand how experimental values measured at different sites at a given time can be compared. Such discriminatory values are calculated for 3 month periods and followed over time for each assay. Again assay modifications, especially assay harmonization efforts, can be noted. Both the process control tool and the variability estimates are based on the results of control compounds tested every time an assay is run. Variability estimates for a limited set of project compounds were computed as well and found to be comparable. This analysis reinforces the need to consider assay variability in decision making, compound ranking and in silico modeling.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Farmacocinética
/
Interpretação Estatística de Dados
/
Ensaios de Triagem em Larga Escala
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Comput Aided Mol Des
Assunto da revista:
BIOLOGIA MOLECULAR
/
ENGENHARIA BIOMEDICA
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Suécia