Bioequivalence tests based on individual estimates using non-compartmental or model-based analyses: evaluation of estimates of sample means and type I error for different designs.
Pharm Res
; 27(1): 92-104, 2010 Jan.
Article
em En
| MEDLINE
| ID: mdl-19876723
ABSTRACT
PURPOSE:
The main objective of this work is to compare the standard bioequivalence tests based on individual estimates of the area under the curve and the maximal concentration obtained by non-compartmental analysis (NCA) to those based on individual empirical Bayes estimates (EBE) obtained by nonlinear mixed effects models.METHODS:
We evaluate by simulation the precision of sample means estimates and the type I error of bioequivalence tests for both approaches. Crossover trials are simulated under H ( 0 ) using different numbers of subjects (N) and of samples per subject (n). We simulate concentration-time profiles with different variability settings for the between-subject and within-subject variabilities and for the variance of the residual error.RESULTS:
Bioequivalence tests based on NCA show satisfactory properties with low and high variabilities, except when the residual error is high, which leads to a very poor type I error, or when n is small, which leads to biased estimates. Tests based on EBE lead to an increase of the type I error, when the shrinkage is above 20%, which occurs notably when NCA fails.CONCLUSIONS:
For small n or data with high residual error, tests based on a global data analysis should be considered instead of those based on individual estimates.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Projetos de Pesquisa
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Equivalência Terapêutica
/
Modelos Estatísticos
Tipo de estudo:
Clinical_trials
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Evaluation_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article