Observation of time-dependent adverse events and the influence of drop-out thereon in long-term safety studies--simulation study under the current practice of post-marketing safety evaluation in Japan.
J Biopharm Stat
; 14(2): 403-14, 2004 May.
Article
em En
| MEDLINE
| ID: mdl-15206536
ABSTRACT
Safety assessment of a new drug should be continuously carried out in the premarketing phase as well as in the postmarketing phase. Considering the actual conditions and problems of postmarketing safety studies in Japan, i.e., the lack of attention to the extent of patients' exposure to the drug (duration and the number of patients), we simulated the number of adverse events to be observed after specified intervals of exposure. This was done by applying different sets of hazard functions for a Weibull distribution under the circumstances that a certain number of patients has dropped out, focusing on rare and delayed adverse events associated with chronically used drugs. By using the result of these simulations, we point out potential problems of underestimating adverse event rates in situations where the hazard rate of the event escalates over time. Patients drop-out from the study also deteriorates the ability to observe such time-dependent adverse events. The simulation can also serve as a useful tool to examine the necessary sample size and the duration of exposure in order to observe and characterize potentially expected adverse events. It is important to take the two key factors into consideration the change of hazard function over time and the effect of drop-out in designing, analyzing, and evaluating safety studies for new drugs.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pacientes Desistentes do Tratamento
/
Vigilância de Produtos Comercializados
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Simulação por Computador
Tipo de estudo:
Evaluation_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Humans
País/Região como assunto:
Asia
Idioma:
En
Revista:
J Biopharm Stat
Assunto da revista:
FARMACOLOGIA
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
Japão