Joint modeling of efficacy, dropout, and tolerability in flexible-dose trials: a case study in depression.
Clin Pharmacol Ther
; 91(5): 863-71, 2012 May.
Article
in En
| MEDLINE
| ID: mdl-22472989
ABSTRACT
Many difficulties may arise during the modeling of the time course of Hamilton Rating Scale for Depression (HAM D)scores in clinical trials for the evaluation of antidepressant drugs (i) flexible designs, used to increase the chance of selecting more efficacious doses, (ii) dropout events, and (iii) adverse effects related to the experimental compound.It is crucial to take into account all these factors when designing an appropriate model of the HAM D time course and to obtain a realistic description of the dropout process. In this work, we propose an integrated approach to the modeling of a double-blind, flexible-dose, placebo-controlled, phase II depression trial that comprises response,tolerability, and dropout. We investigate three different dropout mechanisms in terms of informativeness. Goodness of fit is quantitatively assessed with respect to response (HAM D score) and dropout data. We show that dropout is a complex phenomenon that may be influenced by HAM D evolution, dose changes, and occurrence of drug-related adverse effects.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Patient Dropouts
/
Depression
/
Antidepressive Agents
Type of study:
Clinical_trials
/
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Clin Pharmacol Ther
Year:
2012
Type:
Article
Affiliation country:
Italy