 |
|
Dropout Rates in Placebo-Controlled and Active-Control Clinical Trials of Antipsychotic Drugs
A Meta-analysis
Georg Kemmler, PhD;
Martina Hummer, MD;
Christian Widschwendter, MD;
W. Wolfgang Fleischhacker, MD
Arch Gen Psychiatry. 2005;62:1305-1312.
Context Dropout rates in randomized clinical trials of antipsychotic drugs have consistently been reported to be high, and the use of a placebo-controlled design is hypothesized to be one of the reasons for this.
Objective To investigate this hypothesis in a meta-analysis of available data from pertinent clinical trials.
Data Sources Comprehensive search of PubMed- and MEDLINE-listed journals.
Study Selection Double-blind randomized controlled clinical trials of the second-generation antipsychotics risperidone, olanzapine, quetiapine, amisulpride, ziprasidone, and aripiprazole meeting the following criteria: unselected patient population with a diagnosis of schizophrenia or schizoaffective disorder, change in psychopathologic symptoms as the primary end point, and trial duration of 12 weeks or less.
Data Extraction Sample size, mean age, baseline disease severity, dropout rate, trial design, trial duration, and publication year.
Data Synthesis Thirty-one trials meeting the inclusion criteria were found, comprising 10 058 subjects. Weighted mean dropout rates in the active treatment arms were significantly higher in placebo-controlled trials (PCTs) than in active-control trials: 48.1% (PCTs) vs 28.3% (active-control trials) for second-generation antipsychotics (odds ratio, 2.34; 95% confidence interval, 1.58-3.47) and 55.4% (PCTs) vs 37.2% (active-control trials) for classical antipsychotics (odds ratio, 2.10; 95% confidence interval, 1.29-3.40). Within PCTs, attrition rates were significantly higher in the placebo arms than with second-generation antipsychotics (60.2% vs 48.1%; odds ratio, 1.63; 95% confidence interval, 1.37-1.94). Within the subset of trials in which both second-generation and classical antipsychotics were used, dropout rates were significantly higher with classical antipsychotics.
Conclusions Use of a placebo-controlled design had a major effect on the dropout rates observed. Because high dropout rates affect the generalizability of such studies, it is suggested that, in addition to the PCTs, studies with alternative designs need to be considered when evaluating an antipsychotic’s clinical profile.
Author Affiliations: Departments of General Psychiatry (Dr Kemmler) and Biological Psychiatry (Drs Hummer, Widschwendter, and Fleischhacker), Innsbruck University Clinics, Innsbruck, Austria.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati
What's this?
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
Dropout Rates in Randomized Clinical Trials of Antipsychotics: A Meta-analysis Comparing First- and Second-Generation Drugs and an Examination of the Role of Trial Design Features
Rabinowitz et al.
Schizophr Bull 2009;35:775-788.
ABSTRACT
| FULL TEXT
A Meta-Analysis of Head-to-Head Comparisons of Second-Generation Antipsychotics in the Treatment of Schizophrenia
Leucht et al.
Am. J. Psychiatry 2009;166:152-163.
ABSTRACT
| FULL TEXT
Voucher-Based Incentives for Naltrexone Treatment Attendance in Schizophrenia and Alcohol Use Disorders
Leontieva et al.
Psychiatr. Serv. 2008;59:310-314.
ABSTRACT
| FULL TEXT
Feasibility of Reducing the Duration of Placebo-Controlled Trials in Schizophrenia Research
McMahon et al.
Schizophr Bull 2008;34:292-301.
ABSTRACT
| FULL TEXT
Regulatory policies on medicines for psychiatric disorders: is Europe on target?
BARBUI and GARATTINI
Br. J. Psychiatry 2007;190:91-93.
ABSTRACT
| FULL TEXT
Review: higher rates of attrition in antipsychotic treatment arms of placebo controlled trials than in trials with active comparators.
Stroup
Evid. Based Ment. Health 2006;9:70-70.
FULL TEXT
Ethics of Medication-Free Research in Schizophrenia
Chen and Moreno
Schizophr Bull 2006;32:307-309.
FULL TEXT
Dropout Rates in Antipsychotic Drug Studies
JWatch Psychiatry 2006;2006:7-7.
FULL TEXT
|
