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Cited by 193Schizophrenia research and treatmentStatistical Methods in Clinical TrialsMeta-analysis and systematic reviews

The DOI matches its Crossref record; 29 of the 30 references it cites were found in a registry or an index.

Is the Superior Efficacy of New Generation Antipsychotics an Artifact of LOCF?

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Leucht, S., Engel, R. R., Bauml, J., Davis, J. M.·2006·Schizophrenia Bulletin
DOI 10.1093/schbul/sbl025PMC PMC2632292
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Abstract

It has been argued that the efficacy superiority found in meta-analyses for some of the atypical antipsychotics is an artifact of higher dropout rates due to side effects in the haloperidol group combined with last-observation-carried-forward (LOCF) analyses. We therefore reanalyzed a number of pivotal studies comparing new generation antipsychotics (NGAs) and conventional antipsychotics (CAs). A total of 5 studies (n = 1271) comparing amisulpride and 3 studies (n = 2454) comparing olanzapine with CAs were reanalyzed using original patient data. We applied 4 different models: LOCF, completer analysis, LOCF but excluding dropouts due to adverse events, and LOCF but excluding all dropouts with the exception of dropouts related to efficacy. Effect sizes expressed as standardized mean differences between NGAs and CAs based on the 4 different analysis models were compared. The overall results were not different irrespective of the model used. Single studies, however, showed higher effect sizes when LOCF instead of other models was used. Overall, it does not seem that higher dropout rates due to side effects in the haloperidol groups together with LOCF analyses consistently biased the results in favor of amisulpride and olanzapine. Because the results of the single studies, however, showed that this may occasionally be the case, future studies should look at the data from different angles applying sensitivity analyses, and they may use alternative statistics such as mixed models, which need to be developed further. Ultimately, strategies to reduce dropout rates are needed.

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Research works printed but not linked: 7

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Metadata

Authors
Leucht, S., Engel, R. R., Bauml, J., & Davis, J. M.
Affiliations
  • TUM Klinikum (DE)
  • Ludwig-Maximilians-Universität München (DE)
  • University of Illinois Chicago (US)
ORCID
Venue
Schizophrenia Bulletin
Publisher
Oxford University Press (OUP)
Published
2006-12-07
Volume
33
Issue
1
Pages
183-191
ISSN
  • 0586-7614 (ISSN-L)
  • 1745-1701
DOI
10.1093/schbul/sbl025
PMC
PMC2632292
OpenAlex
W2127313266
Cited by
193
References
30
Citations by year
2026: 1 · 2025: 1 · 2022: 2 · 2021: 1 · 2020: 1 · 2019: 5 · 2018: 7 · 2017: 9 · 2016: 12 · 2015: 22 · 2014: 27 · 2013: 34 · 2012: 41
FWCI
3.18
Type
journal article
Language
en
Open access
Locations
  • Schizophrenia Bulletin (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
  • Social Sciences › Decision Sciences › Statistics, Probability and Uncertainty › Meta-analysis and systematic reviews
Keywords
last observation carried forward, missing data
MeSH terms
Olanzapine, Amisulpride, Benzodiazepines, Flupenthixol, Haloperidol, Humans, Patient Dropouts, Psychiatric Status Rating Scales, Psychotropic Drugs, Schizophrenia, Schizophrenic Psychology, Sulpiride, Bias, Randomized Controlled Trials as Topic, Artifacts, Treatment Outcome

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