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- Document type:
- Journal Article; Clinical Trial
- Author(s):
- Levine, Stephen Z; Goldberg, Yair; Samara, Myrto; Davis, John M; Leucht, Stefan
- Title:
- Joint modeling of dropout and outcome in three pivotal clinical trials of schizophrenia.
- Abstract:
- Dropout is a serious challenge to clinical trials in psychiatry, yet standard outcome analyses with mixed models do not account for dropout, while joint modeling uses dropout from a survival model to adjust the outcome from a mixed model, but is untested in clinical trials of schizophrenia.To compare mixed and joint modeling in three acute phase pivotal placebo controlled trials of schizophrenia.Data were reanalyzed on 611 in-patients with acute schizophrenia who participated in three pivotal randomized controlled trials that compared placebo with olanzapine or risperidone (dropout rates placebo: 62.6% and medication: 37.4%). The outcome measures were BPRS or PANSS total change scores. Mixed-effects models for repeated measures and joint models were computed and compared to examine the time-treatment interaction. Effect size comparisons were made.Antipsychotic treatment was superior to placebo across analyses. Time treatment interactions were significant (p<.05) for the mixed (beta=2.33) and joint models (beta=2.62). Compared with mixed modeling, joint modeling reduced the estimated change score for treatment (21.24 vs 19.74) and placebo (1.64 vs -1.11). The effect size differences between placebo and treatment groups were greater for joint (ES=.89) than mixed modeling (ES=0.83). Sensitivity analysis replicated this trend of results in each of the three trials.Compared to mixed modeling, joint modeling results in a greater separation between treatment and placebo groups. This offers preliminary evidence that joint modeling may be useful in the analysis of antipsychotic placebo controlled RCTs.
- Journal title abbreviation:
- Schizophr Res
- Year:
- 2015
- Journal volume:
- 164
- Journal issue:
- 1-3
- Pages contribution:
- 122-6
- Language:
- eng
- Fulltext / DOI:
- doi:10.1016/j.schres.2015.02.021
- Pubmed ID:
- http://view.ncbi.nlm.nih.gov/pubmed/25790904
- Print-ISSN:
- 0920-9964
- TUM Institution:
- Klinik und Poliklinik für Psychiatrie und Psychotherapie
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