Calibrated meta-analysis to estimate the efficacy of mental health treatments in target populations: an application to paliperidone trials for treatment of schizophrenia
Abstract Backgrounds Meta-analyses can be a powerful tool but need to calibrate potential unrepresentativeness of the included trials to a target population. Estimating target population average treatment effects (TATE) in meta-analyses is important to understand how treatments perform in well-defin...
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| Language: | English |
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BMC
2023-06-01
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| Series: | BMC Medical Research Methodology |
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| Online Access: | https://doi.org/10.1186/s12874-023-01958-w |
| _version_ | 1797789721218252800 |
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| author | Hwanhee Hong Lu Liu Ramin Mojtabai Elizabeth A. Stuart |
| author_facet | Hwanhee Hong Lu Liu Ramin Mojtabai Elizabeth A. Stuart |
| author_sort | Hwanhee Hong |
| collection | DOAJ |
| description | Abstract Backgrounds Meta-analyses can be a powerful tool but need to calibrate potential unrepresentativeness of the included trials to a target population. Estimating target population average treatment effects (TATE) in meta-analyses is important to understand how treatments perform in well-defined target populations. This study estimated TATE of paliperidone palmitate in patients with schizophrenia using meta-analysis with individual patient trial data and target population data. Methods We conducted a meta-analysis with data from four randomized clinical trials and target population data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study. Efficacy was measured using the Positive and Negative Syndrome Scale (PANSS). Weights to equate the trial participants and target population were calculated by comparing baseline characteristics between the trials and CATIE. A calibrated weighted meta-analysis with random effects was performed to estimate the TATE of paliperidone compared to placebo. Results A total of 1,738 patients were included in the meta-analysis along with 1,458 patients in CATIE. After weighting, the covariate distributions of the trial participants and target population were similar. Compared to placebo, paliperidone palmitate was associated with a significant reduction of the PANSS total score under both unweighted (mean difference 9.07 [4.43, 13.71]) and calibrated weighted (mean difference 6.15 [2.22, 10.08]) meta-analysis. Conclusions The effect of paliperidone palmitate compared with placebo is slightly smaller in the target population than that estimated directly from the unweighted meta-analysis. Representativeness of samples of trials included in a meta-analysis to a target population should be assessed and incorporated properly to obtain the most reliable evidence of treatment effects in target populations. |
| first_indexed | 2024-03-13T01:54:42Z |
| format | Article |
| id | doaj.art-a819469d165c4dd3b9da52f94b1fc3c3 |
| institution | Directory Open Access Journal |
| issn | 1471-2288 |
| language | English |
| last_indexed | 2024-03-13T01:54:42Z |
| publishDate | 2023-06-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medical Research Methodology |
| spelling | doaj.art-a819469d165c4dd3b9da52f94b1fc3c32023-07-02T11:19:16ZengBMCBMC Medical Research Methodology1471-22882023-06-0123111010.1186/s12874-023-01958-wCalibrated meta-analysis to estimate the efficacy of mental health treatments in target populations: an application to paliperidone trials for treatment of schizophreniaHwanhee Hong0Lu Liu1Ramin Mojtabai2Elizabeth A. Stuart3Department of Biostatistics and Bioinformatics, School of Medicine, Duke UniversityDepartment of Biostatistics and Bioinformatics, School of Medicine, Duke UniversityDepartment of Mental Health, Bloomberg School of Public Health, Johns Hopkins UniversityDepartment of Mental Health, Bloomberg School of Public Health, Johns Hopkins UniversityAbstract Backgrounds Meta-analyses can be a powerful tool but need to calibrate potential unrepresentativeness of the included trials to a target population. Estimating target population average treatment effects (TATE) in meta-analyses is important to understand how treatments perform in well-defined target populations. This study estimated TATE of paliperidone palmitate in patients with schizophrenia using meta-analysis with individual patient trial data and target population data. Methods We conducted a meta-analysis with data from four randomized clinical trials and target population data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study. Efficacy was measured using the Positive and Negative Syndrome Scale (PANSS). Weights to equate the trial participants and target population were calculated by comparing baseline characteristics between the trials and CATIE. A calibrated weighted meta-analysis with random effects was performed to estimate the TATE of paliperidone compared to placebo. Results A total of 1,738 patients were included in the meta-analysis along with 1,458 patients in CATIE. After weighting, the covariate distributions of the trial participants and target population were similar. Compared to placebo, paliperidone palmitate was associated with a significant reduction of the PANSS total score under both unweighted (mean difference 9.07 [4.43, 13.71]) and calibrated weighted (mean difference 6.15 [2.22, 10.08]) meta-analysis. Conclusions The effect of paliperidone palmitate compared with placebo is slightly smaller in the target population than that estimated directly from the unweighted meta-analysis. Representativeness of samples of trials included in a meta-analysis to a target population should be assessed and incorporated properly to obtain the most reliable evidence of treatment effects in target populations.https://doi.org/10.1186/s12874-023-01958-wSchizophreniaPaliperidone PalmitateTarget PopulationIndividual-Level DataMeta-AnalysisGeneralizability |
| spellingShingle | Hwanhee Hong Lu Liu Ramin Mojtabai Elizabeth A. Stuart Calibrated meta-analysis to estimate the efficacy of mental health treatments in target populations: an application to paliperidone trials for treatment of schizophrenia BMC Medical Research Methodology Schizophrenia Paliperidone Palmitate Target Population Individual-Level Data Meta-Analysis Generalizability |
| title | Calibrated meta-analysis to estimate the efficacy of mental health treatments in target populations: an application to paliperidone trials for treatment of schizophrenia |
| title_full | Calibrated meta-analysis to estimate the efficacy of mental health treatments in target populations: an application to paliperidone trials for treatment of schizophrenia |
| title_fullStr | Calibrated meta-analysis to estimate the efficacy of mental health treatments in target populations: an application to paliperidone trials for treatment of schizophrenia |
| title_full_unstemmed | Calibrated meta-analysis to estimate the efficacy of mental health treatments in target populations: an application to paliperidone trials for treatment of schizophrenia |
| title_short | Calibrated meta-analysis to estimate the efficacy of mental health treatments in target populations: an application to paliperidone trials for treatment of schizophrenia |
| title_sort | calibrated meta analysis to estimate the efficacy of mental health treatments in target populations an application to paliperidone trials for treatment of schizophrenia |
| topic | Schizophrenia Paliperidone Palmitate Target Population Individual-Level Data Meta-Analysis Generalizability |
| url | https://doi.org/10.1186/s12874-023-01958-w |
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