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

Research

Lu Liu¹  Hwanhee Hong¹  Ramin Mojtabai²  Elizabeth A. Stuart² 

[1] Department of Biostatistics and Bioinformatics, School of Medicine, Duke University, 2424 Erwin Road, Ste 1105, 27705, Durham, NC, USA;Department of Mental Health, Bloomberg School of Public Health, Johns Hopkins University, 615 N. Wolfe Street, 21205, Baltimore, MD, USA;

关键词: Schizophrenia;    Paliperidone Palmitate;    Target Population;    Individual-Level Data;    Meta-Analysis;    Generalizability;    Randomized trials;   

DOI  :  10.1186/s12874-023-01958-w

 received in 2022-09-05, accepted in 2023-05-25,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundsMeta-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.MethodsWe 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.ResultsA 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.ConclusionsThe 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.

【 授权许可】

CC BY   
© The Author(s) 2023

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