Efficacy of clozapine compared with other second-generation antipsychotic drugs in patients with treatment-resistant schizophrenia: protocol for a systematic review and individual patient data meta-analysis of randomised controlled trials.

Siafis, Spyridon; Schneider-Thoma, Johannes; Hamza, Tasnim; Bighelli, Irene; Dong, Shimeng; Hansen, Wulf-Peter; Davis, John M; Salanti, Georgia; Leucht, Stefan (2023). Efficacy of clozapine compared with other second-generation antipsychotic drugs in patients with treatment-resistant schizophrenia: protocol for a systematic review and individual patient data meta-analysis of randomised controlled trials. BMJ open, 13(2), e064504. BMJ Publishing Group 10.1136/bmjopen-2022-064504

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INTRODUCTION

Guidelines recommend clozapine for treatment-resistant schizophrenia. However, meta-analysis of aggregate data (AD) did not demonstrate higher efficacy of clozapine compared with other second-generation antipsychotics but found substantial heterogeneity between trials and variation between participants in treatment effects. Therefore, we will conduct an individual participant data (IPD) meta-analysis to estimate the efficacy of clozapine compared with other second-generation antipsychotics while accounting for potentially important effect modifiers.

METHODS AND ANALYSIS

In a systematic review, two reviewers will independently search Cochrane Schizophrenia Group's trial register (without restrictions in date, language or state of publication) and related reviews. We will include randomised controlled trials (RCTs) in participants with treatment-resistant schizophrenia comparing clozapine with other second-generation antipsychotics for at least 6 weeks. We will apply no restrictions in age, gender, origin, ethnicity or setting, but exclude open-label studies, studies from China, experimental studies and phase II of cross-over trials. IPD will be requested from trial authors and cross-check against published results. AD will be extracted in duplicate. Risk of bias will be assessed using Cochrane's Risk of Bias 2 tool.The primary outcome will be overall symptoms of schizophrenia.We will synthesise results using random-effects meta-analysis and meta-regression methods in a 3-level Bayesian model. The model combines IPD with AD when IPD is not available for all studies, and include participant, intervention and study design characteristics as potential effect modifiers. The effect size measures will be mean difference (or standardised mean difference when different scales were used). Confidence in the evidence will be assessed using GRADE.

ETHICS AND DISSEMINATION

This project has been approved by the ethics commission of the Technical University of Munich (#612/21 S-NP). The results will be published open-access in a peer-review journal and a plain-language version of the results will be disseminated.If we need to amend this protocol, we will describe the change and give the rationale in a specific section in the resulting publication 'Changes with respect to the protocol'.

SYSTEMATIC REVIEW REGISTRATION

PROSPERO (#CRD42021254986).

Item Type:

Journal Article (Further Contribution)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Social and Preventive Medicine (ISPM)

Graduate School:

Graduate School for Health Sciences (GHS)

UniBE Contributor:

Hamza, Tasnim A. A., Salanti, Georgia

Subjects:

600 Technology > 610 Medicine & health
300 Social sciences, sociology & anthropology > 360 Social problems & social services

ISSN:

2044-6055

Publisher:

BMJ Publishing Group

Language:

English

Submitter:

Pubmed Import

Date Deposited:

23 Feb 2023 11:22

Last Modified:

26 Feb 2023 02:16

Publisher DOI:

10.1136/bmjopen-2022-064504

PubMed ID:

36810167

Uncontrolled Keywords:

adult psychiatry mental health schizophrenia & psychotic disorders

BORIS DOI:

10.48350/179045

URI:

https://boris.unibe.ch/id/eprint/179045

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